914 results on '"Hao XH"'
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2. Development and validation of diffusive gradients in thin-films for in situ monitoring of ionic liquids in waters.
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Liu SS, Chen SB, Yue YB, Li XH, Zhang C, Ying GG, and Chen CE
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Due to their wide applications, occurrence and "PFAS-like" environmental behaviors, ionic liquids (ILs) represent a new challenge for the environmental monitoring community, who require robust analytical methods that can determine accurately and efficiently their environmentally relevant concentrations. A new passive sampling method based on the diffusive gradients in thin films (DGT) technique was developed for the measurement of imidazole-based ILs in waters using a mixed-mode cation exchange (MCX) resin as the adsorbent. The selected binding gel had a high binding capacity (>170 μg per disc) for ILs. Diffusion coefficients measured using a diffusion cell correlated well with alkyl chain lengths ( r
2 = 0.95) and retention times ( r2 = 0.88), providing a simple and rapid prediction approach for other ILs. The assembled MCX-DGT sampler exhibited a linear accumulation for at least 120 h. MCX-DGT also showed good performance under typical freshwater conditions (pH 5-8, ionic strength 0.001-0.01 M, and humic acid 0-5 mg L-1 ), while still being problematic for aquatic conditions with higher ionic strength (>0.1 M) or DOM (>10 mg L-1 ). Laboratory deployment (for up to 3 days) in spiked natural freshwater (SNW) resulted in linear mass uptakes for the short-chain ILs (C2-C8), and their DGT-measured concentrations agreed well with solution concentrations. However, MCX-DGT significantly overestimated the concentrations of the long-chain ILs (C10-C12) when deployed in SNW for one day or more, which is attributed to the strong competitive adsorption of the long-chain ILs by natural organic matter. In situ field evaluation along with grab sampling found no target ILs in a wastewater treatment plant and its receiving river, implying that these new chemicals might not be widely used in South China now. This is the first report on the DGT technique for ILs and might provide an effective tool for monitoring short chain length ILs in the aquatic environment in the near future.- Published
- 2024
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3. Machine Learning-Based Detection of Bladder Cancer by Urine cfDNA Fragmentation Hotspots that Capture Cancer-Associated Molecular Features.
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Meng XY, Zhou XH, Li S, Shi MJ, Li XH, Yang BY, Liu M, Yi KZ, Wang YZ, Zhang HY, Song J, Wang FB, and Wang XH
- Abstract
Background: cfDNA fragmentomics-based liquid biopsy is a potential option for noninvasive bladder cancer (BLCA) detection that remains an unmet clinical need., Methods: We assessed the diagnostic performance of cfDNA hotspot-driven machine-learning models in a cohort of 55 BLCA patients, 51 subjects with benign conditions, and 11 healthy volunteers. We further performed functional bioinformatics analysis for biological understanding and interpretation of the tool's diagnostic capability., Results: Urinary cfDNA hotspots-based machine-learning model enabled effective BLCA detection, achieving high performance (area under curve 0.96) and an 87% sensitivity at 100% specificity. It outperformed models using other cfDNA-derived features. In stage-stratified analysis, the sensitivity at 100% specificity of the urine hotspots-based model was 71% and 92% for early (low-grade Ta and T1) and advanced (high-grade T1 and muscle-invasive) disease, respectively. Biologically, cfDNA hotspots effectively retrieved regulatory elements and were correlated with the cell of origin. Urine cfDNA hotspots specifically captured BLCA-related molecular features, including key functional pathways, chromosome loci associated with BLCA risk as identified in genome-wide association studies, or presenting frequent somatic alterations in BLCA tumors, and the transcription factor regulatory landscape., Conclusions: Our findings support the applicability of urine cfDNA fragmentation hotspots for noninvasive BLCA diagnosis, as well as for future translational study regarding its molecular pathology and heterogeneity., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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4. The complete mitochondrial genome of Castanopsis carlesii and Castanea henryi reveals the rearrangement and size differences of mitochondrial DNA molecules.
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Tu XD, Xin YX, Fu HH, Zhou CY, Liu QL, Tang XH, Zou LH, Liu ZJ, Chen SP, Lin WJ, and Li MH
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- Phylogeny, Species Specificity, Genome Size, Genome, Mitochondrial, Fagaceae genetics, DNA, Mitochondrial genetics
- Abstract
Background: Castanopsis carlesii is a dominant tree species in subtropical evergreen broad-leaved forests and holds significant ecological value. It serves as an excellent timber tree species and raw material for cultivating edible fungi. Henry Chinquapin (Castanea henryi) wood is known for its hardness and resistance to water and moisture, making it an exceptional timber species. Additionally, its fruit has a sweet and fruity taste, making it a valuable food source. However, the mitogenomes of these species have not been previously reported. To gain a better understanding of them, this study successfully assembled high-quality mitogenomes of C. carlesii and Ca. henryi for the first time., Results: Our research reveals that the mitochondrial DNA (mtDNA) of C. carlesii exhibits a unique multi-branched conformation, while Ca. henryi primarily exists in the form of two independent molecules that can be further divided into three independent molecules through one pair of long repetitive sequences. The size of the mitogenomes of C. carlesii and Ca. henryi are 592,702 bp and 379,929 bp respectively, which are currently the largest and smallest Fagaceae mitogenomes recorded thus far. The primary factor influencing mitogenome size is dispersed repeats. Comparison with published mitogenomes from closely related species highlights differences in size, gene loss patterns, codon usage preferences, repetitive sequences, as well as mitochondrial plastid DNA segments (MTPTs)., Conclusions: Our study enhances the understanding of mitogenome structure and evolution in Fagaceae, laying a crucial foundation for future research on cell respiration, disease resistance, and other traits in this family., (© 2024. The Author(s).)
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- 2024
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5. CRISPR/Cas13a-mediated visual detection: A rapid and robust method for early detection of Nosema bombycis in silkworms.
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Wu YX, Sadiq S, Jiao XH, Zhou XM, Wang LL, Xie XR, Khan I, and Wu P
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The sericulture industry faces a significant threat from the Pebrine disease of silkworms, caused by Nosema bombycis. Nonetheless, the current microscopic diagnostic methods can be time-consuming, labor-intensive, and lacking sensitivity and accuracy. Therefore, it is crucial to develop a novel detection approach that is efficient, highly sensitive, and low-cost. In this regard, the CRISPR/Cas system has the potential to be a fast, accurate, and highly specific method of detection. Herein, using a microplate reader, a portable fluorescence detection device, and test strips as signal output tools respectively, we have efficiently developed three rapid and facile visual detection methods for N. bombycis using a CRISPR/Cas13a system with conjugation of Recombinase polymerase amplification (RPA). We evaluated the sensitivity of this combined technology by comparing it with the positive plasmid standard and the genome standard of N. bombycis. Remarkably, the sensitivity of the CRISPR/Cas13a system for N. bombycis positive plasmid standard based on the microplate reader, portable fluorescence detection device, and test strips was 1 copy/μL, 10 copies/μL, and 1 copy/μL, respectively, while for the N. bombycis genome standards, the detection sensitivity was 10 fg/μL, 10 fg/μL, and 1 fg/μL, respectively. In addition, extensive evaluations have demonstrated that the established technology can accurately detect N. bombycis without cross-reactivity with other pathogens, ensuring a specificity rate of 100%. In brief, this study will provide a practical, efficient, and affordable method for early and rapid detection of N. bombycis in various settings., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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6. An In Vitro Macrophage Response Study of Silk Fibroin and Silk Fibroin/Nano-Hydroxyapatite Scaffolds for Tissue Regeneration Application.
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Wong K, Tan XH, Li J, Hui JHP, and Goh JCH
- Abstract
In recent years, silk fibroin (SF) has been incorporated with low crystallinity nanohydroxyapatite (nHA) as a scaffold for various tissue regeneration applications due to the mechanical strength of SF and osteoconductive properties of nHA. However, currently, there is a lack of understanding of the immune response toward the degradation products of SF with nHA composite after implantation. It is known that particulate fragments from the degradation of a biomaterial can trigger an immune response. As the scaffold is made of degradable materials, the degradation products may contribute to the inflammation. Therefore, in this study, the effects of the enzymatic degradation of the SF/nHA scaffold on macrophage response were investigated in comparison to the control SF scaffold. Since the degradation products of a scaffold can influence macrophage polarization, it can be hypothesized that as the SF and SF/nHA scaffolds were degraded in vitro using protease XIV solution, the degradation products can contribute to the polarization of THP-1-derived macrophages from pro-inflammatory M1 to anti-inflammatory M2 phenotype. The results demonstrated that the initial (day 1) degradation products of the SF/nHA scaffold elicited a pro-inflammatory response, while the latter (day 24) degradation products of the SF/nHA scaffold elicited an anti-inflammatory response. Moreover, the degradation products from the SF scaffold elicited a higher anti-inflammatory response due to the faster degradation of the SF scaffold and a higher amino acid concentration in the degradation solution. Hence, this paper can help elucidate the contributory effects of the degradation products of SF and SF/nHA scaffolds on macrophage response and provide greater insights into designing silk-based biomaterials with tunable degradation rates that can modulate macrophage response for future tissue regeneration applications.
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- 2024
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7. Lymph nodes in oral squamous cell carcinoma: a comprehensive anatomical perspective.
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Wang GR, Zhong NN, Cao LM, Liu XH, Li ZZ, Xiao Y, Zhou K, Yu YF, Liu B, and Bu LL
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Oral squamous cell carcinoma (OSCC) often exhibits a propensity for metastasis to lymph nodes (LNs), significantly influencing prognosis. Neck dissection (ND) is an important part in the treatment of OSCC. Variations in the preference for and pathways of lymph node metastasis (LNM) in different regions of the oral cavity have been observed. Currently, there is a lack of sufficient emphasis on the anatomical perspectives of LNM and ND. This review elucidates the lymphatic system of the maxillofacial regions from an anatomical standpoint, details the distribution of the sentinel LNs across different subsites, and summarizes the various classifications of the cervical LNs. Additionally, we elaborate on the methods used to study the lymphatic system, particularly imaging techniques. Furthermore, we investigate the pathways of cervical LNM and evaluate the efficacy of ND from an anatomical viewpoint. The overall objective of this review is to provide essential anatomical knowledge for managing LNs in OSCC, in the hope of providing patients with effective treatment modalities to enhance their quality of life., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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8. Effects of organic and inorganic selenium mixes in pregnant sows on piglet growth, selenium levels in serum and milk, and selenium deposition in newborn piglet tissues.
