HSV-1-induced N6-methyladenosine reprogramming via ICP0-mediated suppression of METTL14 potentiates oncolytic activity in glioma.

Upon infection with herpes simplex virus 1 (HSV-1), the virus deploys multiple strategies to evade the host's innate immune response. However, the mechanisms governing this phenomenon remain elusive. Here, we find that HSV-1 leads to a decrease in overall m6A levels by selectively reducing METTL14 protein during early infection in glioma cells. Specifically, the HSV-1-encoded immediate-early protein ICP0 interacts with METTL14 within ND10 bodies and serves as an E3 ubiquitin protein ligase, targeting and ubiquitinating METTL14 at the lysine 156 and 162 sites. Subsequently, METTL14 undergoes proteasomal degradation. Furthermore, METTL14 stabilizes ISG15 mRNA mediated by IGF2BP3 to promote antiviral effects. Notably, METTL14 suppression significantly enhances the anti-tumor effect of oncolytic HSV-1 (oHSV-1) in mice bearing glioma xenografts. Collectively, these findings establish that ICP0-guided m6A modification controls the antiviral immune response and suggest that targeting METTL14/ISG15 represents a potential strategy to enhance the oncolytic activity of oHSV-1 in glioma treatment.

Highly flame-retardant materials of different divalent metal ions alginate/silver phosphate: Synthesis, characterizations, and synergistic phosphorus-polymetallic effects.

Three kinds of divalent metal ions (Ca2+, Cu2+, Zn2+) alginate/silver phosphate (MAlg/Ag3PO4) hybrid materials were prepared via an in-situ method, and the composites were characterized by X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and Fourier transform infrared spectrum (FTIR). To investigate their flame-retardant properties and phosphorus-polymetallic flame-retardant effects, the combustion behavior and flammability of the composites were assessed by using the thermogravimetric analysis (TGA), limiting oxygen index (LOI) and micro-calorimeter tests (MCC). The results show that the three composites were thermally stable, among which the LOI of CaAlg/Ag3PO4, CuAlg/Ag3PO4 and ZnAlg/Ag3PO4 were 62.6 %, 46.5 % and 79.8 %, respectively, which were much higher than the prescribed flame retardants which was 27 %. According to the TGA, the thermal stability was ZnAlg/Ag3PO4 > CaAlg/Ag3PO4 > CuAlg/Ag3PO4. The heat release capacity (HRC) of the above three materials was 49 J/(g·K), 69 J/(g·K), 41 J/(g·K), respectively, and the fire safety performance was also in the same order as the thermal stability. By using the thermogravimetric analysis coupled with Fourier transform infrared analysis (TG-FTIR) and pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS), the flame retarding mechanism of MAlg/Ag3PO4 and the synergistic effect of Ag3PO4 and divalent metal ions were proposed based on the experimental data.

Dual-functional marine algal carbon-based materials with highly efficient dye removal and disinfection control.

The design and simple, green preparation of dual-functional materials for the decontamination of both hazardous dyes and pathogenic microorganisms from wastewater remain challenging currently. Herein, a promising marine algal carbon-based material (named C-SA/SP) with both highly efficient dye adsorptive and antibacterial properties was fabricated based on the incorporation of sodium alginate and a low dose of silver phosphate via a facile and eco-friendly approach. The structure, removal of malachite green (MG) and congo red (CR), and their antibacterial performance were studied, and the adsorption mechanism was further interpreted by the statistical physics models, besides the classic models. The results show that the maximum simulated adsorption capacity for MG reached 2798.27 mg/g, and its minimal inhibit concentration for Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was 0.4 mg/mL and 0.2 mg/mL, respectively. The mechanistic study suggests that silver phosphate exerted the effects of catalytic carbon formation and pore formation, while reducing the electronegativity of the material as well, thus improving its dye adsorptive performance. Moreover, the MG adsorption onto C-SA/SP showed vertical orientation and a multi-molecular way, and its adsorption sites were involved in the adsorption process with the increase of temperature. Overall, the study indicates that the as-made dual-functional materials have good applied prospects for water remediation.

A Highly Selective and Sensitive Nano-Silver sol Sensor for Hg2+ and Fe3+: Green Preparation and Mechanism.

