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We initiate the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole-genome sequencing (WGS) individuals and 5,841 high-density genotyping individuals, and identify 81.5 million SNPs and INDELs, of which 38.5% are absent in dbSNP Build 151. We provide a population-specific reference panel and an online imputation server ( https://wbbc.westlake.edu.cn/ ) which could yield substantial improvement of imputation performance in Chinese population, especially for low-frequency and rare variants. By analyzing the singleton density of the WGS data, we find selection signatures in SNX29 , DNAH1 and WDR1 genes, and the derived alleles of the alcohol metabolism genes ( ADH1A and ADH1B ) emerge around 7,000 years ago and tend to be more common from 4,000 years ago in East Asia. Genetic evidence supports the corresponding geographical boundaries of the Qinling-Huaihe Line and Nanling Mountains, which separate the Han Chinese into subgroups, and we reveal that North Han was more homogeneous than South Han. Biobanks of genetic data have been primarily in European populations, which gives us an incomplete understanding of complex traits across populations. Here, the authors initiate the Westlake BioBank for Chinese (WBBC) pilot project with 4,535 whole genome sequences and 5,841 high-density genotypes from China, characterizing large-scale genomic variation in Chinese populations.

Background Birth weight is considered not only to undermine future growth, but also to induce lifelong diseases; the aim of this study is to explore the relationship between birth weight and adult bone mass. Methods We performed multivariable regression analyses to assess the association of birth weight with bone parameters measured by dual-energy X-ray absorptiometry (DXA) and by quantitative ultrasound (QUS), independently. We also implemented a systemic Mendelian randomization (MR) analysis to explore the causal association between them with both fetal-specific and maternal-specific instrumental variables. Results In the observational analyses, we found that higher birth weight could increase the adult bone area (lumbar spine, β -coefficient= 0.17, P < 2.00 × 10 −16 ; lateral spine, β -coefficient = 0.02, P = 0.04), decrease bone mineral content-adjusted bone area (BMCadjArea) (lumbar spine, β -coefficient= − 0.01, P = 2.27 × 10 −14 ; lateral spine, β -coefficient = − 0.05, P = 0.001), and decrease adult bone mineral density (BMD) (lumbar spine, β -coefficient = − 0.04, P = 0.007; lateral spine; β -coefficient = − 0.03, P = 0.02; heel, β -coefficient = − 0.06, P < 2.00 × 10 −16 ), and we observed that the effect of birth weight on bone size was larger than that on BMC. In MR analyses, the higher fetal-specific genetically determined birth weight was identified to be associated with higher bone area (lumbar spine; β -coefficient = 0.15, P = 1.26 × 10 −6 , total hip, β -coefficient = 0.15, P = 0.005; intertrochanteric area, β -coefficient = 0.13, P = 0.0009; trochanter area, β -coefficient = 0.11, P = 0.03) but lower BMD (lumbar spine, β -coefficient = − 0.10, P = 0.01; lateral spine, β -coefficient = − 0.12, P = 0.0003, and heel β -coefficient = − 0.11, P = 3.33 × 10 −13 ). In addition, we found that the higher maternal-specific genetically determined offspring birth weight was associated with lower offspring adult heel BMD ( β -coefficient = − 0.001, P = 0.04). Conclusions The observational analyses suggested that higher birth weight was associated with the increased adult bone area but decreased BMD. By leveraging the genetic instrumental variables with maternal- and fetal-specific effects on birth weight, the observed relationship could be reflected by both the direct fetal and indirect maternal genetic effects.

The interplay among host genetic architecture, gut microbiota, metabolites and bone metabolism remains poorly understood. This study aims to comprehensively investigate the shared genetic factors, causal relationships, and the involvement of blood metabolites between gut microbiota and bone mass, based on datasets from European populations. Here, we estimate the polygenic SNP heritability for 1104 gut microbiota taxa, only 96 (8.7%) showed significant polygenic heritability. We identify 14 distinct gut microbiota taxa with pleiotropic effects on estimated heel bone mineral density (eBMD), 11 of them are found to have a causal association with eBMD. Following sensitivity and validation analyses, we find that the gut microbiota taxa family Bifidobacteriaceae ; genus Bifidobacterium and species Bifidobacterium adolescentis exert causal effects leading to decreased eBMD. Mediation analyses indicate that the impact of these taxa on eBMD may be driven by their influence on circulating stearidonate (18:4n-3) levels via n-3 pathway, with mediating proportion from 77.53% to 87.24%. In conclusion, the genetically informed negative association between bifidobacterial taxa and bone mass may reflect the host–microbe interactions at LCT / MCM6 locus and represent an adaptive microbial response to lactose intolerance, thus, it could potentially be mitigated through supplementation with bifidobacterial probiotics and n-3 polyunsaturated fatty acids. Gut microbiota influence bone health, but the genetic and metabolic mechanisms are unclear. Here, the authors show that specific bifidobacterial taxa causally reduce bone mineral density, partly via n-3 fatty acid metabolism, highlighting host-microbe interactions with potential therapeutic implications.

