Rechargeable Zinc-Air Batteries: Advances, Challenges, and Prospects.

Rechargeable zinc-air batteries (Re-ZABs) are one of the most promising next-generation batteries that can hold more energy while being cost-effective and safer than existing devices. Nevertheless, zinc dendrites, non-portability, and limited charge-discharge cycles have long been obstacles to the commercialization of Re-ZABs. Over the past 30 years, milestone breakthroughs have been made in technical indicators (safety, high energy density, and long battery life), battery components (air cathode, zinc anode, and gas diffusion layer), and battery configurations (flexibility and portability), however, a comprehensive review on advanced design strategies for Re-ZABs system from multiple angles is still lacking. This review underscores the progress and strategies proposed so far to pursuit the high-efficiency Re-ZABs system, including the aspects of rechargeability (from primary to rechargeable), air cathode (from unifunctional to bifunctional), zinc anode (from dendritic to stable), electrolytes (from aqueous to non-aqueous), battery configurations (from non-portable to portable), and industrialization progress (from laboratorial to practical). Critical appraisals of the advanced modification approaches (such as surface/interface modulation, nanoconfinement catalysis, defect electrochemistry, synergistic electrocatalysis, etc.) are highlighted for cost-effective flexible Re-ZABs with good sustainability and high energy density. Finally, insights are further rendered properly for the future research directions of advanced zinc-air batteries.

Circulating Tumor Cell Phenotype Detection and Epithelial-Mesenchymal Transition Tracking Based on Dual Biomarker Co-Recognition in an Integrated PDMS Chip.

Circulating tumor cells (CTCs) are widely considered as a reliable and promising class of markers in the field of liquid biopsy. As CTCs undergo epithelial-mesenchymal transition (EMT), phenotype detection of heterogeneous CTCs based on EMT markers is of great significance. In this report, an integrated analytical strategy that can simultaneously capture and differentially detect epithelial- and mesenchymal-expressed CTCs in bloods of non-small cell lung cancer (NSCLS) patients is proposed. First, a commercial biomimetic polycarbonate (PCTE) microfiltration membrane is employed as the capture interface for heterogenous CTCs. Meanwhile, differential detection of the captured CTCs is realized by preparing two distinct CdTe quantum dots (QDs) with red and green emissions, attached with EpCAM and Vimentin aptamers, respectively. For combined analysis, a polydimethylsiloxane (PDMS) chip with simple structure is designed, which integrates the membrane capture and QDs-based phenotype detection of CTCs. This chip not only implements the analysis of the number of CTCs down to 2 cells mL-1, but enables EMT process tracking according to the specific signals of the two QDs. Finally, this method is successfully applied to inspect the correlations of numbers or proportions of heterogenous CTCs in 94 NSCLS patients with disease stage and whether there is distant metastasis.

Diagnostic performance of radiomics for predicting osteoporosis in adults: a systematic review and meta-analysis.

This study aimed to assess the diagnostic accuracy of radiomics for predicting osteoporosis and the quality of radiomic studies. The study protocol was prospectively registered on PROSPERO (CRD42023425058). We searched PubMed, EMBASE, Web of Science, and Cochrane Library databases from inception to June 1, 2023, for eligible articles that applied radiomic techniques to diagnosing osteoporosis or abnormal bone mass. Quality and risk of bias of the included studies were evaluated with radiomics quality score (RQS), METhodological RadiomICs Score (METRICS), and Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tools. The data analysis utilized the R program with mada, metafor, and meta packages. Ten retrospective studies with 5926 participants were included in the systematic review and meta-analysis. The overall risk of bias and applicability concerns for each domain of the studies were rated as low, except for one study which was considered to have a high risk of flow and time bias. The mean METRICS score was 70.1% (range 49.6-83.2%). There was moderate heterogeneity across studies and meta-regression identified sources of heterogeneity in the data, including imaging modality, feature selection method, and classifier. The pooled diagnostic odds ratio (DOR) under the bivariate random effects model across the studies was 57.22 (95% CI 27.62-118.52). The pooled sensitivity and specificity were 87% (95% CI 81-92%) and 87% (95% CI 77-93%), respectively. The area under the summary receiver operating characteristic curve (AUC) of the radiomic models was 0.94 (range 0.8 to 0.98). The results supported that the radiomic techniques had good accuracy in diagnosing osteoporosis or abnormal bone mass. The application of radiomics in osteoporosis diagnosis needs to be further confirmed by more prospective studies with rigorous adherence to existing guidelines and multicenter validation.

