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Genetic variants and lifestyle factors have been associated with gastric cancer risk, but the extent to which an increased genetic risk can be offset by a healthy lifestyle remains unknown. We aimed to establish a genetic risk model for gastric cancer and assess the benefits of adhering to a healthy lifestyle in individuals with a high genetic risk. In this meta-analysis and prospective cohort study, we first did a fixed-effects meta-analysis of the association between genetic variants and gastric cancer in six independent genome-wide association studies (GWAS) with a case-control study design. These GWAS comprised 21 168 Han Chinese individuals, of whom 10 254 had gastric cancer and 10 914 geographically matched controls did not. Using summary statistics from the meta-analysis, we constructed five polygenic risk scores in a range of thresholds (p=5 × 10−4 p=5 × 10−5 p=5 × 10−6 p=5 × 10−7, and p=5 × 10−8) for gastric cancer. We then applied these scores to an independent, prospective, nationwide cohort of 100 220 individuals from the China Kadoorie Biobank (CKB), with more than 10 years of follow-up. The relative and absolute risk of incident gastric cancer associated with healthy lifestyle factors (defined as not smoking, never consuming alcohol, the low consumption of preserved foods, and the frequent intake of fresh fruits and vegetables), was assessed and stratified by genetic risk (low [quintile 1 of the polygenic risk score], intermediate [quintile 2–4 of the polygenic risk score], and high [quintile 5 of the polygenic risk score]). Individuals with a favourable lifestyle were considered as those who adopted all four healthy lifestyle factors, those with an intermediate lifestyle adopted two or three factors, and those with an unfavourable lifestyle adopted none or one factor. The polygenic risk score derived from 112 single-nucleotide polymorphisms (p<5 × 10−5) showed the strongest association with gastric cancer risk (p=7·56 × 10−10). When this polygenic risk score was applied to the CKB cohort, we found that there was a significant increase in the relative risk of incident gastric cancer across the quintiles of the polygenic risk score (ptrend<0·0001). Compared with individuals who had a low genetic risk, those with an intermediate genetic risk (hazard ratio [HR] 1·54 [95% CI 1·22–1·94], p=2·67 × 10−4) and a high genetic risk (2·08 [1·61–2·69], p<0·0001) had a greater risk of gastric cancer. A similar increase in the relative risk of incident gastric cancer was observed across the lifestyle categories (ptrend<0·0001), with a higher risk of gastric cancer in those with an unfavourable lifestyle than those with a favourable lifestyle (2·03 [1·46–2·83], p<0·0001). Participants with a high genetic risk and a favourable lifestyle had a lower risk of gastric cancer than those with a high genetic risk and an unfavourable lifestyle (0·53 [0·29–0·99], p=0·048), with an absolute risk reduction of 1·12% (95% CI 0·62–1·56). Chinese individuals at an increased risk of incident gastric cancer could be identified by use of our newly developed polygenic risk score. Compared with individuals at a high genetic risk who adopt an unhealthy lifestyle, those who adopt a healthy lifestyle could substantially reduce their risk of incident gastric cancer. National Key R&D Program of China, National Natural Science Foundation of China, 333 High-Level Talents Cultivation Project of Jiangsu Province, and China Postdoctoral Science Foundation.

Objective: The efficacy of melatonin on sleep disorders in Parkinson's disease (PD) is still unclear. The purpose of this study is to investigate the efficacy of melatonin on sleep disorders in PD by summarizing evidence from randomized clinical trials (RCTs). Methods: PubMed, Cochrane Library, EMBASE, and Web of science were searched until 20 August 2021. Results were analyzed using Review Manager 5. 2 software. We used the software of trial sequential analysis (TSA) to avoid false-positive results caused by random errors. Results: We included 7 studies to conduct this systematic review and meta-analysis. Results of the meta-analysis showed that compared with placebo, the subjective sleep quality of PD patients had a significant improvement after receiving melatonin treatment (MD = -2. 19, 95% CI: -3. 53 to -0. 86, P = 0. 001). In this systematic review, we qualitatively analyzed the efficacy of melatonin on the objective sleep quality of PD, and results showed that melatonin exerts a positive effect with good safety and tolerability. However, there isn’t significant improvement in excessive daytime sleepiness assessed by the Epworth Sleepiness Scale (ESS). Conclusion: We found that melatonin can significantly improve the subjective and objective sleep quality of PD patients with good safety and tolerability. Melatonin may be a promising treatment for insomnia in PD patients.

