632 results on '"Zou,Yi"'
Search Results
2. Biosynthesis of (-)-Vinigrol.
- Author
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Xu R and Zou Y
- Abstract
(-)-Vinigrol is one of the most complex and challenging molecules in total synthesis; however, the parallel biosynthetic strategy employed by nature for the synthesis of this compound has not yet been identified. In this study, we identified a minimal gene cluster encoding a diterpene cyclase (VniA) and a cytochrome P450 (VniB) which enables the synthesis of (-)-vinigrol through three steps. VniA first cyclizes geranylgeranyl diphosphate to generate an unusual vinigrol-type diterpene skeleton, and then VniB catalyzes the allylic C(sp
3 )-H iterative oxidation. Further genome mining investigation provides new fungal sources for this rare and valuable vinigrol-type diterpene skeleton., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
- Full Text
- View/download PDF
3. Impact of prostate MRI image quality on diagnostic performance for clinically significant prostate cancer (csPCa).
- Author
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Cheng Y, Zhang L, Wu X, Zou Y, Niu Y, and Wang L
- Subjects
- Humans, Male, Retrospective Studies, Middle Aged, Aged, Artifacts, Signal-To-Noise Ratio, Aged, 80 and over, Predictive Value of Tests, Prostate diagnostic imaging, Prostate pathology, Adult, Prostatic Neoplasms diagnostic imaging, Prostatic Neoplasms pathology, Magnetic Resonance Imaging methods
- Abstract
Objectives: With the widespread clinical application of prostate magnetic resonance imaging (MRI), there has been an increasing demand for lesion detection and accurate diagnosis in prostate MR, which relies heavily on satisfactory image quality. Focusing on the primary sequences involved in Prostate Imaging Reporting and Data System (PI-RADS), this study have evaluated common quality issues in clinical practice (such as signal-to-noise ratio (SNR), artifacts, boundaries, and enhancement). The aim of the study was to determine the impact of image quality on clinically significant prostate cancer (csPCa) detection, positive predictive value (PPV) and radiologist's diagnosis in different sequences and prostate zones., Methods: This retrospective study included 306 patients who underwent prostate MRI with definitive pathological reports from February 2021 to December 2022. All histopathological specimens were evaluated according to the recommendations of the International Society of Urological Pathology (ISUP). An ISUP Grade Group ≥ 2 was considered as csPCa. Three radiologists from different centers respectively performed a binary classification assessment of image quality in the following ten aspects: (1) T2WI in the axial plane: SNR, prostate boundary conditions, the presence of artifacts; (2) T2WI in the sagittal or coronal plane: prostate boundary conditions; (3) DWI: SNR, delineation between the peripheral and transition zone, the presence of artifacts, the matching of DWI and T2WI images; (4) DCE: the evaluation of obturator artery enhancement, the evaluation of dynamic contrast enhancement. Fleiss' Kappa was used to determine the inter-reader agreement. Wilson's 95% confidence interval (95% CI) was used to calculate PPV. Chi-square test was used to calculate statistical significance. A p-value < 0.05 was considered statistically significant., Results: High-quality images had a higher csPCa detection rate (56.5% to 64.3%) in axial T2WI, DWI, and DCE, with significant statistical differences in SNR in axial T2WI (p 0.002), the presence of artifacts in axial T2WI (p 0.044), the presence of artifacts in DWI (p < 0.001), and the matching of DWI and T2WI images (p < 0.001). High-quality images had a higher PPV (72.5% to 78.8%) and showed significant statistical significance in axial T2WI, DWI, and DCE. Additionally, we found that PI-RADS 3 (24.0% to 52.9%) contained more low-quality images compared to PI-RADS 4-5 (20.6% to 39.3%), with significant statistical differences in the prostate boundary conditions in axial T2WI (p 0.048) and the presence of artifacts in DWI (p 0.001). Regarding the relationship between csPCa detection and image quality in different prostate zones, this study found that significant statistical differences were only observed between high- (63.5% to 75.7%) and low-quality (30.0% to 50.0%) images in the peripheral zone (PZ)., Conclusion: Prostate MRI quality may have an impact on the diagnostic performance. The poorer image quality is associated with lower csPCa detection rates and PPV, which can lead to an increase in radiologist's ambiguous diagnosis (PI-RADS 3), especially for the lesions located at PZ., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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4. Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice.
- Author
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Fujikawa R, Ramsaran AI, Guskjolen A, de la Parra J, Zou Y, Mocle AJ, Josselyn SA, and Frankland PW
- Subjects
- Animals, Mice, Male, Memory physiology, Anxiety physiopathology, Fear physiology, Fear psychology, Neural Stem Cells, Behavior, Animal physiology, Stress Disorders, Post-Traumatic physiopathology, Neurogenesis physiology, Hippocampus metabolism, Disease Models, Animal, Extinction, Psychological physiology, Mice, Inbred C57BL
- Abstract
Post-traumatic stress disorder (PTSD) is a hypermnesic condition that develops in a subset of individuals following exposure to severe trauma. PTSD symptoms are debilitating, and include increased anxiety, abnormal threat generalization, and impaired extinction. In developing treatment strategies for PTSD, preclinical studies in rodents have largely focused on interventions that target post-encoding memory processes such as reconsolidation and extinction. Instead, here we focus on forgetting, another post-encoding process that regulates memory expression. Using a double trauma murine model for PTSD, we asked whether promoting neurogenesis-mediated forgetting can weaken trauma memories and associated PTSD-relevant behavioral phenotypes. In the double trauma paradigm, consecutive aversive experiences lead to a constellation of behavioral phenotypes associated with PTSD including increases in anxiety-like behavior, abnormal threat generalization, and deficient extinction. We found that post-training interventions that elevate hippocampal neurogenesis weakened the original trauma memory and decreased these PTSD-relevant phenotypes. These effects were observed using multiple methods to manipulate hippocampal neurogenesis, including interventions restricted to neural progenitor cells that selectively promoted integration of adult-generated granule cells into hippocampal circuits. The same interventions also weakened cocaine place preference memories, suggesting that promoting hippocampal neurogenesis may represent a broadly useful approach in hypermnesic conditions such as PTSD and substance abuse disorders., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
- Published
- 2024
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5. Clinical efficacy and mechanism of the combination of autologous platelet-rich gel and recombinant human acidic fibroblast growth factor in the management of refractory diabetic foot.
- Author
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Sheng X, Hu L, Li T, Zou Y, Fu HY, Xiong GP, Zhu Y, Deng B, Xiong LL, and Yin XL
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Gels, Recombinant Proteins administration & dosage, Recombinant Proteins therapeutic use, Treatment Outcome, Vascular Endothelial Growth Factor A, Nerve Growth Factors therapeutic use, Nerve Growth Factors administration & dosage, Platelet-Rich Plasma, Eye Proteins therapeutic use, Eye Proteins metabolism, Fibroblast Growth Factor 1 therapeutic use, Fibroblast Growth Factor 1 administration & dosage, Combined Modality Therapy, Serpins therapeutic use, Oxidative Stress drug effects, Diabetic Foot therapy, Diabetic Foot drug therapy, Wound Healing drug effects
- Abstract
Objective: This study aims to explore the influence of combining autologous platelet-rich gel (APG) with continuous vacuum-sealed drainage (CVSD) and the exogenous recombinant human acidic fibroblast growth factor (rh-aFGF) on the healing processes of diabetic foot ulcers (DFU). The primary objective is to elucidate the complex molecular mechanisms associated with DFU, providing innovative perspectives for its treatment., Methods: Ninety patients diagnosed with DFU were randomly allocated into three distinct groups. Group A underwent CVSD following wound cleansing to facilitate healing. In Group B, in addition to conventional treatment, negative pressure wound therapy was applied, and rh-aFGF was introduced into normal saline for lavage, building upon the procedures of Group A. Group C received APG along with the interventions applied in Group B. The clinical efficacy of each group was systematically observed and analyzed. Additionally, changes in plasma oxidative stress, inflammatory markers, vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor (PEDF) were assessed both before treatment and 14 days post-treatment., Results: Following treatment, all groups exhibited commendable clinical efficacy. Group C demonstrated a superior wound healing rate, reduced frequency of dressing changes, and shorter wound healing duration (P< 0.05). Compared to baseline measurements, the levels of superoxide dismutase and PEDF increased, while malondialdehyde, VEGF, interleukin-6, interleukin-8, and monocyte chemotactic factor MCP-1 decreased in the wound tissue across all groups. Notably, Group C showed the most significant improvement in clinical efficacy and fortification of molecular mechanisms against oxidative stress (all P< 0.05)., Conclusions: The integrative therapeutic approach combining APG with CVSD and rh-aFGF demonstrates notable efficacy in advancing wound healing. This effectiveness is evident through the reduced frequency of dressing changes and alleviation of wound-related pain. Additionally, the treatment regimen improves the cure rate for challenging, refractory wounds. These favorable outcomes can be attributed to the reduction of oxidative stress levels, attenuation of the local inflammatory response, and the enhancement of the balance between PEDF and VEGF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sheng, Hu, Li, Zou, Fu, Xiong, Zhu, Deng, Xiong and Yin.)
- Published
- 2024
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6. Effects of nutritional stress on soil fertility and antioxidant enzymes of rice in different growth periods.
- Author
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Cai Q, Zou Y, Zhong N, and Jia G
- Abstract
Stress in plants denotes the detrimental impact of alterations in external environmental conditions on regular plant growth and development. Plants employ diverse mechanisms to mitigate or evade nutritional stress-induced damage. In order to investigate the physiological response mechanism of plants to nutritional stress and assess its impact on soil nutrient content and antioxidant enzyme activity in rice, a field experiment was conducted applying five treatments: control, nitrogen (N) deficiency, phosphorus (P) deficiency, potassium (K) deficiency, and full fertilization. Rice leaf and soil samples were concurrently gathered during both the vegetative and reproductive growth stages of rice. Analysis was conducted on soil N, P, and K levels, as well as leaf antioxidant enzyme activities, to investigate the impact of nutrient stress on rice antioxidant enzymes and soil fertility. The research findings indicate that full fertilization treatment enhanced the agronomic properties of the soil compared to the control treatment. In the N-deficiency treatment, reactive oxygen species (ROS) levels increased by 16.53-33.89% during the reproductive growth period compared to the vegetative growth period. The peroxidase (POD) activity decreased by 41.39% and superoxide dismutase (SOD) activity increased by 36.22% under K-deficiency treatment during the reproductive growth period compared to the vegetative growth period. Consequently, applying N and P fertilizer during the vegetative growth period can decrease membrane lipid peroxidation levels by 7.34-72.53%. The full fertilization treatment markedly enhanced rice yield compared to other treatments and increased the Nitrogen activation coefficient (NAC) and Phosphorus activation coefficient (PAC) in the soil, while decreasing the PAC. Elevating NAC levels can stimulate the activity or content of PRO, MDA, and RPS during the vegetative growth stage, whereas in the reproductive growth stage, it will decrease the content of ROS, PRO, and MDA. This data offers valuable insights and theoretical support for nutritional stress research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cai, Zou, Zhong and Jia.)
- Published
- 2024
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7. Cyclo-farnesyl Diphosphate-Dependent Prenylation in Fungi.
