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Musk secreted by male forest musk deer (Moschus berezovskii) musk glands is an invaluable component of medicine and perfume. Musk secretion depends on musk gland maturation; however, the mechanism of its development remains elusive. Herein, using single cell multiome ATAC + gene expression coupled with several bioinformatic analyses, a dynamic transcriptional cell atlas of musk gland development was revealed, and key genes and transcription factors affecting its development were determined. Twelve cell types, including two different types of acinar cells (Clusters 0 and 10) were identified. Single‐nucleus RNA and single‐nucleus ATAC sequencing analyses revealed that seven core target genes associated with musk secretion (Hsd17b2, Acacb, Lss, Vapa, Aldh16a1, Aldh7a1, and Sqle) were regulated by 12 core transcription factors (FOXO1, CUX2, RORA, RUNX1, KLF6, MGA, NFIC, FOXO3, ETV5, NR3C1, HSF4, and MITF) during the development of Cluster 0 acinar cells. Kyoto Encyclopedia of Genes and Genomes enrichment showed significant changes in the pathways associated with musk secretion during acinar cell development. Gene set variation analysis also revealed that certain pathways associated with musk secretion were enriched in 6‐year‐old acinar cells. A gene co‐expression network was constructed during acinar cell development to provide a precise understanding of the connections between transcription factors, genes, and pathways. Finally, intercellular communication analysis showed that intercellular communication is involved in musk gland development. This study provides crucial insights into the changes and key factors underlying musk gland development, which serve as valuable resources for studying musk secretion mechanisms and promoting the protection of this endangered species. [ABSTRACT FROM AUTHOR]

Urban landscape patterns significantly impact land surface temperature (LST) and the urban heat island (UHI) effect. This study employs the boosted regression tree (BRT) model and variance partitioning analysis to examine the contributions and relationships of two-dimensional and three-dimensional building and vegetation patterns to LST, and their marginal effects at different heights. The results show that the dominant indicators affecting LST differ between buildings and vegetation, with three-dimensional building features being slightly more important than two-dimensional features (percentage of landscape of buildings) and two-dimensional vegetation features (three-dimensional green index) having a greater impact than three-dimensional features. When both buildings and vegetation are considered, building patterns still have significant explanatory power. Building height differences influence each indicator's contribution and marginal effects on LST, with lower-height areas seeing a joint dominance of buildings and vegetation on LST changes, and higher-height areas showing greater impact from vegetation indicators. Increasing the percentage of landscape of vegetation (PLAND_V) provides the best cooling effect in lower-building-height areas, but in higher-building-height areas, the cooling effect weakens, requiring additional vegetation indicators to assist in cooling. [ABSTRACT FROM AUTHOR]

Background: Myeloid cells play critical roles in the regulation of myocardial injury and repair. Clonal hematopoiesis (CH)‐related mutations in genes, such as Ten‐eleven Translocation 2 (TET2), can impair myeloid cells and are associated with increased risk of cardiovascular disease (CVD). How Tet2 loss‐of‐function (LOF) impacts myeloid cells and disrupts normal myocardial repair remains unclear. Methods: We established ischemia‐induced myocardial infarction (MI) in a myeloid‐specific Tet2‐deficient mouse model. The echocardiographic assessment was conducted to evaluate the cardiac function. Histological analysis was performed to evaluate morphological changes in infarcted areas and fibrosis. To monitor the dynamic changes of myeloid cells in cardiac tissues during cardiac remodeling after MI, we performed longitudinal analysis on subsets of myeloid cells using flow cytometry. We performed immunofluorescence (IF) staining to examine the DNA damage and genome instability caused by Tet2 LOF. Gene expression was assessed by real‐time qRT‐PCR. Stimulator of Interferon Genes (STING) pathway activation was assessed using various methods, including Western blotting, flow cytometry, ELISA and IF staining of key signaling proteins involved in this pathway. Additionally, H‐151 was used as a pharmacological tool to antagonize augmented STING activation in the murine MI model. Results: We observed a substantial increase of neutrophils in the post‐MI mice, which contributes to adverse outcomes during heart repair. Mechanistically, Tet2‐deficient myeloid cells exhibited increased genome instability, accompanied with augmented activation of the STING pathway. Furthermore, the use of H‐151 a covalent STING binder that targets the cysteine residue at position 91 and functions as a potent STING antagonist, led to a substantial decrease in neutrophil populations in Tet2‐deficient mice following myocardial infarction, thereby reversing adverse cardiac outcomes. Conclusion: Our novel findings establish the rationale for targeting the cGAS‐STING pathway as a promising therapeutic strategy to mitigate cardiovascular disease risk in individuals with clonal hematopoiesis harboring TET2 loss‐of‐function mutations. Highlights: Myeloid‐specific Tet2 depletion promotes neutrophil expansion upon myocardium infarction (MI);Tet2‐deficient myeloid cells exhibit increased genome instability and cGAS‐STING overactivation;STING antagonist H‐151 treatment reduces neutrophil expansion in Tet2‐deficient mice after MI and mitigates deleterious cardiac outcomes. [ABSTRACT FROM AUTHOR]

Connexin-43 (Cx43) gap junctions provide intercellular coupling, which ensures rapid action potential propagation and synchronized heart contraction. Alterations in Cx43 localization and reductions in gap junction coupling occur in failing hearts, contributing to ventricular arrhythmias and sudden cardiac death. Recent reports have found that an internally translated Cx43 isoform, GJA1-20k, is an auxiliary subunit for the trafficking of Cx43 in heterologous expression systems. Here, we have created a mouse model by using CRISPR technology to mutate a single internal translation initiation site in Cx43 (M213L mutation), which generates full-length Cx43, but not GJA1-20k. We found that [GJA1.sup.M213L/M213L] mice had severely abnormal electrocardiograms despite preserved contractile function, reduced total Cx43, and reduced gap junctions, and they died suddenly at 2 to 4 weeks of age. Heterozygous [GJA1.sup.M213L/WT] mice survived to adulthood with increased ventricular ectopy. Biochemical experiments indicated that cytoplasmic Cx43 had a half-life that was 50% shorter than membrane-associated Cx43. Without GJA1-20k, poorly trafficked Cx43 was degraded. The data support that GJA1-20k, an endogenous entity translated independently of Cx43, is critical for Cx43 gap junction trafficking, maintenance of Cx43 protein, and normal electrical function of the mammalian heart., Introduction Intercellular communication between cardiomyocytes via connexin-43 (Cx43) gap junctions enables the rapid spread of electrical signals and synchronous ventricular contraction. Oligomerization of 6 Cx43 molecules gives rise to a [...]

Cardiomyocyte T tubules are important for regulating ion flux. Bridging integrator 1 (BIN1) is a T-tubule protein associated with calcium channel trafficking that is downregulated in failing hearts. Here we find that cardiac T tubules normally contain dense protective inner membrane folds that are formed by a cardiac isoform of BIN1. In mice with cardiac Bin1 deletion, T-tubule folding is decreased, which does not change overall cardiomyocyte morphology but leads to free diffusion of local extracellular calcium and potassium ions, prolonging action-potential duration and increasing susceptibility to ventricular arrhythmias. We also found that T-tubule inner folds are rescued by expression of the BIN1 isoform BIN1+13+17, which promotes N-WASP-dependent actin polymerization to stabilize the T-tubule membrane at cardiac Z discs. BIN1+13+17 recruits actin to fold the T-tubule membrane, creating a 'fuzzy space' that protectively restricts ion flux. When the amount of the BIN1+13+17 isoform is decreased, as occurs in acquired cardiomyopathy, T-tubule morphology is altered, and arrhythmia can result.