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The direct asymmetric α-arylation, allylation and benzylation of NH2 unprotected amino acid esters with aryl halides, allyl and benzyl chlorides are respectively achieved by chiral aldehyde catalysis.

Hepatocellular carcinoma (HCC) is the most predominant pathological type of primary liver cancer and is a serious threat to people's lives and health worldwide. In this study, the Cancer Genome Atlas (TCGA) database was used to explore the immunological role of CCDC137 in hepatocellular carcinoma and its prognostic value, and a predictive model containing CCDC137-related immune modulators was developed using Cox regression analysis. Levels of CCDC137 were significantly higher in liver tissue of HCC patients than in normal tissue, and CCDC137 expression was also significantly correlated with pathological stage, tumor stage, and the expression of CCDC137 was also significantly correlated with pathological stage, tumor stage, and histological grade. The robustness of the predictive ability of the model was fully validated by plotting ROC curves and nomograms and by the external validation cohort of the International Cancer Genome Consortium (ICGC) database. Our model provides additional options for targeted, immune-based systemic therapy.

Increased granulosa cell division is associated with abnormal folliculogenesis in polycystic ovary syndrome (PCOS). Lethal-7i microRNA (let-7i) may play an important role in the follicular development and granulosa cell growth; therefore is let-7i involved in PCOS pathogenesis?The expression of let-7i was measured in granulosa-luteal cells (GLC) from women with or without PCOS. A human granulosa cell line, KGN, was used for the functional study. Mimics and inhibitors of let-7i, lentiviruses expressing insulin-like growth factor 2 mRNA binding protein (IMP2), and small-interfering RNAs were transfected into KGN cells. KGN cell proliferation was determined by 5-ethynyl-2'-deoxyuridine (EdU) and Cell Counting Kit-8 (CCK-8) assays. The cell cycle and apoptosis were assessed by propidium iodide-annexin V (PI-A) staining and fluorescence-activated cell sorting. Oestradiol concentration was determined by enzyme-linked immunoassay. Bioinformatics analysis and luciferase reporter assay were applied to confirm the let-7i target genes.The study showed that let-7i was down-regulated in PCOS GLC (P = 0.001). Mimics of let-7i inhibited KGN proliferation (P = 0.001), and decreased aromatase expression (P = 0.030) and oestradiol production (P = 0.029), whereas let-7i inhibitors had the opposite effect. Bioinformatics analysis and quantitative real-time (qRT) PCR identified IMP2 as a target of let-7i (P = 0.021). qRT-PCR and western blot analysis indicated that IMP2 was up-regulated in GLC in women with PCOS (P = 0.001 and P = 0.044), and IMP2 expression was suppressed by let-7i in KGN cells (P 0.001). Luciferase reporter assay results (P = 0.002), combined with the rescue assay, confirmed that let-7i inhibited KGN cell proliferation and reduced oestradiol concentration by directly targeting IMP2.let-7i was down-regulated in PCOS GLC. Overexpression of let-7i inhibited KGN cell proliferation and decreased oestradiol production in an IMP2-dependent manner, providing a new molecular mechanism for PCOS.

Single-component CsMnxPb1−xBr3 NPLs emitted healthy white light without harmful deep blue light (400–450 nm). Their white LED worked continuously for 240 minutes with a lower color drift of (±0.006, ±0.004).

The direct catalytic hydrocarbylation of readily available amino acids with halohydrocarbons is one of the most straightforward methods leading to disubstituted non-proteinogenic amino acid compounds. However, all the re-ported methodologies depend on N-protected amino acids as starting materials. Herein, we report on three highly efficient aldehyde-catalyzed direct hydrocarbylations of N-unprotected amino acid esters with aryl-, allyl-, and benzyl halides. By promoting a simple chiral BINOL-aldehyde catalyst or combining catalysts of a chiral aldehyde and Lewis acid ZnCl2, the asymmetric arylation, allylation, and benzylation of amino acid esters with the corresponding halohydrocarbons proceed smoothly, producing disubstituted amino acids in moderate-to-high yields and good-to-excellent enantioselectivities. The asymmetric arylation reaction can be applied in the formal synthesis of the clinical candidate compound (+)-AG-041R. Based on the results given by control experiments, three reaction models are proposed to illustrate the stereoselective-control outcomes.