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Jin XH, Park MS, Jang MH, Kim CS, and Kim YY
- Abstract
Objective: This study was conducted to evaluate the effects of organic and inorganic selenium mixes in pregnant sows on piglet growth, selenium levels in serum and milk, and selenium deposition in newborn piglet tissues., Methods: A total of 44 multiparous sows (Yorkshire×Landrace) with average body weight (BW), backfat thickness, and parity were assigned to one of the three treatments with 14 or 15 sows per treatment in a completely randomized design. The treatments were as follows: i) Control, corn-soybean meal-based diet with no addition of selenium premix; ii) ISOS(mixed inorganic selenium and organic selenium) 30, a basal diet supplemented with 0.15 ppm of inorganic Se and 0.15 ppm of organic Se; iii) ISOS50, a basal diet supplemented with 0.25 ppm of inorganic Se and 0.25 ppm of organic Se., Results: At day 21 of lactation, supplementing a high level of mixed Se at 0.50 ppm resulted in higher piglet BW and weight gain than adding a low level of mixed Se at 0.30 ppm (p<0.05). Selenium concentration of colostrum in sows fed ISOS50 diet was significantly higher than those in sows fed ISOS30 diet (p<0.05). Selenium concentrations in the serum at days 90 and 110 of gestation and 24 hours postpartum were highest when sows were fed ISOS50 diet (p<0.05). Additionally, increasing levels of mixed Se led to an increase in piglet serum Se concentration at 24 hours postpartum (p<0.05). Before ingesting colostrum, piglets from sows fed a mixed selenium (Se) diet had significantly higher kidney Se concentrations compared to those from the control group, with the ISOS50 treatment showing the most significant difference (p<0.05)., Conclusion: Supplementation of the gestation diet with 0.5 ppm of mixed Se may improve piglet growth performance, increase Se concentrations in milk, and enhance Se status in the serum of sows, as well as in the serum and tissues of their offspring.
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- 2024
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9. Phloridzin prevents diabetic cardiomyopathy by reducing inflammation and oxidative stress.
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Xie L, Yu ZQ, Zhang R, Zhang ZP, Zhang Y, Jin MY, Ju Y, Zhao XH, and Guo JP
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Oxidative stress and inflammation significantly contribute to the pathogenesis of diabetic cardiomyopathy (DCM). Persistent inflammatory stimuli drive the progression of myocardial fibrosis and impaired cardiac function. Phloridzin (Phl), a natural compound, demonstrates both anti-inflammatory and antioxidant properties. Nevertheless, its therapeutic potential and underlying mechanisms in DCM remain unclear. This study aimed to elucidate the mechanisms through which Phl inhibited myocardial fibrosis and exerted its antioxidative effects. The impact of Phl on DCM was evaluated using a high-fat/high-sugar diet combined with streptozotocin to induce an animal model and an in vitro H9C2 cell model stimulated by high glucose (HG). Untargeted metabolomics identified potential mechanisms underlying myocardial fibrosis. Phl treatment significantly enhanced left ventricular ejection fraction (EF%) and shortening fraction (FS%), while reducing myocardial injury markers, such as lactate dehydrogenase and creatine phosphokinase-MB, and suppressing myocardial collagen fiber accumulation. Simultaneously, Phl attenuated myocardial inflammation via inhibition of MyD88/NF-κB signaling, modulated the Nrf2/GPX4 axis to counter oxidative stress, and mitigated ferroptosis. In vitro, Phl inhibited high glucose-induced myocardial hypertrophy and fibrosis in H9C2 cells, while also repressing NF-κB activation in cardiomyocytes. Metabolomic profiling revealed that Phl ameliorated DCM through modulation of glycerophospholipid metabolic pathways, linking these metabolic shifts to enhanced antioxidant capacity, thereby reflecting its ability to reduce oxidative stress in the myocardium. Collectively, Phl provides cardioprotective effects by alleviating inflammation and oxidative damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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10. Electrocatalytic Aromatic Alcohols Splitting to Aldehydes and H 2 Gas.
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Zhang Z, Leng BL, Zhang SN, Xu D, Li QY, Lin X, Chen JS, and Li XH
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Selective electrocatalytic transformation of alcohols to aldehydes offers an efficient and environmentally friendly platform for the simultaneous production of fine chemicals and pure hydrogen gas. However, traditional alcohol oxidation reactions (AORs) in aqueous electrolyte unavoidably face competitive reactions (e.g., water oxidation and overoxidations reactions) for the presence of active oxygen species from water oxidation, causing an unwanted decrease in final efficiency and selectivity. Here, we developed an integrated all-solid proton generator-transfer electrolyzer to trigger the pure alcohol splitting reaction (ASR). In this splitting process, only O-H and C-H bonds can be cleaved at the proton generator (Pt nanoparticles), thereby completely avoiding all competitive reactions involving oxygen active species to give a > 99% selectivity to aldehydes. The as-generated protons are transported to the cathode by a three-dimensional (3D) conducting network (assemblies of ionomers and carbon spheres) for efficient hydrogen production. Unlike the poor selectivity (<22%) and durability (<3 h) of a conventional AOR electrolyzer, this ASR electrolyzer could be continuously operated at a low cell voltage of 1.2 V for at least 10 days to give a high Faradaic efficiency of 80-93% for aldehyde production.
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- 2024
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11. Preoperative patient-reported outcome measures predict minimal clinically important difference and patient-acceptable symptomatic state following arthroscopic Bankart repair.
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Long Y, Zheng ZZ, Li XH, Cui DD, Deng XH, Guo J, and Yang R
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- Humans, Female, Male, Retrospective Studies, Adult, Joint Instability surgery, Middle Aged, Young Adult, Adolescent, Shoulder Dislocation surgery, Pain Measurement, Patient Reported Outcome Measures, Arthroscopy methods, Minimal Clinically Important Difference
- Abstract
Aims: The aims of this study were to validate the minimal clinically important difference (MCID) and patient-acceptable symptom state (PASS) thresholds for Western Ontario Shoulder Instability Index (WOSI), Rowe score, American Shoulder and Elbow Surgeons (ASES), and visual analogue scale (VAS) scores following arthroscopic Bankart repair, and to identify preoperative threshold values of these scores that could predict the achievement of MCID and PASS., Methods: A retrospective review was conducted on 131 consecutive patients with anterior shoulder instability who underwent arthroscopic Bankart repair between January 2020 and January 2023. Inclusion criteria required at least one episode of shoulder instability and a minimum follow-up period of 12 months. Preoperative and one-year postoperative scores were assessed. MCID and PASS were estimated using distribution-based and anchor-based methods, respectively. Receiver operating characteristic curve analysis determined preoperative patient-reported outcome measure thresholds predictive of achieving MCID and PASS., Results: MCID thresholds were determined as 169.6, 6.8, 7.2, and 1.1 for WOSI, Rowe, ASES, and VAS, respectively. PASS thresholds were calculated as ≤ 480, ≥ 80, ≥ 87, and ≤ 1 for WOSI, Rowe, ASES, and VAS, respectively. Preoperative thresholds of ≥ 760 (WOSI) and ≤ 50 (Rowe) predicted achieving MCID for WOSI score (p < 0.001). Preoperative thresholds of ≤ 60 (ASES) and ≥ 2 (VAS) predicted achieving MCID for VAS score (p < 0.001). A preoperative threshold of ≥ 40 (Rowe) predicted achieving PASS for Rowe score (p = 0.005). Preoperative thresholds of ≥ 50 (ASES; p = 0.002) and ≤ 2 (VAS; p < 0.001) predicted achieving PASS for the ASES score. Preoperative thresholds of ≥ 43 (ASES; p = 0.046) and ≤ 4 (VAS; p = 0.024) predicted achieving PASS for the VAS., Conclusion: This study defined MCID and PASS values for WOSI, Rowe, ASES, and VAS scores in patients undergoing arthroscopic Bankart repair. Higher preoperative functional scores may reduce the likelihood of achieving MCID but increase the likelihood of achieving the PASS. These findings provide valuable guidance for surgeons to counsel patients realistically regarding their expectations., Competing Interests: None declared., (© 2024 The British Editorial Society of Bone & Joint Surgery.)
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- 2024
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12. Suicide among patients with oral cancer: A population-based study.
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Wang GR, Wang HQ, Zhong NN, Cao LM, Li ZZ, Liu XH, Xiao Y, Liu B, and Bu LL
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- Humans, Male, Female, Middle Aged, Risk Factors, Aged, Adult, United States epidemiology, Incidence, Young Adult, Aged, 80 and over, Mouth Neoplasms epidemiology, Mouth Neoplasms psychology, Mouth Neoplasms pathology, Suicide statistics & numerical data, Suicide psychology, SEER Program
- Abstract
Background: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer., Methods: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics., Results: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide., Conclusion: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
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- 2024
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13. Regulating the activity of GABAergic neurons in the ventral pallidum alters the general anesthesia effect of propofol.
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Zhou Y, Dong W, Qiu YK, Shao KJ, Zhang ZX, Yao JQ, Chen TQ, Li ZY, Zhou CR, Jiao XH, Chen Y, Lu H, and Wu YQ
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- Animals, Mice, Male, Mice, Transgenic, Proto-Oncogene Proteins c-fos metabolism, Reflex, Righting drug effects, Reflex, Righting physiology, Wakefulness drug effects, Wakefulness physiology, Mice, Inbred C57BL, Vesicular Inhibitory Amino Acid Transport Proteins, Propofol pharmacology, GABAergic Neurons drug effects, GABAergic Neurons metabolism, Basal Forebrain drug effects, Anesthetics, Intravenous pharmacology, Anesthesia, General methods
- Abstract
The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Ltd.)
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- 2024
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14. Retrograde transurethral injection of indocyanine green better assists complete transperitoneal nephroureterectomy in a single-position.
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Song HC, Wu MH, Liu JX, Cao ZB, Du Y, Shi MJ, Song J, and Li XH
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Background: Complete transperitoneal nephroureterectomy (CTNU) in a single-position is an advanced surgical technique for the treatment of upper urinary tract urothelial carcinoma (UTUC), performed entirely through a transperitoneal approach without the need for patient repositioning. Indocyanine green (ICG) has been extensively studied in urologic surgery, with applications ranging from sentinel lymph node mapping to tumor localization. This study aimed to evaluate the performance of retrograde ureteral fluorescence imaging in CTNU., Methods: This retrospective cohort enrolled 81 patients diagnosed with UTUC and underwent single-position CTNU. Cohorts were divided into two groups according to whether the ICG was applied. Perioperative data and oncology outcomes were recorded and analyzed., Results: In total, 81 eligible participants were finally included, with 40 in the ICG group and 41 in the non-ICG group. The ICG group presented significantly shorter ureter identification time (8.5±3.3 vs. 17.3±4.2 min, P<0.001) and duration of surgery (132±40 vs. 162±49 min, P=0.003), as well as lower estimated blood loss (EBL) (108±94 vs. 183±126 mL, P=0.003) compared to the non-ICG group. The rates of intravesical and extravesical carcinoma recurrence were comparable between the two groups. At a median follow-up of 16.7 months, there were no significant differences in terms of the recurrence-free survival (RFS) and overall survival (OS) between groups., Conclusions: ICG guided ureteral fluorescence imaging in single-position CTNU showed significant advantages in precisely and effectively locating the ureter, with improved surgical outcomes. Meanwhile, the enhanced visualization of the ureteral intramural segment and bladder cuff facilitated the complete removal of the specimen en bloc and the watertight closure of the bladder., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-24-247/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)
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- 2024
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15. ANXA3 as a novel biomarker for sepsis diagnosis: Evidence from integrative WGCNA analysis.
