成都体育学院

Glioma, particularly glioblastoma (GBM), represent a major challenge in neuro-oncology due to their highly aggressive nature and poor therapeutic outcomes. The presence of the blood-brain barrier (BBB) severely restricts the efficient delivery of therapeutic agents to tumor sites, while the frequent emergence of drug resistance further compromises treatment efficacy. In recent years, nanoparticles have emerged as promising drug delivery platforms, demonstrating considerable potential in overcoming the BBB, enhancing targeting specificity, and reversing drug resistance, owing to their favorable biocompatibility and tunable physicochemical properties. This review provides a comprehensive overview of recent advances in the application of nanoparticles for glioma therapy, with a particular focus on strategies for BBB penetration and resistance reversal. Specifically, we summarize the design principles and functional modifications of nanoparticles, as well as their diverse therapeutic mechanisms, including drug delivery, photothermal and photodynamic therapy, ferroptosis induction, and modulation of the tumor microenvironment. In addition, the mechanisms underlying nanoparticle-mediated targeting and controlled drug release are discussed in detail. Importantly, current evidence suggests that nanoparticle-based platforms offer a versatile and effective approach for overcoming key biological barriers and therapeutic resistance in glioma, although their clinical translation remains constrained by challenges related to safety, scalability, and targeting heterogeneity. Future research should focus on the development of multifunctional and personalized nanomedicine strategies, integration with multimodal therapies, and rigorous evaluation of long-term safety and clinical efficacy, in order to facilitate the successful translation of these technologies into clinical practice.

This paper examines the impact resistance and dynamic behavior of nano-reinforced composite football shin guards that are truncated conical panels based on higher-order panel theory. The determination of effective material properties containing graphene nanoplatelets (GNPs), carbon nanotubes (CNTs), nano-silica, nano-clay, nano-alumina, and graphene oxide are identified using the Halpin–Tsai micromechanics model. The governing equations are solved using the analytical method. Parametric studies are done on the effect of nanoparticle type, filler distribution, panel geometry and thickness on the deflection, energy absorption, and impact resistance. It is found that, with 1.5

Objective To explore the effect of oral sodium butyrate on skeletal muscle atrophy in CT26 tumor mice through the gut microbiota-skeletal muscle axis and its potential mechanism. Methods Sixty SPF BALB/c male mice aged 8 weeks were randomly divided into a normal control group (NC, n=18) and a ABX-depleted group (ABX, n=42). The ABX mice were pretreated with a quadruple antibiotic cocktail via oral gavage (0.2 ml per administration, once daily, 6 d per week, for 2 weeks), whereas NC received an equal volume of sterile water. The quadruple antibiotic cocktail consisted of metronidazole (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and gentamicin (1 g/L). Following successful pretreatment, six mice from each group were randomly selected for gut microbiota sequencing analysis and designated as the Abx group and the NC0 group, respectively. Theremaining mice in ABX were subcutaneously inoculated in the dorsum with 0.2 ml of CT26 cell suspension (at a cell density of 1 & times;107/ml). Then these mice were randomly allocated into three subgroups: a control tumor bearing model group (0_NaB, n=12), a tumor-bearing model group receiving low-dose oral sodium butyrate (L_NaB, n=12), a tumor-bearing model group receiving high-dose oral sodium butyrate (H_NaB, n=12). And mice in NC were inoculated at the same site with 0.2 ml of normal saline. The administration dose for L_NaB was 0.3 g/(kg & centerdot;d), that for H_NaB was 0.5 g/(kg & centerdot;d), while NC and 0_NaB were given the same volume of normal saline (0.2ml per time, once daily, 6 d per week, for 4 weeks). The general condition of mice was monitored, and forelimb grip strength gastrocnemius muscle mass and its muscle fiber cross-sectional area were measured for each group. The structural changes in gut microbiota were assessed by 16S rRNA sequencing of cecal contents. Pathological alterations in the intestinal wall were examined via HE staining. Serum and gastrocnemius muscle levels of TNF-alpha, IL-6, IL-1 beta, and LPS were quantified using ELISA. The protein expression of ZO-1 and occludin in the small intestine, as well as proteins associated with the TLR4/MyD88/NF-kappa B signaling pathway in the gastrocnemius muscle, were detected by Western blot analysis. Results (1) The alpha-diversity in Abx was significantly lower than that in NC0 (P<0.01), a significant decrease of the mass and muscle fiber cross-sectional area of the gastrocnemius (P<0.01), with the majority of gut microbiota being effectively depleted. (2) Compared with NC, the subcutaneous tumors of mice in 0_NaB were prominent, a significant increase of the mass and muscle fiber cross-sectional area of the gastrocnemius, accompanied by a significant decrease in body weight at the end of the 3th and 4th week (P<0.05), and a significant weakening of the forelimb grasping strength at the 5th and 6th week (P<0.01). Compared with 0_NaB, the tumor mass of mice in L_NaB and H_NaB showed a significant decreasing trend, and the grip strength of the forelimbs significantly increased at the 5th and 6th week (P<0.05, P<0.01). (3) Compared with 0_NaB, the Shannon and Observed species indices in alpha diversity of L_NaB and H_NaB were significantly increased (P<0.05). At the genus level, compared with 0_NaB, L_NaB exhibited a significant decrease in the relative abundance of Parasutterella (P< 0.01), while H_NaB showed significant reductions in the relative abundances of both Escherichia-Shigella and Parasutterella (P < 0.01). (4) Compared with 0_NaB, the small intestinal tissue structure in L_NaB and H_NaB was more intact, the infiltration of inflammatory cells was significantly reduced, and the capillaries were slightly dilated. The expression levels of ZO-1 and occludin proteins in L_NaB were significantly increased (P<0.01). (5) The LPS concentration in the gastrocnemius muscle and the protein expression levels of TLR4, MyD88, p-I kappa B alpha, and p-NF-kappa B p65 in L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05). The serum TNF-alpha concentration in H_NaB and TNF-alpha concentration in the gastrocnemius muscle of the L_NaB and H_NaB were significantly lower than those in 0_NaB (P<0.05, P<0.01, P<0.01). Conclusion Oral administration of NaB can improve gut microbiota alpha diversity, adjusting its composition, improving intestinal mucosal barrier function, reducing the LPS-induced pro-inflammatory response, and delaying skeletal muscle atrophy. The underlying mechanism may involve down regulation of TLR4/MyD88/NF-kappa B signaling in skeletal muscle.

