How matrine influences gut microbiota imbalance to prevent the progression of diabetes remains unclear. We conduct experiments using mice to simulate the stages of diabetes development and matrine intervention. Combined with amplicon sequencing, we find that the gut microbiota of diabetic mice continuously changes with the progression of the disease. Furthermore, differences in microbial community composition and function can distinguish the matrine intervention group from other groups. Muribaculum is generally enriched in the intervention group, while Lachnospiraceae_incertae_sedis is predominantly enriched in the diabetes group. These microbes may become new targets for diabetes intervention, providing new insights into diabetes treatment.
A portable, low-cost system enables rapid (3 min), on-site quantification of viable probiotics using a microfluidic chip with a fluorescent biosensor and image recognition. It distinguishes live/dead cells with high specificity and a broad range (10⁷–10¹¹ colony-forming units (CFU) mL−1), offering accurate, real-time results for practical applications.
Metatranscriptomic data analysis is a complex task due to its sheer volume and the need for sophisticated bioinformatics tools. To address this, we developed the Read-based Total-infectome Taxonomic Analysis Pipeline (RTTAP), an automated pipeline for metatranscriptomic data analysis that eliminates the need for users to manually select databases, tools, or parameters. RTTAP provides a comprehensive solution for “total-infectome” analysis, enabling simultaneous detection of viruses, bacteria, and fungi. Additionally, RTTAP delivers detailed functional profiling of antibiotic resistance genes (ARGs) and high-resolution viral strain analysis, offering researchers a powerful tool for advanced metatranscriptomic studies. The pipeline's performance was validated using both simulated and real clinical metatranscriptomic datasets, demonstrating high accuracy in taxonomic classification and relative abundance estimation.
Microplastic-induced gut microbial enrichment was dominated by bacteria within Eubacteriales, correlated with the virome, and accompanied by colitis. The polyamine synthetic pathway was activated to maintain glutathionylspermidine homeostasis, concurrent with decreases in pathways involved in the production of energy and reactive oxygen species under microplastic exposure. Tryptophan-serotonin, phenylalanine-phenylethylamine, and tyrosine-thyroxine pathways increased, whereas tryptophan-kynurenine, tryptophan-indole, and tyrosine-tyramine pathways decreased under microplastic exposure. Enterolactone synthesis and cholesterol-derived hormone synthesis were increased under microplastic exposure. Bacteria within Eubacteriales (e.g., Oscillospiraceae bacterium and Clostridiales bacterium) contributed most to metabolic disturbances under microplastic exposure.
Recovering high-contiguity, circular bacterial genomes from complex microbiomes (e.g., gut) is challenged by limitations of short-read and error-prone long-read sequencing. This study comprehensively compares PacBio High-Fidelity (HiFi) sequencing-based metagenome-assembled genomes (MAGs) against Illumina MAGs, Oxford Nanopore Technologies (ONT) MAGs, and isolate whole-genome sequencing genomes from the same sample. HiFi sequencing yielded 31 high-quality MAGs, including 10 complete circular genomes. HiFi MAGs demonstrated significantly higher completeness, continuity, and lower contamination than Illumina or ONT MAGs (p-adj < 0.05).Crucially, HiFi MAGs exhibited closer genomic proximity to corresponding isolates at both single-nucleotide polymorphism and gene presence/absence levels. This benchmarking establishes HiFi as a robust approach for generating MAGs rivaling isolated genome quality, providing critical insights for accurate microbial genomic studies.
Saliva MicroAge is a machine learning-based model designed to estimate biological age and assess health status using globally sourced salivary microbiome data. Trained on 4532 healthy samples, the model achieves high accuracy in predicting chronological age and captures health-related deviations (MicroAgeGap) in various diseases. Taxonomic and functional analyses of key microbial features reveal biological relevance to aging processes, offering a noninvasive and scalable approach for aging monitoring and precision health assessment.
