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Purpose: Atorvastatin is commonly used to treat dyslipidemia; however, individual responses vary considerably. This study endeavors to evaluate the relationship between polymorphisms in the coding sequence (CDS) of SLCO1B1 gene and blood lipid levels before and after atorvastatin treatment among the Chinese Han adults with dyslipidemia., Patients and Methods: A total of 165 Chinese Han adults undergoing atorvastatin therapy were enrolled in this study and followed up quarterly. The complete CDS of the SLCO1B1 gene was sequenced to detect polymorphisms. Statistical analysis was utilized to assess the impacts of sex, age, body mass index (BMI), and polymorphisms on blood lipid levels before and after atorvastatin treatment., Results: Fourteen polymorphisms were identified in the SLCO1B1 CDS. Among them, four polymorphisms had mutant alleles present in over 20 patients. No polymorphism was found to correlate with blood lipid levels before treatment; in contrast, age, sex, and BMI did show correlations ( P <0.05). Notably, females had higher baseline blood lipid levels than males, indicating that sex had a more significant impact on baseline levels than age and BMI. The polymorphism rs2306283 was significantly correlated with the efficacy of atorvastatin ( P <0.05), whereas age, sex, and BMI were not. Carriers of the rs2306283 AA allele experienced a substantially greater reduction in total cholesterol (TC) and triglyceride (TG) levels after atorvastatin treatment. The other polymorphisms did not demonstrate any significant impact on atorvastatin's efficacy., Conclusion: This study delved into the intricate genetic structure of polymorphisms in SLCO1B1 CDS and their roles in lipid metabolism and atorvastatin's efficacy among Chinese Han adults with dyslipidemia. The findings underscore the crucial role of the rs2306283 polymorphism in the response to atorvastatin's efficacy, highlighting the significance of pharmacogenomics in personalized medicine. It is thus advisable to consider genetic testing for SLCO1B1 variants to optimize atorvastatin therapy., Competing Interests: The authors declare no competing interests., (© 2024 Chen et al.)

Proteus mirabilis , a significant pathogenic bacterium within the Enterobacteriaceae family, is widely distributed across various natural environments. This study conducted a genomic comparison analysis of 1,267 strains of P. mirabilis using extensive genome data from public databases. The objective was to elucidate the pan-genomic structure of P. mirabilis , revealing the composition and distribution of core and accessory gene families among different strains. Additionally, an attempt was made to construct a core genome multilocus sequence typing scheme specific to this species in order to enhance the precision of describing genetic diversity and evolutionary relationships. Furthermore, the study delved into the mechanisms of resistance of P. mirabilis to carbapenems and quinolones. Our findings underscore significant challenges posed by P. mirabilis in terms of antibiotic resistance, with widespread resistance observed particularly against beta-lactams and an increasing trend in resistance to carbapenems and quinolones. These results highlight the severity of P. mirabilis as a pathogen and underscore its rapid evolution and adaptability in developing resistance. This study aims to deepen our understanding of the antibiotic resistance of P. mirabilis , providing important insights for the development of future antimicrobial drugs, promoting effective treatment and control of this pathogen, and mitigating its threat to human health., Importance: The bacterium Proteus mirabilis is a common pathogenic bacterium that is known to cause a variety of human infections. The drug-resistant genes carried by P. mirabilis present a significant challenge to clinical treatment, particularly in regard to the organism's notable resistance to commonly used beta-lactam and quinolone drugs. Furthermore, the prevalence of the urease gene cluster of P. mirabilis at the urease gene level may be associated with the formation of kidney stones. The objective of the study is to analyze the bacterium's drug resistance, urease gene clusters, and gene distribution in genomes in order to facilitate the development of antimicrobial drugs and improve the treatment and control of P. mirabilis infections.

Background: Cell loss and mitochondrial dysfunction are key pathological features of idiopathic Parkinson's disease (PD) and multiple system atrophy (MSA). It remains unclear whether disease-specific changes in plasma circulating cell-free nuclear DNA (cf-nDNA) and mitochondrial DNA (cf-mtDNA) occur in patients with PD and MSA. In this study, we investigated whether plasma cf-nDNA, cf-mtDNA levels, as well as cf-mtDNA integrity, are altered in patients with PD and MSA., Methods: TaqMan probe-based quantitative PCR was employed to measure plasma cf-nDNA levels, cf-mtDNA copy numbers, and cf-mtDNA deletion levels in 171 participants, including 76 normal controls (NC), 62 PD patients, and 33 MSA patients. A generalized linear model was constructed to analyze differences in circulating cell-free DNA (cfDNA) biomarkers across clinical groups, while a logistic regression model was applied to assess the predictive values of these biomarkers for developing PD or MSA. Spearman correlations were used to explore associations between the three cfDNA biomarkers, demographic data, and clinical scales., Results: No significant differences in plasma cf-nDNA levels, cf-mtDNA copy numbers, or cf-mtDNA deletion levels were observed among the PD, MSA, and NC groups (all P > 0.05). Additionally, these measures were not associated with the risk of developing PD or MSA. In PD patients, cf-nDNA levels were positively correlated with Hamilton Anxiety Rating Scale scores (Rho = 0.382, FDR adjusted P = 0.027). In MSA patients, cf-nDNA levels were positively correlated with International Cooperative Ataxia Rating Scale scores (Rho = 0.588, FDR adjusted P = 0.011) and negatively correlated with Montreal Cognitive Assessment scores (Rho = -0.484, FDR adjusted P = 0.044). Subgroup analysis showed that PD patients with constipation had significantly lower plasma cf-mtDNA copy numbers than those without constipation ( P = 0.049). MSA patients with cognitive impairment had significantly higher cf-nDNA levels compared to those without ( P = 0.008)., Conclusion: Plasma cf-nDNA level, cf-mtDNA copy number, and cf-mtDNA deletion level have limited roles as diagnostic biomarkers for PD and MSA. However, their correlations with clinical symptoms support the hypothesis that cell loss and mitochondrial dysfunction are involved in PD and MSA development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ying, Li, Zhang, Pang, Hao, Hu and Zhao.)

Competing Interests: Conflict of interest None declared.

Plasmids, as independent genetic elements, carrying resistance or virulence genes and transfer them among different pathogens, posing a significant threat to human health. Under the 'One Health' approach, it is crucial to control the spread of plasmids carrying such genes. To achieve this, a comprehensive characterization of plasmids in pathogens is essential. Here we present the Plasmids in Pathogens Database (PIPdb), a pioneering resource that includes 792 964 plasmid segment clusters (PSCs) derived from 1 009 571 assembled genomes across 450 pathogenic species from 110 genera. To our knowledge, PIPdb is the first database specifically dedicated to plasmids in pathogenic bacteria, offering detailed multi-dimensional metadata such as collection date, geographical origin, ecosystem, host taxonomy, and habitat. PIPdb also provides extensive functional annotations, including plasmid type, insertion sequences, integron, oriT, relaxase, T4CP, virulence factors genes, heavy metal resistance genes and antibiotic resistance genes. The database features a user-friendly interface that facilitates studies on plasmids across diverse host taxa, habitats, and ecosystems, with a focus on those carrying antimicrobial resistance genes (ARGs). We have integrated online tools for plasmid identification and annotation from assembled genomes. Additionally, PIPdb includes a risk-scoring system for identifying potentially high-risk plasmids. The PIPdb web interface is accessible at https://nmdc.cn/pipdb., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Rice (Oryza sativa L.) endosperm is essential to provide nutrients for seed germination and determine grain yield. RNA editing, a post-transcriptional modification essential for plant development, unfortunately, is not fully characterized during rice endosperm development. Here, we perform systematic analyses to characterize RNA editome during rice endosperm development. We find that most editing sites are C-to-U CDS-recoding in mitochondria, leading to increased hydrophobic amino acids and changed structures of mitochondrial proteins. Comparative analysis of RNA editome reveals that CDS-recoding sites present higher editing frequencies with lower variabilities and their resultant recoded amino acids tend to exhibit stronger evolutionary conservation across many land plants. Furthermore, we classify mitochondrial genes into three groups, presenting distinct patterns in terms of CDS-recoding events. Besides, we conduct genome-wide screening to detect pentatricopeptide repeat (PPR) proteins and construct PPR-RNA binding profiles, yielding candidate PPR editing factors related to rice endosperm development. Taken together, our findings provide valuable insights for deciphering fundamental mechanisms of rice endosperm development underlying RNA editing machinery., (© 2024. The Author(s).)