- Author
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Tang YJ and Zou Y
- Subjects
- Molecular Structure, Sesquiterpenes chemistry, Sesquiterpenes metabolism, Fungi chemistry, Fungi metabolism, Polyisoprenyl Phosphates chemistry, Polyisoprenyl Phosphates metabolism, Prenylation, Dimethylallyltranstransferase metabolism, Dimethylallyltranstransferase chemistry
- Abstract
A conserved two-gene cassette in fungi was discovered by genome mining, which encodes a UbiA family intramembrane prenyltansferase (VviA) and a haloacid dehalogenase-like hydrolase family terpene cyclase (VviB), respectively. A series of in vivo and in vitro investigations revealed that VviA exclusively uses VviB-synthesized drim-8-ene diphosphate (cyclo-farnesyl diphosphate) as the native prenyl donor to catalyze prenylation on d-mannitol, showcasing a previously unidentified function of UbiA-type prenyltransferases and a new prenylation manner in fungi.
- Published
- 2024
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8. Saltwater intrusion of the Nandu River under the changing environment in China.
- Author
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Wang Y, Zou Y, He Y, Zhu L, and Ye C
- Subjects
- China, Water Movements, Estuaries, Seawater chemistry, Rivers chemistry, Environmental Monitoring methods, Salinity
- Abstract
Saltwater problems in the Nandu River have gradually intensified in recent years. The effect of runoff variability (RV) on saltwater intrusion has not yet been fully revealed. Long-term trends in runoff and sea level (SL) were analyzed using the Mann-Kendall test and Theil-Sen estimation, and salinity exceedance rates (P
s ) were calculated based on MIKE 11 and daily runoff distributions. As RV increased, Ps decreased the most at 16.0 km (6.7 %) and increased the most at 23.2 km (5.3 %). SL increased by 0.4 m and Ps increased the most at 20.5 km (11.7 %). Constant Ps is projected to move downstream by the 2060s and 210 s, with maximum increases in Ps of 6.2 % and 10.1 %, respectively. The ratio of changes in Ps due to changes in RV and SL is about 0.85. Constant Ps sections can be used to assess the risk of saline intrusion in some of the world's estuaries., 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.)- Published
- 2024
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9. KDM1A/LSD1 inhibition enhances chemotherapy response in ovarian cancer.
- Author
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Chen Y, Johnson JD, Jayamohan S, He Y, Venkata PP, Jamwal D, Alejo S, Zou Y, Lai Z, Viswanadhapalli S, Vadlamudi RK, Kost E, and Sareddy GR
- Subjects
- Humans, Female, Animals, Mice, Cell Line, Tumor, Gene Expression Regulation, Neoplastic drug effects, Apoptosis drug effects, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Cell Proliferation drug effects, Mice, Nude, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Hydrazines, Sulfonamides, Histone Demethylases antagonists & inhibitors, Histone Demethylases metabolism, Histone Demethylases genetics, Ovarian Neoplasms drug therapy, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Ovarian Neoplasms metabolism, Drug Resistance, Neoplasm drug effects, Paclitaxel pharmacology, Cisplatin pharmacology, Xenograft Model Antitumor Assays, Carboplatin pharmacology
- Abstract
Ovarian cancer (OCa) is the deadliest of all gynecological cancers. The standard treatment for OCa is platinum-based chemotherapy, such as carboplatin or cisplatin in combination with paclitaxel. Most patients are initially responsive to these treatments; however, nearly 90% will develop recurrence and inevitably succumb to chemotherapy-resistant disease. Recent studies have revealed that the epigenetic modifier lysine-specific histone demethylase 1A (KDM1A/LSD1) is highly overexpressed in OCa. However, the role of KDM1A in chemoresistance and whether its inhibition enhances chemotherapy response in OCa remains uncertain. Analysis of TCGA datasets revealed that KDM1A expression is high in patients who poorly respond to chemotherapy. Western blot analysis show that treatment with chemotherapy drugs cisplatin, carboplatin, and paclitaxel increased KDM1A expression in OCa cells. KDM1A knockdown (KD) or treatment with KDM1A inhibitors NCD38 and SP2509 sensitized established and patient-derived OCa cells to chemotherapy drugs in reducing cell viability and clonogenic survival and inducing apoptosis. Moreover, knockdown of KDM1A sensitized carboplatin-resistant A2780-CP70 cells to carboplatin treatment and paclitaxel-resistant SKOV3-TR cells to paclitaxel. RNA-seq analysis revealed that a combination of KDM1A-KD and cisplatin treatment resulted in the downregulation of genes related to epithelial-mesenchymal transition (EMT). Interestingly, cisplatin treatment increased a subset of NF-κB pathway genes, and KDM1A-KD or KDM1A inhibition reversed this effect. Importantly, KDM1A-KD, in combination with cisplatin, significantly reduced tumor growth compared to a single treatment in an orthotopic intrabursal OCa xenograft model. Collectively, these findings suggest that combination of KDM1A inhibitors with chemotherapy could be a promising therapeutic approach for the treatment of OCa., (© 2024 Wiley Periodicals LLC.)
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- 2024
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10. A photothermal surface modified with polyelectrolyte multilayers for gene transfection and cell harvest.
- Author
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Zhang Y, Lu K, Yao L, Zhang H, Zhang S, Zou Y, Yu Q, and Chen H
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- Humans, Plasmids chemistry, Plasmids genetics, Nanotubes, Carbon chemistry, Hyaluronic Acid chemistry, Chitosan chemistry, Cell Survival drug effects, Dimethylpolysiloxanes chemistry, Polyethyleneimine chemistry, Hep G2 Cells, Transfection methods, Polyelectrolytes chemistry, Surface Properties, DNA chemistry
- Abstract
Gene transfection, which involves introducing nucleic acids into cells, is a pivotal technology in the life sciences and medical fields, particularly in gene therapy. Surface-mediated transfection, primarily targeting cells adhering to surfaces, shows promise for enhancing cell transfection by localizing and presenting surface-bound nucleic acids directly to the cells. However, optimizing endocytosis for efficient delivery remains a persistent challenge. Additionally, ensuring efficient and non-traumatic cell harvest capability is crucial for applications such as ex vivo cell-based therapy. To address these challenges, we developed a photothermal platform with enzymatic degradation capability for efficient gene transfection and cell harvest. This platform is based on carbon nanotubes (CNTs) doped with poly(dimethylsiloxane) and modified with polyelectrolyte multilayers (PEMs) containing hyaluronic acid and quaternized chitosan, allowing for substantial loading of poly(ethyleneimine)/plasmid DNA (pDNA) complexes through electrostatic interactions. Upon irradiation of near-infrared laser, the photothermal properties of CNTs enable high transfection efficiency by delivering pDNA into attached cells via a membrane disruption mechanism. The engineered cells can be harvested by treating with a non-toxic hyaluronidase solution to degrade PEMs, thus maintaining good viability for further applications. This platform has demonstrated remarkable efficacy across various cell lines (including Hep-G2 cells, Ramos cells and primary T cells), achieving a transfection efficiency exceeding 95 %, cell viability exceeding 90 %, and release efficiency surpassing 95 %, highlighting its potential for engineering living cells., 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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11. The effects of bitter melon (Momordica charantia) on anthropometric indices in adults: A systematic review and meta-analysis of randomized controlled trials.
- Author
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Zou Y, Zou W, Jahangir M, and Haedi A
- Subjects
- Adult, Humans, Body Mass Index, Body Weight drug effects, Plant Extracts administration & dosage, Randomized Controlled Trials as Topic, Momordica charantia chemistry
- Abstract
There is controversial data on the impacts of bitter melon (Momordica charantia) supplementations on anthropometric indices. Thus, we aimed to clarify this role of bitter melon through a systematic review, and meta-analysis of the trials. All clinical trials conducted on the impact of bitter melon on anthropometric indices were published until August 2023 in PubMed, Web of Sciences, Scopus, Embase, and Cochrane Library web databases included. Overall, 10 studies with 448 individuals were included in the meta-analysis. Meta-analysis of 10 trials with 448 participants revealed no significant reductions in body weight (BW) (WMD: 0.04 Kg; 95 %CI: -0.16-0.25; P =0.651), body mass index (BMI) (WMD: -0.18 kg/m2; 95 %CI: -0.43-0.07; P =0.171), waist circumference (WC) (WMD: -0.95 cm; 95 % CI: -3.05-1.16; p =0.372), and percentage of body fat (PBF) (WMD: -0.99; 95 % CI: -2.33-0.35; p =0.141) following bitter melon supplementation. There was no significant impact of bitter melon supplementation on BW, BMI, WC, and PBF. More large-scale and high-quality RCTs are necessary to confirm these results., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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12. Discovery of a polyketide carboxylate phytotoxin from a polyketide glycoside hybrid by β-glucosidase mediated ester bond hydrolysis.
- Author
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Wang X, Kong DK, Zhang HR, and Zou Y
- Abstract
Fungal phytotoxins cause significant harm to agricultural production or lead to plant diseases. Discovering new phytotoxins, dissecting their formation mechanism and understanding their action mode are important for controlling the harmful effects of fungal phytopathogens. In this study, a long-term unsolved cluster (polyketide synthase 16, PKS16 cluster) from Fusarium species was thoroughly investigated and a series of new metabolites including both complex α-pyrone-polyketide glycosides and simple polyketide carboxylates were identified from F. proliferatum . The whole pathway reveals an unusual assembly and inactivation process for phytotoxin biosynthesis, with key points as follows: (1) a flavin dependent monooxygenase catalyzes Baeyer-Villiger oxidation on the linear polyketide side chain of α-pyrone-polyketide glycoside 8 to form ester bond compound 1; (2) a β-glucosidase unexpectedly mediates the ester bond hydrolysis of 1 to generate polyketide carboxylate phytotoxin 2; (3) oxidation occurring on the terminal inert carbons of 2 by intracellular oxidase(s) eliminates its phytotoxicity. Our work identifies the chemical basis of the PKS16 cluster in phytotoxicity, shows that polyketide carboxylate is a new structural type of phytotoxin in Fusarium and importantly uncovers a rare ester bond hydrolysis function of β-glucosidase family enzymes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2024
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13. Schisandrol A Alleviates Allergic Asthma in Mice via Regulating the NF-κB/IκBα and Nrf2/HO-1 Signaling Pathways.
