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1st chew syndrome: Our own experience with intraparotid injection therapy together with botulinum killer type A.
Mycobacterium kansasii (Mk) is a resilient opportunistic human pathogen that causes tuberculosis-like chronic pulmonary disease and mortality stemming from comorbidities and treatment failure. The standard treatment of Mk infections requires costly, long-term, multidrug courses with adverse side effects. The emergence of drug-resistant isolates further complicates the already challenging drug therapy regimens and threatens to compromise the future control of Mk infections. Despite the increasingly recognized global burden of Mk infections, the biology of this opportunistic pathogen remains essentially unexplored. In particular, studies reporting gene function or generation of defined mutants are scarce. Moreover, no transposon (Tn) mutagenesis tool has been validated for use in Mk, a situation limiting the repertoire of genetic approaches available to accelerate the dissection of gene function and the generation of gene knockout mutants in this poorly characterized pathogen. In this study, we validated the functionality of a powerful Tn mutagenesis tool in Mk and used this tool in conjunction with a forward genetic screen to establish a previously unrecognized role of a conserved mycobacterial small RNA gene of unknown function in colony morphology features and biofilm formation. We also combined Tn mutagenesis with next-generation sequencing to identify 12,071 Tn insertions that do not compromise viability in vitro. Finally, we demonstrated the susceptibility of the Galleria mellonella larva to Mk, setting the stage for further exploration of this simple and economical infection model system to the study of this pathogen. © 2020 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.Our previous study of coxsackievirus B3 (CVB3)-induced unfolded protein responses (UPR) found that overexpression of ATF6a enhances CVB3 VP1 capsid protein production and increases viral particle formation. These findings implicate that ATF6a signalling benefits CVB3 replication. However, the mechanism by which ATF6a signalling is transduced to promote virus replication is unclear. In this study, using a Tet-On inducible ATF6a HeLa cell line, we found that ATF6a signalling downregulated the protein expression of the endoplasmic reticulum (ER) degradation-enhancing α-mannosidase-like protein 1 (EDEM1), resulting in accumulation of CVB3 VP1 protein; in contrast, expression of a dominant negative ATF6a had the opposite effect. Furthermore, we found that EDEM1 was cleaved by both CVB3 protease 3C and virus-activated caspase and subsequently degraded via the ubiquitin-proteasome pathway. However, overexpression of EDEM1 caused VP1 degradation, likely via a glycosylation-independent and ubiquitin-lysosome pathway. Finally, we demonstrated that CRISPR/Cas9-mediated knockout of EDEM1 increased VP1 accumulation and thus CVB3 replication. This is the first study to report the ER protein quality control of non-enveloped RNA virus and reveals a novel mechanism by which CVB3 evades host ER quality control pathways through cleavage and degradation of the UPR target gene EDEM1, to ultimately benefit its own replication. © 2020 John Wiley & Sons Ltd.The hierarchically structured core-shell magnetic mesoporous silica nanospheres (Mag-MSNs) have attracted extensive attention, particularly in the studies of reliable preparation methods of the multifunctional materials and the diverse applications of these nanomaterials across a wide range of multidisciplinary researches. These Mag-MSNs have been prepared with well-designed synthesis strategies and used as adsorbent materials, biomedicine and catalysis due to their excellent magnetic responsiveness, large specific surface area and readiness in their surface modification. The surface functionalization of the core-shell Mag-MSNs bridges the gap between heterogeneous and homogeneous phases and greatly extends the properties and application prospects of the materials. selleck chemical The introduction of various molecular matrices into the shell of Mag-MSNs enables the combination of functionalization and magnetic separation technology. In some cases, it is an important feature in the sustainable development process to recover the functionalized core-shell Mag-MSNs after the reaction and reuse them without losing activity. In this review, the design strategies and the construction of the core-shell Mag-MSNs are discussed. Various surface functionalization methods of core-shell Mag-MSNs are summarized and the latest applications of these functionalized nanomaterials in the fields of biomedicine, catalysis and wastewater treatment are demonstrated. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.BACKGROUND We aimed to evaluate the metabolic status of pregnant women by assessing metabolic biomarkers in participants in the Japan Environment and Children's Study (JECS), a nationwide, multicenter, pregnancy and birth cohort. METHODS Pregnant women aged 14-50 years were studied in 15 centers across Japan. Clinical information was obtained using self-administered questionnaires. Blood samples were taken during the first two trimesters to measure metabolic biomarkers. Samples were divided into seven groups according to the weeks of pregnancy. RESULTS Among 82,972 pregnant women, 43 had only type 1 diabetes, 78 had only type 2 diabetes, 2,315 had only gestational diabetes and 354 had only dyslipidemia. HbA1c, total cholesterol, low-density lipoprotein cholesterol, and triglyceride across all the percentiles increased as pre-pregnancy body mass index increased, while high-density lipoprotein cholesterol levels across all the percentiles decreased as body mass index increased. HbA1c was high in participants with type 1 diabetes or type 2 diabetes only but not in those with gestational diabetes or hyperlipidemia only. Participants with type 2 diabetes or dyslipidemia only had high triglyceride in the first trimester, which then decreased in the second trimester. Participants with type 2 diabetes only also showed low high-density lipoprotein cholesterol, while participants with dyslipidemia only showed high total cholesterol and low-density lipoprotein cholesterol throughout. CONCLUSION Metabolic biomarkers were affected by blood sample timing and underlying metabolic disease. The JECS will clarify the influences of metabolic status during pregnancy on the health and development of the offspring in future studies. This article is protected by copyright. All rights reserved.
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