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Background Mesenchymal stem cell (MSC) transplantation is emerging as a promising cell therapeutic strategy in acute liver failure (ALF) clinical research. The potency of MSCs to migrate and engraft into targeted lesions could largely determine their clinical efficacy, in which chemokine/receptor axes play a crucial role. Unfortunately, the downregulation of chemokine receptors expression after in vitro expansion results in a poor homing capacity of MSCs. Methods By evaluating the chemokine expression profile in the liver of ALF patients and ALF mice, we found that CCL2 expression was highly upregulated in damaged livers, while the corresponding receptor, CCR2, was lacking in cultured MSCs. Thus, we genetically modified MSCs to overexpress CCR2 and investigated the targeted homing capacity and treatment efficacy of MSC CCR2 compared to those of the MSC vector control. Results In vivo and ex vivo near-infrared fluorescence imaging showed that MSC CCR2 rapidly migrated and localized to injured livers in remarkably greater numbers following systemic infusion, and these cells were retained in liver lesions for a longer time than MSC vector . Furthermore, MSC CCR2 exhibited significantly enhanced efficacy in the treatment of ALF in mice, which was indicated by a dramatically improved survival rate, the alleviation of liver injury with reduced inflammatory infiltration and hepatic apoptosis, and the promotion of liver regeneration. Conclusions Altogether, these results indicate that CCR2 overexpression enhances the targeted migration of MSCs to damaged livers, improves their treatment effect, and may provide a novel strategy for improving the efficacy of cell therapy for ALF.

Background Crohn's disease (CD) is a chronic non-specific inflammatory bowel disease. Current CD therapeutics cannot fundamentally change the natural course of CD. Therefore, it is of great significance to find new treatment strategies for CD. Preclinical and clinical studies have shown that mesenchymal stromal cells (MSCs) are a promising therapeutic approach. However, the mechanism by which MSCs alleviate CD and how MSCs affect gut microbes are still unclear and need further elucidation. Methods We used 2,4,6-trinitrobenzenesulfonic acid (TNBS) to induce experimental colitis in mice and analysed the microbiota in faecal samples from the control group, the TNBS group and the TNBS + MSC group with faecal 16S rDNA sequencing. Subsequent analyses of alpha and beta diversity were all performed based on the rarified data. PICRUStII analysis was performed on the 16S rRNA gene sequences to infer the gut microbiome functions. Results MSC Treatment improved TNBS-induced colitis by increasing survival rates and relieving symptoms. A distinct bacterial signature was found in the TNBS group that differed from the TNBS + MSC group and controls. MSCs prevented gut microbiota dysbiosis, including increasing α -diversity and the amount of Bacteroidetes Firmicutes and Tenericutes at the phylum level and decreasing the amount of Proteobacteria at the phylum level. MSCs alleviated the increased activities of sulphur and riboflavin metabolism. Meanwhile some metabolic pathways such as biosynthesis of amino acids lysine biosynthesis sphingolipid metabolism and secondary bile acid biosynthesis were decreased in the TNBS group compared with the control group and the TNBS + MSC group Conclusions Overall, our findings preliminarily confirmed that colitis in mice is closely related to microbial and metabolic dysbiosis. MSC treatment could modulate the dysregulated metabolism pathways in mice with colitis, restoring the abnormal microbiota function to that of the normal control group. This study provides insight into specific intestinal microbiota and metabolism pathways linked with MSC treatment, suggesting a new approach to the treatment of CD.

Background: Human olfactory mesenchymal stem cells (OMSC) have become a novel therapeutic option for immune disorder or demyelinating disease due to their immunomodulatory and regenerative potentials. However, the immunomodulatory effects of OMSC still need to be elucidated, and comparisons of the effects of different MSCs are also required in order to select an optimal cell source for further applications. Results: In animal experiments, we found neural functional recovery and delayed EAE attack in the OMSC treatment group. Compared with umbilical cord–derived mesenchymal stem cells (UMSC) treatment group and the control group, the OMSC treatment group had a better neurological improvement, lower serum levels of IFN-γ, and a lower proportion of CD4+IFN-γ+ T splenic lymphocyte. We also observed OMSC effectively suppressed CD4+IFN-γ+ T cell proportion in vitro when co-cultured with human peripheral blood–derived lymphocytes. The OMSC-mediated immunosuppressive effect on human CD4+IFN-γ+ T cells was attenuated by blocking cyclooxygenase activity. Conclusion: Our results suggest that OMSC treatment delayed the onset and promoted the neural functional recovery in the EAE mouse model possibly by suppressing CD4+IFN-γ+ T cells. OMSC transplantation might become an alternative therapeutic option for neurological autoimmune disease.

Mesenchymal stem cell‐derived extracellular vesicles (MSC‐EVs) show powerful potential in the treatment of multiple diseases. However, the low yield of MSC‐EVs severely restricts their clinical application. Here, heat shock (HS), a moderate external stimulus, can enhance EVs release of MSCs by upregulating autophagosome formation. Mechanistically, HS elevates TRPV2 expression to induce Ca2+ influx and then promotes the activity of two succinylases, SUCLG2 and OXCT1, followed by increasing the succinylation of YWHAZ (a 14‐3‐3 protein) at lysine 11 (K11). Acting as an adaptor protein, YWHAZ's succinylation at K11 inhibits its degradation, reinforcing YWHAZ‐ULK1 binding, which upregulates ULK1 S555 phosphorylation to promote autophagosome formation and enhance EV release of MSCs. Additionally, the improved therapeutic efficacy of HS‐treated MSCs via EV release has been shown in two liver injury models—hepatic ischemia/reperfusion injury (HIRI) and acetaminophen‐induced liver injury. These findings proved that HS, an easily implementable and cost‐effective method, can be used to elevate MSC‐EV yield in mass production.

Background: Mesenchymal stem cells (MSCs) have shown positive therapeutic effects on various diseases; however, their functionality can decline during in vitro expansion. Selenium (Se) supplementation has emerged as a strategy for enhancing MSC culture. This study evaluated the effects of different forms of selenium (Na2SeO4, SeMet, ebselen, and chitosan-coated selenium nanoparticles (CS-SeNPs)) on the biological functions of MSCs. Methods: Human umbilical cord-derived MSCs (HUC-MSCs) were cultured in media supplemented with various selenium compounds at specific concentrations. To investigate their biological effects, we assessed cell proliferation, morphology, surface marker expression, and differentiation potential. Furthermore, to elucidate the underlying mechanisms, we analyzed key markers of cellular senescence, including p16, p21, IL-6, IL-8, p27, p53, and reactive oxygen species (ROS) levels. Results: All the selenium treatments promoted hUC-MSC proliferation at specific concentrations. CS-SeNPs and Na2SeO4 exhibited relatively high bioavailability, whereas ebselen and SeMet demonstrated relatively low toxicity. The optimal concentration (0.5 μM CS-SeNPs or 0.25 μM Na2SeO4) significantly enhanced proliferation without altering the hUC-MSC morphology, phenotype, or differentiation capacity. Both CS-SeNPs and Na2SeO4 effectively promoted hUC-MSC proliferation and reduced the senescence of hUC-MSCs by downregulating key senescence-related effectors: the cell cycle inhibitors p16, p21, p27, and p53; and the levels of ROS and senescence-associated secretory phenotype factors (IL-6 and IL-8). Conclusions: Selenium supplementation is an effective strategy for improving MSC expansion and alleviating senescence. The beneficial effects are dependent on the specific selenium compound used, with CS-SeNPs and Na2SeO4 showing particularly strong potential for enhancing the bioavailability and function of hUC-MSCs during in vitro cultivation.

Long non-coding RNAs (lncRNAs) regulate a series of physiological processes and play an important role in development, metabolism and disease. Our previous studies showed that lncRNAs involved in skeletal muscle differentiation. Here, we demonstrated that lncRNA Has2os is highly expressed in skeletal muscle and significantly elevated during skeletal cell differentiation. The knockdown of Has2os inhibited myocyte fusion and impeded the expression of the myogenic factors MyHC and Mef2C. Mechanically, Has2os regulates skeletal muscle differentiation by inhibiting the JNK/MAPK signaling pathway. Furthermore, we also revealed that Has2os is involved in the early stage of regeneration after muscle injury, and the JNK/MAPK signaling pathway is activated at both protein and mRNA levels during early repair. Our results demonstrate the new function of lncRNA Has2os, which plays crucial roles during skeletal muscle differentiation and muscle regeneration, providing a basis for the therapy of lncRNA-related muscle diseases.