- Author
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Dong Y, Zou YZ, Li T, Sun JH, Li H, Zhuang WY, Song Y, and Wang CM
- Abstract
Schisandra chinensis (Turcz) Baill ( S. chinensis ) is the key traditional Chinese medicine for the treatment of asthma used by ancient and modern medical practitioners. However, the material basis and the main mechanism of its antiasthmatic effect remain unclear. Our preliminary results showed that schisandrol A (SCA), a representative monomer of Schisandra lignans, had the best relaxation effect on tracheal rings in isolated rats. In this research, a mouse asthma model was prepared by combining ovalbumin (OVA) with Al (OH)
3 for exploring the antiasthmatic action and the underlying mechanism of SCA. The study results demonstrated that SCA improved the behavior of mice with asthma and pathological changes in their lung tissues and airways, decreased serum immunoglobulin E (IgE) and OVA-IgE levels, interleukin-4 (IL-4), IL-5, IL-13, and eotaxin contents, and leukocytes number in bronchoalveolar lavage fluid. SCA downregulated the gene expressions of keratinocyte-derived protein chemokines and ILs and reduced the expressions of phosphorylated IκB kinase α (p-IKKα) and p-nuclear factor kappa-B (NF-κB) proteins in lung tissues. In addition, it was found that SCA could significantly increase T-superoxide dismutase and catalase activities, decrease malondialdehyde content, and elevate p-IκBα, NF-E2-related-factor 2 (Nrf2), and heme oxygenase-1 (HO-1) protein expressions. In summary, SCA treatment resulted in a significant improvement in the allergic bronchial asthma in mice, and its mechanisms may involve the regulation of the NF-κB/IκBα pathway to reduce inflammatory response and the Nrf2/HO-1 pathway to improve the body's antioxidant capacity. These results suggest that SCA is a key component of S. chinensis in exerting antiasthmatic effects.- Published
- 2024
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14. Low frequency sinusoidal electromagnetic fields promote the osteogenic differentiation of rat bone marrow mesenchymal stem cells by modulating miR-34b-5p/STAC2.
- Author
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Fang X, Liu C, Wei K, Shu Z, Zou Y, Zhang Z, Ding Q, Jing S, Li W, Wang T, Li H, Wu H, Liu C, and Ma T
- Subjects
- Animals, Rats, Female, Osteoporosis genetics, Osteoporosis therapy, Osteoporosis metabolism, Cells, Cultured, MicroRNAs genetics, MicroRNAs metabolism, Osteogenesis genetics, Mesenchymal Stem Cells metabolism, Mesenchymal Stem Cells cytology, Cell Differentiation, Electromagnetic Fields, Rats, Sprague-Dawley
- Abstract
Electromagnetic fields (EMFs) have emerged as an effective treatment for osteoporosis. However, the specific mechanism underlying their therapeutic efficacy remains controversial. Herein, we confirm the pro-osteogenic effects of 15 Hz and 0.4-1 mT low-frequency sinusoidal EMFs (SEMFs) on rat bone marrow mesenchymal stem cells (BMSCs). Subsequent miRNA sequencing reveal that miR-34b-5p is downregulated in both the 0.4 mT and 1 mT SEMFs-stimulated groups. To clarify the role of miR-34b-5p in osteogenesis, BMSCs are transfected separately with miR-34b-5p mimic and inhibitor. The results indicate that miR-34b-5p mimic transfection suppress osteogenic differentiation, whereas inhibition of miR-34b-5p promote osteogenic differentiation of BMSCs. In vivo assessments using microcomputed tomography, H&E staining, and Masson staining show that miR-34b-5p inhibitor injections alleviate bone mass loss and trabecular microstructure deterioration in ovariectomy (OVX) rats. Further validation demonstrates that miR-34b-5p exerts its effects by regulating STAC2 expression. Modulating the miR-34b-5p/STAC2 axis attenuate the pro-osteogenic effects of low-frequency SEMFs on BMSCs. These studies indicate that the pro-osteogenic effect of SEMFs is partly due to the regulation of the miR-34b-5p/STAC2 pathway, which provides a potential therapeutic candidate for osteoporosis., (© 2024. The Author(s).)
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- 2024
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15. Multiband and bidirectional multiplexing asymmetric optical transmission empowered by nanograting-coupled defective multilayer photonic crystal.
- Author
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Wei X, Sun Y, Liang Y, Zou Y, Novitsky A, Fang Y, and Peng W
- Abstract
Asymmetric optical transmission (AOT) has been an enduring hot topic of interest in various fields, including optical communication, information processing, and so on. Particularly, the development of reciprocal micro-nanostructures achieving AOT further facilitates and accelerates the miniaturization and integration of traditional optical components. However, most of these optical components merely consider a single AOT band and transmission in a specified direction, limiting the development of their versatile functions. In this paper, we theoretically propose an all-dielectric metamaterial consisting of a nanograting and a defective multilayer photonic crystal, exhibiting multi-band and bidirectional multiplexing AOT. More specifically, the proposed metamaterial demonstrates both narrowband and wideband AOT for incidence from the nanograting to the photonic crystal, and a completely different narrowband AOT for the opposite incidence, namely, from the photonic crystal to the nanograting. These distinctive AOT spectral features are achieved by matching the diffraction effect of the nanograting with the special energy band of the defective multilayer photonic crystal. Remarkably, the device exhibits a transmittance difference of up to 0.974 and a contrast ratio of up to 0.997 (transmittance ratio of up to 673), with a transmission bandwidth of 62.7 nm for incident light with a wavelength of 624 nm illuminating from the nanograting to the defective multilayer photonic crystal. Furthermore, the bandwidth and number of transmission bands can be flexibly tuned by changing the polarization angle of the incident light, showcasing its excellent polarization multiplexing characteristics. The designed metamaterial provides an effective strategy for the realization of versatile AOT devices and is conducive to expanding the application scenarios of AOT devices., (© 2024. The Author(s).)
- Published
- 2024
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16. Design, synthesis, and antitumor activity evaluation of 1,2,3-triazole derivatives as potent PD-1/PD-L1 inhibitors.
- Author
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Xia Y, Zhang H, Du H, Huang L, Yu C, Wu H, Zhang Y, Xu Y, Zhu Q, and Zou Y
- Abstract
A series of 1,2,3-triazole derivatives targeting the PD-1/PD-L1 pathway were designed, synthesized, and evaluated both in vitro and in vivo. Among them, compound III-4 demonstrated exceptional inhibitory activity against the interaction of PD-1/PD-L1 and showed great binding affinity with hPD-L1, with an IC
50 value of 2.9 nM and a KD value of 3.33 nM. In the co-culture of Hep3B/OS-8/hPD-L1 cells and CD3+ T cells assay, III-4 relieved the inhibition of PD-L1 on PD-1 and promoted the expression of IFN-γ, which shared a comparable effect to that of the PD-1 monoclonal antibody Pembrolizumab (5 μg/mL). Moreover, compound III-5, an ester prodrug derived from III-4, demonstrated significant antitumor effects in the hPD-L1-MC38 C57BL/6 mouse model (TGI: 49.6 %) by oral administration. These findings suggest that compound III-5 holds promise as an inhibitor of the PD-1/PD-L1 interaction for cancer immunotherapy., 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. Published by Elsevier Inc.)- Published
- 2024
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17. In-Situ Synthesized Gel Polymer Electrolyte Enable High Capacity and Long-Cycle-Life Lithium Metal Batteries.
- Author
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Zou Y, Zhao W, Liu S, Fang H, Gao L, Wang Y, Su Y, Chen L, and Liu Z
- Abstract
Solid-state lithium-metal batteries (SSLMBs) have attracted great attention due to their outstanding advantages in safety, electrochemical stability and interfacial compatibility. However, the low ionic conductivity and narrow electrochemical window restrict their practical application. Herein, in-situ polymerization electrolytes (IPEs) crosslinked by acrylonitrile (AN) and ethylene glycol dimethacrylate (EGDMA) exhibit the superior ionic conductivity of 1.77×10
-3 S cm-1 at 25 °C, the ultrahigh lithium transference number (tLi+) of 0.784 and the wider electrochemical stable window (ESW) of 5.65 V. The IPEs make the symmetrical Li||Li cells achieve the highly stable lithium stripping/plating cycling for over 3000 h at 0.1 mA cm-2 . Meanwhile, IPE endows the solid-state LiFePO4 ||Li batteries with an excellent long-cycle performance over 700 cycles at 2.5 C with a capacity retention ratio over 95 %, as well as 1000 cycles at 1 C and superior capacity retention of 85 %. More importantly, the in-situ polymerized electrolytes containing polyacrylonitrile (PAN) open up a new frontier to promote the practical application of solid-state batteries with high safety and high energy density via in-situ solidification technology., (© 2024 Wiley-VCH GmbH.)- Published
- 2024
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18. Low-loss and low-cross talk polarization-insensitive multimode silicon waveguide crossing.
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Chen Y, Wang P, Fu Q, Sun Y, Zou Y, Dai S, Chen W, Chen H, Li J, Dai T, and Yang J
- Abstract
A polarization-insensitive multimode silicon waveguide crossing is investigated and experimentally characterized in this Letter. By employing the particle swarm optimization (PSO) algorithm and finite difference time domain (FDTD) method, the lengths and widths of the waveguides in the proposed device are optimized for attaining wide bandwidth, small insertion loss (IL), low cross talk (CT), and compact size. Measurement results reveal that the footprint of the presented device is 11.92 μm × 11.92 μm. From 1520 to 1600 nm, the measured insertion loss and cross talk are smaller than 0.67 dB and -28.6 dB in the case of the TE
0 mode, lower than 0.65 dB and -28.7 dB in the case of the TE1 mode, less than 0.48 dB and -36.3 dB in the case of the TM0 mode, and lower than 0.62 dB and -28 dB in the case of the TM1 mode.- Published
- 2024
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19. A self-supplied hydrogen peroxide and nitric oxide-generating nanoplatform enhances the efficacy of chemodynamic therapy for biofilm eradication.
- Author
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Jia D, Zou Y, Zhang Y, Xu H, Yang W, Zheng X, Zhang Y, and Yu Q
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- Animals, Mice, Pseudomonas aeruginosa drug effects, Microbial Sensitivity Tests, Metal-Organic Frameworks chemistry, Metal-Organic Frameworks pharmacology, Nanoparticles chemistry, Arginine chemistry, Arginine pharmacology, Copper chemistry, Copper pharmacology, Particle Size, Methicillin-Resistant Staphylococcus aureus drug effects, Surface Properties, Peroxides, Biofilms drug effects, Hydrogen Peroxide pharmacology, Hydrogen Peroxide chemistry, Nitric Oxide metabolism, Nitric Oxide chemistry, Nitric Oxide pharmacology, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents chemistry
- Abstract
Bacterial biofilms present a profound challenge to global public health, often resulting in persistent and recurrent infections that resist treatment. Chemodynamic therapy (CDT), leveraging the conversion of hydrogen peroxide (H
2 O2 ) to highly reactive hydroxyl radicals (•OH), has shown potential as an antibacterial approach. Nonetheless, CDT struggles to eliminate biofilms due to limited endogenous H2 O2 and the protective extracellular polymeric substances (EPS) within biofilms. This study introduces a multifunctional nanoplatform designed to self-supply H2 O2 and generate nitric oxide (NO) to overcome these hurdles. The nanoplatform comprises calcium peroxide (CaO2 ) for sustained H2 O2 production, a copper-based metal-organic framework (HKUST-1) encapsulating CaO2 , and l-arginine (l-Arg) as a natural NO donor. When exposed to the acidic microenvironment within biofilms, the HKUST-1 layer decomposes, releasing Cu2+ ions and l-Arg, and exposing the CaO2 core to initiate a cascade of reactions producing reactive species such as H2 O2 , •OH, and superoxide anions (•O2 - ). Subsequently, H2 O2 catalyzes l-Arg to produce NO, which disperses the biofilm and reacts with •O2 - to form peroxynitrite, synergistically eradicating bacteria with •OH. In vitro assays demonstrated the nanoplatform's remarkable antibiofilm efficacy against both Gram-positive Methicillin-resistant Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa, significantly reducing bacterial viability and EPS content. In vivo mouse model experiments validated the nanoplatform's effectiveness in eliminating biofilms and promoting infected wound healing without adverse effects. This study represents a breakthrough in overcoming traditional CDT limitations by integrating self-supplied H2 O2 with NO's biofilm-disrupting capabilities, offering a promising therapeutic strategy for biofilm-associated infection., 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 Inc. All rights reserved.)- Published
- 2025
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20. Discovery, Characterization and Engineering of the Free l-Histidine C4 -Prenyltransferase.
