BACKGROUND: Senescent human skin primary fibroblast (FB) models have been established for studying aging-related, proliferative, and inflammatory skin diseases. The aim of this study was to compare the transcriptome characteristics of human primary dermal FBs from children and the elderly with four senescence models. METHODS: Human skin primary FBs were obtained from healthy children (FB-C) and elderly donors (FB-E). Senescence models were generated by ultraviolet B irradiation (FB-UVB), D-galactose stimulation (FB-D-gal), atazanavir treatment (FB-ATV), and replication exhaustion induction (FB-P30). Flow cytometry, immunofluorescence staining, real-time quantitative polymerase chain reaction, co-culturing with immune cells, and bulk RNA sequencing were used for systematic comparisons of the models. RESULTS: In comparison with FB-C, FB-E showed elevated expression of senescence-related genes related to the skin barrier and extracellular matrix, proinflammatory factors, chemokines, oxidative stress, and complement factors. In comparison with FB-E, FB-UVB and FB-ATV showed higher levels of senescence and expression of the genes related to the senescence-associated secretory phenotype (SASP), and their shaped immune microenvironment highly facilitated the activation of downstream immune cells, including T cells, macrophages, and natural killer cells. FB-P30 was most similar to FB-E in terms of general transcriptome features, such as FB migration and proliferation, and aging-related characteristics. FB-D-gal showed the lowest expression levels of senescence-related genes. In comparisons with the single-cell RNA sequencing results, FB-E showed almost complete simulation of the transcriptional spectrum of FBs in elderly patients with atopic dermatitis, followed by FB-P30 and FB-UVB. FB-E and FB-P30 showed higher similarity with the FBs in keloids. CONCLUSIONS Each senescent FB model exhibited different characteristics. In addition to showing upregulated expression of natural senescence features, FB-UVB and FB-ATV showed high expression levels of senescence-related genes, including those involved in the SASP, and FB-P30 showed the greatest similarity with FB-E. However, D-galactose-stimulated FBs did not clearly present aging characteristics.
Humans ; Fibroblasts/drug effects* ; Cellular Senescence/physiology* ; Skin/metabolism* ; Child ; Transcriptome/genetics* ; Aged ; Ultraviolet Rays ; Cells, Cultured ; Galactose/pharmacology*

Emotion classification and recognition is a crucial area in emotional computing. Physiological signals, such as electroencephalogram (EEG), provide an accurate reflection of emotions and are difficult to disguise. However, emotion recognition still faces challenges in single-modal signal feature extraction and multi-modal signal integration. This study collected EEG, electromyogram (EMG), and electrodermal activity (EDA) signals from participants under three emotional states: happiness, sadness, and fear. A feature-weighted fusion method was applied for integrating the signals, and both support vector machine (SVM) and extreme learning machine (ELM) were used for classification. The results showed that the classification accuracy was highest when the fusion weights were set to EEG 0.7, EMG 0.15, and EDA 0.15, achieving accuracy rates of 80.19% and 82.48% for SVM and ELM, respectively. These rates represented an improvement of 5.81% and 2.95% compared to using EEG alone. This study offers methodological support for emotion classification and recognition using multi-modal physiological signals.
Humans ; Emotions/physiology* ; Electroencephalography ; Support Vector Machine ; Electromyography ; Signal Processing, Computer-Assisted ; Galvanic Skin Response/physiology* ; Machine Learning ; Male

Skin wound repair is critically regulated by peripheral nerves. Injury or dysfunction of these nerves represents a key factor impairing the healing of pathological wounds, such as diabetic ulcers and deep burns. The mechanisms by which peripheral nerves participate in cutaneous wound healing primarily involve modulation of immune responses, construction of stem cell niches, and promotion of angiogenesis. Sensory neurons initiate and mediate essential local immune responses, contribute to the epidermal stem cell microenvironment, and support regenerative potential. Sympathetic nerves bidirectionally regulate immune homeostasis via the release of various neuromodulators and precisely control the activation of hair follicle stem cells as well as the homeostasis of melanocyte stem cells. Schwann cells also play pivotal roles in immune modulation, balancing repair processes and mitigating scar formation. During revascularization, sensory and autonomic nerve terminals release neurotransmitters that precisely regulate vasomotor activity and angiogenesis, while Schwann cells facilitate the reconstruction of functional vascular networks via potent paracrine signaling. This review systematically summarizes the crucial roles of peripheral nerves in skin wound repair, with emphasis on their regulatory mechanisms in immune responses, stem cell activation and homeostasis, and vascular dynamics, thereby providing insights into the development of novel therapeutic strategies targeting peripheral nerve regulation.
Humans ; Wound Healing/physiology* ; Peripheral Nerves/physiology* ; Schwann Cells/physiology* ; Skin/injuries* ; Animals

