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Background Patients utilize online health information to inform their medical decision-making. YouTube is one of the most popular media platforms with abundant health-related resources, yet the quality of the disseminated information remains unclear. This study aims to evaluate the quality and reliability of content pertaining to diverticulosis and diverticulitis on YouTube. Methods One author queried the terms "diverticulosis," "diverticulitis," "acute diverticulitis," and "chronic diverticulitis" on YouTube. The first 50 videos per search were selected for analysis. Duplicates, non-English videos, or procedural content were excluded. Video characteristics including view count, likes, comments, duration, days since upload, view ratio, video power index, and video sources (professional organizations (POs), health information websites (HIWs), and entertainment/independent users (EIUs)) were collected. Videos were scored using the mDISCERN and Global Quality Score (GQS). Results Sixty-four videos were included. DISCERN scores significantly differed between POs (n=20, mean=4.35), HIWs (n=29, mean=2.97), and EIUs (n=15, mean=1.83). GQS also significantly differed between POs (n=20, mean=4.47), HIWs (n=29, mean=3.62), and EIUs (n=15, mean=2.5). Video characteristics significantly differed between groups, with most user engagement seen in EIUs. Conclusion POs and HIWs disseminate higher quality health information about diverticular disease on YouTube. The higher viewer engagement with EIUs is concerning, as these sources were found to have lower quality content. Although YouTube has the capability to provide valuable information on diverticulosis and diverticulitis, enhanced content screening is needed to ensure accuracy and validation.
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Observational studies suggest dyslipidemia as an atopic dermatitis (AD) risk factor and posit that lipid-lowering drugs may influence AD risk, but the causal link remains elusive. Mendelian randomization was applied to elucidate the causal role of serum lipids in AD and assess the therapeutic potential of lipid-lowering drug targets. Genetic variants related to serum lipid traits and lipid-lowering drug targets were sourced from the Global Lipid Genetics Consortium GWAS data. Comprehensive AD data were collated from the UK Biobank, FinnGen, and Biobank Japan. Colocalization, Summary-data-based Mendelian Randomization (SMR), and mediation analyses were utilized to validate the results and pinpoint potential mediators. Among assessed targets, only Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) was significantly linked to a reduced AD risk, corroborated across three separate AD cohorts. No association between serum lipid concentrations or other lipid-lowering drug targets and diminished AD risk was observed. Mediation analysis revealed that beta nerve growth factor (b-NGF) might mediate approximately 12.8% of PCSK9's influence on AD susceptibility. Our findings refute dyslipidemia's role in AD pathogenesis. Among explored lipid-lowering drug targets, PCSK9 stands out as a promising therapeutic agent for AD.
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Dermatitis Atópica , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Proproteína Convertasa 9 , Humanos , Dermatitis Atópica/genética , Dermatitis Atópica/tratamiento farmacológico , Proproteína Convertasa 9/genética , Lípidos/sangre , Predisposición Genética a la Enfermedad , Hipolipemiantes/uso terapéutico , Dislipidemias/genética , Dislipidemias/tratamiento farmacológico , Femenino , MasculinoRESUMEN
Aim/Introduction: Type 2 diabetes mellitus (T2DM) is one of the most frequent and widespread disease in the world.Obesity is the most significant predictor of T2DM, but the exact mechanism how obesity promotes T2DM remains unknown. Finding specific biomarkers to assist in diagnosing and treating patients with obese and T2DM is critical. Materials and Methods: We collected liver tissues from obesity patients with and without T2DM for proteomic sequencing and immunohistochemistry assay. Analysis Gene Ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG), and protein interaction network (PPI) were performed on the parameters and data derived from the Tandem Mass Tags(TMT)-based proteomics analysis of liver tissues. Transcriptome data were downloaded from the Gene Expression Omnibus(GEO)website and genes that are deferentially expressed in both transcriptome and proteome were selected. Results: We identified 140 deferentially expressed proteins from proteomic sequencing. Six biomarkers were deferentially expressed in both proteome and transcriptome with consistent changes in direction. The protein-protein interaction (PPI) analysis suggested CMPK1, the expression with greatest difference, was the core protein among the six biomarkers. Immunohistochemistry validated CMPK1 was upregulated significantly in the liver tissues of T2DM patients. The correlation analysis revealed that the expression of CMPK1 was significantly associated with key molecules in T2DM-related pathways at both protein and transcriptome levels. Conclusion and Novelty: Our study showed CMPK1 was upregulated in the liver of T2DM patients and provides a possible new target for screening and diagnosing T2DM in patients with obese and a novel theoretical basis for the pathophysiological mechanism of obesity-related metabolic diseases.