Background: Alpha-synuclein oligomers (o-α-syn) are pivotal in the pathogenesis of α-synucleinopathy. Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) serves as an early indicator of the disease, offering insights into disease mechanisms and early intervention. Nevertheless, the diagnostic and predictive potential of o-α-syn in iRBD remains largely unexplored. This study aimed to evaluate the plasma levels of o-α-syn in patients and investigate their utility as biomarkers for diagnosis of and predicting phenoconversion in iRBD., Methods: A total of 143 participants, including 77 polysomnography-confirmed iRBD patients and 66 normal controls (NC), were recruited for this longitudinal observational study. Baseline clinical assessments and plasma collection were conducted for all iRBD patients, with 72 of them undergoing regularly prospective follow-up assessments for parkinsonism or dementia. Plasma levels of o-α-syn were quantified using enzyme-linked immunosorbent assay, and were compared between groups using a general linear model adjusted for age and sex. The diagnostic performance of plasma o-α-syn in iRBD was evaluated by area under the receiver operating characteristic curve (AUC) with 95% CI. Cox regression analysis and Kaplan-Meier survival curves were employed to assess the predictive value of plasma o-α-syn for phenoconversion in iRBD., Results: Plasma o-α-syn levels did not exhibit statistically significant differences among iRBD converter patients, iRBD nonconverter patients, and NC. The AUC for distinguishing NC from iRBD was 0.52 (95% CI: 0.42-0.62, p  = 0.682). Spearman correlation analysis revealed a significant positive correlation between plasma o-α-syn levels and MOCA scores in the iRBD group ( p  < 0.001). Subgroup analyses indicated that iRBD patients with cognitive decline ( p  = 0.058) and depressive symptoms ( p  = 0.017) had notably lower o-α-syn levels compared to those without such symptoms. Over a median follow-up period of 5.83 years, 26 iRBD patients developed neurodegenerative synucleinopathies. Cox regression and Kaplan-Meier survival curve analyses indicated that plasma level of o-α-syn lacked a predictive value for disease conversion in iRBD patients., Conclusion: Despite a potential role in the pathophysiology of iRBD, o-α-syn are not appropriate biomarkers for diagnosing or predicting disease progression. While this study offers insights into the pathogenesis of iRBD and neurodegenerative synucleinopathies, further large-scale longitudinal studies are warranted to validate these findings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ying, Zhang, Wang, Li, Mao, Hu, Zhao and Cai.)

The recently emerged BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 variants have a growth advantage. In this study, we explore the structural bases of receptor binding and immune evasion for the Omicron BA.2.86, JN.1, EG.5, EG.5.1, and HV.1 sub-variants. Our findings reveal that BA.2.86 exhibits strong receptor binding, whereas its JN.1 sub-lineage displays a decreased binding affinity to human ACE2 (hACE2). Through complex structure analyses, we observed that the reversion of R493Q in BA.2.86 receptor binding domain (RBD) plays a facilitating role in receptor binding, while the L455S substitution in JN.1 RBD restores optimal affinity. Furthermore, the structure of monoclonal antibody (mAb) S309 complexed with BA.2.86 RBD highlights the importance of the K356T mutation, which brings a new N-glycosylation motif, altering the binding pattern of mAbs belonging to RBD-5 represented by S309. These findings emphasize the importance of closely monitoring BA.2.86 and its sub-lineages to prevent another wave of SARS-CoV-2 infections., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: The CYP2D6 enzyme is crucial for the metabolism and disposition of a variety of drugs. This study was conducted to examine the relationship between CYP2D6 gene polymorphisms and the response to angiotensin receptor blocker (ARB)-based treatment in patients of Chinese Bai ethnicity with hypertension., Methods: Seventy-two hypertensive adults from the Chinese Bai ethnic group, exhibiting systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg, were recruited. Targeted regional sequencing was utilized to genotype single nucleotide polymorphisms in the CYP2D6 gene, aiming to assess their frequency and to evaluate their influence on the therapeutic efficacy of ARB medications., Results: Our research identified nine significant CYP2D6 polymorphisms associated with the efficacy of ARB treatment in the Bai hypertensive cohort. Specifically, patients possessing certain mutant genotype at rs111564371 exhibited substantially greater reductions in SBP and DBP, with P -values of 0.021 and 0.016, respectively, compared to those carrying the wild genotype. Additionally, these mutant genotype at rs111564371 and rs112568578 were linked to approximately 20% higher overall efficacy rates and a 10% increased achievement rate relative to the wild genotype., Conclusion: Our research with the Bai hypertensive group shows that certain CYP2D6 polymorphisms significantly influence ARB treatment outcomes. Mutations at rs111564371 led to better blood pressure control ( P -values: 0.021 for SBP, 0.016 for DBP), improving ARB efficacy by appromixately 20% and increasing treatment goal achievement by 10% over the wild-type genotype., Statements: Our investigation into CYP2D6 polymorphisms within the Bai hypertensive cohort marks a substantial advancement towards personalized healthcare, underscoring the pivotal influence of genetic constitution on the effectiveness of ARB therapy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

A comprehensive immune landscape for Brucella infection is crucial for developing new treatments for brucellosis. Here, we utilized single-cell RNA sequencing (scRNA-seq) of 290,369 cells from 35 individuals, including 29 brucellosis patients from acute ( n  = 10), sub-acute ( n  = 9), and chronic ( n  = 10) phases as well as six healthy donors. Enzyme-linked immunosorbent assays were applied for validation within this cohort. Brucella infection caused a significant change in the composition of peripheral immune cells and inflammation was a key feature of brucellosis. Acute patients are characterized by potential cytokine storms resulting from systemic upregulation of S100A8 / A9 , primarily due to classical monocytes. Cytokine storm may be mediated by activating S100A8/A9-TLR4-MyD88 signaling pathway. Moreover, monocytic myeloid-derived suppressor cells were the probable contributors to immune paralysis in acute patients. Chronic patients are characterized by a dysregulated Th1 response, marked by reduced expression of IFN-γ and Th1 signatures as well as a high exhausted state. Additionally, Brucella infection can suppress apoptosis in myeloid cells (e.g., mDCs, classical monocytes), inhibit antigen presentation in professional antigen-presenting cells (APCs; e.g., mDC) and nonprofessional APCs (e.g., monocytes), and induce exhaustion in CD8 + T/NK cells, potentially resulting in the establishment of chronic infection. Overall, our study systemically deciphered the coordinated immune responses of Brucella at different phases of the infection, which facilitated a full understanding of the immunopathogenesis of brucellosis and may aid the development of new effective therapeutic strategies, especially for those with chronic infection., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Since late 2019, COVID-19 has significantly impacted the world. Understanding the evolution of SARS-CoV-2 is crucial for protecting against future infectious pathogens. In this study, we conducted a comprehensive chronological analysis of SARS-CoV-2 evolution by examining mutation prevalence from the source countries of VOCs: United Kingdom, India, Brazil, South Africa, plus two countries: United States, Russia, utilizing genomic sequences from GISAID. Our methodological approach involved large-scale genomic sequence alignment using MAFFT, Python-based data processing on a high-performance computing platform, and advanced statistical methods the Maximal Information Coefficient (MIC), and also Long Short-Term Memory (LSTM) models for correlation analysis. Our findings elucidate the dynamics of SARS-CoV-2 evolution, highlighting the virus's changing behaviour over various pandemic stages. Key results include the discovery of three temporal mutation patterns-lineage distinct, long-span, and competitive mutations-with varying levels of impact on the virus. Notably, we observed a convergence of advantageous mutations in the spike protein, especially in the later stages of the pandemic, indicating a substantial evolutionary pressure on the virus. One of the most significant revelations is the predominant role of natural immunity over vaccination-induced immunity in driving these evolutionary changes. This emphasizes the critical need for regular vaccine updates to maintain efficacy against evolving strains. In conclusion, our study not only sheds light on the evolutionary trajectory of SARS-CoV-2 but also underscores the urgency for robust, continuous global data collection and sharing. It highlights the necessity for rapid adaptations in medical countermeasures, including vaccine development, to stay ahead of pathogen evolution. This research provides valuable insights for future pandemic preparedness and response strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Microbial genome sequencing and analysis revealed the presence of abundant silent secondary metabolites biosynthetic gene clusters (BGCs) in streptomycetes. Activating these BGCs has great significance for discovering new compounds and novel biosynthetic pathways., Results: In this study, we found that ovmZ and ovmW homologs, a pair of interdependent transcriptional regulators coding genes, are widespread in actinobacteria and closely associated with the biosynthesis of secondary metabolites. Through co-overexpression of native ovmZ and ovmW in Streptomyces neyagawaensis NRRL B-3092, a silent type II polyketide synthase (PKS) gene cluster was activated to produce gephyromycin A, tetrangomycin and fridamycin E with the yields of 22.3 ± 8.0 mg/L, 4.8 ± 0.5 mg/L and 20.3 ± 4.1 mg/L respectively in the recombinant strain of S.ne/pZ n W n . However, expression of either ovmZ or ovmW failed to activate this gene cluster. Interestingly, overexpression of the heterologous ovmZ and ovmW pair from oviedomycin BGC of S. ansochromogenes 7100 also led to awakening of this silent angucyclinone BGC in S. neyagawaensis., Conclusion: A silent angucyclinone BGC was activated by overexpressing both ovmZ and ovmW in S. neyagawaensis. Due to the wide distribution of ovmZ and ovmW in the BGCs of actinobacteria, co-overexpression of ovmZ and ovmW could be a strategy for activating silent BGCs, thus stimulating the biosynthesis of secondary metabolites., (© 2024. The Author(s).)

