Ningxia Medical University (NXMU, Chinese: 宁夏医科大学; pinyin: Níngxià Yīkē Dàxué), previously known as Ningxia Medical College, is a medical school located in Yinchuan City, Ningxia Province, China.
Oxaliplatin serves as a cornerstone chemotherapeutic agent for solid tumors (e.g., colorectal and gastric cancers); however, its associated dose-limiting peripheral neuropathy (OIPN) severely compromises patients’ quality of life and treatment completion rates. OIPN manifests as acute cold-induced paresthesia and chronic cumulative sensory neuropathy, with complex, incompletely elucidated pathophysiological mechanisms. This review systematically summarizes the core molecular mechanisms of OIPN, focusing on: (1) sensitization of transient receptor potential vanilloid/ankyrin channels (TRPV1/TRPA1), (2) dysregulated expression and function of voltage-gated sodium channels (NaV1.7, NaV1.8), and (3) the critical role of p38 mitogen-activated protein kinase (p38-MAPK) pathway activation in neuronal hyperexcitability and pain signal transduction within dorsal root ganglion (DRG) sensory neurons. Additionally, we delve into dynamic alterations of the DRG immune microenvironment (notably macrophages and T cells) during OIPN initiation/progression, as well as their crosstalk with neurons. To address the clinical dilemma of limited effective preventive/therapeutic approaches, this review outlines limitations of current strategies and highlights the advantages of nanotechnology-based drug delivery systems in enhancing neuroprotective agent bioavailability and enabling targeted delivery. Finally, we hypothesize the integration of salidroside (a natural product with anti-inflammatory/antioxidant properties) with nanotechnology, and propose leveraging cutting-edge tools (spatial transcriptomics, single-cell RNA sequencing) to elucidate its potential mechanistic action in OIPN—providing a theoretical hypothesis and exploratory research directions for precision OIPN prevention and treatment, in the absence of any empirical evidence for salidroside’s efficacy in this specific pathological context.
Human umbilical cord mesenchymal stem cells-derived exosomes (UC-MSCs-exos) have demonstrated considerable potential in osteoporosis treatment. This study explored the underlying mechanisms of UC-MSCs-exos in this context. Osteoporosis cell models were established by treating RAW264.7 cells with RANKL, followed by incubation with UC-MSCs-exos. The effects on osteoclast differentiation were assessed via Western blot and TRAP staining. Transfection of HECTD4, METTL3, and RANK was performed to investigate the regulatory mechanism of UC-MSCs-exos on osteoclast differentiation. MeRIP-qPCR analyzed the impact of METTL3 on RANK m6A modification, and ubiquitination assays examined the influence of HECTD4 on METTL3 ubiquitination. Treatment with UC-MSCs-exos inhibited osteoclast differentiation in the osteoporosis models by decreasing the number of mature osteoclasts and markers such as RANK, ACP5, and CTSK. UC-MSCs-exos also reduced METTL3 levels in these models. When METTL3 was overexpressed in the presence of UC-MSCs-exos, osteoclast differentiation was enhanced. METTL3 promoted RANK protein stability by facilitating its m6A modification. In UC-MSCs-exos-treated models, RANK silencing reversed the effect of METTL3 overexpression on osteoclast differentiation. UC-MSCs-exos were found to contain abundant HECTD4, which promoted METTL3 degradation via ubiquitination. Silencing of HECTD4 promoted osteoclast differentiation in the presence of UC-MSCs-exos, but this was reversed by METTL3 silencing. HECTD4 from UC-MSCs-exos attenuated osteoclast differentiation in osteoporosis by inhibiting RANK m6A modification through METTL3 ubiquitination. These findings suggest that UC-MSCs-exos offer a promising strategy for osteoporosis treatment.
Constructing efficient electron coupled heterojunctions with rapid interfacial charge transfer is an effective method for improving photocatalytic hydrogen evolution (PHE). In this work, a 3D/0D 1T-MoS2/ZnCdS (MS/ ZCS QDs) Schottky junction photocatalyst was successfully synthesized by coupling three-dimensional metallic 1T-MoS2 nanoflowers with ZnCdS quantum dots (ZnCdS QDs) through physical mixing. Both 1T-MoS2 nanoflowers and ZnCdS QDs were prepared by one-step hydrothermal method. In-situ X-ray photoelectron spectroscopy (XPS) and density functional theory (DFT) calculations revealed a strongly electronic coupling interface between 1T-MoS2 and ZnCdS QDs, which established a tight Schottky contact. Femtosecond transient absorption spectroscopy (fs-TAs) revealed ultrafast electron transfer from ZnCdS to 1T-MoS2 within 2.48 ps, effectively suppressing charge recombination and enhancing the electron transfer. DFT analysis further demonstrated that the 1T-MoS2 interface exhibited near-optimal hydrogen adsorption Gibbs free energy (Delta G*H = 0.65 eV), facilitating proton adsorption kinetics. Additionally, the d-band center analysis indicated that MS/ZCS QDs has a more suitable electron occupancy in the bonding and antibonding states compared to a single catalyst, further optimizing the catalytic reaction kinetics for PHE. Consequently, the optimized 7.5MS/ZCS achieved a remarkable H2 evolution rate of 6214.43 mu mol g- 1 h- 1 (10.19-fold higher than pristine ZnCdS QDs), with an apparent quantum efficiency (AQE) of 5.07 % at 420 nm. This work provides a new insight into designing Schottky junction photocatalysts through interfacial electronic coupling with ultrafast electron transfer for efficient solarto-hydrogen conversion.
