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The gut microbiota derived from Parkinson's disease patients, enriched in Bacteroides fragilis (B. fragilis) and Phocaeicola vulgatus (P. vulgatus), may promote the elevations of deoxycholic acid, iso-deoxycholic acid, and ursodeoxycholic acid levels in the systemic circulation. The increased serum bile acids, in turn, contribute to the endothelial cell death and pericyte injury possibly through activating interferon alpha response and TGF-β signaling pathways at the blood-brain barrier in the midbrain, ultimately leading to the neurodegeneration and motor deficits in the germ-free mice.

Interactions between functional oligosaccharides and small intestinal cells are increasingly recognized as critical for maintaining intestinal health. Using xylooligosaccharides (XOS) as a model, we demonstrate that XOS promote growth in piglets primarily by enhancing nutrient transport and increasing villus height in the jejunum. These effects are mediated by XOS-driven modulation of the intestinal microbiota, particularly the enrichment of Lactobacillus reuteri (L. reuteri) as a keystone species. L. reuteri reprograms epithelial energy metabolism toward reduced oxygen dependence, thereby inhibiting epithelial apoptosis and prolonging enterocyte survival. Notably, this protective effect is closely associated with elevated levels of the bile acid glycochenodeoxycholic acid (GCDCA), implicating a bile acid-dependent mechanism. Together, these findings reveal a microbiota- and metabolite-mediated pathway through which XOS regulate epithelial homeostasis and intestinal health.

Fastp has been recognized as one of the most popular FASTQ file preprocessors because of its powerful functions and extreme performance. As its first major update, fastp 1.0 will be formally presented in this paper, including its new features and the implementation principles behind it. Two other popular FASTQ preprocessors, Trimmomatic and Cutadapt, will be compared to demonstrate the great advantages of fastp in terms of simplicity, efficiency, and versatility. Some modules, such as the batch processing scripts, will be introduced on how to apply fastp to process FASTQ files efficiently. Additionally, some software design principles will be highlighted to showcase how to develop a successful bioinformatics software.

The emergence of hypervirulent carbapenem-resistant Klebsiella pneumoniae (hvCRKP) represents an alarming convergence of enhanced virulence and extensive drug resistance. Here, we present a comprehensive genomic analysis of 2563 clonal complex 23 (CC23) isolates from 62 countries spanning 1932–2024. Our findings reveal that CC23-K1, the dominant hypervirulent sublineage, emerged approximately 170 years ago and diversified into seven major clades with distinct regional dominance. We observe that carbapenem resistance in CC23-K1 exhibits notable instability, with at least 130 independent acquisitions and 20 losses of resistance genes, suggesting an evolutionary trade-off between hypervirulence and antimicrobial resistance. Experimental validation demonstrates that capsule production physically impedes plasmid conjugation, while isolates carrying bla_KPC-2, bla_NDM-1, or bla_NDM-5 frequently exhibit substantial deletion of virulence determinants. Conversely, bla_OXA-48-carrying isolates maintain virulence gene integrity, potentially due to their lower hydrolytic activity and reduced fitness costs. The geographic distribution of these resistance mechanisms correlates with regional antimicrobial usage patterns, with European countries with moderate carbapenem use favoring bla_OXA-48 in CC23, while Asian countries with higher consumption show patterns favoring high-efficiency carbapenemases incompatible with complete virulence determinants. We also identified core genomic regions with significantly higher mutation rates in resistant isolates, particularly affecting pathways involved in oxidative phosphorylation and reactive oxygen species production. These findings provide additional insights into CC23 evolution and geographical spread, complementing existing knowledge of carbapenemase distribution patterns observed across K. pneumoniae lineages.

Type 2 Diabetes Mellitus (T2DM) is a growing global health concern that is associated with severe complications including diabetic tendinopathy. In this study, we found that T2DM patients had a significantly higher prevalence of tendon surgery compared to non-T2DM patients, which were alongside impaired ECM and cell adhesion. Notably, metformin-treated T2DM patients had a lower prevalence of tendon surgery compared to other medications, along with improved tendon fiber structure, downregulation of tendon damage marker MMP3, and upregulation of HES1, a Notch signaling effector gene. Metformin also activates Notch signaling in cultured tenocytes, and tendons from diabetic mice and aged monkey. These findings highlight metformin's potential to protect tendons by activating Notch signaling, offering novel insights into its therapeutic benefits beyond glucose regulation.