Pigs are increasingly recognized as promising candidates for clinical xenotransplantation and as large-animal models for biomedical research; however, interspecies differences in gut microbiota, immune function, and metabolism remain major barriers. To address this, we established gut microbiota-humanized (GMH) pigs by transplanting human fecal microbiota into antibiotic-treated pigs. We systemically evaluated alterations in microbiota composition, serum metabolites, and immune cell profiles using integrated metagenomic, quasi-targeted metabolomic and single-cell transcriptomic (scRNA-seq) analyses. Metagenomic profiling revealed a shift in the intestinal microbiota of GMH pigs toward a human-like composition, characterized by enrichment of Bacteroidia and depletion of Bacilli. Metabolomic analysis showed that GMH pigs exhibited serum metabolite profiles more closely resembling those of humans. Among 423 detected serum metabolites, 136 that were lower in control pigs than in humans were upregulated in GMH pigs, whereas 79 that were elevated in control pigs decreased post-transplantation. Notably, pathways related to tryptophan metabolism, bile acid biosynthesis, and fatty acid metabolism were enhanced in GMT pigs, while carbon-related and glycolytic pathways were attenuated, indicating partial convergence toward human metabolic phenotype. Integration of microbial and metabolite data identified 20 and 33 metabolites associated with Bacteroidia and Bacilli, respectively. scRNA-seq profiling of peripheral blood mononuclear cells demonstrated transcriptional and compositional remodeling of T cells, monocytes, and B cell subsets in GMH pigs. These findings demonstrated that human fecal microbiota can reshape both systemic metabolic and immune artitecture in pigs, offering a robust large-animal platform for studying host-microbiota interactions and advancing translational application in xenotransplantation and microbiome-based therapeutics.
Microbial keystone species and gut microbiota composition are highly variable during the pathological development of the behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). Age stratification reveals stage-specific gut microbial signatures in AD-related BPSD. This study highlights the efficacy of electroacupuncture in regard to altering the intestinal microbial landscape in AD-related BPSD and provides novel insights into the application of phased targeted electroacupuncture interventions in the future.
The Qinghai-Tibet Plateau is an extreme ecosystem subject to special climatic conditions that require unique adaptations for its inhabiting organisms. In addition to genetic characteristics, the gut microbiota of animals can regulate the environmental adaptation of their hosts through various gut–organ axes. We performed a multi-omics analysis on six Chinese chicken populations: one high-altitude Tibetan chicken population, one transitional Tibetan chicken population relocated from high to low altitude, and four low-altitude populations. We found that the Tibetan chicken population under the plateau environment indicated a more complex and stochastically dominated gut microbiota with higher functional redundancy. Furthermore, Tibetan chickens had a more effective fatty acid degradation capacity, corresponding to the hypoxic environment. In contrast, chickens living in lowland environments showed stronger immune system responses against health threats, mainly regulated by the phylum Firmicutes. Thus, our findings clarify their adaptation strategies to environmental changes via microbiota-driven gut–organ axes.
This study defined 10,921 tissue-biased genes across 54 normal tissues and 41 cancer types. Tumor-associated tissue-biased genes exhibit downregulation, mutations, and epigenetic modifications, correlating with poor clinical outcomes. Their inactivation promotes tumorigenesis by enhancing stemness and immune evasion, highlighting their value as prognostic biomarkers and therapeutic targets. To facilitate research, we developed a database integrating multi-omics data on these genes for mechanistic and therapeutic exploration.
The keyword matching and gene proximity principles were used to accurately identify core gene clusters in microbial genomes. The metabolic gene clusters can be classified into different taxonomic groups according to Domain, Phylum, Class, Order, Family, Genus, and Species. BioMGCore can achieve batch statistics for secondary metabolites prediction.
This study monitored gut microbiome changes in healthy volunteers following inulin intervention, revealing dynamic and highly individualized shifts in microbial composition and short-chain fatty acid production. Using in vitro batch cultures, correlation analysis, and predictive modeling, we explored the personalized microbiome response. Our findings highlight the individualized response of the gut microbiome to prebiotics and the need for precision nutrition.
