KCNQ1 rs2237895 gene polymorphism increases susceptibility to type 2 diabetes mellitus in Asian populations.

BACKGROUND: The association of single nucleotide polymorphism of KCNQ1 gene rs2237895 with type 2 diabetes mellitus (T2DM) is currently controversial. It is unknown whether this association can be gene realized across different populations. AIM: To determine the association of KCNQ1 rs2237895 with T2DM and provide reliable evidence for genetic susceptibility to T2DM. METHODS: We searched PubMed, Embase, Web of Science, Cochrane Library, Medline, Baidu Academic, China National Knowledge Infrastructure, China Biomedical Liter-ature Database, and Wanfang to investigate the association between KCNQ1 gene rs2237895 and the risk of T2DM up to January 12, 2022. Review Manager 5.4 was used to analyze the association of the KCNQ1 gene rs2237895 polymorphism with T2DM and to evaluate the publication bias of the selected literature. RESULTS: Twelve case-control studies (including 11273 cases and 11654 controls) met our inclusion criteria. In the full population, allelic model [odds ratio (OR): 1.19; 95% confidence interval (95%CI): 1.09-1.29; P < 0.0001], recessive model (OR: 1.20; 95%CI: 1.11-1.29; P < 0.0001), dominant model (OR: 1.27. 95%CI: 1.14-1.42; P < 0.0001), and codominant model (OR: 1.36; 95%CI: 1.15-1.60; P = 0.0003) (OR: 1.22; 95%CI: 1.10-1.36; P = 0.0002) indicated that the KCNQ1 gene rs2237895 polymorphism was significantly correlated with susceptibility to T2DM. In stratified analysis, this association was confirmed in Asian populations: allelic model (OR: 1.25; 95%CI: 1.13-1.37; P < 0.0001), recessive model (OR: 1.29; 95%CI: 1.11-1.49; P = 0.0007), dominant model (OR: 1.35; 95%CI: 1.20-1.52; P < 0.0001), codominant model (OR: 1.49; 95%CI: 1.22-1.81; P < 0.0001) (OR: 1.26; 95%CI: 1.16-1.36; P < 0.0001). In non-Asian populations, this association was not significant: Allelic model (OR: 1.06, 95%CI: 0.98-1.14; P = 0.12), recessive model (OR: 1.04; 95%CI: 0.75-1.42; P = 0.83), dominant model (OR: 1.06; 95%CI: 0.98-1.15; P = 0.15), codominant model (OR: 1.08; 95%CI: 0.82-1.42; P = 0.60. OR: 1.15; 95%CI: 0.95-1.39; P = 0.14). CONCLUSION: KCNQ1 gene rs2237895 was significantly associated with susceptibility to T2DM in an Asian population. Carriers of the C allele had a higher risk of T2DM. This association was not significant in non-Asian populations.

MSRB2 Ameliorates H2O2-induced Chondrocyte Oxidative Stress and Suppresses Apoptosis in Osteoarthritis.

BACKGROUND: Chondrocyte oxidative stress and apoptosis are critical factors contributing to the pathogenesis of osteoarthritis (OA). Methionine sulfoxide reductase B2 (MSRB2) is a mitochondrial protein that protects cells from oxidative stress and is involved in apoptosis. This study aimed to investigated the expression of MSRB2 in articular cartilage tissues and elucidated its effect on H2O2-stimulated chondrocytes. METHODS: Human chondrocytes were cultured in Dulbecco's modified Eagle's medium (DMEM)/F12. MSRB2 overexpression in chondrocytes was achieved by transfecting with an MSRB2 overexpression plasmid. Western blot, quantitative RT-PCR, Immunofluorescence staining, and TUNEL assay were employed in this study. RESULTS: MSRB2 expression was found to be reduced in OA patients. Furthermore, overexpression of MSRB2 in H2O2-induced chondrocytes mitigated apoptosis and enhanced cell viability. Elevated MSRB2 expression diminished chondrocyte ROS contents, decreased cytochrome C (Cyc) in the cytoplasm, and regulated mitochondrial membrane potential to maintain mitochondrial homeostasis. Interestingly, knockdown of charged multivesicular body protein 5 (CHMP5) led to a decreased inMSRB2 expression in chondrocytes. Additionally, protein levels of CHMP5 and MSRB2 were reduced in H2O2-stimulated chondrocytes, and silencing CHMP5 reduced MSRB2 expression. Knockdown of CHMP5 increased cleaved caspase-3 expression in H2O2-induced chondrocytes and elevated TUNEL-positive chondrocytes. CONCLUSION: MSRB2 decreased in OA, and overexpression of MSRB2 alleviated oxidative stress and apoptosis of chondrocyte.

