The protective effects and potential mechanisms of fulvic acid against ethanol-induced gastric mucosal injury in mice.

Fulvic acid (FA) is a kind of natural organic acids extracted from lignite, which is the active ingredient in Wujin oral liquid, a proprietary Chinese medicine used to treat gastric and duodenal ulcers. However, our understanding of the mechanisms of FA remains limited. Currently, the protection of FA and its mechanism were explored using the ethanol-induced gastric mucosal injury mouse model. The histopathological examinations showed FAs at three doses effectively reduced gastric congestion, oedema caused by ethanol, and prevented gastric epithelial cell fall-off. When compared to the model group, FAs reduced IL-1ß and IL-6 levels in serum, as well as IL-1ß, IL-6, TNF-α, and COX-2 expression levels in tissue. Furthermore, FAs significantly inhibited p65, P38 MAPK, and Erk1/2 phosphorylation in damaged gastric tissue. It was indicated FA has good protection against ethanol-induced gastric mucosa injuries in mice and this effect was related to NF-κB and MAPK signalling pathways.

Teach them how to fish or give them fish? The effect of collective narcissism on intergroup help.

Intergroup help contributes to the solution of global issues in particular. However, whether to teach an outgroup how to address their problem permanently, or to directly help them solve the current problem? Collective narcissism might play a crucial role in this process. Based on the core characteristics of collective narcissism, this research explored whether and how collective narcissism would affect people's willingness to give different types of intergroup help. Study 1 examined the correlation between collective narcissism and intergroup help. Studies 2 and 3 investigated the impacts of outgroup threat and ingroup image on the relationship between collective narcissism and intergroup help respectively. In Study 4, the interaction between outgroup threat and ingroup image was further examined. The results showed that collective narcissism reduced participants' willingness to offer intergroup help, especially autonomy-oriented help. For low-threat outgroups, collective narcissism increased participants' willingness to give dependency-oriented help. In contrast, collective narcissism increased participants' willingness to give autonomy-oriented help when refusal to intergroup help tarnished the ingroup image. For high-threat outgroups, collective narcissism did not predict participants' willingness to give intergroup help. These findings suggest that collective narcissists' preferences for intergroup help change with outgroup threat and ingroup image.

PITX2 functions as a transcription factor for GPX4 and protects pancreatic cancer cells from ferroptosis.

Ferroptosis inhibits tumor progression in pancreatic cancer cells, while PITX2 is known to function as a pro-oncogenic factor in various tumor types, protecting them from ferroptosis and thereby promoting tumor progression. In this study, we sought to investigate the regulatory role of PITX2 in tumor cell ferroptosis within the context of pancreatic cancer. We conducted PITX2 knockdown experiments using lentiviral infection in two pancreatic cancer cell lines, namely PANC-1 and BxPC-3. We assessed protein expression through immunoblotting and mRNA expression through RT-PCR. To confirm PITX2 as a transcription factor for GPX4, we employed Chromatin Immunoprecipitation (ChIP) and Dual-luciferase assays. Furthermore, we used flow cytometry to measure reactive oxygen species (ROS), lipid peroxidation, and apoptosis and employed confocal microscopy to assess mitochondrial membrane potential. Additionally, electron microscopy was used to observe mitochondrial structural changes and evaluate PITX2's regulation of ferroptosis in pancreatic cancer cells. Our findings demonstrated that PITX2, functioning as a transcription factor for GPX4, promoted GPX4 expression, thereby exerting an inhibitory effect on ferroptosis in pancreatic cancer cells and consequently promoting tumor progression. Moreover, PITX2 enhanced the invasive and migratory capabilities of pancreatic cancer cells by activating the WNT signaling pathway. Knockdown of PITX2 increased ferroptosis and inhibited the proliferation of PANC-1 and BxPC-3 cells. Notably, the inhibitory effect on ferroptosis resulting from PITX2 overexpression in these cells could be countered using RSL3, an inhibitor of GPX4. Overall, our study established PITX2 as a transcriptional regulator of GPX4 that could promote tumor progression in pancreatic cancer by reducing ferroptosis. These findings suggest that PITX2 may serve as a potential therapeutic target for combating ferroptosis in pancreatic cancer.

The predictive value of serum tumor markers for EGFR mutation in non-small cell lung cancer patients with non-stage IA.