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The sluggish CO2 reduction and evolution reaction kinetics are thorny problems for developing high-performance Li-CO2 batteries. For the complicated multiphase reactions and multielectron transfer processes in Li-CO2 batteries, exploring efficient cathode catalysts and understanding the interplay between structure and activity are crucial to couple with these pendent challenges. In this work, we applied the CoS as a model catalyst and adjusted its electronic structure by introducing sulfur vacancies to optimize the d-band and p-band centers, which steer the orbital hybridization and boost the redox kinetics between Li and CO2, thus improving the discharge platform of Li-CO2 batteries and altering the deposition behavior of discharge products. As a result, a highly efficient bidirectional catalyst exhibits an ultrasmall overpotential of 0.62 V and a high energy efficiency of 82.8% and circulates stably for nearly 600 h. Meanwhile, density functional theory calculations and multiphysics simulations further elucidate the mechanism of bidirectional activity. This work not only provides a proof of concept to design a remarkably efficient catalyst but also sheds light on promoting the reversible Li-CO2 reaction by tailoring the electronic structure.
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BACKGROUND: Endometrial cancer (EC) is one of the gynecologic malignancy cancer with increasing incidence and mortality rates, partly due to aging populations and genetic risks. This study explores the associations between biological age accelerations (BAA) and risk of incident EC and assesses the joint effect of genetic factor and BAA. MATERIALS AND METHODS: Based on the UK Biobank cohort, 132,315 women participants were included for primary analysis and 124,119 white participants for genetic risk analysis. Biological age(BA) was calculated using the Klemera-Doubal (KDM) and PhenoAge method based on clinical biomarkers. We calculated two metrics for BAA (including KDM residual and PhenoAge residual) using residual analysis, comparing them against chronological age. The risk of incident EC was evaluated using multivariable Cox proportional-hazards models, adjusting for relevant covariates. Polygenic risk scores (PRS) were computed from known EC-associated SNPs. RESULTS: Both KDM and PhenoAge residual, were significantly associated with increased EC risk. In fully adjusted models, the highest tertile of KDM and PhenoAge residual was significantly associated with incident EC compared with the lowest group, with HRs of 1.278 (P=0.0044) and 1.424 (P<0.0001), repectively. The population-attributable fractions were 7.84% for KDM residual (P=0.0044), 9.78% for PhenoAge residual (P=0.0005), and 8.47% for genetic risk (P=0.0005). Additionally, joint associations of BAA and genetic risk with incident EC was evaluated. Compared with low genetic risk and low BAA, high genetic risk and high BAA was significantly associated with the incidence of EC with HRs of up to 2.172 (95% CI 1.592-2.963) for KDM and 2.226 (95% CI 1.640-3.022) for PhenoAge. Overall, higher levels of PhenoAge residual were consistently associated with an increased risk of incident EC, regardless of genetic risk. CONCLUSION: BAA and genetics both enhance the risk of incident EC. The effect of the PhenoAge residual is greater than that of the investigated genes, which in turn is greater than that of the KDM residual. These findings highlight the importance of considering both BAA and genetic factors in EC prevention.
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Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their posttranslational modifications were observed in extracts of central nervous system ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (apTKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.
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Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.