The development of highly selective and highly sensitive nanometer colorimetric chemical sensors is an urgent requirement in the immediate detection of heavy metal ions. In this work, silver-nanoparticle (Ag NPs)-based chemosensors were prepared by a simple and green method, in which the silver nitrate, carboxymethyl cellulose sodium (CMS) and Polyvinylpyrrolidone (PVP), and glucose are used as the silver source, double stabilizer and green reductant, respectively. The obtained colloidal CMS/PVP-Ag NPs showed a high dispersibility and stability, and creating a high selectivity and sensitivity to detect Hg2+ and Fe3+ with remarkable and rapid color variation. Low limits of detection (LOD) of 7.1 nM (0-20 µM) and 15.2 nM (20-100 µM) for Hg2+ and 3.6 nM for Fe3+ were achieved. More importantly, the CMS/PVP-Ag NPs has a high sensitivity even in a complex system with multiple heavy ions, the result of the practical ability to detect Hg2+ and Fe3+ in tap water and seawater reached a rational range of 98.33~104.2% (Hg2+) and 98.85~104.80% (Fe3+), indicating the great potential of the as-prepared nanocomposites colorimetric chemosensor for practical applications.

Anti-obesity effect of Angelica keiskei Jiaosu prepared by yeast fermentation on high-fat diet-fed mice.

In this study, an Angelica keiskei (A. keiskei) Jiaosu (FAK) was prepared by yeast fermentation to investigate its anti-obesity effect on high-fat diet (HFD)-fed mice. 70 SPF grade male C57BL/6J mice were randomly divided into 7 groups (n = 10): blank control group (N), high-fat model group (M), positive control group (Orl), unfermented control group (NF), high-dose intervention group (FH), medium-dose intervention group (FM), and low-dose intervention group (FL). The results showed that FAK intervention significantly reduced the body weight, Lee's index and liver index of HFD-fed mice (P < 0.05). Compared with M group, the serum levels of triglyceride (TG), total cholesterol (TC), leptin and glucose (GLU) in FH group were remarkably decreased and that of interleukin-27 (IL-27) were increased (P < 0.05). The levels of TG, and TC in the liver of mice were also markedly decreased in the FH group (P < 0.05). HE staining results showed that the liver cells in the three intervention groups had less degeneration and fatty vacuoles in the cytoplasm, and the liver cords were orderly arranged compared with that of M group. Furthermore, FAK significantly inhibited epididymal adipose tissue cell expansion induced by HFD. FAK up-regulated the protein expression levels of p-AMPK and PPARα to promote lipolysis and down-regulated the expression of PPARγ to reduce lipid synthesis (P < 0.05). Additionally, the results of gut microbiota showed that after the intervention, a decrease trend of F/B value and Deferribacterota was noticed in the FH group compared with M group. At the genus level, FAK intervention significantly increased that of Ileiobacterium compared to the M group (p < 0.05). A rising trend of norank_f_Muribaculaceae, Lactobacillus, and Bifidobacterium were also observed in the HF group. Conclusively, these findings demonstrated that FAK intervention can effectively improve obesity in mice caused by HFD and the potential mechanisms was related to the regulation of serum levels of leptin and IL-27, lipogenesis and lipolysis in adipose tissue and gut microbiota composition.

Structural characterization of polysaccharide purified from Amanita caesarea and its pharmacological basis for application in Alzheimer's disease: endoplasmic reticulum stress.

Alzheimer's disease (AD) leads to progressive declines in memory and learning. This disease may arise from endoplasmic reticulum stress due to protein misfolding, which promotes inflammatory pathway activation and induces neuronal cell apoptosis. Polysaccharide is one of the main active components of the mushroom Amanita caesarea (A. caesarea) and has been proven to act as an antioxidant, immune regulatory and anti-inflammatory agent with neurodevelopmental effects. In this study, polysaccharide isolated from A. caesarea (ACPS2) was subjected to analysis to determine the main components, homogeneity and molecular weight and characterize the structure. Furthermore, APP/PS1 mice were orally treated with ACPS2 for 6 weeks. Structural characterization of ACPS2 revealed a mass average molar mass of 16.6 kDa and a structure containing a main chain and branching. In vivo, treatment with ACPS2 for 6 weeks significantly improved cognition and anxious behavior in APP/PS1 mice using Morris water maze and open-field test. Alleviation of brain injury, amyloid-ß deposition and tau hyperphosphorylation were observed in ACPS2-treated AD mice. No changes in other tissues were observed. ACPS2 appeared to alleviate inflammation in vivo, as determined by decreases in the serum concentrations of tumor necrosis factor-α and interleukin-1ß relative to those in non-treated mice. ACPS2 improved cholinergic system function and stabilized oxidative stress in APP/PS1 mice. Proteomics and bioinformatics analyses showed that the therapeutic effect of ACPS2 is achieved through regulation of oxidative stress-mediated endoplasmic reticulum stress. Furthermore, ACPS2 exerted anti-AD effects by regulating nuclear factor-E2-related factor 2 (Nrf2) signaling, thereby inhibiting endoplasmic reticulum stress and nuclear factor-kappa B (NF-κB) activation.