Emerging evidence indicates that circular RNAs (circRNAs) are implicated in cancer development. This study aimed to evaluate whether circulating circRNAs may serve as novel biomarkers for non‐small cell lung cancer (NSCLC). We used RNA sequencing (RNA‐seq) and quantitative real‐time PCR to explore cancer‐related circRNAs. Bioinformatics and functional analyses were performed to reveal biological effects of circRNAs on lung cancer cells. A total of 5471 distinct circRNAs were identified by total RNA‐seq, in which 185 were differentially expressed between cancerous and adjacent normal tissues. A circRNA derived from exon 5–7 of the FARSA gene, termed circFARSA, was observed to increase in cancerous tissues (P = 0.016), and was more abundant in patients’ plasma than controls (P < 0.001). Overexpression of circFARSA in A549 cell line significantly promoted cell migration and invasion. In silico analysis suggested that circFARSA might sponge miR‐330‐5p and miR‐326, thereby relieving their inhibitory effects on oncogene fatty acid synthase. Summarily, this study revealed circRNA profile of NSCLC for the first time and provided the evidence of plasma circFARSA as a potential noninvasive biomarker for this malignancy. Differences in circRNA expression profiles between NSCLC and adjacent normal tissues. (A) Volcano plots showing differential expression of circRNAs between the two groups. The red points represent the differentially expressed circRNAs with fold change ≥2.0 (log2 scaled) and P < 0.05(−log10 scaled). (B) The distribution of differentially expressed circRNAs in human chromosomes. (C) Hierarchical clustering analysis of the top 10 upregulated and downregulated circRNAs.

To estimate the compressive strength of cement-based materials with mining waste, the dataset based on a series of experimental studies was constructed. The support vector machine (SVM), decision tree (DT), and random forest (RF) models were developed and compared. The beetle antennae search (BAS) algorithm was employed to tune the hyperparameters of the developed machine learning models. The predictive performances of the three models were compared by the evaluation of the values of correlation coefficient (R) and root mean square error (RMSE). The results showed that the BAS algorithm can effectively tune these artificial intelligence models. The SVM model can obtain the minimum RMSE, while the BAS algorithm is inefficient in DT and RF models. The SVM, DT, and RF models can be used to predict the compressive strength of cement-based materials using solid mining waste as aggregate effectively and accurately, with high R values and lower RMSE values. The RF algorithm can obtain the highest value of R and the lowest value of RMSE, demonstrating the highest accuracy. The solid mining waste to cement ratio is the most important variable to affect the compressive strength. Curing time was also an important parameter in the compressive strength of cemented materials, followed by the water-solid ratio of mining waste and fine sand ratio.