Salinity is a key environmental survival factor for all aquatic organisms, especially migratory species. The masu salmon (Oncorhynchus masou) is a representative migratory fish species. Following the freshwater parr stage, anadromous masu salmon briefly inhabit brackish water and transition before migrating to the ocean. To demonstrate the physiological responses of masu salmon (length: 8 ± 0.5 cm, water temperature: 10 ± 0.5 °C) to variations in salinity, we carried out three gradual transfer experiments (gradual daily increases direct transfer experiment of 3.2 (D10), 1.6 (D20), and 1.1 (D30) ppt until reaching 32 ppt) and one (immediate transfer to 32 ppt on day 0) as domestication regimens for masu salmon. The results indicated the following: (1) In the gradual transfer experiment group, growth performance, along with ion and hormone indicators, suggested that the D30 treatment group of anadromous masu salmon exhibited a high level of adaptability. (2) In the direct transfer experiment, in addition to the activity of antioxidant enzymes, both ion concentrations and hormone indicators returned to a stable state within 7 days. Our findings provide a scientific protocol for salinity regulation during the artificial propagation of masu salmon and establish critical acclimation parameters for land-based recirculating aquaculture systems aimed at marine salmonid farming, thereby highlighting their practical value.

In the magnesium alloy melting process, the implementation of anti-burning technology is imperative. This study investigates the oxidation resistance of AZ91D magnesium alloy melting at 730 °C in an open environment under a mixed gas atmosphere, where sulfur is decomposed by pyrite (FeS 2 ) and fluorine is generated from 1,1,1,2-tetrafluoroethane (HFC-134a). By changing the proportion of sulfur and fluorine in the protective atmosphere, it is possible to alter the composition and structure of the protective film. Compared with a single atmosphere protection, a complete and compact protective film was obtained when a mixed protective atmosphere was employed. The optimal effectiveness, density of protective film PBR (Pilling-Bedworth Ratio) = 1.18, was achieved with 0.1% HFC-134a and 0.5 g FeS 2 added at 30 min intervals. The morphology of the surface film was analyzed by scanning electron microscope, the composition by energy-dispersive x-ray spectroscopy, the phase by x-ray diffraction and the film layer composition and the valence states by x-ray photo-electron spectroscopy. The thermodynamic properties and the mechanisms of protective film formation were also analyzed. The established correlations between protective film composition and formation mechanisms contribute valuable knowledge to the field, providing a foundation for advancements in alloy processing and application.

Optically levitated particles in high vacuum offer an exceptionally isolated mechanical platform for photonic control. Effective cooling of their center-of-mass motion is essential not only for enabling ultrasensitive precision sensing but also for opening access to the quantum regime where macroscopic superposition and nonclassical states can be realized. In this review, we present a comprehensive overview of recent advances in active feedback cooling, based on real-time photonic modulation, and passive feedback cooling, driven by optomechanical interactions within optical resonators. We highlight key experimental milestones, including ground state cooling in one and two dimensions, and discuss the emerging applications of these systems in force sensing, inertial metrology, and macroscopic quantum state preparation. Particular attention is given to novel proposals for probing quantum gravity, detecting dark matter and dark energy candidates, and exploring high-frequency gravitational waves. These advancements establish levitated optomechanical systems as a powerful platform for both high-precision metrology and the investigation of fundamental quantum phenomena. Finally, we discuss the current challenges and future prospects in cooling multiple degrees of freedom, device integration, and scalability toward future quantum technologies.

Background Wilms tumor is a highly heritable malignancy. Aberrant METTL14, a critical component of N6-methyladenosine (m 6 A) methyltransferase, is involved in carcinogenesis. The association between genetic variants in the METTL14 gene and Wilms tumor susceptibility remains to be fully elucidated. We aimed to assess whether variants within this gene are implicated in Wilms tumor susceptibility. Methods A total of 403 patients and 1198 controls were analyzed. METTL14 genotypes were assessed by TaqMan genotyping assay. Result Among the five SNPs analyzed, rs1064034 T > A and rs298982 G > A exhibited a significant association with decreased susceptibility to Wilms tumor. Moreover, the joint analysis revealed that the combination of five protective genotypes exerted significantly more protective effects against Wilms tumor than 0–4 protective genotypes with an OR of 0.69. The stratified analysis further identified the protective effect of rs1064034 T > A, rs298982 G > A, and combined five protective genotypes in specific subgroups. The above significant associations were further validated by haplotype analysis and false-positive report probability analysis. Preliminary mechanism exploration indicated that rs1064034 T > A and rs298982 G > A are correlated with the expression and splicing event of their surrounding genes. Conclusions Collectively, our results suggest that METTL14 gene SNPs may be genetic modifiers for the development of Wilms tumor.