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Background Diabetes-associated osteoporosis are partly caused by accumulation of advanced glycation endproducts (AGEs). Glucagon-like peptide-1 (GLP-1) has been shown to regulate bone turnover. Here we explore whether GLP-1 receptor agonist (GLP1RA) can have a beneficial effect on bone in diabetes by ameliorating AGEs. Methods In the present study, we evaluated the effects of the GLP-1 receptor agonist liraglutide, insulin and dipeptidyl peptidase-4 inhibitor saxagliptin on Zucker diabetic fatty rats. Meanwhile, we observed the effect of GLP-1 on AGEs-mediated osteoblast proliferation and differentiation and the signal pathway. Results Liraglutide prevented the deterioration of trabecular microarchitecture and enhanced bone strength. Moreover, it increased serum Alpl , Ocn and P1NP levels and decreased serum CTX . In vitro we confirmed that GLP-1 could attenuate AGEs-mediated damage in osteogenic proliferation and differentiation. Besides, GLP-1 down-regulated the ROS that caused by AGEs and the mRNA and protein expression of Rage . Conclusions Altogether, our findings suggest that GLP-1 receptor agonist promotes osteoblastogenesis and suppresses bone resorption on obese type 2 diabetic rats to a certain degree. The mechanism of these effects may be partly mediated by AGEs-RAGE-ROS pathway via the interaction with GLP-1 receptor.

To reduce the issue of tri-primary color reabsorption, a new approach for single-phase phosphors as light-emitting diodes (LEDs) has been recommended. The structures, morphology, photoluminescence, thermal stability, and luminescence mechanism of a variety of Ca3Bi (PO4)3 (CBPO): Ce3+/Dy3+ phosphors were investigated. XRD characterization showed that all CBPO samples were eulytite structures. Furthermore, the energy transfer process from Ce3+ to Dy3+ in CBPO is systematically investigated in this work, and the color of light can be adjusted by changing the ratio of doped ions. Under UV light, energy is transferred from Ce3+-Dy3+ mainly through quadrupole-quadrupole interactions in the CBPO host, and doping with different Dy3+ concentrations tunes the emission color from blue to white. The thermal stability of the CBPO: 0.04Ce3+, 0.08Dy3+ samples is outstanding, and the CIE coordinates of the samples after emission have little effect with temperature, while their emission intensity at 423 K is as strong as that at room temperature, reaching 90%. The above results indicate that this CBPO material has great potential as a white light phosphor under near-UV excitation at the optimized concentration of Ce3+ and Dy3+.

The development of osteoarthritis (OA) correlates with the expansion of senescent cells in cartilage, which contributes to an inflammatory microenvironment that accelerates matrix degradation and hampers cartilage generation. To address OA, we synthesized small copper sulfide nanoparticles functionalized with anti-beta-2-microglobulin antibodies (B2M-CuS NPs) that catalyze the formation of toxic •OH from H 2 O 2 via peroxidase-like activity. These B2M-CuS NPs are specifically targeted to induce apoptosis in senescent chondrocytes while showing no toxicity toward normal chondrocytes. Furthermore, B2M-CuS NPs enhance the chondrogenesis of normal chondrocytes. Thus, B2M-CuS NPs can effectively treat OA by clearing senescent chondrocytes and promoting cartilage regeneration after intra-articular injection into the knee joints of surgery-induced OA mice. This study uses smart nanomaterials to treat OA with a synergistic strategy that both remodels senescent cartilage and creates a pro-chondrogenic microenvironment.

The impacts of Lactilactilactobacillus sakei (LS), Pediococcus acidilactici (PA), and Latilactobacillus curvatus (LC) on quality properties, protein and lipid oxidation, and microbial dynamics of pickled pepper rabbit meat during refrigerated storage (4 °C for 1, 3, 5, and 7 days) were investigated. The results showed that the addition of lactic acid bacteria bioprotective agents effectively reduced the pH of pickled pepper rabbit meat, inhibited protein and lipid oxidation, suppressed the growth and proliferation of spoilage bacteria, and maintained favorable textural characteristics. Among the tested strains, Latilactobacillus curvatus exhibited the most significant preservation effects throughout the storage period. On day 7 of storage, the TBARS value of the LC group was 20.60% lower than that of the LS group and 14.68% lower than that of the PA group. Similarly, the total carbonyl content was 12.30% lower than the LS group and 6.21% lower than the PA group, while the total sulfhydryl content was 20.81% and 10.12% higher, respectively. Additionally, the TVB-N value was 11.91% lower than the LS group and 4.37% lower than the PA group. Additionally, the Latilactobacillus curvatus group maintained a lower pH, superior elasticity, chewiness, and cohesiveness, while effectively inhibiting spoilage bacterial growth and proliferation. In conclusion, Latilactobacillus curvatus was the most effective bioprotective agent for preserving the storage characteristics of pickled pepper rabbit meat.

