Fluvoxamine inhibits Th1 and Th17 Polarization and Function By Repressing Glycolysis to attenuate autoimmune Progression in Type 1 Diabetes

BACKGROUND: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed. METHOD: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. to study the mechanism involved, we extensively examined the characteristics of CD4 RESULT: Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines. CONCLUSION: Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Facile Fabrication of Superhydrophobic and Flame-Retardant Coatings on Cotton Fabrics

The hydrophilicity and inherent flammability of cotton textiles severely limit their usage. To solve these drawbacks, a superhydrophobic and flame-retardant (SFR) coating made of chitosan (CH), ammonium polyphosphate (APP), and TiO2-SiO2-HMDS composite was applied to cotton fabric using simple layer-by-layer assembly and dip-coating procedures. First, the fabric was alternately immersed in CH and APP water dispersions, and then immersed in TiO2-SiO2-HMDS composite to form a CH/APP@TiO2-SiO2-HMDS coating on the cotton fabric surface. SEM, EDS, and FTIR were used to analyze the surface morphology, element composition, and functional groups of the cotton fabric, respectively. Vertical burning tests, microscale combustion calorimeter tests, and thermogravimetric analyses were used to evaluate the flammability, combustion behavior, thermal degradation characteristics, and flame-retardant mechanism of this system. When compared to the pristine cotton sample, the deposition of CH and APP enhanced the flame retardancy, residual char, heat release rate, and total heat release of the cotton textiles. The superhydrophobic test results showed that the maximal contact angle of SFR cotton fabric was 153.7°, and possessed excellent superhydrophobicity. Meanwhile, the superhydrophobicity is not lost after 10 laundering cycles or 50 friction cycles. In addition, the UPF value of CH/APP@TiO2-SiO2-HMDS cotton was 825.81, demonstrating excellent UV-shielding properties. Such a durable SFR fabric with a facile fabrication process exhibits potential applications for both oil/water separation and flame retardancy

Advanced Machine Learning and Water Quality Index (WQI) Assessment: Evaluating Groundwater Quality at the Yopurga Landfill

As industrial development and population growth continue, water pollution has become increasingly severe, particularly in rapidly industrializing regions like the area surrounding the Yopurga landfill. Ensuring water resource safety and environmental protection necessitates effective water quality monitoring and assessment. This paper explores the application of advanced machine learning technologies and the Water Quality Index (WQI) model as a comprehensive method for accurately assessing groundwater quality near the Yopurga landfill. The methodology involves selecting water quality indicators based on available data and the hydrochemical characteristics of the study area, comparing the performance of Decision Trees, Random Forest, and Xgboost algorithms in predicting water quality, and identifying the optimal algorithm to determine indicator weights. Indicators are scored using appropriate sub-index (SI) functions, and six different aggregation functions are compared to find the most suitable one. The study reveals that the Xgboost model surpasses Decision Trees and Random Forest models in water quality prediction. The top three indicator weights identified are pH, Manganese (Mn), and Nickel (Ni). The SWM model, with a 0% overestimation eclipsing rate and a 34% underestimation eclipsing rate, is chosen as the most appropriate WQI model for evaluating groundwater quality at the Yopurga landfill. According to the WQI results from the SWM aggregation function, the overall water quality in the area ranges from moderately polluted to slightly polluted. These assessment results provide a scientific basis for regional water environment protection

Microstructure and Mechanical Properties of Diffusion-Bonded CoCrNi-Based Medium-Entropy Alloy to DD5 Single-Crystal Superalloy Joint

This study focuses on the diffusion bonding of a CoCrNi-based medium-entropy alloy (MEA) to a DD5 single-crystal superalloy. The microstructure and mechanical properties of the joint diffusion-bonded at variable bonding temperatures were investigated. The formation of diffusion zone, mainly composed of the Ni3(Al, Ti)-type γ′ precipitates and Ni-rich MEA matrix, effectively guaranteed the reliable joining of MEA and DD5 substrates. As the bonding temperature increased, so did the width of the diffusion zone, and the interfacial microvoids significantly closed, representing the enhancement of interface bonding. Both tensile strength and elongation of the joint diffusion-bonded at 1110 °C were superior to those of the joints diffusion-bonded at low temperatures (1020, 1050, and 1080 °C), and the maximum tensile strength and elongation of 1045 MPa and 22.7% were obtained. However, elevated temperature produced an adverse effect that appeared as grain coarsening of the MEA substrate. The ductile fracture of the joint occurred in the MEA substrate (1110 °C), whereas the tensile strength was lower than that of the MEA before diffusion bonding (approximately 1.3 GPa)