BACKGROUND: Neck cooling is a practical method for preventing heat-related illness, however, its effectiveness in general workers is not well established. This study aimed to assess the effects of neck cooling on core body temperature and other physiological markers during exercise in a hot environment. METHODS: This randomized crossover trial was conducted from November 2023 to April 2024 at the Shared-Use Research Center at UOEH. Fourteen healthy adult males participated in the study under two conditions: with neck cooling (COOL) and without neck cooling (CON). All participants completed both conditions, and the order of condition assignment was determined by a random draw. Participants first rested for 10 minutes in a 28.0 °C, 50% relative humidity environment, followed by a rest in a 35.0 °C, 50% relative humidity environment for another 10 minutes. In the COOL condition, participants wore a neck cooler containing 1,200 g of ice while exercising at 50% Heart Rate Reserve on a bicycle ergometer for 20 minutes. Afterward, they rested for 15 minutes in the hot environment while still wearing the cooler. MAIN OUTCOME MEASURES: Core body temperature (rectal and esophageal), forehead skin temperature, and heart rate were continuously monitored and compared using a mixed model. Estimated sweat volume was calculated based on changes in body weight before and after the experiment. RESULTS: At the end of the rest period, no significant differences were observed between the COOL and CON conditions in rectal temperature (37.76 ± 0.18 °C versus 37.75 ± 0.24 °C, p = 0.9493), esophageal temperature (37.75 ± 0.30 °C versus 37.76 ± 0.23 °C, p = 0.7325), forehead skin temperature (36.87 ± 0.29 °C versus 36.88 ± 0.27 °C, p = 0.2160), or heart rate (104.18 ± 7.56 bpm versus 107.52 ± 7.40 bpm, p = 0.1035). Estimated sweat loss was similar between conditions (578 ± 175 g for CON versus 572 ± 242 g for COOL, p = 0.5066). While more participants felt cooler in the COOL condition, RPE showed no significant difference. CONCLUSION Neck cooling did not significantly affect core temperature or perceived exertion. Maintaining close contact with the skin at sufficiently low temperatures or utilizing cooling methods that prevent excessive negative feedback may be necessary to enhance the effectiveness of neck cooling.
Humans ; Male ; Cross-Over Studies ; Exercise/physiology* ; Adult ; Neck/physiology* ; Hot Temperature/adverse effects* ; Young Adult ; Body Temperature ; Heart Rate ; Skin Temperature ; Body Temperature Regulation ; Cold Temperature

Skin, as the body's largest organ, acts as the primary defense mechanism against infection and injury. The maintenance of skin health heavily relies on the regulation of epidermal stem cells, crucial for ensuring epidermal homeostasis, hair regeneration, and the repair of epidermal injuries. Recent studies have placed a growing emphasis on G protein-coupled receptor (GPCR) in the context of understanding epidermal stem cells, uncovering its significant role in determining their fate. The activation of GPCR triggers the subsequent dissociation of the βγ subunits from the α subunit of G protein, leading to the modulation of various downstream signaling pathways, such as the WNT-BMP signaling crosstalk and the Gαs-PKA signaling pathway. These pathways collectively influence the fate of epidermal stem cells. Consequently, targeted GPCR therapy has emerged as a promising strategy for improving skin health by orchestrating the fate of epidermal stem cells, unveiling potential therapeutic targets that demand further investigation.
Humans ; Stem Cells/cytology* ; Receptors, G-Protein-Coupled/physiology* ; Animals ; Epidermal Cells/physiology* ; Signal Transduction ; Epidermis/physiology* ; Skin/cytology*

