PDGFRB upregulation contributes to retinal damages in the rat model of retinal ischemia-reperfusion.

Retinal ischemic disease is a major type of retinal diseases causing vision loss. Identifying the molecular mechanisms mediating the retinal ischemia-reperfusion (RIR) is the key to targeted intervention. In this study, we performed RNA-seq analysis of the retinal tissues of a retinal ischemia-reperfusion model of Sprague-Dawley (SD) rats, followed by differential gene expression analysis, gene ontology (GO) enrichment analysis, and protein-protein interaction (PPI) analysis. After studying we found that: The major biological processes affected after RIR was the regulation of vascular development. PPI analysis unveiled a regulatory module in which Platelet Derived Growth Factor Receptor Beta (PDGFRB) was upregulated. In the RIR cell model of human retinal microvascular endothelial cells (HRCEC) induced by oxygen-glucose deprivation/reperfusion (OGD/R), silencing PDGFRB at least partially rescued the detrimental effect on cell proliferation and in vitro angiogenic ability. In the rat model of RIR, the administration of PDGFR inhibitor alleviated the damages in the retinal microvascular system. Besides, we further demonstrated the protective effect of procyanidin against RIR induced damages in both the cell and animal model by dampening the overexpression of PDGFRB. Together, our data indicate that the upregulation of PDGFRB contributes to RIR-induced damages in retinal microvascular system, which provides a targetable strategy for therapeutic intervention.

Planting Anion Channels in a Negatively Charged Polyamide Layer for Highly Selective Nanofiltration Separation.

A nanofiltration (NF) membrane with high salt permeation and high retention of small organics is appealing for the treatment of high-salinity organic wastewater. However, the conventional negatively charged NF membranes commonly show high retention of divalent anions (e.g., SO42-), and the reported positively charged NF membranes normally suffer super low selectivity for small organics/Na2SO4 and high fouling potential. In this work, we propose a novel "etching-swelling-planting" strategy assisted by interfacial polymerization and mussel-inspired catecholamine chemistry to prepare a mix-charged NF membrane. By X-ray photoelectron spectroscopy depth profiling and pore size distribution analysis, it was found that such a strategy could not only deepen the positive charge distribution but also narrow the pore size. Molecular dynamics confirm that the planted polyethyleneimine chains play an important role to relay SO42- ions to facilitate their transport across the membrane, thus reversing the retention of Na2SO4 and glucose (43 vs 71%). Meanwhile, due to the high surface hydrophilicity and smoothness as well as the preservation of abundant negatively charged groups (-OH and -COOH) inside the separation layer, the obtained membrane exhibited excellent antifouling performance, even for the coking wastewater. This study advances the importance of vertical charge distribution of NF membranes in separation selectivity and antifouling performance.

Zinc oxide nanoparticles from Cyperus rotundus attenuates diabetic retinopathy by inhibiting NLRP3 inflammasome activation in STZ-induced diabetic rats.

Diabetic retinopathy (DRP) is a retinal disease caused by diabetes mellitus, which is categorized by microvascular lesions present in the retina such as vascular leakage, vascular proliferation, and retinal ischemia. The plan of the present study was to the synthesis of Cyperus rotundus-loaded zinc oxide nanoparticles (CR-ZnONPs) which was confirmed by the various characterization methods such as UV-vis spectroscopy, energy dispersive X-ray analysis, Fourier transform infrared, scanning electron microscope, and X-ray diffraction. Also, the effect of CR-ZnONPs on DRP-induced rats was determined by food intake, fasting blood glucose (FBG), HbA1c, insulin, retina thickness, inner nuclear layer (INL), outer nuclear layer (ONL) thickness, lipid peroxidation (LPO), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Furthermore, the status of oxidative stress marker genes (heme oxygenase-1 [HO-1] and nuclear factor erythroid 2-related factor-2 [Nrf2]) and inflammatory marker (procaspase-1, cleaved-caspase-1, interleukin-1ß [IL-1ß], IL-18, and ASC) expressions were examined by using real-time polymerase chain reaction and Western blot analysis techniques. We noted that the synthesized CR-ZnONPs have a crystalline structure, spherical shape, and present various functional groups. The administration of streptozotocin (STZ)-induced DRP rats were increased in the levels of HbA1c, FBG, food intake, LPO, and reduced levels of insulin, SOD, GPx, and CAT. In addition, the gene and protein expression showed the downregulation of HO-1 and Nrf2 and upregulation of procaspase-1, IL-1ß, cleaved-caspase-1, IL-18, and ASC in diabetic rats. Moreover, further histopathological analysis of retinal tissues again confirmed the results of biochemical parameters. In contrast, the DRP rats treated with CR-ZnONPs significantly brought down all the parameters to normal, which indicated that the CR-ZnONPs have better antidiabetic and anti-inflammatory properties.