Right ventricular volume and function by three-dimensional echocardiography: results of the echocardiographic measurements in normal Chinese adults (EMINCA) II.

Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.

CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.

Comparison of surgical and conservative treatment outcomes for type a aortic intramural hematoma.

OBJECTIVE: This study aimed to compare hospital and long-term clinical outcomes associated with various treatment methods for Stanford A type aortic intramural hematoma (IMH) to provide a reference for clinical decision-making. METHODS: In this single-center cohort study, we retrospectively analyzed 73 patients with Type A IMH treated at our center from August 1, 2018 to August 1, 2021. Among these patients, 26 were treated conservatively, and 47 underwent surgical intervention. We next compared this IMH cohort with 154 patients with acute type A aortic dissection (AD) who were treated surgically during the same study period. RESULTS: Computed tomography angiography revealed that the diameter of the ascending aorta of IMH patients treated with surgery was higher than IMH patients treated with conservative therapy (44.92 ± 7.58 mm vs. 51.22 ± 11.85 mm, P < 0.05), while there was no significant difference in other clinical parameters. The in-hospital mortality of patients with IMH who underwent surgical treatment was lower than those undergoing conservative treatment (0% vs. 11.5%, P < 0.05). The long-term mortality of the conservative IMH group was higher than the surgical IMH group (26.1% vs. 8.5%, P < 0.05). There was no significant difference in the surgical parameters and postoperative complications between AD and IMH surgery patients. The proportion of circulatory arrest time in the lower body (19.98 ± 9.39 min vs. 17.51 ± 3.97 min) and arch involvement (98 (63.6%) vs. 22 (46.8%)) in the IMH surgery group was lower than in the AD surgery group (P < 0.05). CONCLUSIONS: Compared with conservative treatment, surgical treatment of IMH significantly improves the survival rate of patients. Thus, surgical intervention should be considered the primary treatment option if feasible. Furthermore, The safety of IMH surgery can be guaranteed just like AD. But we still need in the future evidence on bigger samples.

Clinical characteristics of 4,520 paediatric patients infected with the SARS-CoV-2 omicron variant, in Xi'an, China.

Background and objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has broad tissue tropism and high transmission, which are likely to perpetuate the pandemic. The study aim to analyze the clinicopathogenic characteristics in paediatric patients. Methods: In this single-centre study, we retrospectively included all confirmed cases infected by SARS-CoV-2 infection at Xi'an Children's Hospital, China, from 1 December to 31 December 2022. The demographic, clinical, laboratory, and radiological features of the patients were analysed. Results: A total of 4,520 paediatric patients with SARS-CoV-2 omicron variant infections were included. Of these, 3,861 (85.36%) were outpatients, 659 (14.64%) were hospitalised patients, and nine patients (0.20%) died. Of the nine patients who died, five were diagnosed with acute necrotising encephalopathy (ANE). The most common symptoms were fever in 4,275 (94.59%) patients, cough in 1,320 (29.20%) patients, convulsions in 610 (13.50%) patients, vomiting in 410 (9.07%) patients, runny nose/coryza in 277 (6.13%) patients, hoarseness of voice in 273 (6.04%) patients. A blood cell analysis showed a slight elevation of monocytes (mean: 11.14 ± 0.07%). The main diagnoses for both outpatients and inpatients were respiratory infection with multisystem manifestations. Conclusions: A high incidence of convulsions is a typical characteristic of children infected with SARS-CoV-2. Five of the nine COVID-19 fatalities were associated with ANE. This indicates that nervous system damage in children with SARS-CoV-2 infection is more significant.

GINS2 promotes the progression of human HNSCC by altering RRM2 expression.