This study built a Wenchang chicken haplotype genome and integrated it with 29 others to create a chicken pangenome atlas. Analysis of 354 chickens revealed 185,205 structural variations (SVs), with one-third derived from homology-based and transposable elements. We found 1728 SVs linked to traits, including an EEF1A2 insertion affecting egg-laying rates and a VNTR-mediated SV influencing white feathers. These findings advance chicken genetics research and demonstrate SVs' importance in genomics.
Raman flow cytometry (RFC) enables rapid, high-throughput quality assessment of probiotic products by classifying species/strains, counting viable cells, and quantifying vitality at single-cell resolution. With 10-fold higher throughput and excellent accuracy, RFC outperforms traditional methods and offers a label-free, automated platform for probiotic quality control.
This narrative review uniquely addresses how gut microbiota-derived metabolites mediate overlapping pathologies of insulin resistance, neuroinflammation, and amyloidogenesis in type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD), proposing a framework for dual therapeutic targeting. This study indicates that the key bacteria, such as Akkermansia muciniphila (which releases outer membrane vesicles), Lactobacillus, and Bifidobacterium, as well as their metabolites like short-chain fatty acids (SCFAs), bile acids (BAs), lipopolysaccharide (LPS), and Trimethylamine N-oxide (TMAO) regulate T2DM and AD through complex mechanisms. These include Toll-like receptor 4 (TLR4)/activated B cells (NF-κB)-driven neuroinflammation, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)-mediated insulin resistance, and microbial amyloid cross-seeding, which collectively bridge the two diseases. Multiple signaling pathways, such as G-protein coupled receptor 41/43 (GPR41/43), PI3K/Akt, TLR4/NF-κB, and endoplasmic reticulum (ER) stress-mediated pathways, are critically involved in these processes.
This study has elucidated the role of three swine acute diarrhea syndrome coronavirus (SADS-CoV) accessory proteins in influencing viral pathogenicity and preliminarily explored the host molecular targets and pathways affected by the NS3a, NS7a, and NS7b proteins of SADS-CoV. Our findings suggest that SADS-CoV accessory proteins may modulate viral pathogenicity by affecting host metabolic pathways and immunity.
We selected participants from the NHANES database from 2005 to 2016 for this cross-sectional analysis. Logistic regression and other analytical methods were utilized to analyze the relationship between the intake of dietary live microbes and nondietary prebiotic/probiotic and the prevalence of osteoarthritis (OA) and rheumatoid arthritis (RA). The findings demonstrated a direct relationship between the consumption of nondietary prebiotic/probiotic and the prevalence of developing OA, whereas a greater consumption of dietary live microbes is associated with a lower occurrence of RA. (Graphical abstract was created with BioRender.com).
The longitudinal multi-omics cohort of patients with acute coronary syndrome (LM-ACS) is designed as a real-world prospective cohort of patients with ACS requiring coronary angiography. This study aims to enroll 50,000 participants, with a thorough collection of phenotypic data and multi-omics analyses performed on biological samples. Additionally, long-term follow-up will be conducted to track the incidence of major adverse cardiovascular events (MACEs) over the participants' lifetimes. For this purpose, three follow-up scenarios have been established for ACS patients, differentiated based on whether the patients had acute myocardial infarction (AMI) or unstable angina (UA), and whether they underwent percutaneous coronary intervention (PCI) surgery. The LM-ACS cohort seeks to create a unique resource to advance our understanding of the etiology and clinical outcomes of ACS.
Little has been reported on the effect of arbuscular mycorrhizal fungi (AMF) inoculants from in vitro dual culture system on the growth of maize and its endophytic microbial community. Our results suggest that AMF inoculants play an important role in influencing maize growth and diversity of endophytic bacterial communities. AMF inoculants significantly promote maize growth, especially AMF inoculants with modified Strullu-Romand (MSR) medium. These inoculants also significantly increased the diversity of endophytic microbial communities, especially the abundance of beneficial bacterial flora, thus positively affecting maize growth. This study reveals the utility of AMF inoculants from in vitro dual culture system, which provides a basis for the development of environmentally friendly inoculants.