Background Polycystic ovary syndrome (PCOS), a prevalent endocrine-metabolic disorder affecting reproductive-aged women worldwide, is characterized by oligo-/anovulation, hyperandrogenism, and polycystic ovarian morphology. Despite affecting 6 ~ 20% of women globally, the molecular mechanisms driving PCOS pathogenesis remain poorly understood, hindering the development of targeted therapeutic strategies. Methods To delineate the cellular basis of PCOS pathophysiology, we employed single-cell RNA sequencing (scRNA-seq) data from ovarian theca cells and oocytes of normo-ovulatory controls and PCOS patients. Cellular heterogeneity was systematically mapped using unsupervised clustering, followed by differential expression analysis, pathway enrichment, and pseudotemporal trajectory reconstruction. Key findings were validated in a prenatal dihydrotestosterone-induced murine PCOS model and in vitro theca-interstitial cell cultures treated with AKT activator SC79. Results scRNA-seq identified seven distinct theca cell clusters. PCOS patients exhibited an expanded proportion of theca cells expressing steroidogenic acute regulatory protein (STAR), correlating with elevated androgen production, heightened oxidative stress pathway activity, and diminished PI3K-AKT signaling. Oocytes from PCOS patients also showed increased oxidative stress markers. Pathway enrichment indicated impaired oocyte differentiation and development. Pseudotime trajectory analysis of theca cells revealed altered gene expression patterns linked to AKT signaling, oxidative stress, and androgenesis. Integrative analyses uncovered a novel pathogenic axis: reduced AKT signaling downregulates mitochondrial protease LONP1, impairing mitochondrial homeostasis. This LONP1 deficiency elevates STAR expression, promoting oxidative stress and hyperandrogenemia. Consistent with these findings, ovaries from prenatal androgenized PCOS mice exhibited significantly reduced AKT3 and LONP1 expression alongside elevated STAR expression. Mechanistically, in vitro activation of AKT by SC79 in theca-interstitial cells significantly increased LONP1 protein levels and concurrently decreased STAR protein expression. Conclusions This study identifies a novel pathogenic axis in PCOS where reduced PI3K-AKT signaling downregulates the mitochondrial protease LONP1, and elevated STAR expression may driving hyperandrogenism in ovarian theca cells. These findings, revealed by scRNA-seq in human patients and validated in a prenatal androgenized mouse model and human theca cell cultures, demonstrate that AKT activation rescues LONP1 levels and suppresses STAR. Thus, targeting the AKT-LONP1-STAR pathway presents a promising therapeutic strategy for PCOS.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with the high case-fatality rate, and lack of vaccines. We aimed to systematically analysed the epidemiological characteristics, clinical signs, routine laboratory diagnosis, risk factors, and outcomes. Methods Documents on SFTS were collected by searching the Chinese National Knowledge Infrastructure, Wan Fang Data, PubMed, Embase, and Web of Science databases from 2011 to 2018. Meta-analysis was performed by using Review Manager and Stata software. Results Twenty-five articles involving 4143 cases were included. Diarrhea (odds ratio (OR) =1.60, 95% confidence interval (CI): 1.06 to 2.42, P  = 0.02), and vomiting (OR = 1.56, 95% CI: 1.01 to 2.39, P  = 0.04) on admission were associated with the fatal outcomes of SFTS. Compared to patients with mild symptoms, patients with severe symptoms had significantly elevated levels of lactic acid dehydrogenase (standard mean difference (SMD) =1.27, 95% CI: 0.59 to 1.94), alanine aminotransferase (SMD = 0.55, 95% CI: 0.24 to 0.85), aspirate aminotransferase (SMD = 1.01, 95% CI: 0.69 to 1.32), and creatine kinase (SMD = 1.04, 95% CI: 0.74 to 1.33) but had reduced platelet counts (SMD = -0.87, 95% CI: − 1.16 to − 0.58) and albumin levels (SMD = -1.00, 95% CI: − 1.32 to − 0.68). The risk factors for poor prognosis included age (mean difference (MD) =6.88, 95% CI: 5.41 to 8.35) and farming (OR = 2.01, 95% CI: 1.06 to 3.80). For the risk factors of contracting SFTS, the incidence of SFTS related to tick bites was 24% [95% CI: 0.18 to 0.31]. The pooled case-fatality rate of SFTS patients was 18% [95% CI: 0.16 to 0.21]. Conclusions China is the country with the highest incidence of SFTS. May to July was the peak of the epidemic, and farmers were a high-risk group. The risk factor for SFTS included age (poor prognosis) and tick bites (contracting SFTS). Patients with severe diarrhea and vomiting symptoms on admission should be noted. Clinicians could use routine laboratory parameters and clinical symptoms as references for clinically suspected cases, classification of SFTS, and timely treatment, especially in basic hospitals.

