Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

The present study aimed to investigate the effects of eccentric treadmill exercise on adaptive hypertrophy of skeletal muscle in rats. Thirty-two 3-month-old Sprague Dawley (SD) rats were selected and randomly assigned to one of the four groups based on their body weights: 2-week quiet control group (2C), 2-week downhill running exercise group (2E), 4-week quiet control group (4C), and 4-week downhill running exercise group (4E). The downhill running protocol for rats in the exercise groups involved slope of -16°, running speed of 16 m/min, training duration of 90 min, and 5 training sessions per week. Twenty-four hours after the final session of training, all the four groups of rats underwent an exhaustion treadmill exercise. After resting for 48 h, all the rats were euthanized and their gastrocnemius muscles were harvested for analysis. HE staining was used to measure the cross-sectional area (CSA) and diameter of muscle fibers. Transmission electron microscope was used to observe the ultrastructural changes in muscle fibers. Purithromycin surface labeling translation method was used to measure protein synthesis rate. Immunofluorescence double labeling was used to detect the colocalization levels of lysosomal-associated membrane protein 2 (Lamp2)-leucyl-tRNA synthetase (LARS) and Lamp2-mammalian target of rapamycin (mTOR). Western blot was used to measure the protein expression levels of myosin heavy chain (MHC) IIb and LARS, as well as the phosphorylation levels of mTOR, p70 ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). The results showed that, compared with the 2C group rats, the 2E group rats showed significant increases in wet weight of gastrocnemius muscle, wet weight/body weight ratio, running distance, running time, pre- and post-exercise blood lactate levels, myofibrillar protein content, colocalization levels of Lamp2-LARS and Lamp2-mTOR, and LARS protein expression. Besides these above changes, compared with the 4C group, the 4E group further exhibited significantly increased fiber CSA, fiber diameter, protein synthesis rate, and phosphorylation levels of mTOR, p70S6K, and 4E-BP1. Compared with the quiet control groups, the exercise groups exhibited ultrastructural damage of rat gastrocnemius muscle, which was more pronounced in the 4E group. These findings suggest that eccentric treadmill exercise may promote mTOR translocation to lysosomal membrane, activating mTOR signaling via up-regulating LARS expression. This, in turn, increases protein synthesis rate through the mTOR-p70S6K-4E-BP1 signaling pathway, promoting protein deposition and inducing adaptive skeletal muscle hypertrophy. Although the ultrastructural changes of skeletal muscle are more pronounced, the relatively long training cycles during short-term exercise periods have a more significant effect on promoting gastrocnemius muscle protein synthesis and adaptive hypertrophy.
Animals ; Rats, Sprague-Dawley ; Physical Conditioning, Animal/physiology* ; Rats ; Muscle, Skeletal/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Male ; Hypertrophy ; Adaptation, Physiological/physiology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Ribosomal Protein S6 Kinases, 70-kDa/metabolism* ; Intracellular Signaling Peptides and Proteins

Heat acclimation provides cardiovascular protection in high-temperature environments through multilevel mechanisms; however, the complete molecular basis of its effects remains unclear. In this paper, we systematically review the effects of heat acclimation on blood volume, vascular function, cardiac structure, energy metabolism, and anti-stress regulation, revealing their potential mechanisms in cardiovascular adaptive protection. We also summarizes the multilevel responses induced by heat stress and heat acclimation, including the modulatory effects of heat acclimation on heat shock proteins (HSPs), hypoxia inducible factor 1 (HIF-1), and apoptotic pathways. Additionally, we highlights the comprehensive protective effects of heat acclimation across various stressors (e.g., hypoxia, heat stress). This review provides a significant physiological basis for cardiovascular disease management and sports medicine, emphasizing the potential application of heat acclimation in response to multiple stressors and supporting its role as an effective tool in cardiovascular health management and stress protection interventions.
Humans ; Acclimatization/physiology* ; Hot Temperature ; Heat-Shock Proteins/metabolism* ; Animals ; Heat-Shock Response/physiology* ; Hypoxia-Inducible Factor 1/metabolism* ; Apoptosis/physiology*

