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A new approach to the synthesis of Emitasvir (DAG181), a small molecule hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, is described. Enantioselective enzymatic desymmetrization ...

ObjectivesThe histidine kinase (HK) CHK1 and other protein kinases in Candida albicans are key players in the development of hyphae. This study is designed to determine the functional roles of the S_Tkc domain (protein kinase) and the GAF domain of C. albicans CHK1 in hyphal formation and mucosal invasion.MethodsThe domain mutants CHK25 (ΔS_TkcCHK1/Δchk1) and CHK26 (ΔS_TkcΔgafCHK1/Δchk1) were first constructed by the his1-URA3-his1 method and confirmed by sequencing and Southern blots. A mouse tongue infection model was used to evaluate the hyphal invasion and fungal loads in each domain mutant, full-gene deletion mutant CHK21 (chk1Δ/chk1Δ), re-constituted strain CHK23 (chk1Δ/CHK1), and wild type (WT) from day 1 to day 5. The degree of invasion and damage to the oral mucosa of mice in each strain-infected group was evaluated in vivo and compared with germ tube rate and hyphal formation in vitro.ResultWhen compared with severe mucosal damage and massive hyphal formation in WT- or CHK23-infected mouse tongues, the deletion of S_Tkc domain (CHK25) caused mild mucosal damage, and fungal invasion was eliminated as we observed in full-gene mutant CHK21. However, the deletion of S_Tkc and GAF (CHK26) partially restored the hyphal invasion and mucosal tissue damage that were exhibited in WT and CHK23. Regardless of the in vivo results, the decreased hyphal formation and germ tube in vitro were less apparent and quite similar between CHK25 and CHK26, especially at the late stage of the log phase where CHK26 was closer to WT and CHK23. However, growth defect and hyphal impairment of both domain mutants were similar to CHK21 in the early stages.ConclusionOur data suggest that both protein kinase (S_Tkc) and GAF domains in C. albicans CHK1 are required for hyphal invasiveness in mucosal tissue. The appropriate initiation of cell growth and hyphal formation at the lag phase is likely mediated by these two functional domains of CHK1 to maintain in vivo infectivity of C. albicans.

Supplemental Material, sj-pdf-1-dos-10.1177_15593258211067060 for Serum Metabolomic Analysis of Radiation-Induced Lung Injury in Rats by Yahui Feng, Yiying Gao, Wenling Tu, Yang Feng, Jianping Cao and Shuyu Zhang in Dose-Response

Supplemental Material for Transcriptome Profiling Unveils a Critical Role of IL-17 Signaling-Mediated Inflammation in Radiation-Induced Esophageal Injury in Rats by Jia Yao, Jinkang Zhang, Jinlong Wang, Qian Lai, Weijun Yuan, Zhongyu Liu, Shuanghua Cheng, Yahui Feng, Zhiqiang Jiang, Yuhong Shi, Sheng Jiang, and Wenling Tu in Dose-Response

An efficient procedure for enzymatic desymmetrization of the prochiral diphenol compound 2 was successfully developed to prepare the pharmaceutical intermediate (1S,4R)-8-hydroxy-1,2,3,4-tetrahydro...

An efficient method for the synthesis of (3R)-N-Boc-3-aminoazepane with immobilized ω-transaminase (ω-TA) has been further optimized. In comparison with the crude enzyme powder or wet whole cells, this immobilized enzyme exhibits excellent activity and stability under the optimum process conditions, allowing 20 rounds of enzyme reuse without obvious loss of activity. This procedure simplified the workup and was performed on a multikilogram scale in a reproducible manner to yield (3R)-N-Boc-3-aminoazepane with 99.2% ee and 97.0% purity.

Additional file 1: Supplementary Table 1. Recommended gestational weight gain of different criteria.

Additional file 1. Table S1. Population characteristics by residential region.

An efficient and novel route to (3R)-3-aminoazepane (1) is described. The target is obtained with 99.92% purity, 99.2% ee in seven steps, and 46.2% overall yield. This improved method involves a practical biocatalytic transformation with ω-transaminase to establish the stereogenic center high efficiently as a key step. The developed process was scalable, cost-effective, with a simplified reaction workup, avoiding the use of expensive metal catalyst or chromatography, and commercially viable for the synthesis of 1.

In this paper we analyze the reason of the etching trenches in chemical vapor deposition (CVD) graphene domain and study the influence factor in the distribution and morphology of wrinkles. Graphene is synthesized on Cu substrate. The Cu substrate is annealed at 1050℃ for 60 min with 1000 sccm Ar and 200 sccm H2. After annealing, 500 sccm Ar, 20 sccm H2, and 1 sccm dilute CH4 (mixed with Ar) are introduced into the CVD system for graphene growth. Hydrogen etchings of graphene are conducted with flows of 500 sccm Ar and 200 sccm H2 at atmospheric pressure, and etching are performed at 950 and 1050℃. The striated and reticular etching trenches are observed after etching via optical microscope and scanning electron microscope. Every graphene domain is divided into island structures by these etching trenches. However, the edge of graphene domain is not etched and the size of domain is not changed. Electron backscatter diffraction (EBSD) is conducted to analyze the different morphologies of etching trenches. According to the EBSD analysis, the etching trench is closely associated with the Cu crystal orientation. Different Cu planes result in differences in mode, shape, and density of the etching trench. We conduct a verification experiment to judge whether the etching trenches are caused by the gaps between graphene and Cu substrate or by the hydrogenation of wrinkles. The graphene domains grown on Cu substrate with the same growth condition are etched immediately after growth without cooling process. We select graphene which grows across the Cu grain boundary, via optical microscope. A small number of regular hexagons are observed in graphene surface and the region of Cu boundary, but no etching trench is found. As the graphene growing across Cu boundary is the suspending graphene and there is no etching trench, we consider that the gap between graphene and Cu species is not a significant factor of forming etching trench. For comparison, the etching trenches are observed in the graphene domains with cooling process. Thus, the trench formation is bound up with the cooling process after growth, which can lead to the wrinkle formation on the graphene surface, giving rise to a large thermal expansion coefficient difference between the graphene and Cu species. As a major type of structural imperfection, wrinkles can show that enhanced reactivity is due to hydrogenation because of high local curvature. So we consider that the trench formation is caused by the hydrogenation of wrinkles. Then the as-grown graphene domains are transferred to SiO2 substrate and atomic force microscope (AFM) is employed to measure the surface appearance of graphene. The AMF image shows lots of wrinkles in the graphene surface. The morphology and density of wrinkles are similar to those of the etching trenches extremely. Thus, the AFM testing result provides another evidence to prove that the etching trenches are related to the hydrogenation of wrinkles. From the above we can draw some conclusions. Numerous trenches are observed in the graphene domains after etching, and the trench patterns are closely associated with the Cu crystal orientation. A different Cu crystal orientation leads to variations in mode, shape, and density of the etching trench. We prove that the etching trenches are caused by the hydrogenation on wrinkles formed in the cooling down process instead of the gap between Cu and graphene. This hydrogen etching technology is a convenient way to detect the distribution and morphology of wrinkles. Furthermore, it provides a reference for improving the quality of CVD graphene.