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Repurposing the inhibitors regarding COVID-19 crucial proteins by way of molecular docking approach.
Urban air pollution represents a global problem, since everyday many mutagenic and carcinogens compounds are emitted into the atmosphere, with consequent adverse health effects on humans and biota. Specifically, particulate matter air pollution was associated with increased risks in human mortality and morbidity. In this paper, we analyse the genomic effects on human lymphocytes of different concentrations of annual Turin PM2.5 extract by an in vitro micronuclei assay. Samplings were collected from an urban meteorological-chemical station positioned in Turin (Italy), one of the most polluted cities in Europe. PM2.5 sampled on filters was used for organic extraction in monthly pools and successively aggregated to produce a mixture representative for a full year PM2.5 collection. Lymphocytes were exposed to four concentrations of PM2.5 5, 10, 15 and 20 μg/mL and micronuclei, nucleoplasmic bridges and nuclear buds were scored. With respect to controls, PM2.5 significantly increased the frequencies of all analysed biomarkers at all tested concentrations, whereas the CBPI index was significantly reduced only at the concentration of 20 μg/mL. Such in vitro effects can both to stimulate local authorities to adopt efficient measures for air pollution mitigation and to improve human monitoring to detect early precancer lesions.This study proposed the membrane bioreactor-ultraviolet/chlorine (MBR-UV/Cl2) process for treating polluted surface water with pharmaceutical personal care product (PPCP) contamination. Results showed that MBR-UV/Cl2 effectively removed the organic matters and ammonia at approximately 80% and 95%. MBR-UV/Cl2 was used in the removal of sulfadiazine(SDZ), sulfamethoxazole(SMZ), tetracycline(TC), oxytetracycline(OTC), ciprofloxacin(CIP), ofloxacin(OFX), erythromycin(ERY), roxithromycin(ROX), ibuprofen(IBU) and, naproxen(NAX) at 12.18%, 95.61%, 50.50%, 52.97%, 33.56%, 47.71%, 87.57%, 93.38%, 93.80%, and 71.46% in which their UV/Cl2 contribution was 12.18%, 95.61%, 29.04%, 38.14%, 25.94%, 7.20%, 80.28%, 33.79%, 73.08%, and 23.05%, respectively. The removal of 10 typical PPCPs using UV/Cl2 obtained higher contributions than those of the MBR process, except OTC, ROX, and IBU. The UV/Cl2 process with 3-min hydraulic retention time and chlorine concentration at 3 mg/L effectively removed the trace of PPCPs. MBR-UV/Cl2 has the potential to be developed as an effective technology in treating polluted surface water with PPCP contamination.The oceanic external nitrogen (Nex) deposition to the global ocean is expected to rise significantly owing to human activities. The Southern Ocean (SO) is an important pathway, which brings external influences into the ocean interior. It touches the borders of several developing countries that emit a large amount of anthropogenic nitrogen. To comprehend the dynamics of Nex in the SO, we developed a new method to assess the change in the oceanic uptake of Nex (ΔNex) in the entire SO. We obtained the spatiotemporal distribution of ΔNex in the SO by applying this method to a high-resolution grid data constructed using ship-based observations. During the 1990s to the 2010s, Nex increased significantly by 67 ± 1 Tg-N year-1 in the SO. By comparing this value with the rate of Nex deposition to the ocean, the SO has received ~70% of Nex deposition to the global ocean, indicating that it is the largest uptake region of anthropogenic nitrogen into the ocean interior.Flexible sensors with a high sensitivity and wide-frequency response are essential for structural health monitoring (SHM) while they are attached. Here, carbon nanotube (CNT) films doped with various PVA fractions (CNT/PVA) and ZnO nanowires (nano-ZnO) on zinc sheets were first fabricated by functionalized self-assembly and hydrothermal synthesis processes. A CNT/PVA/nano-ZnO flexible composite (CNT/PVA/ZnO) sandwiched with a zinc wafer was then prepared by the spin-coating method. The piezoresistive and/or piezoelectric capabilities of the CNT/PVA/ZnO composite were comprehensively investigated under cyclic bending and impact loading after it was firmly adhered to a substrate (polypropylene sheet or mortar plate). The results show that the piezoresistive sensitivity and linear stability of the CNT/PVA films doped with 20%, 50%, and 100% PVA during bending are 5.47%/mm, 11.082%/mm, and 11.95%/mm and 2.3%, 3.42%, and 4.78%, respectively. The piezoelectric sensitivity, linear stability, and response accuracy of the CNT/PVA/ZnO composite under impulse loading are 4.87 mV/lbf, 3.42%, and 1.496 ms, respectively. These merits support the use of CNT/PVA/ZnO as a piezoresistive and/or piezoelectric compound sensor to monitor the static/dynamic loads on concrete structures while it is attached.Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer with steadily increasing incidence and poor prognosis. Despite recent success with immunotherapy, 50% of patients still succumb to their diseases. To date, there is no Food and Drug Administration-approved targeted therapy for advanced MCC. Aberrant activation of phosphatidylinositide-3-kinase (PI3K)/AKT/mTOR pathway is frequently detected in MCC, making it an attractive therapeutic target. We previously found PI3K pathway activation in human MCC cell lines and tumors and demonstrated complete clinical response in a Stage IV MCC patient treated with PI3K inhibitor idelalisib. Here, we found that both PI3K-α and -δ isoforms are abundantly expressed in our MCC cell lines and clinical samples; we therefore examined antitumor efficacy across a panel of five PI3K inhibitors with distinctive isoform-specificities, including idelalisib (PI3K-δ), copanlisib (PI3K-α/δ), duvelisib (PI3K-γ/δ), alpelisib (PI3K-α), and AZD8186 (PI3K-β/δ). Of these, copanlisib exerts the most potent antitumor effects, markedly inhibiting cell proliferation, survival, and tumor growth by suppressing PI3K/mTOR/Akt activities in mouse models generated from MCC cell xenografts and patient-derived tumor xenografts. These results provide compelling preclinical evidence for application of copanlisib in advanced MCC with aberrant PI3K activation for which immunotherapy is insufficient, or patients who are unsuitable for immunotherapy.In order to clarify the mechanism and effect of bentonite-supported nanoscale zero-valent iron (nZVI@Bent) on Cr(VI) removal in soil suspended liquid, nZVI@Bent was prepared by liquid-phase reduction method in this research. A number of factors, including the mass ratio of Fe2+ to bentonite during preparation of nZVI@Bent, nZVI@Bent dosage, soil suspended liquid pH value and reaction temperature were assessed to determine their impact on the reduction of Cr(VI) in soil suspended liquid. The nZVI@Bent was characterized by scanning electron microscope (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) to analyze the mechanism of removal of Cr(VI) from the soil. Phosphoramidon order The results showed that the temperature of soil suspended liquid had a significant effect on the removal efficiency. Calculated by the Arrhenius formula, nZVI@Bent removes Cr(VI) from the soil suspended liquid as an endothermic reaction with a reaction activation energy of 47.02 kJ/mol, showed that the reaction occurred easily. The removal of mechanism Cr(VI) from the soil by nZVI@Bent included adsorption and reduction, moreover, the reduction process can be divided into direct reduction and indirect reduction. According to XPS spectrogram analysis, the content of Cr(III) in the reaction product was 2.1 times of Cr(VI), indicated that the reduction effect was greater than the adsorption effect in the process of Cr(VI) removal. The experiment proved that nZVI@Bent can effectively remove Cr(VI) from soil suspension, and can provide technical support for repairing Cr(VI)-polluted paddy fields.Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. We prospectively evaluated endothelial function by assessing flow-mediated dilatation (FMD) of the brachial artery in patients with biopsy-proven NAFLD. This prospective study included 139 patients (50 healthy controls, 47 patients with steatosis and 42 patients with steatohepatitis), all of whom were nondiabetic. Patients with long-standing or uncontrolled hypertension, smokers, and morbidly obese patients were excluded. The medians (ranges) for vascular FMD in the steatohepatitis, steatosis, and control groups were 6% (0-37.5%), 10.8% (0-40%) and 13.6% (0-50%), respectively. The control group had a higher average FMD than the NAFLD group (15.13% vs 10.46%), and statistical significance was reached when the control and steatohepatitis groups were compared (13.6% vs 6%, p = 0.027). Average alanine aminotransferase was significantly higher in the steatohepatitis group than in the steatosis and control groups (54 (U/L) vs 31 (U/L), p = 0.008). Cholesterol levels were similar between all groups. In the multivariate analysis, FMD (OR = 0.85, p = 0.035) and high triglycerides (OR = 76.4, p = 0.009) were significant predictors of steatohepatitis. In the absence of major cardiac risk factors, we demonstrated better endothelial function in healthy controls, evidenced by a higher FMD of the brachial artery than that of patients with steatohepatitis.In modern magnetic resonance imaging, signal detection is performed by dense arrays of radiofrequency resonators. Tight-fitting arrays boost the sensitivity and speed of imaging. However, current devices are rigid and cage-like at the expense of patient comfort. They also constrain posture, limiting the examination of joints. For better ergonomics and versatility, detectors should be flexible, adapt to individual anatomy, and follow posture. Towards this goal, the present work proposes a novel design based on resonators formed by liquid metal in polymer tubes. Textile integration creates lightweight, elastic devices that are worn like pieces of clothing. A liquid-metal array tailored to the human knee is shown to deliver competitive image quality while self-adapting to individual anatomy and adding the ability to image flexion of the joint. Relative to other options for stretchable conductors, liquid metal in elastic tubes stands out by reconciling excellent electrical and mechanical properties with ease of manufacturing.Obesity and type 2 diabetes (T2D) are metabolic disorders influenced by lifestyle and genetic factors that are characterized by insulin resistance in skeletal muscle, a prominent site of glucose disposal. Numerous genetic variants have been associated with obesity and T2D, of which the majority are located in non-coding DNA regions. This suggests that most variants mediate their effect by altering the activity of gene-regulatory elements, including enhancers. Here, we map skeletal muscle genomic enhancer elements that are dynamically regulated after exposure to the free fatty acid palmitate or the inflammatory cytokine TNFα. By overlapping enhancer positions with the location of disease-associated genetic variants, and resolving long-range chromatin interactions between enhancers and gene promoters, we identify target genes involved in metabolic dysfunction in skeletal muscle. The majority of these genes also associate with altered whole-body metabolic phenotypes in the murine BXD genetic reference population.
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