The kidney T lymphocytes emerge as central agents in both physiological surveillance and pathological processes. In this study, we aimed to establish an optimized protocol for isolating and purifying T lymphocytes from mouse and human kidneys to provide support for renal diseases research. To develop an optimized protocol, we evaluated different tissue fragmentation strategies, enzymatic digestion conditions, digestion times and Percoll density gradients to maximize cell yield and viability while preserving surface markers. Subsequently, we applied this method to various kidney disease models and performed single-cell sequencing analysis by using public database. Our analyses revealed mechanical mincing combined with 0.2% collagenase IV and 0.02% DNase I for 45 min, followed by 33-80% Percoll gradient centrifugation, yielded the highest number of viable mononuclear cells with preserved surface markers. This protocol outperformed mechanical grinding and high concentration collagenase digestion, which caused greater mechanical and chemical damage. Flow cytometry confirmed optimal isolation of CD4+ T cells, CD8+ T cells, and double-negative T cells with minimal impact on cell viability and marker expression. This protocol has been applied in ischemia-reperfusion injury, renal fibrosis, cisplatin-induced acute kidney injury models, and normal human kidney tissue, demonstrating its potential for both preclinical and clinical research. In addition, public single-cell RNA-seq data were used as a complementary reference to support the T lymphocyte subset proportions obtained by our method. This optimized method provides a reliable and scalable approach for renal T lymphocytes isolation, advancing kidney diseases research and potential therapeutic applications.

Antiretroviral therapy (ART) effectively suppresses HIV-1 replication, yet T cell dysfunction persists in ART-suppressed people living with HIV-1 (PLWH). While mammalian target of rapamycin (mTOR) signaling drives T cell dysregulation, the role of DNA damage-inducible transcript 4 (DDIT4), a stress-induced mTOR inhibitor, in HIV-1 infection remains undefined. In this study, we aimed to investigate the expression of DDIT4 in immune cells, and clarify its associations with T cell dysfunction in ART-suppressed PLWH. We enrolled 24 ART-suppressed PLWH and 16 people living without HIV (PWoH). DDIT4 mRNA expression in peripheral blood mononuclear cells (PBMCs) was quantified by RT-qPCR. Flow cytometry was employed to assess DDIT4 protein expression together with T cell activation, exhaustion, and senescence markers. DDIT4 transcriptional expression was significantly elevated in ART-suppressed PLWH and positively correlated with hemoglobin levels (r = 0.524, P = 0.010). Notably, DDIT4 was markedly upregulated in gammadelta T cells which displayed memory phenotypes with increased CD38, HLA-DR, TIGIT, and CD57 expression, but diminished CD28 expression. Furthermore, the frequency of DDIT4⁺gammadelta T cells was correlated positively with the frequencies of CD28−CD57+gammadelta T cells, but inversely with CD4⁺ T cell counts, total lymphocytes, and monocytes. During HIV-1 infection, DDIT4 may act as a stress-responsive checkpoint, inducing gammadelta T cell exhaustion and senescence in ART-suppressed PLWH. These findings highlight the potential of DDIT4 as a therapeutic target to restore gammadelta T cells competence and offer novel insights into ART-refractory immune dysfunction.

A substantial proportion of mpox cases occur in people with HIV, but how HIV coinfection and immune status affect clinical outcomes remains unclear. We systematically searched major databases up to March 2025 for observational studies comparing mpox patients with and without HIV coinfection. Pooled effect sizes were calculated using random-effects models. Risk ratios (RRs) or standardized mean differences (SMDs) with 95% confidence intervals were used for dichotomous or continuous outcomes. Post hoc subgroup analyses explored differences by economic development, viral suppression, and advanced HIV disease (AHD) proportion. Among 15,522 patients from 29 studies, 52.43% had HIV. HIV coinfection was associated with higher hospitalization [RR = 1.50, 95% CI (1.17, 1.93)] and mortality [RR = 4.54, 95% CI (2.11, 9.77)]. Coinfected patients had more syphilis, HBV, and HCV coinfections, and higher rates of fever, proctitis, malaise, rectal irritation syndrome, diarrhoea, skin and soft tissue infections, and pneumonia. Blood tests showed lower albumin, calcium, and haemoglobin, and higher CK-MB. Perianal lesions were more common with HIV. HIV coinfection is linked to greater clinical severity, mortality, and STI coinfections. Exploratory analyses suggest poor viral suppression may drive adverse outcomes, and lesion severity relates to immune status. All subgroup findings are post hoc and hypothesis-generating, limited by aggregate data. Intensified monitoring and supportive care, vaccination, and optimized ART initiation are crucial for this population.

