BACKGROUND:In recent years,improving the health of skeletal muscles through exercise has become an important research concern for scholars.Appropriate exercise has a positive effect on skeletal muscles.Among them,how to activate the sphingosine kinase1(SphK1)/sphingosine-1-phase(S1P)/sphingosine-1-phase receptor2(S1PR2)signaling pathway during exercise so as to improve the health of skeletal muscles is receiving attention from researchers. OBJECTIVE:To investigate how exercise improves the health of skeletal muscles through the SphK1/S1P/S1PR2 signaling pathway,and to explore new methods for treating related muscle diseases in order to improve human skeletal muscle health. METHODS:The first author searched for relevant literature from the establishment of the database to the present in the Web of Science,PubMed,CNKI,WanFang,and VIP databases.The search terms were"signaling pathway,SphK1,S1P,S1PR2,skeletal muscle,satellite cell,myogenesis,exercise"in Chinese and English.Finally,69 articles were included for review and analysis. RESULTS AND CONCLUSION:The SphK1/S1P/S1PR2 signaling pathway is a complex regulatory network that triggers downstream signal transduction processes by SphK1 to catalyze the interaction between S1P and receptors such as S1PR2,thereby regulating multiple biological functions of cells,tissues,organs,and systems.The SphK1/S1P/S1PR2 signaling pathway can regulate satellite cell proliferation and myoblast differentiation,improving myogenesis.The physiological basis of the SphK1/S1P/S1PR2 signaling pathway and the potential impact of exercise on it were analyzed through literature research.Acute aerobic exercise can increase the expression of SphK1 in skeletal muscle.Both human and animal studies have confirmed that acute and long-term exercise can increase the expression of S1P in skeletal muscle.In addition,studies have shown that long-term resistance exercise can increase the expression of S1PR2 in skeletal muscle.Some experimental results indicate that acute and long-term exercise have no significant effect on muscle or blood S1P levels,and the reason for different results may be due to different research subjects,methods,intensities,and frequencies selected,while the specific mechanism is not yet clear.Research suggests that exercise can promote the expression of the SphK1/S1P/S1PR2 signaling pathway in skeletal muscle and regulate downstream related signaling pathways.Research on this signaling pathway may provide new strategies and methods for the treatment of skeletal muscle diseases,thereby improving skeletal muscle health.In the future,we should deepen the research on the association between SphK1/S1P/S1PR2 signaling pathway and skeletal muscle health,further reveal its regulatory relationship with satellite cells and myoblasts as well as its interactions with the upstream and downstream pathways,explore its clinical application value,take into account the changes of this pathway when formulating the rehabilitation program,explore the specific mechanisms by which different types of exercise affect the SphK1/S1P/S1PR2 signaling pathway in skeletal muscles,and use the SphK1/S1P/S1PR2 signaling pathway as a potential therapeutic target for diseases.Further development and application of human muscle models should be developed to improve research depth and accuracy.

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.

Objective To investigate the effective components and therapeutic mechanism of Chaihu-Guizhi-Ganjiang decoction in treating chronic non-atrophic gastritis. Methods The primary and secondary ion fragments of chemical components of Chaihu-Guizhi-Ganjiang decoction were obtained by UHPLC-Q-TOF/MS. Comparing with reference standards and literature information, a comprehensive characterization of the chemical constituents of Chaihu-Guizhi-Ganjiang decoction was conducted. Then, the network pharmacology approach was applied to explore the therapeutic mechanism of Chaihu-Guizhi-Ganjiang decoction in treatment of chronic non-atrophic gastritis based on the components in plasma and verified by immunohistochemical results. Results A total of 24 absorbed components of Chaihu-Guizhi-Ganjiang decoction were characterized, including 11 flavonoid glycosides, 3 fatty acids, 3organic acids, 2 gingerols, 2 flavonoids and, 1 each of fatty aldehydes, triterpenoids and amino acids, which mainly acted on TNF-α, IL-6, STAT3, and PTGS2. It exerted therapeutic effects by modulating signaling pathways, including the IL-17 signaling pathway and the AGE-RAGE signaling pathway, etc. Conclusion This study provided the first exploration of the effective components and therapeutic mechanism of Chaihu-Guizhi-Ganjiang decoction in treatment of chronic non-atrophic gastritis by UHPLC-Q-TOF/MS, which could offer scientific references for its further research.