The epicardium plays an important role in cardiomyogenesis during development, while it becomes quiescent in adult heart during homeostasis. This study investigates the efficiency of thymosin β4 (Tβ4) release with RPRHQGVM conjugated to the C-terminus of RADA16-I (RADA-RPR), the functionalized self-assembling peptide (SAP), to activate the epicardium and repairing the infarcted myocardium. Methods: The functionalized SAP was constituted with self-assembling motif, Tβ4-binding site, and cell adhesive ligand. Myocardial infarction (MI) models of the transgenic mice were established by ligation of the left anterior descending coronary artery. At one week after intramyocardial injection of Tβ4-conjugated SAP, the activation of the epicardium was assessed. At four weeks after implantation, the migration and differentiation of epicardium-derived cells (EPDCs) as well as angiogenesis, lymphangiogenesis and myocardial regeneration were examined. Results: We found that the designer RADA-RPR bound Tβ4 and adhered to EPDCs and that Tβ4 released from the functionalized SAP could effectively activate the epicardium and induce EPDCs to differentiate towards cardiovascular cells as well as lymphatic endothelial cells. Moreover, SAP-released Tβ4 (SAP-Tβ4) promoted proliferation of cardiomyocytes. Furthermore, angiogenesis, lymphangiogenesis and myocardial regeneration were enhanced in the MI models at 4 weeks after delivery of SAP-Tβ4 along with attenuation of adverse myocardial remodeling and significantly improved cardiac function. Conclusions: These results demonstrate that sustained release of Tβ4 from the functionalized SAP can activate the epicardium and effectively enhance the repair of infarcted myocardium. We believe the delivery of SAP-Tβ4 may be a promising strategy for MI therapy.

Objectives: The aim of this study was to investigate the effects of berberine on polycystic ovary syndrome (PCOS) with insulin resistance (IR). Design: This study performed 16S rRNA sequencing and metabolomic analysis on dehydroepiandrosterone (DHEA)-induced PCOS rats treated with berberine, focusing on the improvement of PCOS-IR by modifying gut microbiota and metabolism. Methods: Forty-two female Sprague Dawley rats were randomly divided into 4 experimental groups of 8 rats each (PCOS + HFD, PCOS + HFD + BBR, NCD + PCOS, and NCD + PCOS + BBR groups). Homeostasis model assessment of insulin resistance (HOMA-IR) index-related indicators and hormone level in serum were analyzed. 16S rRNA sequencing and metabolomic analysis were performed on DHEA-induced PCOS rats treated with berberine. In addition, the differential microbiotas and metabolites were screened. Also, enrichment analysis was carried out on the differential metabolites. Finally, we constructed a correlation network to analyze the correlation between differential microbiotas and metabolites. Results: Firmicutes and Bacteroidetes were changed at the phylum level, and Romboutsia, Bacteroides, and Clostridium_sensu_stricto_1 were changed at the genus level after berberine treatment. In addition, a total of 26 differential operational taxonomic units and 3 metabolites (glutamine, unsaturated acids [CH = CH], and glucose) between 2 groups were obtained. Moreover, these metabolites were mainly involved in type 2 diabetes mellitus, 2-component system, and ABC transporter Kyoto Encyclopedia of Genes and Genomes pathways. And, 3 microbiotas (Lachnospiraceae_NC2004_group, Flavonifractor, and Parasutterella) were regulated by glucose and glutamine. Limitations: The sample size involved in this study is relatively small. In addition, relevant experiments need to be performed to verify the obtained results from this study, and in-depth functional studies are needed. Conclusions: Berberine is effective in improving the pathological condition in PCOS by regulating the gut microbiotas and metabolites. This study will provide evidence for therapeutic efforts to treat PCOS-IR using berberine.

Background Thinking of the rarity and malignancy of gynecologic tract carcinosarcomas (GTCS), the aim of the study was to investigate the possible predictors of relapse-free survival (RFS) and overall survival (OS) for GTCS patients. Methods We performed a retrospective cohort study of women with GTCS at our hospital between January 2009 and December 2013. We used the Kaplan-Meier method to calculate RFS and OS, and Cox regression analysis to define the survival effects of risk factors. Results A total of 45 GTCS patients were included in the study. The median follow-up time was 46 months. Cox regression analysis showed that lymph node metastasis was significantly associated with worse RFS (HR: 3.145; 95%CI: 1.181-8.378; P=0.022) and OS (HR: 4.065; 95%CI: 1.57-10.524; P=0.004). Pelvic lymphadenectomy had a favorable RFS (HR: 0.213; 95%CI: 0.057-0.796; P= 0.021). Conclusion Lymph node metastasis significantly affected the prognosis of uterine carcinosarcoma. Pelvic lymphadenectomy could reduce the relapse rate of GTCS patients.

