Search

Objective: Lung cancer (LC) is the highest contributor to cancer-associated mortality worldwide. Approximately 85% of all LC incidences involve non-small cell LC (NSCLC). Unfortunately, owing to a significant lack of sensitive and robust bioindicators, most patient diagnoses occur at advanced stages of the disease, thereby resulting in extremely poor patient outcomes. Herein, we elucidated the role of interleukin-17A (IL-17A) among NSCLC patients., Materials and Methods: Circulating IL-17A content was measured using enzyme-linked immunosorbent assay (ELISA), and its diagnostic and prognostic abilities were assessed using the receiver operating characteristic (ROC) curve and Kaplan-Meier analysis, respectively., Results: Our analysis revealed that circulating IL-17A levels were significantly augmented among NSCLC vs. control samples. Moreover, based on our area under the curve (AUC) analysis, circulating IL-17A levels fared considerably better than the standard bioindicator carcinoembryonic antigen (CEA) in both testing and validation cohorts. Notably, we also revealed that the circulating IL-17A levels were accurately and reliably predicted in early-stage NSCLC patients. Besides, we demonstrated a strong correlation between elevated circulating IL-17A expression and worse prognosis among NSCLC patients., Conclusions: Herein, we demonstrated that circulating IL-17A levels can serve as reliable and potent diagnostic and prognostic bioindicators for NSCLC.

Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly men. It's first-line therapy is drugs. But with the progression of the disease or side effects of drugs, surgical treatment will become a better choice. However, either transurethral resection of the prostate, the standard procedure, or enucleation or resection of the prostate based on various laser platforms or plasma technologies cause a high incidence of retrograde ejaculation in their postoperative follow-up. In the past, retrograde ejaculation was usually regarded as the cost of benign prostatic hyperplasia surgery. In recent years, with the continuous improvement of surgical skills and the emergence of new techniques, retrograde ejaculation has aroused the attention of clinicians. This article mainly introduces the mechanism of retrograde ejaculation after benign prostatic hyperplasia surgery and the methods to reduce the incidence of retrograde ejaculation after surgery. These methods mainly include various modified surgery, as well as novel minimally invasive techniques such as prostate embolization and prostatic urethral lift.

Rationale: Pulmonary embolism (PE) is a common cause of cardiovascular death whose major acquired risk factors include postoperative states, pregnancy, malignancy, and age. We report a case of PE that occurred after diagnostic curettage for abnormal uterine bleeding, with a medical history of adenomyosis and hysteromyoma., Patient Concerns and Diagnoses: A 31-year-old Han Chinese female was referred to our hospital with menstrual disorders, increased menstrual flow, and severe anemia. After admission, the patient was treated with a blood transfusion, iron supplementation, and erythropoietin, and diagnostic curettage was performed the following day. On the first postoperative day, the patient developed pulmonary embolism with dyspnea and fever diagnosed by CT pulmonary angiography and significantly elevated D-dimer., Interventions and Outcomes: Molecular weight heparin was administered for PE for 2 weeks, dyspnea was relieved significantly after 2 days of treatment and the uterine bleeding did not increase; and gonadotropin-releasing hormone agonists were administered for adenomyosis after 1 week of anticoagulant therapy to reduce bleeding. We followed up for 6 months, and the patient had no recurrence of thrombosis and uterine bleeding had improved., Conclusion: We speculate that the occurrence of pulmonary embolism was closely related to adenomyosis, hysteromyoma, and curettage in this patient. Treating the presence of both menstrual bleeding and thromboembolism is challenging, and careful management is necessary to avoid therapeutic contradictions., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study was to evaluate the efficacy of an integrated mycotoxin-mitigating agent in reducing the adverse effects of co-occurring dietary aflatoxin B 1 deoxynivalenol and ochratoxin A on broiler breeder hens. 360 30-week-old Hubbard Efficiency Plus broiler breeder hens were allocated into four groups and received a basal diet (BD; Control), BD added 0.15 mg/kg aflatoxin B 1 +1.5 mg/kg deoxynivalenol+0.12 mg/kg ochratoxin A (Toxins), BD plus Toxins with 0.1% TOXO-XL (Toxins + XL1), and BD plus Toxins with 0.2% TOXO-XL (Toxins + XL2), respectively, for 8 weeks, and then received the same BD for another 4 weeks. Compared with control, mycotoxins decreased total egg weigh, egg laying rate, settable eggs rate, hatch of total eggs rate, egg quality, but increased feed/egg ratio and mortality rate, and impaired the liver and oviduct health during weeks 1-8 and(or) 9-12. It also increased PC and MDA concentrations, TUNEL-positive cells and IL-1β and IL-6 expression, and decreased T-AOC, GPX and CAT activities in liver and/or oviduct. Notably, most of these negative changes were mitigated by both dosages of TOXO-XL. Generally, 0.2% TOXO-XL displayed better mitigation effects than 0.1% TOXO-XL. Conclusively, these findings revealed that TOXO-XL could mitigate the combined mycotoxins-induced toxicity on the performance, liver and oviduct health, through the regulation of redox, immunity, and apoptosis in broiler breeder hens., 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 © 2023 Elsevier Ltd. All rights reserved.)

Aim: To evaluate the overall diagnostic performance of magnetic resonance imaging (MRI), different image features, and different image analysis methods in predicting hepatocellular carcinoma (HCC) with cytokeratin 19 (CK19) expression., Materials and Methods: A systematic literature search was performed to identify studies using MRI to predict HCC with CK19 expression between 2012 and 2023. Data were extracted to calculate the pooled sensitivity and specificity. Overall diagnostic performance was assessed using areas under the summary receiver operating characteristic curve (AUC). Subgroup analyses were conducted for specific image features and according to image analysis methods (traditional image feature, radiomics, and combined methods). Z-test statistics was used to analyse the differences in diagnostic performance between combined and individual methods., Results: Eleven studies with 14 datasets (1,278 lesions from 1,264 patients) were included. The overall pooled sensitivity, specificity, and AUC with corresponding 95% confidence intervals were estimated to be 0.72 (0.55, 0.85), 0.88 (0.80, 0.93), and 0.89 (0.86, 0.91) for MRI in predicting HCC with CK19 expression. Combined methods had higher sensitivity than image feature methods (0.86 versus 0.54, p=0.001), with no difference in specificity (0.85 versus 0.87, p=0.641). There were no significant differences between radiomics and combined methods regarding sensitivity (p=0.796) and specificity (p=0.535), respectively., Conclusion: MRI shows moderate sensitivity and high specificity in identifying HCC with CK19 expression. The application of radiomics can improve the sensitivity of MRI in identifying HCC with CK19 expression., (Copyright © 2023. Published by Elsevier Ltd.)

Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aβ 25-35- induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aβ 25-35 -injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aβ 25-35 -induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aβ 25-35 -induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aβ 25-35 -induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling., 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 © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Barite ore is typically associated with difficult-to-remove vein minerals, but commercial barite products require a high BaSO 4 content. We investigated the occurrence state of fluoride in barite ore using various analytical techniques, which indicated that elemental fluorine in barite predominantly exists as fluorite. Fluoride was then leached from barite ore via complexation. The effects of HCl and AlCl 3 concentrations, temperature, time, and liquid-solid ratio on the leaching rate were examined, and the leaching conditions were optimized using an orthogonal array method. The fluorine leaching rate approached 93.11% after stirring for 30 min at 90 °C and 300 rpm with 3 mol/L HCl, 0.4 mol/L AlCl 3 , a liquid-solid ratio of 10:1 mL/g, and an ore sample size of -75 μm + 48 μm. According to the leaching kinetics, the process conformed to the solid membrane diffusion control model at a high temperature and the joint chemical reaction-diffusion control model at a low temperature. The apparent activation energy was 56.88 kJ/mol. Furthermore, aluminum and fluorine coordination numbers increased with increasing Al 3+ /F - molar concentration ratios. Competing complexation reactions of Al 3+ , H + , and F - occurred at three levels. This complexation approach effectively leaches fluoride from barite, improves barite product quality, and reduces environmental pollution., 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 © 2023 Elsevier Ltd. All rights reserved.)