INTRODUCTION: GINS2 exerts a carcinogenic effect in multiple human malignancies, while it is still unclear that the potential roles and underlying mechanisms of GINS2 in HNSCC. METHODS: TCGA database was used to screen out genes with significant differences in expression in HNSCC. Immunohistochemistry and qRT-PCR were used to measure the expression of GINS2 in HNSCC tissues and cells. GINS2 was detected by qRT-PCR or western blot after knockdown or overexpression. Celigo cell counting, MTT, colony formation, and flow cytometric assay were used to check the ability of proliferation and apoptosis. Bioinformatics and microarray were used to screen out the downstream genes of GINS2. RESULTS: GINS2 in HNSCC tissues and cells was up-regulated, which was correlated with poor prognosis. GINS2 gene expression was successfully inhibited and overexpressed in HNSCC cells. Knockdown of GINS2 could inhibit proliferation and increase apoptosis of cells. Meanwhile, overexpression of GINS2 could enhance cell proliferation and colony formation. Knockdown of RRM2 may inhibit HNSCC cell proliferation, while overexpression of RRM2 rescued the effect of reducing GINS2 expression. CONCLUSION: Our study reported the role of GINS2 in HNSCC for the first time. The results demonstrated that in HNSCC cells, GINS2 promoted proliferation and inhibited apoptosis via altering RRM2 expression. Therefore, GINS2 might play a carcinogen in HNSCC, and become a specific promising therapeutic target.

A Real-Time Monitoring Method for Droplet Transfer Frequency in Wire-Filled GTAW Based on Arc Sensing.

Droplet transfer frequency is a decisive factor in welding quality and efficiency in gas tungsten arc welding (GTAW). However, there still needs to be a monitoring method for droplet transfer frequency with high precision and good real-time performance. Therefore, a real-time monitoring method for droplet transfer frequency in wire-filled GTAW using arc sensing is proposed in this paper. An arc signal acquisition system is developed, and the wavelet filtering method filters out noise from the arc signal. An arc signal segmentation method-based on the OTSU algorithm and a feature extraction method for droplet transition based on density-based spatial clustering of applications with noise (DBSCAN)-is proposed to extract the feature signal of the droplet transition. A new conception of droplet transition uniformity is proposed, and it can be used to monitor the weld bead width uniformity. Numerous experiments for monitoring droplet transfer frequency in real time are conducted with typical welding parameters. This method enables the real-time observation of droplet transfer frequency, and the result shows that the average monitoring error is less than 0.05 Hz.

Alterations in Adipocytokine Signaling Pathway and Pyroptosis in Neonatal Hypoxic-ischemic Encephalopathy.

AIMS: The aims of this study are to discover dysregulated adipocytokine signaling pathway and pyroptosis-related genes to predict neonatal hypoxic-ischemic encephalopathy (HIE) occurrence. BACKGROUND: HIE is an important cause of infant death and long-term neurological sequelae. Current treatment options for HIE are relatively limited and the pathogenesis of HIE remains to be fully explored. This study investigated the alterations of adipocytokine signaling pathway and pyroptosis in neonatal HIE. OBJECTIVE: To reveal the alterations of adipocytokine signaling pathway and pyroptosis relevant to HIE occurrence. METHODS: Data on neonatal HIE were downloaded from the Gene Expression Omnibus (GEO) database. Pathway analyses of single-sample gene set enrichment analysis (ss- GSEA) and GSEA were performed on the adipocytokine signaling pathway and pyroptosis. Proportions of immune cells in a single sample were also calculated by ssGSEA and CIBERSORT algorithm. The relationship between the adipocytokine signaling pathway and pyroptosis was analyzed according to Pearson correlation analysis. RESULTS: The activities of KEGG pathways changed after the occurrence of HIE, and adipocytokine signaling pathway was activated with related overexpressed genes. For the three energy metabolisms, carbohydrate metabolism was enhanced; lipid metabolism showed increased fatty acids metabolism and decreased ability of fatty acids synthesis; metabolic levels of phosphate and phenylalanine in amino acid metabolism were elevated. Enhanced pyroptosis and relevant overexpressed genes were accompanied by increased immune cells. A positive connection between adipocytokine signaling pathway and pyroptosis was observed. CONCLUSION: These results indicated that the adipocytokine signaling pathway may promote HIE occurrence by upregulating the expression of pyroptosis-related genes, providing a novel mechanism for HIE.

Long-term exposure to particulate matter is associated with elevated blood pressure: Evidence from the Chinese plateau area.

