Ammonium mitigates cadmium toxicity by activating the bZIP20-APX2/CATA transcriptional module in rice seedlings in an ABA-dependent manner.

The amelioration of cadmium (Cd2+) toxicity in plants by ammonium (NH4+) has been widely investigated. However, the molecular mechanisms underpinning this amelioration have remained ambiguous. Here, we found that NH4+ significantly reduces Cd2+ accumulation and enhances antioxidant capacity by increasing ABA accumulation, which, in turn, improves Cd2+ tolerance in rice seedlings. A combination of qPCR, yeast-one-hybrid and dual-luciferase assays, and CUT&RUN-qPCR methods demonstrates that OsbZIP20 directly binds to the promoters of OsAPX2 and OsCATA, activating their transcription, and we show that the process requires phosphorylation modification of OsbZIP20 by OsSAPK9. Under Cd2+ stress, Osbzip20 and Ossapk9 mutants show reduced peroxidase and catalase activities, higher H2O2 accumulation, and reduced Cd2+ tolerance. In sum, our results elucidate a novel mechanism by which NH4+ enhances Cd2+ resistance, through ABA-SAPK9-bZIP20-APX2/CATA, offering a new strategy for improving Cd2+ resistance in rice.

DNA methylation profiling identifies TBKBP1 as potent amplifier of cytotoxic activity in CMV-specific human CD8+ T cells.

Epigenetic mechanisms stabilize gene expression patterns during CD8+ T cell differentiation. Although adoptive transfer of virus-specific T cells is clinically applied to reduce the risk of virus infection or reactivation in immunocompromised individuals, the DNA methylation pattern of virus-specific CD8+ T cells is largely unknown. Hence, we here performed whole-genome bisulfite sequencing of cytomegalovirus-specific human CD8+ T cells and found that they display a unique DNA methylation pattern consisting of 79 differentially methylated regions (DMRs) when compared to memory CD8+ T cells. Among the top demethylated DMRs in cytomegalovirus-specific CD8+ T cells was TBKBP1, coding for TBK-binding protein 1 that can interact with TANK-binding kinase 1 (TBK1) and mediate pro-inflammatory responses in innate immune cells downstream of intracellular virus sensing. Since TBKBP1 has not yet been reported in T cells, we aimed to unravel its role in virus-specific CD8+ T cells. TBKBP1 demethylation in terminal effector CD8+ T cells correlated with higher TBKBP1 expression at both mRNA and protein level, independent of alternative splicing of TBKBP1 transcripts. Notably, the distinct DNA methylation patterns in CD8+ T cell subsets was stable upon long-term in vitro culture. TBKBP1 overexpression resulted in enhanced TBK1 phosphorylation upon stimulation of CD8+ T cells and significantly improved their virus neutralization capacity. Collectively, our data demonstrate that TBKBP1 modulates virus-specific CD8+ T cell responses and could be exploited as therapeutic target to improve adoptive T cell therapies.

Peritoneal dialysis promotes microbial-driven biosynthesis pathways of sesquiterpenes and triterpenes compounds in end-stage renal disease patients.

The concept of the gut-kidney axis is gaining significant attention due to the close relationship between gut microbiota and kidney disease. Peritoneal dialysis is recognized as a crucial renal replacement therapy for end-stage renal disease (ESRD). The alterations in gut microbiota and related mechanisms after receiving this dialysis method are not fully understood. This study conducted shotgun metagenomic sequencing on fecal samples from 11 end-stage renal disease patients who did not receive dialysis (ESRD_N) and 7 patients who received peritoneal dialysis (ESRD_P). After quality control and correlation analysis of the data, our study is aimed at exploring the impact of peritoneal dialysis on the gut microbiota and health of ESRD patients. Our research findings indicate that the complexity and aggregation characteristics of gut microbiota interactions increase in ESRD_P. In addition, the gut microbiota drives the biosynthesis pathways of sesquiterpenes and triterpenes in ESRD_P patients, which may contribute to blood purification and improve circulation. Therefore, our research will lay the foundation for the prevention and treatment of ESRD.