Cold seeps in the deep sea are closely linked to energy exploration as well as global climate change. The alkane-dominated chemical energy-driven model makes cold seeps an oasis of deep-sea life, showcasing an unparalleled reservoir of microbial genetic diversity. Here, by analyzing 113 metagenomes collected from 14 global sites across 5 cold seep types, we present a comprehensive Cold Seep Microbiomic Database (CSMD) to archive the genomic and functional diversity of cold seep microbiomes. The CSMD includes over 49 million non-redundant genes and 3175 metagenome-assembled genomes, which represent 1895 species spanning 105 phyla. In addition, beta diversity analysis indicates that both the sampling site and cold seep type have a substantial impact on the prokaryotic microbiome community composition. Heterotrophic and anaerobic metabolisms are prevalent in microbial communities, accompanied by considerable mixotrophs and facultative anaerobes, highlighting the versatile metabolic potential in cold seeps. Furthermore, secondary metabolic gene cluster analysis indicates that at least 98.81% of the sequences potentially encode novel natural products, with ribosomally synthesized and post-translationally modified peptides being the predominant type widely distributed in archaea and bacteria. Overall, the CSMD represents a valuable resource that would enhance the understanding and utilization of global cold seep microbiomes., (© The Author(s) 2024. Published by Oxford University Press and Science Press on behalf of the Beijing Institute of Genomics, Chinese Academy of Sciences / China National Center for Bioinformation and Genetics Society of China.)

Background: Infant botulism is caused by botulinum neurotoxin (BoNT), which is mainly produced by Clostridium botulinum . However, there is a lack of longitudinal cohort studies on infant botulism. Herein, we have constructed a cross-sectional and longitudinal cohort of infants infected with C. botulinum . Our goal was to reveal the differences in the intestinal microbiota of botulism-infected and healthy infants as well as the dynamic changes over time through multi-omics analysis., Methods: We performed 16S rRNA sequencing of 20 infants' stools over a period of 3 months and conducted whole genome sequencing of isolated C. botulinum strains from these laboratory-confirmed cases of infant botulism. Through bioinformatics analysis, we focused on the changes in the infants' intestinal microbiota as well as function over time series., Results: We found that Enterococcus was significantly enriched in the infected group and declined over time, whereas Bifidobacterium was significantly enriched in the healthy group and gradually increased over time. 18/20 isolates carried the type B 2 botulinum toxin gene with identical sequences. In silico Multilocus sequence typing found that 20\u00B0 C. botulinum isolates from the patients were typed into ST31 and ST32., Conclusion: Differences in intestinal microbiota and functions in infants were found with botulism through cross-sectional and longitudinal studies and Bifidobacterium may play a role in the recovery of infected infants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Li, Wang, Teng, Luo, Sun, Huang, Hu, Xu and He.)

Background: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022., Methods: Enterococcal strains were screened and verified after retrospective analysis of microbial data. Subsequently, 65 LRE strains (61 Enterococcus faecalis and 4 Enterococcus faecium, MIC ≥ 8 µg/ml), 1 linezolid-intermediate Enterococcus faecium (MIC = 4 µg/ml) and 1 linezolid-susceptible Enterococcus faecium (MIC = 1.5 µg/ml) were submitted for whole-genome sequencing (WGS) analysis and bioinformatics analysis., Results: The optrA gene was found to be the most common linezolid resistance mechanism in our study. We identified the wild-type OptrA and various OptrA variants in 98.5% of LRE strains (61 Enterococcus faecalis and 3 Enterococcus faecium). We also found one linezolid-resistant Enterococcus faecium strain carried both optrA and cfr(D) gene, while one linezolid-resistant Enterococcus faecium only harbored the poxtA gene. Most optrA genes (55/64) were located on plasmids, with impB-fexA-optrA, impB-fexA-optrA-erm(A), fexA-optrA-erm(A), and fexA-optrA segments. A minority of optrA genes (9/64) were found on chromosomes with the Tn6674-like platform. Besides, other possible linezolid resistance-associated mechanisms (mutations in the rplC and rplD genes) were also found in 26 enterococcal strains., Conclusions: Our study suggested that multiple mechanisms of linezolid resistance exist among clinical LRE strains in China., (© 2024. The Author(s).)

Anaerostipes hadrus ( A. hadrus ) is a dominant species in the human gut microbiota and considered a beneficial bacterium for producing probiotic butyrate. However, recent studies have suggested that A. hadrus may negatively affect the host through synthesizing fatty acid and metabolizing the anticancer drug 5-fluorouracil, indicating that the impact of A. hadrus is complex and unclear. Therefore, comprehensive genomic studies on A. hadrus need to be performed. We integrated 527 high-quality public A. hadrus genomes and five distinct metagenomic cohorts. We analyzed these data using the approaches of comparative genomics, metagenomics, and protein structure prediction. We also performed validations with culture-based in vitro assays. We constructed the first large-scale pan-genome of A. hadrus ( n = 527) and identified 5-fluorouracil metabolism genes as ubiquitous in A. hadrus genomes as butyrate-producing genes. Metagenomic analysis revealed the wide and stable distribution of A. hadrus in healthy individuals, patients with inflammatory bowel disease, and patients with colorectal cancer, with healthy individuals carrying more A. hadrus . The predicted high-quality protein structure indicated that A. hadrus might metabolize 5-fluorouracil by producing bacterial dihydropyrimidine dehydrogenase (encoded by the preTA operon). Through in vitro assays, we validated the short-chain fatty acid production and 5-fluorouracil metabolism abilities of A. hadrus . We observed for the first time that A. hadrus can convert 5-fluorouracil to α-fluoro-β-ureidopropionic acid, which may result from the combined action of the preTA operon and adjacent hydA (encoding bacterial dihydropyrimidinase). Our results offer novel understandings of A. hadrus , exceptionally functional features, and potential applications., Importance: This work provides new insights into the evolutionary relationships, functional characteristics, prevalence, and potential applications of Anaerostipes hadrus ., Competing Interests: The authors declare no conflict of interest.

Background: Dyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia., Methods: In this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3' untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview., Results: Eleven distinct polymorphisms at LDLR 3' UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r 2  = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin's efficacy., Conclusions: This research outlined the complex genetic architecture surrounding LDLR 3' UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care., Trial Registration: This multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418)., (© 2024. The Author(s).)