Background and Aims: Magnifying image-enhanced endoscopy (MIEE) is an advanced endoscopy with image enhancement and magnification used in preoperative examination. However, its impact on the detection rate is unknown., Methods: We conducted an open-label, randomized, parallel (1:1:1), controlled trial in 6 hospitals in China. Patients were recruited between February 14, 2022 and July 30, 2022. Eligible patients were aged ≥18 years and undergoing gastroscopy in outpatient departments. Participants were randomly assigned to the MIEE-only mode (o-MIEE) group, white-light endoscopy-only mode (o-WLE) group, and MIEE when necessary mode (n-MIEE) group (initial WLE followed by switching to another endoscope with MIEE if necessary). Biopsy sampling of suspicious lesions of the lesser curvature of the gastric antrum was performed. Primary and secondary aims were to compare detection rates and positive predictive value (PPV) of early cancer and precancerous lesions in these 3 modes, respectively., Results: A total of 5100 recruited patients were randomly assigned to the o-MIEE (n = 1700), o-WLE (n = 1700), and n-MIEE (n = 1700) groups. In the o-MIEE, o-WLE, and n-MIEE groups, 29 (1.51%; 95% confidence interval [CI], 1.05-2.16), 4 (.21%; 95% CI, .08-.54), and 8 (.43%; 95% CI, .22-.85) early cancers were found, respectively (P < .001). The PPV for early cancer was higher in the o-MIEE group compared with the o-WLE and n-MIEE groups (63.04%, 33.33%, and 38.1%, respectively; P = .062). The same trend was seen for precancerous lesions (36.67%, 10.00%, and 21.74%, respectively)., Conclusions: The o-MIEE mode resulted in a significant improvement in diagnosing early upper GI cancer and precancerous lesions; thus, it could be used for opportunistic screening. (Clinical trial registration number: ChiCTR2200064174.)., Competing Interests: Disclosure All authors disclosed no financial relationships. Research support for this study was provided by the Clinical Research Personnel Training Program (2018XLC1009), the Outstanding Talent Pool Key Support Object Projects of Army Medical University, and Chongqing Health Appropriate Technology Promotion Project (2022jstg033)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Over the last decade, many studies have assessed the efficacy of treatments for refractory/relapsed multiple myeloma (R/R MM). While combination therapies show greater efficacy than traditional methods, limited research has targeted elderly patients who might be less resilient to treatments. Our study aimed to evaluate treatment efficacy for these elderly patients., Methods: We carried out a comprehensive review of the literature using a systematic approach. Initially, 4966 citations were retrieved and subsequently narrowed down to 13 eligible randomized controlled trials (RCTs) through our systematic review process from databases like Embase, PubMed, and Cochrane Library from 1 January 2000 to 31 December 2022. Evidence was collated through a frequentist network meta-analysis, using the hazard ratio (HR) for evaluation., Results: Combined therapy of daratumumab, lenalidomide, and dexamethasone (DaraLenDex) was the preferred treatment for R/R MM elderly patients. Its strengths included an HR for progression-free survival (0.15; 95% CI: 0.09-0.25) and a 96% P-score., Conclusions: Our analysis suggests that, pending more comprehensive RCTs, DaraLenDex is the treatment with the highest efficacy for R/R MM in elderly patients.

The formulation and revision of the detection methods of indoor air quality standards is an important, rigorous and delicate endeavor. This paper introduced the formulation and revision of the detection methods of the standards for indoor air quality (GB/T 18883-2022), focusing on the revision process, revision principles, main adjustments and technical points of some key indicators to facilitate users to better understand and apply the detection methods in standards for indoor air quality (GB/T 18883-2022).

BET proteins, which influence gene expression and contribute to the development of cancer, are epigenetic interpreters. Thus, BET inhibitors represent a novel form of epigenetic anticancer treatment. Although preliminary clinical trials have shown the anticancer potential of BET inhibitors, it appears that these drugs have limited effectiveness when used alone. Therefore, given the limited monotherapeutic activity of BET inhibitors, their use in combination with other drugs warrants attention, including the meaningful variations in pharmacodynamic activity among chosen drug combinations. In this paper, we review the function of BET proteins, the preclinical justification for BET protein targeting in cancer, recent advances in small-molecule BET inhibitors, and preliminary clinical trial findings. We elucidate BET inhibitor resistance mechanisms, shed light on the associated adverse events, investigate the potential of combining these inhibitors with diverse therapeutic agents, present a comprehensive compilation of synergistic treatments involving BET inhibitors, and provide an outlook on their future prospects as potent antitumor agents. We conclude by suggesting that combining BET inhibitors with other anticancer drugs and innovative next-generation agents holds great potential for advancing the effective targeting of BET proteins as a promising anticancer strategy., (© 2023. The Author(s).)

Public exposure to radon has attracted increasing public concern. The newly issued "Standards for indoor air quality (GB/T 18883-2022)" has revised the radiological parameters of radon. This study analyzed and discussed the relevant technical contents about the derivation of radon limit, including the distribution level for indoor radon, exposure pathway, health effects, and the process for establishing the standard limits. Specific implementation and evaluation suggestions are also proposed.

A strategy for the synthesis of dibenz[ a , j ]anthracenes (DBAs) from cyclohexa-2,5-diene-1-carboxylic acids is presented. Our approach involves sequential C-H olefination, cycloaddition, and decarboxylative aromatization. In the key step for DBA skeleton construction, the bis-C-H olefination products, 1,3-dienes, are utilized as substrates for [4 + 2] cycloaddition with benzyne. This concise synthetic route allows for regioselective ring formation and functional group introduction. The structural features and photophysical properties of the resulting DBA molecules are discussed.

Interferon-induced tetrapeptide repeat (IFIT) family proteins are an important component of the antiviral immune response. There are four known members of the human IFIT family, namely IFIT1, IFIT2, IFIT3 and IFIT5. More and more evidence shows that IFIT family members are involved in a variety of pathophysiological processes in vivo, regulate the homeostasis and differentiation of a variety of cells including immune cells, and are closely related to a variety of autoimmune diseases, which is expected to become a new therapeutic target. This review reviews the biological roles of different IFIT proteins in various autoimmune diseases, and highlights the potential use of these molecules as biomarkers and prognostic factors in autoimmune diseases, with a view to providing ideas for exploring the diagnosis and treatment of autoimmune diseases., Competing Interests: Declaration of Competing Interest The authors declared that they have no conflicts of interest to this work.We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: Delayed awakening after anesthetic discontinuation during awake craniotomy is associated with somnolence during functional brain mapping. However, predictors of delayed awakening in patients receiving monitored anesthesia care for awake craniotomy are unknown., Methods: This retrospective cohort study analyzed 117 adult patients with supratentorial glioma in or near eloquent areas who received monitored anesthesia care for awake craniotomy between July 2020 and January 2023 at Linkou Chang Gung Memorial Hospital. These patients were divided into two groups according to their time to awakening (ability to speak their names) after propofol cessation: longer or shorter than 20 min (median duration). Because propofol was solely used anesthetic from skin incision to dural opening, parameters in Schnider model for propofol target-controlled infusion, such as age, sex, and BMI, were adjusted or propensity-matched to compare their anesthetic, surgical, and histopathological profiles., Results: After propensity-matched comparisons of age and BMI, significant predictors of delayed awakening included IDH1 wild-type tumors and repeated craniotomies. Subgroup analysis revealed that older age and larger T2 volume were predictors in patients undergoing the first craniotomy, while lower preoperative Karnofsky performance scale scores and depression were predictors in repeated craniotomy cases. Delayed awakening was also associated with somnolence and a lower gross total resection rate., Conclusion: Our retrospective analysis of patients receiving monitored anesthesia care for awake craniotomy revealed that delayed awakening after propofol discontinuation occurred more often in patients with IDH1 wild-type tumors and repeated craniotomies. Also, delayed awakening was associated with somnolence during functional mapping and a lower gross total resection rate., (© 2023. The Author(s).)

