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Increasing evidence has suggested that physical activity may modulate gut microbiome composition. We investigated associations of long-term regular exercise with gut microbiota among middle-aged and older urban Chinese individuals. Gut microbiota was assessed using 16S ribosomal ribonucleic acid gene sequencing of stool samples from 2,151 participants from the Shanghai Women’s Health Study and Shanghai Men’s Health Study. Participants were free of cancer, diabetes, and cardiovascular diseases at the time of stool sample collection. Physical activity was assessed in repeat surveys between 1996 and 2015 using validated questionnaires. Regular exercise was defined as any type of leisure-time physical activity with a standard metabolic equivalent score >3.0. Stool samples were collected using the 95% ethanol method between 2015 and 2018 with an average of 3.0 years (SD = 0.9) after the latest exposure assessment. General linear regression and permutational multivariate analysis of variance were carried out to evaluate associations of microbial α- and β-diversity with regular exercise participation. Logistic regression and linear regression models were used to evaluate the prevalence and relative abundance of individual taxa in association with regular exercise. Regular exercise was significantly associated with β-diversity (Bray–Curtis and Jaccard dissimilarities, both false discovery rates = 0.03%, 0.12% and 0.09% variance explained, respectively) but not with α-diversity. Relative abundance of genus Ruminococcus was significantly lower among regular exercisers compared with nonexercisers (median relative abundance: 0.64% vs. 0.81%, false discovery rate

The carbides in the carburized layer of stainless steel (SS)/carbon steel (CS) clad plates are prone to inducing intergranular cracks and reducing the interfacial bonding strength. In this paper, SS/CS clad plates were fabricated by horizontal continuous liquid–solid composite casting (HCLSCC), and the formation mechanism of the interfacial carbides and their effect on the elimination of carbides in the carburized layer were revealed by numerical simulation and thermodynamic calculations. During the HCLSCC process, the cladding interface encountered re-melting and re-solidification after rapid melting and solidification, resulting in liquid–liquid and solid–solid diffusion at the cladding interface, where the atomic ratio of Cr/C (Cr/C) gradually increased. Therefore, strip M7C3 and M23C6 carbides as well as blocky M23C6 carbides formed at the cladding interface in turn and had a coherent relationship with the matrix. The blocky M23C6 carbides led to an increase of 240% in the interfacial ferrite strength. The formation of interfacial carbides reduced the difference in C activity between the cladding interface and SS, thus preventing the diffusion of C to SS and inhibiting carbide precipitation in the carburized layer of SS, which was beneficial to improving the interfacial bonding strength.

Colonization of specific bacteria in the human mouth were reported to be associated with gastric cancer risk. However, previous studies were limited by retrospective study designs and low taxonomic resolutions. We performed a prospective case-control study nested within three cohorts to investigate the relationship between oral microbiome and gastric cancer risk. Shotgun metagenomic sequencing was employed to characterize the microbiome in pre-diagnostic buccal samples from 165 cases and 323 matched controls. Associations of overall microbial richness and abundance of microbial taxa, gene families, and metabolic pathways with gastric cancer risk were evaluated via conditional logistic regression. Analyses were performed within each cohort and results were combined by meta-analyses. We found that overall microbial richness was associated with decreased gastric cancer risk, with an odds ratio (OR) per standard deviation (SD) increase in Simpson's reciprocal index of 0.77 (95% confidence interval [CI]=0.61-0.99). Nine taxa, 38 gene families, and six pathways also showed associations with gastric cancer risk at P