Influenza viruses undergo frequent genomic mutations, leading to potential cross-species transmission, phenotypic changes, and challenges in diagnostic reagents and vaccines. Accurately evaluating and predicting the risk of such variations remain significant challenges. To address this, we developed the VarEPS-Influ database, an influenza virus variations risk evaluation system (VarEPS-Influ). This database employs a 'multi-dimensional evaluation of mutations' strategy, utilizing various tools to assess the physical and chemical properties, primary, secondary, and tertiary structures, receptor affinity, antibody binding capacity, antigen epitopes, and other aspects of the variation's impact. Additionally, we consider space-time distribution, host species distribution, pedigree analysis, and frequency of mutations to provide a comprehensive risk evaluation of mutations and viruses. The VarEPS-Influ database evaluates both observed variations and virtual variations (variations that have not yet occurred), thereby addressing the time-lag issue in risk predictions. Our current one-stop evaluation system for influenza virus genomic variation integrates 1065290 sequences from 224 927 Influenza A, B and C isolates retrieved from public resources. Researchers can freely access the data at https://nmdc.cn/influvar/., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Importance: Cronobacter is an emerging foodborne opportunistic pathogen, which can cause neonatal meningitis, bacteremia, and NEC by contaminating food. However, the entire picture of foodborne Cronobacter carriage of the mcr genes is not known. Here, we investigated the mcr genes of Cronobacter isolates by whole-genome sequencing and found 133 previously undescribed Cronobacter isolates carrying mcr genes. Further genomic analysis revealed that these mcr genes mainly belonged to the mcr-9 and mcr-10. Genomic analysis of the flanking structures of mcr genes revealed that two core flanking structures were prevalent in foodborne Cronobacter isolates, and the flanking structure carrying IS1R was found for the first time in this study., Competing Interests: The authors declare no conflict of interest.

Background: Fusobacterium nucleatum is a one of the most important anaerobic opportunistic pathogens in the oral and intestinal tracts of human and animals. It can cause various diseases such as infections, Lemierre's syndrome, oral cancer and colorectal cancer. The comparative genomic studies on the population genome level, have not been reported., Results: We analyzed all publicly available Fusobacterium nucleatums' genomic data for a comparative genomic study, focusing on the pan-genomic features, virulence genes, plasmid genomes and developed cgmlst molecular markers. We found the pan-genome shows a clear open tendency and most of plasmids in Fusobacterium nucleatum are mainly transmitted intraspecifically., Conclusions: Our comparative analysis of Fusobacterium nucleatum systematically revealed the open pan-genomic features and phylogenetic tree based on cgmlst molecular markers. What's more, we also identified common plasmid typing among genomes. We hope that our study will provide a theoretical basis for subsequent functional studies., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Hepatocellular carcinoma (HCC) has limited prognostic prediction due to its heterogeneity. Understanding the role of natural killer (NK) cells in HCC is vital for prognosis and immunotherapy guidance. We aimed to identify NK cell marker genes through scRNA-seq and develop a prognostic signature for HCC. Methods: We analyzed scRNA-seq data (GSE149614) from 10 patients and bulk RNA-seq data from 786 patients with clinicopathological information. NK cell marker genes were identified using clustering and marker finding functions. A predictive risk signature was constructed using LASSO-COX algorithm. Functional annotations and immune cell infiltration analysis were performed, and the nomogram's performance was evaluated. Results: We identified 79 NK cell marker genes associated with NK cell-mediated cytotoxicity, apoptosis, and immune response. The multigene signature significantly correlated with overall survival (OS) in TCGA-LIHC cohort and was validated in other cohorts. Low-risk patients exhibited higher immune cell infiltration, including CD8 + T cells. The risk signature was an independent prognostic factor for OS (HR > 1, p < 0.001). The nomogram combining the risk signature and clinical predictors demonstrated robust prognostic ability. Conclusion: We developed a nine-gene signature prognostic model based on NK cell marker genes to accurately assess the prognostic risk of HCC. This model can be a valuable tool for personalized evaluation post-surgery. Our study underscores the potential of NK cells in HCC prognosis and highlights the importance of scRNA-seq analysis in identifying prognostic markers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Identification of plasmids in bacterial genomes is critical for many factors, including horizontal gene transfer, antibiotic resistance genes, host-microbe interactions, cloning vectors, and industrial production. There are several in silico methods to predict plasmid sequences in assembled genomes. However, existing methods have evident shortcomings, such as unbalance in sensitivity and specificity, dependency on species-specific models, and performance reduction in sequences shorter than 10 kb, which has limited their scope of applicability. In this work, we proposed Plasmer, a novel plasmid predictor based on machine-learning of shared k-mers and genomic features. Unlike existing k-mer or genomic-feature based methods, Plasmer employs the random forest algorithm to make predictions using the percent of shared k-mers with plasmid and chromosome databases combined with other genomic features, including alignment E value and replicon distribution scores (RDS). Plasmer can predict on multiple species and has achieved an average the area under the curve (AUC) of 0.996 with accuracy of 98.4%. Compared to existing methods, tests of both sliding sequences and simulated and de novo assemblies have consistently shown that Plasmer has outperforming accuracy and stable performance across long and short contigs above 500 bp, demonstrating its applicability for fragmented assemblies. Plasmer also has excellent and balanced performance on both sensitivity and specificity (both >0.95 above 500 bp) with the highest F1-score, which has eliminated the bias on sensitivity or specificity that was common in existing methods. Plasmer also provides taxonomy classification to help identify the origin of plasmids. IMPORTANCE In this study, we proposed a novel plasmid prediction tool named Plasmer. Technically, unlike existing k-mer or genomic features-based methods, Plasmer is the first tool to combine the advantages of the percent of shared k-mers and the alignment score of genomic features. This has given Plasmer (i) evident improvement in performance compared to other methods, with the best F1-score and accuracy on sliding sequences, simulated contigs, and de novo assemblies; (ii) applicability for contigs above 500 bp with highest accuracy, enabling plasmid prediction in fragmented short-read assemblies; (iii) excellent and balanced performance between sensitivity and specificity (both >0.95 above 500 bp) with the highest F1-score, which eliminated the bias on sensitivity or specificity that commonly existed in other methods; and (iv) no dependency of species-specific training models. We believe that Plasmer provides a more reliable alternative for plasmid prediction in bacterial genome assemblies., Competing Interests: The authors declare no conflict of interest.

ST7 Staphylococcus aureus is highly prevalent in humans, pigs, as well as food in China; however, staphylococcal food poisoning (SFP) caused by this ST type has rarely been reported. On May 13, 2017, an SFP outbreak caused by ST7 S. aureus strains occurred in two campuses of a kindergarten in Hainan Province, China. We investigated the genomic characteristics and phylogenetic analysis of ST7 SFP strains combined with the 91 ST7 food-borne strains from 12 provinces in China by performing whole-genome sequencing (WGS). There was clear phylogenetic clustering of seven SFP isolates. Six antibiotic genes including blaZ, ANT (4')-Ib, tetK, lnuA, norA, and lmrS were present in all SFP strains and also showed a higher prevalence rate in 91 food-borne strains. A multiple resistance plasmid pDC53285 was present in SFP strain DC53285. Among 27 enterotoxin genes, only sea and selx were found in all SFP strains. A ФSa3int prophage containing type A immune evasion cluster ( sea, scn, sak , and chp ) was identified in SFP strain. In conclusion, we concluded that this SFP event was caused by the contamination of cakes with ST7 S. aureus . This study indicated the potential risk of new emergencing ST7 clone for SFP., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Guo, Yu, Wang, Hua, You, Wu, Ji, Zhang, Li, Hu, Wu, Wei, Jin, Meng, Yang, Hu, Long, Hu, Qi, Ma, Bei, Yan, Wang and He.)