CD39 exerts an inhibitory effect on tumour progression by impairing the cytotoxic capacity of natural killer (NK) cells against cancer cells. However, the impact of CD39 expression on the non-cytolytic functions of NK cells in treatment-naïve human immunodeficiency virus type 1 (HIV-1)-infected individuals remains poorly understood. In this study, thirty-four individuals with acute HIV-1 infection (AHI), thirty-eight with chronic HIV-1 infection (CHI), and twenty-four HIV-1-negative healthy controls (HC) were enrolled to explore the role of CD39 expression on NK cells in HIV-1 suppression at different infection stages. Flow cytometry was employed to analyze the immune phenotype and functional characteristics of NK cells. We found that CD39 expression on NK cells was significantly upregulated following HIV-1 infection, and its positive rate was positively associated with HIV-1 viral load in both AHI and CHI individuals. Compared with CD39- NK cells, CD39+ NK cells exhibited reduced activation; in AHI individuals, the activation level of CD39+ NK cells was positively associated with HIV-1 viral load but inversely correlated with CD4+ T-cell counts. In CHI individuals, the interleukin-10 (IL-10)-producing capacity of total NK cells, CD39+ NK cells, and CD39- NK cells was enhanced and positively correlated with HIV-1 viral load. Additionally, across the AHI and CHI groups, the overall IL-10-secreting ability of NK cells was positively correlated with the frequency of CD39+ NK cells. In both AHI and CHI individuals, CD39+ NK cells showed lower T-cell immunoglobulin and ITIM domain (TIGIT) expression than CD39- NK cells, while the CD39+TIGIT+ NK cell subset displayed significantly stronger IL-10-secreting capacity. POM-1, an inhibitor of CD39 ectonucleotidase activity, could enhance IL-10 secretion by NK cells in both HIV-1-infected individuals and the majority of healthy controls, but attenuate interferon-γ (IFN-γ) secretion by NK cells in HIV-1-infected individuals. In contrast, the CD39-blocking antibody A1 reduced IFN-γ secretion without affecting IL-10 secretion by NK cells in both HIV-1-infected individuals and healthy controls. Our findings reveal a novel CD39+ NK cell-associated mechanism that contributes to ineffective HIV-1 control, and suggest that CD39, alone or combined with TIGIT, may serve as a promising target to restore antiviral NK cell function in treatment-naïve individuals living with HIV-1.

Enteroviruses (EV) represent a significant public health concern due to their widespread prevalent and ability to cause disease in humans. Due to the limitations of routine surveillance, which primarily only detect clinically symptomatic cases, environment surveillance of urban sewage has emerged as a valuable and complementary strategy for EV surveillance. A total of 48 sewage samples were collected monthly from two wastewater treatment plants (WWTPs) in Hangzhou, Zhejiang Province from January 2023 to December 2024. Virus isolation and direct next-generation sequencing (NGS) were performed to characterize the EV serotypes profiles in sewage. Reverse transcription polymerase chain reaction (RT-PCR) was used to amplify VP1 gene sequences for molecular epidemiological analysis of EV serotypes. Ten distinct serotypes were isolated and identified from WWTP-QT and sixteen from WWTP-XS via virus isolation. EV-B was the dominant group in both treatment plants, with E3 and E11 representing the most frequently isolated serotypes. Phylogenetic analysis showed that the predominant genotypes in E3 was C6, whereas all E11 included phylogenetic analysis were classified into genotype D5. On the other hand, direct NGS uncovered as many as 108 distinct EV serotypes covering four human-infective species across both WWTPs. CVA4 and CVA6 were the dominant serotypes identified via NGS. Additionally, multiple uncommon serotypes as EV-A76, A89, A90, A92, A114, B74, B79, B98, B101, B106, B107, C96, C99, C113, C116, D70, D94, D111, D120 were detected in sewage. Environment surveillance is an important tool for monitoring EV circulation in the population. Furthermore, direct NGS can serve as a supplementary tool to the routine virus isolation method, particularly in detecting EV serotype diversity and evolution, and identifying uncommon serotypes.

