• Sutton Fabricius opublikował 1 rok, 3 miesiące temu

    Novel hydrazone derivatives 10a-m were prepared from N-Amino-11-azaartemisinin (9) and screened for their antimalarial activity by oral and intramuscular (i.m.) routes against multidrug-resistant Plasmodium yoelii in Swiss mice model. Several of the hydrazone derivatives showed higher order of antimalarial activity. Compounds 10b, 10g, 10m provided 100% protection to the infected mice at the dose of 24 mg/kg × 4 days via oral route. Fluorenone based hydrazone 10m the most active compound of the series, provided 100% protection at the dose of 6 mg/kg × 4 days via intramuscular route and also provided 100% protection at the dose of 12 mg/kg × 4 days via oral route. While artemisinin gave 100% protection at 48 mg/kg × 4 days and only 60% protection at 24 mg/kg × 4 days via intramuscular (i.m.) route. Compound 10m found to be four-fold more active than artemisinin via intramuscular route.NLRP3 inflammasome plays a crucial role in the innate immune system. Our group previously reported that the microglial adenosine 2A receptor (A2AR) regulates canonical neuroinflammation, which is affected by the glutamate concentration. However, the regulatory effect of A2AR on NLRP3 inflammasome and the effects of glutamate concentration remain unknown. Therefore, we aimed to investigate the regulatory effect of microglial A2AR on NLRP3 inflammasome assembly and activation as well as the effects of glutamate concentration on the inflammasome assembly and activation. Experiments were conducted on magnetically sorted primary microglia from P14 mice. The results showed that pharmacological A2AR activation ameliorated NLRP3 activation under no or low glutamate concentrations, but this effect was reversed by high glutamate concentrations. Moreover, the mRNA levels of NLRP3 inflammasome-related genes were not affected by A2AR activation or the glutamate concentration. We further demonstrated that A2AR activation inhibited the interaction between NLRP3 and caspase 1 under no or low glutamate concentrations while promoting their interaction under high glutamate concentrations. The oligomerization of ASC also showed a similar trend. In conclusion, our findings proved that the high glutamate concentration could reverse the inhibition of A2AR on NLRP3 inflammasome activation by modulating its assembly, which provides new insights into the regulatory effect of A2AR on neuroinflammation under different pathological conditions.The Drosophila Bicra (CG11873) gene encodes the sole ortholog of mammalian GLTSCR1 and GLTSCR1L, which are components of a chromatin remodeling complex involved in neoplasia and metastasis of cancer cells. Bicra is highly expressed in Drosophila larval CNS and adult brain, yet its physiological functions in the nervous system remain elusive. Here we report that Bicra is expressed in both neurons and glia of adult brains, and is required for courtship learning and choice ability of male flies. The function of Bicra in the mushroom body, and in particular, Bicra expression in neurons but not glia, is responsible for the male courtship learning and choice performance. This study unravels a novel function of Bicra in cognition-related courtship behaviors in Drosophila, and may provide insight into the neuronal functions of its mammalian orthologs.The proliferation and migration of Schwann cells (SCs) promote nerve regeneration after facial nerve injury. In recent years, the role of long noncoding RNAs (lncRNAs) in regulating SC proliferation and migration has been gradually uncovered. However, there is little evidence on the function of lncRNA RMRP (lnc-RMRP) in SC growth. In the present study, we performed loss-of-function and overexpression assays to explore the function of lnc-RMRP in SCs. The relationships between lnc-RMRP, miR-766-5p and CAND1 (cullin-associated and neddylation-dissociated 1) were analyzed using bioinformatics analysis, luciferase detection, RNA binding protein immunoprecipitation and RNA pulldown methods. CCK-8, EdU, Transwell and wound healing assays were utilized for the detections of cell proliferation and migration. We found that lnc-RMRP silencing enhanced cell proliferation and migration of SCs, while lnc-RMRP overexpression showed the opposite effect. Mechanistically, lnc-RMRP directly bound to and negatively modulated the expression of miR-766-5p. MiR-766-5p knockdown decreased cell viability, proliferation and migration of SCs, and also reversed the effects of lnc-RMRP silencing. In addition, lnc-RMRP positively regulated CAND1 expression by sponging miR-766-5p. Upregulation of CAND1 rescued the function of lnc-RMRP knockdown in regulating SC proliferation and migration. These data suggested that lnc-RMRP played a significant role in SC proliferation and migration, indicating that lnc-RMRP might be a potential therapeutic target for the treatment of facial nerve injury.

    This population-representative study examined the association of Medicaid expansion under the Patient Protection and Affordable Care Act (ACA) with postpartum depressive symptoms among low-income women.

    We used data from the 2009 – 2018 Pregnancy Risk Assessment Monitoring System (PRAMS) surveys for 13 Medicaid expansion and 7 non-expansion states. We used a generalized difference-in-differences approach and log-binomial regression models to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) comparing the likelihood of postpartum depressive symptoms among low-income women (≤138% of the federal poverty level) who delivered in expansion and non-expansion states.

    Adjusting for state and year fixed-effects and individual- and state-level confounders, low-income women who delivered in Medicaid expansion states had a decreased likelihood of postpartum depressive symptoms compared to low-income women who delivered in non-expansion states (PR=0.93, 95% CI 0.80, 1.07). Results were largely consistent across multiple sensitivity analysis specifications. Results were robust to falsification tests among women with incomes >138% of the federal poverty level.