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Biomarcadores , Senescencia Celular , Biología Computacional , Fibroblastos , Envejecimiento de la Piel , Humanos , Envejecimiento de la Piel/genética , Fibroblastos/metabolismo , Biomarcadores/metabolismo , Aprendizaje Automático , Transcriptoma , Colágeno/metabolismo , Regulación hacia Abajo , Piel/metabolismo , Rayos Ultravioleta , Peróxido de Hidrógeno/metabolismoRESUMEN
Background: We aimed to track the global trend of cosmetic treatment outcomes for facial rejuvenation and the differences in modalities used in East Asian and Western populations. Methods: Articles reporting on facial rejuvenation procedures (invasive/noninvasive) were identified in PubMed from 2013 to March 2023 and bibliometrically analyzed for type of published document, citation frequency, authors with most articles, author's affiliation, and frequency distribution of keywords. Results: From 553 articles, most were published in 2021 (nâ =â 86, 15.6%). Western countries (nâ =â 323, 58.4%) contributed more than East Asian (nâ =â 230, 41.6%), with more invasive interventions (nâ =â 355, 64.2%) than noninvasive techniques (nâ =â 198, 35.8%). Numbers of invasive techniques in West versus East Asian countries were 225 (40.7%) versus 135 (24.4%). Main indications were the reduction of facial wrinkles and antiageing treatments. Hyaluronic acid, fillers, and botulinum toxin were the main hotspots for invasive treatments, whereas laser, platelet-rich plasma, and radiofrequency were for noninvasive treatments. Nasolabial folds (13.4%) and glabellar lines (12.4%) were the top research hotspots in the East Asian and Western regions. Common adverse events were pain, erythema, swelling, and bruising. Approximately, 89.3% of publications were from single countries, whereas 10.7% of publications were from international collaborations. Most articles (nâ =â 387; 69.95%) presented their findings using level II evidence. Dermatological surgery (IF = 2.914) had the greatest number of publications (nâ =â 109; 19.71%). Conclusions: The main hotspots were antiaging and youthfulness. This study provides a trend and a new perspective on the future research directions in the field of facial rejuvenation.
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Background: Acute scrotal pain (ASP) is the most common urological emergency in pediatrics, and its causes include testicular torsion (TT), testicular appendage torsion, and epididymo-orchitis. Among them, TT requires prompt and accurate diagnosis and urgent surgical exploration to prevent testicular loss. Conservative anti-infective treatment is recommended for epididymo-orchitis, and surgery is considered only when scrotal abscess formation and sepsis occur. Improving the understanding of TT in primary care doctors, early diagnosis, and timely surgical exploration are essential to improve the survival rate of TT and avoid excessive treatment. This study aimed to explore the risk factors for TT in children with ASP and construct a predictive model. Methods: Clinical data of children who presented with ASP and underwent emergency scrotal exploration surgery were retrospectively analyzed, including general information, physical examination, laboratory tests, and color Doppler ultrasonography (CDU) findings. Based on surgical exploration, the outcomes were categorized as confirmed TT or not. Results: A total of 283 children were included in this study, among whom 134 had TT. The mean age of all patients was 105±47.9 months, with the majority being of Han ethnicity (87.6%) and residing in urban areas (83%). Most patients had normal C-reactive protein levels and negative results in urine routine white blood cell tests (63.3%). After conducting univariate and multivariate logistic regression analyses, we identified laterality, neutrophil count, mean erythrocyte sedimentation rate, epididymal blood flow signal, testicular parenchymal echogenicity, and testicular blood flow signal as independent risk factors influencing the occurrence of TT in ASP patients. Conclusions: This study is the report with the largest sample size on the construction of prediction models for ASP in children in southwestern China. The predictive model we developed demonstrated excellent performance and higher accuracy in predicting TT in children compared to the traditional Testicular Workup for Ischemia and Suspected Torsion (TWIST) score. It can assist pediatric surgeons in diagnosing and treating children with ASP.