Examining the audiovisual therapy effects on hospital groups of varying linear canopy landscapes and those with hydrodynamic forces.

Recent research has highlighted the beneficial effects of urban green spaces on physical and mental health. This study focused on the hospital population and innovatively subdivided the population into four groups: doctors, caregivers, patients and nurses. A total of 96 volunteers participated in this virtual reality experiment to assess the restoration of a linear canopy landscape and a landscape with different levels of hydrodynamics through interactive audiovisual immersion. We utilized pre-research method, brainwave monitoring technique, psychological scales, observation and interviews in this experiment. The research identified five key findings. First, both linear canopy landscapes and those with low to medium hydrodynamic forces significantly enhance physiological and psychological restoration for all groups, with the most substantial physiological benefits observed in doctors and patients, and the greatest psychological relief noted in caregivers. Second, landscapes with medium hydrodynamic forces yield higher restorative effects than those with low forces in hospital settings. Third, green landscapes with medium and low-density canopies prove more conducive to patient recovery compared to those with high-density canopies. Fourth, the inclusion of bird songs does not markedly affect physiological restoration across the hospital groups. Finally, landscapes that incorporate elements of water dynamics, open skies, and lightly foliated canopies draw significant interest from all groups involved. This study advocates for the integration of natural blue and green elements into hospital environments as complementary therapeutic interventions, aiming to alleviate stress and promote health recovery among hospital communities.

The P2X7 receptor mediates NADPH transport across the plasma membrane.

Nicotinamide Adenine Dinucleotide Phosphate (NADPH) plays a vital role in regulating redox homeostasis and reductive biosynthesis. However, if exogenous NADPH can be transported across the plasma membrane has remained elusive. In this study, we present evidence supporting that NADPH can traverse the plasma membranes of cells through a mechanism mediated by the P2X7 receptor (P2X7R). Notably, we observed an augmentation of intracellular NADPH levels in cultured microglia upon exogenous NADPH supplementation in the presence of ATP. The P2X7R-mediated transmembrane transportation of NADPH was validated with P2X7R antagonists, including OX-ATP, BBG, and A-438079, or through P2X7 knockdown, which impeded NADPH transportation into cells. Conversely, overexpression of P2X7 resulted in an enhanced capacity for NADPH transport. Furthermore, transfection of hP2X7 demonstrated the ability to complement NADPH uptake in native HEK293 cells. Our findings provide evidence for the first time that NADPH is transported across the plasma membrane via a P2X7R-mediated pathway. Additionally, we propose an innovative avenue for modulating intracellular NADPH levels. This discovery holds promise for advancing our understanding of the role of NADPH in redox homeostasis and neuroinflammation.

Accurate Mental Stress Detection Using Sequential Backward Selection and Adaptive Synthetic Methods.

The daily experience of mental stress profoundly influences our health and work performance while concurrently triggering alterations in brain electrical activity. Electroencephalogram (EEG) is a widely adopted method for assessing cognitive and affective states. This study delves into the EEG correlates of stress and the potential use of resting EEG in evaluating stress levels. Over 13 weeks, our longitudinal study focuses on the real-life experiences of college students, collecting data from each of the 18 participants across multiple days in classroom settings. To tackle the complexity arising from the multitude of EEG features and the imbalance in data samples across stress levels, we use the sequential backward selection (SBS) method for feature selection and the adaptive synthetic (ADASYN) sampling algorithm for imbalanced data. Our findings unveil that delta and theta features account for approximately 50% of the selected features through the SBS process. In leave-one-out (LOO) cross-validation, the combination of band power and pair-wise coherence (COH) achieves a maximum balanced accuracy of 94.8% in stress-level detection for the above daily stress dataset. Notably, using ADASYN and borderline synthesized minority over-sampling technique (borderline-SMOTE) methods enhances model accuracy compared to the traditional SMOTE approach. These results provide valuable insights into using EEG signals for assessing stress levels in real-life scenarios, shedding light on potential strategies for managing stress more effectively.

FTO promotes gefitinib-resistance by enhancing PELI3 expression and autophagy in non-small cell lung cancer.

The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated in vitro and in vivo. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC.