Objective: To analyze the epidemiological characteristics of influenza in Huzhou City, Zhejiang Province from 2014 to 2023, so as to provide a reference for the improvement of influenza prevention and control measures. Methods: The data of influenza cases in Huzhou City from 2014 to 2023 were collected from the China Disease Prevention and Control Information System. Descriptive epidemiological methods were used to analyze the population and regional distribution characteristics of influenza. Annual percent change (APC) and average annual percent change (AAPC) were used to analyze the trend of influenza incidence in Huzhou City from 2014 to 2023. Results: A total of 83 277 influenza cases were reported in Huzhou City from 2014 to 2023, with an average annual reported incidence of 268.68/105. From 2014 to 2023, the reported incidence of influenza in Huzhou City showed an upward trend (AAPC=68.748%, P<0.05), with a slow upward trend from 2014 to 2021 (APC=31.055%, P<0.05) and a sharp upward trend from 2021 to 2023 (APC=308.782%, P<0.05). The average annual reported incidence of influenza was 270.72/105 in males and 266.54/105 in females, and the difference was not statistically significant (P>0.05). The average annual reported incidence of influenza in children aged 5-<15 years was 1 502.77/100 000. The reported incidences of influenza in Deqing county, Changxing county, and Anji county were 551.44/100 000, 370.47/100 000, and 175.31/100 000, respectively. From 2014 to 2023, the trends of reported influenza incidence in males, females, residents aged 5-<15 years, and 15-<25 years were consistent with the whole population. The reported influenza incidence in each district (county) from 2021 to 2023 was consistent with Huzhou City from 2021 to 2023. Conclusions The reported incidence of influenza in Huzhou City showed an overall upward trend from 2014 to 2023, especially from 2021 to 2023. There was no significant gender difference. The majority of the cases were aged 5-<15 years, and the high incidence areas were Deqing County.

Vaccination is a crucial strategy for the prevention and control of infectious diseases. Virus-like particles (VLPs), composed of structural proteins, have garnered significant attention as a novel type of vaccine due to their excellent safety and immunogenicity. However, similar to most vaccine antigens, VLPs exhibit insufficient thermal stability, which not only restricts the widespread application of vaccines but also increases the risk of vaccine inactivation. This study aims to enhance the stability and shelf life of VLPs derived from type A foot-and-mouth disease virus (FMDV) by employing vacuum freeze-drying technology. The optimal lyoprotectant formulation was determined through single-factor and combinatorial screening. Subsequently, the correlation between the immunogenicity of the freeze-dried vaccine and the content of FMDV VLPs was evaluated via a mouse model. The stability of FMDV VLPs before and after freeze-drying was further assessed by storing them at 4, 25, and 37 ℃ for varying time periods. Results indicated that the lyoprotectant formulation No.1, composed of 7.5% trehalose, 0.1% Tween 80, 50 mmol/L glycine, 1% sodium glutamate, and 3% polyvinylpyrrolidone (PVP), effectively preserved the content of FMDV VLPs during the vacuum freeze-drying process. The immunization trial in mice revealed that the levels of specific antibodies, immunoglobulin G1 (IgG1), interleukin-4 (IL-4), and neutralizing antibodies induced by freeze-dried FMDV VLPs were comparable to those induced by non-freeze-dried FMDV VLPs. The heat treatment results showed that the storage periods of freeze-dried FMDV VLPs at 4, 25, and 37 ℃ were significantly longer than those of non-freeze-dried FMDV VLPs. In conclusion, the selected lyoprotectant formulation effectively improved the stability of FMDV VLPs vaccines. This study provides valuable insights for enhancing the stability of novel subunit vaccines.
Freeze Drying/methods* ; Animals ; Foot-and-Mouth Disease Virus/immunology* ; Mice ; Vaccines, Virus-Like Particle/chemistry* ; Foot-and-Mouth Disease/immunology* ; Vacuum ; Drug Stability ; Mice, Inbred BALB C ; Viral Vaccines/immunology*

Background Mitochondrial biogenesis is pivotal in coal workers' pneumoconiosis fibrosis, yet the role of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)-nuclear respiratory factor 1 (NRF1)-mitochondrial transcription factor A (TFAM) pathway inmitochondrial biogenesis remains elusive, warranting further investigation. Objective To elucidate the role of the PGC-1α-NRF1-TFAM pathway in mitochondrial biogenesis in a rat coal workers' pneumoconiosis model through in vivo and in vitro experiments. Methods (1)n vivo: twelve SPF male SD rats (200-220 g) were randomized into a control group and a coal dust group (n=6 per group). After acclimatization, the coal dust group received 1 mL 50 mg·mL⁻¹ coal dust suspension via intratracheal instillation; the controls received saline. Lung tissues were harvested after two months for histopathology [HE, Masson, and transmission electron microscopy (TEM) ], protein and mRNA analysis, and mitochondrial DNA (mtDNA) quantification by quantitative real-time polymerase chain reaction (qPCR). (2) In vitro: rat lung type II epithelial cells (RLE-6TN) cells were exposed to coal dust (50, 100, 200, and 400 mg·L⁻¹, 24 h). CCK-8 assay determined optimal doses. Ultrastructural changes were analyzed by TEM. Cells were transfected with OE-PGC-1α (PGC-1α overexpression) or shRNA-PGC-1α plasmids (PGC-1α knockdown), and the transfection efficiency was determined by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR). The expression levels of alpah-smooth muscle actin (α-SMA), citrate synthase (CS), PGC-1α, NRF1, TFAM, and fibronectin (Fn) proteins and their corresponding mRNA were detected using Western blot and RT-qPCR, respectively. The relative content of mtDNA was determined by qPCR. Results In vivo: the control group lung samples exhibited soft, pink parenchyma, while the coal dust-exposed lungs showed blackened surfaces with soft texture. The histopathological evaluation revealed intact alveolar walls in the controls versus structural destruction, micro-nodules, and fibrotic areas in the coal dust group. After Masson staining, coal dust deposits were found surrounded by blue collagen fibers in the exposed lungs, but absent in the controls. The coal dust group displayed significant upregulation of fibrotic marker α-SMA and downregulation of mitochondrial biogenesis markers (CS, PGC-1α, NRF1, TFAM) and mtDNA compared to the controls (P<0.05). In vitro: coal dust exposure reduced cell density and induced morphological alterations. TEM revealed evenly distributed normal mitochondria in controls versus mitochondrial swelling, disrupted cristae, and reduced numbers in exposed cells. The mitochondrial biogenesis markers were elevated in the coal dust + OE-PGC-1α group compared to the coal dust + OE-NC group (P<0.05); in contrast, they were decreased in the coal dust + shRNA-PGC-1α group compared to the coal dust + shRNA-NC group (P<0.05). Compared to the control group, the expression levels of the fibrosis marker α-SMA mRNA and protein were increased in the coal dust group (P<0.05). Overexpression of PGC-1α reduced α-SMA expression, while downregulation of PGC-1α increased its expression (P<0.05). Conclusion Coal dust exposure induces mitochondrial dysfunction and pulmonary fibrosis in vivo and in vitro via the PGC-1α-NRF1-TFAM pathway dysregulation. Targeting this pathway may mitigate coal dust-induced fibrosis by restoring mitochondrial biogenesis.

Three-dimensional printed patient-specific instrumentation (3D-PSI) provides a precise and individualized treatment solution for unicompartmental knee arthroplasty (UKA). Currently, this technology is being applied in clinical practice and has demonstrated certain potential. Compared to conventional instrumentation (CI), 3D-PSI offers a broader range of indications, higher-quality preoperative planning, shorter surgical time, a smoother learning curve, more precise osteotomy and prosthesis placement, and better postoperative functional recovery. However, it still has limitations in the rotational alignment of the tibial component. Additionally, the higher cost for patients and increased hospital equipment investment make it less beneficial for surgeons already proficient in CI techniques. Further reliable evidence is needed to compare 3D-PSI with computer navigation and robotic technologies. This review summarizes the advantages and limitations of 3D-PSI assisted UKA and compares 3D-PSI with different auxiliary technologies.

