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Antibiotics are widely used in the breeding production of Bamei pigs, affecting the quality and safety of pork and causing enormous harm to human health, the environment, and public health. The use of probiotic fermented feed to replace antibiotic feed is one of the solutions, which has the potential to improve the intestinal microbiota, promote animal growth, and enhance immunity. The purpose of this study was to evaluate the effect of fermented feed with Lactiplantibacillus (L.) plantarum QP28-1a or Bacillus (B.) subtilis QB8a on feed, growth performance, gut microbiota, and immunity of weaned piglets. A total of 60 freshly weaned piglets from the Tibetan Plateau were randomly divided into five groups and fed basal feed, L. plantarum fermented feed, B. subtilis fermented feed, mixed fermented feed, and antibiotic fermented feed for 60 days, respectively. The results showed fermented feed supplemented with L. plantarum QP28-1a or B. subtilis QB8a significantly lowered the pH of the feed (P < 0.05), produced lactic acid and acetic acid, inhibited the growth of harmful bacteria in the feed, and reduced the feed conversion rate in the group fed mixed fermented feed (P < 0.05). The fermented feed increased the α-diversity and prominently altered the ß-diversity of the intestinal microbiota, increasing the relative abundance of beneficial bacteria such as Lactobacillus and Turicibacter and decreasing the relative abundance of conditional pathogens such as Streptococcus and Clostridium, improving the intestinal microbiota of the Bamei piglets. Notably, the mixed fermented feed improved the immunity of Bamei piglets by modulating the production of pro-inflammatory cytokines, anti-inflammatory cytokines, and inflammatory-related signaling pathways. Spearman's correlation analysis revealed that the increased expression of immune-related cytokines may be associated with a significant enrichment of Lactobacillus, Prevotellaceae, Erysipelotrichaceae, and Ruminococcaceae in the gut. In conclusion, the probiotic fermented feed maintained an acidic environment conducive to suppressing pathogens, reduced the feed conversion ratio, optimized the intestinal microbiota, improved immunity, and alleviated intestinal inflammation that may be caused by weaning, demonstrating the excellent application prospects of L. plantarum QP28-1a and B. subtilis QB8a fermented feed in the feeding of Bamei piglets.

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Palladium (Pd) capture from high-level liquid waste for subsequent photocatalytic applications is desirable for the development of nuclear energy and the reutilization of valuable resources. Herein, we approach our design with a unique porous organic polymer containing thiazolo[5,4-d]thiazole units (denoted as TzPOP-OH). It possesses two potential soft-hard (N-O and S-O) combined coordination sites for Pd(II) coordination and features strong donor-acceptor repeating units and high planarity of linkage enforced by hydrogen bonds for subsequent photocatalysis. Accordingly, TzPOP-OH with three hydroxyl groups on the linkage exhibits a high Pd(II) capacity of 369 mg g-1 at 3 M HNO3, considerably surpassing those of the controlled polymer TzPOP without hydroxyl groups and most other reported materials. Additionally, TzPOP-OH boasts other merits, including outstanding acid tolerance, extraordinary radiation stability, good reusability, and remarkable selectivity. After palladium adsorption, Pd@TzPOP-OH demonstrates impressive photodegradation efficiency to reduce the concentration of rhodamine B in contaminated urban water from 10 to less than 0.1 ppm. This work provides a feasible approach to designing materials with both suitable coordination microenvironments and semiconductor properties for metal separation and photocatalysis.

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Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition. We constructed a combined immunQTL map by integrating data from European and Chinese colorectal cancer (CRC) samples. A polygenic risk score that incorporates these immunQTLs and hits on a genome-wide association study outperformed in CRC risk stratification within 447,495 multiethnic individuals. Using large-scale population cohorts, we identified that the immunQTL rs1360948 is associated with CRC risk and prognosis. Mechanistically, the rs1360948-G-allele increases CCL2 expression, recruiting regulatory T cells that can exert immunosuppressive effects on CRC progression. Blocking the CCL2-CCR2 axis enhanced anti-programmed cell death protein 1 ligand therapy. Finally, we have established a database (CancerlmmunityQTL2) to serve the research community and advance our understanding of immunogenomic interactions in cancer pathogenesis.