The balance between growth and defense in response to nearby or canopy shading in heliotropic plants has been deeply understood. However, the adaptive traits developed by shade-tolerant plants through long-term evolution remain unclear. In this study, the typical shade-tolerant medicinal plant Anoectochilus roxburghii was used as the experimental material.(1) Different planting densities were set, including 8 cm(row spacing) × 8 cm(plant spacing), 6 cm × 6 cm, 4 cm × 4 cm, and 2 cm × 2 cm, to monitor the individual plant responses to nearby shading.(2) Different light environments, including blue light∶red light=3∶2(B3R2), blue light∶red light∶far-red light=3∶2∶1(B3R2FR1), blue light∶red light∶far-red light=3∶2∶2(B3R2FR2), and blue light∶red light∶far-red light=3∶2∶4(B3R2FR4), were set to monitor the morphological and physiological changes in plants in response to actual shading conditions. The results showed that:(1) Moderate increases in planting density helped optimize morphological traits such as stem diameter and leaf area. This not only slightly increased biomass but also significantly improved SOD activity in both leaves and stems, as well as lignin content in stems, thereby enhancing the plant's defense capabilities.(2) Increasing the far-red light in the light environment negatively regulated the plant height of A. roxburghii, which was contrary to the typical shade-avoidance response observed in heliotropic plants. However, it significantly enhanced SOD and POD activity in both stems and leaves, as well as lignin content in stems. Furthermore, it reduced the incidence and disease index of stalk rot, effectively defending against biotic stress. Therefore, the shade-tolerant plant A. roxburghii has specific adaptive strategies for shading conditions. Reasonable dense planting or light environment modulation can synergistically improve yield, medicinal quality, and resistance of A. roxburghii. This study provides a theoretical foundation and technical support for optimizing the regional deployment and cultivation strategies of ecological planting for Chinese medicinal materials.
Orchidaceae/genetics* ; Light ; Plant Leaves/physiology* ; Sunlight ; Adaptation, Physiological/radiation effects* ; Plant Proteins/genetics*

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

OBJECTIVES: This study aims to investigate the impact of glutathione S-transferase (GST) on the environmental adaptability of Streptococcus mutans (S. mutans). METHODS: A GST knockout strain ΔgsT was constructed. Transcriptomic sequencing was performed to analyze the gene expression differences between the wild-type S. mutans UA159 and its GST knockout strain ΔgsT. Comprehensive functional assessments, including acid tolerance assays, hydrogen peroxide challenge assays, nutrient limitation growth assays, and fluorescence in situ hybridization, were conducted to evaluate the acid tolerance, antioxidant stress resistance, growth kinetics, and interspecies competitive ability of ΔgsT within plaque biofilms. RESULTS: Compared with the wild-type S. mutans, 198 genes in ΔgsT were significantly differentially expressed and enriched in pathways related to metabolism, stress response, and energy homeostasis. The survival rate of ΔgsT in acid tolerance assays was markedly reduced (P<0.01). After 15 min of hydrogen peroxide challenge, the survival rate of ΔgsT decreased to 38.12% (wild type, 71.75%). Under nutrient-limiting conditions, ΔgsT exhibited a significantly lower final OD₆₀₀ value than the wild-type strain (P<0.05). In the biofilm competition assays, the proportion of S. mutans ΔgsT in the mixed biofilm (8.50%) was significantly lower than that of the wild type (16.89%) (P<0.05). CONCLUSIONS GST enhances the acid resistance, oxidative stress tolerance, and nutrient adaptation of S. mutans by regulating metabolism-related and stress response-related genes.
Streptococcus mutans/enzymology* ; Biofilms ; Glutathione Transferase/physiology* ; Adaptation, Physiological ; Hydrogen Peroxide/pharmacology* ; Gene Expression Regulation, Bacterial ; Oxidative Stress ; Metabolic Reprogramming

The ability of cells to sense and adapt to metabolic changes and environmental variations is essential for their functions. Recent advances in synthetic biology have uncovered increasing mechanisms through which cells detect changes in metabolism and environmental conditions, leading to broader applications. However, a systematic review on the regulation of cellular metabolism and environmental adaption is currently lacking. This article presents a comprehensive overview of this field from three perspectives. First, it introduces key transmembrane and sensor proteins involved in the cellular perception of metabolic and environmental changes. Next, it summarizes the adaptive regulation mechanisms that natural cells employ when confronted with intracellular and extracellular metabolic changes. Finally, the review explores the application scenarios based on cellular adaptive regulation in three aspects: dynamic control, rational metabolic engineering, and adaptive evolution and makes an outlook on the future development directions in this field. This review not only provides a comprehensive perspective on the mechanisms by which cells sense metabolic and environmental variations, but also lays a theoretical foundation for further innovations in the field of synthetic biology. With the continuous advancement of future technologies, a deeper understanding of cellular adaptive regulation mechanisms holds great potential to drive the development and application of novel biomanufacturing platforms.
Adaptation, Physiological ; Synthetic Biology ; Metabolic Engineering/methods* ; Environment ; Bacteria/genetics*