    Our results indicate that Medicaid expansion may be associated with a small reduction in the likelihood of postpartum depressive symptoms. Future research should examine the potential for implementation of multiple supportive policies to achieve larger gains in treatment and prevention.

    Our results indicate that Medicaid expansion may be associated with a small reduction in the likelihood of postpartum depressive symptoms. Future research should examine the potential for implementation of multiple supportive policies to achieve larger gains in treatment and prevention.Annular configuration is conspicuous in the clinical manifestation of many skin diseases and can be helpful for the diagnosis and differential diagnosis. Variations may include arciform, ring-form, annular, circinate, serpiginous, gyrated, polycyclic, targeted or figurate forms, in different colors, sizes, and numbers, with various textures and surfaces. In infectious dermatoses, the annular reactions can be specific or nonspecific, while the underlying mechanisms remain largely unknown. In the specific reactions caused by direct invasion of the pathogens, the contest between the centrifugal outspread of the infectious agents and the centripetal impedance of the host immune response is supposed to determine the final conformation. Examples include erythema infectiosum, orf, erythema multiforme, and pityriasis rosea of viral origin. Bacterial infections that may display annular lesions include erythrasma, erythema (chronicum) migrans of Lyme borreliosis, secondary syphilis, cutaneous tuberculosis, and leprosy. Superficial mycosis, such as dermatophytosis, candida intertrigo, tinea imbricata, and subcutaneous mycosis, such as chromoblastomycosis, and algae infection protothecosis, are characterized by annular progression of the skin lesions. The creeping serpiginous extension is an alarming sign for the diagnosis of cutaneous larva migrans. A better understanding of the virulence and pathogenicity of the pathogens and the way and type of immune response will help to clarify the pathogenesis.This study examined the performance and microbial community dynamics of an anaerobic volatile fatty acid (VFA) production reactor for treating fruit waste by stepwise increasing organic loading rates (OLRs) from 8 to 24 g volatile total solids (VTS)/(L·d). Results showed that higher VFA concentrations of 52.25-61.90 g chemical oxygen demand (COD)/L can be maintained at each OLR, thereby resulting to a production of 0.70-0.76 g chemical oxygen demand (COD)VFA/g VTS. Notably, an increase in OLR from 8 to 14 g VTS/(L·d) was beneficial for achieving higher VFA concentrations and yields. Moreover, an increase in OLR affected the VFA distribution significantly; acetate and butyrate became dominant in the fermentation liquid at OLRs ≥ 14 g VTS/(L·d). Microbial community dynamics analysis revealed that phyla Firmicutes and Actinobacteriota were predominant at each OLR, and the genera Lactobacillus, Clostridium_sensu_stricto_12, and Caproiciproducens were closely related to anaerobic VFA production.Mature compost and rice bran were used as bulking agents to perform Food Waste Rapid Composting (FWRC) in a patented composting bin. The characteristics of CO2 and N2O emission and the denitrifying community were investigated. The release of CO2 and N2O concentrated in the early composting stage and reduced greatly after 28 h, and the N2O emission peak of the treatment with mature compost was 8.5 times higher than that of rice bran. The high N2O generation resulted from massive denitrifying bacteria and NOx–N in the composting material. The relative abundances of denitrifiers, correspondingly genes of narG and nirK were much higher in the treatment with mature compost, which contributed to the N2O emission. Moreover, the correlation matrices revealed that N2O fluxes correlated well with moisture, pH, temperature, and the abundances of nirK and nosZ genes during FWRC.Bacterial cellulose produced during Kombucha fermentation has recently received lots of attention owing to its desirable mechanical and physicochemical properties and is exploited for different food, textiles and environmental applications. However, lack of information on process feasibility often hinders large-scale manufacturing of Kombucha-based cellulose. Therefore, the current study assesses techno-economic feasibility of a 60-ton annual capacity Kombucha-based cellulose production facility using SuperPro designer. Economic feasibility analysis showed an estimation of 13.72 million US$ as total investment and 3.8 million US$ as operating costs with 89% expenses associated with facility dependent and labour costs. The process feasibility is revealed with a payback time of 4.23 years, 23.64% return on investment and 16.48% internal rate of return. Sensitivity analysis presented that increased volume of fermentation units and automating the process can significantly reduce input costs. Such research is necessary to aid policymakers in facilitating the commercialization of Kombucha-based cellulose at field scale.Anaerobic co-digestion of excess sludge (ES) and different varieties of rice straw including indica rice straw (IRS), japonica rice straw (JRS) and glutinous rice straw (GRS) was investigated in batch and semi-continuous experiments. The batch experiment results showed that the GRS addition presents the highest hydrolysis and methanogenesis rates, its cumulative methane yield (CMY) was 305.75 mL/g VS and its average methane content was 60.56%. After digestion, the structure of GRS was almost completely destroyed, which was beneficial to the degradation of lignocellulose. The digestive process is affected by the abundance of Actinobactereria, Proteobacteria, Methanosaetae and Methanosarcina. The results of semi-continuous digestion were similar to batch digestion. In addition, the addition of GRS increased TN concentration in biogas residue and TP concentration in biogas slurry, but was not conducive to the subsequent dehydration of sludge.

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