Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133+TRPV4high Endothelial Subpopulation in Regulating Flow-Induced Vascular Tone in Mice.

BACKGROUND: Single-cell RNA-Seq analysis can determine the heterogeneity of cells between different tissues at a single-cell level. Coronary artery endothelial cells (ECs) are important to coronary blood flow. However, little is known about the heterogeneity of coronary artery ECs, and cellular identity responses to flow. Identifying endothelial subpopulations will contribute to the precise localization of vascular endothelial subpopulations, thus enabling the precision of vascular injury treatment. METHODS: Here, we performed a single-cell RNA sequencing of 31 962 cells and functional assays of 3 branches of the coronary arteries (right coronary artery/circumflex left coronary artery/anterior descending left coronary artery) in wild-type mice. RESULTS: We found a compendium of 7 distinct cell types in mouse coronary arteries, mainly ECs, granulocytes, cardiac myocytes, smooth muscle cells, lymphocytes, myeloid cells, and fibroblast cells, and showed spatial heterogeneity between arterial branches. Furthermore, we revealed a subpopulation of coronary artery ECs, CD133+TRPV4high ECs. TRPV4 (transient receptor potential vanilloid 4) in CD133+TRPV4high ECs is important for regulating vasodilation and coronary blood flow. CONCLUSIONS: Our study elucidates the nature and range of coronary arterial cell diversity and highlights the importance of coronary CD133+TRPV4high ECs in regulating coronary vascular tone.

Aminopoly(carboxylic acid)-Functionalized PolyHIPE Beads toward Eliminating Trace Heavy Metal Ions from Water.

Many advanced materials are designed for the removal of heavy metal ions from water. However, materials for eliminating trace heavy metal ions from wastewater to meet drinking water standards remain a major challenge. Herein, epoxy group-functionalized open-cellular beads are synthesized by UV polymerization of a water-in-oil-in-water system. The epoxy groups are further transformed into diethylenetriaminepentaacetic acid (DTPA) with hexamethylene diamine as a bridging agent. The resulting material (DTPA@polyHIPE beads) can eliminate trace Cu(II), Cr(III), Pb(II), Fe(III), or Cd(II) from water. When 0.15 g of DTPA@polyHIPE beads are used to adsorb metal ions of 20 mg in 100 mL of water, the residue concentrations of Cu(II), Cr(III), Pb(II), Fe(III), and Cd(II) are reduced to 0.08, 0.06, 0.02, 0.09, and 0.07 mg/L, respectively. The adsorption efficiencies of the beads for these ions are all higher than 99.55%. The adsorbent is durable and exhibits good recyclability by retaining an adsorption capacity of ≥91% after 5 cycles. The negative values of ΔG in the adsorption process indicate that the adsorption is feasible and spontaneous. The chemical adsorption follows the Freundlich adsorption model, indicating a multilayer heterogeneous adsorption. The DTPA@polyHIPE beads have a great potential application in dealing with trace heavy metal ion polluted water.

Complement Factor C1q Mediates Vascular Endothelial Dysfunction in STZ-Induced Diabetic Mice.

Diabetes is a significant global public health issue with implications for vascular endothelial cells (ECs) dysfunction and the subsequent development and advancement of diabetes complications. This study aims to compare the cellular and molecular properties of the aorta in normal and streptozotocin (STZ)-induced diabetic mice, with a focus on elucidating potential mechanism underlying EC dysfunction. Here, we performed a single-cell RNA sequencing survey of 32,573 cells from the aorta of normal and STZ-induced diabetic mice. We found a compendium of 10 distinct cell types, mainly ECs, smooth muscle cells, fibroblast, pericyte, immune cells, and stromal cells. As the diabetes condition progressed, we observed a subpopulation of aortic ECs that exhibited significantly elevated expression of complement (C) molecule C1qa compared with their healthy counterparts. This increased expression of C1qa was found to induce reactive oxygen species (ROS) production, facilitate EC migration and increased permeability, and impair the vasodilation within the aortic segment of mice. Furthermore, AAV-Tie2-shRNA-C1qa was administered into diabetic mice by tail vein injection, showing that inhibition of C1qa in the endothelium led to a reduction in ROS production, decreased vascular permeability, and improved vasodilation. Collectively, these findings highlight the crucial involvement of C1qa in endothelial dysfunction associated with diabetes.

Unraveling the mechanism of flower color variation in Brassica napus by integrated metabolome and transcriptome analyses.