EN1 promotes lung metastasis of salivary adenoid cystic carcinoma by regulating the PI3K-AKT pathway and epithelial-mesenchymal transition.

BACKGROUND: Engrailed homeobox 1 (EN1) is a candidate oncogene that is epigenetically modified in salivary adenoid cystic carcinoma (SACC). We investigated the expression of EN1 in SACC tissues and cells, EN1 promoter methylation, and the role of EN1 in tumour progression in SACC. METHODS: Thirty-five SACC samples were screened for key transcription factors that affect tumour progression. In vitro and in vivo assays were performed to determine the viability, tumorigenicity, and metastatic ability of SACC cells with modulated EN1 expression. Quantitative methylation-specific polymerase chain reaction analysis was performed on SACC samples. RESULTS: EN1 was identified as a transcription factor that was highly overexpressed in SACC tissues, regardless of clinical stage and histology subtype, and its level of expression correlated with distant metastasis. EN1 promoted cell invasion and migration through epithelial-mesenchymal transition in vitro and enhanced SACC metastasis to the lung in vivo. RNA-seq combined with in vitro assays indicated that EN1 might play an oncogenic role in SACC through the PI3K-AKT pathway. EN1 mRNA levels were negatively correlated with promoter hypermethylation, and inhibition of DNA methylation by 5-aza-dC increased EN1 expression. CONCLUSIONS: The transcription factor EN1 is overexpressed in SACC under methylation regulation and plays a pivotal role in SACC progression through the PI3K-AKT pathway. These results suggest that EN1 may be a diagnostic biomarker and a potential therapeutic target for SACC.

Establishment and characterization of SSI cell line from Sebastes schlegelii intestine for investigating the immune response to Pathogenic Bacteria.

As a commercially valuable fish species, Sebastes schlegelii faces threats from pathogenic bacteria like Edwardsiella piscicida during aquaculture. The global host range of E. piscicida encompasses various species, yet its pathogenic mechanism remains incompletely elucidated. Cell lines offer invaluable in vitro resources for studying the pathogen pathogenicity. Here, we established and characterized a cell line derived from the intestinal tissue of the S. schlegelii, designated as SSI. SSI has undergone continuous subculturing for over 80 passages, demonstrating robust growth in DMEM supplemented with 10%-20% FBS and 20 µM HEPES at 24°C. Karyotype analysis and 18S rRNA amplification confirm its origin. SSI exhibits high transfection efficiency for exogenous DNA, making it suitable for gene expression and intestinal function analysis. E. piscicida infects SSI cells at low densities without inducing morphological changes within 6 h of infection, suggesting the potential of SSI as an in vitro model for studying E. piscicida pathogenicity. This cell line provides a valuable tool for investigating mucosal immunity and E. piscicida pathogenic mechanisms in marine fish.

Clinicopathological characteristics and diagnostic accuracy of BRAF mutations in ameloblastoma: A Bayesian network analysis.

OBJECTIVE: This Bayesian network meta-analysis was performed to analyze the associations between clinicopathological characteristics and BRAF mutations in ameloblastoma (AM) patients and to evaluate the diagnostic accuracy. MATERIALS AND METHODS: Four electronic databases were searched from 2010 to 2024. The search terms used were specific to BRAF and AM. Observational studies or randomized controlled trials were considered eligible. The incidence of BRAF mutation and corresponding clinicopathological features in AM patients were subjected to Bayesian network analyses and diagnostic accuracy evaluation. RESULTS: A total of 937 AM patients from 20 studies were included. The pooled prevalence of BRAF mutations in AM patients was 72%. According to the Bayesian network analysis, BRAF mutations are more likely to occur in younger (odds ratio [OR], 2.3; credible interval [CrI]: 1.2-4.5), mandible site (OR, 3.6; 95% CrI: 2.7-5.2), and unicystic (OR, 1.6; 95% CrI: 1.1-2.4) AM patients. Similarly, higher diagnostic accuracy was found in the younger, mandible, and unicystic AM groups. CONCLUSIONS: The incidence, risk, and diagnostic accuracy of BRAF mutation in AM were greater in younger patients, those with mandible involvement, and those with unicystic AM than in patients with other clinicopathological features. In addition, there was a strong concordance in the diagnostic accuracy between molecular tests and immunohistochemical analysis.