Neonatal white matter injury (WMI), a leading cause of cerebral palsy, results from microglial-driven neuroinflammation that affects oligodendrocyte precursor cell (OPC) survival and differentiation. Our prior in vivo research indicated that inosine may protect against maternal inflammation-induced WMI by modulating microglial polarization and inhibiting TLR4/MyD88/NF-κB signaling, but its direct effects on microglia are unknown. This in vitro study used a microglia-conditioned medium (MCM)-OPC approach to explore this question. Primary microglia were stimulated with lipopolysaccharide (LPS) and treated with inosine, followed by the measurement of inflammatory cytokines (TNF-α, IL-1β, IL-6) and TLR4 pathway proteins via ELISA and Western blot. MCM derived from differentially treated microglia was then applied to OPC cultures, where OPC viability, death, proliferation, and differentiation were assessed using CCK-8 assay, propidium iodide (PI) staining, immunofluorescence, and Western blot. Inosine co-treatment significantly decreased LPS-induced secretion of TNF-α, IL-1β, and IL-6 from microglia (P < 0.05) and downregulated TLR4, MyD88, and p-NF-κB p65 expression (P < 0.001, P < 0.01). MCM from inosine-treated microglia mitigated OPC damage caused by activated microglia, as demonstrated by enhanced OPC viability (P < 0.01), reduced apoptosis (evidenced by decreased PI positivity and Cleaved Caspase-3 expression, P < 0.01, P < 0.05), increased proliferation (indicated by elevated Ki67 positivity and NG2 expression, P<0.001, P < 0.01), and improved differentiation (reflected by increased expression of CNPase, Olig2, and MBP, P < 0.001, P < 0.01). These findings suggest that inosine can directly inhibit the overactivation and inflammatory response of microglia in vitro, an effect associated with TLR4/MyD88/NF-κB downregulation. Furthermore, it can indirectly ameliorate the injurious microenvironment for OPC, thereby providing cellular-level mechanistic clues for explaining its neuroprotective role in vivo.
Background Pyogenic spondylitis (PS) and tuberculous spondylitis (TS) present with significant clinical overlap, posing a major diagnostic challenge. We aimed to develop and validate an imaging-based nomogram integrating CT and MRI features to accurately differentiate PS from TS. Method We conducted a multicenter retrospective study including 539 patients with spinal infections (251 PS, 288 TS) diagnosed between June 2021 and May 2025. Patients were divided into training (n = 427) and external validation (n = 112) cohorts. Imaging features were screened using univariate logistic regression. The least absolute shrinkage and selection operator (LASSO) regression was then applied to select the optimal predictive feature subset and mitigate overfitting. A multivariate logistic regression model based on these features constructed the nomogram. We evaluated diagnostic performance using the area under receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA). Internal validation employed 500 bootstrap resamples; external validation used an independent cohort. Results The training cohort comprised 187 (43.8%) PS and 240 (56.2%) TS patients; the external validation cohort had 64 (57.1%) PS and 48 (42.9%) TS patients. LASSO regression identified five key predictors: vertebral involvement pattern (continuous vs. skip/non-continuous), vertebral body T2-weighted signal intensity (hyperintense vs. heterogeneous), MRI abscess wall characteristics (thick/irregular vs. thin/smooth), CT bone destruction type (osteolytic vs. fragmentary), and CT sagittal bone destruction degree (< 1/3 vs. > 2/3). The AUCs of the nomograms for the training and external validation cohorts were 0.908 (95% confidence interval: 0.880-0.936) and 0.899 (95% confidence interval: 0.842-0.955), respectively. Calibration curves showed the optimal concordance between predicted results and the actual observations. DCA indicated that the substantial clinical net benefit across threshold probabilities. Conclusion The developed nomogram is capable of accurately distinguishing between PS and TS, thereby aiding clinicians in making informed decisions promptly upon obtaining relevant data.
