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Hair follicle stem cells are regulated by dermal papilla fibroblasts, their principal signaling niche. Overactivation of Hedgehog signaling in the niche dramatically accelerates hair growth and induces follicle multiplication in mice. On single-cell RNA sequencing, dermal papilla fibroblasts increase heterogeneity to include new Wnt5ahigh states. Transcriptionally, mutant fibroblasts activate regulatory networks for Gli1, Alx3, Ebf1, Hoxc8, Sox18, and Zfp239. These networks jointly upregulate secreted factors for multiple hair morphogenesis and hair-growth-related pathways. Among these is non-conventional TGF-β ligand Scube3. We show that in normal mouse skin, Scube3 is expressed only in dermal papillae of growing, but not in resting follicles. SCUBE3 protein microinjection is sufficient to induce new hair growth, and pharmacological TGF-β inhibition rescues mutant hair hyper-activation phenotype. Moreover, dermal-papilla-enriched expression of SCUBE3 and its growth-activating effect are partially conserved in human scalp hair follicles. Thus, Hedgehog regulates mesenchymal niche function in the hair follicle via SCUBE3/TGF-β mechanism.

The aim of this study was to examine the biological activity and probiotic properties of lactic acid bacteria (LAB) isolated from sweet potato stalk kimchi (SPK). Various LAB and Bacillus spp. are active in the early stages of the fermentation of kimchi made from sweet potato stalk. Four strains of LAB were identified, including SPK2 (Levilactobacillus brevis ATCC 14869), SPK3 (Latilactobacillus sakei NBRC 15893), SPK8 and SPK9 (Leuconostoc mesenteroides subsp. dextranicum NCFB 529). SPK2, SPK3, SPK8, and SPK9 showed 64.64–94.23% bile acid resistance and 78.66–82.61% pH resistance. We identified over 106 CFU/mL after heat treatment at 75 °C. Four strains showed high antimicrobial activity to Escherichia coli and Salmonella Typhimurium with a clear zone of >11 mm. SPK2 had the highest antioxidative potentials, higher than the other three bacteria, with 44.96 μg of gallic acid equivalent/mg and 63.57% DPPH scavenging activity. These results demonstrate that the four strains isolated from sweet potato kimchi stalk show potential as probiotics with excellent antibacterial effects and may be useful in developing health-promoting products. [ABSTRACT FROM AUTHOR]

Cellular dynamics and fate decision in early human embryogenesis remain largely unknown owing to the challenges of performing studies in human embryos.sup.1. Here, we explored whole-genomes of 334 single-cell colonies and targeted deep sequences of 379 bulk tissues obtained from various anatomical locations of seven recently deceased adult human donors. Using somatic mutations as an intrinsic barcode, we reconstructed early cellular phylogenies that demonstrate (1) an endogenous mutational rate that is higher in the first cell division but decreases to approximately one per cell per cell division later in life; (2) universal unequal contribution of early cells to embryo proper, resulting from early cellular bottlenecks that stochastically set aside epiblast cells within the embryo; (3) examples of varying degrees of early clonal imbalances between tissues on the left and right sides of the body, different germ layers and specific anatomical parts and organs; (4) emergence of a few ancestral cells that will substantially contribute to adult cell pools in blood and liver; and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach also provides insights into the age-related mutational processes and loss of sex chromosomes in normal somatic cells. In sum, this study provides a foundation for future studies to complete cellular phylogenies in human embryogenesis. Adult human tissues from diverse sites around the body are used to reconstruct cellular phylogenies from early development, using somatic mutations as an internal barcode., Author(s): Seongyeol Park [sup.1] [sup.2] , Nanda Maya Mali [sup.3] , Ryul Kim [sup.1] , Jeong-Woo Choi [sup.3] [sup.4] , Junehawk Lee [sup.5] , Joonoh Lim [sup.1] , Jung Min [...]

The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.

In this study, the characteristics of ammonia and their effects on secondary particulate matter (PM) formation were analyzed by region in Korea in 2020. The NH3 concentration was high in GJ (11.4 ppb), a neighboring agricultural area, followed by DJ (9.0 ppb) and SE (8.6 ppb), which are located in urban areas. On the other hand, BI (2.6 ppb) and JI (4.5 ppb), which are background regions, demonstrated a lower concentration than other areas. Seasonally, ammonia was high in spring and summer, and it generally increased when human activities are active. Therefore, it is believed that the ammonia in the atmosphere not only changes depending on local emissions, but also based on temperature-dependent phase distribution characteristics. For SE and GJ, regions with relatively high ammonia concentrations, investigations into the effect of ammonia on secondary PM formation were conducted. In both regions, the ammonium-to-sulfate mole ratio tended to increase with increasing ammonia or PM2.5 concentration. It can be assumed that the PM2.5 concentration increases as nitrates are formed under the ammonia-sufficient condition. The adjusted gas ratio is generally greater than 4, indicating that there is a lot of free ammonia. Thus, it is estimated that a reduction in ammonia would not be effective to restrain nitrate formation. [ABSTRACT FROM AUTHOR]