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Summary: As a frequently consumed beverage worldwide, tea is rich in naturally important bioactive metabolites. Combining genetic, metabolomic and biochemical methodologies, here, we present a comprehensive study to dissect the chemical diversity in tea plant. A total of 2837 metabolites were identified at high‐resolution with 1098 of them being structurally annotated and 63 of them were structurally identified. Metabolite‐based genome‐wide association mapping identified 6199 and 7823 metabolic quantitative trait loci (mQTL) for 971 and 1254 compounds in young leaves (YL) and the third leaves (TL), respectively. The major mQTL (i.e., P < 1.05 × 10−5, and phenotypic variation explained (PVE) > 25%) were further interrogated. Through extensive annotation of the tea metabolome as well as network‐based analysis, this study broadens the understanding of tea metabolism and lays a solid foundation for revealing the natural variations in the chemical composition of the tea plant. Interestingly, we found that galloylations, rather than hydroxylations or glycosylations, were the largest class of conversions within the tea metabolome. The prevalence of galloylations in tea is unusual, as hydroxylations and glycosylations are typically the most prominent conversions of plant specialized metabolism. The biosynthetic pathway of flavonoids, which are one of the most featured metabolites in tea plant, was further refined with the identified metabolites. And we demonstrated the further mining and interpretation of our GWAS results by verifying two identified mQTL (including functional candidate genes CsUGTa, CsUGTb, and CsCCoAOMT) and completing the flavonoid biosynthetic pathway of the tea plant. [ABSTRACT FROM AUTHOR]

The primary contribution of this paper is the extension of the gm/ID design methodology to two-stage operational amplifiers with class-AB output stages. First, the circuit is analyzed from the perspective of the gm/ID methodology, with a focus on its performance metrics and constraints. Second, to handle optimization targets and constraints automatically, the circuit sizing task is formulated as a single-objective optimization problem, and an optimizer is employed to obtain the temporary solution automatically. Benefiting from the gm/ID methodology, the gap between analytical equations and circuit simulation is highly reduced. Third, following the temporary solution, a guided fine-tuning method is introduced to further optimize the temporary solution. To demonstrate the effectiveness of this approach, we compared the equation-based method using the square-law model, two simulation-based methods and a commercial tool, Cadence ADE GXL, employing SMIC 55 nm and SMIC 180 nm CMOS technologies. The simulation results confirm the success of the proposed approach, showing that it not only reduces the gap between analytical equations and simulations, but also achieves the best performance metrics. [ABSTRACT FROM AUTHOR]

BackgroundTritium is one of the radionuclides released during the operation of nuclear facilities. The radiation hazard of tritium to human body is internal exposure, which is not only related to the activity of tritium, but also closely related to the chemical form and intake route of tritium. In view of the current standards involving tritium, there is an inconsistency in the control limit of tritiated water (HTO), as well as elemental tritium (HT).PurposeThis study aims to derive and standardize the concentration limits of HTO and HT, as well as the discharge activity concentration limits of HTO.MethodsThe development of tritium concentration control limits and the basis for the formulation of relevant standards were analyzed. According to the current radiation protection standards of China, combined with the latest biodosimetry parameters of tritium in publications of International Atomic Energy Agency (IAEA) and International Commission on Radiological Protection (ICRP), the control limits of derived air concentration (DAC) and water activity concentration for tritium were recalculated. When calculating the recommended limit of air concentration derived from HTO, the skin absorption was converted into the inhalation, and the complete skin absorption was set to half of the inhalation.ResultsSince the dose conversion coefficient used in the current standard is close to that in the new international publications, the recommended limits of HTO are slightly smaller than that specified in the standard, and the corresponding values are basically in the same order of magnitude.ConclusionsThe derived results can provide reference for the standard formulation of radiation protection management. The applicable objects of control limits are also clearly exhibited and distinguished. These objects are only available for people, not for facilities or equipment.

Background and Aims Mesenteric adipose tissue hypertrophy is a hallmark of Crohn's disease [CD], and creeping fat [CF] is unique to CD. Adipose-derived stem cells [ASCs] from inflammatory tissue exhibited altered biological functions. The role of ASCs isolated from CF in intestinal fibrosis and the potential mechanism remain unclear. Methods ASCs were isolated from CF [CF-ASCs] and disease-unaffected mesenteric adipose tissue [Ctrl-ASCs] of patients with CD. A series of in vitro and in vivo experiments were conducted to study the effects of exosomes from CF-ASCs [CF-Exos] on intestinal fibrosis and fibroblast activation. A micro-RNA microarray analysis was performed. Western blot, luciferase assay and immunofluorescence were performed to further detect the underlying mechanisms. Results The results indicated that CF-Exos promoted intestinal fibrosis by activating fibroblasts in a dose-dependent manner. They continuously promoted progression of intestinal fibrosis even after dextran sulphate sodium withdrawal. Further analysis showed that exosomal miR-103a-3p was enriched in CF-Exos and participated in exosome-mediated fibroblast activation. TGFBR3 was identified as a target gene of miR-103a-3p. Mechanistically, CF-ASCs released exosomal miR-103a-3p and promoted fibroblast activation by targeting TGFBR3 and promoting Smad2/3 phosphorylation. We also found that the expression of miR-103a-3p in diseased intestine was positively associated with the degree of CF and fibrosis score. Conclusion Our findings show that exosomal miR-103a-3p from CF-ASCs promotes intestinal fibrosis by activating fibroblasts via TGFBR3 targeting, suggesting that CF-ASCs are potential therapeutic targets for intestinal fibrosis in CD. [ABSTRACT FROM AUTHOR]