Molybdenite Re/Os dating, zircon U–Pb age and geochemistry of granitoids in the Yangchuling porphyry W–Mo deposit (Jiangnan tungsten ore belt), China: implications for petrogenesis, mineralization and geodynamic setting

The Yangchuling W–Mo deposit, located in the Jiangnan porphyry–skarn (JNB) tungsten ore belt, is the first recognized typical porphyry W–Mo deposit in China in the 1980's. Stockworks and disseminated W–Mo mineralization occur in the roof pendant of a 0.3 km2 monzogranitic porphyry stock that intruded into a granodiorite stock, hosted by Neoproterozoic phyllite and slate. LA-ICPMS zircon U–Pb analyses suggest that of the monzogranitic porphyry and granodiorite were formed at 143.8 ± 0.5 Ma and 149.8 ± 0.6 Ma, respectively. Six molybdenite samples yielded a Re–Os weighted mean age of 146.4 ± 1.0 Ma. Geochemical data show that both granodiorite and monzogranitic porphyry are characterized by enrichment of large ion lithophile elements (LILE) relative to high field strength elements (HFSE), indicating a peraluminous nature (A/CNK = 1.01–1.08). Two granitoids are characterized by a negative slope with significant light REE/heavy REE fractionation [(La/Yb)N = 8.38–23.20] and negative Eu anomalies (Eu/Eu* = 0.69–0.76). The P2O5 contents of the Yangchuling granitoids range from 0.12% to 0.17% and exhibit a negative correlation with SiO2, reflecting that they are highly fractionated I-type. They have high initial 87Sr/86Sr ratios (0.7104–0.7116), low negative εNd(t) (−5.05 to −5.67), and homogeneous εHf(t) between −1.39 and −2.17, indicating similar sources. Additionally, two-stage Nd model ages (TDM2) of ~1.3–1.4 Ga and two-stage Hf model ages (TDM2) of ~1.2–1.3 Ga are consistent, indicating that Neoproterozoic crustal rocks of the Shuangqiaoshan Group could have contributed to form the Yangchuling magmas. Considering the two groups of parallel Late Mesozoic ore belts, namely the Jiangnan porphyry–skarn tungsten belt (JNB) in the south and the Middle–Lower Yangtze River porphyry–skarn Cu–Au–Mo–Fe ore belt (YRB) in the north, the Nanling granite-related W–Sn ore belt (NLB) in the south, the neighboring Qin–Hang porphyry–skarn Cu–Mo–hydrothermal Pb–Zn–Ag ore belt (QHB) in the north, as well as the Southeastern Coast porphyry–skarn Cu–Mo–Au ore belt (SCB) recognized in South China in this paper,we propose that the latest Jurassic to earliest Cretaceous granitoids and associated ores were formed during a tearing of the subducting Izanagi slab. This tearing of the subduction slab caused the upwelling of asthenosphere and the resulting mantle–crust interaction. The granitoid-related Wore systems in JNB resulted from the remelting of the Proterozoic crust. The mafic–ultramafic volcanic rocks of the Shuangqiaoshan Group intercalated with phyllite and slate, ophiolitic mélange and magmatic arc rocks, mainly comprising I-type granite, basalt, andesite, rhyolite, pyroclastics, togetherwith subduction-relatedmetasomatized lithosphericmantle, would have provided additional mantle material. In this case, the partial melting of rocks of the Shuangqiaoshan Group can produce S-, I- and transitional type granitoids. After strong differentiation it formed tungsten-bearing granitoids characterized by enrichment of high alkali, silicon and volatile components. In the Yangchuling mine area the smallmonzogranitic porphyry stock has stronger fractionation, volatile content and ore-forming components than the older granodiorite, resulting in the development of the porphyry W–Mo ore system