Jianbo Qing

1. Focal segmental glomerulosclerosis (FSGS) represents a critical pathological feature of glomerular diseases [1]. Most forms of glomerulonephritis eventually develop FSGS as the disease progresse...

Podocytes (PODs) play a critical role in maintaining glomerular filtration function, and their injury is a key driver of progressive podocytopathies (PCPs). Despite their clinical importance, the molecular and spatial mechanisms underlying POD injury remain poorly understood. We generated a single-nucleus RNA sequencing (snRNA-seq) and high-resolution spatial transcriptomic (ST) dataset from kidney tissues of patients with five major PCP subtypes. Our analysis revealed distinct molecular signatures among PCP subtypes, injury-related cytoskeletal alterations, and POD-centered microenvironmental features associated with clinical outcomes. Through integrative analysis, we found PDE4DIP as a previously unrecognized regulator of the POD cytoskeleton. Functional experiments through in vitro and in vivo gene editing demonstrated that PDE4DIP maintains cytoskeletal integrity by scaffolding with AKAP9 and activating RAS-ERK and AKT signaling. Its expression correlated with renal function and prognosis. This study provides the comprehensive snRNA-seq and high-resolution ST atlas of PCPs, offering a valuable resource for understanding POD injury and identifying potential therapeutic targets.

Immune-mediated glomerulonephritis represents a diverse group of kidney disorders caused by dysregulated immune responses and constitutes a major contributor to chronic kidney disease. Its pathogenesis can be conceptualized as a three-step cascade: aberrant activation of innate immunity through pattern-recognition receptors, inflammasome complexes, and complement pathways; adaptive immune dysregulation characterized by imbalanced B- and T-cell responses and the production of pathogenic autoantibodies; and terminal effector injury involving complement-mediated damage and progressive fibrosis. This narrative review summarizes current advances in anti-inflammatory biologics that intervene at these critical points across a broad spectrum of entities, including IgA nephropathy (IgAN), membranous nephropathy (MN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), minimal change nephropathy (MCN), anti-glomerular basement membrane (anti-GBM) disease, ANCA-associated vasculitis (AAV), and C3 glomerulopathy (C3G). Therapies including cytokine inhibitors targeting TNF-α or IL-6, B-cell–depleting antibodies such as anti-CD20, plasma cell–directed agents, and complement blockers against C5 or Factor B have demonstrated clinical benefits in IgAN, MN, and LN, where evidence from randomized controlled trials supports their efficacy in reducing proteinuria and preserving renal function. For other entities such as FSGS, MCN, anti-GBM disease, and C3G, the evidence remains preliminary, based largely on case reports, preclinical models, or early-phase trials. Despite therapeutic advances, challenges persist regarding efficacy variability, infection risks, and financial burden. Future research aims to achieve precision therapy through multi-omics–based stratification, next-generation biologics such as bispecific antibodies and gene therapies, and optimized drug delivery systems, steering immune-mediated glomerulonephritis management toward truly disease-modifying treatment.

Background: Pseudotime inference has become a standard approach for reconstructing dynamic biological processes from single-cell transcriptomic data. However, after a pseudotemporal ordering has been established, systematically identifying and interpreting gene expression trends along pseudotime remains challenging. Existing approaches often rely on clustering-based heuristics or subjective parameter choices, which can compromise interpretability, reproducibility, and scalability in large datasets. Results: We present scTrends , an automated and interpretable framework for gene-level trend classification and strength quantification along a given pseudotime trajectory. Importantly, scTrends does not perform pseudotime inference; instead, it operates downstream of established pseudotime methods to characterize expression dynamics once a temporal ordering is available. scTrends models pseudotime-binned gene expression profiles using generalized additive models and assigns genes to predefined temporal trend categories through a hierarchical, rule-based procedure combined with empirical significance testing, data-adaptive parameter selection, and quantitative assessment of trend strength. This enables simultaneous identification of the direction, shape, and magnitude of gene expression changes along pseudotime. We applied scTrends tothree distinct datasets: human PBMC, human brain, and mouse pancreas, using three different pseudotime inference methods ( CytoTRACE v2, Monocle3 , and scVelo , respectively). scTrends systematically characterized gene expression dynamics during T cell differentiation, oligodendrocyte precursor differentiation, and pancreatic endocrine cell maturation. The analysis revealed diverse monotonic, non-monotonic, and complex expression patterns, with varying strengths, consistent with known biological processes. Benchmarking analyses further demonstrate that scTrends is computationally efficient and scalable to large single-cell datasets, with modest memory requirements, making it suitable for diverse applications across a range of biological systems. Conclusions: scTrends provides a systematic, automated, and resource-efficient solution for gene-level trend analysis in single-cell pseudotime studies, enabling reproducible characterization of dynamic expression patterns across diverse biological systems.