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This study investigated the causal enhancing effect of transcranial photobiomodulation (tPBM) over the left inferior frontal gyrus (LIFG) on syntactically complex Mandarin Chinese first language (L1) and second language (L2) sentence processing performances. Two (L1 and L2) groups of participants (thirty per group) were recruited to receive the double-blind, sham-controlled tPBM intervention via LIFG, followed by the sentence processing, the verbal working memory (WM), and the visual WM tasks. Results revealed a consistent pattern for both groups: (a) tPBM enhanced sentence processing performance but not verbal WM for linear processing of unstructured sequences and visual WM performances; (b) Participants with lower sentence processing performances under sham tPBM benefited more from active tPBM. Taken together, the current study substantiated that tPBM enhanced L1 and L2 sentence processing, and would serve as a promising and cost-effective noninvasive brain stimulation (NIBS) tool for future applications on upregulating the human language faculty.

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The improvement in the utilization rate and nutritional value of soybean meal (SBM) represents a significant challenge in the feed industry. This study conducted a 50 kg SBM fermentation based on the 300 g small-scale fermentation of SBM in early laboratory research, to explore the combined effects of lactic acid bacteria (LAB) and acid protease on fermentation quality, chemical composition, microbial population, and macromolecular protein degradation during fermentation and aerobic exposure of SBM in simulated actual production. The results demonstrated that the increase in crude protein content and reduction in crude fiber content were considerably more pronounced after fermentation for 30 days (d) and subsequent aerobic exposure, compared to 3 d. It is also noteworthy that the treated group exhibited a greater degree of macromolecular protein degradation relative to the control and 30 d of fermentation relative to 3 d. Furthermore, after 30 d of fermentation, adding LAB and protease significantly inhibited the growth of undesired microbes including coliform bacteria and aerobic bacteria. In the mixed group, the microbial diversity decreased significantly, and Firmicutes replaced Cyanobacteria for bacteria in both groups' fermentation.

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The structure of human language is inherently hierarchical. The left posterior inferior frontal gyrus (LpIFG) is proposed to be a core region for constructing syntactic hierarchies. However, it remains unclear whether LpIFG plays a causal role in syntactic processing in Mandarin Chinese and whether its contribution depends on syntactic complexity, working memory, or both. We addressed these questions by applying inhibitory continuous theta-burst stimulation (cTBS) over LpIFG. Thirty-two participants processed sentences containing embedded relative clauses (i.e., complex syntactic processing), syntactically simpler coordinated sentences (i.e., simple syntactic processing), and non-hierarchical word lists (i.e., word list processing) after receiving real or sham cTBS. We found that cTBS significantly increased the coefficient of variation, a representative index of processing stability, in complex syntactic processing (esp., when subject relative clause was embedded) but not in the other two conditions. No significant changes in d' and reaction time were detected in these conditions. The findings suggest that (a) inhibitory effect of cTBS on the LpIFG might be prominent in perturbing the complex syntactic processing stability but subtle in altering the processing quality; and (b) the causal role of the LpIFG seems to be specific for syntactic processing rather than working memory capacity, further evidencing their separability in LpIFG. Collectively, these results support the notion of the LpIFG as a core region for complex syntactic processing across languages.