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Low-grade cervical intraepithelial neoplasia (CIN1) is an early stage of cervical cancer development. Previously, we reported that exposure to polycyclic aromatic hydrocarbons (PAHs) increases the risk of cervical precancerous lesions, especially in females with a high-risk human papillomavirus (HR-HPV) infection. However, the effects of PAHs on CIN1 progression remain unclear. A community-based prospective cohort study was conducted to evaluate the role of exposure to PAHs in the progression of CIN1. A total of 564 patients diagnosed with CIN1 were followed-up at 6, 12, and 24 months, post-diagnosis, to determine CIN1 reversion, persistence, and progression. Exposure to PAHs was determined by the urine 1-hydroxipayrene (1-OHP) level. Our results showed that the 1-OHP level was significantly higher in patients with CIN1 persistence/progression than in those with reversion (P < .05). High exposure to PAHs increased the risk of CIN1 persistence/progression, with hazard ratios (HR), 95% confidence intervals (CI) of (1.62, 1.24-2.67), (1.98, 1.42-2.75), and (2.37, 1.61-3.49) at 6, 12, and 24 months, post-diagnosis, respectively. The effect was enhanced with HR-HPV positivity, as determined at 6 (1.82, 1.24-2.67), 12 (3.02, 1.74-5.23), and 24 (2.51, 1.48-4.26) months, post-diagnosis. Moreover, the predictive value of exposure to PAHs for CIN1 persistence/progression was higher in HR-HPV-positive patients than in HR-HPV-negative patients. The results revealed that exposure to PAHs facilitated the malignant progression of CIN1 and hindered its reversal, particularly in patients with HR-HPV infection. Our findings provide novel insights into early prevention and intervention targeting the initiation and progression of cervical neoplasia.
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Progresión de la Enfermedad , Hidrocarburos Policíclicos Aromáticos , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Displasia del Cuello del Útero/epidemiología , Displasia del Cuello del Útero/virología , Displasia del Cuello del Útero/patología , Hidrocarburos Policíclicos Aromáticos/efectos adversos , China/epidemiología , Adulto , Neoplasias del Cuello Uterino/virología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patología , Persona de Mediana Edad , Estudios Prospectivos , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/epidemiología , Estudios de Cohortes , Exposición a Riesgos Ambientales/efectos adversosRESUMEN
The behavior of pigs is intricately tied to their health status, highlighting the critical importance of accurately recognizing pig behavior, particularly abnormal behavior, for effective health monitoring and management. This study addresses the challenge of accommodating frequent non-rigid deformations in pig behavior using deformable convolutional networks (DCN) to extract more comprehensive features by incorporating offsets during training. To overcome the inherent limitations of traditional DCN offset weight calculations, the study introduces the multi-path coordinate attention (MPCA) mechanism to enhance the optimization of the DCN offset weight calculation within the designed DCN-MPCA module, further integrated into the cross-scale cross-feature (C2f) module of the backbone network. This optimized C2f-DM module significantly enhances feature extraction capabilities. Additionally, a gather-and-distribute (GD) mechanism is employed in the neck to improve non-adjacent layer feature fusion in the YOLOv8 network. Consequently, the novel DM-GD-YOLO model proposed in this study is evaluated on a self-built dataset comprising 11,999 images obtained from an online monitoring platform focusing on pigs aged between 70 and 150 days. The results show that DM-GD-YOLO can simultaneously recognize four common behaviors and three abnormal behaviors, achieving a precision of 88.2%, recall of 92.2%, and mean average precision (mAP) of 95.3% with 6.0MB Parameters and 10.0G FLOPs. Overall, the model outperforms popular models such as Faster R-CNN, EfficientDet, YOLOv7, and YOLOv8 in monitoring pens with about 30 pigs, providing technical support for the intelligent management and welfare-focused breeding of pigs while advancing the transformation and modernization of the pig industry.
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BACKGROUND: Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined. METHODS: Utilizing the UK Biobank cohort, we assessed biological age using the Klemera-Doubal and PhenoAge method. BAA was quantified by residual analysis compared to chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analyses was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations. RESULTS: A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF (26% per standard deviation [SD] increase in KDM-BA acceleration, 95% confidence intervals [CI]: 23%-28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32%-35%). Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk. CONCLUSIONS: In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions.