Two New Methods of Supine Venographically Guided Popliteal Vein Puncture: A Retrospective Study.

OBJECTIVE: Presently, the prone position is necessary for popliteal vein puncture access, but it makes the patients uncomfortable and does not allow traditional femoral or jugular access. To address these deficiencies, this study introduces two new methods, anterior and medial access carried out in the supine position. METHODS: Venous interventions with punctures in the popliteal vein of 120 limbs in 97 patients were performed during the period from February 2017 to April 2019. After puncture, venographic guidance was achieved by dorsal vein injection of contrast medium. Interventional therapy was performed after puncture and insertion of the introducer sheath. RESULTS: In all, 120 limbs were punctured in the popliteal vein, with technical success in 118 (98.3% in total) cases: 100%, 96.1%, and 100% successful punctures in, respectively, 32 anterior, 49 medial, and 37 posterior access cases. A comparison of the three groups revealed that the fluoroscopy time and duration of puncture were longer in the medial and anterior access groups than in the posterior access group. The rate of intra-operative and post-operative complications was 7.5% (9/120), with no statistically significant difference between the three access groups. Compared with the pre-operative median score of 2.5, the post-operative SVS (Society of Vascular Surgery) score of the popliteal vein was reduced to 1.5 in the anterior and 0.5 in the medial groups. CONCLUSION: Medial and anterior puncture of the popliteal vein in the supine position can be used as a safe alternative in venous endovascular therapy. The two new methods can mitigate frailty or respiratory problems resulting from the prone position and facilitate traditional femoral and jugular access.

The anti-breast cancer property of physcion via oxidative stress-mediated mitochondrial apoptosis and immune response.

CONTEXT: Physcion (Phy) exerts several pharmacological effects including anti-inflammatory, antioxidant, and antitumor properties. OBJECTIVE: This study investigates the cytotoxicity and its underlying mechanisms of Phy on breast cancer. MATERIALS AND METHODS: Human breast cancer cell MCF-7 was treated with 5-400 µM Phy for 24 h, MCF-7-xenografted BALB/c nude mice and immunosuppressive mice model induced by cyclophosphamide were intraperitoneally injected with 0.1 mL/mouse normal saline (control group) and 30 mg/kg Phy every other day for 14 or 28 days, and pathological examination, ELISA and western blot were employed to investigate the Phy anti-breast cancer property in vitro and in vivo. RESULTS: In MCF-7 cells, Phy 24 h treatment significantly reduced the cell viability at dose of 50-400 µM and 24 h, with an IC50 of 203.1 µM, and 200 µM Phy induced 56.9, 46.9, 36.9, and 46.9% increment on LDH and caspase-3, -8 and -9. In MCF-7-xenograft tumour nude mice and immunosuppressive mice, 30 mg/kg Phy treatment inhibited tumour growth from the 8th day, and reduced Bcl-2 and Bcl-xL >50%, HO-1 and SOD-1 > 70% in tumour tissues of immunosuppressive mice. In addition, Phy reduced nuclear factor erythroid 2-related factor 2 > 30% and its downstream proteins, and enhanced the phosphorylation of nuclear factor-kappa B > 110% and inhibitor of NF-кB α > 80% in the tumour tissues of BALB/c mice. DISCUSSION AND CONCLUSIONS: This research demonstrated that Phy has an anti-breast cancer property via the modulation of oxidative stress-mediated mitochondrial apoptosis and immune response, which provides a scientific basis for further research on its clinical applications.