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Zhang JX, Xing XH, Lu RY, Liu MX, Xu WH, Zhang HC, Zhao QJ, and Wang Y
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Sepsis is a dysregulated immune response to infection that comes with multiple organ dysfunction and high mortality. The management of sepsis relies heavily on early recognition and diagnosis, but current diagnostic methods have limitations in timeliness, sensitivity, and discriminability. This study aims to discover novel biomarkers for sepsis diagnosis. Four datasets from different regions were analyzed using weighted gene co-expression network analysis (WGCNA), and genes with high Gene Significance values across these datasets were overlapped. Finally, two genes, CD177 and ANXA3 , were identified. ANXA3 was validated as a potential sepsis biomarker by checking multiple datasets and Receiver Operating Characteristic (ROC) Curve Analysis. Of note, ANXA3 could distinguish not only between adult and child sepsis patients and healthy controls, but also between septic shock and cardiogenic shock. Moreover, a murine sepsis model was established and the results showed that the transcription of ANXA3 in peripheral blood of septic mice was significantly higher than that of healthy controls, while Escherichia coli infection alone did not significantly increase the transcription level of this gene. Subsequent studies of sepsis in mice revealed that the predictive effect of Anxa3 on sepsis could be observed as early as 6 h post-modeling. Interestingly, ANXA3 expression was predominantly up-regulated in myeloid cells, up-regulated in spleen, down-regulated in lung, and not detected in liver after sepsis modeling. Taken together, this study provides a way for the discovery of biomarkers and finds that ANXA3 may be a novel diagnostic biomarker for sepsis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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16. Lymph node metastasis diagnosis of postoperative OSCC patients by analyzing extracellular vesicles in drainage fluid based on microfluidic isolation.
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Li ZZ, Cai ZM, Zhu WT, Zhong NN, Cao LM, Wang GR, Xiao Y, Zhu ZQ, Liu XH, Wu K, He RX, Zhao XZ, Liu B, Cai B, and Bu LL
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- Humans, Microfluidics methods, Carcinoma, Squamous Cell surgery, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell metabolism, Biomarkers, Tumor metabolism, Female, Lab-On-A-Chip Devices, Male, Postoperative Period, Middle Aged, Drainage methods, Extracellular Vesicles metabolism, Mouth Neoplasms surgery, Mouth Neoplasms pathology, Mouth Neoplasms metabolism, Lymphatic Metastasis
- Abstract
Lymph node metastasis (LNM) is a typical marker in oral squamous cell carcinoma (OSCC) indicating poor prognosis. Pathological examination by artificial image acquisition and analysis, as the main diagnostic method for LNM, often takes a week or longer which may cause great anxiety of the patient and also retard timely treatment. However, there are few efficient fast LNM diagnosis methods in clinical applications currently. Our previous study profiled the proteomics of extracellular vesicles (EVs) derived from postoperative drainage fluid (PDF) and showed the potential of detecting specific EVs that expressed aspartate β-hydroxylase (ASPH) for LNM diagnosis in OSCC patients. Considering that the analysis of ASPH
+ PDF-EVs is challenging due to their low abundance (counting less than 10% of total EVs in PDF) and the complex EV isolation process of ultra-centrifugation, we developed a facile platform containing two microfluidic chips filled with antibody-modified microbeads to isolate ASPH+ PDF-EVs, with both the capture and retrieval rate reaching around 90%. Clinical sample analysis based on our method revealed that a mean of 6 × 106 /mL ASPH+ PDF-EVs could be isolated from LNM+ OSCC patients compared to 2.5 × 106 /mL in LNM- OSCC ones. When combined with enzyme-linked immunosorbent assay (ELISA) technique that was commonly used in clinical laboratories in hospitals, this microfluidic platform could precisely distinguish postoperative OSCC patients with LNM or not in several hours, which were validated by a double-blind test containing 6 OSCC patients. We believe this strategy has promise for early diagnosis of LNM in postoperative OSCC patients and finally helps guiding timely and reasonable treatment in clinic., (© 2024. The Author(s).)- Published
- 2024
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17. Lnc557 promotes Bombyx mori nucleopolyhedrovirus replication by interacting with BmELAVL1 to enhance its stability and expression.
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Lin S, Shen ZY, Wang MD, Zhou XM, Xu T, Jiao XH, Wang LL, Guo XJ, and Wu P
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- Animals, Viral Proteins metabolism, Viral Proteins genetics, Insect Proteins metabolism, Insect Proteins genetics, Nucleopolyhedroviruses genetics, RNA, Long Noncoding genetics, RNA, Long Noncoding metabolism, Virus Replication, Bombyx virology, Bombyx genetics, Bombyx metabolism
- Abstract
Bombyx mori nucleopolyhedrovirus (BmNPV) is a major pathogen that threatens the growth and sustainability of the sericultural industry. Currently, accumulated studies showed that long non-coding RNAs (lncRNAs) play important roles in the genesis and progression of various viruses and host-pathogens interactions. However, the functions and regulatory mechanisms of lncRNAs in insect-virus interaction are still limited. In this study, transcriptome sequencing and ribosome profiling sequencing (Ribo-seq) were performed in the BmNPV-infected midgut and control tissue, and a total of 9 differentially expressed (DE) lncRNAs and 27 small ORFs (sORFs) with micropeptide coding potential were identified. Among them, lncRNA XR_001139971.3 (lnc557) is verified to be significantly up-regulated upon BmNPV infection and may have the potential to encode a small peptide (ORF-674). The subcellular localization experiment showed that lnc557 was expressed in the cytoplasm. Overexpression of lnc557 promotes BmNPV replication and vice versa. By combining RNA pull-down, mass spectrometry, protein truncation and RNA immunoprecipitation (RIP) assays, we confirmed that lnc557 can bind to the RRM-5 domain of BmELAVL1 protein. Subsequently, we found that lnc557 could promote the expression of BmELAVL1 by enhancing the stability of BmELAVL1. Further, enhancing the expression of BmELAVL1 can promote the proliferation of BmNPV, while knockdown shows the opposite effect. Our data suggest that lnc557-mediated BmELAVL1 expression enhancement could play a positive role in BmNPV replication, which will provide a new insight into the molecular mechanism of interaction between Bombyx mori and virus., Competing Interests: Declaration of competing interest The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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18. GLT-1 downregulation in hippocampal astrocytes induced by type 2 diabetes contributes to postoperative cognitive dysfunction in adult mice.
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Jiao XH, Wan J, Wu WF, Ma LH, Chen C, Dong W, Liu YQ, Jin CH, Sun A, Zhou Y, Li ZY, Liu Q, Wu YQ, and Zhou CH
- Subjects
- Animals, Mice, Male, Diabetes Mellitus, Experimental complications, Diabetes Mellitus, Experimental metabolism, Diet, High-Fat adverse effects, Mice, Transgenic, Excitatory Amino Acid Transporter 2 metabolism, Excitatory Amino Acid Transporter 2 biosynthesis, Excitatory Amino Acid Transporter 2 genetics, Astrocytes metabolism, Postoperative Cognitive Complications etiology, Postoperative Cognitive Complications metabolism, Hippocampus metabolism, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 metabolism, Down-Regulation, Mice, Inbred C57BL
- Abstract
Aims: Type 2 diabetes mellitus (T2DM) is related to an increased risk of postoperative cognitive dysfunction (POCD), which may be caused by neuronal hyperexcitability. Astrocyte glutamate transporter 1 (GLT-1) plays a crucial role in regulating neuron excitability. We investigated if T2DM would magnify the increased neuronal excitability induced by anesthesia/surgery (A/S) and lead to POCD in young adult mice, and if so, determined whether these effects were associated with GLT-1 expression., Methods: T2DM model was induced by high fat diet (HFD) and injecting STZ. Then, we evaluated the spatial learning and memory of T2DM mice after A/S with the novel object recognition test (NORT) and object location test (OLT). Western blotting and immunofluorescence were used to analyze the expression levels of GLT-1 and neuronal excitability. Oxidative stress reaction and neuronal apoptosis were detected with SOD2 expression, MMP level, and Tunel staining. Hippocampal functional synaptic plasticity was assessed with long-term potentiation (LTP). In the intervention study, we overexpressed hippocampal astrocyte GLT-1 in GFAP-Cre mice. Besides, AAV-Camkllα-hM4Di-mCherry was injected to inhibit neuronal hyperexcitability in CA1 region., Results: Our study found T2DM but not A/S reduced GLT-1 expression in hippocampal astrocytes. Interestingly, GLT-1 deficiency alone couldn't lead to cognitive decline, but the downregulation of GLT-1 in T2DM mice obviously enhanced increased hippocampal glutamatergic neuron excitability induced by A/S. The hyperexcitability caused neuronal apoptosis and cognitive impairment. Overexpression of GLT-1 rescued postoperative cognitive dysfunction, glutamatergic neuron hyperexcitability, oxidative stress reaction, and apoptosis in hippocampus. Moreover, chemogenetic inhibition of hippocampal glutamatergic neurons reduced oxidative stress and apoptosis and alleviated postoperative cognitive dysfunction., Conclusions: These findings suggest that the adult mice with type 2 diabetes are at an increased risk of developing POCD, perhaps due to the downregulation of GLT-1 in hippocampal astrocytes, which enhances increased glutamatergic neuron excitability induced by A/S and leads to oxidative stress reaction, and neuronal apoptosis., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
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- 2024
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19. Inflammatory bowel disease and osteoporosis: Common genetic effects, pleiotropy, and causality.
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Hu YQ, Jin XJ, Lei SF, Yu XH, and Bo L
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- Humans, Female, Male, Osteoporosis genetics, Osteoporosis etiology, Inflammatory Bowel Diseases genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Bone Density genetics, Genetic Pleiotropy, Mendelian Randomization Analysis, Linkage Disequilibrium, Polymorphism, Single Nucleotide
- Abstract
Introduction: Previous studies have shown that inflammatory bowel disease (IBD) is associated with osteoporosis (OP) and bone mineral density (BMD), but the underlying genetic mechanisms are unclear. Our study wanted to explore the genetic and causal relationship between IBD and OP., Materials and Methods: Based on large-scale genome-wide association summary statistics and individual-level datasets (i.e., the UK Biobank), this study performed linkage disequilibrium score regression (LDSC), pleiotropic analysis under the composite null hypothesis (PLACO), and Mendelian randomization (MR) analyses to explore the genetic association, the pleiotropic genes and the causal relationship between IBD and BMD., Results: LDSC revealed significant genetic correlations between IBD and BMD (e.g., forearm BMD (rg = -0.3479, P = 0.019) and femoral neck BMD (rg = -0.1335, P = 0.0307). PLACO identified 14 overlapping pleiotropic loci, 1 shared risk gene (CDYL), and multiple shared pathways, revealing possible mechanisms for IBD and OP. MR analysis demonstrated a causal association between IBD and BMD., Conclusions: Our study indicates that IBD may increase the risk of OP and reveals a complex genetic mechanism linking IBD and the risk of osteoporosis, which has important implications for diagnosing and treating IBD and OP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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20. Integrated cell wall and transcriptomic analysis revealed the mechanism underlying zinc-induced alleviation of cadmium toxicity in Cosmos bipinnatus.