Efficacy of electro-acupuncture on pregnancy outcomes for women undergoing in vitro fertilization: study protocol for a pilot randomized controlled trial.

Introduction: In vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes. Methods and analysis: This clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes. Ethics and dissemination: Ethics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi'nan Women and Children Hospital (number 2021-007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2300074455.

Assessment of Breeding Potential of Foxtail Millet Varieties Using a TOPSIS Model Constructed Based on Distinctness, Uniformity, and Stability Test Characteristics.

Foxtail millet (Setaria italica) is an important cereal crop with rich nutritional value. Distinctness, Uniformity, and Stability (DUS) are the prerequisites for the application of new variety rights for foxtail millet. In this study, we investigated 32 DUS test characteristics of 183 foxtail millet resources, studied their artificial selection trends, and identified the varieties that conform to breeding trends. The results indicated significant differences in terms of the means, ranges, and coefficients of variation for each characteristic. A correlation analysis was performed to determine the correlations between various DUS characteristics. A principal component analysis was conducted on 31 test characteristics to determine their primary characteristics. By plotting PC1 and PC2, all the germplasm resources could be clearly distinguished. The trends in foxtail millet breeding were identified through a differential analysis of the DUS test characteristics between the landrace and cultivated varieties. Based on these breeding trends, the optimal solution types for multiple evaluation indicators were determined; the weight allocation was calculated; and a specific TOPSIS algorithm was designed to establish a comprehensive multi-criteria decision-making model. Using this model, the breeding potential of foxtail millet germplasm resources were ranked. These findings provided important reference for foxtail millet breeding in the future.

Molecular Characterization and Classification of HER2-Positive Breast Cancer Inform Tailored Therapeutic Strategies.

HER2-positive breast cancer is an aggressive subtype that accounts for 15-20% of all breast cancers. Recent studies have suggested that HER2-positive breast cancer is a group of heterogeneous diseases with different sensitivities to standard treatment regimens. Revealing the molecular heterogeneity of HER2-positive breast cancer could potentially enable more precise treatment strategies. Here, we performed multiomics profiling on a HER2-positive breast cancer cohort and identified four transcriptome-based subtypes. The classical HER2 (HER2-CLA) subtype comprised 28.3% of the samples and displayed high ERBB2 activation and significant benefit from anti-HER2 therapy. The immunomodulatory (HER2-IM) subtype (20%) featured an immune-activated microenvironment, potentially suitable for de-escalated treatment and immunotherapy. The luminal-like (HER2-LUM) subtype (30.6%) possessed similar molecular features of hormone receptor-positive HER2-negative breast cancer, suggesting endocrine therapy and CDK4/6 inhibitors as a potential therapeutic strategy. Lastly, the basal/mesenchymal-like (HER2-BM) subtype (21.1%), had a poor response to current anti-HER2 dual-targeted therapies and could potentially benefit from tyrosine kinase inhibitors. The molecular characteristics and clinical features of the subtypes were further explored across multiple cohorts, and the feasibility of the proposed treatment strategies was validated in patient-derived organoid and patient-derived tumor fragment models. This study elucidates the molecular heterogeneity of HER2-positive breast cancer and paves the way for a more tailored treatment.

Exploring the Impact of Short Term Travel on Gut Microbiota and Probiotic Bacteria Mediated Stability.

Although travelers are frequently accompanied by abdominal discomfort and even diarrhea, not every trip can cause this issue. Many studies have reported that intestinal microbes play an important role in it. However, little is known about the reason for the dynamics of these intestinal microbes. Here, we delved into the effects of short-term travel on the gut microbiota of 12 healthy individuals. A total of 72 fecal samples collected before and after one-week travel, alongside non-traveling controls, underwent amplicon sequencing and a series of bioinformatic analyses. We found that travel significantly increased intra-individual gut microbiota fluctuations without diarrhea symptoms. In addition, the initial composition of the gut microbiota before travel emerged as a crucial factor in understanding these fluctuations. Travelers with stable microbiota exhibited an enrichment of specific probiotic bacteria (Agathobaculum, Faecalibacterium, Bifidobacterium, Roseburia, Lactobacillus) before travel. Another batch of data validated their predictive role in distinguishing travelers with and without the gut microbial disorder. This work provided valuable insights into understanding the relationship between gut microbiota and travel. It offered a microbiota-centric perspective and a potential avenue for interventions to preserve gut health during travel.

scBlood: A comprehensive single-cell accessible chromatin database of blood cells.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

A Flexible Temperature Sensor Integrated at Needle Tip for In Situ Acupoint Temperature Monitoring.