Brassica napus is one of the most important oil crops in the world. Breeding oilseed rape with colorful flowers can greatly enhance the ornamental value of B. napus and thus improve the economic benefits of planting. As water-soluble flavonoid secondary metabolites, anthocyanins are very important for the synthesis and accumulation of pigments in the petals of plants, giving them a wide range of bright colors. Despite the documentation of over 60 distinct flower shades in B. napus, the intricacies underlying flower color variation remain elusive. Particularly, the mechanisms driving color development across varying flower color backgrounds necessitate further comprehensive investigation. This research undertook a comprehensive exploration through the integration of transcriptome and metabolome analyses to pinpoint pivotal genes and metabolites underpinning an array of flower colors, including beige, beige-red, yellow, orange-red, deep orange-red, white, light-purple, and purple. First, we used a two-way BLAST search to find 275 genes in the reference genome of B. napus Darmor v10 that were involved in making anthocyanins. The subsequent scrutiny of RNA-seq outcomes underscored notable upregulation in the structural genes F3H and UGT, alongside the MYB75, GL3, and TTG1 transcriptional regulators within petals, showing anthocyanin accumulation. By synergizing this data with a weighted gene co-expression network analysis, we identified CHS, F3H, MYB75, MYB12, and MYB111 as the key players driving anthocyanin synthesis in beige-red, orange-red, deep orange-red, light-purple, and purple petals. By integrating transcriptome and weighted gene co-expression network analysis findings with anthocyanin metabolism data, it is hypothesized that the upregulation of MYB75, which, in turn, enhances F3H expression, plays a pivotal role in the development of pigmented oilseed rape flowers. These findings help to understand the transcriptional regulation of anthocyanin biosynthesis in B. napus and provide valuable genetic resources for breeding B. napus varieties with novel flower colors.

Ru-regulated electronic structure CoNi-MOF nanosheets advance water electrolysis kinetics in alkaline and seawater media.

Herein, an ion-exchange strategy is utilized to greatly improve the kinetics of hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) by Ru-modified CoNi- 1,3,5-Benzenetricarboxylic acid (BTC)-metal organic framework nanosheets (Ru@CoNi-MOF). Due to the higher Ni active sites and lower electron transfer impedance, Ru@CoNi-MOF catalyst requires the overpotential as low as 47 and 279 mV, at a current density of 10 mA/cm2 toward HER and OER, respectively. Significantly, the mass activity of Ru@CoNi-MOF for HER and OER are 25.9 and 10.6 mA mg-1, nearly 15.2 and 8.8 times higher than that of Ni-MOF. In addition, the electrolyzer of Ru@CoNi-MOF demonstrates exceptional electrolytic performance in both KOH and seawater environment, surpasses the commercial Pt/C||IrO2 couple. Theoretical calculations prove that introducing Ru atoms in - CoNi-MOF modulates the electronic structure of Ni, optimizes adsorption energy for H* and reduces energy barrier of metal organic frameworks (MOFs). This modification significantly improves the kinetic rate of the Ru@CoNi-MOF during water splitting. Certainly, this study highlights the utilization of MOF nanosheets as advanced HER/OER electrocatalysts with immense potential, and will paves a way to develop more efficient MOFs for catalytic applications.

Genetics in Ischemic Stroke: Current Perspectives and Future Directions.

Ischemic stroke is a heterogeneous condition influenced by a combination of genetic and environmental factors. Recent advancements have explored genetics in relation to various aspects of ischemic stroke, including the alteration of individual stroke occurrence risk, modulation of treatment response, and effectiveness of post-stroke functional recovery. This article aims to review the recent findings from genetic studies related to various clinical and molecular aspects of ischemic stroke. The potential clinical applications of these genetic insights in stratifying stroke risk, guiding personalized therapy, and identifying new therapeutic targets are discussed herein.

TRPC5 is essential in endothelium-dependent contraction of aorta from diet-induced obese mice.

The role of the Ca2+-permeable ion channel TRPC5 in regulating vasocontraction in obesity is poorly understood. Here, we investigated whether TRPC5 contributes to vascular dysfunction in obesity by promoting endothelium-dependent contraction via activation of cytosolic phospholipase A2 (cPLA2) in the aortic endothelial cells of obese mice. Acetylcholine-induced endothelium-dependent relaxation and contraction in the aorta were measured using wire myography. PLA2 activity was measured by the fluorogenic PLA2 substrate Bis-BODIPY™ FL C11-PC. The intracellular Ca2+ level in response to acetylcholine was measured by Fluo-4 fluorescence. Endothelium-derived contracting factors were assessed by enzyme immunoassay. Diet-induced obesity (DIO) attenuated endothelium-dependent vasodilation, enhanced endothelium-dependent contraction (EDC), and increased the expression of TRPC5 in the mouse aorta. Activation of TRPC5 promoted EDC in the wild-type mouse aorta, whereas pharmacological inhibition and genetic knockout of TRPC5 decreased EDC in the DIO mouse aorta. Moreover, cPLA2 phosphorylation and activity were higher in aortic endothelial cells from DIO mice, and this was attenuated by inhibition and knockout of TRPC5. Cyclooxygenase 2 (COX-2) expression was increased in DIO mouse endothelium and was decreased by a TRPC5 inhibitor and knockout of TRPC5. Release of prostaglandins F2α (PGF2α) and E2 (PGE2) was involved in TRPC5-regulated EDC in DIO mice. This study demonstrated that TRPC5 contributes to endothelial and vascular dysfunction and is involved in EDC through activation of cPLA2 and enhanced COX-2-PGF2α/PGE2 levels in DIO mice.