Background: Lung cancer is the most common and deadliest cancer worldwide, and approximately 90% of all lung cancer deaths are caused by tumor metastasis. Tumor-derived exosomes could potentially promote tumor metastasis through the delivery of metastasis-related molecules. However, the function and underlying mechanism of exosomal long noncoding RNA (lncRNA) in lung cancer metastasis remain largely unclear., Methods: Cell exosomes were purified from conditioned media by differential ultracentrifugation and observed using transmission electron microscopy, and the size distributions were determined by nanoparticle tracking analysis. Exosomal lncRNA sequencing (lncRNA-seq) was used to identify long noncoding RNAs. Cell migration and invasion were determined by wound-healing assays, two-chamber transwell invasion assays and cell mobility tracking. Mice orthotopically and subcutaneously xenografted with human cancer cells were used to evaluate tumor metastasis in vivo. Western blot, qRT‒PCR, RNA-seq, and dual-luciferase reporter assays were performed to investigate the potential mechanism. The level of exosomal lncRNA in plasma was examined by qRT‒PCR. MS2-tagged RNA affinity purification (MS2-TRAP) assays were performed to verify lncRNA-bound miRNAs., Results: Exosomes derived from highly metastatic lung cancer cells promoted the migration and invasion of lung cancer cells with low metastatic potential. Using lncRNA-seq, we found that a novel lncRNA, lnc-MLETA1, was upregulated in highly metastatic cells and their secreted exosomes. Overexpression of lnc-MLETA1 augmented cell migration and invasion of lung cancer. Conversely, knockdown of lnc-MLETA1 attenuated the motility and metastasis of lung cancer cells. Interestingly, exosome-transmitted lnc-MLETA1 promoted cell motility and metastasis of lung cancer. Reciprocally, targeting lnc-MLETA1 with an LNA suppressed exosome-induced lung cancer cell motility. Mechanistically, lnc-MLETA1 regulated the expression of EGFR and IGF1R by sponging miR-186-5p and miR-497-5p to facilitate cell motility. The clinical datasets revealed that lnc-MLETA1 is upregulated in tumor tissues and predicts survival in lung cancer patients. Importantly, the levels of exosomal lnc-MLETA1 in plasma were positively correlated with metastasis in lung cancer patients., Conclusions: This study identifies lnc-MLETA1 as a critical exosomal lncRNA that mediates crosstalk in lung cancer cells to promote cancer metastasis and may serve as a prognostic biomarker and potential therapeutic target for lung cancer diagnosis and treatment., (© 2023. Italian National Cancer Institute ‘Regina Elena’.)

Post-traumatic stress disorder (PTSD) has been reported to be associated with a higher risk of cardiovascular disease. The amygdala may have an important role in regulating cardiovascular function. This study aims to explore the effect of amygdala glutamate receptors (GluRs) on cardiovascular activity in a rat model of PTSD. A compound stress method combining electrical stimulation and single prolonged stress was used to prepare the PTSD model, and the difference of weight gain before and after modeling and the elevated plus maze were used to assess the PTSD model. In addition, the distribution of retrogradely labeled neurons was observed using the FluoroGold (FG) retrograde tracking technique. Western blot was used to analyze the changes of amygdala GluRs content. To further investigate the effects, artificial cerebrospinal fluid (ACSF), non-selective GluR blocker kynurenic acid (KYN) and AMPA receptor blocker CNQX were microinjected into the central nucleus of the amygdala (CeA) in the PTSD rats, respectively. The changes in various indices following the injection were observed using in vivo multi-channel synchronous recording technology. The results indicated that, compared with the control group, the PTSD group exhibited significantly lower weight gain (P < 0.01) and significantly decreased ratio of open arm time (OT%) (P < 0.05). Retrograde labeling of neurons was observed in the CeA after microinjection of 0.5 µL FG in the rostral ventrolateral medulla (RVLM). The content of AMPA receptor in the PTSD group was lower than that in the control group (P < 0.05), while there was no significant differences in RVLM neuron firing frequency and heart rate (P > 0.05) following ACSF injection. However, increases in RVLM neuron firing frequency and heart rate were observed after the injection of KYN or CNQX into the CeA (P < 0.05) in the PTSD group. These findings suggest that AMPA receptors in the amygdala are engaged in the regulation of cardiovascular activity in PTSD rats, possibly by acting on inhibitory pathways.

Feldspar is a high-abundance mineral in the earth's crust, and its natural weathering and dissolution processes are an important phenomenon on the earth's surface. This study focused on the dissolution behavior of silicon (Si) and aluminum (Al) in feldspar minerals (microcline and albite) when exposed to low-molecular-weight organic acids (LMWOAs). Various analytical techniques, including atomic absorption spectrophotometer, X-ray diffraction, scanning electron microscope, and Fourier-transform infrared spectroscopy, were employed to investigate these processes. The results revealed that the concentration of Si and Al released from alkali feldspar increased after treatment with LMWOAs, exhibiting non-stoichiometric dissolution. The Si/Al release ratio from feldspar deviated from the expected value of three. Among the LMWOAs tested, oxalic acid was found to be more effective in dissolving aluminum, while citric acid showed greater efficacy in dissolving silicon. Notably, the composite acid demonstrated the highest capacity for feldspar dissolution, with values of 538 μM (Si) and 287 µM (Al) after treatment for 720 h, respectively. The dissolution data for Si and Al in the organic acid solution was fittingly described by a first-order equation, with high correlation coefficients (R 2 ≥ 0.992). The characterization of feldspar powders indicated that the (040) crystal plane of feldspar was particularly susceptible to attack by organic acids. In the presence of these acids, the chemical bonds Si (Al)-O, Si-Si(Al), and O-Si(Al)-O shifted to higher wavenumbers. Additionally, the surface corrosion morphology of feldspar exhibited distinct nanostructures, which became more pronounced with increasing exposure time. It was also observed that the reactivity of feldspar increased over time. These findings provide valuable insights into the natural dissolution process of feldspar and offer a new perspective for the study of this phenomenon.

Chondrosarcoma is the second most common type of bone cancer. At present, the most effective clinical course of action is surgical resection. Cisplatin is the chemotherapeutic medication most widely used for the treatment of chondrosarcoma; however, its effectiveness is severely hampered by drug resistance. In the current study, we compared cisplatin-resistant chondrosarcoma SW1353 cells with their parental cells via RNA sequencing. Our analysis revealed that glutamine metabolism is highly activated in resistant cells but glucose metabolism is not. Amphiregulin (AR), a ligand of the epidermal growth factor receptor, enhances glutamine metabolism and supports cisplatin resistance in human chondrosarcoma by promoting NADPH production and inhibiting reactive oxygen species (ROS) accumulation. The MEK, ERK, and NrF2 signaling pathways were shown to regulate AR-mediated alanine-serine-cysteine transporter 2 (ASCT2; also called SLC1A5) and glutaminase (GLS) expression as well as glutamine metabolism in cisplatin-resistant chondrosarcoma. The knockdown of AR expression in cisplatin-resistant chondrosarcoma cells was shown to reduce the expression of SLC1A5 and GLS in vivo . These results indicate that AR and glutamine metabolism are worth pursuing as therapeutic targets in dealing with cisplatin-resistant human chondrosarcoma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Cadmium (Cd) is a common contaminant in aquatic environments. However, little is known about the mechanisms underlying Cd toxicity in the freshwater snail Cipangopaludina cathayensis (Heude, 1890). This study to investigate the toxic effects of Cd on the standard metabolism, antioxidant activities, immune function, and hepatopancreas transcriptome profiles of C. cathayensis. C. cathayensis was exposed to 0.25, 0.5, 1.0, or 1.5 mg/L Cd for 3 h, with results showing that Cd significantly inhibited oxygen consumption and ammonia excretion and disrupted the respiratory metabolism of C. cathayensis. In addition, the O:N ratio dropped below 7, indicating that C. cathayensis may rely exclusively on proteins as an energy source under Cd stress. To understand how Cd impacts the antioxidant activities, immune function, and transcriptional profiles, C. cathayensis were exposed to 0.5 (low exposure, L14) or 1.5 (high exposure, H14) mg/L Cd for 14 days. Our results indicate that Cd exposure leads to oxidative stress and immunosuppression, with the latter effect being larger for exposure to higher Cd concentrations. A total of 2172 differentially expressed genes (DEGs) were identified by transcriptome analysis of the hepatopancreas, of which 885 were upregulated and 1287 were downregulated. Gene ontology and KEGG analyses revealed that the DEGs in the H14 group are enriched for energy generation terms and the "oxidative phosphorylation" pathway, respectively. Therefore, up-regulation of energy metabolism may be an adaptive strategy under Cd stress. Moreover, several genes involved in antioxidant activity were downregulated, whereas genes related to reactive oxygen species generation were upregulated. In addition, many immunity-related genes were identified within the DEGs, indicating that Cd toxicity may affect immune defense. Further, DEGs in the H14 group were enriched for disease-associated pathways. Taken together, our results indicate that Cd exposure leads to metabolic disorders, oxidative stress, and immunosuppression and thus may potentially contribute to disease outbreaks., Competing Interests: Declaration of Competing Interest The authors have declared that no conflict of interest exists., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance., Methods: The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups., Results: The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group ( P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group ( P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group ( P <0.001), though there was no significant difference in MFI., Conclusion: The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.

