This study systematically investigates the organic fouling behavior of a superhydrophilic polyvinylidene fluoride (PVDF) ultrafiltration membrane functionalized via post-fabrication tethering of ...surface-tailored silica nanoparticles to poly(methacrylic acid)-grafted PVDF membrane surface. Sodium alginate (SA), Suwannee River natural organic matter (SRNOM), and bovine serum albumin (BSA) were used as model organic foulants to investigate the antifouling behavior of the superhydrophilic membrane with combined-fouling (mixture of foulants) and individual-fouling (single foulant) tests. A membrane bioreactor (MBR) plant supernatant was also used to verify the organic antifouling property of the superhydrophilic membrane under realistic conditions. Foulant size distributions and foulant–membrane interfacial forces were measured to interpret the observed membrane fouling behavior. Molecular weight cutoff measurements confirmed that membrane functionalization did not adversely affect the intrinsic membrane selectivity. Both filtration tests with the synthetic foulant-mixture solution (containing SA, SRNOM, and BSA) and MBR plant supernatant demonstrated the reliability and durability of the antifouling property of the superhydrophilic membrane. The conspicuous reduction in foulant–membrane interfacial forces for the functionalized membrane further verified the antifouling properties of the superhydrophilic membrane, suggesting great potential for applications in wastewater treatment.
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•Superhydrophilic PVDF UF membrane exhibits fouling resistance with a mixture of model organic foulants.•Superhydrophilic PVDF UF membrane exhibits fouling resistance with a wastewater (MBR) plant effluent.•Antifouling resistance correlates with reduction of foulant–membrane adhesion forces.•Surface functionalization does not degrade membrane selectivity.
Stress is well known to contribute to the development of both neurological and psychiatric diseases. In the central nervous system, a role for STING (stimulator of interferon genes) in modulating ...immunological responses has been widely suggested, and this protein possesses both neurotoxic and neuroprotective properties. However, the potential role of the STING signalling pathway and the underlying regulatory mechanism in chronic stress have not been well established. In this study, C57BL/6 mice were subjected to intermittent restraint stress for 14 days (6 h/day), and sucrose preference, elevated plus maze, and tail suspension tests were performed by mice subjected to chronic restraint stress (RST). Here, we showed that RST mice displayed depression-like behaviours, accompanied by increased levels of proinflammatory cytokines in the brain. We also observed remarkably decreased levels of the pathway components STING, p-TBK1 (phospho-TANK-binding kinase-1), and p-IRF3 (phospho-interferon regulatory factor-3) in the hippocampus and the prefrontal cortex of RST mice. Significant reductions in STING fluorescence intensity were also observed in the hippocampus and the prefrontal cortex of RST mice. Next, fluorescently labelled latex beads, flow cytometry, and CD68-positive cell counts were utilized to evaluate the phagocytic abilities of microglia in vivo and in vitro. Importantly, our results first indicated that activation of the STING pathway by administration of the STING agonist 2′3-cGAMP enhanced microglial phagocytosis and suppressed the release of the proinflammatory cytokines TNF-α, IL-6, and IL-1β in the brains of RST mice, which further led to antidepressant effects. Based on the results of our study, the amelioration of stress-driven depression-like behaviours by activation of the STING pathway is associated with the suppression of neuroinflammation and enhanced phagocytosis.
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•Chronic restraint stress induces depression-like behaviours and neuroinflammation.•The number of microglia is increased and cells are activated towards a proinflammatory phenotype during chronic stress.•STING activation enhances microglial phagocytosis through STING-dependent IFN-β signalling and inhibits the production of proinflammatory cytokines in the brain.•Activation of the STING signalling pathway ameliorates depression-like behaviours during chronic stress.
A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal 2.2.1azabicyclic ring system was discovered. Optimization of antiviral ...potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37–45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.