Metallo-β-lactamases (MBLs) are a group of enzymes that can inactivate most commonly used β-lactam-based antibiotics. Among MBLs, New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an urgent threat to public health as evidenced by its success in rapidly disseminating worldwide since its first discovery. Here we report the biochemical and genetic characteristics of a novel MBL, ElBla2, from the marine bacterium Erythrobacter litoralis HTCC 2594. This enzyme has a higher amino acid sequence similarity to NDM-1 (56%) than any previously reported MBL. Enzymatic assays and secondary structure alignment also confirmed the high similarity between these two enzymes. Whole genome comparison of four Erythrobacter species showed that genes located upstream and downstream of elbla2 were highly conserved, which may indicate that elbla 2 was lost during evolution. Furthermore, we predicted two prophages, 13 genomic islands and 25 open reading frames related to insertion sequences in the genome of E. litoralis HTCC 2594. However, unlike NDM-1, the chromosome encoded ElBla2 did not locate in or near these mobile genetic elements, indicating that it cannot transfer between strains. Finally, following our phylogenetic analysis, we suggest a reclassification of E . litoralis HTCC 2594 as a novel species: Erythrobacter sp. HTCC 2594.

Leclercia sp. W6 and W17, which belong to the Enterobacteriaceae, were isolated from a stomach sample from a 78-year-old female gastric cancer patient, and genomic sequencing and analysis were performed. The genome of Leclercia sp. W6 consists of one chromosome with a size of 4,945,486 bp, while that of Leclercia sp. W17 contains one chromosome and two plasmids with a total size of 5,125,645 bp. Average nucleotide identity (ANI) calculations indicated that strains W6 and W17 exhibited similarities < 91.0% to other strains within the Enterobacteriaceae, except for six Leclercia strains. Phylogenomic analysis based on core-genome showed that strains W6 and W17 belong to the genus Leclercia, and phylogenetic analysis based on ANI values revealed that strains W6 and W17 formed an independent clade from those six Leclercia strains. Furthermore, comparative genomic analysis revealed that strains W6 and W17 had 5086 orthologous clusters (OCs) in their pan-genomes, and 59 exclusive OCs which were absent in their closest relatives. Genomic annotations revealed that the genomes of strains W6 and W17 encoded genes related to multidrug resistance clusters, multiple antibiotic resistance loci, and multidrug efflux pumps and had an identical urease gene cluster and a dissimilatory nitrate reduction pathway. Bioinformatic analyses indicated that strains W6 and W17 represented a novel species within the genus Leclercia. Genomic annotations revealed that these strains encoded genes related to multidrug resistance, nitrate reduction, and urease activity, which contribute to gastric malignant transformation. This will broaden our knowledge of the genetic mechanisms of the Enterobacteriaceae and help improve the clinical conditions of gastric cancer patients.

Previous studies have reported that genes relating to JAK-STAT pathway ( IFIH1, TYK2 and IL-10 ) conferred the susceptibility to SLE. In this study, we performed a meta-analysis (including 43 studies) to evaluate the association between IFIH1 (9288 patients and 24,040 controls), TYK2 (4928 patients and 11,536 controls), IL-10 (3623 patients and 4907 controls) polymorphisms and systemic lupus erythematosus (SLE) in a comprehensive way. We found that IFIH1 rs1990760_T allele was associated with risk of SLE in overall population under three models (allelic: P  = 2.56 × 10 −11 , OR 1.135, 95% CI 1.094–1.179, dominant: P  = 1.8 × 10 −8 , OR 1.203, 95% CI 1.128–1.284, recessive: P  = 2.6 × 10 −7 , OR 1.163, 95% CI 1.098–1.231). A strong association had been observed between TYK2 polymorphism rs2304256_C allele and SLE in Europeans ( P  = 5.82 × 10 −5 , OR 1.434, 95% CI 1.203–1.710). When coming to overall population, TYK2 rs2304256_C showed a significant association with SLE under recessive model ( P  = 8.05 × 10 −3 , OR 1.314, 95% CI 1.074–1.608). However, the other two SNPs (rs12720270, rs280519) of TYK2 were not significant. The results also indicated an association between IL-10 rs1800896_G allele and SLE in Asians under recessive model ( P  = 4.65 × 10 −3 , OR 2.623, 95% CI 1.346–5.115), while, IL-10 rs1800896_G had a trend of association with SLE in European population in dominant model ( P  = 1.21 × 10 −2 , OR 1.375, 95% CI 1.072–1.764). In addition, we found IL-10 rs1800896 GG homozygote might be associated with increased susceptibility to SLE (GG vs AA, P  = 4.65 × 10 −3 , OR 1.539, 95% CI 1.142–2.072). We concluded that IFIH1 rs1990760_T and TYK2 rs2304256_C alleles were significantly associated with SLE, and IL-10 rs1800896 GG homozygote might have an enhancement effect on SLE risk.

