Cell Type-Specific Expression of Long Noncoding RNAs in Human Diabetic Kidneys Identifies TARID as a Key Regulator of Podocyte Function.

This study provides a resource for kidney (cell type-specific) long noncoding (lnc)RNA expression and demonstrates the importance of lncRNAs in renal health. We identified 174 cell type-specific lncRNAs in the human kidney, with 54 showing altered expression in diabetic kidney disease. TCF21 antisense RNA inducing promoter demethylation (TARID), a podocyte-specific lncRNA upregulated in diabetic kidney disease, is crucial for actin cytoskeleton reorganization in podocytes.

Multimodal spatial transcriptomic characterization of mouse kidney injury and repair.

The transition from acute kidney injury to chronic kidney disease is characterized by significant changes in the cellular composition and molecular interactions within the kidney. Utilizing high-resolution Xenium and whole transcriptome Visium spatial transcriptomics platforms, we analyze over a million cells on 12 male mouse kidneys across six stages of renal injury and repair. We define and validate 20 major kidney cell populations and delineate distinct cellular neighborhoods through this multimodal spatial analysis.

Mosaic Loss of Y Chromosome Defines a Proximal Tubular Cell State Associated with Recovery from DGF and of Allograft Quality and Functional Reserve Post DCD Kidney Transplantation.

Objective: To determine the drivers of proximal tubular cell regeneration and repair over time in the setting of recovery from delayed graft function (DGF) post donation after cardiac death (DCD) kidney transplantation.

Background: DCD Kidney allografts are at increased risk of graft loss. Despite this, due to organ shortages, DCD transplantation is increasing, which offers a novel and valuable platform for the study of adaptive/maladaptive repair mechanisms after injury.

Effect of urolithin A on intracellular survival of by regulating AKT-FOXO1-mediated autophagy.

Tuberculosis (TB), resulting from (Mtb), is one of the leading causes of morbidity and mortality in humans worldwide. Host-directed therapy (HDT) is a novel approach for treating TB, particularly those with drug resistance. Urolithin A (UroA) produced through bioconversion of plant-derived ellagic acid by gut microbes has been proven to have multiple beneficial effects in a variety of diseases without showing undesired adverse reactions.

Underlying mechanisms and treatment of acetaminophen‑induced liver injury (Review).

Acetaminophen (APAP) is safe at therapeutic doses; however, when ingested in excess, it accumulates in the liver and leads to severe hepatotoxicity, which in turn may trigger acute liver failure (ALF). This is known as APAP poisoning and is a major type of drug‑related liver injury. In the United States, APAP poisoning accounts for ≥50% of the total number of ALF cases, making it one of the most common triggers of ALF.

Troglitazone Reduction of Intracellular Mycobacterium tuberculosis Survival Via Macrophage Autophagy Through LKB1-AMPKα Signaling.

Tuberculosis caused by Mycobacterium tuberculosis (Mtb), results in significant disease and death worldwide. Host-directed therapy, including conventional drugs, is a promising antituberculosis strategy that shows synergistic antibacterial effects when combined with antituberculosis drugs. Here, the mycobactericidal effect of 3 antidiabetic drugs was examined.

Multiomics profiling of mouse polycystic kidney disease progression at a single-cell resolution.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to kidney failure. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single-nucleus multimodal atlas of an orthologous mouse PKD model at early, mid, and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes.

Histopathologic Analysis of Human Kidney Spatial Transcriptomics Data: Toward Precision Pathology.

The application of spatial transcriptomics (ST) technologies is booming and has already yielded important insights across many different tissues and disease models. In nephrology, ST technologies have helped to decipher the cellular and molecular mechanisms in kidney diseases and have allowed the recent creation of spatially anchored human kidney atlases of healthy and diseased kidney tissues. During ST data analysis, the computationally annotated clusters are often superimposed on a histologic image without their initial identification being based on the morphologic and/or spatial analyses of the tissues and lesions.

Injury-induced Foxm1 expression in the mouse kidney drives epithelial proliferation by a cyclin F-dependent mechanism.

Acute kidney injury (AKI) strongly upregulates the transcription factor Foxm1 in the proximal tubule in vivo, and Foxm1 drives epithelial proliferation in vitro. Here, we report that deletion of Foxm1 either with a nephron-specific Cre driver or by inducible global deletion reduced proximal tubule proliferation after ischemic injury in vivo. Foxm1 deletion led to increased AKI to chronic kidney disease transition, with enhanced fibrosis and ongoing tubule injury 6 weeks after injury.

A genetically inducible endothelial niche enables vascularization of human kidney organoids with multilineage maturation and emergence of renin expressing cells.

Vascularization plays a critical role in organ maturation and cell-type development. Drug discovery, organ mimicry, and ultimately transplantation hinge on achieving robust vascularization of in vitro engineered organs. Here, focusing on human kidney organoids, we overcame this hurdle by combining a human induced pluripotent stem cell (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing a role in endothelial cell development) that directs endothelial differentiation in vitro, with a non-transgenic iPSC line in suspension organoid culture.

Multi-omics profiling of mouse polycystic kidney disease progression at a single cell resolution.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to end-stage kidney disease. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single nucleus multimodal atlas of an orthologous mouse PKD model at early, mid and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes.