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Yu XF, Zeng XX, Wang XY, Du J, Wang XH, Liu YJ, Chen ML, Zhang XY, Xiao X, Yang LJ, Lei T, Gao SP, Li X, Jiang MY, and Tao Q
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- Transcriptome drug effects, Gene Expression Profiling, Gene Expression Regulation, Plant drug effects, Plant Roots drug effects, Plant Roots metabolism, Plant Roots genetics, Cadmium toxicity, Zinc metabolism, Zinc toxicity, Zinc pharmacology, Cell Wall metabolism, Cell Wall drug effects
- Abstract
Plant growth is severely harmed by cadmium (Cd) contamination, while the addition of zinc (Zn) can reduce the toxic effects of Cd. However, the interaction between Cd and Zn on the molecular mechanism and cell wall of Cosmosbipinnatus is unclear. In this study, a transcriptome was constructed using RNA-sequencing. In C. bipinnatus root transcriptome data, the expression of 996, 2765, and 3023 unigenes were significantly affected by Cd, Zn, and Cd + Zn treatments, respectively, indicating different expression patterns of some metal transporters among the Cd, Zn, and Cd + Zn treatments. With the addition of Zn, the damage to the cell wall was reduced, both the proportion and content of polysaccharides in the cell wall were changed, and Cd accumulation was decreased by 32.34%. In addition, we found that Cd and Zn mainly accumulated in pectins, the content of which increased by 30.79% and 61.4% compared to the CK treatment. Thus, Zn could alleviate the toxicity of Cd to C. bipinnatus. This study revealed the interaction between Cd and Zn at the physiological and molecular levels, broadening our understanding of the mechanisms of tolerance to Cd and Zn stress in cosmos., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
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- 2024
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21. Comparison of systematic and combined biopsy for the detection of prostate cancer.
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Huang JL, Huang D, Chun TT, Yao C, Zhan YL, Ruan XH, Lai TC, Tsang CF, Pang KH, Ng AT, Xu DF, Ho BS, and Na R
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- Humans, Male, Middle Aged, Retrospective Studies, Aged, Magnetic Resonance Imaging methods, Biopsy methods, Neoplasm Grading, Prostatic Neoplasms pathology, Prostatic Neoplasms diagnosis, Prostatic Neoplasms diagnostic imaging, Prostate-Specific Antigen blood, Image-Guided Biopsy methods, Prostate pathology, Prostate diagnostic imaging
- Abstract
Abstract: Systematic prostate biopsy has limitations, such as overdiagnosis of clinically insignificant prostate cancer and underdiagnosis of clinically significant prostate cancer. Magnetic resonance imaging (MRI)-guided biopsy, a promising alternative, might improve diagnostic accuracy. To compare the cancer detection rates of systematic biopsy and combined biopsy (systematic biopsy plus MRI-targeted biopsy) in Asian men, we conducted a retrospective cohort study of men who underwent either systematic biopsy or combined biopsy at two medical centers (Queen Mary Hospital and Tung Wah Hospital, Hong Kong, China) from July 2015 to December 2022. Descriptive statistics were calculated, and univariate and multivariate logistic regression analyses were performed. The primary and secondary outcomes were prostate cancer and clinically significant prostate cancer. A total of 1391 participants were enrolled. The overall prostate cancer detection rates did not significantly differ between the two groups (36.3% vs 36.6%, odds ratio [OR] = 1.01, 95% confidence interval [CI]: 0.81-1.26, P = 0.92). However, combined biopsy showed a significant advantage in detecting clinically significant prostate cancer (Gleason score ≥ 3+4) in patients with a total serum prostate-specific antigen (tPSA) concentration of 2-10 ng ml -1 (systematic vs combined: 11.9% vs 17.5%, OR = 1.58, 95% CI: 1.08-2.31, P = 0.02). Specifically, in the transperineal biopsy subgroup, combined biopsy significantly outperformed systematic biopsy in the detection of clinically significant prostate cancer (systematic vs combined: 12.6% vs 24.0%, OR = 2.19, 95% CI: 1.21-3.97, P = 0.01). These findings suggest that in patients with a tPSA concentration of 2-10 ng ml -1 , MRI-targeted biopsy may be of greater predictive value than systematic biopsy in the detection of clinically significant prostate cancer., (Copyright © 2024 Copyright: ©The Author(s)(2024).)
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- 2024
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22. Transurethral enucleation of bladder tumor containing non-functional paraganglioma: A case report.
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Song HC, Liu JX, Song J, and Li XH
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- Humans, Male, Urethra surgery, Treatment Outcome, Middle Aged, Urinary Bladder Neoplasms surgery, Urinary Bladder Neoplasms pathology, Paraganglioma surgery, Paraganglioma diagnostic imaging, Paraganglioma pathology
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- 2024
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23. Giant pelvic malignant solitary fibrous tumor with heart failure: A treatment dilemma.
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Song HC, Wu MH, and Li XH
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- Humans, Pelvic Neoplasms diagnostic imaging, Pelvic Neoplasms surgery, Male, Female, Middle Aged, Solitary Fibrous Tumors surgery, Solitary Fibrous Tumors diagnostic imaging, Solitary Fibrous Tumors pathology, Heart Failure etiology
- Abstract
Competing Interests: Declaration of competing interest The authors declare no conflict of interest for this article.
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- 2024
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24. Less is more: Exploring neoadjuvant immunotherapy as a de-escalation strategy in head and neck squamous cell carcinoma treatment.
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Cao LM, Zhong NN, Chen Y, Li ZZ, Wang GR, Xiao Y, Liu XH, Jia J, Liu B, and Bu LL
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- Humans, Neoadjuvant Therapy methods, Squamous Cell Carcinoma of Head and Neck therapy, Squamous Cell Carcinoma of Head and Neck immunology, Squamous Cell Carcinoma of Head and Neck drug therapy, Squamous Cell Carcinoma of Head and Neck pathology, Head and Neck Neoplasms therapy, Head and Neck Neoplasms immunology, Head and Neck Neoplasms pathology, Head and Neck Neoplasms drug therapy, Immunotherapy methods, Immune Checkpoint Inhibitors therapeutic use
- Abstract
Head and neck squamous cell carcinoma (HNSCC) constitutes a significant global cancer burden, given its high prevalence and associated mortality. Despite substantial progress in survival rates due to the enhanced multidisciplinary approach to treatment, these methods often lead to severe tissue damage, compromised function, and potential toxicity. Thus, there is an imperative need for novel, effective, and minimally damaging treatment modalities. Neoadjuvant treatment, an emerging therapeutic strategy, is designed to reduce tumor size and curtail distant metastasis prior to definitive intervention. Currently, neoadjuvant chemotherapy (NACT) has optimized the treatment approach for a subset of HNSCC patients, yet it has not produced a noticeable enhancement in overall survival (OS). In the contemporary cancer therapeutics landscape, immunotherapy is gaining traction at an accelerated pace. Notably, neoadjuvant immunotherapy (NAIT) has shown promising radiological and pathological responses, coupled with encouraging efficacy in several clinical trials. This potentially paves the way for a myriad of possibilities in treatment de-escalation of HNSCC, which warrants further exploration. This paper reviews the existing strategies and efficacies of neoadjuvant immune checkpoint inhibitors (ICIs), along with potential de-escalation strategies. Furthermore, the challenges encountered in the context of the de-escalation strategies of NAIT are explored. The aim is to inform future research directions that strive to improve the quality of life (QoL) for patients battling HNSCC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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25. MRI T2w Radiomics-Based Machine Learning Models in Imaging Simulated Biopsy Add Diagnostic Value to PI-RADS in Predicting Prostate Cancer: A Retrospective Diagnostic Study.
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Liu JC, Ruan XH, Chun TT, Yao C, Huang D, Wong HL, Lai CT, Tsang CF, Ho SH, Ng TL, Xu DF, and Na R
- Abstract
Background: Currently, prostate cancer (PCa) prebiopsy medical image diagnosis mainly relies on mpMRI and PI-RADS scores. However, PI-RADS has its limitations, such as inter- and intra-radiologist variability and the potential for imperceptible features. The primary objective of this study is to evaluate the effectiveness of a machine learning model based on radiomics analysis of MRI T2-weighted (T2w) images for predicting PCa in prebiopsy cases., Method: A retrospective analysis was conducted using 820 lesions (363 cases, 457 controls) from The Cancer Imaging Archive (TCIA) Database for model development and validation. An additional 83 lesions (30 cases, 53 controls) from Hong Kong Queen Mary Hospital were used for independent external validation. The MRI T2w images were preprocessed, and radiomic features were extracted. Feature selection was performed using Cross Validation Least Angle Regression (CV-LARS). Using three different machine learning algorithms, a total of 18 prediction models and 3 shape control models were developed. The performance of the models, including the area under the curve (AUC) and diagnostic values such as sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were compared to the PI-RADS scoring system for both internal and external validation., Results: All the models showed significant differences compared to the shape control model (all p < 0.001, except SVM model PI-RADS+2 Features p = 0.004, SVM model PI-RADS+3 Features p = 0.002). In internal validation, the best model, based on the LR algorithm, incorporated 3 radiomic features (AUC = 0.838, sensitivity = 76.85%, specificity = 77.36%). In external validation, the LR (3 features) model outperformed PI-RADS in predictive value with AUC 0.870 vs. 0.658, sensitivity 56.67% vs. 46.67%, specificity 92.45% vs. 84.91%, PPV 80.95% vs. 63.64%, and NPV 79.03% vs. 73.77%., Conclusions: The machine learning model based on radiomics analysis of MRI T2w images, along with simulated biopsy, provides additional diagnostic value to the PI-RADS scoring system in predicting PCa.
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- 2024
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26. Single-cell transcriptomics of blood identified IFIT1 + neutrophil subcluster expansion in NTM-PD patients.