Obesity can cause the progression of kidney disease through hemodynamic, structural, and metabolic changes, and predispose individuals to arterio-nephrosclerosis, diabetic nephropathy, and focal segmental glomerulosclerosis (FSGS), leading to chronic kidney disease (CKD). Obesity-Related Glomerulopathy (ORG) is defined as clinical obesity and biopsy-proven glomerulomegaly with or without the existence of FSGS. However, pathologic changes of ORG are not pathognomonic or specific. Glomerular hypertrophy, maladaptive segmental glomerulosclerosis, as well as in some cases diabetic-like changes may be seen secondary to any cause of acquired or congenital reduced nephron mass with compensatory hypertrophy as well as glomerular hypoxia. This review aims to provide a comprehensive overview of the mechanisms causing ORG and explore current diagnostic challenges and therapeutic strategies, emphasizing the role of weight management and emerging targeted therapies.

Key Points: Upregulation of Bmpr2 was identified as a central cause of glomerular endothelial cell activation and injury in lupus nephritis. Glomerular endothelial cells with elevated Bmpr2 expression promoted inflammatory differentiation of macrophages. C5a mediated the increase in Bmpr2 expression in glomerular endothelial cells. Background: Lupus nephritis, a severe complication of SLE, is closely associated with the abnormal activation of glomerular endothelial cells. Despite its significance, the core mechanisms underlying glomerular endothelial cell activation remain elusive. Methods: We performed single-nucleus RNA sequencing (snRNA-seq) on kidney tissues from lupus nephritis patients and mouse models to investigate transcriptional alterations in glomerular endothelial cells and validated our findings in two lupus nephritis models: pristane-induced lupus nephritis and murphy roths large/ lpr mice. Genetically modified mice and cultured cells were used to further validate the key discoveries. Results: Bmpr2 was identified as a critical regulator, showing significant upregulation in glomerular endothelial cells from both lupus nephritis patients and mouse models. Elevated Bmpr2 expression correlated with enhanced glomerular endothelial cell proliferation and migration and increased expression of adhesion molecules (Vcam1, Icam1). BMPR2 activated SMA- and MAD-related proteins-dependent pathways, leading to the upregulation of downstream targets ID1 and ID3, thereby promoting glomerular endothelial cell hyperactivation. Bmpr2 overexpression amplified glomerular endothelial cell proliferation and migration, whereas inhibition of inhibitor of DNA binding signaling by 4-[6-[4-[2-(4-Morpholinyl)ethoxy]phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]quinoline (DMH2) or endothelial-specific Bmpr2 knockout attenuated these effects. Moreover, targeting BMPR2 signaling reduced the infiltration of CD86 ⁺ macrophages into lupus nephritis kidneys. Coculture experiments confirmed that Bmpr2 -activated glomerular endothelial cells promoted macrophage differentiation into an inflammatory phenotype. Complement component C5a was identified as a critical upstream inducer of Bmpr2 in glomerular endothelial cells, and inhibition of C5a signaling with the C5aR1 antagonist PMX-53 effectively suppressed Bmpr2 upregulation. Conclusions: These findings highlight BMPR2 as a key regulator of glomerular endothelial cell injury and macrophage-mediated inflammation in lupus nephritis. Targeting BMPR2 or its upstream activators, such as C5a, effectively treated and improved lupus nephritis.