Background: Clostridium difficile infection (CDI) is common in patients with inflammatory bowel disease (IBD) and has been reported as a risk factor for poor outcome. However, gut microbiome and mycobiome of IBD patients with CDI have been barely investigated. This study aimed to assess the gut microbiome and mycobiome in IBD patients with CDI., Methods: We collected fecal samples from patients with active IBD and concomitant CDI (IBD-CDI group, n=25), patients with active IBD and no CDI (IBD-only group, n=51), and healthy subjects (HC, n=40). Patients' characteristics including demographic data, disease severity, and medication history were collected. Metagenomic sequencing, taxonomic and functional analysis were carried out in the samples., Results: We found that the bacterial alpha diversity of the IBD-CDI group was decreased. The bacterial and fungal beta diversity variations between IBD patients and HC were significant, regardless of CDI status. But the IBD-CDI group did not significantly cluster separately from the IBD-only group. Several bacterial taxa, including Enterococcus faecium , Ruminococcus gnavus , and Clostridium innocuum were overrepresented in the IBD-CDI group. Furthermore, IBD patients with CDI were distinguished by several fungal taxa, including overrepresentation of Saccharomyces cerevisiae . We also identified functional differences in IBD patients with CDI include enrichment of peptidoglycan biosynthesis. The network analysis indicated specific interactions between microbial markers in IBD-CDI patients., Conclusion: IBD patients with CDI had pronounced microbial dysbiosis. Gut micro-ecological changes in IBD patients with CDI might provide insight into the pathological process and potential strategies for diagnosis and treatment in this subset of patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yu, Ge, Xu, Tan, Tian, Shi, Dai, Li, Hu and Qian.)

The massive quantities of bacterial genomic data being generated have facilitated in-depth analyses of bacteria for pan-genomic studies. However, the pan-genome compositions of one species differed significantly between different studies, so we used Staphylococcus aureus as a model organism to explore the influences driving bacterial pan-genome composition. We selected a series of diverse strains for pan-genomic analysis to explore the pan-genomic composition of S. aureus at the species level and the actual contribution of influencing factors (sequence type [ST], source of isolation, country of isolation, and date of collection) to pan-genome composition. We found that the distribution of core genes in bacterial populations restrained under different conditions differed significantly and showed "local core gene regions" in the same ST. Therefore, we propose that ST may be a key factor driving the dynamic distribution of bacterial genomes and that phylogenetic analyses using whole-genome alignment are no longer appropriate in populations containing multiple ST strains. Pan-genomic analysis showed that some of the housekeeping genes of multilocus sequence typing (MLST) are carried at less than 60% in S. aureus strains. Consequently, we propose a new set of marker genes for the classification of S. aureus, which provides a reference for finding a new set of housekeeping genes to apply to MLST. In this study, we explored the role of driving factors influencing pan-genome composition, providing new insights into the study of bacterial pan-genomes. IMPORTANCE We sought to explore the impact of driving factors influencing pan-genome composition using Staphylococcus aureus as a model organism to provide new insights for the study of bacterial pan-genomes. We believe that the sequence type (ST) of the strains under consideration plays a significant role in the dynamic distribution of bacterial genes. Our findings indicate that there are a certain number of essential genes in Staphylococcus aureus; however, the number of core genes is not as high as previously thought. The new classification method proposed herein suggests that a new set of housekeeping genes more suitable for Staphylococcus aureus must be identified to improve the current classification status of this species.

Foodborne botulism is a rare but life-threatening illness resulting from the action of a potent toxin mainly produced by Clostridium botulinum. It grows in an oxygen-deficient environment and is extremely viable in meat and soy products, making it one of the most virulent bacteria. How to track foodborne botulism events quickly and accurately has become a key issue. Here, we investigated two foodborne botulism events that occurred in Xinjiang in 2019 based on whole-genome sequencing and also successfully traced the relationship between clinical and food C. botulinum isolates using whole-genome core gene markers. All 59 isolates were classified as group I strains. Of the strains isolated in this study, 44 were found to be botulinum toxin A(B), and 15 isolates contained only the toxin B locus. Both the toxin A and B gene segments were located on the chromosome and organized in an ha cluster. Antibiotic resistance and virulence factors were also investigated. A set of 329 universal core gene markers were established using C. botulinum strains from a public database. These core gene markers were applied to the published C. botulinum genomes, and three outbreaks were identified. This work demonstrates that universal core gene markers can be used to trace foodborne botulism events, and we hope that our work will facilitate this effort in future. IMPORTANCE In this study, we analyzed 59 foodborne botulism (FB)-related strains isolated in Xinjiang Province, China. Our findings not only reveal the group classification, neurotoxin locus organization, antibiotic resistance and virulence factors of these strains but also establish a set of core gene markers for tracing foodborne botulism events, which was verified using published genomes. These findings indicate that these gene markers might be used as a potential tracing tool for FB events caused by C. botulinum group I strains, which have relatively stable genomic components.

Unique anatomical and physiological features have made hamster species desirable research models. Comparative genomics and phylogenetic analysis of the hamster family members to clarify their evolution and genetic relationship, can provide a genetic basis for the comprehension of the variable research results obtained using different hamster models. The Syrian golden hamster (Mesocricetus auratus) is the most widely used species. In this study, we sequenced the complete mitochondrial genome (mitogenome) of M. auratus, compared it with the mitogenome of other Cricetinae subfamily species, and defined its phylogenetic position in the Cricetidae family. Our results show that the mitogenome organization, gene arrangement, base composition, and genetic analysis of the protein coding genes (PCGs) of M. auratus are similar to those observed in previous reports on Cricetinae species. Nonetheless, our analysis clarifies some striking differences of M. auratus relative to other subfamily members, namely distinct codon usage frequency of TAT (Tyr), AAT (Asn), and GAA (Glu) and the presence of the conserved sequence block 3 (CSB-3) in the control region of M. auratus mitogenome and other hamsters (not found in Arvicolinae). These results suggest the particularity of amino acid codon usage bias of M. auratus and special regulatory signals for the heavy strand replication in Cricetinae. Additionally, Bayesian inference/maximum likelihood (BI/ML) tree shows that Cricetinae and Arvicolinae are sister taxa sharing a common ancestor, and Neotominae split prior to the split between Cricetinae and Arvicolinae. Our results support taxonomy revisions in Cricetulus kamensis and Cricetulus migratorius, and further revision is needed within the other two subfamilies. Among the hamster research models, Cricetulus griseus is the species with highest sequence similarity and closer genetic relationship with M. auratus. Our results show mitochondrial DNA diversity of M. auratus and other Cricetinae species and provide genetic basis for judgement of different hamster models, promoting the development and usage of hamsters with regional characteristics., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The development of monocytes in bone marrow is a complex process with multiple steps. We used RNA-seq data to analyze the transcriptome profiles in developing stages of monocytes, including hematopoietic stem cells (HSCs), common myeloid progenitors (CMPs), granulocyte-monocyte progenitors (GMPs), and monocytes. We found that genes related to potassium and other cation transmembrane activities and ion binding were upregulated during the differentiation of HSCs into CMPs. Protein transport and membrane surface functional molecules were significantly upregulated in the GMP stage. The CD42RAC and proteasome pathways are significantly upregulated during the development of HSCs into monocytes. Transcription factors Ank1, Runx2, Hmga2, Klf1, Nfia, and Bmyc were upregulated during the differentiation of HSCs into CMPs; Gfi1 and Hmgn2 were highly expressed during the differentiation of CMPs into GMPs; Seventeen transcription factors including Foxo1, Cdkn2d, Foxo3, Ep300, Pias1, Nfkb1, Creb1, Bcl6, Ppp3cb, Stat5b, Nfatc4, Mef2a, Stat6, Ifnar2, Irf7, Irf5, and Cebpb were identified as potentially involved in the development of GMPs into monocytes in mice and humans. In metabolism pathway regulation, HSCs have high glucose, lipid, and nucleic acid metabolism activities; CMPs mainly up regulate the TCA cycle related genes; and GMPs have extremely active metabolisms, with significantly elevated pentose phosphate pathway, TCA cycle, histidine metabolism, and purine metabolism. In the monocyte phase, the tricarboxylic acid (TCA) cycle is reduced, and the anaerobic glycolysis process becomes dominated. Overall, our studies offer the kinetics and maps of gene transcriptional expressions and cell metabolisms during monocyte development in bone marrow., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Bossila, Li, Hu and Zhao.)

Complete and accurate reference genomes and annotations provide fundamental resources for functional genomics and crop breeding. Here we report a de novo assembly and annotation of a pea cultivar ZW6 with contig N50 of 8.98 Mb, which features a 243-fold increase in contig length and evident improvements in the continuity and quality of sequence in complex repeat regions compared with the existing one. Genome diversity of 118 cultivated and wild pea demonstrated that Pisum abyssinicum is a separate species different from P. fulvum and P. sativum within Pisum. Quantitative trait locus analyses uncovered two known Mendel's genes related to stem length (Le/le) and seed shape (R/r) as well as some candidate genes for pod form studied by Mendel. A pan-genome of 116 pea accessions was constructed, and pan-genes preferred in P. abyssinicum and P. fulvum showed distinct functional enrichment, indicating the potential value of them as pea breeding resources in the future., (© 2022. The Author(s).)

Glaciers represent a unique inventory of microbial genetic diversity and a record of evolution. The Tibetan Plateau contains the largest area of low-latitude glaciers and is particularly vulnerable to global warming. By sequencing 85 metagenomes and 883 cultured isolates from 21 Tibetan glaciers covering snow, ice and cryoconite habitats, we present a specialized glacier microbial genome and gene catalog to archive glacial genomic and functional diversity. This comprehensive Tibetan Glacier Genome and Gene (TG2G) catalog includes 883 genomes and 2,358 metagenome-assembled genomes, which represent 968 candidate species spanning 30 phyla. The catalog also contains over 25 million non-redundant protein-encoding genes, the utility of which is demonstrated by the exploration of secondary metabolite biosynthetic potentials, virulence factor identification and global glacier metagenome comparison. The TG2G catalog is a valuable resource that enables enhanced understanding of the structure and functions of Tibetan glacial microbiomes., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

CodY is a dominant regulator in low G + C, Gram-positive Firmicutes that governs the regulation of various metabolic pathways and cellular processes. By using various bioinformatics analyses and DNA affinity precipitation assay (DAPA), this study confirmed the presence of CodY orthologues and corresponding regulons in Gram-negative Synergistetes. A novel palindromic sequence consisting of AT-rich arms separated by a spacer region of variable length and sequence was identified in the promoters of the putative codY -containing operons in Synergistetes. The consensus sequence from genera Synergistes and Cloacibacillus (5'-AATTTTCTTAAAATTTCSCTTGATATTTACAATTTT) contained three AT-rich regions, resulting in two palindromic sequences; one of which is identical to Firmicutes CodY box (5'-AATTTTCWGAAAATT). The function of the consensus sequence was tested by using a recombinant CodY protein (His-CodY DSM ) of Cloacibacillus evryensis DSM19522 in DAPA. Mutations in the central AT-rich sequence reduced significantly the binding of His-CodY DSM , whereas mutations in the 5' or 3' end AT-rich sequence slightly reduced the binding, indicating that CodY DSM could recognize both palindromic sequences. The proposed binding sequences were found in the promoters of multiple genes involved in amino acids biosynthesis, metabolism, regulation, and stress responses in Synergistetes. Thus, a CodY-like protein from Synergistetes may function similarly to Firmicutes CodY.

Purpose: The aim of this study was to screen the possible pathogenic genes of one family with tuberous sclerosis complexes (TSCs)., Patients and Methods: All family members were examined through detailed clinical evaluations, auxiliary examinations and CT. Then, we selected five members from this TSC family as the test samples. They were analysed by a new exon group sequencing method. Single nucleotide polymorphisms (SNPs) were screened by using databases, such as dbSNP and HAPMAP, and then the candidate genes were selected. Genes were analysed, and finally, the most likely mutation sites were screened. The results were examined by Sanger sequencing., Results: In this TSC family, we identified c.913+2T>G, a splicing site mutation in the 9th intron region of TSC1. Family members without TSC did not have this mutation., Conclusion: The mutations in the intron regions cannot be ruled out as a pathogenic factor for TSC., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Wang et al.)

Background: Dandruff is a chronic, recurring, and common scalp problem that is caused by several etiopathogeneses with complex mechanisms. Management of this condition is typically achieved via antifungal therapies. However, the precise roles played by microbiota in the development of the condition have not been elucidated. Despite their omnipresence on human scalp little is known about the co-occurrence/co-exclusion network of cutaneous microbiota., Results: We characterized the scalp and hair surface bacterial and fungal communities of 95 dandruff-afflicted and healthy individuals residing in China. The degree distributions of co-occurrence/co-exclusion network in fungi-bacteria and bacteria-bacteria were higher in the healthy group (P < 0.0001), whereas the betweenness values are higher in the dandruff group (P < 0.01). Meanwhile, the co-occurrence/co-exclusion network among fungi-fungi and fungi-bacteria showed that compared to the healthy group, the dandruff group had more positive links (P < 0.0001). In addition, we observed that Malassezia slooffiae, Malassezia japonica and Malassezia furfur, were more abundant in the dandruff group than in the healthy group. These microbiota were co-exclusion by either multiple bacterial genera or Malassezia sp. in healthy group. The lactic acid bacteria on the scalp and hair surface, especially the genera Lactobacillus and Lactococcus, exhibit a negative correlation with multiple bacterial genera on the scalp and hair surface. Lactobacillus plantarum and Pediococcus lactis isolated on the healthy human scalp can inhibit the growth of Staphylococcus epidermidis in vitro., Conclusions: We showed that microbial networks on scalp and hair surface with dandruff were less integrated than their healthy counterparts, with lower node degree and more positive and stronger links which were deemed to be unstable and may be more susceptible to environmental fluctuations. Lactobacillus bacteria have extensive interactions with other bacteria or fungi in the scalp and hair surface micro-ecological network and can be used as targets for improving scalp health., (© 2022. The Author(s).)

Escherichia coli sequence type 405 is an emerging antibiotic-resistant clonal group associated with the global dissemination of extended-spectrum β-lactamase-producing E. coli . In this study, we report the genome assembly and characterization of a uropathogenic E. coli ST405 strain, SZESBLEC201, based on long and short reads obtained from the Nanopore and Illumina sequencing platforms, respectively. Whole-genome sequencing revealed that SZESBLEC201 harbors a 5,020,403 bp chromosome and three plasmids, namely, pSZESBLEC201-1, pSZESBLEC201-2, and pSZESBLEC201-3. pSZESBLEC201-1 (111,621 bp) belongs to the IncFIA-FIB type and harbors bla CTX-M-15 . However, this plasmid does not harbor conjugative transfer-associated genes, rendering pSZESBLEC201-1 unable to be conjugatively transferred. pSZESBLEC201-2 (95,138 bp) is a phage-like plasmid that shows a strong genome synteny with Escherichia phage P1 but with the absence of mobile genetic elements and some regulatory genes. pSZESBLEC201-3 (92,865 bp) belongs to the IncI1 type and carries bla CTX-M-24 . In contrast to pSZESBLEC201-1, pSZESBLEC201-3 retains its full active conjugation machinery and can be transferred via conjugation. The genetic features of the genome show that the SZESBLEC201 has a unique virulence pattern compared with genetically similar strains found in the same country (China). The plasmid backbones exhibit a high degree of similarity to those of geographically distant isolates, highlighting the global spread of bla CTX-M genes and the genome plasticity of this clonal group. The coexistence of two bla CTX-M variants in the same strain increases the risk of the emergence of new bla CTX-M variants. Further studies on phage-like plasmids are necessary to provide insights into their biological activities and clinical significance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yao, Zhu, Zou, Shenkutie, Hu, Qu, He and Leung.)

Baylisascaris schroederi, a roundworm (ascaridoid) parasite specific to the bamboo-feeding giant panda (Ailuropoda melanoleuca), represents a leading cause of mortality in wild giant panda populations. Here, we present a 293-megabase chromosome-level genome assembly of B. schroederi to infer its biology, including host adaptations. Comparative genomics revealed an evolutionary trajectory accompanied by host-shift events in ascaridoid parasite lineages after host separations, suggesting their potential for transmission and rapid adaptation to new hosts. Genomic and anatomical lines of evidence, including expansion and positive selection of genes related to the cuticle and basal metabolisms, indicate that B. schroederi undergoes specific adaptations to survive in the sharp-edged bamboo-enriched gut of giant pandas by structurally increasing its cuticle thickness and efficiently utilizing host nutrients through gut parasitism. Additionally, we characterized the secretome of B. schroederi and predicted potential drug and vaccine targets for new control strategies. Overall, this genome resource provides new insights into the host adaptation of B. schroederi to the giant panda as well as the host-shift events in ascaridoid parasite lineages. Our findings on the unique biology of B. schroederi will also aid in the development of prevention and treatment measures to protect giant panda populations from roundworm parasitism., (Copyright © 2021 Beijing Institute of Genomics. Published by Elsevier B.V. All rights reserved.)

Healthcare-associated infections (HAIs) seriously threaten patient health in intensive care units (ICUs). Profiling the microbial composition and diversity in ICU is important to prevent HAI-related spreading. Given that microbial communities vary across different environments, the time-scale characteristics of pathogens in ICUs have not been explored in China. In our study, to study the bacterial communities of two different ICUs in China, we proceeded dynamic monitoring using 16S rRNA sequencing for a whole year among the bed sheets, bed rails, shared pulse oximeters, bedside lockers, nurses' hands, floor, and carts. Our results showed that the microbial composition significantly changed within months. Significant differences in alpha and beta diversities were also observed among the 12 sampling months in each ICU. Additionally, we found the persistence of several HAI-related bacteria, including Acinetobacter, Pseudomonas, Staphylococcus, Escherichia, and Enterococcus. Source tracking analysis showed that most bacteria in both ICUs came from buildings or human skin. With deep investigations of hospital microbial surveillance on a long-term time-scale, we hope that these results will provide constructive guidelines to prevent the spread of HAIs in ICUs., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2021. Published by Elsevier B.V.)

We present a method of mapping data from publicly available genomics and publication resources to the Resource Description Framework (RDF) and implement a server to publish linked open data (LOD). As one of the largest and most comprehensive semantic databases about coronaviruses, the resulted gcCov database demonstrates the capability of using data in the LOD framework to promote correlations between genotypes and phenotypes. These correlations will be helpful for future research on fundamental viral mechanisms and drug and vaccine designs. These LOD with 62,168,127 semantic triplets and their visualizations are freely accessible through gcCov at https://nmdc.cn/gccov/., Competing Interests: The authors declare that they have no competing interests., (© 2022 The Authors. mLife published by John Wiley & Sons Australia, Ltd. on behalf of Institute of Microbiology, Chinese Academy of Sciences.)

Acinetobacter baumannii is a common pathogen in hospitals and usually causes bacteremia, pneumonia, meningitis, peritonitis and other diseases. Isolates carried NDM-1 gene can make several antibiotics such as carbapenems and other beta-lactams ineffective. Nowadays, the number of A. baumannii strains carrying NDM-1 has been climbing year by year in recent years. To characterise the transmission of NDM-1 in A. baumannii, we collected 2576 human-derived genomes of A. baumannii strains from NCBI database and found that 186 strains contained NDM-1 gene. The multi-locus sequence typing, phylogenetic tree, NDM-1 gene organization and the single nucleotide polymorphisms of NDM-1 were investigated. We hope that our work will provide a theoretical basis for the prevention of dissemination of NDM-1 in A. baumannii., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In 2002, the first crop genome was published using the rice cultivar 93-11, which is the progenitor of the first super-hybrid rice. The genome sequence has served as a reference genome for the indica cultivars, but the assembly has not been updated. In this study, we update the 93-11 genome assembly to a gap-less sequence using ultra-depth single molecule real-time (SMRT) reads, Hi-C sequencing, reference-guided, and gap-closing approach. The differences in the genome collinearity and gene content between the 93-11 and the Nipponbare reference genomes confirmed to map the indica cultivar sequencing data to the 93-11 genome, instead of the reference. Furthermore, time-course transcriptome data showed that the expression pattern was consistently correlated with the stages of seed development. Alternative splicing of starch synthesis-related genes and genomic variations of waxy make it a novel resource for targeted breeding. Collectively, the updated high quality 93-11 genome assembly can improve the understanding of the genome structures and functions of Oryza groups in molecular breeding programs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Gao, Nie, Tan, Xie, Bi, Sun, Luo, Zhu, Geng, Liu, Lin, Cui, Hu and Wu.)

The genomic variations of SARS-CoV-2 continue to emerge and spread worldwide. Some mutant strains show increased transmissibility and virulence, which may cause reduced protection provided by vaccines. Thus, it is necessary to continuously monitor and analyze the genomic variations of SARS-COV-2 genomes. We established an evaluation and prewarning system, SARS-CoV-2 variations evaluation and prewarning system (VarEPS), including known and virtual mutations of SARS-CoV-2 genomes to achieve rapid evaluation of the risks posed by mutant strains. From the perspective of genomics and structural biology, the database comprehensively analyzes the effects of known variations and virtual variations on physicochemical properties, translation efficiency, secondary structure, and binding capacity of ACE2 and neutralizing antibodies. An AI-based algorithm was used to verify the effectiveness of these genomics and structural biology characteristic quantities for risk prediction. This classifier could be further used to group viral strains by their transmissibility and affinity to neutralizing antibodies. This unique resource makes it possible to quickly evaluate the variation risks of key sites, and guide the research and development of vaccines and drugs. The database is freely accessible at www.nmdc.cn/ncovn., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Effectively enhancing the activity of inhibitory neurons has great therapeutic potentials since their reduced function/activity has significant contributions to pathology in various brain diseases. We showed previously that NMDAR positive allosteric modulator GNE-8324 and M-8324 selectively increase NMDAR activity on the inhibitory neurons and elevates their activity in vitro and in vivo. Here we examined the impact of long-term administering M-8324 on the functions and transcriptional profiling of parvalbumin-containing neurons in two representative brain regions, primary auditory cortex (Au1) and prelimbic prefrontal cortex (PrL-PFC). We found small changes in key electrophysiological parameters and RNA levels of neurotransmitter receptors, Na + and Ca 2+ channels. In contrast, large differences in cell adhesion molecules and K + channels were found between Au1 and PrL-PFC in drug-naïve mice, and differences in cell adhesion molecules became much smaller after M-8324 treatment. There was also minor impact of M-8324 on cell cycle and apoptosis, suggesting a fine safety profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xia, Zhang, Deng, Ma, Masri, Wang, Bao, Hu and Zhou.)

Coding regions have complex interactions among multiple selective forces, which are manifested as biases in nucleotide composition. Previous studies have revealed a decreasing GC gradient from the 5'-end to 3'-end of coding regions in various organisms. We confirmed that this gradient is universal in eukaryotic genes, but the decrease only starts from the ∼ 25th codon. This trend is mostly found in nonsynonymous (ns) sites at which the GC gradient is universal across the eukaryotic genome. Increased GC contents at ns sites result in cheaper amino acids, indicating a universal selection for energy efficiency toward the N-termini of encoded proteins. Within a genome, the decreasing GC gradient is intensified from lowly to highly expressed genes (more and more protein products), further supporting this hypothesis. This reveals a conserved selective constraint for cheaper amino acids at the translation start that drives the increased GC contents at ns sites. Elevated GC contents can facilitate transcription but result in a more stable local secondary structure around the start codon and subsequently impede translation initiation. Conversely, the GC gradients at four-fold and two-fold synonymous sites vary across species. They could decrease or increase, suggesting different constraints acting at the GC contents of different codon sites in different species. This study reveals that the overall GC contents at the translation start are consequences of complex interactions among several major biological processes that shape the nucleotide sequences, especially efficient energy usage., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), has caused immense global disruption. With the rapid accumulation of SARS-CoV-2 genome sequences, however, thousands of genomic variants of SARS-CoV-2 are now publicly available. To improve the tracing of the viral genomes' evolution during the development of the pandemic, we analyzed single nucleotide variants (SNVs) in 121,618 high-quality SARS-CoV-2 genomes. We divided these viral genomes into two major lineages (L and S) based on variants at sites 8782 and 28144, and further divided the L lineage into two major sublineages (L1 and L2) using SNVs at sites 3037, 14408, and 23403. Subsequently, we categorized them into 130 sublineages (37 in S, 35 in L1, and 58 in L2) based on marker SNVs at 201 additional genomic sites. This lineage/sublineage designation system has a hierarchical structure and reflects the relatedness among the subclades of the major lineages. We also provide a companion website (www.covid19evolution.net) that allows users to visualize sublineage information and upload their own SARS-CoV-2 genomes for sublineage classification. Finally, we discussed the possible roles of compensatory mutations and natural selection during SARS-CoV-2's evolution. These efforts will improve our understanding of the temporal and spatial dynamics of SARS-CoV-2's genome evolution., (© 2021 Science China Press. Published by Elsevier B.V. and Science China Press.)

