Notes

Protocol for that National Health professional Well being Study (NNHS): any web-based ambispective cohort study.
Despite their comparable performance to commercial solar systems, lead-based perovskite (Pb-perovskite) solar cells exhibit limitations including Pb toxicity and instability for industrial applications. To address these issues, two types of Pb-free materials have been proposed as alternatives to Pb-perovskite perovskite-based and non-perovskite-based materials. In this review, we summarize the recent progress on solar cells based on antimony/bismuth (Sb/Bi) chalcohalides, representing Sb/Bi non-perovskite semiconductors containing chalcogenides and halides. Two types of ternary and quaternary chalcohalides are described, with their classification predicated on the fabrication method. We also highlight their utility as interfacial layers for improving other solar cells. This review provides clues for improving the performances of devices and design of multifunctional solar systems.A 2D scanning micromirror with piezoelectric thin film aluminum nitride (AlN), separately used as actuator and sensor material, is presented. For endoscopic applications, such as fluorescence microscopy, the devices have a mirror plate diameter of 0.7 mm with a 4 mm2 chip footprint. After an initial design optimization procedure, two micromirror designs were realized. Different spring parameters for x- and y-tilt were chosen to generate spiral (Design 1) or Lissajous (Design 2) scan patterns. An additional layout, with integrated tilt angle sensors, was introduced (Design 1-S) to enable a closed-loop control. The micromirror devices were monolithically fabricated in 150 mm silicon-on-insulator (SOI) technology. Si (111) was used as the device silicon layer to support a high C-axis oriented growth of AlN. The fabricated micromirror devices were characterized in terms of their scanning and sensor characteristics in air. A scan angle of 91.2° was reached for Design 1 at 13 834 Hz and 50 V. For Design 2 a scan angle of 92.4° at 12 060 Hz, and 123.9° at 13 145 Hz, was reached at 50 V for the x- and y-axis, respectively. The desired 2D scan patterns were successfully generated. A sensor angle sensitivity of 1.9 pC/° was achieved.Liver fibrosis represents the wound healing response to sustained hepatic injury with activation of hepatic stellate cells (HSCs). The I148M variant of the PNPLA3 gene represents a risk factor for development of severe liver fibrosis. Activated HSCs carrying the I148M variant display exacerbated pro-inflammatory and pro-fibrogenic features. We aimed to examine whether the I148M variant may impair Hedgehog and Yap signaling, as key pathways implicated in the control of energy expenditure and maintenance of myofibroblastic traits. First, we show that TGF-β rapidly up-regulated the PNPLA3 transcript and protein and Yap/Hedgehog target gene expression. In addition, HSCs overexpressing PNPLA3 I148M boosted anaerobic glycolysis, as supported by higher lactate release and decreased phosphorylation of the energy sensor AMPK. These cells displayed higher Yap and Hedgehog signaling, due to accumulation of total Yap protein, Yap promoter activity and increased downstream targets expression, compared to WT cells. HSCs exposed to TGF-β and leptin rapidly increased total Yap, together with a reduction in its inhibited form, phosphorylated Yap. In line, Yap-specific inhibitor Verteporfin strongly abolished Yap-mediated genes expression, at baseline as well as after TGF-β and leptin treatments in HSCs with I148M PNPLA3. Finally, Yap transcriptional activity was strongly reduced by a combination of Verteporfin and Rosiglitazone, a PPARγ synthetic agonist. In conclusion, HSCs carrying the PNPLA3 variant show activated Yap/Hedgehog pathways, resulting in altered anaerobic glycolysis and enhanced synthesis of Hedgehog markers and sustained Yap signaling. TGF-β and leptin exacerbate Yap/Hedgehog-related fibrogenic genes expression, while Yap inhibitors and PPARγ agonists abrogate these effects in PNPLA3 I148M carrying HSCs.Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a global health concern and its treatment is problematic due to the rise in antimicrobial resistance (AMR). Rapid detection of patients infected with AMR positive S. Typhi is, therefore, crucial to prevent further spreading. Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated genes (CRISPR-Cas), is an adaptive immune system that initially was used for typing purposes. Later, it was discovered to play a role in defense against phages and plasmids, including ones that carry AMR genes, and, at present, it is being explored for its usage in diagnostics. Despite the availability of whole-genome sequences (WGS), very few studied the CRISPR-Cas system of S. Typhi, let alone in typing purposes or relation to AMR. In the present study, we analyzed the CRISPR-Cas system of S. Typhi using WGS data of 1059 isolates obtained from Bangladesh, India, Nepal, and Pakistan in combination with demographic data and AMR status. Osh. From this work, we conclude that there are strong correlations between variations identified in the S. Typhi CRISPR-Cas system and endemic AMR positive S. Typhi isolates.Leukoencephalopathy with calcifications and cysts (LCC) is a triad of neuroradiological symptoms characteristic of Labrune syndrome, which was first described in 1996. For 20 years, the diagnosis was only based on clinical, neuroradiological and histopathological findings. Differential diagnosis included a wide spectrum of diseases. Finally, in 2016, genetic mutation in the SNORD118 gene was confirmed to cause Labrune syndrome. The authors describe a case of a teenage girl with progressive headaches, without developmental delay, presenting with calcifications and white matter abnormality in