Background: The emergence of single-cell (SC) and spatial transcriptomics (ST) has revolutionized our understanding of gene expression dynamics in complex tissues. However, it also presents challenges for data analysis and visualization, particularly due to the complexity of ST data and the diversity of analysis platforms. The SCNT (Single-Cell, Single-Nucleus, and Spatial Transcriptomics Analysis and Visualization Tools) package was developed to address these challenges by providing an efficient and user-friendly tool for processing, analyzing, and visualizing SC and ST data. Results: SCNT is an R-based package that integrates widely used tools such as Seurat and ggplot2 , enabling seamless conversion between Seurat and H5ad formats. The package supports high-resolution spatial visualization, including customizable gene expression and clustering plots. SCNT also simplifies key data analysis steps, such as quality control, dimensionality reduction, and doublet detection, significantly enhancing workflow efficiency. We tested SCNT on publicly available PBMC dataset, Visum and Visium HD human kidney tissue data, demonstrating its effectiveness. Conclusions: SCNT offers a valuable tool for researchers exploring SC and ST data. Its simplicity, flexibility, and powerful visualization capabilities provide a streamlined workflow for both novice and advanced users. Future developments will focus on expanding support for additional ST platforms and enhancing mult-omics data integration.

Vascular access thrombosis (VAT) is a common complication in patients with end-stage renal disease (ESRD), significantly impacting hemodialysis efficacy and patient survival. Currently, temporary dialysis access is typically established via deep vein catheterization (VC), however, this method is highly invasive and associated with risks of infection and other complications. This study aims to explore the feasibility of using direct anastomosis indwelling needle puncture (DAINP) for temporary dialysis access. Between March 2023 and March 2024, patients VAT were recruited at Sir Run Run Shaw Hospital of Zhejiang University School of Medicine to undergo DAINP. Clinical data, including age, gender, dry and wet body weight, and blood biochemical parameters, were collected. Patient VA types, locations, and insertion vessels were documented. Detailed assessments and records of VAT were performed for all patients, including the distance of thrombus from the anastomosis, residual blood flow at the VA anastomosis, and corresponding selection of the DAINP insertion site. Ultrasound was utilized to measure and record the puncture depth. Concurrently, clinical data of patients undergoing venous catheterization (VC) for temporary dialysis access were collected. The operative time for both groups, defined as the interval from ultrasound assessment initiation to completion of the procedure, was recorded and compared. A total of 74 patients successfully underwent DAINP, with a 100% puncture success rate. Among them, 20 patients had residual blood flow at the VA stump, and the distance between the anastomosis and arterial flow was ≥ 1 cm. Patients with VA located at the elbow demonstrated the greatest puncture depth. Moreover, the operative time for the DAINP group was significantly shorter compared to the 17 patients who underwent VC for VAT during the same period. However, patients with VA located in the groin required a longer operative time for DAINP. This study demonstrates that DAINP provides a rapid and safe method for establishing temporary hemodialysis access in VAT patients, effectively reducing the invasiveness and risks associated with traditional VC.

1. The prevalence of kidney diseases is steadily rising worldwide, with limited therapeutic options available for most conditions. This limitation largely stems from our incomplete understanding of...

(1) Objective: Identification of potential genetic biomarkers for various glomerulonephritis (GN) subtypes and discovering the molecular mechanisms of GN. (2) Methods: four microarray datasets of GN were downloaded from Gene Expression Omnibus (GEO) database and merged to obtain the gene expression profiles of eight GN subtypes. Then, differentially expressed immune-related genes (DIRGs) were identified to explore the molecular mechanisms of GN, and single-sample gene set enrichment analysis (ssGSEA) was performed to discover the abnormal inflammation in GN. In addition, a nomogram model was generated using the R package “glmnet”, and the calibration curve was plotted to evaluate the predictive power of the nomogram model. Finally, deep learning (DL) based on a multilayer perceptron (MLP) network was performed to explore the characteristic genes for GN. (3) Results: we screened out 274 common up-regulated or down-regulated DIRGs in the glomeruli and tubulointerstitium. These DIRGs are mainly involved in T-cell differentiation, the RAS signaling pathway, and the MAPK signaling pathway. ssGSEA indicates that there is a significant increase in DC (dendritic cells) and macrophages, and a significant decrease in neutrophils and NKT cells in glomeruli, while monocytes and NK cells are increased in tubulointerstitium. A nomogram model was constructed to predict GN based on 7 DIRGs, and 20 DIRGs of each subtype of GN in glomeruli and tubulointerstitium were selected as characteristic genes. (4) Conclusions: this study reveals that the DIRGs are closely related to the pathogenesis of GN and could serve as genetic biomarkers in GN. DL further identified the characteristic genes that are essential to define the pathogenesis of GN and develop targeted therapies for eight GN subtypes.