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Wang P, Yang GL, He YF, Shen YH, Hao XH, Liu HP, Shen HB, Wang L, and Sha W
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- Humans, Male, Middle Aged, Female, Mycobacterium Infections, Nontuberculous immunology, Mycobacterium Infections, Nontuberculous blood, Mycobacterium Infections, Nontuberculous diagnosis, Mycobacterium avium Complex immunology, Aged, Mycobacterium abscessus immunology, T-Lymphocytes immunology, Adult, Neutrophils immunology, Single-Cell Analysis, RNA-Binding Proteins genetics, RNA-Binding Proteins immunology, Transcriptome, Adaptor Proteins, Signal Transducing genetics
- Abstract
Objective: Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is caused by an imbalance between pathogens and impaired host immune responses. Mycobacterium avium complex (MAC) and Mycobacterium abscessus (MAB) are the two major pathogens that cause NTM-PD. In this study, we sought to dissect the transcriptomes of peripheral blood immune cells at the single-cell resolution in NTM-PD patients and explore potential clinical markers for NTM-PD diagnosis and treatment., Methods: Peripheral blood samples were collected from six NTM-PD patients, including three MAB-PD patients, three MAC-PD patients, and two healthy controls. We employed single-cell RNA sequencing (scRNA-seq) to define the transcriptomic landscape at a single-cell resolution. A comprehensive scRNA-seq analysis was performed, and flow cytometry was conducted to validate the results of scRNA-seq., Results: A total of 27,898 cells were analyzed. Nine T-cells, six mononuclear phagocytes (MPs), and four neutrophil subclusters were defined. During NTM infection, naïve T-cells were reduced, and effector T-cells increased. High cytotoxic activities were shown in T-cells of NTM-PD patients. The proportion of inflammatory and activated MPs subclusters was enriched in NTM-PD patients. Among neutrophil subclusters, an IFIT1
+ neutrophil subcluster was expanded in NTM-PD compared to healthy controls. This suggests that IFIT1+ neutrophil subcluster might play an important role in host defense against NTM. Functional enrichment analysis of this subcluster suggested that it is related to interferon response. Cell-cell interaction analysis revealed enhanced CXCL8-CXCR1/2 interactions between the IFIT1+ neutrophil subcluster and NK cells, NKT cells, classical mononuclear phagocytes subcluster 1 (classical Mo1), classical mononuclear phagocytes subcluster 2 (classical Mo2) in NTM-PD patients compared to healthy controls., Conclusions: Our data revealed disease-specific immune cell subclusters and provided potential new targets of NTM-PD. Specific expansion of IFIT1+ neutrophil subclusters and the CXCL8-CXCR1/2 axis may be involved in the pathogenesis of NTM-PD. These insights may have implications for the diagnosis and treatment of NTM-PD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
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27. The role of SEMG1 overexpression in OSCC tumorigenesis and its relation with metabolic molecules.
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Wang J, Zhong NN, Yi JR, Liu XH, Wang HQ, Liu B, Man QW, and Bu LL
- Abstract
Objectives: This study aimed to investigate the expression and biological significance of Semenogelin 1 (SEMG1), a member of the cancer-testis antigen family, in oral squamous cell carcinoma (OSCC). Further, we explored its potential association with metabolism-related molecules., Methods: SEMG1 expression levels in OSCC were determined through immunohistochemistry, flow cytometry, and Western blot analyses. To decipher the biological implications of SEMG1 in OSCC, the CAL27 OSCC cell line was either stably overexpressed with SEMG1 or subjected to SEMG1-shRNA knockdown. The relationship between clinicopathological parameters and SEMG1 expression in OSCC patients was also assessed., Results: SEMG1 was found to be overexpressed in OSCC, though its expression was not influenced by the pathological grade. The fluorescent dihydroethidium assay indicated that SEMG1 augmented reactive oxygen species production. The mitochondrial membrane potential assay suggested a significant upregulation of mitochondrial membrane potential by SEMG1. Cell cycle assessments highlighted that SEMG1 overexpression led to a notable rise in cells entering the S-phase. Additionally, a strong correlation between SEMG1 expression and both ENO1 and PKM2 expression in OSCC was observed., Conclusions: The findings underscore the elevated expression of SEMG1 in OSCC and its contributory role in the tumorigenesis of OSCC patients., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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28. Incomplete Histologic Healing and Diminished Biomechanical Strength of Meniscus-Bone Interface After Medial Meniscus Posterior Root Transosseous Repair in a Goat Model.
- Author
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Deng XH, Wang JS, Chen Z, Zeng WK, Peng HM, Yan WT, Jiang C, Song B, Li WP, and Zhang ZZ
- Abstract
Purpose: To enhance the understanding of histologic healing after repairing medial meniscal posterior root tears (MMPRTs) at an early stage, utilizing a goat model., Methods: Eighteen adult goats, totaling 36 knee joints, were allocated into 3 groups (n = 12): sham group (Sham), root tear group (RT), and root tear with transosseous suture group (RTS). At 12- and 24-week intervals postsurgery, all the knees were harvested for imaging, macroscopic, histologic, and biomechanical assessments., Results: The intact root served as a meniscus-bone interface that connected the tibial and circular fibers of the meniscus with a bony insertion and a root-meniscus transition. A direct fibrous connection was displayed at the bony insertion proximal to the synovium in the RTS group, while the remaining regions of the root displayed indirect fibrous healing. The healing in the RT group was disjointed and reminiscent of scar tissue. The RTS group exhibited a more pronounced coronal extrusion compared to the Sham group (0.42 ± 0.09 vs 0.19 ± 0.02, P = .0012) but was improved relative to that of the RT group (0.49 ± 0.02, P = .0028). The failure load and stiffness of the RTS group were notably higher than those of the RT group, with a strength of 42.67% and a stiffness of 83.75% of the intact root. All the samples ruptured at the root-meniscus transitions., Conclusions: The incomplete healing may be attributed to the histologic factors underlying the low healing rate and persistent medial meniscal extrusion. Notably, the region attached to the posterior cruciate ligament exhibited superior healing compared to other regions of the bony insertion in the repaired group. Conversely, the root-meniscus transition displayed discontinuity, representing a mechanical weakness in the healing process., Clinical Relevance: Modifications of bone tunnel positioning and suture placement could be undertaken in subsequent studies to enhance the healing of the root-meniscus transition., Competing Interests: Disclosures The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was supported by National Natural Science Foundation of China (82022046, 82172416), Natural Science Foundation of Guangdong Province (2020B1515020014, 2022A1515011714, 2022A1515010215), Guangdong Basic and Applied Basic Research Foundation (2021A1515012337), Guangdong Science and Technology Collaborative Innovation Center for Sports (2019B110210004), and Fundamental Research Funds for the Central Universities (23xkjc006). All authors (X-H.D., J-S.W., Z.C., W-K.Z., H-M.P., W-T.Y., C.J., B.S., W-P.L., Z-Z.Z.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)
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- 2024
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29. Lewis Acid Catalyzed Cycloaddition of Bicyclobutanes with Ynamides for the Synthesis of Polysubstituted 2-Amino-bicyclo[2.1.1]hexenes.
- Author
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Hu QQ, Wang LY, Chen XH, Geng ZX, Chen J, and Zhou L
- Abstract
Synthesis of bicyclic scaffolds has gained significant attention in drug discovery due to their potential to mimic benzene bioisosteres. Here, we present a mild and scalable Sc(OTf)
3 -catalyzed [3+2] cycloaddition of bicyclo[1.1.0]butanes (BCBs) with ynamides, yielding a diverse array of polysubstituted 2-amino-bicyclo[2.1.1]hexenes in good to excellent yields. These products offer valuable starting materials for the construction of novel functionalized bicyclo[1.1.0]butanes. Preliminary mechanistic studies indicate that the reaction involves a nucleophilic addition of ynamides to bicyclo[1.1.0]butanes, followed by an intramolecular cyclization of in situ generated enolate and keteniminium ion. We expect that these findings will encourage utilization of complex bioisosteres and foster further investigation into BCB-based cycloaddition chemistry., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
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30. Constructing B─N─P Bonds in Ultrathin Holey g-C 3 N 4 for Regulating the Local Chemical Environment in Photocatalytic CO 2 Reduction to CO.
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Hussien MK, Sabbah A, Qorbani M, Putikam R, Kholimatussadiah S, Tzou DM, Elsayed MH, Lu YJ, Wang YY, Lee XH, Lin TY, Thang NQ, Wu HL, Haw SC, Wu KC, Lin MC, Chen KH, and Chen LC
- Abstract
The lack of intrinsic active sites for photocatalytic CO
2 reduction reaction (CO2 RR) and fast recombination rate of charge carriers are the main obstacles to achieving high photocatalytic activity. In this work, a novel phosphorus and boron binary-doped graphitic carbon nitride, highly porous material that exhibits powerful photocatalytic CO2 reduction activity, specifically toward selective CO generation, is disclosed. The coexistence of Lewis-acidic and Lewis-basic sites plays a key role in tuning the electronic structure, promoting charge distribution, extending light-harvesting ability, and promoting dissociation of excitons into active carriers. Porosity and dual dopants create local chemical environments that activate the pyridinic nitrogen atom between the phosphorus and boron atoms on the exposed surface, enabling it to function as an active site for CO2 RR. The P-N-B triad is found to lower the activation barrier for reduction of CO2 by stabilizing the COOH reaction intermediate and altering the rate-determining step. As a result, CO yield increased to 22.45 µmol g-1 h-1 under visible light irradiation, which is ≈12 times larger than that of pristine graphitic carbon nitride. This study provides insights into the mechanism of charge carrier dynamics and active site determination, contributing to the understanding of the photocatalytic CO2 RR mechanism., (© 2024 Wiley‐VCH GmbH.)- Published
- 2024
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31. Role of the circRNA_34414/miR-6960a-5p/SIRT3 axis in postoperative delirium via CA1 Vglut1+ neurons in older mice.
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Wang HB, Liu Q, Liu YP, Dong W, Wan J, Jiao XH, Wu YQ, Li TZ, and Miao HH
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- Animals, Mice, Male, CA1 Region, Hippocampal metabolism, CA1 Region, Hippocampal drug effects, Mice, Inbred C57BL, Tibial Fractures surgery, Membrane Potential, Mitochondrial drug effects, Membrane Potential, Mitochondrial physiology, Sirtuin 3 metabolism, Sirtuin 3 genetics, Delirium metabolism, MicroRNAs metabolism, MicroRNAs genetics, RNA, Circular metabolism, Neurons metabolism, Neurons drug effects, Postoperative Complications metabolism
- Abstract
Aims: Postoperative delirium (POD) is a common neurological complication in elderly patients after anesthesia/surgery. The main purpose of this study is to explore the effect of circRNA-targeted miRNA regulating SIRT3 on mitochondrial function through ceRNA mechanism under the surgical model of tibial fracture and to further explore the potential mechanism of postoperative delirium mediated by circRNA, so as to provide new ideas for clinical diagnosis and prevention of POD., Methods: The surgical model of tibial fracture under sevoflurane anesthesia caused acute delirium-like behavior in elderly mice. We observed that the decrease of SIRT3 and mitochondrial dysfunction was related to POD, and miRNA and circRNA (circRNA_34414) related to SIRT3 were further studied. Through luciferase and RAP, we observed that circRNA_34414, as a miRNA sponge, was involved in the regulation of SIRT3 expression., Results: Postoperative delirium in elderly mice showed decreased expression of hippocampal circRNA_34414, increased expression of miR-6960-5p, decreased expression of SIRT3, and impaired mitochondrial membrane potential. Overexpression of circRNA_34414, or knockdown of miR-6960-5p, or overexpression of SIRT3 in hippocampal CA1 glutamatergic neurons significantly upregulated hippocampal SIRT3 expression, increased mitochondrial membrane potential levels, and significantly ameliorated postoperative delirium in aged mice; CircRNA_34414 ameliorates postoperative delirium in mice, possibly by targeting miR-6960-5p to upregulate SIRT3., Conclusions: CircRNA_34414 is involved in the improvement of postoperative delirium induced by anesthesia/surgery by upregulating SIRT3 via sponging miR-6960-5p., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
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- 2024
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32. BLA-involved circuits in neuropsychiatric disorders.