Background: Ambient air pollution could increase the risk of hypertension; however, evidence regarding the relationship between long-term exposure to particulate matter and elevated blood pressure in plateau areas with lower pollution levels is limited. Methods: We assessed the associations of long-term exposure to particulate matter (PM, PM1, PM2.5, and PM10) with hypertension, diastolic blood pressure (DBP), systolic blood pressure (SBP) and pulse pressure (PP) in 4.235 Tibet adults, based on the baseline of the China multi-ethnic cohort study (CMEC) in Lhasa city, Tibet from 2018-19. We used logistic regression and linear regression models to evaluate the associations of ambient PM with hypertension and blood pressure, respectively. Results: Long-term exposure to PM1, PM2.5, and PM10 is positively associated with hypertension, DBP, and SBP, while negatively associated with PP. Among these air pollutants, PM10 had the strongest effect on hypertension, DBP, and SBP, while PM2.5 had the strongest effect on PP. The results showed for hypertension odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.58, 2.51 per interquartile range (IQR) µg/m3 increase in PM1, OR = 1.93; 95% CI = 1.55, 2.40 per IQR µg/m3 increase in PM2.5, and OR = 2.12; 95% CI = 1.67, 2.68 per IQR µg/m3 increase in PM10. Conclusions: Long-term exposure to ambient air pollution was associated with an increased risk of hypertension, elevated SBP and DBP levels, and decreased PP levels. To reduce the risk of hypertension and PP reduction, attention should be paid to air quality interventions in plateau areas with low pollution levels.

Development of an immune-related diagnostic predictive model for oral lichen planus.

Oral lichen planus (OLP) was a chronic inflammatory disease of unknown etiology with a 1.4% chance of progressing to malignancy. However, it has been suggested in several studies that immune system disorders played a dominant role in the onset and progression of OLP. Therefore, this experiment aimed to develop a diagnostic prediction model for OLP based on immunopathogenesis to achieve early diagnosis and treatment and prevent cancer. In this study, 2 publicly available OLP datasets from the gene expression omnibus database were filtered. In the experimental group (GSE52130), the level of immune cell infiltration was assessed using MCPcounter and ssGSEA algorithms. Subsequently, differential expression analysis and gene set enrichment analysis were performed between the OLP and control groups. The resulting differentially expressed genes were intersected with immunologically relevant genes provided on the immunology database and analysis portal database (ImmPort) website to obtain differentially expressed immunologically relevant genes (DEIRGs). Furthermore, the gene ontology and kyoto encyclopedia of genes and genomes analyses were carried out. Finally, protein-protein interaction network and least absolute shrinkage and selection operator regression analyses constructed a model for OLP. Receiver operating characteristic curves for the experimental and validation datasets (GSE38616) were plotted separately to validate the model's credibility. In addition, real-time quantitative PCR experiment was performed to verify the expression level of the diagnostic genes. Immune cell infiltration analysis revealed a more significant degree of inflammatory infiltration in the OLP group compared to the control group. In addition, the gene set enrichment analysis results were mainly associated with keratinization, antibacterial and immune responses, etc. A total of 774 differentially expressed genes was obtained according to the screening criteria, of which 65 were differentially expressed immunologically relevant genes. Ultimately, an immune-related diagnostic prediction model for OLP, which was composed of 5 hub genes (BST2, RNASEL, PI3, DEFB4A, CX3CL1), was identified. The verification results showed that the model has good diagnostic ability. There was a significant correlation between the 5 hub diagnostic biomarkers and immune infiltrating cells. The development of this model gave a novel insight into the early diagnosis of OLP.

Effectiveness and safety of glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes: evidence from a retrospective real-world study.

Introduction: Global phase III clinical trials have shown superior hypoglycemic efficacy to insulin and other oral hypoglycemic agents. However, there is a scarcity of real-world data comparing different glucagon-like peptide 1 receptor agonist (GLP-1RA) directly. This study aimed to assess the safety and effectiveness of various GLP-1RA in treating type 2 diabetes mellitus (T2DM) in a real-world clinical setting and identify predictive factors for favorable treatment outcomes. Methods: This was a retrospective, single-center, real-world study. The changes in HbA1c, fasting plasma glucose (FPG), body weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), and the percentage of participants who achieved HbA1c of <7%, 7%-8%, and ≥ 8% after GLP-1RA treatment was analyzed. The clinical factors that affect the effectiveness of GLP-1RA were analyzed. Results: At baseline, the 249 participants had a mean baseline HbA1c of 8.7 ± 1.1%. After at least three months of follow-up, the change in HbA1c was -0.89 ± 1.3% from baseline. Dulaglutide exerted a more significant hypoglycemic effect than immediate-release exenatide. The percentage of participants who achieved HbA1c<7% was substantial, from 6.0% at baseline to 28.9%. Average body weight decreased by 2.02 ± 3.8 kg compared to baseline. After GLP-1RA treatment, the reduction in SBP was 2.4 ± 7.1 mmHg from baseline. A shorter duration of diabetes and a higher baseline HbA1c level were more likely to achieve a good response in blood glucose reduction. Conclusions: This study provided real-world evidence showing that GLP-1RA significantly improved HbA1c, body weight, and SBP. The results can inform the decision-making about GLP-1RA treatment in daily clinical practice.