Long periods of sleep deprivation (SD) have serious effects on health. While the α2 adrenoceptor agonist dexmedetomidine (DEX) can improve sleep quality for patients who have insomnia, the effect of ...DEX on cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h SD daily for seven days. DEX (100 μg/kg) was administered intravenously twice daily (at 1:00 p.m. and 3:00 p.m.) during seven days of SD. We found that systemic administration of DEX attenuated cognitive deficits by performing the Y maze and novel object recognition tests and increased DCX+, SOX2+, Ki67+, and BrdU+NeuN+/NeuN+ cell numbers in the dentate gyrus (DG) region of SD mice by using immunofluorescence, western blotting, and BrdU staining. DEX did not reverse the decrease in DCX+, SOX2+, or Ki67+ cell numbers in SD mice after administration of the α2A-adrenoceptor antagonist BRL-44408. Furthermore, the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) expression was upregulated in SD+DEX mice compared with SD mice. Luminex analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of neuroinflammation, including IL-1α, IL-2, CCL5, and CXCL1. Our results suggested that DEX alleviated the impaired learning and memory of SD mice potentially by inducing hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway and by suppressing neuroinflammation, and α2A adrenoceptors are required for the neurogenic effects of DEX after SD. This novel mechanism may add to our knowledge of DEX in the clinical treatment of impaired memory caused by SD.
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•Dexmedetomidine ameliorates memory impairment induced by sleep deprivation.•Dexmedetomidine promotes adult hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway.•Dexmedetomidine inhibits hippocampal neuroinflammation in sleep-deprived mice.
Despite the potentially important effect of temperature on membrane fouling, very few investigations have been conducted on full-scale membrane bioreactors (MBRs) regarding seasonal variation of ...fouling. In this study, fouling behavior in a full-scale MBR (capacity 60,000m3/d) in northern China was monitored for a whole year. As the mixed liquor temperature dropped from 27 to 13°C, the filtration resistance increased from 0.6×1013 to 2.6×1013m−1, which was attributable to higher concentration of supernatant organics at lower temperatures. Humic substances were the predominant supernatant organics (10–25mg/L) in comparison with polysaccharides and proteins (both 5–15mg/L). The dependence of seasonal supernatant fouling potential on hydrophilic/hydrophobic composition and molecular weight distribution of the organics were analyzed based on statistical correlation. Humic substances in all hydrophobicity and molecular weight ranges correlated closely with the fouling potential. Hydrophilic polysaccharides and large-molecular-weight proteins were also found to contribute to the fouling potential.
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•Seasonal variation of fouling behavior was found in a full-scale MBR.•Concentrations of supernatant organics correlated negatively with temperature.•Supernatant organic characteristics impacted the fouling potential.•Humics, hydrophilic polysaccharides and large proteins dominated fouling.
As the manufacturing industry is the foundation of the national economy, many countries have made concerted efforts to promote the transition upgrading of manufacturing enterprises from political, ...industrial, and academic circles. This study employed content analysis to explore the transition upgrading factors for manufacturing enterprises from an energy source perspective. With the help of FsQCA (Fuzzy-sets qualitative comparative analysis), which can mine multivariate combination relationships using a small number of samples, this study quantitatively calculated the transition paths and energy source combinations of manufacturing enterprises. Three transition upgrading paths were proposed, including an innovation-oriented path, a business-oriented path, and an efficiency-oriented path. The results indicate that manufacturing enterprises can realize transition upgrading based on three key methods, including innovation resources and innovation activities, strategic layout, and production operation + network relationship (peripheral). Such a finding validated the rationality of the theoretical path design and improved the research depth and precision. Multiple case analyses of Huawei, Haier, and Lenovo reveal that manufacturing enterprises used three ways to promote transition upgrading: the joint action of innovation activities and innovation resources; the uni-directional causal effect of strategic layout adjustment to increase market value; and the coordination and matching role of network relations dominated by production and operation. We conclude that this study provides an effective decision-making basis and management reference for manufacturing enterprises, so that enterprises can choose an appropriate energy accumulation method and scientifically realize the transition upgrading.
China has been the forerunner of large-scale membrane bioreactor （MBR） application. Since the first large-scale MBR （≥ 10 000 m^3·d^-1） was put into operation in 2006, the engineering implementation ...of MBR in China has attained tremendous development. This paper outlines the commercial application of MBR since 2006 and provides a variety of engineering statistical data, covering the fields of municipal wastewater, industrial wastewater, and polluted surface water treatment. The total treatment capacity of MBRs reached 1× 10^6 m^3·d^-1 in 2010, and has currently exceeded 4.5 × 10^6 m^3·d^-1 with -75% of which pertaining to municipal wastewater treatment. The anaerobic/anoxic/aerobie-MBR and its derivative processes have been the most popular in the large-scale municipal application, with the process features and typical ranges of parameters also presented in this paper. For the treatment of various types of industrial wastewater, the configurations of the MBR-based processes are delineated with representative engineering cases. In view of the significance of the cost issue, statistics of capital and operating costs are also provided, including cost structure and energy composition. With continuous stimulation from the environmental stress, political propulsion, and market demand in China, the total treatment capacity is expected to reach 7.5 × 10^6 m^3·d^-1 by 2015 and a further expansion of the market is foreseeable in the next five years. However, MBR application is facing several challenges, such as the relatively high energy consumption. Judging MBR features and seeking suitable application areas should be of importance for the long-term development of this technology.
This study aimed to analyze the association between driver mutations and predictive markers for some anti–tumor agents in non–small cell lung cancer (NSCLC). A cohort of 785 Chinese patients with ...NSCLC who underwent resection from March 2016 to November 2017 in the First Affiliated Hospital of Guangzhou Medical University was investigated. The specimens were subjected to hybridization capture and sequence of 8 important NSCLC‐related driver genes. In addition, the slides were tested for PD‐L1, excision repair cross‐complementation group 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthase (TS) and β‐tubulin III by immunohistochemical staining. A total of 498 (63.4%) patients had at least 1 driver gene alteration. Wild‐type, EGFR rare mutation (mut), ALK fusion (fus), RAS mut, RET fus and MET mut had relatively higher proportions of lower ERCC1 expression. EGFR 19del, EGFR L858R, EGFR rare mut, ALK fus, HER2 mut, ROS1 fus and MET mut were more likely to have TS low expression. Wild‐type, EGFR L858R, EGFR rare mut and BRAF mut were associated with lower β‐tubulin III expression. In addition, wild‐type, RAS mut, ROS1 fus, BRAF and MET mut had higher proportion of PD‐L1 high expression. As a pilot validation, 21 wild‐type patients with advanced NSCLC showed better depth of response and response rate to taxanes compared with pemetrexed/gemcitabine (31.2%/60.0% vs 26.6%/45.5%). Our study may aid in selecting the optimal salvage regimen after targeted therapy failure, or the chemo‐regimen where targeted therapy has not been a routine option. Further validation is warranted.
Our study provides enlightenment for clinical practice. This study showed the association between driver mutations and sensitivity markers for some commonly used anti–tumor agents, and may aid in selecting optimal salvage regimens after targeted therapy failure or chemo‐regimens where targeted therapy has not been a routine option. In addition, the results explain why patients differ in sensitivity to various drugs from the perspective of gene mutations.
To separate and concentrate NH4＋ and PO43 from the synthetic wastewater to the concentrated solution through a novel electrochemical reactor with circulated anode and cathode using the difference of ...the concentration between electrode chamber and middle chamber.In recent years, the research on electrochemical processes have been focused on phosphate and ammonium removal and recovery. Among the wide range of possibilities with regards to electrochemical processes, capacitive deionization （CDI） saves the most energy while at the same time does not have continuity and selectivity. In this study, a new electrochemical reactor with electrolyte cyclic flowing in the electrode chambers was constructed to separate and concentrate phosphate and ammonium continuously and selectively from wastewater, based on the principle of CDI. At the concentration ratio of NaCI solution between the electrode chambers and the middle chamber （r） of 25 to 1, phosphate and ammonium in concentration level of domestic wastewater can be removed and recovered continuously and selectively as struvite. Long-term operation also indicated the ability to continuously repeat the reaction and verified sustained stability. Further, the selective recovery at the certain r could also be available to similar technologies for recovering other kinds of substances.
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