Objective: The predictive value of serum tumor markers (STMs) in assessing epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC), particularly those with non-stage IA, remains poorly understood. The objective of this study is to construct a predictive model comprising STMs and additional clinical characteristics, aiming to achieve precise prediction of EGFR mutations through noninvasive means. Materials and methods: We retrospectively collected 6711 NSCLC patients who underwent EGFR gene testing. Ultimately, 3221 stage IA patients and 1442 non-stage IA patients were analyzed to evaluate the potential predictive value of several clinical characteristics and STMs for EGFR mutations. Results: EGFR mutations were detected in 3866 patients (57.9 %) of all NSCLC patients. None of the STMs emerged as significant predictor for predicting EGFR mutations in stage IA patients. Patients with non-stage IA were divided into the study group (n = 1043) and validation group (n = 399). In the study group, univariate analysis revealed significant associations between EGFR mutations and the STMs (carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and cytokeratin-19 fragment (CYFRA21-1)). The nomogram incorporating CEA, CYFRA 21-1, pathology, gender, and smoking history for predicting EGFR mutations with non-stage IA was constructed using the results of multivariate analysis. The area under the curve (AUC = 0.780) and decision curve analysis demonstrated favorable predictive performance and clinical utility of nomogram. Additionally, the Random Forest model also demonstrated the highest average C-index of 0.793 among the eight machine learning algorithms, showcasing superior predictive efficiency. Conclusion: CYFRA21-1 and CEA have been identified as crucial factors for predicting EGFR mutations in non-stage IA NSCLC patients. The nomogram and 8 machine learning models that combined STMs with other clinical factors could effectively predict the probability of EGFR mutations.

Triglyceride-glucose index and mortality risk in individuals with or without chronic kidney disease: Insights from a national survey of United States adults, 1999-2018.

BACKGROUND AND AIMS: The Triglyceride-Glucose Index (TyG) has been proposed as a predictor to mortality, yet its association remains incompletely understood for individuals with or without chronic kidney disease (CKD). METHODS AND RESULTS: We analyzed data from the National Health and Nutrition Examination Survey spanning the years 1999-2018. CKD was defined as eGFR level <60 ml/min/1.73 m2 or urinary albumin creatinine ratio ≥30 mg/g. We employed the Cox proportional-hazards model to evaluate the incident risk of mortality associated with TyG among both non-CKD and CKD individuals. In the current analysis, 19,426 individuals were without CKD, while 2975 individuals had CKD. The overall mean TyG was 8.65, with significant difference between non-CKD and CKD individuals (8.60 vs 8.95, P < 0.001). The TyG index exhibited linear associations with incident cardiovascular disease (CVD) mortality and all-cause mortality among non-CKD and CKD individuals, respectively. A per-unit increase in the TyG index was significantly associated with CVD mortality for both non-CKD (HR = 1.24, 95%CI = 1.09-1.41) and CKD participants (HR = 1.19, 95%CI = 1.04-1.36), with no significant difference in the associations between the two groups (P = 0.091). For both non-CKD and CKD participants, TyG index was significantly associated with CVD mortality and all-cause mortality among those with age <65, but not for those with age ≥65. CONCLUSIONS: Our findings underscore the TyG index's as a valuable predictive tool for assessing the risk of all-cause and CVD mortality in both individuals with and without CKD.

Three-in-One Zinc Anodes Created by a Large-scale Two-Step Method Achieving Excellent Long-Term Cyclic Reversibility and Thin Electrode Integrity.

Practical aqueous zinc-ion batteries require low-cost thin zinc anodes with long-term reversible stripping/depositing. However, thin zinc anodes encounter more severe issues than thick zinc, such as dendrites and uneven stripping, resulting in subpar performance and limited lifetimes. Here, this work proposes a three-in-one zinc anode obtained by a large-scale two-step method to address the above issues. In a three-in-one zinc anode, the copper foil as an inactive current collector solves the gradual reduction of the active area when only the pure zinc as an active current collector. This work develops an automatic electroplating device that can continuously deposit a zinc layer on a conducting foil to meet the demand for zinc-coated copper foils. The sodium carboxymethylcellulose (CMC)-zinc fluoride (ZnF2) protective layer prevents direct contact between zinc and separator, and provides a uniform and sufficient supply of zinc ions. The CMC-ZnF2-coated copper foil performs up to 3000 reversible zinc deposition/stripping cycles with a cumulative capacity of 6 Ah cm-2 and an average Coulombic efficiency of 99.94%. The Zn||ZnVO cell using the three-in-one anode achieved a high capacity retention of over 70% after 15 000 cycles. The proposed three-in-one anode and the automatic electroplating device will facilitate industrialization of practical thin zinc anodes.