Breast cancer (BC), specifically HER2-positives subtype, has a poor prognosis. Nevertheless, the development of anti-HER2 therapy yielded satisfactory outcomes. Therefore, evaluating patient HER2 status and ascertaining responsiveness to anti-HER2 therapy is crucial. The advent of deep learning has propelled the artificial intelligence (AI) revolution, leading to an increased applicability of AI in predictive models. In the field of medicine, AI is an emerging modality that is gaining momentum for facilitating cancer diagnosis and treatment, particularly in the effective management of breast cancer. This study aims to provide a comprehensive review of current diagnostic and predictive models that utilize data obtained from histopathological slides, radiomics, and HER2 binding sites. Advancements and practical applications of these models were also evaluated. Additionally, we examined existing obstacles that AI encounters for anti-HER2 therapy. We also proposed future directions for integrating AI in assessing and managing anti-HER2 therapy. The findings of this study offer valuable insights into the evaluation of AI-based anti-HER2 therapy, emphasizing key concepts and obstacles that, if addressed, could facilitate the integration of AI-assisted anti-HER2 therapy. The integration of AI has the potential to enhance the precision and customization of screening and treatment protocols for HER2+ breast cancer.
TCfinder is a tumor cell identification tool, based on pathway activity and deep neural network (DNN). Across different platforms of scRNA-seq datasets, TCfinder demonstrates robust identification efficiency. It outperforms existing tumor cell identification tools and performs under sparse data. TCfinder is freely available as an R package at: https://github.com/XSLiuLab/TCfinder.
Heterosis, or hybrid vigor, is characterized by the enhanced performance of F1 progeny in terms of yield, biomass, and environmental adaptation compared to their parental lines. Recent studies underscore the significant influence of soil microbes on heterosis, revealing that plant genotypes shape microbial communities which, in turn, have the potential to support plant growth through complex host-microbe interactions. The deeper insight into microbial roles suggests innovative ways to boost crop performance and sustainability by managing the plant microbiome to further enhance heterosis
Hepatocellular carcinoma (HCC) is a prevalent malignant tumor with a range of risk factors, including viral infections, alcoholic liver disease, exposure to fungal toxins, obesity, and type 2 diabetes. Despite advancements in early detection and treatment, HCC continues to exhibit a high rate of recurrence. Patients in advanced stages have a poor prognosis, and the survival rate after cancer metastasis is notably low. Consequently, there exists an urgent necessity for novel treatment strategies. Nanomedicine possesses superior attributes, such as targeted administration and responsive drug release within the tumor microenvironment. These systems demonstrate potential in HCC treatment by facilitating the transportation of diverse therapeutic drugs. This comprehensive review aims to delve into the application of nanoparticle drug delivery systems in the management of liver tumors, with particular emphasis on formulation, targeted strategies specific to liver tumors, and various methods of drug release. By offering insights into the utilization of nanoparticle drug delivery systems in the realm of liver tumor treatment, this review endeavors to assist readers in exploring their vast potential.
Antibiotic pretreatment is routine for chronic dacryocystitis (DC) patients. Herein, the longitudinal effects of antibiotic pretreatment before dacryocystorhinostomy for DC patients were evaluated. Conjunctival and nasal swabs were collected longitudinally from 33 DC patients with and without antibiotic pretreatment, both before dacryocystorhinostomy and at 1, 2, and 4 weeks postdacryocystorhinostomy. Additionally, conjunctival sac swabs were collected from 46 healthy volunteers and 14 other ocular diseases patients. Comparisons focused on ocular/nasal microbiota and recovery outcomes. Compared to healthy participants, DC patients without antibiotic pretreatment exhibited greater ocular microbiota diversity before dacryocystorhinostomy. Although clinical recovery rates were comparable, our results suggest that, after antibiotic pretreatment, the ocular microbiota richness and diversity, and the composition alteration tendency, significantly changed 4 weeks after surgery. This implies that the ocular microbiota was more disturbed in patients who underwent antibiotic pretreatment compared to those without such treatment. Furthermore, two types of ocular microbiota and three types of nasal microbiota were identified in ocular diseases. This study provides comprehensive data on the ocular and nasal microbiota in DC patients with and without antibiotic pretreatment, along with other ocular diseases. This finding suggested that antibiotic pretreatment may not be necessary before dacryocystorhinostomy for DC patients, especially for nonsevere cases.