OBJECTIVES: To investigate the inhibitory effect of multimerin-2 (MMRN2) overexpression on growth and metastasis of cutaneous melanoma cells. METHODS: Clinical data of patients with cutaneous melanoma were obtained from the GEO database to compare MMRN2 expressions between normal and tumor tissues. A protein-protein interaction network was constructed using the STRING database, and the intersecting genes from GEPIA2.0 were subjected to GO and KEGG enrichment analysis. The prognostic relevance of MMRN2 expression level was assessed using Cox regression and "timeROC". The correlations of MMRN2 expression level with immune infiltration and angiogenesis-related genes were analyzed using GSCA database and the ssGSEA algorithm. Colony-forming assay, Transwell assay, and wound healing assay were used to examine the changes in proliferation and migration of cultured cutaneous melanoma cells following MMRN2 knockdown. In a mouse model bearing cutaneous melanoma xenograft, the effect of MMRN2 knockdown on vital organ pathologies, survival of the mice and GM-CSF, CXCL9, and TGF‑β1 protein expressions were analyzed. RESULTS: MMRN2 was significantly upregulated in metastatic cutaneous melanoma (P<0.001). Protein interaction network analysis identified 15 intersecting genes, which were enriched in endothelium development and cell-cell junctions. In patients with cutaneous melanoma, a high MMRN2 expression was correlated with a poor prognosis, an advanced T stage, a greater Breslow depth, and ulceration (P<0.05). MMRN2 expression level was strongly correlated with 24 immune cell types (P<0.001), fibroblasts, endothelial cells, and expressions of the pro-angiogenic genes (KCNJ8, SLCO2A1, NRP1, and COL3A1; P<0.001). In cultured B16F10 cells, MMRN2 knockdown significantly suppressed cell proliferation, migration and invasion and caused remo-deling of the immunosuppressive microenvironment. CONCLUSIONS MMRN2 overexpression drives progression of cutaneous melanoma by enhancing tumor metastasis, angiogenesis and immune evasion, highlighting its potential as a therapeutic target for melanomas.
Humans ; Melanoma/metabolism* ; Animals ; Cell Movement ; Prognosis ; Skin Neoplasms/metabolism* ; Mice ; Cell Proliferation ; Neoplasm Invasiveness ; Cell Line, Tumor ; Protein Interaction Maps

Purpose: Erectile dysfunction (ED) is a common male sexual dysfunction. Gut microbiota plays an important role in various diseases. To investigate the effects and mechanisms of intestinal flora dysregulation induced by high-fat diet (HFD) on erectile function. Materials and Methods: Male Sprague–Dawley rats aged 8 weeks were randomly divided into the normal diet (ND) and HFD groups. After 24 weeks, a measurement of erectile function was performed. We performed 16S rRNA sequencing of stool samples. Then, we established fecal microbiota transplantation (FMT) rat models by transplanting fecal microbiota from rats of ND group and HFD group to two new groups of rats respectively. After 24 weeks, erectile function of the rats was evaluated and 16S rRNA sequencing was performed, and serum samples were collected for the untargeted metabolomics detection. Results: The erectile function of rats and the species diversity of intestinal microbiota in the HFD group was significantly lower, and the characteristics of the intestinal microbiota community structure were also significantly different between the two groups. The erectile function of rats in the HFD-FMT group was significantly lower than that of rats in the ND-FMT group. The characteristics of the intestinal microbiota community structure were significantly different. In the HFD-FMT group, 27 metabolites were significantly different and they were mainly involved in the several inflammation-related pathways. Conclusions Intestinal microbiota disorders induced by HFD can damage the intestinal barrier of rats, change the serum metabolic profile, induce low-grade inflammation and apoptosis in the corpus cavernosum of the penis, and lead to ED.