Electromagnetic fields can regulate the fundamental biological processes involved in bone remodeling. As a non-invasive physical therapy, electromagnetic fields with specific parameters have demonstrated therapeutic effects on bone remodeling diseases, such as fractures and osteoporosis. Electromagnetic fields can be generated by the movement of charged particles or induced by varying currents. Based on whether the strength and direction of the electric field change over time, electromagnetic fields can be classified into static and time-varying fields. The treatment of bone remodeling diseases with static magnetic fields primarily focuses on fractures, often using magnetic splints to immobilize the fracture site while studying the effects of static magnetic fields on bone healing. However, there has been relatively little research on the prevention and treatment of osteoporosis using static magnetic fields. Pulsed electromagnetic fields, a type of time-varying field, have been widely used in clinical studies for treating fractures, osteoporosis, and non-union. However, current clinical applications are limited to low-frequency, and research on the relationship between frequency and biological effects remains insufficient. We believe that different types of electromagnetic fields acting on bone can induce various “secondary physical quantities”, such as magnetism, force, electricity, acoustics, and thermal energy, which can stimulate bone cells either individually or simultaneously. Bone cells possess specific electromagnetic properties, and in a static magnetic field, the presence of a magnetic field gradient can exert a certain magnetism on the bone tissue, leading to observable effects. In a time-varying magnetic field, the charged particles within the bone experience varying Lorentz forces, causing vibrations and generating acoustic effects. Additionally, as the frequency of the time-varying field increases, induced currents or potentials can be generated within the bone, leading to electrical effects. When the frequency and power exceed a certain threshold, electromagnetic energy can be converted into thermal energy, producing thermal effects. In summary, external electromagnetic fields with different characteristics can generate multiple physical quantities within biological tissues, such as magnetic, electric, mechanical, acoustic, and thermal effects. These physical quantities may also interact and couple with each other, stimulating the biological tissues in a combined or composite manner, thereby producing biological effects. This understanding is key to elucidating the electromagnetic mechanisms of how electromagnetic fields influence biological tissues. In the study of electromagnetic fields for bone remodeling diseases, attention should be paid to the biological effects of bone remodeling under different electromagnetic wave characteristics. This includes exploring innovative electromagnetic source technologies applicable to bone remodeling, identifying safe and effective electromagnetic field parameters, and combining basic research with technological invention to develop scientifically grounded, advanced key technologies for innovative electromagnetic treatment devices targeting bone remodeling diseases. In conclusion, electromagnetic fields and multiple physical factors have the potential to prevent and treat bone remodeling diseases, and have significant application prospects.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Objective To explore the effect of stress hyperglycemia (SHG) on new-onset atrial fibrillation (NOAF) in patients with acute myocardial infarction (AMI). Methods A total of 1 321 patients with non-diabetic AMI who were admitted to the hospital from February 2024 to February 2025 were retrospectively selected. The occurrence of SHG was assessed according to the blood glucose level at admission. All patients received standard treatment after admission. The occurrence of NOAF during hospitalization was recorded. According to the presence or absence of NOAF occurrence, the patients were classified into NOAF group (n=118) and no-NOAF group (n=1,203). The clinical data of the two groups were collected and compared. Multivariate logistic regression analysis was applied to analyze the factors influencing the occurrence of NOAF in AMI patients. Results Among the 1 321 patients, 369 cases (27.93%) had SHG according to their blood glucose test at admission. After the completion of hospitalization, 118 of the 1321 patients developed NOAF, with an incidence rate of 8.93%. Multivariate logistic regression analysis revealed that SHG (OR=2.776, 95%CI: 1.384-5.567), smoking history (OR=2.680, 95%CI: 1.457-4.931), Killip grading at admission (OR=2.779, 95%CI: 1.361-5.671), Gensini score (OR=1.119, 95%CI: 1.038-1.205), time from onset to revascularization (OR=1.114, 95%CI: 0.973-1.275), and NT-proBNP (OR=1.123, 95%CI: 1.049-1.203) were independent influencing factors of NOAF in patients with AMI (P<0.05). Conclusion SHG, smoking history, Killip grading at admission, Gensini score, NT-proBNP, and time from onset to revascularization may influence the occurrence of NOAF in AMI patients during hospitalization, which should be given high attention.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

Acute burns and chronic wounds frequently fail to heal owing to various reasons. Most drugs currently used for wound therapy in clinical practice have notable drawbacks, making their application a substantial concern. For instance, anti-inflammatory drugs can exert multisystem toxicity, and cellular therapies are costly and difficult to retain. In recent years, natural functional proteins derived from animals and plants have gained increasing attention owing to their unique biological activities, low cost, and broad application prospects in wound therapy. Herein, we isolated a new protein (JH015Y) from amphibians and demonstrated its excellent wound repair and regeneration properties compared with those of epidermal growth factor, both in vitro and in vivo. JH015 protein increased the proliferative ability of human keratinocytes and skin fibroblasts by 47.73 and 41.40%, respectively. In vivo, the medium-dose (0.5 mg/dose) groups of JH015Y protein demonstrated accelerated wound healing from day 4, with wound healing rates 1.26, 1.27, and 1.14 times that of the blank group in acute wounds, burn wounds, and diabetic ulcer, respectively. Histological analysis of Masson-stained sections indicated that the JH015Y protein contributed to collagen deposition on the wound surface, markedly reduced inflammatory cell infiltration, and exhibited low biological toxicity. Accordingly, the JH015Y protein is a promising biotherapeutic agent for accelerated wound repair and regeneration.