During storage and transportation, meat is susceptible to the effects of microorganisms, endogenous enzymes, and oxygen, leading to issues such as moisture loss, spoilage, and deterioration. Superchilling, as a preservation method that combines the benefits of refrigeration and freezing, can effectively slow the growth and reproduction of microorganisms, control protein and lipid oxidation, reduce water loss, and maintain the quality and sensory properties of meat. This paper reviews the current application status of superchilling technology in meat preservation, focusing on the mechanisms of ice crystal formation, water retention, tenderness preservation, protein and fat oxidation control, and microbial growth inhibition under superchilling conditions. Additionally, it summarizes the research progress on the combined application of superchilling with emerging technologies such as electric fields, magnetic fields, and electron beams in meat preservation and explores its potential and future prospects for improving meat quality. The aim is to provide scientific evidence and technical support for the application of superchilling technology in enhancing meat quality.

Sir2-HerA is a widely distributed antiphage system composed of a RecA-like ATPase (HerA) and an effector with potential NADase activity (Sir2). Sir2-HerA is believed to provide defense against phage infection in Sir2-dependent NAD + depletion to arrest the growth of infected cells. However, the detailed mechanism underlying its antiphage activity remains largely unknown. Here, we report functional investigations of Sir2-HerA from Staphylococcus aureus ( Sa Sir2-HerA), unveiling that the NADase function of Sa Sir2 can be allosterically activated by the binding of Sa HerA, which then assembles into a supramolecular complex with NADase activity. By combining the cryo-EM structure of Sa Sir2-HerA in complex with the NAD + cleavage product, it is surprisingly observed that Sir2 protomers that interact with HerA are in the activated state, which is due to the opening of the α15-helix covering the active site, allowing NAD + to access the catalytic pocket for hydrolysis. In brief, our study provides a comprehensive view of an allosteric activation mechanism for Sir2 NADase activity in the Sir2-HerA immune system. Deletion of cellular NAD+ via Sir2-depentent NADase provides immunity against phage infection in the Sir2-HerA immune system. Here the authors reveal supramolecular assembly for the allosteric activation on Sir2 NADase function in the Sir2-HerA antiphage system.

Clostridium butyricum is a key anaerobic probiotic due to its ability to produce butyric acid and form spores. In this study, four strains were isolated from pig feces using tryptose sulfite cycloserine (TSC) plates and specific primers sequentially. The optimal strain, C. butyricum HADIG-CB003, identified via gas chromatography and enzyme tests, produced 1.54 g/L of butyric acid, with cellulase and amylase activities of 20.88 ± 1.27 U/mL and 16.04 ± 0.46 U/mL, respectively. In reinforced clostridial medium, it produced 2.48 L of gas per liter, with hydrogen making up 59.68% (1.48 L). The adhesion rate to porcine intestinal epithelial cells (IEC-J2) was 9.16% in vitro. Twelve 3-week-old male Kunming mice were split into two groups and fed a basal diet with or without 1 × 10 10 CFU (colony-forming unit)/kg HADIG-CB003 for 2 weeks. The HADIG-CB003 diet did not significantly affect body weight or the feed-to-gain ratio but reduced harmful bacteria like Salmonella enterica and increased beneficial gut bacteria, elevating the Firmicutes / Bacteroidetes ratio ( p  < 0.05). Moreover, the HADIG-CB003 diet significantly increased fecal butyric acid levels and decreased microbial species richness (Chao1 index) in the cecal contents of the mice. The study shows that a TSC double-layer plate, PCR screening, and 16S rRNA sequencing effectively screen C. butyricum in pig feces. Additionally, adding HADIG-CB003 to Kunming mice diets significantly changed their gut microbiota in 2 weeks. Key points • This study presents an affordable and straightforward method for screening and fermenting C. butyricum that does not require anaerobic culture equipment. • This study suggests that C. butyricum HADIG-CB003 possesses the potential to enhance the intestinal health of host organisms.

Objectives The objectives of this paper is to conduct a bibliometric analysis to examine the research status and development trend of anterior cruciate ligament injury and reconstruction in children and adolescents over the past 20 years. Design Descriptive Research. Methods This study obtained information regarding studies on Anterior Cruciate Ligament Reconstruction in Children and Adolescents from the Web of Science Core Collection database. Visual and bibliometric analysis were conducted using VOSviewer, Origin 2022, Pajek64 5.18and Excel 2019. These analytic tools facilitated the analysis of various aspects, including countries/regions, institutions, authors, journals and keywords related to the research. Results From 2003 to 2023, a total of 1328 articles were retrieved in WOS, and 637 articles were selected by two authors. The most productive institutions are Childrens Hosp Philadelphia, Kocher, ms. Their articles have the highest number of publications and citations. The American journal of sports medicine is the most frequently cited journal for articles on anterior cruciate ligament reconstruction in children and adolescents. The most common keywords used in these articles were “anterior cruciate ligament reconstruction”, “injury, children, adolescent”, and “skeletally immature patients”. Conclusions This study provides valuable insights into the research focus of anterior cruciate ligament reconstruction in children and adolescents. In recent years, there has been significant attention paid to areas of “the return to sport, re-repture rate and functional recovery after anterior cruciate ligament reconstruction” in this specific population. These aspects have emerged as key directions for future research in this field.

Objective Diabetic osteoporosis is a secondary complication of diabetes mellitus, characterized by reduced bone mass, increased bone fragility, and impaired fracture healing. However, the mechanisms underlying diabetic bone loss remain to be fully elucidated. More importantly, there is an urgent need to identify therapeutic agents that not only lower blood glucose levels but also alleviate bone loss. Therefore, this study aims to investigate the mechanisms of diabetes-associated bone loss and to explore potential therapeutic agents. Methods We established a mouse model of type 2 diabetes (T2D) induced by streptozotocin and a high-fat diet (HFD). Bone mass and osteoclast numbers were assessed using micro-CT and TRAP staining. In vitro, the effects of MSDC-0160 (MSD) on osteoclast differentiation and function were evaluated through TRAP staining and bone resorption assays. To elucidate the molecular mechanisms underlying MSD-mediated inhibition of osteoclastogenesis, qPCR, Western blotting, and immunofluorescence staining were performed. Finally, micro-CT scanning and immunohistochemical staining were conducted to examine the effects of MSD on bone microstructure and the bone microenvironment in T2D mice, as well as to clarify specific mechanism of action. Results T2D mice exhibited significant bone loss and enhanced osteoclast activation. Moreover, mitochondrial pyruvate carrier (MPC) activity was elevated in osteoclasts of T2D mice. Given the potential for mitigating diabetic bone loss by inhibiting MPC activity, we selected MSD, a novel insulin sensitizer that also serves as an MPC inhibitor. Further detailed investigations revealed that MSD suppresses osteoclast differentiation and function by reducing the energy supply required for osteoclast maturation. This effect results from impaired mitochondrial oxidative phosphorylation (OXPHOS) and reduced mitochondrial biogenesis. In vivo administration of MSD significantly ameliorated bone loss and reduced osteoclast numbers in T2D mice. Conclusion Our findings indicate that the bone loss in T2D mice is associated with excessive osteoclast activation, where MPC playing a crucial role in osteoclast differentiation and maturation. MSD, a novel insulin sensitizer, mitigates diabetic bone loss by suppressing MPC activity in osteoclasts.

Background Heterotopic ossification (HO) pathogenesis involves ROS-driven stem cell differentiation. Carnosic acid (CA), a natural antioxidant, remains unexplored for HO. Methods In vitro, tendon-derived stem cells (TDSCs) were stimulated with IL-1β, and CA was used for intervention to assess its effects on differentiation and ROS production via real-time quantitative PCR (qPCR), western blotting (WB), and immunofluorescence. Additionally, a burn and Achilles tendon transection-induced mouse model of traumatic HO was established to evaluate the therapeutic potential of CA. Results In vitro, CA activated nuclear factor erythroid 2-related factor 2 (Nrf2) and inhibited nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1), leading to increased antioxidant enzyme activity and reduced intracellular ROS levels. CA also regulated the PTEN/AKT signaling pathway, suppressing osteogenic and chondrogenic differentiation of TDSCs. In vivo, micro-computed tomography (Micro-CT) and histological analyses demonstrated that CA activated Nrf2 and enhanced antioxidant enzyme expression, thereby inhibiting osteogenic and chondrogenic factor expression in Achilles tendon tissue and reducing HO formation. Conclusions CA is a novel HO therapeutic by dual targeting of oxidative stress and differentiation pathways.