Fair evaluation of federated learning algorithms for automated breast density classification: The results of the 2022 ACR-NCI-NVIDIA federated learning challenge.

The correct interpretation of breast density is important in the assessment of breast cancer risk. AI has been shown capable of accurately predicting breast density, however, due to the differences in imaging characteristics across mammography systems, models built using data from one system do not generalize well to other systems. Though federated learning (FL) has emerged as a way to improve the generalizability of AI without the need to share data, the best way to preserve features from all training data during FL is an active area of research. To explore FL methodology, the breast density classification FL challenge was hosted in partnership with the American College of Radiology, Harvard Medical Schools' Mass General Brigham, University of Colorado, NVIDIA, and the National Institutes of Health National Cancer Institute. Challenge participants were able to submit docker containers capable of implementing FL on three simulated medical facilities, each containing a unique large mammography dataset. The breast density FL challenge ran from June 15 to September 5, 2022, attracting seven finalists from around the world. The winning FL submission reached a linear kappa score of 0.653 on the challenge test data and 0.413 on an external testing dataset, scoring comparably to a model trained on the same data in a central location.

The efficacy and safety of short-term and low-dose IL-2 combined with tocilizumab to treat rheumatoid arthritis.

Background: Immunotherapy targeting factors related to immune imbalance has been widely employed for RA treatment. This study aimed to evaluate the efficacy and safety of low-dose interleukin (IL)-2 combined with tocilizumab (TCZ), a biologics targeting IL-6, in RA patients. Methods: Fifty adults with active RA who met the criteria with complete clinical data were recruited, and divided into three groups: control group (n=15), IL-2 group (n=26), and IL-2+TCZ group (n=9). In addition to basic treatment, participants in the IL-2 group received IL-2 (0.5 MIU/day), while participants in the IL-2+TCZ group received IL-2 (0.5 MIU/day) along with one dose of TCZ (8 mg/kg, maximum dose: 800 mg). All subjects underwent condition assessment, laboratory indicators and safety indicators detection, and records before treatment and one week after treatment. Results: Compared with the baseline, all three groups showed significant improvement in disease conditions, as evidenced by significantly reduced disease activity indicators. The low-dose IL-2 and combination treatment groups demonstrated a violent proliferation of Tregs, while the absolute number of Th1, Th2, and Th17 cells in the latter group showed a decreasing trend. The decrease in the Th17/Treg ratio was more pronounced in the IL-2+TCZ groups. No significant adverse reactions were observed in any of the patients. Conclusion: Exogenous low doses of IL-2 combined TCZ were found to be safe and effective in reducing effector T cells and appropriately increasing Treg levels in RA patients with high effector T cell levels. This approach helps regulate immune homeostasis and contributes to the prevention of disease deterioration. Clinical trial registration: https://www.chictr.org.cn/showprojEN.html?proj=13909, identifier ChiCTR-INR-16009546.

Integrative analysis of single-cell and bulk RNA sequencing unveils a machine learning-based pan-cancer major histocompatibility complex-related signature for predicting immunotherapy efficacy.

Major histocompatibility complex (MHC) could serve as a potential biomarker for tumor immunotherapy, however, it is not yet known whether MHC could distinguish potential beneficiaries. Single-cell RNA sequencing datasets derived from patients with immunotherapy were collected to elucidate the association between MHC and immunotherapy response. A novel MHCsig was developed and validated using large-scale pan-cancer data, including The Cancer Genome Atlas and immunotherapy cohorts. The therapeutic value of MHCsig was further explored using 17 CRISPR/Cas9 datasets. MHC-related genes were associated with drug resistance and MHCsig was significantly and positively associated with immunotherapy response and total mutational burden. Remarkably, MHCsig significantly enriched 6% top-ranked genes, which were potential therapeutic targets. Moreover, we generated Hub-MHCsig, which was associated with survival and disease-special survival of pan-cancer, especially low-grade glioma. This result was also confirmed in cell lines and in our own clinical cohort. Later low-grade glioma-related Hub-MHCsig was established and the regulatory network was constructed. We provided conclusive clinical evidence regarding the association between MHCsig and immunotherapy response. We developed MHCsig, which could effectively predict the benefits of immunotherapy for multiple tumors. Further exploration of MHCsig revealed some potential therapeutic targets and regulatory networks.

Factors Impacting One-year Follow-up Visit Adherence after Bariatric Surgery in West China: A Mixed Methods Study.