Complete wound regeneration preserves skin structure and physiological functions, including sensation and perception of stimuli, whereas incomplete wound regeneration results in fibrosis and scarring. Amniotic fluid stem cells (AFSCs) would be a kind of cell population with self-renewing and non-immunogenic ability that have a considerable role in wound generation. They are easy to harvest, culture, and store; moreover, they are non-tumorigenic and not subject to ethical restrictions. They can differentiate into different kinds of cells that replenish the skin, subcutaneous tissues, and accessory organs. Additionally, AFSCs independently produce paracrine effectors and secrete them in exosomes, thereby modulating local immune cell activity. They demonstrate anti-inflammatory and immunomodulatory properties, regulate the physicochemical microenvironment of the wound, and promote full wound regeneration. Thus, AFSCs are potential resources in stem cell therapy, especially in scar-free wound healing. This review describes the biological characteristics and clinical applications of AFSCs in treating wounds and provide new ideas for the treatment of wound healing.
Humans ; Amniotic Fluid ; Wound Healing/physiology* ; Regeneration/physiology* ; Skin/pathology* ; Cicatrix ; Stem Cells

Sweat gland is one of the important appendage organs of the skin, which plays an important role in thermoregulation and homeostasis maintenance. Sweat glands are damaged and unable to self-repair after burns, resulting in perspiration disorders eventually. However, current clinical strategies cannot restore the function of the damaged sweat glands effectively. Therefore, it is urgent to seek treatments that can promote the regeneration of sweat glands and restore their normal functions. Stem cells have extensive sources, low immunogenicity, high proliferation capacity, and multi-directional differentiation potential, which have become a focus in the field of regenerative medicine. In recent years, a variety of stem cells have been induced to differentiate into sweat gland-like tissue with certain secretory function, which provides treatment direction for sweat gland regeneration after burns in clinic. This article reviews the recent research advances on the application of stem cells in sweat gland regeneration from the perspectives of the manner by which stem cells transform into sweat gland cells in different environments and their influencing factors.
Cell Differentiation/physiology* ; Regeneration/physiology* ; Skin ; Stem Cells ; Sweat Glands/physiology*