A comprehensive approach to lifestyle intervention based on a calorie-restricted diet ameliorates liver fat in overweight/obese patients with NAFLD: a multicenter randomized controlled trial in China.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a globally increasing health epidemic. Lifestyle intervention is recommended as the main therapy for NAFLD. However, the optimal approach is still unclear. This study aimed to evaluate the effects of a comprehensive approach of intensive lifestyle intervention (ILI) concerning enhanced control of calorie-restricted diet (CRD), exercise, and personalized nutrition counseling on liver steatosis and extrahepatic metabolic status in Chinese overweight and obese patients with NAFLD. METHODS: This study was a multicenter randomized controlled trial (RCT) conducted across seven hospitals in China. It involved 226 participants with a body mass index (BMI) above 25. These participants were randomly assigned to two groups: the ILI group, which followed a low carbohydrate, high protein CRD combined with exercise and intensive counseling from a dietitian, and a control group, which adhered to a balanced CRD along with exercise and standard counseling. The main measure of the study was the change in the fat attenuation parameter (FAP) from the start of the study to week 12, analyzed within the per-protocol set. Secondary measures included changes in BMI, liver stiffness measurement (LSM), and the improvement of various metabolic indexes. Additionally, predetermined subgroup analyses of the FAP were conducted based on variables like gender, age, BMI, ethnicity, hyperlipidemia, and hypertension. RESULTS: A total of 167 participants completed the whole study. Compared to the control group, ILI participants achieved a significant reduction in FAP (LS mean difference, 16.07 [95% CI: 8.90-23.25] dB/m) and BMI (LS mean difference, 1.46 [95% CI: 1.09-1.82] kg/m2) but not in LSM improvement (LS mean difference, 0.20 [95% CI: -0.19-0.59] kPa). The ILI also substantially improved other secondary outcomes (including ALT, AST, GGT, body fat mass, muscle mass and skeletal muscle mass, triglyceride, fasting blood glucose, fasting insulin, HbA1c, HOMA-IR, HOMA-ß, blood pressure, and homocysteine). Further subgroup analyses showed that ILI, rather than control intervention, led to more significant FAP reduction, especially in patients with concurrent hypertension (p < 0.001). CONCLUSION: In this RCT, a 12-week intensive lifestyle intervention program led to significant improvements in liver steatosis and other metabolic indicators in overweight and obese Chinese patients suffering from nonalcoholic fatty liver disease. Further research is required to confirm the long-term advantages and practicality of this approach. TRIAL REGISTRATION: This clinical trial was registered on ClinicalTrials.gov (registration number: NCT03972631) in June 2019.

Homologous-magnetic dual-targeted metal-organic framework to improve the Anti-hepatocellular carcinoma efficacy of PD-1 inhibitor.

The insufficient abundance and weak activity of tumour-infiltrating lymphocytes (TILs) are two important reasons for the poor efficacy of PD-1 inhibitors in hepatocellular carcinoma (HCC) treatment. The combined administration of tanshinone IIA (TSA) and astragaloside IV (As) can up-regulate the abundance and activity of TILs by normalising tumour blood vessels and reducing the levels of immunosuppressive factors respectively. For enhancing the efficacy of PD-1 antibody, a magnetic metal-organic framework (MOF) with a homologous tumour cell membrane (Hm) coating (Hm@TSA/As-MOF) is established to co-deliver TSA&As into the HCC microenvironment. Hm@TSA/As-MOF is a spherical nanoparticle and has a high total drug-loading capacity of 16.13 wt%. The Hm coating and magnetic responsiveness of Hm@TSA/As-MOF provide a homologous-magnetic dual-targeting, which enable Hm@TSA/As-MOF to counteract the interference posed by ascites tumour cells and enhance the precision of targeting solid tumours. Hm coating also enable Hm@TSA/As-MOF to evade immune clearance by macrophages. The release of TSA&As from Hm@TSA/As-MOF can be accelerated by HCC microenvironment, thereby up-regulating the abundance and activity of TILs to synergistic PD-1 antibody against HCC. This study presents a nanoplatform to improve the efficacy of PD-1 inhibitors in HCC, providing a novel approach for anti-tumour immunotherapy in clinical practice.

Nano-selenium repaired the damage caused by fungicides on strawberry flavor quality and antioxidant capacity by regulating ABA biosynthesis and ripening-related transcription factors.