PURPOSE: Quality follow-up (FU) is crucial after bariatric surgery. However, poor adherence after surgery is prevalent. This research aimed to explore the factors related to FU adherence after bariatric surgery in West China. MATERIALS AND METHODS: This study used a sequential explanatory mixed-methods research design. Participants (n = 177) were identified from the West China Hospital. Demographic information, disease profile, treatment information, and post-surgery FU information were obtained from the bariatric surgery database of the Division of Gastrointestinal Surgery of the West China Hospital. The survey data were analyzed using logistic regression. Semi-structured interviews with participants (n = 10) who had low adherence were conducted. The recording was transcribed verbatim and entered into qualitative data analysis software. Qualitative data were analyzed using a content analysis approach. RESULTS: Multiple logistic regression revealed that living in Chengdu (OR, 2.308), being employed (OR, 2.532), non-smoking (OR, 2.805), and having less than five years of obesity (OR, 2.480) were positive predictors of FU adherence within one year. Semi-structured interviews suggested that factors related to adherence to FU were lack of motivation, lack of opportunity, insufficient ability, and beliefs regarding consequences. CONCLUSION: Factors impacting one-year FU visit adherence after bariatric surgery include not only demographic and disease-related factors but also social and family factors. These results will provide evidence to support healthcare professionals in developing personalized postoperative FU management strategies.

Efficacy and safety of bimekizumab in the treatment of psoriatic arthritis: a systematic review and meta-analysis.

BACKGROUND: Bimekizumab, a humanized monoclonal IgG1 antibody targeting both interleukin (IL)-17A and IL-17F, could be effective for treating Psoriatic arthritis (PsA). This study aimed to systematically evaluate the efficacy and safety of bimekizumab in the management of PsA. RESEARCH DESIGN AND METHODS: A comprehensive literature search by August 2023 was performed through PubMed, Embase, Cochrane Controlled Register of Trials, and ClinicalTrials.gov. investigating the efficacy or safety data of bimekizumab in the treatment of PsA. Data was pooled using the random-effects models. Egger tests were used to evaluate potential publication bias. RESULTS: A total of 4 RCTs, involving 892 PsA patients and 467 placebo controls, were included in this analysis. Bimekizumab significantly increased the rates of PASI75 and PASI100 compared with placebos [RR = 7.22, 95% CI (5.24, 9.94), p < 0.001; RR = 10.12, 95% CI (6.00, 17.09), p < 0.001]. The rate of overall adverse events was slightly higher in the bimekizumab group [RR = 1.42, 95% CI (1.05, 1.93) p = 0.023). However, there were fewer adverse severe drug reactions in the bimekizumab group compared to the placebo. CONCLUSION: Bimekizumab had a significant clinical benefit in managing PsA and an acceptable safety profile.

Enterococcus casseliflavus regulates amino acid metabolism in edible insect Clanis bilineata tsingtauica: a functional metagenomics study.

Introduction: The soybean hawkmoth, Clanis bilineata tsingtauica, is an edible insect that possesses high nutritional, medicinal and economic value. It has developed into a characteristic agricultural industry in China. Methods: The dominant gut bacterium in diapause larvae of soybean hawkmoths was identified by metagenomics, and the effect of diapause time on gut microbiome composition, diversity and function was investigated. Results: Enterococcus and Enterobacter were measured to be the dominant genera, with Enterococcus casseliflavus and Enterococcus pernyi being the dominant species. Compared to the controls, the relative abundance of E. casseliflavus and E. pernyi on day 14 was lower by 54.51 and 42.45%, respectively. However, the species richness (including the index of Chao and ACE) of gut microbiota increased on day 28 compared to controls. The gene function was mainly focused on carbohydrate and amino acid metabolism. Metabolic pathways annotated for amino acids on day 14 increased by 9.83% compared to controls. It is speculated that diapause soybean hawkmoths may up-regulate amino acid metabolism by reducing E. casseliflavus abundance to maintain their nutritional balance. Additionally, tetracycline, chloromycetin and ampicillin were screened as the top three antibiotics against E. casseliflavus. Discussion: This study not only extends our knowledge of gut microbiome in soybean hawkmoths at the species level, but also provides an initial investigation of gene functionality in interaction with insect hosts.

Cancer immunometabolism: advent, challenges, and perspective.