Background： Most studies on enhanced recovery after surgery （ERAS） for gastric cancer exclude patients who received neoadjuvant chemotherapy. Here, we aimed to evaluate whether patients who received neoadjuvant chemotherapy can be enrolled into the ERAS program for locally advanced gastric cancer. Methods： From April 2015 to July 2017, 114 patients who received neoadjuvant chemotherapy for locally advanced gastric cancer were randomized into ERAS and standard care （SC） groups. Postoperative length of stay, complications, bowel function, and nutritional status were recorded. Results： The postoperative length of stay of the ERAS group was shorter compared with that of the SC group （5.9 ± 5.6 vs. 8.1 ± 5.3 days, P=0.037）.The postoperative complication rate was 9.3% in the ERAS group and 11.5% in the SC group（P=0.700）.The time to first flatus （2.7 ± 2.0 vs. 4.5 ± 4.6 days, P = 0.010） and time to a semi-liquid diet （3.2 ± 2.1 vs. 6.3 ± 4.9 days, P 〈 0.001） in the ERAS group were shorter compared with those in the SC group. On the 10thday after surgery, the values of weight, total protein, albumin, and prealbumin of the ERAS group were lower compared with those of the SC group. Conclusions： Patients who received neoadjuvant chemotherapy could be enrolled into ERAS programs for locally advanced gastric cancer. The nutritional status of these patients was not adversely affected.

In this study, we isolated an environmental clone of Ochrobactrum intermedium , strain 2745-2, from the formation water of Changqing oilfield in Shanxi, China, which can degrade crude oil. Strain 2745-2 is aerobic and rod-shaped with optimum growth at 42 °C and pH 5.5. We sequenced the genome and found a single chromosome of 4 800 175 bp, with a G+C content of 57.63%. Sixty RNAs and 4737 protein-coding genes were identified: many of the genes are responsible for the degradation, emulsification, and metabolizing of crude oil. A comparative genomic analysis with related clinical strains (M86, 229E, and LMG3301 T ) showed that genes involved in virulence, disease, defense, phages, prophages, transposable elements, plasmids, and antibiotic resistance are also present in strain 2745-2.

To assess the efficacy and safety of L-oxiracetam, a novel nootropic agent, in improving cognition in patients with TBI, we performed a multicentre, double-blind, randomized controlled trial in China. Participants aged 18 to 75 years with TBI (Glasgow Coma Scale score of 10 to 15) were recruited from 51 hospitals from 2019 to 2024. Patients were randomly assigned to L-oxiracetam, 4 g/day, oxiracetam 6 g/day, or placebo in 2:2:1. The primary outcome was the change in the Loewenstein Occupational Therapy Cognitive Assessment (LOTCA) score from baseline to 90 days post treatment. Secondary outcomes included changes in additional cognitive evaluations, neurological function, activities of daily living (ADL), and adverse events (AEs). The trial was approved by the China National Medical Products Administration (2016L03521), and registered at Clinicaltrials.gov (NCT04205565) and Chinadrugtrials.org.cn (CTR20192539). Five hundred and ninety patients were included (mean age (SD), 50.9 (14.5); 421 males). The least squares (LS) mean of LOTCA change from baseline to 90 days post treatment was 20.45 (95% confidence interval [CI] 17.23, 23.66) in the L-oxiracetam group, 15.90 (95% CI 12.71, 19.10) in the oxiracetam group, and 11.47 (95% CI 7.75, 15.20) in the placebo group ( P value < 0.05 for all groups). The LS mean difference of the L-oxiracetam was significantly higher than the placebo group (8.97, 95% CI 5.69,12.26; P  < 0.001; Cohen’s d  = 0.48 [95% CI: 0.26,0.69]) and the oxiracetam group (4.54, 95% CI 1.85,7.23). Secondary efficacy outcomes did not differ between the L-oxiracetam and oxiracetam groups. The proportion of serious AEs did not differ among the three groups. L-oxiracetam could improve cognitive function in patients with mild-to-moderate TBI. L-oxiracetam might be more efficacious than oxiracetam. No significant safety concerns were reported. Despite limitations such as loss to follow-up, the findings of this study provide important evidence for the clinical management of cognitive dysfunction following TBI. Future studies in real-world clinical settings are warranted to further substantiate the efficacy of L-oxiracetam and oxiracetam.

Colorectal cancer remains one of the most common types of cancer and leading causes of cancer death worldwide. Although we have made steady progress in chemotherapy and targeted therapy, evidence suggests that the majority of patients undergoing drug therapy experience severe, debilitating, and even lethal adverse drug events which considerably outweigh the benefits. The identification of suitable biomarkers will allow clinicians to deliver the most appropriate drugs to specific patients and spare them ineffective and expensive treatments. Prognostic and predictive biomarkers have been the subjects of many published papers, but few have been widely incorporated into clinical practice. Here, we want to review recent biomarker data related to colorectal cancer, which may have been ready for clinical use.