Background & Aims Intestinal mucositis, a severe complication of antineoplastic therapeutics, is characterized by mucosal injury and inflammation in the small intestine. Therapies for the prevention and treatment of this disease are needed. We investigated whether 2’-fucosyllactose (2’-FL), an abundant oligosaccharide in human milk, protects intestinal integrity and ameliorates intestinal mucositis. Methods A mouse small intestinal epithelial (MSIE) cell line, mouse enteroid cultures, and human gastrointestinal tumor cell lines (AGS and HT29) were co-treated with the chemotherapy agent 5-fluorouracil (5-FU) and 2’-FL. Mice were injected intraperitoneally with 5-FU to induce intestinal mucositis. 2’-FL was administered in the drinking water to mice before (pretreatment) or concurrently with 5-FU injection. Body weight and pathologic changes were analyzed. Results 2’-FL alleviated 5-FU inhibition of cell growth in MSIE cells, but not in AGS and HT29 cells. The 5-FU–induced apoptosis in MSIE cells and enteroids was suppressed by 2’-FL. Compared with 5-FU treatment alone, 2’-FL pretreatment protected against body weight loss, and ameliorated inflammation scores, proinflammatory cytokine production, shortening of villi, epithelial cell apoptosis, goblet cell loss, and tight junctional complex disruption in the small intestine. 2’-FL concurrent treatment had less of an effect on intestinal mucositis than 2’-FL pretreatment. Interestingly, no effect of 2’-FL was observed on 5-FU–induced S-phase arrest in MSIE, AGS, and HT29 cells. Neither pretreatment nor concurrent treatment with 2’-FL affected 5-FU–induced inhibition of proliferation in MSIE cells. Conclusions This study shows a novel direct effect of 2’-FL in protecting small intestinal epithelial cells against apoptosis stimulated by 5-FU, which may contribute to prevention of 5-FU–induced intestinal mucositis., Graphical abstract

By combining data from 160,500 individuals with breast cancer and 226,196 controls of Asian and European ancestry, we conducted genome- and transcriptome-wide association studies of breast cancer. We identified 222 genetic risk loci and 137 genes that were associated with breast cancer risk at a p

Background DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer (PCa). However, it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores (PRSs). Here, we aimed to develop and validate an improved PRS for PCa risk by incorporating genetically predicted gene expression and DNA methylation, and other genomic information using an integrative method. Methods Using data from the PRACTICAL consortium, we derived multiple sets of genetic scores, including those based on available single‐nucleotide polymorphisms through widely used methods of pruning and thresholding, LDpred, LDpred‐funt, AnnoPred, and EBPRS, as well as PRS constructed using the genetically predicted gene expression and DNA methylation through a revised pruning and thresholding strategy. In the tuning step, using the UK Biobank data (1458 prevalent cases and 1467 controls), we selected PRSs with the best performance. Using an independent set of data from the UK Biobank, we developed an integrative PRS combining information from individual scores. Furthermore, in the testing step, we tested the performance of the integrative PRS in another independent set of UK Biobank data of incident cases and controls. Results Our constructed PRS had improved performance (C statistics: 76.1%) over PRSs constructed by individual benchmark methods (from 69.6% to 74.7%). Furthermore, our new PRS had much higher risk assessment power than family history. The overall net reclassification improvement was 69.0% by adding PRS to the baseline model compared with 12.5% by adding family history. Conclusions We developed and validated a new PRS which may improve the utility in predicting the risk of developing PCa. Our innovative method can also be applied to other human diseases to improve risk prediction across multiple outcomes., An integrative score incorporating genetically predicted gene expression and DNA methylation and other genomic and non‐genomic information advanced our understanding of using genomic information to stratify subjects for prostate cancer.

PURPOSE: Oral microbiome plays an important role in oral health and systemic diseases, including cancer. We aimed to prospectively investigate the association of oral microbiome with lung cancer risk. METHODS: We analyzed 156 incident lung cancer cases (73 European Americans and 83 African Americans) and 156 individually matched controls nested within the Southern Community Cohort Study. Oral microbiota were assessed using 16S rRNA gene sequencing in pre-diagnostic mouth rinse samples. Paired t-test and the permutation multivariate analysis of variance test were used to evaluate lung cancer risk association with alpha diversity or beta diversity, respectively. Conditional logistic regression models were used to evaluate the association of individual bacterial abundance or prevalence with lung cancer risk. RESULTS: No significant differences were observed for alpha or beta diversity between lung cancer cases and controls. Abundance of families Lachnospiraceae_[XIV], Peptostreptococcaceae_[XI] and Erysipelotrichaceae, and species Parvimonas micra was associated with decreased lung cancer risk, with odds ratios (ORs) and 95% confidence intervals (CIs) of 0.76 (0.59–0.98), 0.80 (0.66–0.97), 0.81 (0.67–0.99), and 0.83 (0.71–0.98), respectively (all P