For decades, great strides have been made in the field of immunometabolism. A plethora of evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism to the center stage of innate and adaptive immunomodulation. Given this, we focus on changes in immunometabolism, a converging series of biochemical events that alters immune cell function, propose the immune roles played by diversified metabolic derivatives and enzymes, emphasize the key metabolism-related checkpoints in distinct immune cell types, and discuss the ongoing and upcoming realities of clinical treatment. It is expected that future research will reduce the current limitations of immunotherapy and provide a positive hand in immune responses to exert a broader therapeutic role.

Improved isoprene detection performance of Si-doped WO3 films deposited by sputtering and post-annealing.

Si-doped WO3 films were sputtered at room temperature and then annealed in air at 500 °C. The Si doping resulted in structural distortion from space group P21/n to Pc. A high density of pores with a diameter of ∼20 nm was observed in the films, which is ideal for gas sensing applications because of the easy diffusion of gas. Isoprene sensitivity, which is defined as the resistance ratio measured in pure air and in air containing 5 ppm isoprene, was greatly improved by the Si doping. The films containing 6.3 at% Si showed the highest sensitivity of 7.7 at a working temperature of 325 °C. However, despite a lower sensitivity of 6.9 measured at 350 °C, the films exhibited better gas selectivity for isoprene over a range of reference gases, including methanol, ethanol, acetone, CO and CO2. The response and recovery times of the films were very short, being less than 1.5 and 3.0 seconds, respectively. Detailed characterization with a range of techniques verified that the increase in gas sensitivity in the Si-doped films was related to better oxygen adsorbability as a consequence of an increase in positively-charged oxygen vacancies introduced by the aliovalent substitution of W6+ by Si4+.

Occupation-Dependent Particle Separation in One-Dimensional Non-Hermitian Lattices.

We unveil an exotic phenomenon arising from the intricate interplay between non-Hermiticity and many-body physics, namely, an occupation-dependent particle separation for hardcore bosons in a one-dimensional lattice driven by unidirectional non-Hermitian pumping. Taking hardcore bosons as an example, we find that a pair of particles occupying the same unit cell exhibit an opposite non-Hermitian pumping direction to that of unpaired ones occupying different unit cells. By turning on an intracell interaction, many-body eigenstates split in their real energies, forming separable clusters in the complex energy plane with either left-, right-, or bipolar-types of non-Hermitian skin effect (NHSE). The dependency of skin accumulating directions on particle occupation is further justified with local sublattice correlation and entanglement entropy of many-body eigenstates. Dynamically, this occupation-dependent NHSE manifests as uni- or bidirectional pumping for many-body initial states, allowing for spatially separating paired and unpaired particles. Our results unveil the possibility of designing and exploring novel non-Hermitian phases originated from particle nonconservation in subsystems (e.g., orbitals, sublattices, or spin species) and their spatial configurations.

Roxadustat Versus Erythropoietin: The Comparison of Efficacy in Reversing Ventricular Remodeling in Dialysis Patients with Anaemia.

Background: Renal anaemia and left ventricular hypertrophy are the main complications of chronic kidney disease and are shared among dialysis patients. This retrospective study aimed to compare the efficacies of the hypoxia-inducible factor prolyl hydroxylase inhibitor roxadustat and recombinant human erythropoietin in reversing ventricular remodeling in dialysis patients with renal anaemia. Methods: A total of 204 participants underwent baseline examinations, including echocardiograms and laboratory tests, before being administered either treatment for at least 24 weeks from January 2018 to October 2021, after which follow-up examinations were conducted at 6 months. Propensity score matching based on key variables included age, gender, cardiovascular diseases, cardiovascular medications, dialysis course and the vascular access at baseline was performed to include populations with similar characteristics between groups. Results: In total, 136 patients were included with roxadustat or recombinant human erythropoietin. The left ventricular mass index after treatment with roxadustat and recombinant human erythropoietin both significantly decreased after 6 months, but there was no significant difference in the change in left ventricular mass index between the two groups. In addition, the left ventricular end-diastolic diameters and left ventricular wall thickness, systolic blood pressure, and diastolic blood pressure significantly decreased in the roxadustat group. Roxadustat and recombinant human erythropoietin also increased haemoglobin significantly, but there was no significant difference in the change in haemoglobin between the two groups. The results of multiple linear regression showed that the change in haemoglobin was independent factor affecting the improvement of left ventricular mass index. Conclusions: The increase of haemoglobin was associated with improving left ventricular hypertrophy in dialysis patients. However, the beneficial effects between roxadustat and recombinant human erythropoietin on left ventricular mass index did not show clear superiority or inferiority in six months.