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Chen XW, Liu Z, Dai S, and Zou Y
- Subjects
- Protein Engineering, Models, Molecular, Substrate Specificity, Imidazoles chemistry, Imidazoles metabolism, Histidine chemistry, Histidine metabolism, Dimethylallyltranstransferase metabolism, Dimethylallyltranstransferase chemistry, Dimethylallyltranstransferase genetics
- Abstract
Prenylation of amino acids is a critical step for synthesizing building blocks of prenylated alkaloid family natural products, where the corresponding prenyltransferase that catalyzes prenylation on free l-histidine (l-His) has not yet been identified. Here, we first discovered and characterized a prenyltransferase FunA from the antifungal agent fungerin pathway that efficiently performs C4 -dimethylallylation on l-His. Crystal structure-guided engineering of the prenyl-binding pocket of FunA, a single M181A mutation, successfully converted it into a C4 -geranyltransferase. Furthermore, FunA and its variant FunA-M181A show broad substrate promiscuity toward substrates that vary in substituents of the imidazole ring. Our work furthers our knowledge of free amino acid prenyltransferase and expands the arsenal of alkylation biocatalysts for imidazole-containing small molecules.
- Published
- 2024
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21. Integrative multi-omics characterization of hepatocellular carcinoma in hispanic patients.
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Das D, Wang X, Chiu YC, Bouamar H, Sharkey FE, Lopera JE, Lai Z, Weintraub ST, Han X, Zou Y, Chen HH, Zeballos Torrez CR, Gu X, Cserhati M, Michalek JE, Halff GA, Chen Y, Zheng S, Cigarroa FG, and Sun LZ
- Abstract
Background: The incidence and mortality rates of hepatocellular carcinoma (HCC) among Hispanic individuals in the United States are much higher than in non-Hispanic white people. We conducted multi-omics analyses to elucidate molecular alterations in HCC among Hispanic patients., Methods: Paired tumor and adjacent non-tumor samples were collected from 31 Hispanic HCCs in South Texas (STX-Hispanic) for genomic, transcriptomic, proteomic, and metabolomic profiling. Serum lipids were profiled in 40 Hispanic and non-Hispanic patients with or without clinically diagnosed HCC., Results: Exome sequencing revealed high mutation frequencies of AXIN2 and CTNNB1 in STX Hispanic HCCs, suggesting a predominant activation of the Wnt/β-catenin pathway. TERT promoter mutations were also significantly more frequent in the Hispanic cohort (Fisher's exact test, p < .05). Cell cycles and liver function were positively and negatively enriched, respectively, with gene set enrichment analysis. Gene sets representing specific liver metabolic pathways were associated with dysregulation of corresponding metabolites. Negative enrichment of liver adipogenesis and lipid metabolism corroborated with a significant reduction in most lipids in serum samples of HCC patients (paired t-test, p < .0001). Two HCC subtypes from our Hispanic cohort were identified and validated with the TCGA liver cancer cohort. Patients with better overall survival showed higher activity of immune and angiogenesis signatures, and lower activity of liver function-related gene signatures. They also had higher levels of immune checkpoint and immune exhaustion markers., Conclusions: Our study revealed specific molecular features of Hispanic HCC and potential biomarkers for therapeutic management. It provides a unique resource for studying Hispanic HCC., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2024
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22. Concurrent TB and HIV therapies effectively control clinical reactivation of TB during co-infection but fail to eliminate chronic immune activation.
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Sharan R, Zou Y, Lai Z, Singh B, Shivanna V, Dick E Jr, Hall-Ursone S, Khader S, Mehra S, Alvarez X, Rengarajan J, and Kaushal D
- Abstract
The majority of Human Immunodeficiency Virus (HIV) negative individuals exposed to Mycobacterium tuberculosis ( Mtb ) control the bacillary infection as latent TB infection (LTBI). Co-infection with HIV, however, drastically increases the risk to progression to tuberculosis (TB) disease. TB is therefore the leading cause of death in people living with HIV (PLWH) globally. Combinatorial antiretroviral therapy (cART) is the cornerstone of HIV care in humans and reduces the risk of reactivation of LTBI. However, the immune control of Mtb infection is not fully restored by cART as indicated by higher incidence of TB in PLWH despite cART. In the macaque model of co-infection, skewed pulmonary CD4
+ TEM responses persist, and new TB lesions form despite cART treatment. We hypothesized that regimens that concurrently administer anti-TB therapy and cART would significantly reduce TB in co-infected macaques than cART alone, resulting in superior bacterial control, mitigation of persistent inflammation and lasting protective immunity. We studied components of TB immunity that remain impaired after cART in the lung compartment, versus those that are restored by concurrent 3 months of once weekly isoniazid and rifapentine (3HP) and cART in the rhesus macaque (RM) model of LTBI and Simian Immunodeficiency Virus (SIV) co-infection. Concurrent administration of cART + 3HP did improve clinical and microbiological attributes of Mtb /SIV co-infection compared to cART-naïve or -untreated RMs. While RMs in the cART + 3HP group exhibited significantly lower granuloma volumes after treatment, they, however, continued to harbor caseous granulomas with increased FDG uptake. cART only partially restores the constitution of CD4 + T cells to the lung compartment in co-infected macaques. Concurrent therapy did not further enhance the frequency of reconstituted CD4+ T cells in BAL and lung of Mtb /SIV co-infected RMs compared to cART, and treated animals continued to display incomplete reconstitution to the lung. Furthermore, the reconstituted CD4+ T cells in BAL and lung of cART + 3HP treated RMs exhibited an increased frequencies of activated, exhausted and inflamed phenotype compared to LTBI RMs. cART + 3HP failed to restore the effector memory CD4+ T cell population that was significantly reduced in pulmonary compartment post SIV co-infection. Concurrent therapy was associated with the induction of Type I IFN transcriptional signatures and led to increased Mtb -specific TH1 /TH17 responses correlated with protection, but decreased Mtb -specific TNFa responses, which could have a detrimental impact on long term protection. Our results suggest the mechanisms by which Mtb /HIV co-infected individuals remain at risk for progression due to subsequent infections or reactivation due of persisting defects in pulmonary T cell responses. By identifying lung-specific immune components in this model, it is possible to pinpoint the pathways that can be targeted for host-directed adjunctive therapies for TB/HIV co-infection., Competing Interests: Conflicts of Interest Statement The authors have declared that no conflict of interest exists.- Published
- 2024
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23. Microstructure and Properties of Mg-Gd-Y-Zn-Mn High-Strength Alloy Welded by Friction Stir Welding.
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Wang J, Wan Z, Wang X, Wang J, Zou Y, Wang J, and Pan F
- Abstract
Mg-Gd-Y-Zn-Mn (MVWZ842) is a kind of high rare earth magnesium alloy with high strength, high toughness and multi-scale strengthening mechanisms. After heat treatment, the maximum tensile strength of MVWZ842 alloy is more than 550 MPa, and the elongation is more than 5%. Because of its great mechanical properties, MVWZ842 has broad application potential in aerospace and rail transit. However, the addition of high rare earth elements makes the deformation resistance of MVWZ842 alloy increase to some extent. This leads to the difficulty of direct plastic processing forming and large structural part shaping. Friction stir welding (FSW) is a convenient fast solid-state joining technology. When FSW is used to weld MVWZ842 alloy, small workpieces can be joined into a large one to avoid the problem that large workpieces are difficult to form. In this work, a high-quality joint of MVWZ842 alloy was achieved by FSW. The microstructure and properties of this high-strength magnesium alloy after friction stir welding were studied. There was a prominent onion ring characteristic in the nugget zone. After the base was welded, the stacking fault structure precipitated in the grain. There were a lot of broken long period stacking order (LPSO) phases on the retreating side of the nugget zone, which brought the effect of precipitation strengthening. Nano-α-Mn and the broken second phase dispersed in the matrix in the nugget zone, which made the grains refine. A relatively complete dynamic recrystallization occurred in the nugget zone, and the grains were refined. The welding coefficient of the welded joint exceeded 95%, and the hardness of the weld nugget zone was higher than that of the base. There were a series of strengthening mechanisms in the joint, mainly fine grain strengthening, second phase strengthening and solid solution strengthening.
- Published
- 2024
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24. Long-Term Survival Trend of Gynecological Cancer: A Systematic Review of Population-Based Cancer Registration Data.
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Zhou XH, Yang DN, Zou YX, Tang DD, Chen J, Li ZY, Shen QM, Xu Q, and Xiang YB
- Subjects
- Humans, Female, Registries, Survival Rate, Uterine Cervical Neoplasms mortality, Uterine Cervical Neoplasms epidemiology, Genital Neoplasms, Female mortality, Genital Neoplasms, Female epidemiology
- Abstract
Gynecological cancer significantly affect the health of women. This review aimed to describe the global patterns and trends in the survival of patients with gynecological cancers. We searched PubMed, Embase, Web of Science, SinoMed, and SEER for survival analyses of cancer registration data of cervical, endometrial, and ovarian cancers published between 1980 and 2022. Globally, the highest 5-year observed survival rate for cervical cancer was 76.5% in Anshan, Liaoning, China (2008-2017). The 5-year observed survival rates of endometrial and ovarian cancers were higher in Finland (1995-1999, 82.5%) and Singapore (1988-1992, 62.0%). The 5-year relative survival rate of cervical cancer patients was higher in Haining, Zhejiang, China (2011-2014, 85.8%). Korea ranked first at 89.0% and 64.5% for endometrial and ovarian cancers, respectively. Survival rates have improved for cervical, endometrial, and ovarian cancers. Patients aged ≥ 75 years and those with advanced-stage disease had the worst 5-year survival rates. Survival rates were better for squamous cell carcinoma in cervical cancer, for endometrial carcinoma and mucinous adenocarcinoma in endometrial cancer, and for germ cell and sex-cord stromal tumors in ovarian cancer. Over the past four decades, the survival rates of gynecological cancers have increased globally, with notable increases in cervical and endometrial cancers. Survival rates are higher in developed countries, with a slow-growing trend. Future studies should focus on improving survival, especially in ovarian cancer patients., (Copyright © 2024 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)
- Published
- 2024
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25. Advances in Cyclodextrins and Their Derivatives in Nano-Delivery Systems.