Recently, studies have shown that pesticides may have adverse effects on the flavor quality of the fruits, but there is still a lack of appropriate methods to repair the damage. This study investigated the effects and mechanism of applying the emerging material, nano­selenium, and two fungicides (Boscalid and Pydiflumetofen) alone or together on the flavor quality and antioxidant capacity of strawberries. The results showed that the two fungicides had a negative impact on strawberry color, flavor, antioxidant capacity and different enzymatic systems. The color damage was mainly attributed to the impact on anthocyanin content. Nano­selenium alleviated the quality losses by increasing sugar-acid ratio, volatiles, anthocyanin levels, enzyme activities and DPPH scavenging ability and reducing ROS levels. Results also showed that these damage and repair processes were related to the regulation of flavor and ripening related transcription factors (including FaRIF, FaSnRK1, FaMYB10, FaMYB1, FaSnRK2.6 and FaABI1), the upregulation of genes on sugar-acid, volatile, and anthocyanin synthesis pathways, as well as the increase of sucrose and ABA signaling molecules. In addition, the application of nano-Se supplemented the selenium content in fruits, and was harmless to human health. This information is crucial for revealing the mechanisms of flavor damage caused by pesticides to strawberry and the repaired of nano­selenium, and broadens the researching and applying of nano­selenium in repairing the damage caused by pesticides.

Investigating the impact of virtual simulation experiment and massive open online course (MOOC) on medical students' wound debridement training: a quasi-experimental study.

OBJECTIVE: This study aims to evaluate the impact of virtual simulation experiment teaching model and Massive Open Online Course (MOOC) teaching model on the teaching effect in debridement teaching. METHODS: The study adopted a quasi-experimental design and used virtual simulation technology to construct a virtual simulation experimental teaching platform for debridement. This study was conducted at the Second Clinical College of Wuhan University. The experimental group was composed of 135 third-year clinical medicine students in the 2020 grade, who received the virtual simulation experimental teaching model; the control group was 122 third-year students in the same major in the 2019 grade, who used the MOOC teaching model. The performance of the two groups of students was evaluated through theoretical tests and animal experiment operation. In addition, the effectiveness of the experimental teaching model and student satisfaction were evaluated through questionnaire surveys. RESULTS: The theoretical test scores and animal experiment report scores of the experimental group were significantly higher than those of the control group, and the debridement animal experiment operation time of the experimental group was shorter than that of the control group, and the difference was statistically significant (P < 0.05). The post-class questionnaire survey of the experimental group showed that most students were satisfied with the virtual simulation experimental teaching model and believed that it represented the future teaching trend. CONCLUSIONS: In the teaching of debridement, virtual simulation experiment is an effective t teaching model, which not only helps to improve student performance, but also significantly reduces skill operation time and is recognized by students.

Changes of Potent Odorants in Salted Duck Egg Yolk before and after Roasting.

As the second most widely consumed eggs, duck eggs are made into preserved eggs, salted duck eggs, and roasted duck eggs to extend their shelf-life. To investigate the differences in potent odorants (POs) between salted duck egg yolk (SDEY) and roasted duck egg yolk (RDEY), the volatiles in SDEY and RDEY were extracted through solvent extraction coupled with solvent-assisted flavor evaporation and were assayed with gas chromatography-mass spectrometry-olfactometry. A total of 45 volatiles were identified in two samples, 24 odor-active compounds (OACs) were screened, and more OACs were in RDEY. The flavor-dilution (FD) factors of OACs were obtained by aroma extract dilution analysis and ranged from 3 to 6561. Twenty-two OACs with FD factors ≥ 9 were quantitated, and the results indicated the concentrations of OACs in yolk increased greatly after salted duck eggs were roasted. Based on the concentrations and thresholds, odor activity values (OAVs) were determined; 17 odorants with OAVs ≥ 1 were determined as POs. Acetoin was the most PO in SDEY; there were more POs in RDEY, including 2-ethyl-3,6-dimethylpyrazine, acetoin, 2-acetyl-3-methylthiophene, dihydro-4-hydroxy-2(3H)-furanone, etc. The outcomes obtained have reference values for making better use of duck eggs in the food industry.

Investigation of obesity and its related factors among Chinese medical staff: a cross-sectional pilot study.