Investigation on the Attitude of Middle School Students with Depression in the City Toward Professional Psychological Help-Seeking.

Background: Many middle school students are depressed due to pressure from family, study, life, and communication. With the increasing depression of middle school students, professional psychological counseling institutions have also become more numerous. Therefore, students need to be guided to correctly recognize difficulties and seek professional psychological assistance. Aim: We aimed to investigate the depression status of middle school students in the city and analyze their attitude towards professional psychological help-seeking. Methods: A total of 2485 students from two classes of each grade from six middle schools in the city were randomly selected as the research objects. They were subjected to answer the general questionnaire and professional psychological help-seeking attitude questionnaire to analyze their depression status, psychological help-seeking status, and attitude towards professional psychological help-seeking. Results: 2485 questionnaires were distributed, and 2205 valid questionnaires were returned. A total of 791 (35.9%) of students had depressive symptoms. The detection rate and depression scores in girls were significantly higher than in boys, and the detection rate in junior high school students in the city was notably higher than in high school students and students from rural areas (P<0.05). Only 31 (3.9%) middle school students with depressive symptoms have sought professional psychological help. The scores of self-cognition, stigma tolerance, interpersonal openness, and trust scores of middle school students with depressive symptoms in help-seeking attitude were significantly lower than those of normal students, while self-stigma scores were significantly higher in those with depressive symptoms (P<0.001). Conclusion: Middle school students in the city with depression have a poor attitude towards professional psychological help-seeking. Educators should positively and correctly guide depressed middle school students to seek professional psychological assistance when they need help.

Microplastics pollution in the Asian water tower: Source, environmental distribution and proposed mitigation strategy.

Microplastics generated from fragmentation of leftover plastics and industrial waste has reached in the remotely located Asian water tower (AWT) region, the 3rd pole of earth and origin site of several freshwater rivers. The accumulation of microplastics in AWT ecosystem has potential to alter the climatic condition contributing in global warming and disturbing the biodiversity structural dynamics. The present paper provides a comprehensive critical discussion over quantitative assessment of microplastics in different ecosystems (i.e. river, lakes, sediment and snow or glacier) of AWT. The hydrodynamic fate and transport of microplastics and their ecological impact on hydromorphology and biodiversity of AWT has been exemplified. Furthermore, key challenges, perspectives and research directions are identified to mitigate microplastics associated problems. During survey, the coloured polyethylene and polyurethane fibers are the predominant microplastics found in most areas of AWT. These bio-accumulated MPs alter the rhizospheric community structure and deteriorate nitrogen fixation process in plants. Significance in climate change, MPs pollution is enhancing the emissions of greenhouse gases (NH3 by ∼34% and CH4 by ∼9%), contributing in global warming. Considering the seriousness of MPs pollution, this review study can enlighten the pathways to investigate the effect of MPs and to develop monitoring tools and sustainable remediation technologies with feasible regulatory strategies maintaining the natural significance of AWT region.

S-allyl-L-cysteine protects hepatocytes from indomethacin-induced apoptosis by attenuating endoplasmic reticulum stress.