Transcriptomic, epigenomic, and spatial metabolomic cell profiling redefines regional human kidney anatomy.

A large-scale multimodal atlas that includes major kidney regions is lacking. Here, we employed simultaneous high-throughput single-cell ATAC/RNA sequencing (SHARE-seq) and spatially resolved metabolomics to profile 54 human samples from distinct kidney anatomical regions. We generated transcriptomes of 446,267 cells and chromatin accessibility profiles of 401,875 cells and developed a package to analyze 408,218 spatially resolved metabolomes.

Nomogram for predicting the risk of nonalcoholic fatty liver disease in older adults in Qingdao, China: A cross-sectional study.

Background And Objectives: To explore the risk factors for non-alcoholic fatty liver disease (NAFLD) and to establish a non-invasive tool for the screening of NAFLD in an older adult population.

Methods And Study Design: A total of 131,161 participants were included in this cross-sectional study. Participants were randomly divided into training and validation sets (7:3).

depletion induces inflammation and apoptosis in injured renal proximal tubule epithelial cells.

In the aftermath of acute kidney injury (AKI), surviving proximal tubule epithelia repopulate injured tubules to promote repair. However, a portion of cells fail to repair [termed failed-repair proximal tubule cells (FR-PTCs)] and exert ongoing proinflammatory and profibrotic effects. To better understand the molecular drivers of the FR-PTC state, we reanalyzed a mouse ischemia-reperfusion injury single-nucleus RNA-sequencing (snRNA-seq) atlas to identify Traf2 and Nck interacting kinase () to be exclusively expressed in FR-PTCs but not in healthy or acutely injured proximal tubules after AKI (2 and 6 wk) in mice.

Electronic structure and magnetothermal properties of two-dimensional ScCl.

Two-dimensional ferromagnetic materials with intrinsic half-metallic properties have strong application advantages in nanoscale spintronics. Herein, density functional theory calculations show that monolayer ScCl is a ferromagnetic metallic material when undoped ( = 0), and the transition from metal to half-metal occurs with the continuous doping of holes. On the contrary, as the concentration of doped electrons increases, the system will exhibit metallic characteristics, which is particularly evident from a variation in spin polarizability.

High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing.

Emerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based in situ sequencing (dRNA HybISS, Cartana part of 10xGenomics) to compare male and female healthy mouse kidneys and the male kidney injury and repair timecourse. A pre-selected panel of 200 genes is used to identify cell state dynamics patterns during injury and repair.

Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing.

Renal proximal tubule epithelial cells have considerable intrinsic repair capacity following injury. However, a fraction of injured proximal tubule cells fails to undergo normal repair and assumes a proinflammatory and profibrotic phenotype that may promote fibrosis and chronic kidney disease. The healthy to failed repair change is marked by cell state-specific transcriptomic and epigenomic changes.

Epigenetic reprogramming driving successful and failed repair in acute kidney injury.

Acute kidney injury (AKI) causes epithelial damage followed by subsequent repair. While successful repair restores kidney function, this process is often incomplete and can lead to chronic kidney disease (CKD) in a process called failed repair. To better understand the epigenetic reprogramming driving this AKI-to-CKD transition we generated a single nucleus multiomic atlas for the full mouse AKI time course, consisting of ~280,000 single nucleus transcriptomes and epigenomes.

Sequencing of Physically Interacting Cells in Human Kidney Allograft Rejection to Infer Contact-dependent Immune Cell Transcription.

Background: Rejection requires cell-cell contact involving immune cells. Inferring the transcriptional programs of cell-cell interactions from single-cell RNA-sequencing (scRNA-seq) data is challenging as spatial information is lost.

Methods: We combined a CD45 pos enrichment strategy with Cellular Indexing of Transcriptomes and Epitopes by sequencing based quantification of leukocyte surface proteins to analyze cell-cell interactions in 11 human kidney transplant biopsies encompassing a spectrum of rejection diagnoses.

A single-cell multiomic analysis of kidney organoid differentiation.

Kidney organoids differentiated from pluripotent stem cells are powerful models of kidney development and disease but are characterized by cell immaturity and off-target cell fates. Comparing the cell-specific gene regulatory landscape during organoid differentiation with human adult kidney can serve to benchmark progress in differentiation at the epigenome and transcriptome level for individual organoid cell types. Using single-cell multiome and histone modification analysis, we report more broadly open chromatin in organoid cell types compared to the human adult kidney.

Drug‑resistant : From molecular mechanisms to potential therapeutics (Review).

Bacterial drug resistance is increasingly becoming an important problem that needs to be solved urgently in modern clinical practices. Infection caused by is a serious threat to the life and health of patients. The drug resistance rate of strains is increasing, thus research on the drug resistance of has also seen an increase.

Ferromagnetic vanadium disulfide VS monolayers with high Curie temperature and high spin polarization.

The structural, electronic, and magnetic properties of vanadium disulfide VS monolayers were investigated using first-principles calculations and Monte Carlo (MC) simulations. The results of molecular dynamics simulations and phonon dispersion showed that the VS monolayer has good dynamic and thermodynamic stabilities. Based on the results of the band structure, we also explore the effect of carrier concentrations on the spin gap, spin polarization and the direction of the easy magnetic axis.