BACKGROUND: Many studies have covered the prevalence of obesity in different populations. However, studies on the prevalence and predictors of obesity among medical staff are lacking. The aim of our study is to investigate the prevalence of obesity among medical staff and to identify the related predictors. METHODS: Using a snowballing recruitment strategy in the form of an electronic questionnaire, a cross-sectional survey was conducted among 1201 medical staff from cooperative hospitals between January and March 2022. We designed a questionnaire to investigate the participants' demographic, lifestyle, diet, physical activity, and work status. RESULTS: The overall prevalence of obesity was 8.5%, with males (13.7%) having a greater incidence than females (5.7%) (p < 0.001). Multiple logistic regression analyses showed that alcohol drinking (OR, 2.34; 95% CI 1.23-4.42, p = 0.01), sugar-sweetened beverages consumed > 3/week (OR, 2.50; 95% CI 1.02-6.15, p = 0.046), and working a night shift > 1/week (OR, 2.17; 95% CI 1.02-4.61, p = 0.043) were independent predictive factors for obesity in men. For women, having midnight snack having midnight snack (OR, 2.93;95% CI 1.24-6.96, p = 0.015), good sleep quality (OR, 4.47; 95% CI 1.10-21.70, p = 0.038), and working a night shift > 1/week (OR, 3.62; 95% CI 1.73-7.57, p = 0.001) were independently associated with obesity. CONCLUSIONS: Obesity presented a low prevalence among medical staff. Alcohol drinking, drinking sugar-sweetened beverages > 3/week, and night shift > 1/week predicted a higher risk of obesity in males. In females, having midnight snack, good sleep quality, and night shift > 1/week were independently associated with obesity. LEVEL OF EVIDENCE: V, descriptive study.

[Screening value and correlation of body measurement indices for metabolic syndrome in the population undergoing physical examinations in Chengdu during 2018-2020].

OBJECTIVE: To investigate the screening value and correlation of body measurement indicators for metabolic syndrome(MS) and to provide evidence for MS screening. METHODS: Through a cross-sectional research approach, data from individuals aged 18 and above who participated in health examinations at the North Health Management Center of Sichuan Provincial People's Hospital from 2018 to 2020 were reviewed. Data including height, weight, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, smoking history, and alcohol consumption history were collected. Subsequently, a body shape index(ABSI), body roundness index(BRI), body adiposity index(BAI), abdominal volume index(AVI), relative fat mass index(RFM), and body mass index(BMI) were computed. The individuals were then divided into MS and non-MS groups. The value of body measurement indices in screening for MS in the population aged 18 and above was assessed using ROC curves. Regression analysis was employed to explore the correlation between body measurement indices and MS. RESULTS: A total of 73 411 valid health examination data were obtained, including 44 426 males and 28 985 females. The MS group comprised 9181 males(21%) and 1668 females(6%). In the comparison between the MS and non-MS groups, there were statistically significant differences in ABSI((0.08±0.00) vs. (0.08±0.00)), BRI((4.95±0.67) vs. (4.17±0.68)), BAI((28.08±3.52) vs. (26.39±3.39)), AVI((17.51±2.77) vs. (12.85±2.91)), BMI((27.15±2.99) vs. (23.00±3.04)) and RFM((29.77±5.35) vs. (27.13±6.39))(P<0.05). Univariate Logistic regression analysis showed that ABSI(OR=2.303, 95%CI 1.190-4.457), BRI(OR=4.596, 95%CI 4.446-4.752), BAI(OR=1.144, 95%CI 1.137-1.151), AVI(OR=1.668, 95%CI 1.652-1.684), RFM(OR=1.067, 95%CI 1.064-1.071) and BMI(OR=1.516, 95%CI 1.503-1.528) were associated with MS(P<0.05). Multifactorial Logistic regression analysis corrected for sex, age, smoking and alcohol consumption showed that ABSI(OR=1.767, 95% CI 4.237-7.371), BRI(OR=5.441, 95% CI 5.228-5.663), BAI(OR=1.269, 95% CI 1.260-1.279), AVI(OR=1.648, 95% CI 1.631-1.665), RFM(OR=1.504, 95% CI 1.491-1.517) and BMI(OR=1.508, 95% CI 1.495-1.522) were associated with MS(P<0.05). The ROC curve analysis showed that in adults, the AVI had the highest screening value for MS in males(AUC=0.855, optimal cutoff value=16.18), followed by RFM(AUC=0.844, optimal cutoff value=25.71), BMI(AUC=0.811, optimal cutoff value=25.21), BRI(AUC=0.793, optimal cutoff value=4.39), BAI(AUC=0.709, optimal cutoff value=25.88), and ABSI(AUC=0.671, optimal cutoff value=0.08). In adult females, the RFM had the highest screening value for MS(AUC=0.918, optimal cutoff value=37.01), followed by AVI(AUC=0.911, optimal cutoff value=13.43), BRI(AUC=0.901, optimal cutoff value=4.71), BMI(AUC=0.860, optimal cutoff value=23.94), ABSI(AUC=0.804, optimal cutoff value=0.08), and BAI(AUC=0.797, optimal cutoff value=29.92). CONCLUSION: ABSI, BRI, BAI, AVI, BMI and RFM are all capable of screening for MS. Among males, AVI has the highest screening value for MS, followed by RFM, BMI, BRI, BAI and ABSI. Among females, RFM has the highest screening value for MS, followed by AVI, BRI, BMI, ABSI and BAI. ABSI, BRI, BAI, AVI, RFM and BMI are positively correlated with MS.