BACKGROUND: Few population-based studies have evaluated the influence of long-term diet on the gut microbiome, and data among Asian populations are lacking. OBJECTIVE: We examined the association of long-term diet quality, comprising 8 food groups (fruit, vegetables, dairy, fish/seafood, nuts/legumes, refined grains, red meat, and processed meat), with gut microbiome among Chinese adults. METHODS: Included were 1920 men and women, enrolled in 2 prospective cohorts (baseline 1996–2006), who remained free of cardiovascular diseases, diabetes, and cancer at stool collection (2015–2018) and had no diarrhea or antibiotic use in the last 7 d before stool collection. Microbiome was profiled by 16S rRNA sequencing. Long-term diet was assessed by repeated surveys at baseline and follow-ups (1996–2011), with intervals of 5.2 to 20.5 y between dietary surveys and stool collection. Associations of dietary variables with microbiome diversity and composition were evaluated by linear or negative binomial hurdle models, adjusting for potential confounders. False discovery rate (FDR)

ObjectiveTo prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.Design and settingA nested case–control study within two prospective cohort studies, the Shanghai Women’s Health Study (n=74 941) and the Shanghai Men’s Health Study (n=61 480).ParticipantsLifetime never-smokers who had no cancer at baseline. Cases were subjects who were diagnosed with incident lung cancer (n=114) and were matched 1:1 with controls on sex, age (≤2 years), date (≤30 days) and time (morning/afternoon) of sample collection, antibiotic use during the week before sample collection (yes/no) and menopausal status (for women).Main outcomes and measuresMetagenomic shotgun sequencing was used to measure the community structure and abundance of the oral microbiome in pre-diagnostic oral rinse samples of each case and control. Multivariable logistic regression models were used to estimate the association of lung cancer risk with alpha diversity metrics and relative abundance of taxa. The Microbiome Regression-Based Kernel Association Test (MiRKAT) evaluated the association between risk and the microbiome beta diversity.ResultsSubjects with lower microbiota alpha diversity had an increased risk of lung cancer compared with those with higher microbial alpha diversity (Shannon: ptrend=0.05; Simpson: ptrend=0.04; Observed Species: ptrend=0.64). No case–control differences were apparent for beta diversity (pMiRKAT=0.30). After accounting for multiple comparisons, a greater abundance of Spirochaetia (ORlow 1.00 (reference), ORmedium 0.61 (95% CI 0.32 to 1.18), ORhigh 0.42 (95% CI 0.21 to 0.85)) and Bacteroidetes (ORlow 1.00 (reference), ORmedium 0.66 (95% CI 0.35 to 1.25), ORhigh 0.31 (95% CI 0.15 to 0.64)) was associated with a decreased risk of lung cancer, while a greater abundance of the Bacilli class (ORlow 1.00 (reference), ORmedium 1.49 (95% CI 0.73 to 3.08), ORhigh 2.40 (95% CI 1.18 to 4.87)) and Lactobacillales order (ORlow 1.00 (reference), ORmedium 2.15 (95% CI 1.03 to 4.47), ORhigh 3.26 (95% CI 1.58 to 6.70)) was associated with an increased risk of lung cancer.ConclusionsOur prospective study of never-smokers suggests that lower alpha diversity was associated with a greater risk of lung cancer and the abundance of certain specific taxa was associated with altered risk, providing further insight into the aetiology of lung cancer in the absence of active tobacco smoking.

Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case–Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98–1.02; arachidonic acid OR = 1.00, 95% CI = 0.99–1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87–1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

Light-stimulated artificial synapse shows broad application prospects in the field of neuromorphic computing. Implementation of an all-inorganic solid oxide phototransistor will be compatible with ...

Enhancing the reliability and sensitivity of gas sensors based on FETs has been of extensive concern for their practical application. However, few reports are available on nanofiber FET gas sensors...