Objective: Adequate brain swelling resolution prior to cranioplasty (CP) is an important yet loosely defined issue. Despite efforts to balance timely CP and patient safety, heterogeneous study methodologies have led to conflicting results. This study aims to standardize this issue through quantifying degree of brain swelling resolution using a proposed Visual CP Scale., Methods: The proposed Visual CP Scale is validated through a 2-pronged approach. The first prong involves a national survey in Taiwan, where neurosurgeons were surveyed to determine what constitutes a patient's readiness for CP. The second prong involves a large retrospective cohort, where the correlations between timing, degree of brain swelling resolution, and post-CP complication rates, are evaluated., Results: In the national Taiwan CP Survey, 124 out of 772 neurosurgeons (17.2%) completed the survey. Respondents who chose higher grades on the Visual CP Scale preferred later CP timings. In the retrospective data, 378 out of 770 (49.1%) patients had pre-CP brain images, allowing for the utilization of the Visual CP Scale. A Visual CP Scale score of greater than or equal to 4 was associated with fewer complications after CP., Conclusions: The timing of CP should be determined by the degree of brain swelling resolution, not vice versa. The proposed Visual CP Scale offers an objective method for assessing brain swelling resolution, making it an adjuvant tool for clinical decision-making and future research related to CP., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Adipocytes store a significant amount of cholesterol and triglycerides. However, whether cholesterol modulates adipocyte function remains largely unknown. We modulated the cholesterol level in adipocytes to examine its effect on the secretion of adiponectin, an important hormone specifically secreted by adipocytes. Treating differentiated 3T3-L1 adipocytes with 4 mM methyl-β-cyclodextrin (MβCD), a molecule with a high affinity for cholesterol, rapidly depleted cholesterol in adipocytes. Interestingly, MβCD treatment increased adiponectin in the medium without affecting its intracellular level, suggesting a modulation of secretion. By contrast, cholesterol addition did not affect adiponectin secretion, suggesting that cholesterol-depletion-induced intracellular cholesterol trafficking, but not reduced cholesterol level, accounted for MβCD-induced adiponectin secretion. MβCD-induced adiponectin secretion was reduced after 10 μg/mL U18666A treatment that suppressed cholesterol transport out of late endosomes/lysosomes. Depleting Niemann-Pick type C1 (NPC1) or NPC2 proteins, which mediate endosomal/lysosomal cholesterol export, consistently reduced MβCD-induced adiponectin secretion. Furthermore, treatment with 1 μM bafilomycin A1, which neutralized acidic endosomes/lysosomes, also attenuated MβCD-induced adiponectin secretion. Finally, MβCD treatment redistributed cellular adiponectin to lower-density fractions in sucrose gradient fractionation. Our results show that MβCD-mediated cholesterol depletion elevates the secretion of adiponectin, highlighting the involvement of endosomes and lysosomes in adiponectin secretion in adipocytes.

Background: Lung cancer has the highest mortality rate in the world, and mounting evidence suggests that cancer stem cells (CSCs) are associated with poor prognosis, recurrence, and metastasis of lung cancer. It is urgent to identify new biomarkers and therapeutic targets for targeting lung CSCs., Methods: We computed the single-sample gene set enrichment analysis (ssGSEA) of 1554 Reactome gene sets to identify the mRNA expression-based stemness index (mRNAsi)-associated pathways using the genome-wide RNA sequencing data of 509 patients from The Cancer Genome Atlas (TCGA) cohort of lung adenocarcinoma (LUAD). Phenotypic effects of ubiquitin-specific peptidase 5 (USP5) on the CSC-like properties and metastasis were examined by in vitro sphere formation assay, migration assay, invasion assay, and in vivo xenografted animal models. Cycloheximide chase assay, co-immunoprecipitation assay, and deubiquitination assay were performed to confirm the effect of USP5 on the deubiquitination of β-catenin., Results: We demonstrated that USP5 expression were positively correlated with the stemness-associated signatures and poor outcomes in lung cancer specimens. Silencing of endogenous USP5 reduced CSC-like characteristics, epithelial-mesenchymal transition (EMT), and metastasis in vitro and in vivo. Furthermore, USP5 interacted with β-catenin, which resulted in deubiquitination, stabilization of β-catenin, and activation of Wnt/β-catenin pathway. Accordingly, expression of USP5 was positively correlated with the enrichment score of the Wnt/TCF pathway signature in human lung cancer. Silencing of β-catenin expression suppressed USP5-enhancing sphere formation. Targeting USP5 with the small molecule WP1130 promoted the degradation of β-catenin, and showed great inhibitory effects on sphere formation, migration, and invasion. Finally, we identified a poor-prognosis subset of tumors characterized by high levels of USP5, Wnt signaling score, and Stemness score in both TCGA-LUAD and Rousseaux&#95;2013 datasets., Conclusions: These findings reveal a clinical evidence for USP5-enhanced Wnt/β-catenin signaling in promoting lung cancer stemness and metastasis, implying that targeting USP5 could provide beneficial effects to improve lung cancer therapeutics., (© 2023. BioMed Central Ltd., part of Springer Nature.)

One of the highly attractive research directions in the electrochemiluminescence (ECL) field is how to regulate and improve ECL efficiency. Quantum dots (QDs) are highly promising ECL materials due to their adjustable luminescence size and strong luminous efficiency. MoS 2 NSs@QDs, an ECL emitter, is synthesized via hydrothermal methods, and its ECL mechanism is investigated using cyclic voltammetry and ECL-potential curves. Then, a stable and vertical attachment of a triplex DNA (tsDNA) probe to the MoS 2 nanosheets (NSs) is applied to the electrode. Next, an innovative ECL sensor is courageously empoldered for precise and ultrasensitive detection of target miRNA-199a through the agency of ECL-resonance energy transfer (RET) strategy and a dextrous target-initiated catalytic three-arm DNA junction assembly (CTDJA) based on a toehold strand displacement reaction (TSDR) signal amplification approach. Impressively, the ingenious system not only precisely regulates the distance between energy donor-acceptor pairs leave energy less loss and more ECL-RET efficiency, but also simplifies the operational procedure and verifies the feasibility of this self-assembly process without human intervention. This study can expand MoS 2 NSs@QDs utilization in ECL biosensing applications, and the proposed nucleic acid amplification strategy can become a miracle cure for ultrasensitive detecting diverse biomarkers, which helps researchers to better study the tumor mechanism, thereby unambiguously increasing cancer cure rates and reducing the risk of recurrence.

Aim: To describe the clinical and radiologic features of retrolaminar migration silicone oil (SiO) and observe the dynamic position of ventricular oil accumulation in supine and prone., Methods: For this retrospective study, 29 patients who had a history of SiO injection treatment and underwent unenhanced head computed tomography (CT) were included from January 2019 to October 2022. The patients were divided into migration-positive and negative groups. Clinical history and CT features were compared using Whitney U and Fisher's exact tests. The dynamic position of SiO was observed within the ventricular system in supine and prone. CT images were visually assessed for SiO migration along the retrolaminar involving pathways for vision (optic nerve, chiasm, and tract) and ventricular system., Results: Intraocular SiO migration was found in 5 of the 29 patients (17.24%), with SiO at the optic nerve head ( n =1), optic nerve ( n =4), optic chiasm ( n =1), optic tract ( n =1), and within lateral ventricles ( n =1). The time interval between SiO injection and CT examination of migration-positive cases was significantly higher than that of migration-negative patients (22.8±16.5mo vs 13.1±2.6mo, P <0.001). The hyperdense lesion located in the frontal horns of the right lateral ventricle migrated to the fourth ventricle when changing the position from supine to prone., Conclusion: Although SiO retrolaminar migration is unusual, the clinician and radiologist should be aware of migration routes. The supine combined with prone examination is the first-choice method to confirm the presence of SiO in the ventricular system., (International Journal of Ophthalmology Press.)