Adaptive Intermediate Class-Wise Distribution Alignment: A Universal Domain Adaptation and Generalization Method for Machine Fault Diagnosis.

Many transfer learning methods have been proposed to implement fault transfer diagnosis, and their loss functions are usually composed of task-related losses, distribution distance losses, and correlation regularization losses. The intrinsic parameters and trade-off parameters between losses, however, need to be tuned according to the specific diagnosis tasks; thus, the generalization abilities of these methods in multiple tasks are limited. Besides, the alignment goal of most domain adaptation (DA) mechanisms dynamically changes during the training process, which will result in loss oscillation, slow convergence and poor robustness. To overcome the above-mentioned issues, a novel and simple transfer learning diagnosis method named adaptive intermediate class-wise distribution alignment (AICDA) model is proposed, and it is established via the proposed AICDA mechanism, dynamic intermediate alignment (DIA) adaptive layer and AdaSoftmax loss. The AICDA mechanism develops an adaptive intermediate distribution as the alignment goal of multiple source domains and target domains, and it can simultaneously align the global and class-wise distributions of these domains. The DIA layer is designed to adaptively achieve domain confusion without the distribution distance loss and the correlation regularization loss. Meanwhile, to ensure the classification performance of the AICDA mechanism, AdaSoftmax loss is proposed for boosting the separability of Softmax loss. Finally, in order to evaluate the effectiveness and universality of the AICDA diagnosis model to the most degree, various multisource mixed fault transfer diagnosis tasks of wind turbine planetary gearboxes, including DA and domain generalization (DG), are implemented, and the experimental results indicate that our proposed AICDA model has a higher diagnosis accuracy and a stronger generalization ability than other state-of-the-art transfer learning methods.

The role of sialidase Neu1 in respiratory diseases.

Neu1 is a sialidase enzyme that plays a crucial role in the regulation of glycosylation in a variety of cellular processes, including cellular signaling and inflammation. In recent years, numerous evidence has suggested that human NEU1 is also involved in the pathogenesis of various respiratory diseases, including lung infection, chronic obstructive pulmonary disease (COPD), asthma, and pulmonary fibrosis. This review paper aims to provide an overview of the current research on human NEU1 and respiratory diseases.

Genetic prediction of modifiable lifestyle factors for erectile dysfunction.

Background: The causal relationship between certain lifestyle factors and erectile dysfunction (ED) is still uncertain. Aim: The study sought to investigate the causal effect of 9 life factors on ED through 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR). Methods: Genetic instruments to proxy 9 risk factors were identified by genome-wide association studies. The genome-wide association studies estimated the connection of these genetic variants with ED risk (n = 223 805). We conducted SVMR, inverse variance-weighting, Cochran's Q, weighted median, MR-Egger, MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier), and MVMR analyses to explore the total and direct relationship between life factors and ED. Outcomes: The primary outcome was defined as self or physician-reported ED, or using oral ED medication, or a history of surgery related to ED. Results: In SVMR analyses, suggestive associations with increased the risk of ED were noted for ever smoked (odds ratio [OR], 5.894; 95% confidence interval [CI], 0.469 to 3.079; P = .008), alcohol consumption (OR, 1.495; 95% CI, 0.044 to 0.760; P = .028) and body mass index (BMI) (OR, 1.177; 95% CI, 0.057 to 0.268; P = .003). Earlier age at first intercourse was significantly related to reduced ED risk (OR, 0.659; 95% CI, -0.592 to -0.244; P = 2.5 × 10-6). No strong evidence was found for the effect of coffee intake, time spent driving, physical activity, and leisure sedentary behaviors on the incidence of ED (All P > .05). The result of MVMR analysis for BMI (OR, 1.13; 95% CI, 1.01 to 1.25; P = .045) and earlier age at first intercourse (OR, 0.77; 95% CI, 0.56 to 0.99; P = .018) provided suggestive evidence for the direct impact on ED, while no causal factor was detected for alcoholic drinks per week and ever smoked. Clinical implications: This study provides evidence for the impact of certain modifiable lifestyle factors on the development of ED. Strengths and limitations: We performed both SVMR and MVMR to strengthen the causal relationship between exposures and outcomes. However, the population in this study was limited to European ancestry. Conclusion: Ever smoked, alcoholic drinks per week, BMI, and age first had sexual intercourse were causally related to ED, while the potential connection between coffee intake, physical activity, recreational sedentary habits, and increased risk of ED needs to be further confirmed.