Objectives: There are significant clinical challenges associated with alopecia treatment, including poor efficiency of related drugs and insufficient hair follicles (HFs) for transplantation. Skin‐derived precursors (SKPs) exhibit great potential as stem cell‐based therapies for hair regeneration; however, the proliferation and hair‐inducing capacity of SKPs gradually decrease during culturing.Materials and Methods: We describe a 3D co‐culture system accompanied by kyoto encyclopaedia of genes and genomes and gene ontology enrichment analyses to determine the key factors and pathways that enhance SKP stemness and verified using alkaline phosphatase assays, Ki‐67 staining, HF reconstitution, Western blot and immunofluorescence staining. The upregulated genes were confirmed utilizing corresponding recombinant protein or small‐interfering RNA silencing in vitro, as well as the evaluation of telogen‐to‐anagen transition and HF reconstitution in vivo.Results: The 3D co‐culture system revealed that epidermal stem cells and adipose‐derived stem cells enhanced SKP proliferation and HF regeneration capacity by amphiregulin (AREG), with the promoted stemness allowing SKPs to gain an earlier telogen‐to‐anagen transition and high‐efficiency HF reconstitution. By contrast, inhibitors of the phosphoinositide 3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) pathways downstream of AREG signalling resulted in diametrically opposite activities.Conclusions: By exploiting a 3D co‐culture model, we determined that AREG promoted SKP stemness by enhancing both proliferation and hair‐inducing capacity through the PI3K and MAPK pathways. These findings suggest AREG therapy as a potentially promising approach for treating alopecia.

Background: The ability to assess adverse outcomes in patients with community-acquired pneumonia (CAP) could improve clinical decision-making to enhance clinical practice, but the studies remain insufficient, and similarly, few machine learning (ML) models have been developed.Objective: We aimed to explore the effectiveness of predicting adverse outcomes in CAP through ML models.Methods: A total of 2,302 adults with CAP who were prospectively recruited between January 2012 and March 2015 across three cities in South America were extracted from DryadData. After a 70:30 training set: test set split of the data, nine ML algorithms were executed and their diagnostic accuracy was measured mainly by the area under the curve (AUC). The nine ML algorithms included decision trees, random forests, extreme gradient boosting (XGBoost), support vector machines, Naïve Bayes, K-nearest neighbors, ridge regression, logistic regression without regularization, and neural networks. The adverse outcomes included hospital admission, mortality, ICU admission, and one-year post-enrollment status.Results: The XGBoost algorithm had the best performance in predicting hospital admission. Its AUC reached 0.921, and accuracy, precision, recall, and F1-score were better than those of other models. In the prediction of ICU admission, a model trained with the XGBoost algorithm showed the best performance with AUC 0.801. XGBoost algorithm also did a good job at predicting one-year post-enrollment status. The results of AUC, accuracy, precision, recall, and F1-score indicated the algorithm had high accuracy and precision. In addition, the best performance was seen by the neural network algorithm when predicting death (AUC 0.831).Conclusions: ML algorithms, particularly the XGBoost algorithm, were feasible and effective in predicting adverse outcomes of CAP patients. The ML models based on available common clinical features had great potential to guide individual treatment and subsequent clinical decisions.

The skin is a multi‐layered structure composed of the epidermis, dermis and hypodermis. The epidermis originates entirely from the ectoderm, whereas the dermis originates from various germ layers depending on its anatomical location; thus, there are different developmental patterns of the skin. Although the regulatory mechanisms of epidermal formation are well understood, mechanisms regulating dermis development are not clear owing to the complex origin. It has been shown that several morphogenetic pathways regulate dermis development. Of these, transforming growth factor‐β (TGF‐β) and fibroblast growth factor (FGF) signalling pathways are the main modulators regulating skin cell induction, fate decision, migration and differentiation. Recently, the successful generation of human skin by modulating TGF‐β and FGF signals further demonstrated the irreplaceable roles of these pathways in skin regeneration. This review provides evidence of the role of TGF‐β and FGF signalling pathways in the development of different skin layers, especially the disparate dermis of different body regions. This review also provides new perspectives on the distinct developmental patterns of skin and explores new ideas for clinical applications in the future.

Numerous researches have demonstrated the therapeutic potential of adipose‐derived stem cell exosomes (ADSC‐Exos) in promoting wound healing. In this study, we aimed to investigate the impact of ADSC‐Exos on diabetic wound fibroblasts and elucidate its possible mechanisms. CCK‐8, Edu, cell scratch, and Transwell tests were used to evaluate the function of ADSC‐Exos on rat skin fibroblasts (RSFs) in high‐glucose (HG) medium. The targeting effect of ADSC‐Exo‐derived microRNA (miRNA) and TGF‐ β 1 was assessed using bioinformatic analysis and then confirmed with western blot and dual luciferase reporter assays. ADSC‐Exos, miR‐204‐5p mimic, and anti‐miR‐204‐5p mimic were used to stimulate RSFs, and the levels of TGF‐ β 1/Smad pathway were analyzed by western blot. In vivo, digital photo and tissue section staining were used to evaluate the therapeutic effect of ADSC‐Exos on diabetic wounds. The data showed that ADSC‐Exos enhance the proliferation and migration of fibroblasts under HG conditions, reduce excessive myofibroblast differentiation and collagen deposition, and promote scarless healing of diabetic wounds. Additionally, miR‐204‐5p in ADSC‐Exos targets TGF‐ β 1 to inhibit p‐Smad2/3, Col I, and alpha‐smooth muscle actin ( α ‐SMA), thereby reducing fibrosis. These findings suggest that ADSC‐Exos have potential prospects for promoting diabetic wound healing.

Chronic and acute stress caused by emotional or physical insults can affect the function of other organs via the brain‐body axis. As one of the smallest organs in mammalian, hair follicles are highly susceptible to stress. Under stress, the sympathetic nerves release norepinephrine (NA), which acts directly on the β‐2 adrenergic receptors on melanocyte stem cells (MeSCs) within the hair follicles, causing the MeSCs to lose quiescence and enter a rapid proliferation state followed by differentiation and migration, leading to rapid loss of MeSCs and, ultimately, grey hair. Here, we screened out β‐2 blockers forming the ZINC 15 compound database, found a natural product isoliensinine, and was effective in preventing stress‐induced hair greying in mice. The study sheds light on the development of products that use natural compounds to prevent stress‐induced hair greying.