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Sciatic nerve injury was considered to be one of the most common peripheral nerve injuries, posing a major threat to patients. miR-874-3p previously reported to modulate key biological processes including cell proliferation, immune response, and apoptosis. However, its specific role and underlying mechanism in sciatic nerve injury remain largely uncharacterized. In this study, we demonstrated that exosomal miR‑874‑3p derived from bone marrow mesenchymal stem cells (BMSCs) alleviates key pathological features of sciatic nerve injury in a cellular model. BMSCs were isolated from Sprague Dawley rats and identified by Flow Cytometry (FCM). Exosomes were extracted from BMSCs using differential centrifugation. The morphology of BMSCs-derived exosomes was observed via TEM. The related gene and protein expression were respectively determined by qPCR and western blot. Cell viability and apoptosis were respectively assessed by CCK-8 kits and FCM. The level of ROS, MDA, SOD and GSH-Px were respectively detected using corresponding kit. Inflammatory factors were measured by ELISA. The dual-luciferase reporter assay served to determine the connection of miR-874-3p with KPNA4. miR-874-3p was markedly upregulated in BMSCs-derived exosomes. The supplementation of BMSCs-Exos miR-874-3p maintained cell viability and diminished apoptosis. Moreover, it modulated the intracellular levels of oxidative stress-associated proteins within cells and concurrently suppressed the release of inflammatory factor, consequently decelerating neuronal impairment. Furthermore, the regulatory effects of BMSC-Exos miR-874-3p on cell proliferation, apoptosis, cytokine release, and oxidative stress were mediated by the inhibition of KPNA4, as evidenced by the fact that KPNA4 overexpression abolished these effects. Exosomal miR‑874‑3p from BMSCs alleviated OGD/R‑induced neuronal injury by targeting KPNA4. BMSCs-derived exosomal miR-874-3p alleviated OGD/R-induced PC12 cells injury. Protective roles against OGD/R-induced injury were exerted by miR-874-3p through down-regulating KPNA4. Exosomal miR-874-3p regulated OGD/R-induced PC12 cells injury by targeting KPNA4.
The increasing global prevalence of pollen-induced respiratory allergy highlights the need for precise and accessible methods of allergen identification. In this study, we developed a sensing platform based on carbon dots (CDs) for the detection of Art v1, the primary allergen in mugwort (Artemisia) pollen. Biomass-derived CDs were synthesized from Xanthii Fructus using a microwave-assisted hydrothermal method. The synthesis process was carefully designed to retain the specific bioactive components from the plant precursor, which endowed the CDs with inherent molecular recognition toward Art v1. The correlation between the retained component content and the recognition capability of the CDs was established through FTIR and XPS analyses. Subsequently, a ratiometric fluorescent probe was constructed by integrating the CDs with a Ru(bpy)3Cl2·6H2O reference signal into a portable test strip sensor. This probe allows visual assessment through distinct color shifts under UV light. Furthermore, when coupled with a smartphone-based colorimetric readout system, the platform facilitates accurate and highly selective identification and quantification of Art v1 within 5 min. The detection range was 0.5–80 nM, with a limit of detection of 0.186 nM. The sensor demonstrated robust on-site detection capability in complex biological and environmental matrices, with recovery rates ranging from 90.5
It has been increasingly recognized that, to a significant extent, the peripheral immune system is playing a role in the etiology of Parkinson’s disease (PD). It has been reported recently that there may be multiple types of genetic susceptibility factors influencing the risk of PD through alterations in the functions of particular immune cells; at present, the precise mechanisms involved remain unclear. Based on a multi-dimensional causality inference model that included data from genome-wide association studies (GWAS), expression quantitative trait loci (eQTL), protein quantitative trait loci (pQTL) and single-cell eQTL (sc-eQTL), we performed both cross-tissue Mendelian randomization (MR) analysis and immune cell-specific MR analysis to investigate the association between genetic risk factors and peripheral immune functions based on individuals with PD. We found that the genetic prediction of CPNE1 expression had a negative association with PD risk in whole blood, substantia nigra and several immune cell types. The results support a possible protective relationship between CPNE1 and PD risk; however, the subsequent biological mechanism remains unclear. Genetically predicted CPNE1 expression showed a significant association with lower PD risk at the level of immune cells in nine different subtypes: T cells, monocytes, natural killer cells and so on. In addition, the exploratory immune-infiltration analysis of peripheral-blood transcriptomics data showed that there was a positive correlation of CPNE1 expression with the inferred number of regulatory T-cells; therefore, this result requires confirmation in subsequent studies. Our results suggest that CPNE1 could be a candidate factor for the reduced PD risk in blood, substantia nigra and several immune cell subsets. The above results suggest that peripheral immune regulation is likely associated with the link between CPNE1-relevant pathways and PD; however, it cannot determine the intermediate steps linking peripheral immune effects to neuroprotection in the brain.
The incidence of global head and neck cancer has increased markedly in the last 10 years, and its prognosis is poor, which seriously endangers people’s life and health. At present, there are few studies on its pathogenesis. Golgi integral membrane protein 4 (GOLIM4) is a major member of the Golgi apparatus transporter complex, and its role in tumor is unclear. The present study found that GOLIM4 was the key target protein downstream of stromal interaction molecule 1 (STIM1), which can inhibit the proliferation of head and neck cancer cells FaDu (human pharyngeal squamous carcinoma cell) and Tca-8113 (human tongue squamous carcinoma cell) with knockdown of GOLIM4 by lentivirus. And the decreased expression of GOLIM4 induced cellular apoptosis. Further experiments revealed that FaDu cell cycle progression was changed after GOLIM4 silence, G1 phase arrest and the number of G2/M cells decreased significantly. It was also found that the cells in S-phase decreased markedly after GOLIM4 was knocked down compared with the control group by 5-bromo-2′-deoxyuridine (BrdU) incorporation experiment. In conclusion, we found that GOLIM4, as the target gene downstream of STIM1, inhibited the proliferation of head and neck cancer, promoted apoptosis, and regulated cell cycle progression, and GOLIM4 is a novel oncogene in head and neck cancer and might help in developing promising targetted therapies for head and neck cancer patients.
Copper-based catalysts play a pivotal role in various industrial catalytic processes, but they face inherent limitations in activating the reactants and stabilizing active components in strong reduction reaction atmosphere at high temperature. Herein, a lattice confinement strategy is proposed to stabilize Cu ion against reduction during CO preferential oxidation in excess H2 above 200 degrees C. Operando DRIFT spectroscopy, isotope-labeling experiments and theoretical simulations collectively demonstrate that the confinement effect not only strengthens the synergistic interaction between CuOx and CeO2 through electronic coupling but also triggers the lattice distortion. Simultaneously, lattice-confined Cu ions within CeO2 facilitate the electron penetration into the antibonding pi* orbital of chemisorbed O2 molecules, thereby promoting the activation of O2 and facilitating CO oxidation. As a result, the lattice confined catalyst exhibits the excellent activity and cycling stability, which realizes 100 % CO conversion at 140-240 degrees C and almost maintains initial activity after the catalytic reaction. This study provides an alternative strategy for stable catalyst design in reduction reaction atmosphere.