Background:Despite the global success of antiretroviral therapy (ART) in reducing human immunodeficiency virus (HIV) related morbidity and mortality, late presentation of HIV infection remains a major challenge. This study aims to explore whether the immune dysregulation of pathological proliferation exists in late presenters (LP). Methods:People living with HIV (PLWH) were recruited and divided into LP group (n=55, defined as the presence of an AIDS-defining event and/or CD4 count <350 cells/μL) and non-late-presenters (n-LP) group (n=54). We evaluated the phenotype and function of CD4+ T cells in PLWH, and their correlation with clinical parameters. Mass cytometry was used to detect and analyze the phenotypic and functional characteristics of CD4+ T cells following ART. Results:The LP exhibited significantly lower CD4+ T cell counts compared to n-LP. A higher proportion of CD4+ T cell subpopulations with characteristics of proliferation (Ki67), activation (HLA-DR), exhaustion (PD-1) and senescence (CD57) was observed in LP. Besides, the proportion of CD4+ T cells with "pathological proliferation" properties (such as Ki67+CD57+, Ki67+HLA-DR+, Ki67+CD38+) in LP was much higher than that in n-LP. We found that the immune dysregulation characterized by pathological proliferation is related to multiple clinical parameters in LP. Conclusion:LP have persistent immune dysfunction post-ART, characterized by excessive and pathological T cell proliferation accompanied by activation or senescence. Future studies focusing on this pathological proliferation phenomenon will be essential to improve immune recovery, long-term prognosis, and health outcomes in advanced patients.

Porcine circovirus type 3 (PCV3), initially identified in the United States in 2016, is associated with multisystemic inflammation, myocarditis, reproductive failure in sows, and growth retardation in piglets, posing a significant economic threat to the swine industry. In this study, prokaryotic-expressed recombinant PCV3 Cap protein was used to immunize mice and rabbits. A monoclonal antibody (mAb 4G1) was generated through hybridoma technology, targeting a novel linear epitope (37DYYDKK42) within the first β-sheet of the Cap structure. This epitope exhibits high conservation (99.35%, 1239/1247) based on sequence alignment analysis, and residues 39 and 42 are critical residues affecting mAb binding. Subsequently, using rabbit polyclonal antibody (pAb) as the capture antibody and mAb 4G1 as the detection antibody, a double antibody sandwich ELISA (DAS-ELISA) method was developed. The assay demonstrates a cut-off value of 0.271, a detection limit for positive pig serum is 1:800, and shows no cross-reactivity with other swine pathogens. Intra- and inter-assay coefficients of variation were <10%, with a linear detection range for Cap protein down to 3.4 ng/mL. The coincidence rate between the DAS-ELISA and qPCR was 93.33% (70/75) for PCV3 detection in serum, with a kappa value of 0.837. This study establishes a simple, sensitive, and operationally efficient DAS-ELISA and provides a reference for monitoring PCV3 infection in swine herds.

Cognitive impairment (CI) continues to be a concern for people living with HIV-1 (PLWH) in the era of antiretroviral therapy (ART), yet the underlying mechanisms remain unclear. We aimed to elucidate the structural and functional brain alterations and peripheral immune profile of PLWH with CI, as well as the correlation between them. PLWH were divided into CI (n= 30) and cognitive normal (CN, n= 59) groups based on the Montreal Cognitive Assessment, and underwent multi-modal magnetic resonance imaging. Mass cytometry was utilized to profile immune cells, while the liquid chip technique was employed to measure plasma levels of cytokines and chemokines. Spearman correlation analyses were conducted for correlation analysis. Here, we found that the gray matter volume in left supramarginal gyrus was reduced, and the ReHo in the right middle frontal gyrus and the functional connectivity between right middle frontal gyrus and left postcentral gyrus were enhanced in CI group compared to CN group. Additionally, the frequencies of naïve CD8+T cells (Tn) and CD31lowCD8+ Tn were significantly correlated with gray matter volume in the left supramarginal gyrus. The amplitude of low frequency fluctuations in a specific brain region of frontal-middle lobe was negatively correlated with the frequencies of non-classical monocytes (nCM) and their subpopulations (CCR2lownCM, CD57lownCM and CD127+nCM), and positively associated with the plasma interleukin 25 and transforming growth factor-α levels. These findings suggest the association between peripheral immunity and the brain abnormalities in PLWH, highlighting a potential role of the immune-brain-cognition axis in the pathogenesis of CI in Chinese PLWH.

Short-chain fatty acids (SCFAs), key metabolites produced by gut microbiota, have neuroprotective effects in neurodegenerative diseases by modulating immune responses. However, their role in human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) remains largely unexplored. We recruited HAND patients, HIV Control, and healthy controls (HC). Plasma SCFAs and SCFA-producing gut microbiota were quantified via gas chromatography-mass spectrometry and fecal metagenomic analysis. Inflammatory cytokine levels were measured using liquid chromatography. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive accuracy of SCFAs for HAND. Plasma SCFAs were significantly reduced in HAND patients, correlating with a decrease in SCFA-producing gut bacteria, such as Prevotella and its related species. Reduced SCFAs were positively correlated with pro-inflammatory cytokines and cognitive impairment, while being negatively correlated with anti-inflammatory cytokines. ROC curve analysis demonstrated that several SCFAs exhibited strong predictive accuracy for HAND status. SCFAs may influence cognitive function by modulating inflammatory responses, and identifies plasma SCFAs as potential biomarkers and therapeutic targets for HAND. Further investigation is needed to delineate the mechanisms that SCFAs influence HAND pathology.

Protein biomarkers from plasma extracellular vesicles (EVs) have been extensively identified in various diseases. To explore biomarkers associated with diabetic retinopathy (DR) progression, we designed two cohorts, discovery and validation cohorts, including four groups: healthy control, type 2 diabetes mellitus, non-proliferative DR (NPDR), and proliferative DR (PDR). A total of 32 differentially expressed proteins (DEPs) were screened by proteomic analysis in the four groups of the discovery cohort. Among them, four hub proteins, CELA3A, CELA3B, GLUD1, and CTRC, were identified to be related to DR progression, and their correlation with clinical characteristics was further analyzed. Subsequently, enzyme-linked immunosorbent assay in the validation cohort confirmed that the expression levels of CELA3A, CELA3B, and CTRC were consistent with the proteomic results. Receiver operator characteristic curve analysis found that the AUC values of three hub proteins and their composed panels distinguishing NPDR/PDR from DM were all > 0.7, except for DM-NPDR of CELA3B. In addition, CELA3A, CELA3B, and CTRC proteins were significantly correlated with some clinical indicators of DR. This study indicates that the plasma EV proteins CELA3A, CELA3B, and CTRC are expected to become biomarkers to monitor DR progression and provide guidance for DR diagnosis.

Low-level viraemia (LLV) following antiretroviral therapy (ART) in people living with HIV (PLWH) has not received sufficient attention. To the determine the prevalence of LLV and its association with virological failure (VF), we systematically reviewed evidence-based interventions for PLWH. We searched PubMed, the Cochrane Library, Embase, and Web of Science from inception to 22 May 2024. Cohorts with samples sizes smaller than 1000 in size were excluded. Data from 16 cohort studies, encompassing 13,49,306 PLWH, revealed a pooled prevalence of LLV of 13.81%. Relative risk (RR) and 95% confidence intervals (CI) identified the following risk factors for LLV: viral load (VL) ≥ 105 copies/mL at baseline (1.79, 1.11-2.88), AIDS-defined illness at baseline (1.24, 1.10-1.40), and protease inhibitor-based regimen at ART initiation (1.53, 1.45-1.62) are the risk factors for LLV. Conversely, CD4 count ≥200 cells/μL at baseline (0.90, 0.82-0.98), non-nucleoside reverse transcriptase inhibitor-based regimen (0.81, 0.68-0.96) and the integrase strand transfer inhibitor (INSTI)-based regimen (0.60, 0.42-0.85) were associated with a reduced risk of LLV. Pooling the adjusted hazard ratio (aHR) and the 95% CI, we found that LLV increased the risk of VF with rising VL among 96,711 PLWH (aHR 2.77, 95% CI 2.03-3.76) and increased the risk of all-cause mortality at high VL levels among 14,229 PLWH (aHR 1.66, 95% CI 1.16-2.37). Therefore, the prevalence of LLV in PLWH should not be overlooked. This study aims to guide better management strategies to improve clinical outcomes in patients with LLV.

Kidney transplantation is the optimal treatment for end-stage renal disease (ESRD), but acute rejection (AR) remains a major factor affecting graft survival and patient prognosis. Currently, renal biopsy is the gold standard for diagnosing AR, but its invasiveness limits the application of dynamic monitoring. This study aims to analyze changes of immune cell and gene expression in the peripheral blood of AR recipients and construct a non-invasive AR diagnosis strategy. All datasets were downloaded from the GEO database. Single cells were annotated based on the expression profiles of surface proteins and changes of immune cell in the peripheral blood of AR and stable transplant (STA) recipients were compared. The high-dimensional weighted gene co-expression network analysis (hdWGCNA) algorithm was used to analyze gene modules related to AR and to screen out hub genes by integrating bulk RNA-Seq. Based on hub genes, consensus clustering stratified recipients into two sub-clusters and a non-invasive AR diagnostic model was constructed using Convolutional Neural Networks (CNNs). Additionally, we also constructed a predictive model for long-term graft survival through combinations of 111 machine learning algorithms and validated the expression of hub genes in the rat AR model. AR recipients had higher abundance of memory B cells, effector memory T cells, terminally differentiated effector memory T cells (TEMRA), and NK T cells but lower Tregs in the peripheral blood compared to STA recipients. Through hdWGCNA analysis, we identified gene modules associated with these immune cells and screened out four hub immune-related genes (TBX21, CX3CR1, STAT1, and NKG7) after integrating bulk RNA-Seq. Based on these hub genes, recipients can be stratified into two sub-clusters with distinct clinical outcomes and biological characteristics. We also innovatively constructed a non-invasive AR diagnostic model using CNNs, which can effectively address the issues caused by batch effects and demonstrate a high diagnostic accuracy. Besides, the predictive model for long-term graft survival constructed using the RSF algorithm can divided recipients into high- and low-risk groups, with significantly higher rates of AR and long-term graft failed in the high-risk group. This study successfully identified immune cell subsets and hub genes related to AR. Based on hub genes, we successfully identified two distinct molecular sub-clusters of kidney transplant recipients, and constructed a non-invasive diagnostic model for AR and a predictive model for long-term graft survival. These models offer new tools for precise diagnosis and prognosis in kidney transplantation and may advance precision medicine.

Early antiretroviral therapy (ART) is essential for controlling HIV-1 replication and boosting immune function. γδ T cells, as a vital component of the innate immune system, are implicated in the antiviral response. However, their immunological profile during acute HIV-1 infection and the early stages of ART remains unclear. This study aimed to delineate the immunological landscape of γδ T cells in individuals with acute HIV-1 infection undergoing early ART. We enrolled 65 participants who initiated ART immediately post-diagnosis and assessed the phenotypes and functions of γδ T cells using flow cytometry. We demonstrated that early ART significantly increased the frequency of Vδ2 T cells, while the Vδ1 T cell frequency remained stable and showed an inverse relationship with CD4+ T cell counts after ART. Early ART normalized the activation and PD-1 expression in Vδ1 and Vδ2 T cells, aligning with healthy controls (HCs) levels. Nevertheless, the proliferation of these cells, particularly within the PD-1+ subset, remains elevated post-ART. We also noted a reduction in perforin secretion in PD-1+ Vδ1 and Vδ2 T cells of people living with HIV (PLWH). Furthermore, Vδ1 T cells were identified as the predominant regulatory T cells, with TGF-β production and co-expression of CD127 and CXCR4, negatively correlated with CD8+ T cell activation. Our study elucidates the dynamic immunological characteristics of γδ T cells in acute HIV-1 infection and early ART, contributing to the understanding of their role in HIV-1 pathogenesis and the potential for γδ T cell-based immunotherapeutic strategies.

BackgroundDepressive disorders are highly prevalent among people with HIV (PWH) and are related to aberrant inflammation and immune responses. However, there is currently a lack of investigation into the neurological, inflammatory, endocrine, and immune aspects of HIV-associated depressive disorders (HADD).MethodsThe study involved 33 HIV-positive men who have sex with men with depressive disorders (HADD group) and 47 without neuropsychiatric disorders (HIV control group). Participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans and assessments of peripheral blood. Peripheral blood cytokines, plasma concentrations of hormone and neurotrophic factors, and immune cell levels were determined using liquid chip, enzyme-linked immunosorbent assay, and flow cytometry, respectively. The correlation of imaging alterations with clinical variables and peripheral blood indicators was assessed.ResultsCompared to the HIV control group, the HADD group exhibited a higher fractional amplitude of low-frequency fluctuations in the left superior parietal gyrus, lower regional homogeneity in the left precentral gyrus, and reduced voxel-wise functional connectivity for the seed region in the right precentral gyrus with clusters in the right cuneus, etc. Furthermore, the HADD group had higher levels of interferon-gamma, a higher frequency of non-classical monocytes, and higher expression levels of perforin and CD38 on specific cells. These imaging results were significantly correlated with peripheral blood indicators and clinical variables.ConclusionThis rs-fMRI study provides considerable evidence for abnormal intrinsic brain activity in people with HADD. Furthermore, our data also indicate the detrimental effects of depression-related inflammation on PWH. Therefore, it is imperative to increase attention to HADD and implement effective preventive interventions accordingly.

To explore whether intravesical chemotherapy (IVC) between primary and second transurethral resection of bladder tumor (TURBT) affects the prognosis of non-muscle invasive bladder cancer (NMIBC) patients receiving Bacillus Calmette-Guérin (BCG) treatment. NMIBC patients who underwent a second TURBT and subsequent BCG treatment between 2012 and 2023 at the Affiliated Hospital of Xuzhou Medical University were retrospectively analyzed. These patients were divided into Group A, which received IVC between TURBT, and Group B, which did not. Recurrence-free survival (RFS) was compared among the different risk subgroups. A total of 292 NMIBC patients were included in this study. In the entire cohort, IVC treatment between the primary and second TURBT was associated with longer RFS (P = 0.009). When stratified by risk groups, in intermediate-risk patients, the difference in RFS between the groups was not statistically significant (P = 0.434). By contrast, for high-risk patients, the treated group exhibited a better prognosis compared to the non-treated group (85.6% vs. 77.6%, P = 0.007). In both univariate and multivariate COX regression analyses, after adjusting for clinical factors such as tumor stage and tumor grade, the IVC between the primary and second TURBT remained an independent prognostic factor for NMIBC patients (HR 0.571, 95% CI [0.380, 0.859], p = 0.007). IVC treatment administered between the primary and second TURBT has been demonstrated to enhance RFS of high-risk NMIBC patients undergoing BCG treatment, whereas it is not applicable to intermediate-risk patients.

Introduction: HIV-1 genetic diversity in China is largely driven by recombination between predominant strains such as CRF01_AE and CRF07_BC. This study reports the identification and characterization of a novel second-generation CRF, designated CRF188_0107, identified among men who have sex with men (MSM) in Henan Province, China. Methods: Near-full-length genomes (NFLGs) were amplified from plasma samples of five epidemiologically unlinked individuals using a near-endpoint dilution nested PCR approach. Phylogenetic analysis was performed using IQ-TREE under the GTR model, recombination breakpoints were identified with SimPlot v3.5.1 and Bootscan, and Bayesian evolutionary analysis was conducted in BEAST v1.10.5 to estimate the time of the most recent common ancestor (tMRCA). Drug resistance mutations were analyzed using the Stanford HIVdb program. Results: All five NFLGs formed a distinct monophyletic clade separate from known CRFs. Recombination analysis revealed a mosaic structure consisting of nine segments with eight breakpoints, characterized by four inserted CRF07_BC fragments within a CRF01_AE backbone. The tMRCA was estimated between 2019 and 2023. No major drug resistance mutations were detected against PIs, NRTIs, NNRTIs, or INSTIs. Discussion: This study identifies CRF188_0107, a novel HIV-1 recombinant derived from CRF01_AE and CRF07_BC, among MSM in Henan, China. The strain shows a complex mosaic genome and emerged around 2019–2023. Some segments suggest a previously unrecognized CRF01_AE sublineage in the region. Our findings underscore the critical need for sustained molecular surveillance among key populations like MSM to monitor the rapid evolution and potential public health impact of novel HIV-1 recombinants in China.

Purpose:Renal ischemia-reperfusion injury (IRI) is a major posttransplant complication that promotes maladaptive repair and fibrosis, leading to allograft failure. However, the role of lactylation in these processes remains unclear. This study aimed to identify lactylation-associated biomarkers and their therapeutic potential in the IRI-induced maladaptive repair of kidney allografts and subsequent fibrosis. Methods:A gene set encompassing genes involved in the enzymatic regulation of lactylation was summarized, which includes key substrate proteins, lactylation "writers" and "erasers". Single-cell RNA-seq data were used to identify overall and cell-specific lactylation activity after IRI and in fibrotic samples. hdWGCNA analysis was used to identify hub genes, followed by predictive model construction using machine-learning algorithms. The relationships between hub genes and renal function, immune cell infiltration, and fibrotic biomarkers were also analyzed. Pseudotime trajectory analysis was used to investigate hub genes expression changes along fibrosis progression. Finally, RT-qPCR of hub genes and immunohistochemical staining were performed in a mouse model of unilateral IRI-fibrosis fibrosis. Results:Lactylation activity was elevated after IRI and in fibrotic samples, particularly in a subset of T cells, highlighting its importance in fibrogenesis. Four hub genes (HLA-E, IGHM, CORO1A, and TUBA1A) emerged as fibrosis biomarkers and showed robust predictive value for patient and graft survival (area under the curve of 0.83, 0.86, and 0.87 at 1, 2, and 3 years, respectively). Drug sensitivity and molecular docking analyses revealed the potential for repurposing existing drugs to target these genes. Lastly, experimental validation confirmed the increased mRNA expression of the hub genes. Conclusion:This multi-omics study identified a key lactylation-associated hub T cell potentially implicated in post-IRI induced maladaptive repair. Four lactylation-related T-cell biomarkers (CORO1A, HLA-E, IGHM, and TUBA1A) predicted allograft maladaptive repair and survival, providing a precise framework for early risk stratification and potential therapeutic intervention.

This bibliometric analysis investigates the role of antioxidant therapy in addressing neuropathic pain, emphasizing mechanistic insights and research trends from 2003 to 2024. Neuropathic pain, often unresponsive to standard treatments, is closely associated with oxidative stress as a key factor in its pathophysiology. This study utilizes the Web of Science Core Collection to analyze 699 articles related to "antioxidants" and "neuropathic pain." CiteSpace software was employed to examine publication trends, global collaborations, co-citation networks, and research hotspots. Results indicate a consistent rise in research activity, peaking in 2022, with China, India, and Italy as leading contributors. The University of Florence and Universidade Federal de Santa Maria emerged as prominent institutions, while influential authors included Pol Olga and Trevisan Gabriela. Key studies highlighted oxidative stress and neuropathic pain mechanisms, with neuroinflammation and specific molecular pathways gaining attention as emerging research foci. The findings underscore the growing interest in antioxidant therapies as potential interventions for neuropathic pain. Despite significant advances in understanding underlying mechanisms, there is a need for further exploration of novel antioxidants and their clinical applications. Enhanced international collaboration and the use of advanced molecular techniques are essential to drive future progress in this field.