Fuzzy information recognition and translation processing in English interpretation based on a generalized maximum likelihood ratio algorithm.

English interpretation plays a vital role as a critical link in cross-language communication. However, there are various types of ambiguous information in many interpreting scenarios, such as ambiguity, ambiguous vocabulary, and syntactic structures, which may lead to inaccuracies and fluency issues in translation. This article proposes a method based on the generalized maximum likelihood ratio algorithm (GLR) to identify and process fuzzy information in English interpretation to improve the quality and efficiency of performance. Firstly, we systematically analyzed the common types of fuzzy information in interpretation and delved into the basic principles and applications of the generalized maximum likelihood ratio algorithm. This algorithm is widely used in natural language processing to solve uncertainty problems and has robust modeling and inference capabilities, making it suitable for handling fuzzy information in interpretation. Then, we propose a fuzzy information recognition model based on the generalized maximum likelihood ratio algorithm. This model utilizes a large-scale interpretation corpus for training and identifies potential fuzzy information in the interpretation process through statistical analysis and pattern recognition. Once fuzzy information is detected, we adopt a series of effective translation processing strategies, including contextual inference and adaptation, to ensure the accuracy and naturalness of interpretation. Finally, we conducted a series of experiments to evaluate the performance of the proposed method. The experimental results show that the fuzzy information recognition and translation processing method based on the generalized maximum likelihood ratio algorithm performs well in different interpretation scenarios, significantly improving the quality and fluency of interpretation and reducing ambiguity caused by fuzzy information.

Depression, anxiety and brain volume after hearing loss and tinnitus: cohort study in the UK Biobank.

BACKGROUND: Hearing loss and tinnitus have been proposed as potential indicators of impaired mental health and brain morphological changes. AIMS: To assess the associations of hearing loss and tinnitus with the risk of depression and anxiety and with brain volume. METHOD: We conducted a community-based cohort study including 129 610 participants aged 40-69 years at recruitment to the UK Biobank with a follow-up period during 2006-2021 to estimate the risk of depression and anxiety after detection of hearing loss and reported tinnitus. We also assessed the associations of hearing loss and tinnitus with brain volume in a subsample with available brain magnetic resonance imaging data (N = 5222). RESULTS: We observed an increased risk of depression among individuals with hearing loss (hazard ratio [HR] 1.14, 95% CI 1.03-1.26), tinnitus (HR 1.30, 95% CI 1.21-1.41) or both (HR 1.32, 95% CI 1.15-1.52), compared with individuals with neither hearing loss nor tinnitus. Similar results were noted for anxiety (HR 1.18, 95% CI 1.07-1.30 for hearing loss; HR 1.32, 95% CI 1.22-1.43 for tinnitus; and HR 1.48, 95% CI 1.30-1.68 for both). Hearing loss was associated with decreased overall brain volume as well as decreased volume of different brain regions. The latter associations disappeared after adjustment for whole intracranial volume. Tinnitus was associated with greater left accumbens and right occipital pole volume after adjustment for the whole intracranial volume. CONCLUSIONS: Individuals with tinnitus are at increased risk of depression and anxiety. Hearing loss, on the other hand, is associated with both mood disorders and altered brain morphology.

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis.