neuroimaging. Follow-up studies showed the progression of leukoencephalopathy and cyst formation. The first symptoms and initial imaging results posed diagnostic challenges. The final diagnosis was established based on genetic results. The authors discuss the possible therapy of LCC with Bevacizumab.Adenosine is a purine nucleoside, responsible for the regulation of multiple physiological and pathological cellular and tissue functions by activation of four G protein-coupled receptors (GPCR), namely A1, A2A, A2B, and A3 adenosine receptors (ARs). GluR antagonist In recent years, extensive progress has been made to elucidate the role of adenosine in pain regulation. Most of the antinociceptive effects of adenosine are dependent upon A1AR activation located at peripheral, spinal, and supraspinal sites. The role of A2AAR and A2BAR is more controversial since their activation has both pro- and anti-nociceptive effects. A3AR agonists are emerging as promising candidates for neuropathic pain. Although their therapeutic potential has been demonstrated in diverse preclinical studies, no AR ligands have so far reached the market. To date, novel pharmacological approaches such as adenosine regulating agents and allosteric modulators have been proposed to improve efficacy and limit side effects enhancing the effect of endogenous adenosine. This review aims to provide an overview of the therapeutic potential of ligands interacting with ARs and the adenosinergic system for the treatment of acute and chronic pain.Anthocyanins are responsible for the red color of strawberry, they are a subclass of flavonoids synthesized in cytosol and transferred to vacuole to form the visible color. Previous studies in model and ornamental plants indicated members of the glutathione S-transferase (GST) gene family were involved in vacuolar accumulation of anthocyanins. In the present study, a total of 130 FaGST genes were identified in the genome of cultivated strawberry (Fragaria × ananassa), which were unevenly distributed across the 28 chromosomes from the four subgenomes. Evolutionary analysis revealed the expansion of FaGST family was under stable selection and mainly drove by WGD/segmental duplication event. Classification and phylogenetic analysis indicated that all the FaGST genes were clarified into seven subclasses, among which FaGST1, FaGST37, and FaGST97 belonging to Phi class were closely related to FvRAP, an anthocyanin-related GST of wildwood strawberry, and this clade was clustered with other known anthocyanin-related GSTs. RNAseq-based expression analysis at different developmental stages of strawberry revealed that the expression of FaGST1, FaGST37, FaGST39, FaGST73, and FaGST97 was gradually increased during the fruit ripening, consistent with the anthocyanins accumulation. These expression patterns of those five FaGST genes were also significantly correlated with those of other anthocyanin biosynthetic genes such as FaCHI, FaCHS, and FaANS, as well as anthocyanin regulatory gene FaMYB10. These results indicated FaGST1, FaGST37, FaGST39, FaGST73, and FaGST97 may function in vacuolar anthocyanin accumulation in cultivated strawberry.The serine/threonine kinase, GSK-3, is a promising drug discovery target for treating multiple pathological disorders. Most GSK-3 inhibitors that were developed function as ATP competitive inhibitors, with typical limitations in specificity, safety and drug-induced resistance. In contrast, substrate competitive inhibitors (SCIs), are considered highly selective, and more suitable for clinical practice. The development of SCIs has been largely neglected in the past because the ambiguous, undefined nature of the substrate-binding site makes them difficult to design. In this study, we used our previously described structural models of GSK-3 bound to SCI peptides, to design a pharmacophore model and to virtually screen the "drug-like" Zinc database (~6.3 million compounds). We identified leading hits that interact with critical binding elements in the GSK-3 substrate binding site and are chemically distinct from known GSK-3 inhibitors. Accordingly, novel GSK-3 SCI compounds were designed and synthesized with IC50 values of~1-4 μM. Biological activity of the SCI compound was confirmed in cells and in primary neurons that showed increased β-catenin levels and reduced tau phosphorylation in response to compound treatment. We have generated a new type of small molecule GSK-3 inhibitors and propose to use this strategy to further develop SCIs for other protein kinases.To promote the newest discoveries in oral cancer research, a special issue "Frontiers in Oral Cancer-Basic and Clinical Sciences" in the Journal of Clinical Medicine (JCM) was opened from September 2019 to April 2020 [...].An epidemic of chronic kidney disease of unknown origin (CKDu) has emerged in the past two decades in agricultural communities, characterized by progressive renal failure with a dearth of early clinical symptoms. The aim of this study is to improve understanding of the natural history of this disease and to evaluate the impact of an educational and behavioral intervention on the trajectories of renal decline among a cohort of Guatemalan sugarcane workers. We identified groups of workers based on their kidney function during a longitudinal parent study conducted among sugarcane workers during the 2016-2017 harvest season. At the study's first time point in February 2017, workers who developed abnormal kidney function (AKF) (estimated glomerular filtration rate, eGFR, less then 60 mL/min per 1.73 m2) were placed in the AKF group, workers with reduced kidney function (RKF) (eGFR 60-89) were placed in the RKF group, and workers who maintained normal kidney function (NKF) (eGFR ≥ 90) were placed in the NKF group.
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