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Ma LH, Li S, Jiao XH, Li ZY, Zhou Y, Zhou CR, Zhou CH, Zheng H, and Wu YQ
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- Humans, Animals, Basolateral Nuclear Complex physiology, Basolateral Nuclear Complex physiopathology, Mental Disorders physiopathology, Mental Disorders therapy
- Abstract
The basolateral amygdala (BLA) is the subregion of the amygdala located in the medial of the temporal lobe, which is connected with a wide range of brain regions to achieve diverse functions. Recently, an increasing number of studies have focused on the participation of the BLA in many neuropsychiatric disorders from the neural circuit perspective, aided by the rapid development of viral tracing methods and increasingly specific neural modulation technologies. However, how to translate this circuit-level preclinical intervention into clinical treatment using noninvasive or minor invasive manipulations to benefit patients struggling with neuropsychiatric disorders is still an inevitable question to be considered. In this review, we summarized the role of BLA-involved circuits in neuropsychiatric disorders including Alzheimer's disease, perioperative neurocognitive disorders, schizophrenia, anxiety disorders, depressive disorders, posttraumatic stress disorders, autism spectrum disorders, and pain-associative affective states and cognitive dysfunctions. Additionally, we provide insights into future directions and challenges for clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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33. A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.
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Song BL, Wang JQ, Zhang GX, Yi NB, Zhang YJ, Zhou L, Guan YH, Zhang XH, Zheng WF, Qiao ZY, and Wang H
- Subjects
- Humans, Animals, Peptides chemistry, Peptides metabolism, Nanoparticles chemistry, Mice, Nanofibers chemistry, Cell Line, Tumor, Mitochondria metabolism, Reactive Oxygen Species metabolism, Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Antineoplastic Agents chemical synthesis, Porphyrins chemistry
- Abstract
The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies., (© 2024 Wiley-VCH GmbH.)
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- 2024
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34. CHIP-mediated ubiquitin degradation of BCAT1 regulates glioma cell proliferation and temozolomide sensitivity.
- Author
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Lu Z, Wang XY, He KY, Han XH, Wang X, Zhang Z, Qu XH, Chen ZP, Han XJ, and Wang T
- Subjects
- Humans, Animals, Cell Line, Tumor, Mice, Mice, Nude, Ubiquitin metabolism, Brain Neoplasms metabolism, Brain Neoplasms pathology, Brain Neoplasms genetics, Brain Neoplasms drug therapy, Proteolysis drug effects, Male, Gene Expression Regulation, Neoplastic drug effects, Female, Temozolomide pharmacology, Temozolomide therapeutic use, Ubiquitin-Protein Ligases metabolism, Ubiquitin-Protein Ligases genetics, Cell Proliferation drug effects, Glioma metabolism, Glioma pathology, Glioma genetics, Glioma drug therapy, Ubiquitination, Transaminases metabolism, Transaminases genetics
- Abstract
Glioma, a malignant and infiltrative neoplasm of the central nervous system, poses a significant threat due to its high mortality rates. Branched-chain amino acid transaminase 1 (BCAT1), a key enzyme in branched-chain amino acid (BCAA) catabolism, exhibits elevated expression in gliomas and correlates strongly with poor prognosis. Nonetheless, the regulatory mechanisms underlying this increased BCAT1 expression remains incompletely understood. In this study, we reveal that ubiquitination at Lys360 facilitates BCAT1 degradation, with low ubiquitination levels contributing to high BCAT1 expression in glioma cells. The Carboxyl terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase, interacts with BCAT1 via its coiled-coil (CC) domain, promoting its K48-linkage ubiquitin degradation through proteasomal pathway. Moreover, CHIP-mediated BCAT1 degradation induces metabolic reprogramming, and impedes glioma cell proliferation and tumor growth both in vitro and in vivo. Furthermore, a positive correlation is observed between low CHIP expression, elevated BCAT1 levels, and unfavorable prognosis among glioma patients. Additionally, we show that the CHIP/BCAT1 axis enhances glioma sensitivity to temozolomide by reducing glutathione (GSH) synthesis and increasing oxidative stress. These findings underscore the critical role of CHIP/BCAT1 axis in glioma cell proliferation and temozolomide sensitivity, highlighting its potential as a diagnostic marker and therapeutic target in glioma treatment., (© 2024. The Author(s).)
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- 2024
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35. Electrocatalytic water-to-oxygenates conversion: redox-mediated versus direct oxygen transfer.
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Leng BL, Lin X, Chen JS, and Li XH
- Abstract
Electrocatalytic oxygenation of hydrocarbons with high selectivity has attracted much attention for its advantages in the sustainable and controllable production of oxygenated compounds with reduced greenhouse gas emissions. Especially when utilizing water as an oxygen source, by constructing a water-to-oxygenates conversion system at the anode, the environment and/or energy costs of producing oxygenated compounds and hydrogen energy can be significantly reduced. There is a broad consensus that the generation and transformation of oxygen species are among the decisive factors determining the overall efficiency of oxygenation reactions. Thus, it is necessary to elucidate the oxygen transfer process to suggest more efficient strategies for electrocatalytic oxygenation. Herein, we introduce oxygen transfer routes through redox-mediated pathways or direct oxygen transfer methods. Especially for the scarcely investigated direct oxygen transfer at the anode, we aim to detail the strategies of catalyst design targeting the efficient oxygen transfer process including activation of organic substrate, generation/adsorption of oxygen species, and transformation of oxygen species for oxygenated compounds. Based on these examples, the significance of balancing the generation and transformation of oxygen species, tuning the states of organic substrates and intermediates, and accelerating electron transfer for organic activation for direct oxygen transfer has been elucidated. Moreover, greener organic synthesis routes through heteroatom transfer and molecular fragment transfer are anticipated beyond oxygen transfer.
- Published
- 2024
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36. [Risk factors for recurrence of childhood acute lymphoblastic leukemia after treatment with the Chinese Children's Cancer Group ALL-2015 protocol].
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Chen X, Lei XY, Guan XM, Dou Y, Wen XH, Guo YX, Gao HQ, and Yu J
- Subjects
- Humans, Child, Male, Female, Risk Factors, Child, Preschool, Retrospective Studies, Infant, Recurrence, Adolescent, Antineoplastic Combined Chemotherapy Protocols therapeutic use, East Asian People, Precursor Cell Lymphoblastic Leukemia-Lymphoma drug therapy, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics
- Abstract
Objectives: To investigate the cumulative incidence of recurrence (CIR) in children with acute lymphoblastic leukemia (ALL) after treatment with the Chinese Children's Cancer Group ALL-2015 (CCCG-ALL-2015) protocol and the risk factors for recurrence., Methods: A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019. CIR was calculated, and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia (B-ALL) were analyzed., Results: Among the 852 children with ALL, 146 (17.1%) experienced recurrence, with an 8-year CIR of 19.8%±1.6%. There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group ( P >0.05). For the 146 children with recurrence, recurrence was mainly observed in the very early stage ( n =62, 42.5%) and the early stage ( n =46, 31.5%), and there were 42 children with bone marrow recurrence alone (28.8%) in the very early stage and 27 children with bone marrow recurrence alone (18.5%) in the early stage. The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene ( HR =4.177, 95% CI : 2.086-8.364, P <0.001) and minimal residual disease≥0.01% on day 46 ( HR =2.013, 95% CI : 1.163-3.483, P =0.012) were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol., Conclusions: There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol, mainly bone marrow recurrence alone in the very early stage and the early stage, and minimal residual disease≥0.01% on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.
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- 2024
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37. Combined detection of serum EFNA1 and MMP13 as diagnostic biomarker for gastric cancer.
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Chu LY, Wu FC, Guo HP, Xie JJ, Qu QQ, Li XH, Xu YW, Peng YH, and Qiu B
- Subjects
- Humans, Female, Male, Middle Aged, Aged, ROC Curve, Adult, Case-Control Studies, Early Detection of Cancer methods, Stomach Neoplasms blood, Stomach Neoplasms diagnosis, Biomarkers, Tumor blood, Matrix Metalloproteinase 13 blood
- Abstract
We previously identified that serum EFNA1 and MMP13 were potential biomarker for early detection of esophageal squamous cell carcinoma. In this study, our aim is to explore the diagnostic value of serum EFNA1 and MMP13 for gastric cancer. We used enzyme-linked immunosorbent assay (ELISA) to detect the expression levels of serum EFNA1 and MMP13 in 210 GCs and 223 normal controls. The diagnostic value of EFNA1 and MMP13 was evaluated in an independent cohorts of GC patients and normal controls (n = 238 and 195, respectively). Receiver operating characteristics were used to calculate diagnostic accuracy. In training and validation cohorts, serum EFNA1 and MMP13 levels in the GC groups were significantly higher than those in the normal controls (P < 0.001). The area under the curve (AUC) of the combined detection of serum EFNA1 and MMP13 for GC was improved (0.794), compared with single biomarker used. Similar results were observed in the validation cohort. Importantly, the combined measurement of serum EFNA1 and MMP13 to detect early-stage GC also had acceptable diagnostic accuracy in training and validation cohort. Combined detection of serum EFNA1 and MMP13 could help identify early-stage GC, suggesting that it may be a promising tool for the early detection of GC., (© 2024. The Author(s).)
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- 2024
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38. Electron Divergence of Cu δ- and Pd δ+ in Cu 3 Pd Alloy-Based Heterojunctions Boosts Concerted C≡C Bond Binding and the Volmer Step for Alkynol Semihydrogenation.
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Lin X, Hu FS, Li QY, Xu D, Xu YS, Zhang Z, Chen JS, and Li XH
- Abstract
Electrocatalytic semihydrogenation of alkynols presents a sustainable alternative to conventional thermal methodologies for the high-value production of alkenols. The design of efficient catalysts with superior catalytic and energy efficiency for semihydrogenation poses a significant challenge. Here, we present the application of an electron-divergent Cu
3 Pd alloy-based heterojunction in promoting the electrocatalytic semihydrogenation of alkynols to alkenols using water as the proton source. The tunable electron divergence of Cuδ- and Pdδ+ , modulated by rectifying contact with nitrogen-rich carbons, enables the concerted binding of active H species from the Volmer step of water dissociation and the C≡C bond of alkynols on Pdδ+ sites. Simultaneously, the pronounced electron divergence of Cu3 Pd facilitates the universal adsorption of OH species from the Volmer step and alkynols on the Cuδ- sites. The electron-divergent dual-center substantially boosts water dissociation and inhibition of completing hydrogen evolution to give a turnover frequency of 2412 h-1 , outperforming the reported electrocatalysts' value of 7.3. Moreover, the continuous production of alkenols at industrial-related current density (-200 mA cm-2 ) over the efficient and durable Cu3 Pd-based electrolyzer could achieve a cathodic energy efficiency of 45 mol kW·h-1 , 1.7 times the bench-marked reactors, promising great potential for sustainable industrial synthesis.- Published
- 2024
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39. Human amniotic mesenchymal stem cells-derived conditioned medium and exosomes alleviate oxidative stress-induced retinal degeneration by activating PI3K/Akt/FoxO3 pathway.