OBJECTIVE: To investigate the effect and mechanism of Shuangshi Tonglin Capsules (SSTL) in the treatment of prostate fibrosis (PF). METHODS: Human prostate stromal cells (WPMY-1) were used for in vitro experiments to establish PF cell models induced with estradiol (E₂). The cell proliferation, migration and clonogenic capacity were determined by cell counting kit-8, scratch assay, and crystal violet staining, respectively. Sprague-Dawley rats were used for in vivo experiments. The changes in histomorphology and organ index of rat prostate by SSTL were determined. Pathologic changes and collagen deposition changes in rat prostate were observed by haematoxylin and eosin (HE) and Masson staining. Enzyme-linked immunosorbent assay kits were used to determine changes in rat PF markers fibroblast growth factor-23 (FGF-23), E₂ and prostate specific antigen (PSA). Mechanistically, changes in oxidative stress indicators by SSTL were determined in WPMY-1 cells and PF rats. Then the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and transforming growth factor-β1 (TGF-β1)/Smad pathway-related proteins as well as Nrf2 and TGF-β1 mRNA were further detected by Western blot or quantitative real-time polymerase chain reaction both in vivo and in vitro. RESULTS: In the efficacy study, SSTL significantly reduced the proliferation, migration, and clonogenic ability of cells, improved the morphology of the glandular tissue, significantly reduced the prostate index, reduced glandular fibrous tissue and collagen deposition, and resulted in a significant decrease in the levels of FGF-23, E₂ and PSA (P<0.01 or P<0.05). In the mechanistic study, SSTL ameliorated oxidative stress by significantly increasing superoxide dismutase and glutathione peroxidase levels and decreasing malondialdehyde level in WPMY-1 cells and rats (P<0.01 or P<0.05). SSTL significantly elevated the expressions of Nrf2, HO-1, NAD(P)H quinone oxidoreductase 1 (NQO-1), and Smad7 proteins in both cells and rats, and significantly decreased the expressions of TGF-β1, collagen I, α-smooth muscle actin and Smad4 proteins (P<0.01 or P<0.05). SSTL also elevated the content of Nrf2 mRNA and decreased the content of TGF-β1 mRNA in cells and rats (P<0.01 or P<0.05). The Nrf2 inhibitor ML385 was added in in vitro experiments to further validate the pathway relevance. CONCLUSION SSTL was effective in improving PF in vivo and in vitro, and its mechanism of action may function through the Nrf2/TGF-β1 signaling pathway.
Male ; NF-E2-Related Factor 2/metabolism* ; Animals ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Humans ; Fibrosis ; Prostate/drug effects* ; Cell Proliferation/drug effects* ; Capsules ; Cell Movement/drug effects* ; Oxidative Stress/drug effects* ; Rats

Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.

Bacterial biofilms can make traditional antibiotics impenetrable and even promote the development of antibiotic-resistant strains. Therefore, non-antibiotic strategies to effectively penetrate and eradicate the formed biofilms are urgently needed. Here, we demonstrate the development of self-propelled biohybrid microrobots that can enhance the degradation and penetration effects for Pseudomonas aeruginosa biofilms in minimally invasive strategy. The biohybrid microrobots (CR@Alg) are constructed by surface modification of Chlamydomonas reinhardtii (CR) microalgae with alginate lyase (Alg) via biological orthogonal reaction. By degrading the biofilm components, the number of CR@Alg microrobots with fast-moving capability penetrating the biofilm increases by around 2.4-fold compared to that of microalgae. Massive reactive oxygen species are subsequently generated under laser irradiation due to the presence of chlorophyll, inherent photosensitizers of microalgae, thus triggering photodynamic therapy (PDT) to combat bacteria. Our algae-based microrobots with superior biocompatibility eliminate biofilm-infections efficiently and tend to suppress the inflammatory response in vivo, showing huge promise for the active treatment of biofilm-associated infections.

Metabolic dysfunction-associated steatohepatitis (MASH), a severe type of metabolic dysfunction-associated steatotic liver disease (MASLD), is a leading etiology of end-stage liver disease worldwide, posing significant health and economic burdens. microRNA-320 (miR-320), a ubiquitously expressed and evolutionarily conserved miRNA, has been reported to regulate lipid metabolism; however, whether and how miR-320 affects MASH development remains unclear. By performing miR-320 in situ hybridization with RNAscope, we observed a notable downregulation of miR-320 in hepatocytes during MASH, correlating with disease severity. Most importantly, miR-320 downregulation in hepatocytes exacerbated MASH progression as demonstrated that hepatocyte-specific miR-320 deficient mice were more susceptible to high-fat, high-fructose, high-cholesterol diet (HFHC) or choline-deficient, amino acid-defined, high-fat diet (CDAHFD)-induced MASH compared with control littermates. Conversely, restoration of miR-320 in hepatocytes ameliorated MASH-related steatosis and fibrosis by injection of adeno-associated virus 8 (AAV8) carrying miR-320 in different types of diet-induced MASH models. Mechanistic studies revealed that miR-320 specifically regulated fibroblast growth factor 1 (FGF1) production in hepatocytes by inhibiting regulator factor X1 (RFX1) expression. Notably, knockdown of Rfx1 in hepatocytes mitigated MASH by enhancing FGF1-mediated AMPK activation. Our findings underscore the therapeutic potential of hepatic miR-320 supplementation in MASH treatment by inhibiting RFX1-mediated FGF1 suppression.

Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks