Shenzhen Zhongshan Urological Hospital

Immunosenescence is a fundamental hallmark of aging, characterized by differential susceptibility across immune cell lineages. T lymphocytes are particularly vulnerable; however, the distribution and dynamics of aging-associated immune markers across T cell subsets remain incompletely characterized. In this study, we enrolled 462 healthy individuals stratified into six groups spanning 20 to over 70years. Using multiparametric spectral flow cytometry, we systematically characterized T lymphocyte subsets, capturing both immunophenotypic diversity and functional status. We identified a progressive age-associated decline in the frequencies of CD8+, γδ+, and Vδ2+ T cells, alongside an increase in CD4+ T cells. Aging was marked by the reduction of naive T cells and an expansion of terminally differentiated effector memory populations. Among all subsets, CD8+ T cells exhibited the greatest sensitivity to age-associated immunophenotypic remodeling, characterized by reduced expression of CD27 and CD28, and increased expression of senescence-associated surface markers including CD57 and KLRG1, together with elevated cytotoxic effector molecules including IFN-γ and granzyme B. Using these parameters, we defined 10 immune biomarkers through machine learning approaches that accurately predicted chronological age (R2=0.81, P<0.001). We further reconstructed the trajectory of T cell aging using ISTA-based sparse coding, which can capture aging-related immunophenotypic patterns in over 80% of individuals across age groups. Together, these findings demonstrate the dynamic remodeling of T lymphocytes across the human lifespan and provide a foundation for immune age modeling and risk stratification for unhealthy aging.

Unexplained recurrent spontaneous abortion (URSA) involves aberrant trophoblast cell death. Cuproptosis, a newly identified form of metabolic cell death, is not clearly associated with URSA. This study clarifies the association between URSA and trophoblast cell cuproptosis. This study analyzed cuproptosis-related gene expression in the trophoblast cells of patients with URSA using RNA sequencing (RNA-Seq). Copper ion levels in trophoblast cells were quantified using inductively coupled plasma mass spectrometry (ICP-MS). The regulation of trophoblast cell activity by cuproptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and the mouse embryo assay (MEA). The activation mechanism of trophoblast cell cuproptosis was delineated using RNA immunoprecipitation (RIP), RNA pull-down assay and RNA half-life assay. A mouse model of immune spontaneous abortion was used to evaluate the effect of L-Glutathione reduced (GSH) on abortion rates. The SLC31A1 protein, a copper ion transporter, is overexpressed in trophoblast cells of patients with URSA and activates trophoblast cell cuproptosis. The N6-adenosine-methyltransferase 70 kDa subunit (METTL3) protein binds to SLC31A1 mRNA, promoting N6-methyladenosine (m6A) modification. Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), an m6A-binding protein, binds to the m6A site of SLC31A1 mRNA, reducing mRNA degradation. GSH inhibits trophoblast cell cuproptosis, reducing the abortion rate in the mouse model of immune spontaneous abortion. In conclusion, in trophoblast cells of patients with URSA, the METTL3 protein promotes m6A modification of SLC31A1 mRNA, and IGF2BP3 enhances SLC31A1 mRNA stability, inducing intracellular copper accumulation, activating cuproptosis and ultimately leading to URSA.

Manipulation of motile cells is crucial for biological research and clinical applications. However, obtaining Z-axis visual feedback under monocular microscopy remains a challenge for robotic micromanipulation. Traditional depth-from-focus and depth-from-defocus methods fail to handle motile cells due to time-consuming focus search or inaccurate defocus modeling. This paper addresses these limitations by reformulating depth estimation as a fine-grained multi-class depth classification problem that exploits the shallow depth-of-field characteristic of microscopy. We propose a Fine-Grained Attention Fusion Module (FGAF-Module) that combines multi-scale grouped convolution for extracting subtle depth-related features with attention mechanisms to focus on discriminative regions in cell images. Additionally, channel-based feature augmentation methods, including CrossNorm and SelfNorm, enhance fine-grained feature discrimination while improving model generalization to handle morphological variations during cell movement. A weighted loss function further guides the model to distinguish between adjacent depth categories by penalizing errors proportionally to depth differences. For network training evaluation, the FGAF-module enhanced network achieved 83.52% top-1 classification accuracy and 96.88% top-3 classification accuracy while maintaining real-time performance at 90 frames per second. To demonstrate the capability of our approach in providing visual feedback for robotic manipulation of motile cells, the trained depth estimation model was integrated into a robotic sperm aspiration system. The model provided real-time visual depth feedback to guide 3D pipette localization during sperm aspiration procedures, achieving a 92% success rate for live motile sperm aspiration. These results validate the effectiveness of fine-grained classification for monocular depth estimation in micromanipulation applications.

ABSTRACT This study investigated fertility-related quality of life among married women of reproductive age (20–45 years) with endometriosis-associated infertility, focusing on the mediating role of family resilience between infertility-related stress and fertility-related quality of life. A cross-sectional survey was conducted between January 2024 and April 2025 at a tertiary hospital gynecology and reproductive center in Guangdong Province, China. Data were collected via structured questionnaires and analyzed using IBM SPSS Statistics 25.0 and AMOS 26.0. Results indicated moderate levels of fertility-related stress (M = 70.92, SD = 13.98). Pearson correlation analysis revealed a significant negative association between fertility-related stress and fertility-related quality of life (r = -0.435, p < 0.01), while family resilience showed a positive correlation with fertility-related quality of life (r = 0.377, p < 0.01). Mediation analysis demonstrated that family resilience partially mitigated the negative impact of stress on fertility-related quality of life (standardized indirect effect = -0.11, 95% CI [−0.18, −0.06], p < 0.001). The findings suggest that while fertility-related stress directly impairs fertility-related quality of life in this population, family resilience serves as a protective buffer. Clinically, interventions aimed at strengthening family support and adaptive capacity may help reduce stress and improve well-being in women with endometriosis-associated infertility.

Maternal hypertensive Disorders (MHD), including gestational hypertension, preeclampsia, and eclampsia, remain a major contributor to maternal and neonatal morbidity and mortality worldwide. While global healthcare advancements have improved maternal survival, the incidence of MHD continues to rise, particularly in low- and middle-income countries (LMICs). This study aimed to comprehensively assess the global and regional trends in the burden of MHD among women aged 15–49 years from 1990 to 2021 using data from the Global Burden of Disease (GBD) 2021 study. We examined disparities across countries and Socio-Demographic Index (SDI) regions, analyzed the influence of demographic and epidemiological factors through decomposition analysis, and projected future trends in MHD burden through 2050 using a Bayesian age-period-cohort (BAPC) model. We extracted incidence, mortality, and disability-adjusted life years (DALYs) of women aged 15–49 years from the GBD 2021 database across 204 countries. Temporal trends were analyzed using Joinpoint regression and the estimated annual percentage change (EAPC). Socioeconomic disparities were evaluated using the SDI, and future projections were conducted using a BAPC model with sensitivity analysis. The global MHD mortality (AAPC: -2.16%; 95% CI: -2.1 to -2.21) and incidence (AAPC: -0.5%, 95% CI: -0.45% to -0.56%) rate has declined. Decomposition analysis revealed that population growth and epidemiological changes were the main drivers of the increasing incidence, while aging had a less pronounced effect. Health inequality analysis demonstrated a clear negative correlation between MHD burden and socioeconomic development, highlighting the disproportionate impact on disadvantaged populations. The global burden of MHD exhibits significant regional disparities, with an declined trend in incidence. To address this persistent challenge, targeted interventions focusing on strengthening healthcare systems, improving access to quality obstetric care, and addressing socioeconomic inequities are urgently needed.

BackgroundChronic endometritis (CE) has been widely recognized as a potential cause of infertility, however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of persistent CE. Here, we aimed to analyze the impact of platelet-rich plasma (PRP) treatment on pregnancy outcomes and the endometrial microenvironment in patients with persistent CE.MethodsA total of 89 infertility patients were selected, including 56 non-CE (as the control group) and 33 persistent CE. The persistent CE patients received an intrauterine infusion of PRP four times before embryo transfer. Immunohistochemistry staining and transcriptomic sequencing were used to investigate the uterine-specific role of PRP in patients with persistent CE.ResultsThe implantation rate and clinical pregnancy rate were significantly increased in the cured CE group compared to the non-cured CE group. After PRP treatment, the proportions of endometrial CD8+ T cells, CD56+ NK cells, Foxp3+ Treg cells, and T-bet+ Th1 cells were significantly decreased in patients with persistent CE. Specifically, DEG analysis showed that genes implicated in endometrial receptivity-related and antimicrobial were upregulated and genes involved in the immune response processes were downregulated in cured CE patients after PRP treatment. Functional enrichment analysis suggested that the effects of changes in leukocyte chemotaxis-related genes played a critical role in the endometrial immune environment.ConclusionsAutologous PRP treatment has been shown as a potentially successful therapy for improving pregnancy outcomes by reconstructing the uterine local immune microenvironment to improve endometrial receptivity in patients with persistent CE.

Helicobacter pylori (H. pylori) manipulates the host immune system to establish a persistent colonization, posing a serious threat to human health, but the mechanisms remain poorly understood. Here we integrate single-cell RNA sequencing and TCR profiling for analyzing 187,192 cells from 11 H. pylori-negative and 12 H. pylori-positive individuals to describe the human gastric ecosystem reprogrammed by H. pylori infection, as manifested by impaired antigen presentation and phagocytosis function. We further delineate a monocyte-to-C1QC+ macrophage differentiation trajectory driven by H. pylori infection, while T cell responses exhibit broad functional impairment and hyporesponsiveness with restricted clonal expansion capacity. We also identify an HLA-DRs- and CTLA4-expressing T cell population residing in H. pylori-inhabited stomach that potentially contribute to immune evasion. Together, our findings provide single-cell resolution information into the immunosuppressive microenvironment shaped by H. pylori infection, offering critical insights for developing novel therapeutic approaches to eliminate this globally prevalent pathogen.