Objective: Genome-wide association studies (GWAS) have identified more than 50 loci for lung cancer risk. However, susceptibility genes and the underlying mechanisms for these risk loci remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify susceptibility genes for lung cancer. Methods: Transcriptome data from normal lung tissue and whole-genome sequencing data from 444 participants of European ancestry in the Genotype-Tissue Expression (GTEx, version 8) were used to build lung-tissue models to predict gene expression levels. Lung-tissue prediction models were successfully established for 10,802 genes with a model performance r > 0.1 and P < 0.05. We also built joint-tissue models using the joint-tissue imputation (JTI) framework, which leverages transcriptome data from lung tissue and 48 other tissue types from the 444 participants in GTEx. Joint-tissue models were successfully established for 12,629 genes with a model performance r > 0.1 and P < 0.05. These prediction models were applied to the GWAS data comprised of 29,266 lung cancer cases and 56,450 controls of European ancestry, in order to evaluate genetically predicted gene expression levels in association with lung cancer risk. Results: We found 44 genes whose genetically predicted expression levels were significantly associated with overall lung cancer risk at the Bonferroni correction significance threshold. Among the 44 genes, four were located at least 500kb away from any of the leading variants identified previously in GWAS. Of these four genes, only the CCHCR1 gene has been reported in previous TWAS, and the other three genes, LY6G5B, PRSS16, and C19orf54, have never been reported in previous GWAS or TWAS. For each of these three novel genes, consistent associations were observed in both lung-tissue and joint-tissue models. For the 40 genes located in previously identified GWAS loci, after adjusting for GWAS-identified variants, the associations for the majority of them became non-significant. However, the associations did not change materially for UCKL1 or PRPF6. These results suggest that the associations for these two genes were independent from previous GWSA-identified signals. We also identified 10 genes located at least 500kb away from GWAS-identified loci that were associated with lung cancer histological subtypes, e.g., adenocarcinoma (DCBLD1 and AQP3), squamous cell carcinoma (ZSCAN26, BLOC1S2, ABCF1, and ZSCAN9), and small cell lung cancer (BTN2A2, TMA16, RP11-218F10.3, and FRS3). An additional 7 genes located in GWAS loci were associated with risk of lung cancer histological subtypes but not with overall lung cancer risk, including 4 genes for adenocarcinoma (TP63, STN1, FAM227B, and TPRG1) and 3 genes for squamous cell carcinoma (DDAH2, OR2H2, and NELFE). Conclusion: Our TWAS identified lung cancer susceptibility genes, providing new insight into the genetics of lung cancer etiology. Citation Format: Tianying Zhao, Jiajun Shi, Yaohua Yang, Jie Ping, Xiao Ou Shu, Wei Zheng, Jirong Long, Qiuyin Cai. Transcriptome-wide association study identifies susceptibility loci and genes for lung cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB045.

Growing evidence suggests that gut microbiota may influence chemotherapy efficacy. However, little research has been done on the relationship between the gut microbiome and chemotherapy-induced toxicity. We conducted a prospective study among 301 chemotherapy-treated breast cancer patients who were recruited into the Vietnamese Breast Cancer Study and had a pre-chemotherapy stool sample collected. The stool collection included 134 pre- and 167 post-breast cancer surgery samples. Chemotherapy-induced toxicities during the first-line treatment were captured via medical chart reviews and patient-reported outcomes and graded using the National Cancer Institute Common Toxicity Criteria of Adverse Events classification. Gut microbiome composition was measured by shotgun metagenomic sequencing. Associations of pre-chemotherapy gut microbial diversity, taxa abundance, and microbial metabolic pathways with severe (i.e., grade ≥ 3) hematological and gastrointestinal (GI) toxicities were evaluated via multivariable logistic regression. A substantial proportion of study participants experienced severe hematological (39.2%) and GI (13.3%) toxicities. Reduction in α- and β-diversities (P Citation Format: Sang M. Nguyen, Huong T. Tran, Jirong Long, Martha J. Shrubsole, Hui Cai, Yaohua Yang, Qiuyin Cai, Thuan V. Tran, Wei Zheng, Xiao-Ou Shu. Gut microbiome in association with chemotherapy-induced toxicities among breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3041.