Temperature can reflect vital activities, and researchers have attempted to guide Chinese medicine diagnosis and treatment by observing acupoint temperature changes. Integrating a temperature sensor at the needle tip enables in situ acupoint temperature measurement. However, the sensor needles for acupoint temperature monitoring designed in previous studies were fabricated by manually soldering thermistor beads and metal wires, making mass production difficult. In this work, using MEMS manufacturing technology, a flexible temperature sensor that can be integrated at the needle tip is proposed and can be mass-produced on silicon wafers. The sensor uses a Pt thermistor as the temperature-sensing element and has a slender flexible structure with dimensions of 125 µm width by 3.2 cm length. As the sensor is inserted into a hollow needle, the Pt thermistor is glued to the needle tip. In the temperature range of 30 °C to 50 °C, the fabricated temperature sensor has a sensitivity of 5.00 Ω∙°C-1, a nonlinearity of ±0.39%FS, and a repeatability error of ±2.62%FS. Additionally, the sensor has been applied to in vivo acupoint temperature monitoring experiments in rats and demonstrated good performance, suggesting its promise for future research on acupoint temperature.

Recognition and management of stent malposition in the portal vein during endoscopic retrograde cholangiopancreatography: A case report.

BACKGROUND: Portal vein injury is an uncommon complication of endoscopic retrograde cholangiopancreatography (ERCP), for which stent malpositioning in the portal vein is very rare and can lead to fatal events. We report a case of biliary stent migration to the portal vein and a novel method for its safe removal under the guidance of portal angiography. Moreover, we reviewed the literature and summarized reports on the identification and management of this condition. CASE SUMMARY: A 59-year-old woman with pancreatic cancer presented with abdominal pain and a high fever 20 days after the placement of two plastic biliary stents under the guidance of ERCP. Blood cultures and laboratory tests revealed sepsis, which was treated with antibiotics. A contrast-enhanced computed tomography scan revealed that one of the biliary stents in the main portal vein was malpositioned. To safely remove the stent, portal angiography was performed to visualize the portal vein and to allow the management of any bleeding. The two stents were removed without obvious bleeding, and an uncovered self-expanding metal stent was placed in the common bile duct for drainage. The patient had an uneventful 6-month follow-up period, except for self-resolving portal vein thrombosis. CONCLUSION: The combination of endoscopic and angiographic techniques allowed uneventful management of stent malposition in the portal vein.

Antibiotic feeding changes the bacterial community of Chilo suppressalis and thereby affects its pesticide tolerance.

BACKGROUND: Owing to the widespread use of chemical pesticides to control agricultural pests, pesticide tolerance has become a serious problem. In recent years, it has been found that symbiotic bacteria are related to pesticides tolerance. To investigate the potential role of microorganisms in the pesticide tolerance of Chilo suppressalis, this study was conducted. RESULTS: The insect was fed with tetracycline and cefixime as the treatment group (TET and CFM, respectively), and did not add antibiotics in the control groups (CK). The 16S rDNA sequencing results showed that antibiotics reduced the diversity of C. suppressalis symbiotic microorganisms but did not affect their growth and development. In bioassays of the three C. suppressalis groups (TET, CFM, and CK), a 72 h LC50 fitting curve was calculated to determine whether long-term antibiotic feeding leads to a decrease in pesticide resistance. The CK group of C. suppressalis was used to determine the direct effect of antibiotics on pesticide tolerance using a mixture of antibiotics and pesticides. Indirect evidence suggests that antibiotics themselves did not affect the pesticide tolerance of C. suppressalis. The results confirmed that feeding C. suppressalis cefixime led to a decrease in the expression of potential tolerance genes to chlorantraniliprole. CONCLUSIONS: This study reveals the impact of antibiotic induced changes in symbiotic microorganisms on the pesticide tolerance of C. suppressalis, laying the foundation for studying the interaction between C. suppressalis and microorganisms, and also providing new ideas for the prevention and control of C. suppressalis and the creation of new pesticides.