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Ji XY, Zou YX, Lei HF, Bi Y, Yang R, Tang JH, and Jin QR
- Abstract
The diversity of cyclodextrins and their derivatives is increasing with continuous research. In addition to monomolecular cyclodextrins with different branched chains, cyclodextrin-based polymers have emerged. The aim of this review is to summarize these innovations, with a special focus on the study of applications of cyclodextrins and their derivatives in nano-delivery systems. The areas covered include nanospheres, nano-sponges, nanogels, cyclodextrin metal-organic frameworks, liposomes, and emulsions, providing a comprehensive and in-depth understanding of the design and development of nano-delivery systems.
- Published
- 2024
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26. Neural and immune roles in osteoarthritis pain: Mechanisms and intervention strategies.
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Zou Y, Liu C, Wang Z, Li G, and Xiao J
- Abstract
Pain is the leading symptom for most individuals with osteoarthritis (OA), a complex condition marked by joint discomfort. Recently, the dynamic interplay between the nervous and immune systems has become a focal point for understanding pain regulation. Despite this, there is still a substantial gap in our comprehensive understanding of the neuroimmune interactions and their effects on pain in OA. This review examines the bidirectional influences between immune cells and nerves in OA progression. It explores current approaches that target neuroimmune pathways, including promoting M2 macrophage polarization and specific neuronal receptor targeting, for effective pain reduction., Translational Potential Statement: This review provides a comprehensive overview of the mechanisms underlying the interplay between the immune system and nervous system during the progression of OA, as well as their contributions to pain. Additionally, it compiles existing intervention strategies targeting neuroimmunity for the treatment of OA pain. This information offers valuable insights for researchers seeking to address the challenge of OA pain., (© 2024 The Authors.)
- Published
- 2024
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27. Accumulated β-catenin is associated with human atrial fibrosis and atrial fibrillation.
- Author
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Bai Y, Li R, Hao JF, Chen LW, Liu ST, Zhang XL, Lip GYH, Yang JK, Zou YX, and Wang H
- Subjects
- Aged, Animals, Female, Humans, Male, Mice, Middle Aged, Cadherins metabolism, Connexin 43 metabolism, Gap Junctions metabolism, Glycogen Synthase Kinase 3 beta metabolism, Mice, Inbred C57BL, Atrial Fibrillation pathology, Atrial Fibrillation metabolism, beta Catenin metabolism, Fibrosis, Heart Atria metabolism, Heart Atria pathology, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology
- Abstract
Background: Atrial fibrillation (AF) is associated with increased risk of stroke and mortality. It has been reported that the process of atrial fibrosis was regulated by β-catenin in rats with AF. However, pathophysiological mechanisms of this process in human with AF remain unclear. This study aims to investigate the possible mechanisms of β-catenin in participating in the atrial fibrosis using human right atrial appendage (hRAA) tissues ., Methods: We compared the difference of β-catenin expression in hRAA tissues between the patients with AF and sinus rhythm (SR). The possible function of β-catenin in the development of AF was also explored in mice and primary cells., Results: Firstly, the space between the membrane of the gap junctions of cardiomyocytes was wider in the AF group. Secondly, the expression of the gap junction function related proteins, Connexin40 and Connexin43, was decreased, while the expression of β-catenin and its binding partner E-cadherin was increased in hRAA and cardiomyocytes of the AF group. Thirdly, β-catenin colocalized with E-cadherin on the plasma membrane of cardiomyocytes in the SR group, while they were dissociated and accumulated intracellularly in the AF group. Furthermore, the expression of glycogen synthase kinase 3β (GSK-3β) and Adenomatous Polyposis Coli (APC), which participated in the degradation of β-catenin, was decreased in hRAA tissues and cardiomyocytes of the AF group. Finally, the development of atrial fibrosis and AF were proved to be prevented after inhibiting β-catenin expression in the AF model mice., Conclusions: Based on human atrial pathological and molecular analyses, our findings provided evidence that β-catenin was associated with atrial fibrosis and AF progression., (© 2024. The Author(s).)
- Published
- 2024
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28. Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.
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Zhao R, Ren B, Xiao Y, Tian J, Zou Y, Wei J, Qi Y, Hu A, Xie X, Huang ZJ, Shu Y, He M, Lu J, and Tai Y
- Subjects
- Animals, Mice, Action Potentials, Male, GABAergic Neurons physiology, GABAergic Neurons metabolism, Neuronal Plasticity physiology, Homeostasis, Axon Initial Segment metabolism, Axons physiology, Axons metabolism, Synapses physiology
- Abstract
Homeostatic plasticity maintains the stability of functional brain networks. The axon initial segment (AIS), where action potentials start, undergoes dynamic adjustment to exert powerful control over neuronal firing properties in response to network activity changes. However, it is poorly understood whether this plasticity involves direct synaptic input to the AIS. Here, we show that changes of GABAergic synaptic input from chandelier cells (ChCs) drive homeostatic tuning of the AIS of principal neurons (PNs) in the prelimbic (PL) region, while those from parvalbumin-positive basket cells do not. This tuning is evident in AIS morphology, voltage-gated sodium channel expression, and PN excitability. Moreover, the impact of this homeostatic plasticity can be reflected in animal behavior. Social behavior, inversely linked to PL PN activity, shows time-dependent alterations tightly coupled to changes in AIS plasticity and PN excitability. Thus, AIS-originated homeostatic plasticity in PNs may counteract deficits elicited by imbalanced ChC presynaptic input at cellular and behavioral levels.
- Published
- 2024
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29. [Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections].
- Author
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Fu CK, Liu H, Wang LX, Zou YH, Li MQ, Lin YM, Sun WH, Wei X, Hu YE, Xie YM, and Li YY
- Subjects
- Humans, China, Injections, Pharmacovigilance, Medicine, Chinese Traditional standards, Medicine, Chinese Traditional adverse effects, Drugs, Chinese Herbal adverse effects, Drugs, Chinese Herbal standards, Drugs, Chinese Herbal administration & dosage
- Abstract
In 2019, the newly revised Drug Administration Law of the People's Republic of China was issued and implemented,clearly proposing that China should establish a pharmacovigilance system. As a new traditional Chinese medicine(TCM) dosage form created in China, TCM injections have been widely used in clinic, and its pharmacovigilance has attracted much attention. In response to this situation, the project team convened a group of clinical, pharmaceutical and evidence-based medicine experts from all over the country to form an expert group, which formulated the Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections in strict accordance with the requirements of the group standards of the Chinese Association of Chinese Medicine.From the perspective of clinical application and considering the key elements of pharmacovigilance for clinical application of TCM injections, the guidelines put forward suggestions on the decision making of pharmacovigilance for clinical application of TCM injections from four key links, namely the monitoring and reporting, signal recognition, risk assessment and risk control, according to China's pharmacovigilance regulations and learning from foreign pharmacovigilance guidelines.
- Published
- 2024
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30. Effectiveness of a Teach-Back Education Program on Perioperative Pain in Patients With Lung Cancer: An Intervention Study Using Behavior Change Wheel.
- Author
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Wang P, Zhang Q, Li GP, Xu N, Wang Z, Zhao YH, Zou YY, Liu YF, and Wang LM
- Subjects
- Humans, Female, Male, Middle Aged, Prospective Studies, Aged, China, Patient Education as Topic methods, Patient Education as Topic standards, Patient Education as Topic statistics & numerical data, Pain, Postoperative therapy, Adult, Lung Neoplasms complications, Lung Neoplasms surgery, Pain Measurement methods, Pain Management methods, Pain Management standards, Pain Management statistics & numerical data
- Abstract
Objective: To assess the effect of a teach-back educational intervention using Behavior Change Wheel (BCW) framework on perioperative pain among patients with lung cancer., Methods: A prospective quasi-experimental study was conducted in 88 patients with lung cancer from a tertiary hospital in China. According to the order of admission, they were allocated to either control group or intervention group, with 44 patients in each group. Patients in the control group received routine nursing care, while patients in the intervention group were given a teach-back education program based on BCW framework. The visual analog scale (VAS) was adopted to evaluate patients' pain on the day of surgery (T0), 1 (T1), 2 (T2), and 3 (T3) days after surgery. We also recorded the use of patient-controlled analgesia (PCA), the length of hospital stay, and the degree of patients' satisfaction., Results: Rest pain, pain when coughing, and pain during activity that patients in the intervention group experienced were significantly less severe than those in the control group on T0 and T1. The pain when coughing in the intervention group was also significantly milder on T2 and T3. In addition, the number of self-control time, use duration, and total dose of PCA were significantly lower in the intervention group. Moreover, patients' satisfaction of nursing service was significantly higher in the intervention group., Conclusion: A teach-back education program based on BCW framework was effective in pain management among the perioperative patients with lung cancer. This study demonstrates the application of teach-back method and the BCW in the development of patient education intervention to mitigate perioperative pain., 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. Published by Elsevier Inc.)
- Published
- 2024
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31. Towards mixed physical node reservoir computing: light-emitting synaptic reservoir system with dual photoelectric output.
- Author
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Lian M, Gao C, Lin Z, Shan L, Chen C, Zou Y, Cheng E, Liu C, Guo T, Chen W, and Chen H
- Abstract
Memristor-based physical reservoir computing holds significant potential for efficiently processing complex spatiotemporal data, which is crucial for advancing artificial intelligence. However, owing to the single physical node mapping characteristic of traditional memristor reservoir computing, it inevitably induces high repeatability of eigenvalues to a certain extent and significantly limits the efficiency and performance of memristor-based reservoir computing for complex tasks. Hence, this work firstly reports an artificial light-emitting synaptic (LES) device with dual photoelectric output for reservoir computing, and a reservoir system with mixed physical nodes is proposed. The system effectively transforms the input signal into two eigenvalue outputs using a mixed physical node reservoir comprising distinct physical quantities, namely optical output with nonlinear optical effects and electrical output with memory characteristics. Unlike previously reported memristor-based reservoir systems, which pursue rich reservoir states in one physical dimension, our mixed physical node reservoir system can obtain reservoir states in two physical dimensions with one input without increasing the number and types of devices. The recognition rate of the artificial light-emitting synaptic reservoir system can achieve 97.22% in MNIST recognition. Furthermore, the recognition task of multichannel images can be realized through the nonlinear mapping of the photoelectric dual reservoir, resulting in a recognition accuracy of 99.25%. The mixed physical node reservoir computing proposed in this work is promising for implementing the development of photoelectric mixed neural networks and material-algorithm collaborative design., (© 2024. The Author(s).)
- Published
- 2024
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32. Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females.
- Author
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Naratadam GT, Mecklenburg J, Shein SA, Zou Y, Lai Z, Tumanov AV, Price TJ, and Akopian AN
- Subjects
- Animals, Female, Male, Mice, Peripheral Nervous System Diseases chemically induced, Peripheral Nervous System Diseases genetics, Nerve Regeneration drug effects, Neuralgia chemically induced, Neuralgia genetics, Transcriptome, Pain, Ganglia, Spinal metabolism, Ganglia, Spinal drug effects, Paclitaxel adverse effects
- Abstract
This study investigated the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hindpaws and dorsal root ganglia (DRG). Bulk RNA-seq was used to examine these gene expression changes at 1, 16, and 31 days post-last PTX. At these time points, differentially expressed genes (DEGs) were predominantly related to the reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis. These processes are accompanied by the regulation of DEGs related to the cytoskeleton, extracellular matrix organization, and cellular energy production. This gene plasticity during the progression of persistent painful neuropathy could be interpreted as a biological process linked to tissue regeneration/degeneration. In contrast, gene plasticity related to immune processes was minimal at 1-31 days after PTX. It was also noted that despite similarities in biological processes and pain chronicity between males and females, specific DEGs differed dramatically according to sex. The main conclusions of this study are that gene expression plasticity in hindpaw and DRG during PTX neuropathy progression similar to tissue regeneration and degeneration, minimally affects immune system processes and is heavily sex-dependent at the individual gene level., (© 2024. The Author(s).)