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BACKGROUND: Early detection of colorectal neoplasms can reduce the colorectal cancer (CRC) burden by timely intervention for high-risk individuals. However, effective risk prediction models are lacking for personalized CRC early screening in East Asian (EAS) population. We aimed to develop, validate, and optimize a comprehensive risk prediction model across all stages of the dynamic adenoma-carcinoma sequence in EAS population. METHODS: To develop precision risk-stratification and intervention strategies, we developed three trans-ancestry PRSs targeting colorectal neoplasms: (1) using 148 previously identified CRC risk loci (PRS148); (2) SNPs selection from large-scale meta-analysis data by clumping and thresholding (PRS183); (3) PRS-CSx, a Bayesian approach for genome-wide risk prediction (PRSGenomewide). Then, the performance of each PRS was assessed and validated in two independent cross-sectional screening sets, including 4600 patients with advanced colorectal neoplasm, 4495 patients with non-advanced adenoma, and 21,199 normal individuals from the ZJCRC (Zhejiang colorectal cancer set; EAS) and PLCO (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial; European, EUR) studies. The optimal PRS was further incorporated with lifestyle factors to stratify individual risk and ultimately tested in the PLCO and UK Biobank prospective cohorts, totaling 350,013 participants. RESULTS: Three trans-ancestry PRSs achieved moderately improved predictive performance in EAS compared to EUR populations. Remarkably, the PRSs effectively facilitated a thorough risk assessment across all stages of the dynamic adenoma-carcinoma sequence. Among these models, PRS183 demonstrated the optimal discriminatory ability in both EAS and EUR validation datasets, particularly for individuals at risk of colorectal neoplasms. Using two large-scale and independent prospective cohorts, we further confirmed a significant dose-response effect of PRS183 on incident colorectal neoplasms. Incorporating PRS183 with lifestyle factors into a comprehensive strategy improves risk stratification and discriminatory accuracy compared to using PRS or lifestyle factors separately. This comprehensive risk-stratified model shows potential in addressing missed diagnoses in screening tests (best NPV = 0.93), while moderately reducing unnecessary screening (best PPV = 0.32). CONCLUSIONS: Our comprehensive risk-stratified model in population-based CRC screening trials represents a promising advancement in personalized risk assessment, facilitating tailored CRC screening in the EAS population. This approach enhances the transferability of PRSs across ancestries and thereby helps address health disparity.

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Rice anaerobic fermentation is a significant source of greenhouse gas (GHG) emissions, and in order to efficiently utilize crop residue resources to reduce GHG emissions, rice straw anaerobic fermentation was regulated using lactic acid bacteria (LAB) inoculants (FG1 and TH14), grass medium (GM) to culture LAB, and Acremonim cellulolyticus (AC). Microbial community, GHG emission, dry matter (DM) loss, and anaerobic fermentation were analyzed using PacBio single-molecule real-time and anaerobic fermentation system. The epiphytic microbial diversity of fresh rice straw was extremely rich and contained certain nutrients and minerals. During ensiling, large amounts of GHG such as carbon dioxide are produced due to plant respiration, enzymatic hydrolysis reactions, and proliferation of aerobic bacteria, resulting in energy and DM loss. Addition of FG1, TH14, and AC alone improved anaerobic fermentation by decreasing pH and ammonia nitrogen content (P < 0.05) and increased lactic acid content (P < 0.05) when compared to the control, and GM showed the same additive effect as LAB inoculants. Microbial additives formed a co-occurrence microbial network system dominated by LAB, enhanced the biosynthesis of secondary metabolites, diversified the microbial metabolic environment and carbohydrate metabolic pathways, weakened the amino acid metabolic pathways, and made the anaerobic fermentation cleaner. This study is of great significance for the effective utilization of crop straw resources, the promotion of sustainable livestock production, and the reduction of GHG emissions.IMPORTANCETo effectively utilize crop by-product resources, we applied microbial additives to silage fermentation of fresh rice straw. Fresh rice straw is extremely rich in microbial diversity, which was significantly reduced after silage fermentation, and its nutrients were well preserved. Silage fermentation was improved by microbial additives, where the combination of cellulase and lactic acid bacteria acted as enzyme-bacteria synergists to promote lactic acid fermentation and inhibit the proliferation of harmful bacteria, such as protein degradation and gas production, thereby reducing GHG emissions and DM losses. The microbial additives accelerated the formation of a symbiotic microbial network system dominated by lactic acid bacteria, which regulated silage fermentation and improved microbial metabolic pathways for carbohydrates and amino acids, as well as biosynthesis of secondary metabolites.