To analyze the association between exposure to air pollution and respiratory disease of primary school students in Chongqing City. Eight districts and counties were randomly selected based on the air pollution situation in Chongqing City. In each selected district and county, one primary school was randomly selected. A questionnaire survey was conducted on all primary school students in Grades 3-5 by the end of 2019. Air quality data from the nearest environmental monitoring sites were collected. A logistic regression model was used to analyze the impact of the living environment, lifestyle and air pollution on the respiratory disease of surveyed students. This study included 5 918 primary school students, with a prevalence rate of respiratory disease of 21.54%. The prevalence rates of boys and girls were 23.38% and 19.59%, respectively. The average Air quality index (AQI) of the surveyed school was 67, and the rates of exceeding standards of PM 10 , PM 2.5 , NO 2 and O 3 were 1.16%, 6.92%, 0.99% and 5.65%, respectively. The level of SO 2 and CO did not exceed the standard. After adjusting for relevant factors, logistic regression analysis showed that primary school students in areas with high exposure to air pollution ( OR =2.52), using air pollution related-chemicals at home ( OR =1.47), passive smoking ( OR =1.27), and keeping pets at home ( OR =1.18) had a higher risk of respiratory disease (all P <0.05). In addition, the average annual values of AQI ( OR =1.18), PM 10 ( OR =1.20), PM 2.5 ( OR =1.35), and NO 2 ( OR =1.11) increased the risk of respiratory diseases in primary school students (all P <0.05). In conclusion, the respiratory disease of primary school students in Chongqing City is related to the living environment, behavior habits and ambient air quality. The increased exposure concentration of PM 10 , PM 2.5 and NO 2 in air pollutants can lead to an increased risk of respiratory disease among primary school students.

Vascular calcification often occurs in patients with chronic renal failure (CRF), which significantly increases the incidence of cardiovascular events in CRF patients. Our previous studies identified the crosstalk between the endothelial cells (ECs) and vascular smooth muscle cells (VSMCs), and the paracrine effect of VSMCs, which regulate the calcification of VSMCs. Herein, we aim to investigate the effects of exosomes secreted by high phosphorus (HPi) -induced adventitial fibroblasts (AFs) on the calcification of VSMCs and the underlying mechanism, which will further elucidate the important role of AFs in high phosphorus vascular wall microenvironment. The conditioned medium of HPi-induced AFs promotes the calcification of VSMCs, which is partially abrogated by GW4869, a blocker of exosomes biogenesis or release. Exosomes secreted by high phosphorus-induced AFs (AFs HPi -Exos) show similar effects on VSMCs. miR-21-5p is enriched in AFs HPi -Exos, and miR-21-5p enhances osteoblast-like differentiation of VSMCs by downregulating cysteine-rich motor neuron 1 (Crim1) expression. AFs HPi -Exos and exosomes secreted by AFs with overexpression of miR-21-5p (AFs miR21M -Exos) significantly accelerate vascular calcification in CRF mice. In general, AFs HPi -Exos promote the calcification of VSMCs and vascular calcification by delivering miR-21-5p to VSMCs and subsequently inhibiting the expression of Crim1. Combined with our previous studies, the present experiment supports the theory of vascular wall microenvironment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

A series of O-phenanthroline silver(I) complexes were synthesized and characterized by infrared (IR) spectroscopy, mass spectrometry (MS), 1 H nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray crystallography. The cytotoxicity of the silver(I) complex (P-131) was evaluated in the cancer cell lines HCT-116, HeLa, and MDA-MB-231 and the normal cell line LO2 via MTT assays. The 50% inhibition concentration (IC 50 ) of P-131 on HCT116 cell line is 0.86 ± 0.03 μM. It is far lower than the IC 50 value of cisplatin (9.08 ± 1.10 μM), the IC 50 value of normal cell LO2 (76.20 ± 0.48 μM) is much higher than that of cisplatin (3.99 ± 0.74 μM), indicating that its anticancer effect is stronger than that of cisplatin, and its biological safety is greater than that of cisplatin. Furthermore, anticancer mechanistic studies showed that P-131 inhibited cell proliferation by blocking DNA synthesis and acted temporally on the nucleus in dividing HCT-116 cells. Moreover, P-131 increased intracellular reactive oxygen species (ROS) levels in a dose-dependent manner. Notably, 10 mg/kg P-131 showed better antitumor effects than oxaliplatin in an HCT116 human colorectal xenograft mouse model without inducing toxicity. Moreover, the microdilution broth method was used to evaluate the antimicrobial properties of P-131 against Pseudomonas aeruginosa and Candida albicans. A biofilm eradication study was also performed using the crystal violet method and confocal laser scanning microscopy., 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 © 2023. Published by Elsevier Inc.)

BH3 mimetics exert anticancer activity by inhibiting anti-apoptotic BCL2 proteins. However, accumulating evidence indicates that the off-target effects of these drugs tightly modulates their anticancer activities. In this study, we investigated whether the BCL2L1 inhibitor A-1331852 induced the death of U937 acute myeloid leukemia (AML) cells through a non-BCL2L1-targeted effect. A-1331852-induced apoptosis in U937 cells was characterized by increased ROS production, downregulation of MCL1, and loss of mitochondrial membrane potential. Ectopic expression of MCL1 alleviated A-1331852-induced mitochondrial depolarization and cytotoxicity in U937 cells. A-1331852-induced ROS production increased p38 MAPK phosphorylation and inhibited MCL1 transcription. Inhibition of p38 MAPK activation restored MCL1 expression in A-1331852-treated cells. A-1331852 triggered p38 MAPK-mediated Cullin 3 downregulation, which in turn increased PP2Acα expression, thereby reducing CREB phosphorylation. A-1331852 reduced the binding of CREB to the MCL1 promoter, leading to the inhibition of CREB-mediated MCL1 transcription. Furthermore, A-1331852 acted synergistically with the BCL2 inhibitor ABT-199 to induce U937 and ABT-199-resistant U937 cell death by inhibiting MCL1 expression. A similar phenomenon caused A-1331852-induced MCL1 downregulation and cytotoxicity in AML HL-60 cells. Collectively, our data suggest that A-1331852 shows an off-target effect of inhibiting MCL1 transcription, ultimately leading to U937 and HL-60 cell death., 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 © 2023 Elsevier Inc. All rights reserved.)

Purpose: Neuroplasticity is an ability to maintain neural circuit function when facing damages. It is one of the reasons that making brain tumors notorious. Therefore, we evaluated the characteristics of patients with primary brain tumors, compared neuropsychological deficits between patients who had awake craniotomy with left- or right-sided tumors, and analyzed the association between white matter tracts and neuropsychological deficits in patients with right-sided tumors., Methods: Using the registration dataset of Chang Gung Memory Hospital between 2014 and 2020, this study included a total of 698 adult patients who received craniotomy for primary brain tumors (538 of conventional craniotomy; 160 of awake craniotomy). Neuropsychological assessments were arranged in patients as preoperative evaluation for awake craniotomies., Results: A lower proportion of right-sided tumors was noted in patient who had awake craniotomy than those who had conventional craniotomy (33.8% and 51.5%, p < 0.001). In awake craniotomy, 88.7% of patients with left-sided tumors and 77.8% of patients with right-sided tumors had neuropsychological impairment. Patients with left-sided tumors had worse preoperative performance compared to those with right-sided tumors in global function (36.2% and 8.0%, p < 0.001), language domain (57.6% and 22.2%, p < 0.001), and attention (36.0% and 18.5%, p = 0.02). Furthermore, in those with right-sided low-grade gliomas, patients involving pathway of superior longitudinal fasciculus (SLF) I had a higher risk of deficits than those without involvement in verbal memory (p = 0.001, Odd ratio = 11.2, 95% CI = 1.8 ~ 71.4) and visual memory (p = 0.048, Odd ratio = 10.5, 95% CI = 1.0 ~ 111)., Conclusion: In awake craniotomy, patients with left-sided brain tumors had worse cognitive function than those with right-sided tumors in terms of global function, language, and attention. 77% of patients with right-sided tumors had neuropsychological impairment. Therefore, a comprehensive neuropsychological evaluation and awake craniotomy are necessary for patients with brain tumors., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Post-traumatic stress disorder (PTSD) is a serious psychiatric disorder, and there is an association between it and the development of cardiovascular disease. The aim of this study was to explore whether there is a glutamatergic pathway connecting the medial habenula (MHb) with the rostral ventrolateral medulla (RVLM) that is involved in the regulation of cardiovascular function in a rat model of PTSD. Vesicular glutamate transporter 2 (VGLUT2)-positive neurons in the MHb region were retrogradely labeled with FluoroGold (FG) by the double-labeling technique of VGLUT2 immunofluorescence and FG retrograde tracing. Rats belonging to the PTSD model group were microinjected with artificial cerebrospinal fluid (ACSF) or kynurenic acid (KYN; a nonselective glutamate receptor blocker) into their RVLM. Subsequently, with electrical stimulation of MHb, the discharge frequency of the RVLM neurons, heart rate, and blood pressure were found to be significantly increased after microinjection of ACSF using an in vivo multichannel synchronous recording technology; however, this effect was inhibited by injection of KYN. The expression of N-methyl-D-aspartic acid (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits was significantly increased in RVLM of PTSD model rats analyzed by the Western blotting technique. These findings suggest that there may be a glutamatergic pathway connection between MHb and RVLM and that this pathway may be involved in the regulation of cardiovascular function in the PTSD model rats, by acting on NMDA and AMPA receptors in the RVLM., Competing Interests: None