Fine-needle aspiration cytology and imaging examinations are commonly used diagnostic tools for papillary thyroid carcinoma (PTC). However, these methods have limitations. Inflammatory proteins have the potential to serve as diagnostic and prognostic markers, as well as treatment targets. The expression profile and diagnosis effect of inflammatory proteins in PTC are not well understood. Here, 18 healthy volunteers (as healthy control), 12 patients with nodular goiter, and 34 patients with PTC were collected to analyze serum inflammatory proteins by proximity extension assay. Receiver operating characteristic curve analysis was used to evaluate the diagnostic potential of differential expression of proteins via the area under the curve (AUC) analysis. A total of 36 differentially expressed inflammatory proteins were found among PTC, nodular goiter, and healthy control. The combination diagnosis derived from the logistic regression analysis exhibited promising diagnostic capabilities in distinguishing nodular goiter from healthy control (AUC = 0.88), distinguishing PTC from healthy control (AUC = 0.89), and distinguishing PTC from nodular goiter (AUC = 0.87). Whereas the combination diagnosis derived from the least absolute shrinkage and selection operator (LASSO) exhibited promising diagnostic capabilities in distinguishing nodular goiter from healthy control (AUC = 0.92), distinguishing PTC from healthy control (AUC = 0.93), and distinguishing PTC from nodular goiter (AUC = 0.93). Overall, this study offers potential biomarkers for distinguishing between PTC and nodular goiter in clinical practice. The combination derived from the LASSO algorithm outperforms logistic regression.
Glycosylation plays a pivotal role in the physiological and pathological processes of male reproduction. It impacts thousands of proteins and is actively ongoing through all stages of reproduction, including spermatogenesis, maturation, capacitation, and fertilization. However, our grasp on glycosylation within male reproductive processes remains limited, largely due to the technical hurdles. Recent advancements have seen the mapping of the glycoproteome of human semen, utilizing cutting-edge glycoproteomic technologies. This breakthrough lays the groundwork for in-depth research into the influence of glycosylation on male reproductive system and related disorders. Nevertheless, the field faces numerous challenges that necessitate further advancements in glycoproteomic methodologies. In this analysis, we evaluated the potential applications of advanced glycoproteomic techniques in the study of male reproduction and summarized the detailed profiling of the human semen glycome and glycoproteome. Our current understanding of glycosylation's role within the male reproductive system alongside recent progress in glycoproteomics may equip biologists with a comprehensive insight. Furthermore, this analysis brought together findings on abnormal glycosylation and its link to male reproductive disorders in the view of glycomics and glycoproteomics. It can facilitate the clinical application of glyco-related biomarkers and targets in the treatment of infertility.