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BACKGROUND: Dysregulation of enhancer transcription occurs in multiple cancers. Enhancer RNAs (eRNAs) are transcribed products from enhancers that play critical roles in transcriptional control. Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers. METHODS: Initially, a comprehensive analysis of eRNA quantitative trait loci (eRNAQTLs) was performed in The Cancer Genome Atlas (TCGA), and functional features were characterized using multi-omics data. To establish the first eRNAQTL profiles for colorectal cancer (CRC) in China, epigenomic data were used to define active enhancers, which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples. Finally, large-scale case-control studies (34,585 cases and 69,544 controls) were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk. RESULTS: A total of 300,112 eRNAQTLs were identified across 30 different cancer types, which exert their influence on eRNA transcription by modulating chromatin status, binding affinity to transcription factors and RNA-binding proteins. These eRNAQTLs were found to be significantly enriched in cancer risk loci, explaining a substantial proportion of cancer heritability. Additionally, tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer. Moreover, the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer, highlighting their potential as therapeutic targets. Furthermore, multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China (OR = 0.91, 95%CI 0.88-0.95, P = 2.92 × 10-7) and Europe (OR = 0.92, 95%CI 0.88-0.95, P = 4.61 × 10-6). Mechanistically, rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786, which functioned as a transcriptional activator promoting the expression of its target gene SENP7. These two genes synergistically suppressed tumor cell proliferation. Our curated list of variants, genes, and drugs has been made available in CancereRNAQTL ( http://canernaqtl.whu.edu.cn/#/ ) to serve as an informative resource for advancing this field. CONCLUSION: Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability, pinpointing the potential of eRNA-based therapeutic strategies in cancers.

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Due to the similar sources of swage irrigation, organic fertilizer, and sludge application, microplastics (MPs) and antibiotics coexist inevitably in the agriculture soils. However, the impacts of MPs with different polymer types and aging status on the bio-accessibility of co-existing antibiotics in soils remained unclear. Therefore, we using the diffusive gradients films for organic compounds devices (o-DGT) to evaluated the distribution of sulfadiazine (SDZ) in both paddy soil and saline soil amended with 0.5 % (w/w) MPs. Four polymer types (polyethylene: PE, polypropylene: PP, polyamide: PA, and polyethylene terephthalate: PET) and two aging statuses (aged PE and aged PP) of MPs were used in this study. Results showed that soil properties significantly influence the partition of SDZ in soil and soil solution, and SDZ gained a lower degradation rate but higher mobility in saline soil. MPs pose different impacts on partition of SDZ between paddy soil and saline soil. Notably, PP reduced the labile solid phase-solution phase partition coefficient (Kdl) by 17.7 % in paddy soil, while PE, PP, and aPE increased the Kdl value by 2.00, 1.62, and 2.81 times in saline soil. Besides, in saline soil, all the MPs reduced the SDZ concentration in the soil solution, while significantly increased the SDZ in o-DGT phase. Conversely, MPs did not impact the SDZ's o-DGT concentration in paddy soil. Additionally, MPs increased the R value of SDZ in two soils, especially in saline soil. It suggested that MPs could potentially enhance the resupply of SDZ from soil to plants, particularly under saline conditions. Furthermore, aged MPs had a more pronounced effect on these indicators compared to virgin MPs in saline soil. Therefore, MPs in soil poses a potential risk for biota's uptake of SDZ, particularly in fragile environment. Moreover, the risk intensifies with aged MPs.

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OBJECTIVE: This study aims to investigate the relationship between psychological resilience, thriving at work, and work performance among nurses, as well as analyse the mediating role of thriving at work in the relationship between psychological resilience and the work performance of nurses. The findings are intended to serve as a reference for nursing managers to design tailored work performance intervention programs. METHOD: Using convenience sampling, 308 clinical nurses were selected from a tertiary hospital in Changsha City, Hunan Province, China, from February to April 2023. The Connor-Davidson Resilience Scale (CD-RISC), the Thriving at Work Scale, and the Work Performance Scale were employed for the questionnaire survey. Pearson correlation analysis was used to explore the relationship between psychological resilience, thriving at work and work performance. The SPSS 26.0 software's 'Process' plugin was utilised for mediation effect analysis. RESULTS: Significantly positive correlations were found between psychological resilience and thriving at work (r = 0.806, P < 0.01), thriving at work and work performance (r = 0.571, P < 0.01) as well as psychological resilience and work performance (r = 0.572, P < 0.01). Psychological resilience significantly predicted work performance positively (ß = 0.558, t = 11.165, P < 0.01), and this prediction remained significant when thriving at work (the mediating variable), was introduced (ß = 0.371, t = 4.772, P < 0.01). Psychological resilience significantly predicted thriving at work positively (ß = 0.731, t = 20.779, P < 0.01), and thriving at work significantly predicted work performance positively (ß = 0.256, t = 3.105, P < 0.05). The mediating effect size of thriving at work between psychological resilience and work performance was 33.49% (P < 0.05). CONCLUSION: Thriving at work plays a partial mediating role between psychological resilience and work performance. The level of work performance among clinical nurses was relatively high. Nursing managers can enhance thriving at work by fostering psychological resilience among clinical nurses, thereby further improving their work performance to ensure high-quality and efficient nursing care.