Drug-induced liver injury (DILI) can lead to acute liver failure, a lethal condition which may require liver transplantation. Hepatotoxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) accounts for ~ 10% of all DILI. In the current study, we determined whether indomethacin, one of the most commonly used NSAIDS, induced apoptosis in hepatocytes and investigated the underlying mechanism. Meanwhile, we investigated the protective effect of S-allyl-L-cysteine (SAC), an active garlic derivative, on indomethacin-induced hepatocyte apoptosis, and its implication on endoplasmic reticulum (ER) stress. We found that indomethacin triggered ER stress, as indicated by the elevated expression of phosphorylated eukaryotic translation initiation factor 2α (eIF2α), C/EBP homologous protein (CHOP) and spliced XBP1 in a rat liver BRL-3A cell line. Following indomethacin treatment, caspase 3 activation and hepatocyte apoptosis were also observed. Inhibition of ER stress by chemical chaperone 4-phenyl butyric acid alleviated cell apoptosis caused by indomethacin, indicating that ER stress is involved in indomethacin-induced hepatocyte apoptosis. Moreover, SAC abated indomethacin-induced eIF2α phosphorylation, inhibited CHOP upregulation and its nuclear translocation, abrogated the activation of caspase 3 and finally, protected hepatocytes from apoptosis. In conclusion, SAC protects indomethacin-induced hepatocyte apoptosis through mitigating ER stress and may be suitable for development into a potential new therapeutic agent for the treatment of DILI.

miR-200-3p suppresses cell proliferation and reduces apoptosis in diabetic retinopathy via blocking the TGF-ß2/Smad pathway.

Increasing evidence has shown that microRNAs (miRNAs) play an important role in the pathogenesis of diabetic retinopathy (DR). However, the role and mechanism of miRNA in regulating high glucose (HG)-induced ARPE-19 cell injury are still not well understood. The present study aimed to investigate the effects of miR-200a-3p on DR progression and reveal the underlying mechanisms of their effects. In the present study, we observed that miR-200a-3p was significantly decreased, while transforming growth factor-ß2 (TGF-ß2) expression was up-regulated in ARPE-19 cells treated with HG and retina tissues of DR rats. Subsequently, overexpression of miR-200a-3p significantly promoted cell proliferation, reduced apoptosis, as well as inhibited the levels of inflammatory cytokines secreted, matrix metalloprotease 2/9 (MMP2/9), and vascular endothelial growth factor (VEGF) in HG-injured ARPE-19 cells. Moreover, miR-200a-3p was proved to target TGF-ß2 mRNA by binding to its 3' untranslated region (3'UTR) using a luciferase reporter assay. Mechanistically, overexpression of miR-200a-3p reduced HG-induced ARPE-19 cell injury and reduced inflammatory cytokines secreted, as well as down-regulated the expression of VEGF via inactivation of the TGF-ß2/Smad pathway in vitro. In vivo experiments, up-regulation of miR-200a-3p ameliorated retinal neovascularization and inflammation of DR rats. In conclusion, our findings demonstrated that miR-200a-3p-elevated prevented DR progression by blocking the TGF-ß2/Smad pathway, providing a new therapeutic biomarker for DR treatment in the clinic.

Graphitic carbon nitride (g-C3N4) nanosheets functionalized composite membrane with self-cleaning and antibacterial performance.

Membrane fouling significantly impedes membrane performance and thus short lifespan of the membrane. Membranes that functionalized with photocatalytic activity are deemed as an effective and novel approach to settle membrane fouling. The membranes with self-cleaning and antibacterial performance were fabricated via facilely filtering g-C3N4 nanosheets onto polyacrylonitrile (PAN) porous substrates. The g-C3N4 nanosheets were exfoliated by acid etching and ultrasound treatment, and the exfoliated nanosheets was verified by Fourier transform infrared spectra, Atomic force microscopy and X-ray diffraction. The g-C3N4 nanosheets functionalized composite membranes have a water permeability of 11.70 L m-2 h-1 bar-1 and a good antibacterial activity. In addition, the membranes could be restored their original permeability and their surfaces were close to initial color even after three cycles rejecting dyes and post treatment under irradiation with visible light. Besides, the degradable and antimicrobial mechanisms of the membranes were investigated respectively. These g-C3N4 nanosheets composite membranes with self-cleaning and antimicrobial properties have a potential feasibility in water treatment, and provide an alternative method for fabricating self-cleaning membranes.