The 45 diploid cotton species identified worldwide exhibit remarkable morphological diversity. Modern cotton breeding is limited by incomplete understanding of the genetic variation in these species, suggesting a need for pan-genomic comprehensive analyses. In this study, a high-quality super pan-genome was built using 22 representative diploid cottons species and their adaptive evolution was investigated. The genomes of the twenty-two species yielded an average of 923,706 transposable elements (TEs) per assembly, with TE proportions ranging from 62.29% to 88.92%. The inferring ancestor genome structure (IAGS) showed that the D5 genome was closer to the ancestor, and the K2 genome accumulated more fissions and fusions. A gene-based super pan-genome identified 67,807 genes, including 22,384 core, 34,093 variable, and 11,330 specific genes. The structural variations (SVs) were unevenly distributed on the chromosomes, and 321 hotspot regions were detected, containing 90 genes associated with fiber initiation and/or elongation. During the eastward diffusion of diploid cotton, the genome size and structure experienced significant changes. We investigated the foliar nectary in 17 diploid cotton species, and identified a 444-bp deletion in the promoter sequence of GoNe that explained the lack of foliar nectary in G. gossypiodes (D6) and G. schwendimanii (D11). This pan-genome construction and comprehensive analysis for diploid cotton provided insight into dynamic genomic variation during diploid cotton expansion and can facilitate effective modern cotton breeding.
Bacteria often exist and function as a community, known as the bacterial microbiota, which consists of vast numbers of bacteria belonging to many bacterial species (taxa). Characterizing the bacterial microbiota needs high-throughput approaches that enable the identification and quantification of many bacterial cells, and such approaches have been under development for more than 30 years. In this review, we describe the history of high-throughput technologies based on 16S ribosomal RNA (rRNA) gene-amplicon sequencing for the characterization of bacterial microbiotas. Then, we summarize the features and applications of current 16S rRNA gene-amplicon sequencing approaches, including a recent achievement that enables the identification of individual cells with single-base accuracy for 16S rRNA genes and the quantification of many identified cells. Furthermore, we present the prospects for further technical development, including the combined use of high-throughput methods and other informative analyses, such as whole-genome sequencing in the common unit of the cell, which enables bacterial microbiota characterization based on both the number of cells and their functions.
Generative artificial intelligence (AI) holds immense potential for medical applications, but the lack of a comprehensive evaluation framework and methodological deficiencies in existing studies hinder its effective implementation. Standardized assessment guidelines are crucial for ensuring reliable and consistent evaluation of generative AI in healthcare. Our objective is to develop robust, standardized guidelines tailored for evaluating generative AI performance in medical contexts. Through a rigorous literature review utilizing the Web of Sciences, Cochrane Library, PubMed, and Google Scholar, we focused on research testing generative AI capabilities in medicine. Our multidisciplinary team of experts conducted discussion sessions to develop a comprehensive 32-item checklist. This checklist encompasses critical evaluation aspects of generative AI in medical applications, addressing key dimensions such as question collection, querying methodologies, and assessment techniques. The checklist and its broader assessment framework provide a holistic evaluation of AI systems, delineating a clear pathway from question gathering to result assessment. It guides researchers through potential challenges and pitfalls, enhancing research quality and reporting and aiding the evolution of generative AI in medicine and life sciences. Our framework furnishes a standardized, systematic approach for testing generative AI's applicability in medicine. For a concise checklist, please refer to Table S or visit GenAIMed.org.
Dysregulation of the gut microbiota often leads to immune-related disorders, indigestion, or diarrhea. Here, Jiaxing Black (JXB) pig, a local Chinese pig breed known for its great tolerance and digestibility of nutrients, was employed for a metagenomic and transcriptomic integrative analysis to reveal the gut microbiota-genes and gut microbiota-pathway interactions. A total of 452 differentially expressed genes, and 174 phyla were found between the JXB and the Duroc × Landrace × Yorkshire (DLY) pigs. Detailed analysis revealed that the differences in colon gene expression signatures between the JXB and DLY are mainly enriched in metabolic and inflammatory responses, with Lactobacillus and Lachnospiraceae enriched in DLY and JXB, respectively. Notably, Pacebacteria, Streptophyta, and Aerophobetes were found to participate in the PI3K-Akt mediated immune response in both pig breeds; however, they only accelerated the metabolism in the intestines of JXB pigs. Moreover, the host could regulate microbe metabolism and immune response by Ig-like domain-containing protein and ITIH2, PAEP, and TDRD9, respectively. Taken together, our results revealed both common and breed-specific regulations of host genes by gut microbiota in two pig breeds.