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Purebred Bamei piglets present problems, including slow growth, respiratory disease, and post-weaning stress. This study investigated the effects of Lactobacillus plantarum QP28-1- and Bacillus subtilis QB8-fermented feed supplementation on the growth performance, immunity, and intestinal microflora of Bamei piglets from Qinghai, China. A total of 48 purebred Bamei piglets (25 days; 6.8 ± 0.97 kg) were divided into the following four groups for a 28-day diet experiment: basal feed (CK); diet containing 10% Lactobacillus plantarum-fermented feed (L); diet containing 10% Bacillus subtilis-fermented feed (B); and diet containing a mixture of 5% Lactobacillus plantarum + 5% Bacillus subtilis-fermented feed (H). The daily weight gain and daily food intake of group H increased (p < 0.05), and the feed/weight gain ratios of the groups fed with fermented feed decreased more than that of the CK group. The levels of three immune factors, namely immunoglobulin (Ig)M, IgG, and interferon-γ, were higher (p < 0.05), whereas those of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 were lower (p < 0.05) in the fermented feed groups than in the CK group. Total protein was higher (p < 0.05), while urea nitrogen, total cholesterol and triglycerides were lower (p < 0.05) in the mixed-fermented feed group than in the CK group. Analysis of the gut microbiota showed that the addition of fermented feed increased the α-diversity of the gut microbiota, increasing the abundances of probiotics including Lactobacillus, Muribaculaceae, Ruminococcaceae, Prevotellaceae, and Rikenellaceae. Additionally, correlation analysis demonstrated that several of these probiotic bacteria were closely related to serum immunity. In conclusion, fermented feed supplementation rebuilt the intestinal microbiota of Bamei piglets, thereby reducing the feed/weight ratio, improving feed intake, and enhancing immunity.

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Heparin is one of the most widely used natural drugs, and has been the preferred anticoagulant and antithrombotic agent in the clinical setting for nearly a century. Heparin also shows increasing therapeutic potential for treating inflammation, cancer, and microbial and viral diseases, including COVID-19. With advancements in synthetic biology, heparin production through microbial engineering of heparosan offers a cost-effective and scalable alternative to traditional extraction from animal tissues. Heparosan serves as the starting carbon backbone for the chemoenzymatic synthesis of bioengineered heparin, possessing a chain length that is critically important for the production of heparin-based therapeutics with specific molecular weight (MW) distributions. Recent advancements in metabolic engineering of microbial cell factories have resulted in high-yield heparosan production. This review systematically analyzes the key modules involved in microbial heparosan biosynthesis and the latest metabolic engineering strategies for enhancing production, regulating MW, and optimizing the fermentation scale-up of heparosan. It also discusses future studies, remaining challenges, and prospects in the field.

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Root exudates are pivotal in plant stress responses, however, the impact of microplastics (MPs) on their release and characteristics remains poorly understood. This study delves into the effects of 0.05 % and 0.1 % (w/w) additions of polyethylene (PE) MPs on the growth and physiological properties of lettuce (Lactuca sativa L.) following 28 days of exposure. The release characteristics of root exudates were assessed using UV-vis and 3D-EEM. The results indicated that PE increased leaf number but did not significantly affect other agronomic traits or pigment contents. Notably, 0.05 % PE increased the total root length and surface area compared to the 0.1 % addition, while a non-significant trend towards decreased root activity was observed with PE MPs. PE MPs with 0.1 % addition notably reduced the DOC concentration in root exudates by 37.5 %, while 0.05 % PE had no impact on DOC and DON concentrations. PE addition increased the SUVA254, SUVA260, and SUVA280 values of root exudates, with the most pronounced effect seen in the 0.05 % PE treatment. This suggests an increase of aromaticity and hydrophobic components induced by PE addition. Fluorescence Regional Integration (FRI) analysis of 3D-EEM revealed that aromatic proteins (region I and II) were dominant in root exudates, with a slight increase in fulvic acid-like substances (region III) under 0.1 % PE addition. Moreover, prolonged PE exposure induced ROS damage in lettuce leaves, evidenced by a significant increase in content and production rate of O2·-. The decrease in CAT and POD activities may account for the lettuce's response to environmental stress, potentially surpassing its tolerance threshold or undergoing adaptive regulation. These findings underscore the potential risk of prolonged exposure to PE MPs on lettuce growth.