Background: This study aimed to compare the predictive value of two diagnostic criteria for bronchopulmonary dysplasia (BPD) in preterm infants with gestational age (GA) < 32 weeks for death or severe respiratory morbidity at corrected age of 18-24 months., Methods: In this retrospective cohort study, clinical data from July 2019 to September 2021 were classified by 2018 National Institute of Child Health and Human Development (NICHD) and 2019 Jensen definitions of BPD. Based on the follow-up results, the enrolled population was divided into adverse outcome group and normal outcome group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to explore the risk factors of adverse outcomes and evaluate the predictive value of both diagnostic criteria., Results: Of 451 infants, 141 (31.3%) had adverse outcomes, which increased with increasing severity of BPD. Logistic regression analysis showed only BPD was an independent risk factor for adverse outcomes in preterm infants. ROC analysis revealed that both diagnostic criteria showed similar predictive values (2018 NICHD definition AUC = 0.771 vs. 2019 Jensen definition AUC = 0.770), with specificities of 93.5% and 96.8%, respectively; however, combining them separately with GA or birth weight did not improve their predictive values., Conclusions: The two novel definitions of BPD demonstrate similar predictive values in predicting death or severe respiratory morbidity at corrected age of 18-24 months, with higher specificity observed in both., (© 2023. BioMed Central Ltd., part of Springer Nature.)

OH-terminated self-assembled monolayers, as protein-resistant surfaces, have significant potential in biocompatible implant devices, which can avoid or reduce adverse reactions caused by protein adhesion to biomaterial surfaces, such as thrombosis, immune response and inflammation. Here, molecular dynamics simulations were performed to evaluate the degree of protein adsorption on the self-assembled monolayer terminated with two hydrophilic OH groups ((OH) 2 -SAM) at packing densities ( Σ ) of 4.5 nm -2 and 6.5 nm -2 , respectively. The results show that the structure of the (OH) 2 -SAM itself, i.e. , a nearly perfect hexagonal-ice-like hydrogen bond structure in the OH matrix of the (OH) 2 -SAM at Σ = 4.5 nm -2 sharply reduces the number of hydrogen bonds ( i.e. , 0.7 ± 0.27) formed between the hydrophobic (OH) 2 -SAM surface and protein. While for Σ = 6.5 nm -2 , the hydrophilic (OH) 2 -SAM surface can provide more hydrogen bonding sites to form hydrogen bonds ( i.e. , 6.2 ± 1.07) with protein. The number of hydrogen bonds formed between the (OH) 2 -SAM and protein at Σ = 6.5 nm -2 is ∼8 times higher than that at Σ = 4.5 nm -2 , reflecting the excellent resistance to protein adsorption exhibited by the structure of the (OH) 2 -SAM itself at Σ = 4.5 nm -2 . Compared with a traditional physical barrier effect formed by a large number of hydrogen bonds between the (OH) 2 -SAM and water at Σ = 6.5 nm -2 , the structure of the (OH) 2 -SAM itself at Σ = 4.5 nm -2 proposed in this study significantly improves the performance of the (OH) 2 -SAM resistance to protein adsorption, which provides new insights into the mechanism of resistance to protein adsorption on the (OH) 2 -SAM.

Ethnopharmacological Relevance: Panax notoginseng (Burk.) F. H. Chen belongs to the Araliaceae family. It has been used by traditional Chinese people in Northeast Asia for centuries as an antidiabetic, antioxidant, antitumor agent, etc. Endophytic or rhizospheric microorganisms play key roles in plant defense mechanisms, and they are essential in the discovery of pharmaceuticals and valuable new secondary metabolites. In particular, endophytic or rhizospheric microorganisms of traditional medicinal plants., Aim of the Study: To discover valuable new secondary metabolites from rhizosphere soil Streptomyces sp. SYP-A7185 of P. notoginseng, and to explore potential bioactivities and targets of metabolites protrusive function., Materials and Methods: The metabolites were obtained via column chromatography and identified by multiple spectroscopic analyses. The antitumor, antioxidant, antibacterial, and antiglycosidases effects of isolated metabolites were tested using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetazolium bromide (MTT), 2,2-diphenyl-1-picrylhydrazyl (DPPH), 96-well turbidimetric, and α-glucosidase inhibitory assays. The potential antitumor targets were predicted through network pharmacological approaches. The interactions between metabolites and target were verified by molecular docking and biolayer interferometry (BLI) assay. The effects of cancer cells migration were detected through wound healing assays in A549 and MCF-7. Other cellular validation experiments including reverse transcription-quantitative PCR (RT‒qPCR) and western blotting (WB) were used to confirm the hypothesis of network pharmacology., Results: Five different chemotypes of anthraquinone derivatives (1-10), including six new compounds (3, 6-10), were identified from Streptomyces sp. SYP-A7185. Compounds 1-6 and 9 displayed moderate to strong cytotoxicity on five human cancer cell lines (A549, HepG2, MCF-7, MDA-MD-231, and MGC-803). Moreover, matrix metalloproteinase-2 (MMP2) were predicted as a potential antitumor target of metabolites 1-6 and 9 by comprehensive network pharmacology analysis. Later, BLI assays revealed strong intermolecular interactions between MMP2 and antitumor metabolites, and molecular docking results showed the interaction of metabolites 1-6 and 9 with MMP2 was dependent on the crucial amino acid residues of LEU-83, ALA-84, LEU-117, HIS-131, PRO-135, GLY-136, ALA-140, PRO-141, TYR-143, and THR-144. These results implied that metabolites (1-6 and 9) might inhibit cancer cell migration besides cancer cell proliferation. After that, the cell wound healing assay showed that the cell migration processes were also inhibited after the treatments of compounds 1 and 3 in A549 and MCF-7 cells. In addition, the RT‒qPCR and WB results demonstrated that the gene expression levels of MMP2 were decreased after the treatment with compounds 1 and 3 in A549 and MCF-7 cells. Besides, compound 2 displayed moderate antioxidant activity (EC 50 , 27.43 μM), compounds 3 and 6 exhibited moderate antibacterial activity, and compound 3 inhibited α-glucosidase with an IC 50 value of 13.10 μM., Conclusions: Anthraquinone metabolites, from rhizosphere soil Streptomyces sp. of P. notoginseng, possess antitumor, antioxidant, antibacterial, and antiglycosidase activities. Moreover, metabolites 1 and 3 inhibit cancer cells migration through downregulating MMP2., Competing Interests: Declaration of competing interest The authors have declared that no competing interests exist., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Lung cancer is associated with a high mortality rate and often complicated with malignant pleural effusion (MPE), which has a very poor clinical outcome with a short life expectancy. However, our understanding of cell-specific mechanisms underlying the pathobiology of pleural metastasis remains incomplete. Methods: We analyzed single-cell transcriptomes of cells in pleural effusion collected from patients with lung cancer and congestive heart failure (as a control), respectively. Soluble and complement factors were measured using a multiplex cytokine bead assay. The role of ferroptosis was evaluated by GPX4 small interfering RNA (siRNA) transfection and overexpression. Results: We found that the mesothelial-mesenchymal transition (MesoMT) of the pleural mesothelial cells contributed to pleural metastasis, which was validated by lung cancer/mesothelial cell co-culture experiments. The ferroptosis resistance that protected cancer from death which was secondary to extracellular matrix detachment was critical for pleural metastasis. We found a universal presence of immune-suppressive lipid-associated tumor-associated macrophages (LA-TAMs) with complement cascade alteration in the MPE of the lung cancer patients. Specifically, upregulated complement factors were also found in the MPE, and C5 was associated with poor overall survival in the lung cancer patients with epidermal growth factor receptor mutation. Plasmacytoid dendritic cells (pDCs) exhibited a dysfunctional phenotype and pro-tumorigenic feature in the primary cancer. High expression of the gene set extracted from pDCs was associated with a poor prognosis in the lung cancer patients. Receptor-ligand interaction analysis revealed that the pleural metastatic niche was aggravated by cross-talk between mesothelial cells-cancer cells/immune cells via TNC and ICAM1 . Conclusions: Taken together, our results highlight cell-specific mechanisms involved in the pathobiological development of pleural metastasis in lung cancer. These results provide a large-scale and high-dimensional characterization of the pleural microenvironment and offer a useful resource for the future development of therapeutic drugs in lung cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Three hitherto unknown eight-electron rhodium/silver alloy nanoclusters, [RhAg 21 {S 2 P(O n Pr) 2 } 12 ] ( 1 ), [RhHAg 20 {S 2 P(O n Pr) 2 } 12 ] ( 2 ), and [RhH 2 Ag 19 {S 2 P(O n Pr) 2 } 12 ] ( 3 ), have been isolated and fully characterized. Cluster 1 contains a regular Rh@Ag 12 icosahedral core, whereas 2 and 3 exhibit distorted RhH@Ag 12 and RhH 2 @Ag 12 icosahedral cores. The single-crystal neutron structure of 2 located the encapsulated hydride at the center of an enlarged RhAg 3 tetrahedron. A similar position was found by neutron diffraction for one of the hydrides in 3 , whereas the other hydride is trigonally coordinated to Rh and an elongated Ag-Ag edge. The solid-state structures of 1 - 3 possess C 1 symmetry due to the asymmetric arrangement of the surrounding capping Ag atoms. Our investigation shows that the insertion of one hydride dopant provokes the elimination of one capping silver atom on the cluster surface, resulting in the general formula [RhH x @Ag 21- x {S 2 P(O n Pr) 2 } 12 ] ( x = 0-2), which maintains the same number of cluster electrons as well as neutral charge. Clusters 1 - 3 exhibit an intense emission band in the NIR region. Contrarily to their PdAg 21 and PdHAg 20 relatives, the 4d orbitals of the encapsulated heterometal are somewhat involved in the optical processes.