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BACKGROUND: The Warburg effect is a hallmark characteristic of colorectal cancer (CRC). Despite extensive research, the role of long non-coding RNAs (lncRNAs) in influencing the Warburg effect remains incompletely understood. Our study aims to identify lncRNAs that may modulate the Warburg effect by functioning as competing endogenous RNAs (ceRNAs). METHODS: Utilizing bioinformatics approaches, we extracted glycolysis-associated gene data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and identified 101 glycolysis-related lncRNAs in CRC. We employed Univariable Cox regression, Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis, and Multivariable Cox regression to develop a prognostic model comprising four glycolysis-linked lncRNAs. We then constructed a prognostic nomogram integrating this lncRNA model with other relevant clinical parameters. RESULTS: The prognostic efficacy of our four-lncRNA signature and its associated nomogram was validated in both training and validation cohorts. Functional assays demonstrated significant glycolysis and hexokinase II (HK2) inhibition following the silencing of RUNDC3A - AS1, a key lncRNA in our prognostic signature, highlighting its regulatory importance in the Warburg effect. CONCLUSIONS: Our research illuminates the critical role of glycolysis-centric lncRNAs in CRC. The developed prognostic model and nomogram underscore the pivotal prognostic and regulatory significance of the lncRNA RUNDC3A - AS1 in the Warburg effect in colorectal cancer.
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Neoplasias Colorrectales , Progresión de la Enfermedad , Glucólisis , ARN Largo no Codificante , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Humanos , Glucólisis/genética , Pronóstico , Hexoquinasa/genética , Hexoquinasa/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Masculino , Nomogramas , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Aging represents a multifaceted process culminating in the deterioration of biological functions. Despite the introduction of numerous anti-aging strategies, their therapeutic outcomes have often been less than optimal. Consequently, discovering new targets to mitigate aging effects is of critical importance. We applied Mendelian randomization (MR) to identify potential pharmacological targets against aging, drawing upon summary statistics from both the Decode and FinnGen cohorts, with further validation in an additional cohort. To address potential reverse causality, bidirectional MR analysis with Steiger filtering was utilized. Additionally, Bayesian co-localization and phenotype scanning were implemented to investigate previous associations between genetic variants and traits. Summary-data-based Mendelian randomization (SMR) analysis was conducted to assess the impact of genetic variants on aging via their effects on protein expression. Additionally, mediation analysis was orchestrated to uncover potential intermediaries in these associations. Finally, we probed the systemic implications of drug-target protein expression across diverse indications by MR-PheWas analysis. Utilizing a Bonferroni-corrected threshold, our MR examination identified 10 protein-aging associations. Within this cohort of proteins, MST1, LCT, GMPR2, PSMB4, ECM1, EFEMP1, and ISLR2 appear to exacerbate aging risks, while MAX, B3GNT8, and USP8 may exert protective influences. None of these proteins displayed reverse causality except EFEMP1. Bayesian co-localization inferred shared variants between aging and proteins such as B3GNT8 (rs11670143), ECM1 (rs61819393), and others listed. Mediator analysis pinpointed 1,5-anhydroglucitol as a partial intermediary in the influence LCT exhibits on telomere length. Circulating proteins play a pivotal role in influencing the aging process, making them promising candidates for therapeutic intervention. The implications of these proteins in aging warrant further investigation in future clinical research.