The human microbiome is now recognized as a central regulator of cancer biology, intricately shaping tumor development, immune dynamics, and therapeutic response. This comprehensive review delineates the multifaceted roles of bacteria, viruses, and fungi in modulating the tumor microenvironment and systemic immunity across diverse cancer types. We synthesize current evidence on how microbial dysbiosis promotes carcinogenesis via chronic inflammation, metabolic reprogramming, genotoxic stress, immune evasion, and epigenetic remodeling. This review emphasizes organ-specific microbiome signatures and highlights their potential as non-invasive biomarkers for early detection, treatment stratification, and prognosis. Furthermore, we explore the impact of intratumoral microbiota on cancer therapies, uncovering how microbial metabolites and host–microbe interactions shape therapeutic efficacy and resistance. Finally, advances in microbiome-targeted strategies, such as probiotics, fecal microbiota transplantation, and engineered microbes offer new avenues for adjunctive cancer therapy. This review provides a roadmap for future investigation and underscores the transformative promise of microbiome modulation in cancer prevention and treatment.

By combining ultra-deep short-read shotgun metagenomic sequencing with 5-sample co-assembly across 600 agricultural soil samples, we significantly enhanced the representation and recovery of microbial communities in both clay and sandy soils. Despite an average of 107 Gb clean reads per sample, projections indicated that 1–4 Tb per sample would be required to capture 95% of the microbial community. Co-assembly of five biological replicates markedly improved metagenomic recovery, yielding up to 3.7× more metagenome-assembled genomes, up to 95% more unique genes, and broader recovery of prokaryotic phyla compared to single-sample assemblies.

Prophages are ubiquitously present in bacterial genomes, significantly influencing host physiological and ecological functions. We present Prophage SOS-dependency Predictor (PSOSP), a novel bioinformatics tool that predicts prophages induction modes by analyzing the Heterology Index (HI) of LexA protein binding to target DNA, classifying prophages into SOS-dependent prophages (SdPs) and SOS-independent prophages (SiPs). PSOSP was experimentally validated to accurately distinguish SdPs from SiPs in a test set, achieving 100% sensitivity and specificity. Applying PSOSP to 49,333 complete bacterial genomes, we inferred prophage induction modes in 15,493 bacterial genomes and identified 11,806 SiPs. These SiPs are widely distributed across 145 bacterial genera and exhibit distinct genomic features compared to SdPs. Correspondingly, the hosts of these two prophage types are hypothesized to differ in their physiological characteristics. These findings, powered by PSOSP, provide not only novel insights into the diverse induction mechanisms but also a critical methodology for future phage–host interaction studies.

Gemcitabine resistance drives bladder cancer recurrence and progression. Using high-throughput drug screening in bladder cancer cells, we identified Bavachalcone (Bava) as a potent gemcitabine sensitizer. Mechanistically, Bava simultaneously targets transferrin receptor (TFRC) and epidermal growth factor receptor (EGFR). It competes with transferrin (Tf) for TFRC binding, reducing cellular iron influx, and inhibits EGFR-mediated phosphorylation of TFRC at tyrosine 20 (Y20). These actions disrupt mitochondria iron utilization and impairs respiration. The combination of Bava and gemcitabine synergistically inhibits the repair of gemcitabine-induced DNA damage, while suppressing the iron-dependent ATR-CHEK1-E2F1 pathway and downregulating RRM1 expression. Patient-derived xenograft models confirmed the superior antitumor efficacy of the Bava-gemcitabine co-treatment compared to monotherapies. Clinically, elevated TFRC and RRM1 expression correlates with poor prognosis, supporting their utility as biomarkers of bladder cancer. Our study identified Bava as the first small-molecule TFRC inhibitor that overcomes gemcitabine resistance through iron modulation, providing both mechanistic insights and a promising therapeutic strategy for bladder cancer.