Global and Regional Estimate of HIV-Associated Stroke Burden: A Meta-Analysis and Population Attributable Modeling Study.

BACKGROUND: This study aimed to determine the correlation between human-immunodeficiency-virus (HIV) infection and stroke, as well as to estimate the global, regional, and national burden of HIV-associated stroke. METHODS: A registered meta-analysis was performed by searching PubMed, Embase, and Web of Science for relevant literature up to October 31, 2022. The pooled relative risk of stroke in HIV-infected people was calculated using a random-effects model. HIV prevalence and disability-adjusted life years (DALYs) datasets were obtained from the Joint United Nations Program on HIV and AIDS, and the Global Health Data Exchange, respectively. The population attributable fraction was estimated and delivered to calculate the HIV-associated DALYs of stroke from 1990 to 2019, at the global, regional, and national levels. Pearson correlation analysis were conducted to assess the correlation between the age-standardized rate or estimated annual percentage changes and the sociodemographic index. RESULTS: Out of 10 080 identified studies, 11 were included in this meta-analysis. Compared with individuals without HIV-infection, the pooled relative risk of stroke in HIV-infected individuals was 1.40 (95% CI, 1.18-1.65). From 1990 to 2019, the global population attributable fraction of HIV-associated stroke increased almost 3-fold, while the HIV-associated DALYs increased from 18 595 (95% CI, 7485-31 196) in 1990 to 60 684 (95% CI, 24 281-101 894) in 2019. Meanwhile, HIV-associated DALYs varied by region, with Eastern and Southern Africa having the highest value of 126 160 in 2019. Moreover, countries with middle social development index were shouldering the highest increase trend of the HIV-associated DALYs age-standardized rates. CONCLUSIONS: HIV-infected individuals face a significantly higher risk of stroke, and the global burden of HIV-associated stroke has increased over the past 3 decades, showing regional variations. Eastern and Southern Africa bear the highest burden, while Eastern Europe and Central Asia have seen significant growth. Health care providers, researchers, and decision-makers should give increased attention to stroke prevention and management in HIV-endemic areas. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42022367450.

Perturbations in gut microbiota composition in patients with polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: The results of human observational studies on the correlation between gut microbiota perturbations and polycystic ovary syndrome (PCOS) have been contradictory. This study aimed to perform the first systematic review and meta-analysis to evaluate the specificity of the gut microbiota in PCOS patients compared to healthy women. METHODS: Literature through May 22, 2023, was searched on PubMed, Web of Science, Medline, Embase, Cochrane Library, and Wiley Online Library databases. Unreported data in diversity indices were filled by downloading and processing raw sequencing data. Systematic review inclusion: original studies were eligible if they applied an observational case-control design, performed gut microbiota analysis and reported diversity or abundance measures, sampled general pre-menopausal women with PCOS, and are longitudinal studies with baseline comparison between PCOS patients and healthy females. Systematic review exclusion: studies that conducted interventional or longitudinal comparisons in the absence of a control group. Two researchers made abstract, full-text, and data extraction decisions, independently. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodologic quality. Hedge's g standardized mean difference (SMD), confidence intervals (CIs), and heterogeneity (I2) for alpha diversity were calculated. Qualitative syntheses of beta-diversity and microbe alterations were performed. RESULTS: Twenty-eight studies (n = 1022 patients, n = 928 control) that investigated gut microbiota by collecting stool samples were included, with 26 and 27 studies having provided alpha-diversity and beta-diversity results respectively. A significant decrease in microbial evenness and phylogenetic diversity was observed in PCOS patients when compared with control participants (Shannon index: SMD = - 0.27; 95% CI, - 0.37 to - 0.16; phylogenetic diversity: SMD = - 0.39; 95% CI, -- 0.74 to - 0.03). We also found that reported beta-diversity was inconsistent between studies. Despite heterogeneity in bacterial relative abundance, we observed depletion of Lachnospira and Prevotella and enrichment of Bacteroides, Parabacteroides, Lactobacillus, Fusobacterium, and Escherichia/Shigella in PCOS. Gut dysbiosis in PCOS, which might be characterized by the reduction of short-chain fatty acid (SCFA)-producing and bile-acid-metabolizing bacteria, suggests a shift in balance to favor pro-inflammatory rather than anti-inflammatory bacteria. CONCLUSIONS: Gut dysbiosis in PCOS is associated with decreased diversity and alterations in bacteria involved in microbiota-host crosstalk. TRIAL REGISTRATION: PROSPERO registration: CRD42021285206, May 22, 2023.

Erbin accelerates TFEB-mediated lysosome biogenesis and autophagy and alleviates sepsis-induced inflammatory responses and organ injuries.

Mounting attention has been focused on defects of the autophagy-lysosomal pathway in sepsis, however, the precise mechanisms governing the autophagy-lysosomal process in sepsis are poorly known. We have previously reported that Erbin deficiency aggravated the inflammatory response and organ injuries caused by sepsis. In the present study, we found that Erbin knockout impaired the autophagy process in both muramyl dipeptide (MDP)-induced bone marrow-derived macrophages (BMDMs) and sepsis mouse liver and lung, as detected by the accumulation of LC3-II and SQSTM1/p62, and autophagosomes. Pretreatment with autophagy inhibitor chloroquine (CQ) further aggravated inflammatory response and organ injuries in vivo and in vitro sepsis model. We also observed that the impaired lysosomal function mediated autophagic blockade, as detected by the decreased expression of ATP6V, cathepsin B (CTSB) and LAMP2 protein. Immunoprecipitation revealed that the C-terminal of Erbin (aa 391-964) interacts with the N-terminal of transcription factor EB (TFEB) (aa 1-247), and affects the stability of TFEB-14-3-3 and TFEB-PPP3CB complexes and the phosphorylation status of TFEB, thereby promote the nucleus translocation of TFEB and the TFEB target genes transcription. Thus, our study suggested that Erbin alleviated sepsis-induced inflammatory responses and organ injuries by rescuing dysfunction of the autophagy-lysosomal pathway through TFEB-14-3-3 and TFEB-PPP3CB pathway.

Global and regional estimates of cervical cancer burden associated with human immunodeficiency virus infection from 1990 to 2019.

Previous studies reported human immunodeficiency virus (HIV) could enhance human papillomavirus (HPV)-induced cervical cancer. Therefore, the burden of cervical cancer associated with HIV across different regions and time periods need to be assessed. We aim to investigate the global burden of cervical cancer associated with HIV infection. Age standardized rates (ASRs) of cervical cancer disability-adjusted life-years (DALYs) in females (≥15 years old) were calculated by standardization, according the age-specific DALYs numbers extracted from GBD data set 2019. Population attributable fractions was calculated by combining the published risk ratio, with the HIV prevalence (≥15 years old) from Joint United Nations Programme on HIV and AIDS (UNAIDS), and transferred to estimate the HIV-associated cervical cancer burden. Expected annual percentage changes (EAPCs) was calculated to describe the temporal trend of ASR from 1990 to 2019. Pearson correlation analysis were conducted to assess the correlation between the ASR or EAPCs and the socio-demographic index. The worldwide DALYs ASR caused by HIV-associated cervical cancer rose from 3.78 (95% confidence interval [CI]: 2.19-5.56) in 1990 to 9.50 (95% CI: 5.66-13.79) in 2019 per 100k population. In 2019, the region with the greatest burden was Eastern and Southern Africa, with the highest DALYs of 273 900 (95% CI: 149 100-476 400) and ASR of 254.44 per 100k population (95% CI: 168.86-329.28). Notably, the Eastern Europe and Central Asia regions had the highest EAPC (14.07%) of HIV-associated DALYs ASR. Women in Eastern and Southern Africa experience the greatest burden of HIV-associated cervical cancer, while the Eastern Europe and Central Asia regions had witnessed the largest increase over the last 30 years. Prioritize the promotion of HPV vaccination and cervical cancer screening for women living with HIV were crucial in these regions.

Cytokines and chemokines involved in HLA-B27-positive ankylosing spondylitis-associated acute anterior uveitis.

Purpose: Acute anterior uveitis (AAU) is the most common extra-articular symptom of ankylosing spondylitis (AS). This study aims to reveal the cytokines and chemokines involved in the immunopathogenesis of human leucocyte antigen (HLA)-B27+ AS-associated AAU. Methods: Twenty-one HLA-B27+ AS-associated AAU patients and 21 healthy controls (HCs) were recruited for this study. Serum cytokine concentrations in all 42 subjects were determined by the Meso Scale Discovery (MSD) electrochemiluminescence method. In each sample, 34 cytokines, 10 chemokines, eight angiogenesis mediators, and four vascular injury mediators were measured. The differences in cytokine and chemokine concentrations were compared between the two groups. Results: Concentrations of serum IL-3, TNF-α, IL-6, IL-17D, IL-22, IP10/CXCL10, MIP-3α/CCL20, sFlt-1/VEGFR-1, CRP, and MCP-4/CCL13 were significantly higher in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). In contrast, concentrations of serum IL-4, IL-8, MIP-1α/CCL3, Eotaxin-3/CCL26, PlGF, VEGF-C, and VEGF-D were significantly lower in patients with HL-B27+ AS-associated AAU than in HCs (p < 0.05). Conclusions: Significant differences were detected in the levels of several cytokines and chemokines in the serum of HLA-B27+ AS-associated AAU compared with HCs. Some novel differential cytokines and chemokines that have not been reported in other kinds of uveitis were also identified. These results reveal the underlying pathogenesis of HLA-B27+ AS-associated AAU and could potentially aid in clinical diagnosis.

TSAb Modulates Microglia M1 Polarization via Activation of the TSHR-Mediated NF-κB Signaling Pathway.

INTRODUCTION: Thyrotropin receptor-stimulating antibody (TSAb) is a pathogenic antibody in the serum of patients with Graves' disease. The binding of TSAb to thyroid-stimulating hormone receptor (TSHR) in non-thyroid tissue may be associated with the occurrence and development of Graves' disease-related complications. However, only few studies have been conducted on the effects of TSAb on the brain, and the pathogenesis of acute hyperthyroidism myopathy (ATM) is unclear. Therefore, this study aimed to explore the effect of TSAb on the polarization of BV-2 cells in the brain and its possible mechanism and provide a basic experimental basis for ATM. METHODS: BV-2 cells were treated with different concentrations of TSAb. The relative survival rate of BV-2 cells was determined using the CCK-8 assay; the migration ability of BV-2 cells was detected using the Transwell migration assay; and the expression levels of M1/M2 polarization markers (CD86, inducible nitric oxide synthase [iNOS], CD206, and arginase 1 [Arg-1]), TSHR, tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB) protein in BV-2 cells were measured using WB. RESULTS: Compared with the negative control group, the proliferative activity of BV-2 cells was significantly increased in the 20, 50, and 100 ng/mL TSAb groups, and the migration ability of BV-2 cells was significantly enhanced in the 50 and 100 ng/mL TSAb groups. The expression levels of M1 polarization markers (CD86 and iNOS), TSHR, TNF-α, and NF-κB protein in BV-2 cells treated with 50 and 100 ng/mL TSAb for 24 h were significantly upregulated, whereas those of M2 polarization markers (CD206 and Arg-1) significantly decreased. CONCLUSIONS: TSAb can induce abnormal activation of microglia, polarize to the M1 phenotype, and promote the inflammatory cascade reaction, in which TSHR plays a key role in NF-κB activation and proinflammatory cytokine release.

Formation of pre-metastatic niches induced by tumor extracellular vesicles in lung metastasis.

There are a number of malignant tumors that metastasize into the lung as one of their most common sites of dissemination. The successful infiltration of tumor cells into distant organs is the result of the cooperation between tumor cells and distant host cells. When tumor cells have not yet reached distant organs, in situ tumor cells secrete extracellular vesicles (EVs) carrying important biological information. In recent years, scholars have found that tumor cells-derived EVs act as the bridge between orthotopic tumors and secondary metastases by promoting the formation of a pre-metastatic niche (PMN), which plays a key role in awakening dormant circulating tumor cells and promoting tumor cell colonization. This review provides an overview of multiple routes and mechanisms underlying PMN formation induced by EVs and summaries study findings that underline a potential role of EVs in the intervention of lung PMN, both as a target or a carrier for drug design. In this review, the underlying mechanisms of EVs in lung PMN formation are highlighted as well as potential applications to lung metastasis diagnosis and treatment.