NADPHnet: a novel strategy to predict compounds for regulation of NADPH metabolism via network-based methods.

Identification of compounds to modulate NADPH metabolism is crucial for understanding complex diseases and developing effective therapies. However, the complex nature of NADPH metabolism poses challenges in achieving this goal. In this study, we proposed a novel strategy named NADPHnet to predict key proteins and drug-target interactions related to NADPH metabolism via network-based methods. Different from traditional approaches only focusing on one single protein, NADPHnet could screen compounds to modulate NADPH metabolism from a comprehensive view. Specifically, NADPHnet identified key proteins involved in regulation of NADPH metabolism using network-based methods, and characterized the impact of natural products on NADPH metabolism using a combined score, NADPH-Score. NADPHnet demonstrated a broader applicability domain and improved accuracy in the external validation set. This approach was further employed along with molecular docking to identify 27 compounds from a natural product library, 6 of which exhibited concentration-dependent changes of cellular NADPH level within 100 µM, with Oxyberberine showing promising effects even at 10 µM. Mechanistic and pathological analyses of Oxyberberine suggest potential novel mechanisms to affect diabetes and cancer. Overall, NADPHnet offers a promising method for prediction of NADPH metabolism modulation and advances drug discovery for complex diseases.

A new evaluation system for drug-microbiota interactions.

The drug response phenotype is determined by a combination of genetic and environmental factors. The high clinical conversion failure rate of gene-targeted drugs might be attributed to the lack of emphasis on environmental factors and the inherent individual variability in drug response (IVDR). Current evidence suggests that environmental variables, rather than the disease itself, are the primary determinants of both gut microbiota composition and drug metabolism. Additionally, individual differences in gut microbiota create a unique metabolic environment that influences the in vivo processes underlying drug absorption, distribution, metabolism, and excretion (ADME). Here, we discuss how gut microbiota, shaped by both genetic and environmental factors, affects the host's ADME microenvironment within a new evaluation system for drug-microbiota interactions. Furthermore, we propose a new top-down research approach to investigate the intricate nature of drug-microbiota interactions in vivo. This approach utilizes germ-free animal models, providing foundation for the development of a new evaluation system for drug-microbiota interactions.

Differential relationships between autistic traits and anthropomorphic tendencies in adults and early adolescents.

Anthropomorphism, the attribution of human-like qualities (e.g., mental states) to nonhuman entities, is a universal but variable psychological experience. Adults with professionally diagnosed autism or high levels of subclinical autistic traits consistently show greater tendencies to anthropomorphize, which has been hypothesized to reflect 1) a compensatory mechanism for lack of social connectedness and 2) a persistence of childhood anthropomorphism into adulthood. Here, we directly tested these hypotheses in a general population sample consisting of both adults (N=685, 17-58 years old) and early adolescents (N=145, 12-14 years old) using the refined 9-item Anthropomorphism Questionnaire (AnthQ9), which measures both present and childhood anthropomorphic tendencies. We found that adults with heightened autistic traits reported increased present anthropomorphism (e.g., tend more to perceive computers as having minds), which held even after controlling for social connectedness. In contrast, adolescents with heightened autistic traits did not show increased present anthropomorphism, but rather reported reduced childhood anthropomorphism (e.g., less likely to perceive toys as having feelings) after controlling for social connectedness. We also found evidence that the present and childhood subscales of the AnthQ9 may tap into fundamentally different aspects of anthropomorphism. The results suggest that increased anthropomorphic tendencies in adults with heightened autistic traits cannot be explained solely by increased sociality motivation, but may be due to delayed development of anthropomorphism, although alternative possibilities of measurement problems cannot be ruled out. Implications for the measurement of anthropomorphism and its relation with theory of mind were also discussed.

Distinct characteristics of the gut virome in patients with osteoarthritis and gouty arthritis.

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.