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Peng ZQ, Guan XH, Yu ZP, Wu J, Han XH, Li MH, Qu XH, Chen ZP, Han XJ, and Wang XY
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- Humans, Culture Media, Conditioned pharmacology, Apoptosis, Cells, Cultured, Reactive Oxygen Species metabolism, Membrane Potential, Mitochondrial, Blotting, Western, Animals, Cell Survival, Hydrogen Peroxide toxicity, Oxidative Stress, Mesenchymal Stem Cells metabolism, Exosomes metabolism, Amnion cytology, Phosphatidylinositol 3-Kinases metabolism, Proto-Oncogene Proteins c-akt metabolism, Retinal Degeneration metabolism, Retinal Degeneration pathology, Retinal Degeneration etiology, Signal Transduction, Forkhead Box Protein O3 metabolism, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology
- Abstract
Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H
2 O2 -induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2 O2 -induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)- Published
- 2024
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40. Circulating miRNA-21 as a diagnostic biomarker for acute coronary syndrome: a systematic review and meta-analysis of diagnostic test accuracy study.
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He JG, Li S, Wu XX, Chen XH, Yan D, Wang XJ, and Dang ZW
- Abstract
Background: Both early detection and treatment for acute coronary syndrome (ACS) have positively affected prognosis. A microRNA, miRNA-21 (miR-21), may have additional diagnostic potential for ACS among the others. This systematic review and meta-analysis aimed to evaluate the potential role of miR-21 in identifying ACS., Methods: PubMed, EMBASE and CENTRAL databases were searched up to March 17, 2024, for case-control and cohort studies assessing the diagnostic value of circulating miR-21 in patients with ACS. The search was limited to studies published in either English or Chinese. The primary outcome was the discriminative ability to circulate miR-21 for ACS, represented by the area under the standard receiver operating characteristic curve (AUC) analysis. Meta-analyses combined the AUCs using a random-effects model. Heterogeneity among the studies was detected by the I
2 and Q statistics. The quality of the studies included was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. Publication bias analysis was assessed constructing by the Egger's test (PROSPERO: CRD42020209424)., Results: Eleven case-control studies containing a total of 2,413 subjects with 1,236 ACS cases and 1,177 controls were included. The mean age of participants in these studies ranges between 51.0 and 69.0 years. The meta-analysis showed an overall pooled AUC of 0.779 [95% confidence interval (CI): 0.715-0.843], with high heterogeneity noted between the studies (Q statistic =190.64, I2 =94.23%, P<0.001). In subgroup analyses according to the subtypes of ACS, a pooled AUC of 0.767 (95% CI: 0.648-0.887) was derived from the studies focused on acute myocardial infarction cases only. The pooled AUC for unstable angina was 0.770 (95% CI: 0.718-0.822). In subgroup analyses according to the types of control groups, pooled AUC for ACS versus healthy controls was 0.779 (95% CI: 0.715-0.843), whereas the pooled AUC for ACS versus unhealthy controls was 0.740 (95% CI: 0.645-0.836). The quality assessment showed that the studies' overall quality was moderate. No evidence of publication bias was noted (P=0.49)., Conclusions: Circulating miR-21 shows abilities to differentiate between ACS and non-ACS, suggesting its potential as a novel diagnostic biomarker for ACS. However, the evidence is weakened by high heterogeneity observed among the studies. Further research is essential before it can be applied in clinical practice., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-23-385/coif). The authors have no conflicts of interest to declare., (2024 Cardiovascular Diagnosis and Therapy. All rights reserved.)- Published
- 2024
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41. Effect of exogenous γ-aminobutyric acid on physiological property, antioxidant activity, and cadmium uptake of quinoa seedlings under cadmium stress.
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Hao XH, Liu KX, and Zhang MY
- Subjects
- Plant Roots metabolism, Plant Roots growth & development, Plant Roots drug effects, Malondialdehyde metabolism, Stress, Physiological drug effects, Superoxide Dismutase metabolism, Photosynthesis drug effects, Oxidative Stress drug effects, Seedlings drug effects, Seedlings metabolism, Seedlings growth & development, Cadmium metabolism, Cadmium toxicity, Chenopodium quinoa metabolism, Chenopodium quinoa drug effects, Chenopodium quinoa growth & development, gamma-Aminobutyric Acid metabolism, Antioxidants metabolism, Hydrogen Peroxide metabolism
- Abstract
Increasing cadmium (Cd) pollution has negative effects on quinoa growth and production. Gamma-aminobutyric acid (GABA) confers plants with stress resistance to heavy metals; however, the mechanism remains unclear. We explored the effects of exogenous GABA on the physiological characteristics, antioxidant capacity, and Cd accumulation of quinoa seedlings under Cd stress using hydroponic experiments. Partial least-squares regression was used to identify key physical and chemical indices of seedlings affecting Cd accumulation. Compared with those of the CK group, exposure to 10 and 25 µmol·L-1 Cd significantly reduced the photosynthetic pigment contents, photosynthesis, and biomass accumulation of quinoa seedlings; resulted in shorter and thicker roots; decreased the length of the lateral roots; decreased the activities of superoxide dismutase (SOD) and peroxide (POD); and increased H2O2 and malondialdehyde (MDA) contents. Exogenous GABA reduced the Cd content in the stem/leaves and roots of quinoa seedlings under Cd stress by 13.22-21.63% and 7.92-28.32%, decreased Cd accumulation by 5.37-6.71% and 1.91-4.09%, decreased the H2O2 content by 38.21-47.46% and 45.81-55.73%, and decreased the MDA content by 37.65-48.12% and 29.87-32.51%, respectively. GABA addition increased the SOD and POD activities in the roots by 2.78-5.61% and 13.81-18.33%, respectively, under Cd stress. Thus, exogenous GABA can reduce the content and accumulation of Cd in quinoa seedlings by improving the photosynthetic characteristics and antioxidant enzyme activity and reducing the degree of lipid peroxidation in the cell membrane to alleviate the toxic effect of Cd stress on seedling growth., (© 2024 The Author(s).)
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- 2024
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42. Robust Quantum Gates against Correlated Noise in Integrated Quantum Chips.
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Yi K, Hai YJ, Luo K, Chu J, Zhang L, Zhou Y, Song Y, Liu S, Yan T, Deng XH, Chen Y, and Yu D
- Abstract
As quantum circuits become more integrated and complex, additional error sources that were previously insignificant start to emerge. Consequently, the fidelity of quantum gates benchmarked under pristine conditions falls short of predicting their performance in realistic circuits. To overcome this problem, we must improve their robustness against pertinent error models besides isolated fidelity. Here, we report the experimental realization of robust quantum gates in superconducting quantum circuits based on a geometric framework for diagnosing and correcting various gate errors. Using quantum process tomography and randomized benchmarking, we demonstrate robust single-qubit gates against quasistatic noise and spatially correlated noise in a broad range of strengths, which are common sources of coherent errors in large-scale quantum circuits. We also apply our method to nonstatic noises and to realize robust two-qubit gates. Our Letter provides a versatile toolbox for achieving noise-resilient complex quantum circuits.
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- 2024
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43. [Prediction of liberation cutting intensity effect on the growth of Korean pine in secondary forest based on double dummy variable model].
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Hao XH, Mu CC, Cui YR, Ji WH, Xu W, and Zhao HM
- Subjects
- China, Models, Theoretical, Ecosystem, Conservation of Natural Resources, Forecasting, Pinus growth & development, Forests
- Abstract
"Planting conifer and reserving broadleaved tree" is an effective way to restore broad-leaved pine forest of temperate zone in Northeast China. Liberation cutting can promote the growth of Korean pine ( Pinus koraiensis ) under forest crown and accelerate the succession. However, how liberation cutting intensity affects the growth of Korean pine in secondary forest is still unclear. Taking the "Planting conifer and reserving broadleaved tree" Korean pine forest in Changbai Mountain as the object, we constructed a growth model of diameter at breast height (DBH) and tree height of Korean pine with double dummy variables (liberation cutting intensity and tree classification) to predict the growth of Korean pine plantation under different liberation cutting intensities, i.e . control (no liberation cutting), light-intensity liberation cutting (retaining upper canopy closure 0.6), medium-intensity liberation cutting (0.4), heavy-intensity liberation cutting (0.2) and clear cutting (cutting all upper broadleaf trees) stands. We analyzed the effects of liberation cutting intensities on DBH, tree height, and the ratio of tree height to DBH. The results showed that among six theoretical growth equations, the Gompertz model on the DBH ( R
2 =0.46) and tree height ( R2 =0.81) was optimal basic model. The R2 of the DBH model was increased to 0.65 and 0.89, respectively, after the single dummy variable and the double dummy variable were introduced into the basic model, while the R2 of the tree height model was increased to 0.84 and 0.94. Therefore, the double dummy variable model was the most suitable for predicting the growth of Korean pine. The growth of DBH of pressed tree increased with the increases of liberation cutting intensity (increase by 145.8%-933.3%) during the whole simulation period (0-80 a). Average and dominant trees showed the same pattern at 42 and 60 a. In the early and middle stages of liberation cutting (20 and 42 a), clear cutting and heavy-intensity liberation cutting had similar effects on the height growth of dominant trees (64.8%-68.5%), average trees (100.0%-144.2%), and pressed trees (138.5%-183.9%). The effects of medium-intensity liberation cutting and light-intensity liberation cutting on the height growth were similar (24.3%-35.1%, 56.0%-92.3%, 84.6%-103.2%). While in the middle and late period (42 and 80 a), height growth of three grade trees increased with the increases of liberation cutting intensity. Under each liberation cutting intensity, the ratio of height to DBH of the dominant, average, and pressed trees increased successively, ranging from 0.50-0.95, 0.64-1.23, and 0.73-4.33, respectively. Only the pressed tree decreased with the increases of liberation cutting intensity at 0-80 a. Therefore, about 40 years after the implementation of liberation cutting, the promoting effect of different liberation cutting intensities on DBH growth was significantly weakened, the promoting effect on tree height growth was significantly enhanced, and the ratio of tree height to diameter began to increase. In order to alleviate forest competition, second liberation cutting should be carried out for light-intensity liberation cutting and medium-intensity liberation cutting stands to further release the growth potential of Korean pine, and thinning management should be carried out in clear cutting and heavy-intensity liberation cutting stands.- Published
- 2024
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44. [Exploration of cancer biological characteristics in people with different five movements and six climates constitution based on pan-cancer Bulk RNA-Seq].