- Published
- 2024
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33. The Research Progress of Magnesium Alloy Building Formwork.
- Author
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Wang J, Wan Z, Wang J, Zou Y, Xu J, Wang J, and Pan F
- Abstract
Building formwork is a kind of temporary supporting structure consumable material used in the construction field. In recent years, building formwork has gradually developed to become lighter, more environmentally friendly, and have higher performance. This sets higher requirements for the materials used to make building formwork. There is an urgent need to find a lighter and more durable material for building formwork. Magnesium alloys possess the advantages of low density, high alkali resistance, and high strength. As a building formwork material, it can reduce the weight of formwork and improve its durability. Therefore, a magnesium alloy is considered a material with high potential for building formwork. Currently, magnesium alloy building formwork has attracted the attention of many companies and research and development institutions, with preliminary research applications and good feedback on usage effects. It is highly possible to obtain the opportunity to put it into market application. However, to be applied on a large scale, there are still some important problems that need to be solved. These problems fall into three main areas, including the relatively low processing efficiency of magnesium alloy materials, the unstable price of magnesium alloys, and the fact that the formwork is easily corroded during storage. Firstly, at present, the main processing methods for magnesium alloy building formwork are casting and extrusion, and the production efficiency of both methods needs to be improved. Secondly, high-performance magnesium alloy materials are usually more expensive, which is not conducive to the large-scale application of the formwork. The price of magnesium alloys has fluctuated greatly in recent years, which increases the difficulty of promoting magnesium alloy building formwork. Thirdly, in the atmosphere, the oxide film on the surface of the magnesium alloy cannot play an effective role in corrosion resistance. So, surface treatment is necessary for magnesium alloy building formwork. Among the various surface treatment methods for magnesium alloys, the chemical conversion method has the advantages of being easy to operate, cost-effective, and having good corrosion resistance. It may be a very suitable protective method for large-scale applications of magnesium alloy building formwork and possesses excellent potential for application. The future of magnesium alloy building formwork will focus on new low-cost materials, high-efficiency processing technology, and low-cost green anti-corrosion technology. With in-depth research and the maturation of technology, magnesium alloy formwork is expected to play a more important role in the construction industry., Competing Interests: The authors declare no conflicts of interest.
- Published
- 2024
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34. Thermoelectric Properties Regulated by Quantum Size Effects in Quasi-One-Dimensional γ-Graphdiyne Nanoribbons.
- Author
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Li M, Liu Q, Zou Y, Wang J, and Fan C
- Abstract
Using density functional theory combined with the first principles calculation method of non-equilibrium Green's function (NEGF-DFT), we studied the thermoelectric (TE) characteristics of one-dimensional γ-graphdiyne nanoribbons (γ-GDYNRs). The study found that the thermal conductivity of γ-GDYNRs has obvious anisotropy. At the same temperature and geometrical size, the lattice thermal conductivity of zigzag-edged γ-graphdiyne nanoribbons (γ-ZGDYNRs) is much lower than that of armchair-edged γ-graphdiyne nanoribbons (γ-AGDYNRs). We disclose the underlying mechanism for this intrinsic orientation. That is, γ-AGDYNRs have more phonon dispersion over the entire frequency range. Furthermore, the orientation dependence increases when the width of the γ-GDYNRs decreases. These excellent TE properties allow armchair-edged γ-graphdiyne nanoribbons with a planar width of 1.639 nm (γ-Z(2)GDYNRs) to have a higher power factor and lower thermal conductivity, ultimately resulting in a significantly higher TE conversion rate than other γ-GDYNR structures.
- Published
- 2024
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35. Dysregulated expression of miR-140 and miR-122 compromised microglial chemotaxis and led to reduced restriction of AD pathology.
- Author
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Song C, Li S, Mai Y, Li L, Dai G, Zhou Y, Liang X, Zou OM, Wang Y, Zhou L, Liu J, and Zou Y
- Subjects
- Animals, Mice, Humans, Male, Female, ADAM10 Protein metabolism, ADAM10 Protein genetics, Amyloid Precursor Protein Secretases metabolism, Amyloid Precursor Protein Secretases genetics, Mice, Transgenic, Aged, Gene Expression Regulation, MicroRNAs metabolism, MicroRNAs genetics, Alzheimer Disease metabolism, Alzheimer Disease pathology, Alzheimer Disease genetics, Microglia metabolism, Microglia pathology, Mice, Inbred C57BL, Chemotaxis physiology
- Abstract
Background: Deposition of amyloid β, which is produced by amyloidogenic cleavage of APP by β- and γ-secretase, is one of the primary hallmarks of AD pathology. APP can also be processed by α- and γ-secretase sequentially, to generate sAPPα, which has been shown to be neuroprotective by promoting neurite outgrowth and neuronal survival, etc. METHODS: The global expression profiles of miRNA in blood plasma samples taken from 11 AD patients as well as from 14 age and sex matched cognitively normal volunteers were analyzed using miRNA-seq. Then, overexpressed miR-140 and miR-122 both in vivo and in vitro, and knock-down of the endogenous expression of miR-140 and miR-122 in vitro. Used a combination of techniques, including molecular biology, immunohistochemistry, to detect the impact of miRNAs on AD pathology., Results: In this study, we identified that two miRNAs, miR-140-3p and miR-122-5p, both targeting ADAM10, the main α-secretase in CNS, were upregulated in the blood plasma of AD patients. Overexpression of these two miRNAs in mouse brains induced cognitive decline in wild type C57BL/6J mice as well as exacerbated dyscognition in APP/PS1 mice. Although significant changes in APP and total Aβ were not detected, significantly downregulated ADAM10 and its non-amyloidogenic product, sAPPα, were observed in the mouse brains overexpressing miR-140/miR-122. Immunohistology analysis revealed increased neurite dystrophy that correlated with the reduced microglial chemotaxis in the hippocampi of these mice, independent of the other two ADAM10 substrates (neuronal CX3CL1 and microglial TREM2) that were involved in regulating the microglial immunoactivity. Further in vitro analysis demonstrated that both the reduced neuritic outgrowth of mouse embryonic neuronal cells overexpressing miR-140/miR-122 and the reduced Aβ phagocytosis in microglia cells co-cultured with HT22 cells overexpressing miR-140/miR-122 could be rescued by overexpressing the specific inhibitory sequence of miR-140/miR-122 TuD as well as by addition of sAPPα, rendering these miRNAs as potential therapeutic targets., Conclusions: Our results suggested that neuroprotective sAPPα was a key player in the neuropathological progression induced by dysregulated expression of miR-140 and miR-122. Targeting these miRNAs might serve as a promising therapeutic strategy in AD treatment., (© 2024. The Author(s).)
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- 2024
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36. A new multivariate index for ecological security assessment in the China-Myanmar border region.
- Author
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Zou Y, Wang S, Luo X, Jin H, Xiao X, and Li Y
- Subjects
- China, Myanmar, Ecology, Conservation of Natural Resources, Biodiversity, Ecosystem
- Abstract
The coordination of development efforts and ecological conservation in China's border regions is a significant challenge due to the overlap of biodiversity hotspots, ecologically fragile zones, and impoverished areas. Achieving the harmonious integration of ecological preservation and economic development relies on the fundamental assessment of ecological security (ES). However, comprehensive assessments of ES in border regions remain limited. This study introduces a new index, the multivariate ecological security index (MESI), which integrates ecosystem vigor, organization, elasticity, services and risk. Here, the MESI was utilized to assess the temporal and spatial changes in ES and its associated impact factors in the China-Myanmar border region (CMBR) from 2000 to 2020. The MESI provides a clear representation of the actual ES status in the CMBR, exhibiting a significant correlation with the eco-environmental quality index (EEQI; p < 0.01). The ES status exhibited notable spatial heterogeneity in the CMBR, consisting primarily of both relatively safe and safe levels, which accounted for approximately 85% of the total area. From 2000 to 2020, the CMBR experienced a gradual improvement in ES status, with the area experiencing an increase in the ES level accounting for 23.41% of the total area, which exceeded the proportion of the area experiencing a decrease in the ES level (4.71%). The combined impact of multiple factors exerted a greater influence on ES than did individual factors alone. Notably, human factors increasingly influenced the ES status during the study period. The results of this study provide valuable insights for ecological preservation and sustainable management in the CMBR, and the MESI can be extended to assess the ES of other regions., 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 Ltd.. All rights reserved.)
- Published
- 2024
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37. Discovery of highly potent PARP7 inhibitors for cancer immunotherapy.
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Yang J, Liu B, Yan W, Zhao X, Wang C, Zhu Q, Zou Y, Xu Y, and Gu H
- Subjects
- Humans, Structure-Activity Relationship, Molecular Structure, Animals, Mice, Poly(ADP-ribose) Polymerases metabolism, Cell Line, Tumor, Neoplasms drug therapy, Neoplasms pathology, Mice, Inbred BALB C, Poly(ADP-ribose) Polymerase Inhibitors pharmacology, Poly(ADP-ribose) Polymerase Inhibitors chemistry, Poly(ADP-ribose) Polymerase Inhibitors chemical synthesis, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Drug Screening Assays, Antitumor, Immunotherapy, Drug Discovery, Dose-Response Relationship, Drug, Cell Proliferation drug effects
- Abstract
PARP7 has been proven to play an important role in immunity. Substantial upregulation of PARP7 is observed in numerous cancerous cell types, consequently resulting in the inhibition of type Ⅰ interferon signaling pathways. Therefore, inhibiting the activity of PARP7 can enhance type Ⅰ interferon signaling to exert an anti-tumor immune response. In this study, we reported the identification of a newly found PARP7 inhibitor (XLY-1) with higher inhibitory activity (IC
50 = 0.6 nM) than that of RBN-2397 (IC50 = 6.0 nM). Additionally, XYL-1 displayed weak inhibitory activity on PARP1 (IC50 > 1.0 μM). Mechanism studies showed that XYL-1 could enhance the type Ⅰ interferon signaling in vitro. Pharmacodynamic experiments showed that 50 mg/kg XYL-1 could significantly inhibit tumor growth (TGI: 76.5 %) and related experiments showed that XYL-1 could restore type Ⅰ interferon signaling and promote T cell infiltration in tumor tissues. Taken together, XYL-1 shows promise as a potential candidate for developing cancer immunotherapy agents., 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 Inc. All rights reserved.)- Published
- 2024
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38. Gut Microbiota-Derived 3-Hydroxybutyrate Blocks GPR43-Mediated IL6 Signaling to Ameliorate Radiation Proctopathy.
