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TCGH(TC4+GH4169)composite material was prepared by selective laser melting(SLM). The optimum forming process parameters of TCGH composite material were investigated, and the microstructure and mechanical properties of as-deposited samples and heat-treated samples were studied. The results show that the optimum process parameters for fabrication of TCGH composite material are scanning speed of 900 mm/s with laser power of 150 W, and density higher than 99.5%. The addition of GH4169 powder changes the solid phase transformation behavior of TC4 titanium alloy material, and the as-deposited structure shows obvious high temperature solidification characteristics, which makes the forming characteristics of progressive scanning overlap and layer-by-layer scanning accumulation obvious. The original coarse columnar β grain size along the printing direction is significantly reduced, and the tensile strength of the composite is improved. Compared with the as-deposited sample, the microstructure of the heat-treated sample is transformed into a near-equiaxed structure. At the same time, with the increase of heat treatment temperature, the dissolution of the second phase leads to the dominant solid solution strengthening effect of the composite material, which improves the tensile strength and plasticity of the composite material.

Cullin-RING E3 ubiquitin ligases (CRLs), the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells, represent core cellular machinery for executing protein degradation and maintaining proteostasis. Here, we asked what roles Cullin proteins play in human mesenchymal stem cell (hMSC) homeostasis and senescence. To this end, we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models: replicative senescent hMSCs, Hutchinson-Gilford Progeria Syndrome hMSCs, and Werner syndrome hMSCs. Among all family members, we found that CUL2 deficiency rendered hMSCs the most susceptible to senescence. To investigate CUL2-specific underlying mechanisms, we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells (hESCs). When we differentiated these into hMSCs, we found that CUL2 deletion markedly accelerates hMSC senescence. Importantly, we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2 (a known negative regulator of proliferation) through the substrate receptor protein APPBP2, which in turn down-regulates one of the canonical aging marker-P21waf1/cip1, and thereby delays senescence. Our work provides important insights into how CRL2APPBP2-mediated TSPYL2 degradation counteracts hMSC senescence, providing a molecular basis for directing intervention strategies against aging and aging-related diseases. [ABSTRACT FROM AUTHOR]

The testis is pivotal for male reproduction, and its progressive functional decline in aging is associated with infertility. However, the regulatory mechanism underlying primate testicular aging remains largely elusive. Here, we resolve the aging-related cellular and molecular alterations of primate testicular aging by establishing a single-nucleus transcriptomic atlas. Gene-expression patterns along the spermatogenesis trajectory revealed molecular programs associated with attrition of spermatogonial stem cell reservoir, disturbed meiosis and impaired spermiogenesis along the sequential continuum. Remarkably, Sertoli cell was identified as the cell type most susceptible to aging, given its deeply perturbed age-associated transcriptional profiles. Concomitantly, downregulation of the transcription factor Wilms' Tumor 1 (WT1), essential for Sertoli cell homeostasis, was associated with accelerated cellular senescence, disrupted tight junctions, and a compromised cell identity signature, which altogether may help create a hostile microenvironment for spermatogenesis. Collectively, our study depicts in-depth transcriptomic traits of non-human primate (NHP) testicular aging at single-cell resolution, providing potential diagnostic biomarkers and targets for therapeutic interventions against testicular aging and age-related male reproductive diseases. [ABSTRACT FROM AUTHOR]

A novel two-dimensional carbon allotrope has been proposed using density functional theory (DFT) calculations. The cell contains 24 carbon atoms and is composed of five-, six-, and seven-membered rings, named LC567. It is low in energy and has excellent dynamic, thermal, and mechanical stability. Our results demonstrate that the theoretical capacity of monolayer LC567 is up to 1117 mA h g−1, and the lithium diffusion barrier is also very low, around 0.18 eV, which is superior to graphene and most reported two-dimensional anode materials. In addition, LC567 exhibits quite low open circuit voltage during the process of Li ion insertion. For the bulk of LC567, it still exhibits high capacity and ideal open circuit voltage, revealing its potential application as an anode for lithium batteries. Meanwhile, we discuss the mechanism of the high capacity and low diffusion barrier of LC567 as an anode material for lithium batteries, and find that the high capacity and low diffusion barrier properties may be related to the pentagonal carbon rings (C5). [ABSTRACT FROM AUTHOR]

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth. [ABSTRACT FROM AUTHOR]

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence. [ABSTRACT FROM AUTHOR]