Abstract Study objectives To prospectively investigate the association between sleep traits and lung cancer risk, accounting for the interactions with genetic predisposition of lung cancer. Methods We included 469 691 individuals free of lung cancer at recruitment from UK Biobank, measuring sleep behaviors with a standardized questionnaire and identifying incident lung cancer cases through linkage to national cancer and death registries. We estimated multivariable-adjusted hazard ratios (HRs) for lung cancer (2177 incident cases) across four sleep traits (sleep duration, chronotype, insomnia, and snoring) and examined the interaction and joint effects with a lung cancer polygenic risk score. Results A U-shaped association was observed for sleep duration and lung cancer risk, with an 18% higher risk (95% confidence interval [CI]: 1.07 to 1.30) for short sleepers and a 17% higher risk (95% CI: 1.02 to 1.34) for long sleepers compared with normal sleepers (7–8 h/day). Evening preference was associated with elevated lung cancer risk compared with morning preference (HR: 1.25; 95% CI: 1.07 to 1.46), but no association was found for insomnia or snoring. Compared with participants with favorable sleep traits and low genetic risk, those with both unfavorable sleep duration (<7 hours or >8 hours) or evening preference and high genetic risk showed the greatest lung cancer risk (HRsleep duration: 1.83; 95% CI: 1.47 to 2.27; HRchronotype: 1.85; 95% CI: 1.34 to 2.56). Conclusions Both unfavorable sleep duration and evening chronotype were associated with increased lung cancer incidence, especially for those with low to moderate genetic risk. These results indicate that sleep behaviors as modifiable risk factors may have potential implications for lung cancer risk.

The association of B lymphocytes and B lymphocyte subsets and Parkinson's disease (PD) is increasingly acknowledged. However, there is inconsistence in the alterations of B lymphocytes or B lymphocyte subsets in peripheral blood of PD patients. To comprehensively understand its changes in PD patients,it is necessary to conduct a systematic review on this subject. PubMed, Cochrane Library, and MEDLINE databases were searched until 3 February 2024. We included 20 studies (n=2658) to conduct this systematic review. We conducted a qualitative analysis to assess the alterations of B lymphocytes and B lymphocyte subsets in the peripheral blood of individuals with PD. And studies reviewed demonstrated a significant decrease in the number of B cells, as well as immune dysregulation in the B lymphocyte subsets of these patients' peripheral blood. Studies reviewed demonstrated that PD is linked to abnormalities in B lymphocytes and/or B lymphocytes subsets in peripheral blood. This study provides a novel perspective into the pathogenesis of PD, and future investigations into the B lymphocytes and/or B lymphocyte subsets as biomarkers and therapeutic targets for PD is warranted.

The prevalence of antimicrobial resistance reduces the effectiveness of antimicrobial drugs in the prevention and treatment of infectious diseases caused by pathogens such as bacteria, fungi, and viruses. Microbial secondary metabolites have been recognized as important sources for new drug discovery and development, yielding a wide range of structurally novel and functionally diverse antimicrobial drugs for the treatment of a variety of diseases that are considered good producers of novel antimicrobial drugs. Bacteria produce a wide variety of antimicrobial compounds, and thus, antibiotics derived from natural products still dominate over purely synthetic antibiotics among the antimicrobial drugs developed and introduced over the last four decades. Among them, Pseudomonas aeruginosa secondary metabolites constitute a richly diverse source of antimicrobial substances with good antimicrobial activity. Therefore, they are regarded as an outstanding resource for finding novel bioactive compounds. The exploration of antimicrobial compounds among Pseudomonas aeruginosa metabolites plays an important role in drug development and biomedical research. Reports on the secondary metabolites of Pseudomonas aeruginosa, many of which are of pharmacological importance, hold great promise for the development of effective antimicrobial drugs against microbial infections by drug-resistant pathogens. In this review, we attempt to summarize published articles from the last twenty-five years (2000–2024) on antimicrobial secondary metabolites from Pseudomonas aeruginosa.