- Author
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Ge Z, Chen C, Chen J, Jiang Z, Chen L, Wei Y, Chen H, He L, Zou Y, Long X, Zhan H, Wang H, Wang H, and Lu Y
- Subjects
- Animals, Mice, Humans, Radiation Injuries metabolism, Disease Models, Animal, Proctitis metabolism, Mice, Inbred C57BL, Male, Akkermansia metabolism, Gastrointestinal Microbiome, Interleukin-6 metabolism, Interleukin-6 genetics, Receptors, G-Protein-Coupled metabolism, Receptors, G-Protein-Coupled genetics, Signal Transduction, 3-Hydroxybutyric Acid metabolism, 3-Hydroxybutyric Acid pharmacology
- Abstract
Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota-derived 3-hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6-mediated radiation damage. Irradiated cell-fecal microbiota co-culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43-mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut-immune axis in radiation pathophysiology, with potential therapeutic applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
- Published
- 2024
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39. Analysis of factors influencing the recurrence of diabetic foot ulcers.
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Hu L, Liu W, Yin L, Yi X, Zou Y, and Sheng X
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Risk Factors, Diabetic Foot epidemiology, Recurrence
- Abstract
Objective: The aim of this study is to investigate the factors influencing the recurrence of diabetic foot ulcers (DFU) and provide guidance for reducing the recurrence rate., Methods: A total of 211 patients diagnosed with DFU who were hospitalized and discharged from the hospital from October 2015 to January 2020 were included as the study cohort. Participants were divided into two groups according to whether the foot ulcer recurred during the 2-year follow-up period: a recurrence group (n = 84) and a non-recurrence group (n = 127). The following data were collected and analyzed for the two groups of patients: general information, foot information, laboratory indicators, diabetes comorbidities, and complications., Results: (1) The overall recurrence rate of diabetic foot ulcers (DFU) within 2 years was 39.8%, indicating a high recurrence rate. (2) Significant differences were observed between the two patient groups in terms of BMI, HbA1c, TBIL, CRP, financial situation, foot deformity, first ulcer on the sole of the foot, previous amputation history, Wagner grade of the first ulcer, osteomyelitis, DFU duration (>60 days), lower limb vascular reconstruction, peripheral arterial disease (PAD), and diabetic peripheral neuropathy (DPN) (t = 2.455; Z = -1.988, -3.731, -3.618; χ2 = 7.88, 5.004, 3.906, 17.178, 16.237, 5.007, 24.642, 4.782, 29.334, 10.253). No significant differences were found for the other indicators. (3) Logistic regression analysis revealed that TBIL (OR = 0.886, p = 0.036) was a protective factor against ulcer recurrence. In contrast, PAD, previous amputation history, DPN, and the first ulcer on the sole of the foot (OR = 3.987, 6.758, 4.681, 2.405; p < 0.05 or p < 0.01) were identified as risk factors for ulcer recurrence., Conclusion: Early screening and preventive education targeting high-risk factors such as DPN, PAD and the initial ulcer location on the sole of the foot are essential to mitigate the high long-term recurrence rate of DFU. Furthermore, the protective role of TBIL in preventing ulcer recurrence underscores the importance of monitoring bilirubin levels as part of a comprehensive management strategy for DFU patients., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)
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- 2024
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40. Biosynthesis and Assembly Logic of Fungal Hybrid Terpenoid Natural Products.
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Yuan GY, Zhang JM, Xu YQ, and Zou Y
- Abstract
In recent decades, fungi have emerged as significant sources of diverse hybrid terpenoid natural products, and their biosynthetic pathways are increasingly unveiled. This review mainly focuses on elucidating the various strategies underlying the biosynthesis and assembly logic of these compounds. These pathways combine terpenoid moieties with diverse building blocks including polyketides, nonribosomal peptides, amino acids, p-hydroxybenzoic acid, saccharides, and adenine, resulting in the formation of plenty of hybrid terpenoid natural products via C-O, C-C, or C-N bond linkages. Subsequent tailoring steps, such as oxidation, cyclization, and rearrangement, further enhance the biological diversity and structural complexity of these hybrid terpenoid natural products. Understanding these biosynthetic mechanisms holds promise for the discovery of novel hybrid terpenoid natural products from fungi, which will promote the development of potential drug candidates in the future., (© 2024 Wiley-VCH GmbH.)
- Published
- 2024
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41. Dispersal limitation and environmental filtering effects: The taxonomic and functional beta diversity of ground beetles along the altitudinal gradient in Chinese warm-temperature forests.
- Author
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Shen Y, Zou Y, Song K, and Wan X
- Abstract
Beta diversity patterns along environmental gradients and underlying mechanisms constitute key research inquiries in biogeography. However, ecological processes often also influence the functional traits of biological communities, making the assessment of functional β-diversity crucial. Ground beetles (Coleoptera: Carabidae) are one of the most species-rich groups in the insect community, displaying strong habitat specificity and morphological differences. In this study, we explored the patterns of taxonomic and functional beta diversity in ground beetle communities along the altitudinal gradient of warm-temperature forests. By partitioning beta diversity into turnover and nestedness components, we evaluated their relationship with spatial distance. Our findings indicate a decline in species and functional trait similarity with increasing elevation and geographic distance. Further analysis attributed both types of beta diversity in carabids to a combination of dispersal limitation and environmental filtering, with elevation and geographic distance emerging as significant factors. Interestingly, forest-type variations were found to have no impact on the beta diversity of these communities. Our study reveals the impact of environmental filtering and dispersal limitation on both taxonomic and functional beta-diversity, shedding light on carabid community assembly in localized warm-temperature forest areas in eastern China., Competing Interests: The authors declare no potential conflict of interest., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)
- Published
- 2024
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42. The effect of stretching exercises before orthotic treatment on the immediate in-orthosis correction of the patients with adolescent idiopathic scoliosis: A pilot study.
- Author
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Luo CL, Wu HD, Beygi BH, Liu S, Zou YY, Shang LJ, and Wong MS
- Abstract
Background: Stretching exercise is generally used for improving flexibility. However, its application to promote orthotic treatment for patients with adolescent idiopathic scoliosis (AIS) remains unknown., Objective: This study was to explore the effect of pre-orthosis stretching exercises on spinal flexibility and initial in-orthosis correction for the patients with AIS., Study Design: A pilot-controlled study., Methods: An experimental group (EG) of 13 subjects (10 girls and 3 boys) with AIS allocating to self-stretching exercises and a control group (CG) of 19 AIS subjects (14 girls and 5 boys) with no stretching before orthosis fitting were recruited. The spinal flexibility of the EG was evaluated with an ultrasound imaging system and physical measurements. The initial in-orthosis correction rates between the 2 groups were compared with the independent t test, and the correlation analysis between the spinal flexibility measured from ultrasound images and physical measurement was performed with the Pearson correlation test., Results: The initial Cobb angle of EG and CG were 25.70° ± 7.30° and 28.09° ± 5.58°, respectively. No significant difference was observed between the initial in-orthosis Cobb angle of EG (11.13° ± 6.80°) and CG (15.65° ± 9.10°) (p = 0.06). However, the spinal flexibility after stretching exercises was improved (p < 0.001), and the spinal flexibility changes measured with ultrasound and physical forward-bending method were significantly correlated (r = 0.57, p < 0.05)., Conclusion: Stretching exercises before orthotic treatment could improve the spinal flexibility but did not cause a better in-orthosis correction. A study with a larger sample size and longer follow-up period should be conducted to investigate the long-term effect of stretching exercises., (Copyright © 2024 International Society for Prosthetics and Orthotics.)
- Published
- 2024
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43. Pilot study of circulating cell-free mitochondrial DNA in relation to brain structure in youth bipolar disorder.
- Author
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Shao S, Zou Y, Kennedy KG, Dimick MK, Andreazza AC, Young LT, Goncalves VF, MacIntosh BJ, and Goldstein BI
- Abstract
Background: Mitochondrial dysfunction is implicated in the neuropathology of bipolar disorder (BD). Higher circulating cell-free mitochondrial DNA (ccf-mtDNA), generally reflecting poorer mitochondrial health, has been associated with greater symptoms severity in BD. The current study examines the association of serum ccf-mtDNA and brain structure in relation to youth BD. We hypothesized that higher ccf-mtDNA will be associated with measures of lower brain structure, particularly in the BD group., Methods: Participants included 40 youth (BD, n = 19; Control group [CG], n = 21; aged 13-20 years). Serum ccf-mtDNA levels were assayed. T1-weighted brain images were acquired using 3T-MRI. Region of interest (ROI) analyses examined prefrontal cortex (PFC) and whole brain gray matter, alongside exploratory vertex-wise analyses. Analyses examined ccf-mtDNA main-effects and ccf-mtDNA-by-diagnosis interaction effects controlling for age, sex, and intracranial volume., Results: There was no significant difference in ccf-mtDNA levels between BD and CG. In ROI analyses, higher ccf-mtDNA was associated with higher PFC surface area (SA) (β = 0.32 p < 0.001) and PFC volume (β = 0.32 p = 0.002) in the overall sample. In stratified analyses, higher ccf-mtDNA was associated with higher PFC SA within both subgroups (BD: β = 0.39 p = 0.02; CG: β = 0.24 p = 0.045). Higher ccf-mtDNA was associated with higher PFC volume within the BD group (β = 0.39 p = 0.046). In vertex-wise analyses, higher ccf-mtDNA was associated with higher SA and volume in frontal clusters within the overall sample and within the BD group. There were significant ccf-mtDNA-by-diagnosis interactions in three frontal and parietal clusters, whereby higher ccf-mtDNA was associated with higher neurostructural metrics in the BD group but lower neurostructural metrics in CG., Conclusions: Contrasting our hypothesis, higher ccf-mtDNA was consistently associated with higher, rather than lower, regional neuralstructural metrics among youth with BD. While this finding may reflect a compensatory mechanism, future repeated-measures prospective studies evaluating the inter-relationship among ccf-mtDNA, mood, and brain structure across developmental epochs and illness stages are warranted., (© 2024. The Author(s).)
- Published
- 2024
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44. The Role and Treatment Strategies of Ammonia-Related Metabolism in Tumor Microenvironment.
- Author
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Ye Q, Li D, Zou Y, and Yuan Y
- Abstract
Tumor cells achieve their adaptability through various metabolic reprogramming processes. Among them, ammonia, as a traditional metabolic waste, plays an increasingly important role in the tumor microenvironment along with its associated metabolites. Other cells in the microenvironment can also reshape the immune status of the microenvironment by regulating ammonia-related metabolism, and targeting this metabolic aspect has emerged as a potential strategy for tumor treatment. In this study, we have systematically reviewed the source and destination of ammonia in tumor cells, as well as the links between ammonia and other biological processes. We have also analyzed the ammonia-related metabolic regulation of other cells (including T cells, macrophages, dendritic cells, natural killer cells, myeloid-derived suppressor cells, and stromal cells) in the tumor microenvironment, and summarized the tumor treatment methods that target this metabolism. Through ammonia-related metabolic reprogramming, tumor cells obtain the energy they need for rapid growth and proliferation. Multiple immune cells and stromal cells in the microenvironment also interact with each other through this metabolic regulation, ultimately leading to immune suppression. Despite the heterogeneity of tumors and the complexity of cellular functions, further research into therapeutic interventions targeting ammonia-related metabolism is warranted. This review has focused on the role and regulation of ammonia-related metabolism in tumor cells and other cells in the microenvironment, and highlighted the efficacy and prospects of targeted ammonia-related metabolism therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2024
- Full Text
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45. Discovery of novel EGFR-PROTACs capable of degradation of multiple EGFR-mutated proteins.