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Envejecimiento , Análisis de la Aleatorización Mendeliana , Humanos , Envejecimiento/genética , Teorema de BayesRESUMEN
As a common hyperglycemic disease, type 1 diabetes mellitus (T1DM) is a complicated disorder that requires a lifelong insulin supply due to the immune-mediated destruction of pancreatic ß cells. Although it is an organ-specific autoimmune disorder, T1DM is often associated with multiple other autoimmune disorders. The most prevalent concomitant autoimmune disorder occurring in T1DM is autoimmune thyroid disease (AITD), which mainly exhibits two extremes of phenotypes: hyperthyroidism [Graves' disease (GD)] and hypo-thyroidism [Hashimoto's thyroiditis, (HT)]. However, the presence of comorbid AITD may negatively affect metabolic management in T1DM patients and thereby may increase the risk for potential diabetes-related complications. Thus, routine screening of thyroid function has been recommended when T1DM is diagnosed. Here, first, we summarize current knowledge regarding the etiology and pathogenesis mechanisms of both diseases. Subsequently, an updated review of the association between T1DM and AITD is offered. Finally, we provide a relatively detailed review focusing on the application of thyroid ultrasonography in diagnosing and managing HT and GD, suggesting its critical role in the timely and accurate diagnosis of AITD in T1DM.
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BACKGROUND: Elderly-onset seborrheic dermatitis (SD) seriously affects the quality of life. However, associations between air pollution exposures and elderly-onset SD incidence have not been elucidated. OBJECTIVES: Investigate air pollution's role in the incidence of elderly-onset SD. METHODS: We engaged a prospective cohort analysis utilizing the UK Biobank database. Exposure data for specific air pollutants (PM2.5, PM2.5-10, NOX, NO2, and PM10) spanning various years was incorporated. Through a composite air pollution score constructed from five pollutants and employing Cox proportional hazards models, the relationship between pollution and SD was delineated. RESULTS: Our examination of 193,995 participants identified 3,363 SD cases. Higher concentrations of specific pollutants, particularly in the upper quartile (Q4), were significantly linked to an elevated SD risk. Notably, PM2.5, PM10, NO2, and NOX exhibited hazard ratios of 1.11, 1.15, 1.22, and 1.15, respectively. The correlation was further solidified with a positive association between air pollution score increments and SD onset. Intriguingly, this association was accentuated in certain demographics, including younger males, the socioeconomically deprived, smokers, daily alcohol consumers, and those engaging in regular physical activity. CONCLUSIONS: Our findings revealed that air pollution exposures were associated with elderly-onset SD incidence. These results emphasize the importance of preventing environmental exposures to the risk of SD development.
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BACKGROUND: Recent research advancements have indicated a potential association between gut microbiota and cerebrovascular diseases, although the precise causative pathways and the directionality of this association remain to be fully elucidated. OBJECTIVE: This study utilized a bidirectional two-sample Mendelian Randomization (MR) methodology to explore the causal impact of gut microbiota compositions on the risk of cerebrovascular disease. METHODS: Genome-wide Association Study (GWAS) data pertaining to gut microbiota were obtained from the MiBioGen consortium. For Ischemic Stroke (IS), Transient Ischemic Attack (TIA), Vascular Dementia (VD), and Subarachnoid Hemorrhage (SAH), GWAS summary data were sourced from the FinnGen consortium, the IEU Open GWAS project, and the GWAS catalog, respectively. RESULTS: Our MR analyses identified that specific bacterial strains, notably those involved in the production of Short-chain Fatty Acids (SCFAs), including Barnesiella, Ruminococcus torques group, and Coprobacter, serve as protective factors against IS, TIA, and SAH. Linkage Disequilibrium Score Regression (LDSC) analysis corroborated a significant genetic correlation between these gut microbiota strains and various forms of cerebrovascular disease. In contrast, reverse MR analysis failed to establish a bidirectional causal relationship between genetically inferred gut microbiota profiles and these cerebrovascular conditions. CONCLUSION: This investigation has pinpointed particular strains of gut microbiota that play protective or detrimental roles in cerebrovascular disease pathogenesis. These findings offer valuable insights that could be pivotal for the clinical management, prevention, and treatment of cerebrovascular diseases.