This study was to evaluate the efficacy of TOXO-XL (XL), an integrated mycotoxin-mitigating agent, on aflatoxin B 1 (AFB 1 )-induced damage in Leghorn male hepatoma (LMH), porcine jejunum epithelial cell line (IPEC-J2) and porcine alveolar macrophages (3D4/21) cells, and to explore its potential mechanisms. The results showed that 30% inhibition concentration (IC 30 ) of AFB 1 in LMH, IPEC-J2 and 3D4/21 cells was 0.5, 15.0, and 2.5 mg/L, respectively. Notably, cell viability, ROS, apoptosis and DNA lesion induced by AFB 1 (IC 30 ) could be ameliorated by the supplementation with XL at the dosage of 0.025, 0.025 and 0.005%, respectively. Additionally, the migration and phagocytosis abilities impaired by AFB 1 were also restored by XL in 3D4/21. Further experiments revealed that XL supplementation markedly attenuated AFB 1 -induced inflammatory response by decreasing IL-1β, IL-6 and IL-10 in LMH, IL-6 in IPEC-J2 and IL-1β in 3D4/21 cells. Meanwhile, XL supplementation reversed the alterations of BAX, BCL-2 and caspase-3 induced by AFB 1 in the three cells, suggesting that AFB 1 -induced apoptosis may be suppressed via the mitochondria-dependent pathway. Furthermore, XL may have a protective effect on the intestinal barrier through the restoration of occludin protein. Conclusively, these findings indicated that XL could alleviate AFB 1 -induced cytotoxicity in the three cells, potentially through the regulation of cytokines, ROS, apoptotic and DNA damage signaling., 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 © 2023 Elsevier Ltd. All rights reserved.)

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unexplained causes. Its pathological features include synovial tissue hyperplasia, inflammatory cell infiltration in joint cavity fluid, cartilage bone destruction, and joint deformation. C-C motif chemokine ligand 3 (CCL3) belongs to inflammatory cell chemokine. It is highly expressed in inflammatory immune cells. Increasingly, studies have shown that CCL3 can promote the migration of inflammatory factors to synovial tissue, the destruction of bone and joint, angiogenesis, and participate in the pathogenesis of RA. These symptoms indicate that the expression of CCL3 is highly correlated with RA disease. Therefore, this paper reviews the possible mechanism of CCL3 in the pathogenesis of RA, which may provide some new insights for the diagnosis and treatment of RA., (© 2023. The Author(s).)

Pesticide pollution is one of the most important factors for global bee declines. Despite many studies have revealed that the most important Chinese indigenous species，Apis cerana, is presenting a high risk on exposure to neonicotinoids, the toxicology information on Apis cerana remain limited. This study was aimed to determine the acute and chronic toxic effects of thiacloprid (IUPAC name: {(2Z)-3-[(6-Chloro-3-pyridinyl)methyl]-1,3-thiazolidin-2-ylidene}cyanamide) on behavioral and physiological performance as well as genome-wide transcriptome in A. cerana. We found the 1/5 LC 50 of thiacloprid significantly impaired learning and memory abilities after both acute and chronic exposure, nevertheless, has no effects on the sucrose responsiveness and phototaxis climbing ability of A. cerana. Moreover, activities of detoxification enzyme P450 monooxygenases and CarE were increased by short-term exposure to thiacloprid, while prolonged exposure caused suppression of CarE activity. Neither acute nor chronic exposure to thiacloprid altered honey bee AChE activities. To further study the potential defense molecular mechanisms in Asian honey bee under pesticide stress, we analyzed the transcriptomes of honeybees in response to thiacloprid stress. The transcriptomic profiles revealed consistent upregulation of immune- and stress-related genes by both acute or chronic treatments. Our results suggest that the chronic exposure to thiacloprid produced greater toxic effects than a single administration to A. cerana. Altogether, our study deepens the understanding of the toxicological characteristic of A. cerana against thiacloprid, and could be used to further investigate the complex molecular mechanisms in Asian honey bee under pesticide stress., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Medial arterial calcification (MAC), a systemic vascular disease different from atherosclerosis, is associated with an increased incidence of cardiovascular events. Several studies have demonstrated that ambient temperature is one of the most important factors affecting cardiovascular events. However, there has been limited research on the effect of different ambient temperatures on MAC. In the present study, we showed that cold temperature exposure (CT) in mice slowed down the formation of vitamin D (VD)-induced vascular calcification compared with room temperature exposure (RT). To investigate the mechanism involved, we isolated plasma-derived exosomes from mice subjected to CT or RT for 30 days (CT-Exo or RT-Exo, respectively). Compared with RT-Exo, CT-Exo remarkably alleviated the calcification/senescence formation of vascular smooth muscle cells (VSMCs) and promoted autophagy by activating the phosphorylation of AMP-activated protein kinase (p-AMPK) and inhibiting phosphorylation of mammalian target of rapamycin (p-mTOR). At the same time, CT-Exo promoted autophagy in β-glycerophosphate (β-GP)-induced VSMCs. The number of autophagosomes and the expression of autophagy-related proteins ATG5 and LC3B increased, while the expression of p62 decreased. Based on a microRNA chip microarray assay and real-time polymerase chain reaction, miR-320a-3p was highly enriched in CT-Exo as well as thoracic aortic vessels in CT mice. miR-320a-3p downregulation in CT-Exo using AntagomiR-320a-3p inhibited autophagy and blunted its anti-calcification protective effect on VSMCs. Moreover, we identified that programmed cell death 4 (PDCD4) is a target of miR-320a-3p, and silencing PDCD4 increased autophagy and decreased calcification in VSMCs. Treatment with CT-Exo alleviated the formation of MAC in VD-treated mice, while these effects were partially reversed by GW4869. Furthermore, the anti-arterial calcification protective effects of CT-Exo were largely abolished by AntagomiR-320a-3p in VD-induced mice. In summary, we have highlighted that prolonged cold may be a good way to reduce the incidence of MAC. Specifically, miR-320a-3p from CT-Exo could protect against the initiation and progression of MAC via the AMPK/mTOR autophagy pathway., (© 2023. The Author(s).)