The alteration of pulmonary artery pressure is an important physiological indicator to reflect the organism's adaptation to acclimatization or the pathological injury in response to high-altitude hypoxic environment. The effects of hypoxic stress at different altitudes for different time on pulmonary artery pressure are different. There are many factors involved in the changes of pulmonary artery pressure, such as the contraction of pulmonary arterial smooth muscle, hemodynamic changes, abnormal regulation of vascular activity and abnormal changes of cardiopulmonary function. Understanding of the regulatory factors of pulmonary artery pressure in hypoxic environment is crucial in clarifying the relevant mechanisms of hypoxic adaptation, acclimatization, prevention, diagnosis, treatment and prognosis of acute and chronic high-altitude diseases. In recent years, great progress has been made in the study regarding the factors affecting pulmonary artery pressure in response to high-altitude hypoxic stress. In this review, we discuss the regulatory factors and intervention measures of pulmonary arterial hypertension induced by hypoxia from the aspects of hemodynamics of circulatory system, vasoactive state and changes of cardiopulmonary function.
Humans ; Altitude ; Arterial Pressure ; Acclimatization ; Hypoxia ; Muscle, Smooth

Autoimmunity associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been well-described as the mechanism of development of thyroid dysfunction following Coronavirus Disease 19 (COVID-19) infection and SARS-CoV-2 vaccination. However, the occurrence of thyroid eye disease (TED) after SARS-CoV-2 vaccination is scarcely described. The postulated mechanisms include immune reactivation, molecular mimicry and the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). We report a case of new-onset TED after receiving the SARSCoV- 2 vaccine.
Thyroid eye disease ; SARS-CoV-2 vaccine ; Molecular Mimicry

OBJECTIVE: To observe the effect of electroacupuncture (EA) on laparoscope postoperative shivering in patients undergoing general anesthesia and explore its effect mechanism. METHODS: A total of 80 patients with elective laparoscopic resection of intestinal tumor under general anesthesia were randomly divided into an EA group and a tramadol group, 40 cases in each group. Thirty min prior to the end of the operation, in the EA group, EA was exerted at Neimadian and Zusanli (ST 36), with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in intensity, and lasting 30 min. In the tramadol group, tramadol hydrochloride injection was dropped intravenously, 1 mg/kg. The conditions of shivering, dizziness, nausea, vomiting and agitation were observed in the post-anesthesia care unit (PACU). Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed before treatment (T₀), at the moment of extubation (T₁), in 3 min of extubation (T₂) and 1 h after operation (T₃). Using ELISA, at T₀ and T₃, the expression levels of interleukin 6 (IL-6) and 5-hydroxytryptamine (5-HT) in plasma were detected separately. Choking and agitation were recorded during extubation. RESULTS: ① In the EA group, the incidence of shivering, dizziness, nausea, vomiting and agitation in the PACU was lower than that in the tramadol group (P<0.05). ②Compared with T₀, HR, SBP and DBP were increased at T₁ and T₂ in the tramadol group (P<0.05). HR, SBP and DBP in the EA group were lower than the tramadol group at T₁ and T₂ (P<0.05). ③Compared with T₀, the expression levels of IL-6 and 5-HT in plasma were increased at T₃ in the tramadol group (P<0.05). The expression levels of IL-6 and 5-HT in the EA group were lower than the tramadol group at T₃ (P<0.05). ④The incidence of choking and agitation during exudation in the EA group was lower than that in the tramadol group (P<0.05). CONCLUSION Electroacupuncture can reduce the incidence of laparoscopic postoperative shivering under general anesthesia. The potential mechanism mays related to the modulation of the expression levels of IL-6 and 5-HT caused by surgical trauma.
Anesthesia, General/adverse effects* ; Electroacupuncture ; Humans ; Laparoscopes ; Postoperative Period ; Shivering