BACKGROUND: Evidence of the effects of metabolically healthy obesity (MHO) on atherosclerosis is limited; the transition effects of metabolic health and obesity phenotypes have been ignored. We examined the association between metabolic health and the transition to atherosclerosis risk across body mass index (BMI) categories in a community population. METHODS: This cross-sectional study was based on a national representative survey that included 50,885 community participants aged ≥40 years. It was conducted from 01 December 2017 to 31 December 2020, in 13 urban and 13 rural regions across Hunan China. Metabolic health was defined as meeting less than three abnormalities in blood pressure, glucose, high-density lipoprotein cholesterol, triglycerides, or waist circumference. The participants were cross-classified at baseline based on their metabolic health and obesity. In addition, the relationship between atherosclerosis and transitions in metabolic health status based on 4733 participants from baseline to the second survey after 2 years was considered. The relationship between metabolic health status and the risk of transition to Carotid atherosclerosis (CA) was assessed using logistic regression and Cox proportional hazards regression analyses. RESULTS: In this study, the mean age of the participants was 60.7 years (standard deviation [SD], 10.91), 53.0% were female, and 51.2% had CA. As compared with metabolically healthy normal weight (MHN), those with MHO phenotype (odd ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.21), metabolically unhealthy normal weight (OR 1.27, 95% CI 1.19-1.35), metabolically unhealthy overweight (OR 1.41, 95% CI 1.33-1.48), and metabolically unhealthy obese (OR 1.54, 95% CI 1.44-1.64) had higher risk for CA. However, during the follow-up of 2 years, almost 33% of the participants transitioned to a metabolically unhealthy status. As compared with stable healthy normal weight, transition from metabolically healthy to unhealthy status (hazard ratios [HR] 1.21, 95% [CI] 1.02-1.43) and stable metabolically unhealthy overweight or obesity (MUOO) (HR 1.32, 95% CI 1.17-1.48) were associated with higher risk of CA. CONCLUSIONS: In the community population, obesity remains a risk factor for CA despite metabolic health. However, the risks were highest for metabolically unhealthy status across all BMI categories. A large proportion of metabolically healthy overweight or participants with obesity converts to an unhealthy phenotype over time, which is associated with an increased risk of CA.

Satellite Cell-Derived Exosomes: A Novel Approach to Alleviate Skeletal Muscle Atrophy and Fibrosis.

Skeletal muscle atrophy coincides with extensive fibrous tissue hyperplasia in muscle-atrophied patients, and fibrous tissue plays a vital role in skeletal muscle function and hinders muscle fiber regeneration. However, effective drugs to manage skeletal muscle atrophy and fibrosis remain elusive. This study isolated and characterized exosomes derived from skeletal muscle satellite cells (MuSC-Exo). The study investigated their effects on denervated skeletal muscle atrophy and fibrosis in Sprague Dawley (SD) rats via intramuscular injection. MuSC-Exo demonstrated the potential to alleviate skeletal muscle atrophy and fibrosis. The underlying mechanism using single-cell RNA sequencing data and functional analysis are analyzed. Mechanistic studies reveal close associations between fibroblasts and myoblasts, with the transforming growth factor ß1 (TGF-ß1)-Smad3-Pax7 axis governing fibroblast activation in atrophic skeletal muscle. MuSC-Exo intervention inhibited the TGF-ß1/Smad3 pathway and improved muscle atrophy and fibrosis. In conclusion, MuSC-Exo-based therapy may represent a novel strategy to alleviate skeletal muscle atrophy and reduce excessive fibrotic tissue by targeting Pax7 through the TGF-ß1/Smad3 pathway.

An integrated network pharmacology, molecular docking and experiment validation study to investigate the potential mechanism of Isobavachalcone in the treatment of osteoarthritis.

BACKGROUND: In many different plants, including Dorstenia and Psoralea corylifolia L., Isobavachalcone (IBC) is a naturally occurring flavonoid chemical having a range of biological actions, including anti-inflammatory, immunomodulatory, and anti-bacterial. The "Theory of Medicinal Properties" of the Tang Dynasty states that Psoralea corylifolia L. has the ability to alleviate discomfort in the knees and waist. One of the most widespread chronic illnesses, osteoarthritis (OA), is characterized by stiffness and discomfort in the joints. However, there hasn't been much research done on the effectiveness and underlying processes of IBC in the treatment of osteoarthritis. AIM OF THE STUDY: To investigate the potential efficacy and mechanism of IBC in treating osteoarthritis, we adopted an integrated strategy of network pharmacology, molecular docking and experiment assessment. MATERIALS AND METHODS: The purpose of this research was to determine the impact of IBC on OA and the underlying mechanisms. IBC and OA possible targets and processes were predicted using network pharmacology, including the relationship between IBC and OA intersection targets, Cytoscape protein-protein interaction (PPI) to obtain key potential targets, and GO and KEGG pathway enrichment analysis to reveal the probable mechanism of IBC on OA. Following that, in vitro tests were carried out to confirm the expected underlying processes. Finally, in vivo tests clarified IBC's therapeutic efficacy on OA. RESULTS: We anticipated and validated that the impact of IBC on osteoarthritis is mostly controlled by the PI3K-AKT-NF-κB signaling pathway by combining the findings of network pharmacology analysis, molecular docking and Experiment Validation. CONCLUSIONS: This study reveals the IBC has potential to delay OA development.