To delineate the molecular recognition features of the FGF7–FGFR2b signaling axis relevant to meniscus regeneration, we integrated AI-based structural modeling (AlphaFold3), mutational energetics, molecular dynamics (MD) simulations, and isothermal titration calorimetry (ITC). Structural analysis of the predicted FGF7–FGFR2b complex revealed a stable interfacial hydrogen-bond network. In silico alanine scanning identified three critical receptor hotspot residues—Lys25, Arg112, and Asp144—whose substitutions were predicted to significantly destabilize the interface by elevating mutation energies (> 1.5 kcal/mol) and reducing polar-contact retention. MD simulations confirmed that both single and triple hotspot mutations (K25A/R112A/D144A) led to increased conformational fluctuations and impaired complex stability relative to the wild-type. Quantitative binding assays via ITC validated these findings, demonstrating a high-affinity interaction for the wild-type complex (K = 2.31 × 10^7 L/mol), whereas each hotspot mutation markedly reduced the binding constant. These results map a discrete receptor recognition patch essential for FGF7 coordination and provide a structural foundation for modulating the STAT/MAPK signaling pathway to enhance fibrocartilage repair during meniscus healing.

The high global prevalence of anxiety disorders, coupled with the limitations of existing treatments, constitutes a severe public health challenge. Chronic stress, as a core environmental trigger, has garnered increasing attention for its mechanism of mediating brain-derived neurotrophic factor (BDNF) imbalance through neuroinflammation. BDNF dysregulation may contribute to anxiety disorders, particularly in subtypes with heightened neuroinflammation. The objective of this review is to comprehensively and methodically explores the potential role of the "M1-like microglia-A1-like astrocyte axis (M1-A1 axis)" in linking chronic stress to BDNF dysregulation in anxiety disorders, and to provide a theoretical basis for intervention strategies targeting this axis. By synthesizing recent relevant clinical and preclinical evidence, this review integrates evidence from molecular to systems levels, focusing on the activation mechanisms of neuroinflammation under chronic stress, the crosstalk between glial cells, and their regulatory network on BDNF. Chronic stress is associated with peripheral and central cascades through hypothalamic-pituitary-adrenal (HPA) axis activation and gut microbiota disruption. Within the central nervous system (CNS), stress induces microglial polarization toward the pro-inflammatory microglial subpopulations (hereinafter referred to as M1-like microglia). The signals released by M1-like microglia, such as Interleukin-1 alpha (IL-1α), Tumor Necrosis Factor-alpha (TNF-α), and Complement Component 1q (C1q) (ITC), drive astrocytes to transform into the neurotoxic astrocyte states (hereinafter referred to as A1-like astrocyte), forming the "M1-A1 axis". This axis contributes to BDNF dysregulation through the following mechanisms: (1) Release of pro-inflammatory cytokines inhibits BDNF transcription and translation; (2) Induction of astrocytic lactate metabolism disruption, which impairs neuronal energy supply and acidifies the microenvironment, further amplifying inflammation and affecting BDNF expression; (3) Compromise of the blood-brain barrier(BBB)enables peripheral immune cells to penetrate into the CNS, and these cells work in synergy with central glial cells to amplify inflammation. The reduction in BDNF and the imbalance in the ratio of its precursor to mature form ultimately lead to impaired synaptic plasticity in brain regions like the hippocampus (HIP) and amygdala, precipitating anxiety-like behaviors. Existing pharmacological interventions are inadequate to reverse this pathological process. The M1-A1 axis may serve as a key node linking chronic stress to BDNF dysregulation and anxiety disorders. Targeting the phenotypic transformation of glial cells, repairing the BBB, or modulating glial cell metabolism (e.g., lactate shuttle) may represent potential strategies requiring further validation. Future research should focus on the spatiotemporal dynamics of this axis and its clinical translation.