- Author
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Du Y, Shi S, Shu C, He Y, Xu W, Wu D, Tian Y, Kong M, He J, Xie W, Qiu Y, Xu Y, Zou Y, and Zhu Q
- Subjects
- Humans, Animals, Structure-Activity Relationship, Drug Discovery, Mice, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors chemistry, Protein Kinase Inhibitors chemical synthesis, Drug Screening Assays, Antitumor, Molecular Structure, Cell Line, Tumor, Dose-Response Relationship, Drug, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Lung Neoplasms metabolism, Mice, Nude, Proteolysis Targeting Chimera, ErbB Receptors metabolism, ErbB Receptors antagonists & inhibitors, ErbB Receptors genetics, Antineoplastic Agents pharmacology, Antineoplastic Agents chemistry, Antineoplastic Agents chemical synthesis, Cell Proliferation drug effects, Proteolysis drug effects, Mutation
- Abstract
Although three generations of Epidermal growth factor receptor (EGFR) - TK inhibitors have been approved for the treatment of Non-small-cell lung cancers (NSCLC), their clinical application is still largely hindered by acquired drug resistance mediated new EGFR mutations and side effects. The Proteolysis targeting chimera (PROTAC) technology has the potential to overcome acquired resistance from mutant EGFR through a novel mechanism of action. In this study, we developed the candidate degrader IV-3 by structural modifications of the lead compound 13, which exhibited limited antiproliferative activity against HCC-827 cells. Compared to compound 13, IV-3 exhibited remarkable anti-proliferative activity against HCC-827 cells, NCI-H1975 cells, and NCI-H1975-TM cells (IC
50 = 0.009 μM, 0.49 μM and 3.24 μM, respectively), as well as significantly inducing degradation of EGFR protein in these cell lines (DC50 = 17.93 nM, 0.25 μM and 0.63 μM, respectively). Further investigations confirmed that IV-3 exhibited superior anti-tumor activity in all xenograft tumor models through the degradation of mutant EGFR protein. Moreover, IV-3 showed no inhibitory activity against A431 and A549 cells expressing wild-type EGFR, thereby eliminating potential toxic side effects emerging from wild-type EGFR inhibition. Overall, our study provides promising insights into EGFR-PROTACs as a potential therapeutic strategy against EGFR-acquired mutation., 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
- Full Text
- View/download PDF
46. Axo-axonic synaptic input drives homeostatic plasticity by tuning the axon initial segment structurally and functionally.
- Author
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Zhao R, Ren B, Xiao Y, Tian J, Zou Y, Wei J, Qi Y, Hu A, Xie X, Huang ZJ, Shu Y, He M, Lu J, and Tai Y
- Abstract
The stability of functional brain network is maintained by homeostatic plasticity, which restores equilibrium following perturbation. As the initiation site of action potentials, the axon initial segment (AIS) of glutamatergic projection neurons (PyNs) undergoes dynamic adjustment that exerts powerful control over neuronal firing properties in response to changes in network states. Although AIS plasticity has been reported to be coupled with the changes of network activity, it is poorly understood whether it involves direct synaptic input to the AIS. Here we show that changes of GABAergic synaptic input to the AIS of cortical PyNs, specifically from chandelier cells (ChCs), are sufficient to drive homeostatic tuning of the AIS within 1-2 weeks, while those from parvalbumin-positive basket cells do not. This tuning is reflected in the morphology of the AIS, the expression level of voltage-gated sodium channels, and the intrinsic neuronal excitability of PyNs. Interestingly, the timing of AIS tuning in PyNs of the prefrontal cortex corresponds to the recovery of changes in social behavior caused by alterations of ChC synaptic transmission. Thus, homeostatic plasticity of the AIS at postsynaptic PyNs may counteract deficits elicited by imbalanced ChC presynaptic input., Teaser: Axon initial segment dynamically responds to changes in local input from chandelier cells to prevent abnormal neuronal functions.
- Published
- 2024
- Full Text
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47. Disruption of recombination machinery alters the mutational landscape in plant organellar genomes.
- Author
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Waneka G, Broz AK, Wold-McGimsey F, Zou Y, Wu Z, and Sloan DB
- Abstract
Land plant organellar genomes have extremely low rates of point mutation yet also experience high rates of recombination and genome instability. Characterizing the molecular machinery responsible for these patterns is critical for understanding the evolution of these genomes. While much progress has been made towards understanding recombination activity in land plant organellar genomes, the relationship between recombination pathways and point mutation rates remains uncertain. The organellar targeted mutS homolog MSH1 has previously been shown to suppress point mutations as well as non-allelic recombination between short repeats in Arabidopsis thaliana . We therefore implemented high-fidelity Duplex Sequencing to test if other genes that function in recombination and maintenance of genome stability also affect point mutation rates. We found small to moderate increases in the frequency of single nucleotide variants (SNVs) and indels in mitochondrial and/or plastid genomes of A. thaliana mutant lines lacking radA , recA1 , or recA3 . In contrast, osb2 and why2 mutants did not exhibit an increase in point mutations compared to wild type (WT) controls. In addition, we analyzed the distribution of SNVs in previously generated Duplex Sequencing data from A. thaliana organellar genomes and found unexpected strand asymmetries and large effects of flanking nucleotides on mutation rates in WT plants and msh1 mutants. Finally, using long-read Oxford Nanopore sequencing, we characterized structural variants in organellar genomes of the mutant lines and show that different short repeat sequences become recombinationally active in different mutant backgrounds. Together, these complementary sequencing approaches shed light on how recombination may impact the extraordinarily low point mutation rates in plant organellar genomes.
- Published
- 2024
- Full Text
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48. Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis.
- Author
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Hu J, Liu W, Zou Y, Jiao C, Zhu J, Xu Q, Zou J, Sun Y, and Guo W
- Abstract
Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth, differentiation, and survival. The activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's disease. Thus, the identification of SHP2 activators and a complete understanding of their mechanism is required. We used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open conformation. Oleanolic acid was identified as a suitable candidate. By binding to R362, K364, and K366 in the active center of the PTP domain, oleanolic acid maintained the active open state of SHP2, which facilitated the binding between SHP2 and its substrate. This oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6R α and inhibiting the activation of STAT3. Furthermore, via the activation of SHP2 and subsequent attenuation of the STAT3-Th17 axis, oleanolic acid effectively mitigated colitis in mice. This protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor SHP099. These findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors.)
- Published
- 2024
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49. A Cytochrome P450 Catalyzes Oxidative Coupling Formation of Insecticidal Dimeric Indole Piperazine Alkaloids.
- Author
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He Q, Zhang HR, and Zou Y
- Subjects
- Animals, Biocatalysis, Dimerization, Indole Alkaloids chemistry, Indole Alkaloids metabolism, Molecular Structure, Oxidation-Reduction, Alkaloids chemical synthesis, Alkaloids metabolism, Cytochrome P-450 Enzyme System metabolism, Cytochrome P-450 Enzyme System chemistry, Insecticides chemical synthesis, Insecticides chemistry, Piperazines chemistry
- Abstract
Cytochrome P450 (CYP450)-catalyzed oxidative coupling is an efficient strategy for using simple building blocks to construct complex structural scaffolds of natural products. Among them, heterodimeric coupling between two different monomers is relatively scarce, and the corresponding CYP450s are largely undiscovered. In this study, we discovered a fungal CYP450 (CpsD) and its associated cps cluster from 37208 CYP450s of Pfam PF00067 family member database and subsequently identified a group of new skeleton indole piperazine alkaloids (campesines A-G) by combination of genome mining and heterologous synthesis. Importantly, CYP450 CpsD mainly catalyzes intermolecular oxidative heterocoupling of two different indole piperazine monomers to generate an unexpected 6/5/6/6/6/6/5/6 eight-ring scaffold through the formation of one C-C bond and two C-N bonds, illuminating its first dimerase role in this family of natural products. The proposed catalytic mechanism of CpsD was deeply investigated by diversified substrate derivatization. Moreover, dimeric campesine G shows good insecticidal activity against the global honeybee pest Galleria mellonella. Our study shows a representative example of discovering new skeleton monomeric and dimeric indole piperazine alkaloids from microbial resources, expands our knowledge of bond formation by CYP450s and supports further development of the newly discovered and engineered campesine family compounds as potential biopesticides., (© 2024 Wiley-VCH GmbH.)
- Published
- 2024
- Full Text
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50. Energy competition remodels the metabolic glucose landscape of psoriatic epidermal cells.
- Author
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Liu W, Jiang J, Li Z, Xiao Y, Zhou S, Wang D, Zou Y, Liu T, Li K, Liang H, Wang N, Xiang X, Xie Q, Zhan R, Zhang J, Zhou X, Yang L, Chuong CM, and Lei M
- Subjects
- Humans, Animals, Mice, Disease Models, Animal, Single-Cell Analysis, Epidermal Cells metabolism, Reactive Oxygen Species metabolism, Energy Metabolism, Epidermis metabolism, Epidermis pathology, Imiquimod, Male, Psoriasis metabolism, Psoriasis pathology, Glucose metabolism, Keratinocytes metabolism, Cell Proliferation, Cell Differentiation
- Abstract
Rationale: Skin cells actively metabolize nutrients to ensure cell proliferation and differentiation. Psoriasis is an immune-disorder-related skin disease with hyperproliferation in epidermal keratinocytes and is increasingly recognized to be associated with metabolic disturbance. However, the metabolic adaptations and underlying mechanisms of epidermal hyperproliferation in psoriatic skin remain largely unknown. Here, we explored the role of metabolic competition in epidermal cell proliferation and differentiation in psoriatic skin. Methods: Bulk- and single-cell RNA-sequencing, spatial transcriptomics, and glucose uptake experiments were used to analyze the metabolic differences in epidermal cells in psoriasis. Functional validation in vivo and in vitro was done using imiquimod-like mouse models and inflammatory organoid models. Results: We observed the highly proliferative basal cells in psoriasis act as the winners of the metabolic competition to uptake glucose from suprabasal cells. Using single-cell metabolic analysis, we found that the "winner cells" promote OXPHOS pathway upregulation by COX7B and lead to increased ROS through glucose metabolism, thereby promoting the hyperproliferation of basal cells in psoriasis. Also, to prevent toxic damage from ROS, basal cells activate the glutathione metabolic pathway to increase their antioxidant capacity to assist in psoriasis progression. We further found that COX7B promotes psoriasis development by modulating the activity of the PPAR signaling pathway by bulk RNA-seq analysis. We also observed glucose starvation and high expression of SLC7A11 that causes suprabasal cell disulfide stress and affects the actin cytoskeleton, leading to immature differentiation of suprabasal cells in psoriatic skin. Conclusion: Our study demonstrates the essential role of cellular metabolic competition for skin tissue homeostasis., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)
- Published
- 2024
- Full Text
- View/download PDF
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