Pesticide residue detection technology for herbal medicine: current status, challenges, and prospects.

The domains of cancer therapy, disease prevention, and health care greatly benefit from the use of herbal medicine. Herbal medicine has become the mainstay of developing characteristic agriculture in the planting area increasing year by year. One of the most significant factors in affecting the quality of herbal medicines is the pesticide residue problem caused by pesticide abuse during the cultivation of herbal medicines. It is urgent to solve the problem of detecting pesticide residues in herbal medicines efficiently and rapidly. In this review, we provide a comprehensive description of the various methods used for pesticide residue testing, including optical detection, the enzyme inhibition rate method, molecular detection methods, enzyme immunoassays, lateral immunochromatographic, nanoparticle-based detection methods, colorimetric immunosensor, chemiluminescence immunosensor, smartphone-based immunosensor, etc. On this basis, we systematically analyze the mechanisms and some of the findings of the above detection strategies and discuss the challenges and prospects associated with the development of pesticide residue detection tools.

Effects of simulated acid rain on hydrochemical factors and microbial community structure in red soil aquifers.

Acid rain can lower the pH of groundwater and affect its hydrogeochemistry and microbial ecology. However, the effects of acid rain on the hydrogeochemistry and microbial ecology of red soil groundwater systems in southern China are poorly understood. Previous research had mainly investigated the sources and patterns of groundwater acidification, but not the microbial mechanisms that contribute to this process and their associations with hydrochemical factors. To address this knowledge gap, we conducted a soil column experiment to simulate the infiltration of acid rain through various filter materials (coarse, medium, and fine sand) and to examine the hydrochemical and microbial features of the infiltrate, which can reveal how simulated acid rain (pH 3.5-7.0) alters the hydrochemistry and microbial community composition in red soil aquifers. The results showed that the pH of the leachate decreased due to simulated acid rain, and that the leaching efficiency of nitrogen and metal ions was influenced by the particle size of the filter media. Illumina 16S rRNA gene sequencing revealed that the leachate was dominated by Proteobacteria, Patescibacteria, Actinobacteria, and Acidobacteria, with Proteobacteria accounting for 67.04-74.69% of the bacterial community and containing a high proportion of nitrifying and denitrifying bacteria. Additionally, several genera with heavy metal tolerance, such as Burkholderia-Caballeronia-Paraburkholderia, Delftia, Methylversatilis, Aquicella, and Ralstonia, were widely distributed in the leachate, indicating the strong adaptive capacity of the microbial population. A correlation analysis between the hydrochemical factors and the microbial community structure revealed that pH was the most influential factor, followed by NO2--N, Fe, Al, Cu, Mn, and others. These results indicate that acidification modifies the hydrochemical conditions of the aquifer, creating an environment that is unfavorable for microbial growth and survival. However, some microorganisms may acquire resistance genes to cope with environmental changes.

Inhibition of RIPK1 alleviating vascular smooth muscle cells osteogenic transdifferentiation via Runx2.

Vascular calcification (VC) is recognized as a crucial risk factor for cardiovascular diseases. Our previous report revealed that the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) plays a role in this process. However, the underlying molecular mechanisms remain elusive. Notably, receptor-interacting protein kinase 1 (RIPK1) has been implicated in the development of cardiovascular diseases, yet its role and mechanisms in VC remain unexplored. To address this gap, we established models using chronic kidney disease mice and calcifying VSMCs to investigate the impact of RIPK1 on VC. Subsequently, a RIPK1-specific inhibitor (NEC-1) was applied in both in vitro and in vivo models. Our findings indicate significant activation of RIPK1 in calcified human arterial tissue, as well as in animal and cellular models. RIPK1 activation promotes the osteogenic transdifferentiation of VSMCs. Treatment with the NEC-1 substantially reduced VC. These results demonstrate that RIPK1 is a target for preventing VC.