Objective: To investigate the regulatory effects of bio-intensity electric field on the transformation of human skin fibroblasts (HSFs). Methods: The experimental research methods were used. HSFs were collected and divided into 200 mV/mm electric field group treated with 200 mV/mm electric field for 6 h and simulated electric field group placed in the electric field device without electricity for 6 h. Changes in morphology and arrangement of cells were observed in the living cell workstation; the number of cells at 0 and 6 h of treatment was recorded, and the rate of change in cell number was calculated; the direction of cell movement, movement velocity, and trajectory velocity within 3 h were observed and calculated (the number of samples was 34 in the simulated electric field group and 30 in 200 mV/mm electric field group in the aforementioned experiments); the protein expression of α-smooth muscle actin (α-SMA) in cells after 3 h of treatment was detected by immunofluorescence method (the number of sample was 3). HSFs were collected and divided into simulated electric field group placed in the electric field device without electricity for 3 h, and 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group which were treated with electric fields of corresponding intensities for 3 h. Besides, HSFs were divided into simulated electric field group placed in the electric field device without electricity for 6 h, and electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group treated with 200 mV/mm electric field for corresponding time. The protein expressions of α-SMA and proliferating cell nuclear antigen (PCNA) were detected by Western blotting (the number of sample was 3). Data were statistically analyzed with Mann-Whitney U test, one-way analysis of variance, independent sample t test, and least significant difference test. Results: After 6 h of treatment, compared with that in simulated electric field group, the cells in 200 mV/mm electric field group were elongated in shape and locally adhered; the cells in simulated electric field group were randomly arranged, while the cells in 200 mV/mm electric field group were arranged in a regular longitudinal direction; the change rates in the number of cells in the two groups were similar (P>0.05). Within 3 h of treatment, the cells in 200 mV/mm electric field group had an obvious tendency to move toward the positive electrode, and the cells in simulated electric field group moved around the origin; compared with those in simulated electric field group, the movement velocity and trajectory velocity of the cells in 200 mV/mm electric field group were increased significantly (with Z values of -5.33 and -5.41, respectively, P<0.01), and the directionality was significantly enhanced (Z=-4.39, P<0.01). After 3 h of treatment, the protein expression of α-SMA of cells in 200 mV/mm electric field group was significantly higher than that in simulated electric field group (t=-9.81, P<0.01). After 3 h of treatment, the protein expressions of α-SMA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were 1.195±0.057, 1.606±0.041, and 1.616±0.039, respectively, which were significantly more than 0.649±0.028 in simulated electric field group (P<0.01). Compared with that in 100 mV/mm electric field group, the protein expressions of α-SMA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly increased (P<0.01). The protein expressions of α-SMA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were 0.730±0.032, 1.561±0.031, and 1.553±0.045, respectively, significantly more than 0.464±0.020 in simulated electric field group (P<0.01). Compared with that in electric field treatment 1 h group, the protein expressions of α-SMA in electric field treatment 3 h group and electric field treatment 6 h group were significantly increased (P<0.01). After 3 h of treatment, compared with that in simulated electric field group, the protein expressions of PCNA of cells in 100 mV/mm electric field group, 200 mV/mm electric field group, and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 100 mV/mm electric field group, the protein expressions of PCNA of cells in 200 mV/mm electric field group and 400 mV/mm electric field group were significantly decreased (P<0.05 or P<0.01); compared with that in 200 mV/mm electric field group, the protein expression of PCNA of cells in 400 mV/mm electric field group was significantly decreased (P<0.01). Compared with that in simulated electric field group, the protein expressions of PCNA of cells in electric field treatment 1 h group, electric field treatment 3 h group, and electric field treatment 6 h group were significantly decreased (P<0.01); compared with that in electric field treatment 1 h group, the protein expressions of PCNA of cells in electric field treatment 3 h group and electric field treatment 6 h group were significantly decreased (P<0.05 or P<0.01); compared with that in electric field treatment 3 h group, the protein expression of PCNA of cells in electric field treatment 6 h group was significantly decreased (P<0.01). Conclusions: The bio-intensity electric field can induce the migration of HSFs and promote the transformation of fibroblasts to myofibroblasts, and the transformation displays certain dependence on the time and intensity of electric field.
Actins/biosynthesis* ; Cell Differentiation/physiology* ; Cell Movement/physiology* ; Electric Stimulation Therapy ; Electricity ; Fibroblasts/physiology* ; Humans ; Myofibroblasts/physiology* ; Proliferating Cell Nuclear Antigen/biosynthesis* ; Skin/cytology*

Epidermal stem cells play an pivotal role in skin self-renewal, wound repair, and re-epithelialization process. The emergence of new technologies and concepts such as single-cell sequencing and gene knockout further revealed a new mechanism of epidermal stem cells in epidermal self-renewal and wound repair, providing new ideas for wound repair. In this review, the mechanisms of proliferation, differentiation, and migration of epidermal stem cells are discussed. Combined with the analysis of researches on stem cell heterogeneity and cell plasticity, the physiological function of epidermal stem cells can be further understood. The application advances of epidermal stem cells in wound repair is also summarized, which would provide some advice for workers engaged in clinical and basic research on wound repair.
Epidermal Cells/physiology* ; Epidermis ; Humans ; Re-Epithelialization ; Skin ; Soft Tissue Injuries ; Stem Cells

Hypertrophic scar is a pathological repair result of excessive accumulation of extracellular matrix after skin damage, which affects the appearance and function of patients with varying degrees. The degree of scar formation is directly related to the strength of inflammatory reaction during wound healing, and excessive or prolonged inflammatory response increases the incidence of hypertrophic scars. Interleukin-6 (IL-6) is a pleiotropic cytokine that is involved in regulating the fibrotic network composed of fibroblasts, macrophages, keratinocytes, and vascular endothelial cells, and is closely related to the formation of hypertrophic scars. This article reviews the role of IL-6 and its signaling pathway in hypertrophic scar formation.
Cicatrix, Hypertrophic/pathology* ; Endothelial Cells/metabolism* ; Fibroblasts/metabolism* ; Humans ; Interleukin-6 ; Skin/pathology* ; Wound Healing/physiology*