- Author
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Tang XH, Chu BW, Li CT, Wang YF, Xia ZH, Li ZM, Tian XY, Wang CY, Chen Q, Hao S, Tao W, Wang JM, Wu MH, and Zheng XH
- Subjects
- Humans, Precision Medicine, RNA-Seq, Medicine, Chinese Traditional, Body Constitution genetics, Neoplasms genetics, Neoplasms drug therapy
- Abstract
According to the theory of five movements and six climates, the innate constitution plays a crucial role in determining the underlyingpa thological mechanisms of diseases later in life. Previous studies have demonstrated a close association between the constitution, as defined by the theory of five movements and six climates, and the development of various types of tumors. Furt hermore,the tumorsubtype determined by the constitution has prognostic implications. This highlights the potential of utilizing the fivemovements and six climates theory to guide the implementation of precision medicine strategies in thefield of oncology. However, no resear ch has yet been conducted to investigate the use of this theory in guiding the development of tumor molecular classification and precisi onmedicine strategies. The objective of this research is to uncover the biological characteristics of each constitution within a pancanc ercohort and identify potential anti-tumor drugs that are applicable to patients with different constitutional types. By doing so, we aimto c ontribute to the establishment of a precision medicine strategy for tumors derived from the original concepts of traditional Chi nesemedicine(TCM). In this study, we obtainedpan-cancer Bulk RNA-Seq data from UCSC Xena, GWAS cohort data from the UKBiobank, and cis-eQTLs data from eQ TLGen and GTEx V8. We employed machine learning methods to screen for hub genes associated with each constitution. Subsequently, we utilized informatics tools to explore the biological characteristics of each constitut iondefined by the theory of five movements and six bioclimates. Further, potential anti-tumor drugs suitable for patients with differen tconstitutional types were identified through mendelian randomization, molecular docking, and drug-like prediction techniques. Withinthe pan-cancer cohort, significant differences were observed among different constitutions in terms of progression-free interval, biological f unctions, immune cell abundance, tumor drug sensitivity, and immunotherapy response. These findings suggest that the five movements and six climates theory can guide tumor molecular classification and the development of precision medicine strategies. Moreover,the biological characteristics inherent to each constitution partially shed light on the scientific implications of Chinese medicinetheories, offering a fresh perspective towards clinical cancer treatment. Through molecular docking and drug-like prediction, several po tential anti-tumor drugs such as 17-beta-estradiol, serotonin, trans-resveratrol, and linoleic acid were identified. Overall, the util izationof multi-omics approaches pro vides a powerful tool to unravel the scientific foundations of TCM theories. The elucidation of themu lti-omics features associated witheach constitution in tumors serves as the basis for applying the five movements and six climates theoryto tumor molecular classification and the development of precision medicine strategies.
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- 2024
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45. [The Efficacy and Influencing Factors of Cyclosporine Alone in the Treatment of Children with Acquired Aplastic Anemia].
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Qin HC, Guan XM, Hu YN, Lei XY, Dou Y, Yu J, and Wen XH
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- Humans, Female, Male, Child, Treatment Outcome, Platelet Count, Immunosuppressive Agents therapeutic use, Child, Preschool, Adolescent, Bone Marrow, Anemia, Aplastic drug therapy, Cyclosporine therapeutic use
- Abstract
Objective: To analyze the efficacy and influencing factors of cyclosporine (CsA) alone in the treatment of children with acquired aplastic anemia (AA)., Methods: The clinical data of children diagnosed with AA and treated with CsA alone from January 1, 2016 to December 31, 2020 in the Children's Hospital of Chongqing Medical University were collected, and the efficacy and influencing factors of CsA treatment were evaluated., Results: Among the 119 patients, there were 62 male and 57 female, with a median age of 7 years and 1 month. There were 45 cases of very severe AA (VSAA), 47 cases of severe AA (SAA), and 27 cases of non-severe AA (NSAA). At 6 months after treatment, the efficacy of VSAA was lower than that of SAA and NSAA, and there was a statistical difference ( P < 0.01). 6 cases died early, 16 cases relapsed, 2 cases progressed to AML and ALL. The results of univariate analysis showed that the high proportion of lymphocyte in the bone marrow at 6 months was an adverse factor for the efficacy of CsA, while high PLT count was a protective factor ( P =0.008, P =0.002). The ROC curve showed that the cut-off values of PLT count and the proportion of bone marrow lymphocyte at 6 months were 16.5×10
9 /L, 68.5%, respectively. Multivariate analysis showed that the high proportion of lymphocyte in bone marrow at 6 months was an independent adverse factor for IST ( P =0.020, OR =0.062), and high PLT count was a protective factor ( P =0.044, OR =1.038). At 3 months of treatment, CsA response and NSAA were the risk factor for recurrence ( P =0.001, 0.031)., Conclusion: The efficacy of NSAA was higher than that of SAA and VSAA after 6 months of treatment with CsA alone. A high PLT count at the initial diagnosis was a good factor for the effectiveness of CsA, and a high proportion of bone marrow lymphocyte was an unfavorable factor. CsA response at 3 months and NSAA were risk factors for recurrence.- Published
- 2024
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46. [Application of discrete element method (DEM) in pharmaceutical process of solid traditional Chinese medicine preparations].
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Wu YF, Wang ZQ, Wan XH, Hu HQ, Yang YQ, Ai B, Yang M, and Wu ZF
- Subjects
- Chemistry, Pharmaceutical methods, Drug Compounding methods, Drugs, Chinese Herbal chemistry, Drugs, Chinese Herbal analysis, Medicine, Chinese Traditional
- Abstract
In recent years, the application of numerical simulation in the research and development(R&D) as well as the pharmaceutical processes of new drugs has expanded considerably. The discrete element method(DEM), an important approach among numerical simulation methods, offers an effective tool for the simulation of discontinuous media. Referring to the research progress of DEM and the formulation of solid traditional Chinese medicine(TCM) preparations in recent years, this paper summarizes and analyzes the application of DEM in the pharmaceutical processes of solid TCM preparations, and discusses the challenges of its application in these processes, in order to provide new methods and ideas for promoting the high-quality production of TCM preparations.
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- 2024
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47. [Role of Telomere in Clonal Evolution of Acquired Aplastic Anemia--Review].
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Li DN and Wen XH
- Subjects
- Telomere Shortening, Clonal Evolution, Survival Rate, Recurrence, Telomerase genetics, Telomerase metabolism, Genomic Instability genetics, Humans, Anemia, Aplastic genetics, Anemia, Aplastic pathology, Telomere Homeostasis genetics
- Abstract
Studies have found that 1/3 patients with acquired aplastic anemia have shortened telomere length, and the shorter the telomere, the longer the disease course, the more prone to relapse, the lower the overall survival rate, and the higher the probability of clonal evolution. The regulation of telomere length is affected by many factors, including telomerase activity, telomerase-related genes, telomere regulatory proteins and other related factors. Telomere shortening can lead to genetic instability and increases the probability of clonal evolution in patients with acquired aplastic anemia. This article reviews the role of telomere in the clonal evolution of acquired aplastic anemia and factors affecting telomere length.
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- 2024
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48. Targeted inhibition of branched-chain amino acid metabolism drives apoptosis of glioblastoma by facilitating ubiquitin degradation of Mfn2 and oxidative stress.
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Lu Z, Sun GF, He KY, Zhang Z, Han XH, Qu XH, Wan DF, Yao D, Tou FF, Han XJ, and Wang T
- Subjects
- Humans, Animals, Cell Line, Tumor, Mice, Mitochondrial Proteins metabolism, Ubiquitin metabolism, Signal Transduction drug effects, Male, Ubiquitination drug effects, Reactive Oxygen Species metabolism, Oxidative Stress drug effects, Apoptosis drug effects, Glioblastoma metabolism, Glioblastoma pathology, GTP Phosphohydrolases metabolism, Amino Acids, Branched-Chain metabolism
- Abstract
Glioblastoma is one of the most challenging malignancies with high aggressiveness and invasiveness and its development and progression of glioblastoma highly depends on branched-chain amino acid (BCAA) metabolism. The study aimed to investigate effects of inhibition of BCAA metabolism with cytosolic branched-chain amino acid transaminase (BCATc) Inhibitor 2 on glioblastoma, elucidate its underlying mechanisms, and explore therapeutic potential of targeting BCAA metabolism. The expression of BCATc was upregulated in glioblastoma and BCATc Inhibitor 2 precipitated apoptosis both in vivo and in vitro with the activation of Bax/Bcl2/Caspase-3/Caspase-9 axis. In addition, BCATc Inhibitor 2 promoted K63-linkage ubiquitination of mitofusin 2 (Mfn2), which subsequently caused lysosomal degradation of Mfn2, and then oxidative stress, mitochondrial fission and loss of mitochondrial membrane potential. Furthermore, BCATc Inhibitor 2 treatment resulted in metabolic reprogramming, and significant inhibition of expression of ATP5A, UQCRC2, SDHB and COX II, indicative of suppressed oxidative phosphorylation. Moreover, Mfn2 overexpression or scavenging mitochondria-originated reactive oxygen species (ROS) with mito-TEMPO ameliorated BCATc Inhibitor 2-induced oxidative stress, mitochondrial membrane potential disruption and mitochondrial fission, and abrogated the inhibitory effect of BCATc Inhibitor 2 on glioblastoma cells through PI3K/AKT/mTOR signaling. All of these findings indicate suppression of BCAA metabolism promotes glioblastoma cell apoptosis via disruption of Mfn2-mediated mitochondrial dynamics and inhibition of PI3K/AKT/mTOR pathway, and suggest that BCAA metabolism can be targeted for developing therapeutic agents to treat glioblastoma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
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- 2024
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49. Diagnosis and therapy of tacrolimus toxicity in a liver transplant recipient during COVID-19 treatment.
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Zhu F, Wang YM, Ni M, Liang Y, Huang JH, Wang XH, Cheng F, and Lu L
- Subjects
- Humans, Tacrolimus adverse effects, COVID-19 Drug Treatment, Immunosuppressive Agents adverse effects, Transplant Recipients, COVID-19 Testing, Liver Transplantation adverse effects, COVID-19
- Published
- 2024
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50. Exploiting BRAF mutations in the therapeutic approach towards oral and maxillofacial tumors.
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Yi JR, Zhong NN, Lin H, Liu XH, Yang Y, Liu B, and Man QW
- Subjects
- Humans, Imidazoles therapeutic use, Oximes therapeutic use, Pyridones therapeutic use, Pyridones administration & dosage, Pyrimidinones therapeutic use, Antineoplastic Agents therapeutic use, Mouth Neoplasms therapy, Mouth Neoplasms genetics, Mouth Neoplasms pathology, Neoadjuvant Therapy methods, Molecular Targeted Therapy, Proto-Oncogene Proteins B-raf genetics, Mutation, Ameloblastoma genetics, Ameloblastoma therapy, Ameloblastoma diagnosis
- Abstract
Oral and maxillofacial tumors pose a significant clinical challenge due to their tendency to recur, despite advancements in surgical removal techniques. The jaw's intricate structure further complicates treatments and affects patient quality of life. Consequently, emphasis has shifted towards pharmacological interventions, to potentially reduce invasive surgical procedures. One promising approach targets BRAF mutations, specifically the common V600E mutation. BRAF, a critical protein kinase, regulates cell growth and differentiation via the RAS-RAF-MEK-ERK-MAP kinase pathway. A specific nucleotide change at position 1799, swapping Thymine (T) for Adenine (A), results in the V600E mutation, causing unchecked cell growth. This mutation is common in certain oral and maxillofacial tumors like ameloblastoma. A recent neoadjuvant therapy targeting BRAF, involving the use of dabrafenib and trametinib, has showcased a promising, safe, and effective strategy for organ preservation in the treatment of mandibular ameloblastoma. This convergence of molecular insights and targeted therapies holds the key to managing BRAF-mutated oral and maxillofacial tumors effectively, promising improved patient outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)
- Published
- 2024
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