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BACKGROUND: Findings on the association of genetic factors and colorectal cancer (CRC) survival are limited and inconsistent, and revealing the mechanism underlying their prognostic roles is of great importance. This study aimed to explore the relationship between functional genetic variations and the prognosis of CRC and further reveal the possible mechanism. METHODS: We first systematically performed expression quantitative trait locus (eQTL) analysis using The Cancer Genome Atlas (TCGA) dataset. Then, the Kaplan-Meier analysis was used to filter out the survival-related eQTL target genes of CRC patients in two public datasets (TCGA and GSE39582 dataset from the Gene Expression Omnibus database). The seven most potentially functional eQTL single nucleotide polymorphisms (SNPs) associated with six survival-related eQTL target genes were genotyped in 907 Chinese CRC patients with clinical prognosis data. The regulatory mechanism of the survival-related SNP was further confirmed by functional experiments. RESULTS: The rs71630754 regulating the expression of endoplasmic reticulum aminopeptidase 1 ( ERAP1 ) was significantly associated with the prognosis of CRC (additive model, hazard ratio [HR]: 1.43, 95% confidence interval [CI]: 1.08-1.88, P = 0.012). The results of dual-luciferase reporter assay and electrophoretic mobility shift assay showed that the A allele of the rs71630754 could increase the binding of transcription factor 3 (TCF3) and subsequently reduce the expression of ERAP1 . The results of bioinformatic analysis showed that lower expression of ERAP1 could affect the tumor immune microenvironment and was significantly associated with severe survival outcomes. CONCLUSION: The rs71630754 could influence the prognosis of CRC patients by regulating the expression of the immune-related gene ERAP1 . TRIAL REGISTRATION: No. NCT00454519 ( https://clinicaltrials.gov/ ).

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Genome-wide association studies (GWASs) have identified over 140 colorectal cancer (CRC)-associated loci; however, target genes at the majority of loci and underlying molecular mechanisms are poorly understood. Here, we utilized a Bayesian approach, integrative risk gene selector (iRIGS), to prioritize risk genes at CRC GWAS loci by integrating multi-omics data. As a result, a total of 105 high-confidence risk genes (HRGs) were identified, which exhibited strong gene dependencies for CRC and enrichment in the biological processes implicated in CRC. Among the 105 HRGs, CEBPB, located at the 20q13.13 locus, acted as a transcription factor playing critical roles in cancer. Our subsequent assays indicated the tumor promoter function of CEBPB that facilitated CRC cell proliferation by regulating multiple oncogenic pathways such as MAPK, PI3K-Akt, and Ras signaling. Next, by integrating a fine-mapping analysis and three independent case-control studies in Chinese populations consisting of 8,039 cases and 12,775 controls, we elucidated that rs1810503, a putative functional variant regulating CEBPB, was associated with CRC risk (OR=0.90, 95%CI=0.86-0.93, P=1.07×10-7). The association between rs1810503 and CRC risk was further validated in three additional multi-ancestry populations consisting of 24,254 cases and 58,741 controls. Mechanistically, the rs1810503 A to T allele change weakened the enhancer activity in an allele-specific manner to decrease CEBPB expression via long-range promoter-enhancer interactions, mediated by the transcription factor, REST, and thus decreased CRC risk. In summary, our study provides a genetic resource and a generalizable strategy for CRC etiology investigation, and highlights the biological implications of CEBPB in CRC tumorigenesis, shedding new light on the etiology of CRC.

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IMPORTANCE: Feed shortage in the tropics is a major constraint to the production of livestock products such as milk and meat. In order to effectively utilize of local feed resources, the selected lactic acid bacteria (LAB) strain was used to prepare Napier grass and sugarcane top silage. The results showed that the two silages inoculated with LAB formed a co-occurrence microbial network dominated by Lactiplantibacillus during the fermentation process, regulated the microbial community structure and metabolic pathways, and improved the silage fermentation quality. This is of great significance for alleviating feed shortage and promoting sustainable production of livestock.