Urinary stones and urinary tract infection (UTI) are the most common diseases in urology and they are characterized by high incidence and high recurrence rate in China. Previous studies have shown that urinary stones are closely associated with gut or urine microbiota. Calcium oxalate stones are the most common type of urinary stones. However, the profile of urinary tract microorganisms of calcium oxalate stones with UTI is not clear. In this research, we firstly found two novel clusters in patients with calcium oxalate stones (OA) that were associated with the WBC/HP (white blood cells per high-power field) level in urine. Two clusters in the OA group (OA1 and OA2) were distinguished by the key microbiota Firmicutes and Enterobacteriaceae. We found that Enterobacteriaceae enriched in OA1 cluster was positively correlated with several infection-related pathways and negatively correlated with a few antibiotics-related pathways. Meantime, some probiotics with higher abundance in OA2 cluster such as Bifidobacterium were positively correlated with antibiotics-related pathways, and some common pathogens with higher abundance in OA2 cluster such as Enterococcus were positively correlated with infection-related pathways. Therefore, we speculated that as a sub-type of OA disease, OA1 was caused by Enterobacteriaceae and the lack of probiotics compared with OA2 cluster. Moreover, we also sequenced urine samples of healthy individuals (CK), patients with UTI (I), patients with uric acid stones (UA), and patients with infection stones (IS). We identified the differentially abundant taxa among all groups. We hope the findings will be helpful for clinical treatment and diagnosis of urinary stones., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shen, Zhu, Dong, Wang, Fan, Li, Chen, Hu, He and Li.)

Background: High salt intake is a known risk factor of hypertension, which in turn increases the risk of stroke and cardiovascular diseases. The aim of this study was to develop and evaluate a method for predicting 24-hour urinary sodium excretion (UNa24h) using casual urine specimens in Chinese hypertensive patients., Methods: A total of 966 patients with hypertension were included from 8 provinces across China. A UNa24h prediction model (Sun&#95;C method) was developed for males and females using linear regression based on age, weight, sodium concentration in the spot urine (UNaspot), and creatinine concentration in the spot urine (UCrspot). The data were split into the training (70%) and testing (30%) sets to, respectively, develop and evaluate the Sun&#95;C method., Results: Compared with the Kawasaki, INTERSALT, and Tanaka methods, Sun&#95;C method achieved a low and consistent mean bias (1.1 mmol/d) within the range from 106 to 212 mmol/d of UNa24h (equivalent to NaCl intake of 6-12 g/d). In addition, the Sun&#95;C method showed no significant difference between the measured and estimated UNa24h in a paired t-test (P = 0.689). At individual level, Sun&#95;C method had 79.8% of individuals at the cutoff under ±30% level., Conclusions: Sun&#95;C method may prove a reasonable method to estimate the daily dietary sodium intakes (particularly in the range of 6-12 g/d of NaCl) in Chinese hypertensive patients using spot urine measurements. As the amount of data increases in the future, the performance of our formulae will be further improved., (© American Journal of Hypertension, Ltd 2021. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Recombination is one of the most important molecular mechanisms of prokaryotic genome evolution, but its exact roles are still in debate. Here we try to infer genome-wide recombination within a species, utilizing a dataset of 149 complete genomes of Escherichia coli from diverse animal hosts and geographic origins, including 45 in-house sequenced with the single-molecular real-time platform. Two major clades identified based on physiological, clinical and ecological characteristics form distinct genetic lineages based on scarcity of interclade gene exchanges. By defining gene-based syntenies for genomic segments within and between the two clades, we build a fine-scale recombination map for this representative global E. coli population. The map suggests extensive within-clade recombination that often breaks physical linkages among individual genes but seldom interrupts the structure of genome organizational frameworks as well as primary metabolic portfolios supported by the framework integrity, possibly due to strong natural selection for both physiological compatibility and ecological fitness. In contrast, the between-clade recombination declines drastically when phylogenetic distance increases to the extent where a 10-fold reduction can be observed, establishing a firm genetic barrier between clades. Our empirical data suggest a critical role for such recombination events in the early stage of speciation where recombination rate is associated with phylogenetic distance in addition to sequence and gene variations. The extensive intraclade recombination binds sister strains into a quasisexual group and optimizes genes or alleles to streamline physiological activities, whereas the sharply declined interclade recombination split the population into clades adaptive to divergent ecological niches., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Objectives: Klebsiella pneumoniae carbapenemase (KPC) has spread across the world. The present study focused on exploring the sequences of two new KPC-harbouring plasmids in K. pneumoniae., Methods: Eighteen KPC-harbouring K. pneumoniae isolates were collected from a tertiary teaching hospital in 2014 in Fujian, China, among which two new KPC-harbouring plasmids (pF77 and pF5) we identified. The characteristics of the plasmids and the isolates carrying them were investigated in detail., Results: The two KPC-harbouring plasmids (pF5 and pF77) carried the antimicrobial resistance genes bla KPC-2 , bla CTX-M-65 , bla SHV-12 , catA2 and fosA3. Detailed sequence comparison revealed that the two plasmids might have evolved from recombination of the previously reported plasmids pKP1034 and pCT-KPC, which were considered to evolve from ancestor plasmids pHN7A8, pKPC-LK30 and pKPHS2. Plasmids pF5 and pF77 were non-conjugative and were mainly identified in sequence type 11 (ST11) K. pneumoniae isolates. Additionally, 4-55 core single nucleotide polymorphisms (SNPs) were identified in each pair of sequenced isolates that carried the identified plasmids., Conclusion: Plasmids pF5 and pF77 as well as the previously reported plasmids pKP1034 and pCT-KPC were all detected in 2013-2014 in South China and were carried by ST11 K. pneumoniae isolates. SNP analysis indicated high similarity of the sequenced isolates. Therefore, spread of the group of plasmids may be due to an outbreak of clonal dissemination of ST11 KPC-producing K. pneumoniae. This study also highlights the importance of plasmid analysis in the surveillance and control of antibiotic resistance spread in clinical isolates., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Amlodipine is one of the most used members of calcium channel blockers (CCB), available to treat hypertension. It is mainly metabolized by the Cytochrome P450 3A4/5 (CYP3A4/5) in the liver. Peripheral edema emerges as the major adverse drug reaction to amlodipine and is the primary reason for discontinuation of amlodipine therapy. However, genetic changes in CYP3A5 may lead to changes in the tolerability of amlodipine., Purpose: In this study, we were interested whether variants in CYP3A5 have a role to play in amlodipine-induced peripheral edema., Methods: A total number of 240 Chinese Han patients that have experienced hypertension were included in the study. Sixty-four patients had experienced amlodipine-induced peripheral edema, while the remaining 176 patients with no history of edema formed the control group. Twenty-four single-nucleotide polymorphisms (SNPs) of CYP3A5 gene were sequenced by targeted region sequencing method. The relationship of these genetic variants with amlodipine-induced peripheral edema risk was assessed using logistic regression., Results: The allele frequencies of CYP3A5*1D (rs15524), CYP3A5*1E (rs4646453) and CYP3A5*3 (rs776746) were significantly different between cases and controls ( P <0.05). The CYP3A5 *3/*3 (CC) or CYP3A5 *1D/*1D (AA) carriers showed an increased risk of amlodipine-induced peripheral edema in dominant model. Meanwhile, patients carrying CYP3A5 *1E (AC/AA) showed a reduced risk of peripheral edema. Furthermore, we found a strong linkage disequilibrium among rs15524, rs4646453 and rs776746., Conclusion: Our study reveals for the first time that CYP3A5 *1D, *1E and *3 were associated with amlodipine-induced peripheral edema in Chinese Han patients with hypertension. However, further studies comprising larger number of samples, more related genes and other factors are wanted., Competing Interests: All authors declare that they have no conflicts of interest for this work., (© 2021 Liang et al.)