Introduction: MicroRNAs may be implicated in the acquisition of drug resistance in chronic myeloid leukemia as they regulate the expression of not only BCR-ABL1 but also genes associated with the activation of drug transfer proteins or essential signaling pathways., Methods: To understand the impact of specifically expressed miRNAs in chronic myeloid leukemia and their target genes, we collected peripheral blood mononuclear cells (PBMC) from patients diagnosed with chronic myeloid leukemia (CML) and healthy donors to determine whole miRNA expression by small RNA sequencing and screened out 31 differentially expressed microRNAs (DE-miRNAs) with high expression. With the utilization of miRNA set enrichment analysis tools, we present here a comprehensive analysis of the relevance of DE-miRNAs to disease and biological function. Furthermore, the literature-based miRNA-target gene database was used to analyze the overall target genes of the DE-miRNAs and to define their associated biological responses. We further integrated DE-miRNA target genes to identify CML miRNA targeted gene signature singscore (CMTGSS) and used gene-set enrichment analysis (GSEA) to analyze the correlation between CMTGSS and Hallmark gene-sets in PBMC samples from clinical CML patients. Finally, the association of CMTGSS stratification with multiple CML cell lineage gene sets was validated in PBMC samples from CML patients using GSEA., Results: Although individual miRNAs have been reported to have varying degrees of impact on CML, overall, our results show that abnormally upregulated miRNAs are associated with apoptosis and aberrantly downregulated miRNAs are associated with cell cycle. The clinical database shows that our defined DE-miRNAs are associated with the prognosis of CML patients. CMTGSS-based stratification analysis presented a tendency for miRNAs to affect cell differentiation in the blood microenvironment., Conclusion: Collectively, this study defined differentially expressed miRNAs by miRNA sequencing from clinical samples and comprehensively analyzed the biological functions of the differential miRNAs in association with the target genes. The analysis of the enrichment of specific myeloid differentiated cells and immune cells also suggests the magnitude and potential targets of differentially expressed miRNAs in the clinical setting. It helps us to make links between the different results obtained from the multi-faceted studies to provide more potential research directions., 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 © 2023 Wu, Lai, Lu, Lai, Chen, Chen, Ho, Wu and Chiu.)

The distribution range of root-knot nematode Meloidogyne graminicola is rapidly expanding, posing a severe threat to rice production. In this study, the sequences of cytochrome oxidase subunit I ( COI ) genes of rice M. graminicola populations from all reported provinces in China were amplified and sequenced by PCR. The distribution pattern and phylogenetic tree showed that all 54 M. graminicola populations in China have distinct geographical distribution characteristics; specifically, cluster 1 (southern China), cluster 2 (central south and southwest China), and cluster 3 (central and eastern China). The high haplotype diversity (Hd = 0.646) and low nucleotide diversity (π = 0.00682), combined with the negative value of Tajima's D (-1.252) and Fu's Fs (-3.06764), suggested that all nematode populations were expanding. The existence of high genetic differentiation (Fst = 0.5933) and low gene flow (Nm = 0.3333) indicated that there was a block of gene exchange between most populations. Mutation accumulation with population expansion might be directly responsible for the high genetic differentiation; therefore, the tested nematode population showed high within-group genetic variation (96.30%). The haplotype Hap8 was located at the bottom of the network topology, with the widest distribution and the highest frequency (59.26%), indicating that it was the ancestral haplotype. The populations in cluster 3 were newly invasive according to the lowest frequency of occurrence of Hap8, the highest number of endemic haplotypes, and the highest total haplotype frequency (60%). In contrast, cluster 1 having the highest genetic diversity (Hd = 0.772, π = 0.01127) indicated that it was the most primitive. Interestingly, the highest gene flow (Nm > 1), lowest genetic differentiation (Fst ≤ 0.33), and closest genetic distance (0.000) only occurred between the Guangdong/Hainan population and others, which suggested that there might be channels for gene exchange between them and that long-distance dispersal occurred. This suggestion is further confirmed by the weak correlation between genetic distance and geographical distance. Based on these data, a hypothesis can be drawn that M. graminicola populations in China were spreading from south to north, specifically from Guangdong and Hainan Provinces to other regions. Natural selection (including anthropogenic) and genetic drift were the main drivers of their evolution. Coincidentally, this hypothesis was consistent with the gradual warming trend and the chronological order of reporting these populations. The main factors influencing current M. graminicola population expansion and distribution patterns might be geography, climate, long-distance seedling transport, interregional operations of agricultural machinery, and rotation mode. It reminds human beings of the necessity to be vigilant about preventing nematode disease according to local conditions all year round., Competing Interests: The author(s) declare no conflict of interest.

DNA barcoding has greatly facilitated studies of taxonomy, biodiversity, biological conservation, and ecology. Here, we establish a reliable DNA barcoding library for Chinese snakes, unveiling hidden diversity with implications for taxonomy, and provide a standardized tool for conservation management. Our comprehensive study includes 1638 cytochrome c oxidase subunit I (COI) sequences from Chinese snakes that correspond to 17 families, 65 genera, 228 named species (80.6% of named species) and 36 candidate species. A barcode gap analysis reveals gaps, where all nearest neighbour distances exceed maximum intraspecific distances, in 217 named species and all candidate species. Three species-delimitation methods (ABGD, sGMYC, and sPTP) recover 320 operational taxonomic units (OTUs), of which 192 OTUs correspond to named and candidate species. Twenty-eight other named species share OTUs, such as Azemiops feae and A. kharini, Gloydius halys, G. shedaoensis, and G. intermedius, and Bungarus multicinctus and B. candidus, representing inconsistencies most probably caused by imperfect taxonomy, recent and rapid speciation, weak taxonomic signal, introgressive hybridization, and/or inadequate phylogenetic signal. In contrast, 43 species and candidate species assign to two or more OTUs due to having large intraspecific distances. If most OTUs detected in this study reflect valid species, including the 36 candidate species, then 30% more species would exist than are currently recognized. Several OTU divergences associate with known biogeographic barriers, such as the Taiwan Strait. In addition to facilitating future studies, this reliable and relatively comprehensive reference database will play an important role in the future monitoring, conservation, and management of Chinese snakes., (© 2023 John Wiley & Sons Ltd.)

Background: Although the neural mechanisms of the theory of mind (ToM) in children with autism spectrum disorder (ASD) through fMRI using the social animation task have been investigated, little is known in adults with ASD. Therefore, the present study aimed to explore the neural substrates of ToM in adults with ASD. Moreover, we aimed to elucidate the relationship between brain activation and behavior of social interaction in adults with ASD., Methods: Twenty-four healthy controls and 24 adults with the clinical diagnosis of ASD were recruited. Participants were asked to complete the social animation task in functional magnetic resonance imaging. The imaging analyses of within (whole brain analysis) and between (5 regions of interest) group comparisons were conducted to explore the process of ToM. The correlation analyses were further conducted to explore the relationship between neural activations associated with ToM and social interaction abilities assessed by ADI-R., Results: The ASD group showed greater activation in the left precuneus and right superior temporal gyrus (STG) than the control group. For correlation analyses, greater right STG activation was positively correlated with autistic symptoms assessed by the ADI-R in the ASD group., Conclusion: ASD adults might spend a lot of effort on identification processing, thereby influencing social communication skills. Also, the neural deficits of ToM in ASD adults might be associated with their social interaction difficulties., Competing Interests: Declaration of Competing Interest All authors report no biomedical financial interests or potential conflicts of interest., (Copyright © 2022 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Resistance training is employed for pursuing muscle strength characterized by activation of mammalian target of rapamycin (mTOR)-mediated hypertrophic signaling for protein production. Endurance training elevates peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) signaling of mitochondrial adaptations for oxidative phosphorylation. Now, emerging evidence suggests that, like endurance training, resistance training also elicits profound effects on mitochondrial adaptations in skeletal muscle, which means that resistance training yields both strength and endurance phenotypes in myofibers, which has treatment value for the muscle loss and poor aerobic capacity in humans. Our review outlines a brief overview of muscle hypertrophic signals with resistance training, and focuses on the effects of resistance training on mitochondrial biogenesis and respiration in skeletal muscle. This study provides novel insights into the therapeutic strategy of resistance training for the metabolically dysfunctional individuals with declined mitochondrial function., Competing Interests: The authors declared there was no conflict of interest., (Thieme. All rights reserved.)

Abstract: Mounting evidence indicates that microRNAs (miRNAs) play critical roles in various pathophysiological conditions and diseases, but the physiological roles of extracellular miRNAs on the disease-related ion channels remain largely unknown. Here, we showed that miR-1306-3p evoked action potentials and induced inward currents of the acutely isolated rat dorsal root ganglion (DRG) neurons. The miR-1306-3p-induced effects were significantly inhibited by A317491, a potent inhibitor of the P2X3 receptor (P2X3R), or disappeared after the knockdown of P2X3Rs in DRG neurons. We further identified R180, K315, and R52 as the miR-1306-3p interaction sites on the extracellular domain of P2X3Rs, which were distinct from the orthosteric ATP-binding sites. Intrathecal injection of miR-1306-3p produced visceral pain but not somatic pain in normal control rats. Conversely, intrathecal application of a miR-1306-3p antagomir and A317491 significantly alleviated visceral pain in a rat model of chronic visceral pain. Together, our findings suggest that miR-1306-3p might function as an endogenous ligand to activate P2X3Rs, eventually leading to chronic visceral pain., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)