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BACKGROUND: Dietary patterns have been associated with several cancers, especially gastrointestinal cancer (GIC). However, whether a healthy dietary pattern could modify the risk of GIC among people with different genetic backgrounds is not clear. OBJECTIVE: The objective of the study was to investigate how dietary patterns and genetic susceptibility contribute to the risk of GIC independently and jointly. METHODS: This large-scale prospective cohort study included 105,463 participants in UK Biobank who were aged 40-72 y and cancer-free at baseline. Dietary intake (Oxford WebQ) was used to calculate dietary pattern scores including dietary approach to stop hypertension (DASH) score and healthful plant-based diet index (hPDI). Genetic risk was quantified by a polygenic risk score (PRS) comprising 129 known GIC-associated loci. Cox proportional hazards regression was performed to estimate the associations of dietary patterns and PRS with GIC incidence after adjusting for potential confounders. RESULTS: Over a median follow-up of 11.70 y, 1,661 participants were diagnosed with GIC. DASH and hPDI were associated with 20% and 36% reductions, respectively, in GIC risk. Low PRS was associated with a 30 % decrease in GIC risk (HR: 0.70; 95% CI: 0.62, 0.79). Participants with healthy dietary scores at high-genetic risk had a lower GIC risk with HR of 0.77 (95% CI: 0.60, 0.98) for DASH and 0.66 (95% CI: 0.52, 0.84) for hPDI than those with unhealthy dietary score. Participants with both high-dietary score and low-genetic risk showed the lowest risk of GIC, with HR of 0.58 (95% CI: 0.45, 0.75) for DASH and 0.45 (95% CI: 0.34, 0.58) for hPDI. CONCLUSIONS: Adherence to DASH and hPDI were associated with a lower risk of some gastrointestinal cancers, and these 2 dietary patterns may partly compensate for genetic predispositions to cancer. Our results advance the development of precision medicine strategies that consider both dietary patterns and genetics to improve gastrointestinal health.

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The development of efficient and selective organic synthetic approaches for complex molecules has garnered significant attention due to the need for precise control over molecular structures and functions. Rotaxanes, a type of mechanically interlocked molecules (MIMs), have shown promising applications in various fields including sensing, catalysis, and material science. However, the highly selective synthesis of oligo[n]rotaxanes (mostly n≥3) through controlling host-guest complexation and supramolecular threading assembly process still remains an ongoing challenge. In particular, the utilization of two-dimensional (2D) macrocycles with structural shape-persistency for the synthesis of oligo[n]rotaxanes is rare. In this concept, research on cooperatively threaded host-guest complexation with hydrogen-bonded (H-bonded) aramide macrocycles and selective synthetic protocols of oligo[n]rotaxanes has been summarized. The high efficiency and selectivity in synthesis are ascribed to the synergistic interplay of multiple non-covalent bonding interactions such as hydrogen bonding and intermolecular π-π stacking of macrocycles within the unique supramolecular structure of threaded host-guest complexes. This review focuses on the latest progress in the concepts, synthesis, and properties of H-bonded aramide macrocycle-based oligorotaxanes, and presents an in-depth outlook on challenges in this emerging field.

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Left ventricular regional wall thickness (LVRWT) is an independent predictor of morbidity and mortality in cardiovascular diseases (CVDs). To identify specific genetic influences on individual LVRWT, we established a novel deep learning algorithm to calculate 12 LVRWTs accurately in 42,194 individuals from the UK Biobank with cardiac magnetic resonance (CMR) imaging. Genome-wide association studies of CMR-derived 12 LVRWTs identified 72 significant genetic loci associated with at least one LVRWT phenotype (P < 5 × 10-8), which were revealed to actively participate in heart development and contraction pathways. Significant causal relationships were observed between the LVRWT traits and hypertrophic cardiomyopathy (HCM) using genetic correlation and Mendelian randomization analyses (P < 0.01). The polygenic risk score of inferoseptal LVRWT at end systole exhibited a notable association with incident HCM, facilitating the identification of high-risk individuals. The findings yield insights into the genetic determinants of LVRWT phenotypes and shed light on the biological basis for HCM etiology.

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