IntroductionHeat-related illnesses can lead to morbidity, which are anticipated to increase frequency with predictions of increased global surface temperatures and extreme weather events. Although heat acclimation training (HAT) could prevent heat-related diseases, the mechanisms underlying HAT-promoting beneficial changes in organ function, immunity, and gut microbes remain unclear.MethodsIn the current study, we recruited 32 healthy young soldiers and randomly divided them into 4 teams to conduct HATs for 10 days: the equipment-assisted training team at high temperature (HE); the equipment-assisted training team under normal hot weather (NE); the high-intensity interval training team at high temperature (HIIT), and the control team without training. A standard heat tolerance test (HTT) was conducted before (HTT-1st) and after (HTT-2nd) the training to judge whether the participants met the heat acclimation (HA) criteria.ResultsWe found that the participants in both HE and NE teams had significantly higher acclimation rates (HA/total population) than whom in the HIIT team. The effects of HAT on the participants of the HE team outperformed that of the NE team. In the HA group, the differences of physiological indicators and plasma organ damage biomarkers (ALT, ALP, creatinine, LDH, α-HBDH and cholinesterase) before and after HTT-2nd were significantly reduced to those during HTT-1st, but the differences of immune factors (IL-10, IL-6, CXCL2, CCL4, CCL5, and CCL11) elevated. The composition, metabolism, and pathogenicity of gut microbes changed significantly, with a decreased proportion of potentially pathogenic bacteria (Escherichia-Shigella and Lactococcus) and increased probiotics (Dorea, Blautia, and Lactobacillus) in the HA group. Training for a longer time in a high temperature and humidity showed beneficial effects for intestinal probiotics.ConclusionThese findings revealed that pathogenic gut bacteria decrease while probiotics increase following HA, with elevated immune factors and reduced organ damage during heat stress, thereby improving the body’s heat adaption.

Background: Osteoarthritis (OA) is a common degenerative joint disease with a higher prevalence in females than in males. Sex may be a key factor affecting the progression of OA. This study aimed to investigate critical sex-difference-related genes in patients with OA and confirm their potential roles in OA regulation.Methods: OA datasets GSE12021, GSE55457, and GSE36700 were downloaded from the Gene Expression Omnibus database to screen OA-causing genes that are differentially expressed in the two sexes.Cytoscape was used to construct a protein-protein interaction network and determine hub genes. Synovial tissues of patients (male and female) with OA and female non-OA healthy controls were obtained to confirm the expression of hub genes and screen the key genes among them. Destabilization of the medial meniscus (DMM)-induced OA mice model was established to verify the screened key genes. Hematoxylin and eosin (HE) staining and Safranin O-fast green dye staining were employed to observe synovial inflammation and pathological cartilage status.Results: The abovementioned three datasets were intersected to obtain 99 overlapping differentially expressed genes, of which 77 were upregulated and 22 were downregulated in female patients with OA.The hub genes screened were EGF, AQP4, CDC42, NTRK3, ERBB2, STAT1, and CaMK4. Among them, Ca 2+ /calmodulin-dependent protein kinase-4 (CaMK4) was identified as a key sex-related gene for OA. It was significantly higher in female OA patients than in the cases of male patients. Moreover, CaMK4 was significantly increased in female patients with OA compared with the female non-OA group. These results suggest that CaMK4 plays an important role in the progression of OA. OA mouse models demonstrated that CaMK4 expression in the mice knee joint synovial tissue elevated after DMM, with aggravated synovial inflammation and significant cartilage damage. Cartilage damage improved after intraperitoneal administration of the CaMK4 inhibitor KN-93.Conclusions: CaMK4 is a key sex-related gene influencing the progression and pathogenesis of OA and may be considered as a new target for OA treatment.