Association between estrogen and kidney function: population based evidence and mutual bidirectional Mendelian randomization study.

Background: Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear.

Methods: The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013-2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies.

Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis.

In this study, we integrated transcriptomic and metabolomic analyses to achieve a comprehensive understanding of the underlying mechanisms of diabetic cardiomyopathy (DCM) in a diabetic rat model. Functional and molecular characterizations revealed significant cardiac injury, dysfunction, and ventricular remodeling in DCM. A thorough analysis of global changes in genes and metabolites showed that amino acid metabolism, especially the breakdown of branched-chain amino acids (BCAAs) such as valine, leucine, and isoleucine, is highly dysregulated.

Structure of the Kaposi's sarcoma-associated herpesvirus gB in post-fusion conformation.

Discovered in 1994 in lesions of an AIDS patient, Kaposi's sarcoma-associated herpesvirus (KSHV) is a member of the gammaherpesvirus subfamily of the family, which contains a total of nine that infect humans. These viruses all contain a large envelope glycoprotein, glycoprotein B (gB), that is required for viral fusion with host cell membrane to initial infection. Although the atomic structures of five other human herpesviruses in their postfusion conformation and one in its prefusion conformation are known, the atomic structure of KSHV gB has not been reported.

Exploring the link between serum uric acid and colorectal cancer: Insights from genetic evidence and observational data.

Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide. Urate, known for its antioxidant properties, may influence CRC risk and prognosis, but research on this is limited. We used Mendelian randomization (MR) analysis to explore the causal relationship between serum urate levels and CRC risk.

Loss of Kmt2c or Kmt2d primes urothelium for tumorigenesis and redistributes KMT2A-menin to bivalent promoters.

Members of the KMT2C/D-KDM6A complex are recurrently mutated in urothelial carcinoma and in histologically normal urothelium. Here, using genetically engineered mouse models, we demonstrate that Kmt2c/d knockout in the urothelium led to impaired differentiation, augmented responses to growth and inflammatory stimuli and sensitization to oncogenic transformation by carcinogen and oncogenes. Mechanistically, KMT2D localized to active enhancers and CpG-poor promoters that preferentially regulate the urothelial lineage program and Kmt2c/d knockout led to diminished H3K4me1, H3K27ac and nascent RNA transcription at these sites, which leads to impaired differentiation.