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Trastornos Cerebrovasculares , Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Microbioma Gastrointestinal/fisiología , Humanos , Ácidos Grasos Volátiles/metabolismo , Factores Protectores , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
BACKGROUND: Aberrant methylation is common during the initiation and progression of colorectal cancer (CRC), and detecting these changes that occur during early adenoma (ADE) formation and CRC progression has clinical value. AIM: To identify potential DNA methylation markers specific to ADE and CRC. METHODS: Here, we performed SeqCap targeted bisulfite sequencing and RNA-seq analysis of colorectal ADE and CRC samples to profile the epigenomic-transcriptomic landscape. RESULTS: Comparing 22 CRC and 25 ADE samples, global methylation was higher in the former, but both showed similar methylation patterns regarding differentially methylated gene positions, chromatin signatures, and repeated elements. High-grade CRC tended to exhibit elevated methylation levels in gene promoter regions compared to those in low-grade CRC. Combined with RNA-seq gene expression data, we identified 14 methylation-regulated differentially expressed genes, of which only AGTR1 and NECAB1 methylation had prognostic significance. CONCLUSION: Our results suggest that genome-wide alterations in DNA methylation occur during the early stages of CRC and demonstrate the methylation signatures associated with colorectal ADEs and CRC, suggesting prognostic biomarkers for CRC.
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The objective of this study is to explore the correlation of metal levels with assisted reproductive technology (ART) outcomes in polycystic ovary syndrome (PCOS) patients. The individuals were recruited who met the research criteria, only tubal factor or male infertility served as the control group (n = 40) and patient group was PCOS patients (n = 35). Individuals (n = 75) were divided into PCOS group (n = 35) and control group (n = 40). The normal body mass index (BMI) group (control) includes women with BMI < 25 kg/m2 in PCOS group (n = 24) and control group (n = 33), and BMI ≥ 25 kg/m2 in PCOS group (n = 11) and control group (n = 7). We performed an analysis of insulin resistance (IR) (n = 15) group and without insulin resistance (NIR) group (n = 20) in PCOS patient and control patients. Comparing difference demographic data, ART outcomes and the metal levels in every group respectively, the correlation of metal levels and ART outcomes in control participants and PCOS patients were analyzed by the Spearman correlation analysis, and multiple linear regression model was used to examine the association between the concentration of 19 metals and ART outcomes in PCOS group and control group. Plasma manganese (Mn), titanium (Ti), sodium (Na), magnesium (Mg), copper (Cu), calcium (Ca)/Mg ratio, and Cu/zinc (Zn) ratio levels in PCOS patients were higher than that in control, while Zn and Ca levels were lower in PCOS patients than that in control. The Mg levels had a positive connection with the number of eggs recovered, and the iron (Fe) levels were positively associated with the number of transplanted embryos in PCOS-IR. In PCOS-NIR, Mn levels positively correlated with the number of follicles and the number of good embryos. Silver (Ag) levels were negatively correlated with the number of follicles, and aluminum (Al) levels were negatively related with the normal fertilization and the number of good embryos. The Spearman analysis in PCOS-BMI ≥ 25 group exhibited that nickel (Ni) levels were negatively associated with the number of follicles. The plasma metal levels seem to affect the clinical manifestations and in vitro fertilization outcomes in assisted reproduction.
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Developing highly efficient catalysts is significant for Li-CO2 batteries. However, understanding the exact structure of catalysts during battery operation remains a challenge, which hampers knowledge-driven optimization. Here we use X-ray absorption spectroscopy to probe the reconstruction of CoSx (x = 8/9, 1.097, and 2) pre-catalysts and identify the local geometric ligand environment of cobalt during cycling in the Li-CO2 batteries. We find that different oxidized states after reconstruction are decisive to battery performance. Specifically, complete oxidation on CoS1.097 and Co9S8 leads to electrochemical performance deterioration, while oxidation on CoS2 terminates with Co-S4-O2 motifs, leading to improved activity. Density functional theory calculations show that partial oxidation contributes to charge redistributions on cobalt and thus facilitates the catalytic ability. Together, the spectroscopic and electrochemical results provide valuable insight into the structural evolution during cycling and the structure-activity relationship in the electrocatalyst study of Li-CO2 batteries.