The Brassica rapa (B. rapa) species displays enormous phenotypic diversity, with leafy vegetables, storage root vegetables and oil crops. These different crops all have different flowering time, which determine their growing season and cultivation area. Little is known about the effects of diverse temperature and day-lengths on flowering time QTL associated with FLC paralogues. We phenotyped the flowering time of a doubled haploid population, established from a cross between Yellow sarson and Pak choi under diverse environmental conditions. We identified flowering-time QTL (fQTL) in different photoperiod and temperature regimes in the greenhouse, and studied their colocation with known flowering time genes. As several fQTL colocalized with FLC paralogues, we studied the expression patterns of four FLC paralogues during the course of vernalization in parental lines. Under all environmental conditions tested the major fQTL that mapped to the BrFLC2_A02 locus was detected, however its effect decreased when plants were grown at low temperatures. Another fQTL that mapped to the FLC paralogue, BrFLC5_A03 was also identified under all tested environments, while no fQTL colocated with BrFLC1_A10 or BrFLC3_A03. Furthermore, the vernalization treatment decreased expression of all BrFLC paralogues in the parental lines, and showed the lowest transcript level after 28 days of vernalization. Transcript abundance stayed low after returning the plants for seven days to normal growth temperature. Interestingly, transcript abundance of BrFLC3_A03 and BrFLC5_A03 was repressed much stronger and already reached lowest levels after 14d in the early-flowering type YS-143. This study improves understanding of the effects of daylength and vernalization on flowering time in B. rapa and the role of the different BrFLC paralogues therein.

Background: Increased granulosa cell division is associated with abnormal folliculogenesis in polycystic ovary syndrome (PCOS). As the most abundant microRNA molecule in the development of follicles, let-7i was found to be differentially expressed in PCOS patients and controls. This study aimed to investigate the role of let-7i in PCOS and explore its related mechanisms.Methods: The expression of let-7i was measured in GCs from women with PCOS and without PCOS. An immortalized human granulose cell line, KGN, was used for the functional study. Let-7i mimics, let-7i inhibitors, lentiviruses expressing IMP2 and small-interfering RNA were transfected respectively into KGN cells. KGN cell proliferation was determined by an EdU assay kit and cck-8. Cell cycle and apoptosis were determined by PI staining and flow cytometry analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were utilized to evaluate genes expression. Estradiol biosynthesis was determined by ELISA analysis. Bioinformatics analysis and luciferase reporter assay were applied to confirm the target gene of let-7i.Results: let-7i was down-regulated in PCOS GCs. Let-7i mimics (150 nM) inhibited KGN proliferation, arrested cell cycle progression, and decreased aromatase expression and estradiol production, while the let-7i inhibitors (150 nM) had the opposite effect. Bioinformatics analysis and qRT-PCR identified IMP2 was a target of let-7i. QRT-PCR and western blot analysis indicated that IMP2 was up-regulated in PCOS GCs and the expression of IMP2 was suppressed by let-7i in KGN. The further luciferase reporter assay combined with rescue assay validated that let-7i inhibited KGN proliferation and estradiol production by directly targeting IMP2 mRNA.Conclusions: Let-7i was down-regulated in PCOS GCs. Let-7i overexpression inhibited KGN proliferation and decreased estradiol production in an IMP2-dependent manner, providing insights into the pathogenesis of PCOS.

Objective: To investigate the treatment/amelioration effects of berberine on insulin resistance (IR) associated with polycystic ovary syndrome (PCOS). Methods: 16S amplicon and metabolomics analyses were performed on different groups of rat models treated with berberine. We used 16S amplicon analysis to demonstrate the microbiota with the quasi-likelihood (QL) F-test of the edgeR package. We performed different metabolite analysis using principal component analysis (PCA), partial least squares discrimination analysis (PLS-DA), and orthogonal partial least squares discrimination analysis (OPLS-DA). We then constructed a correlation network of different microbiotas and metabolites through relevance, and analyzed correlations between/among different microbiotas and metabolites. Results: We obtained a total of 43 different microbiota bacterial communities, including 20 bacteria that were up-regulated and 23 that were down-regulated at the genus level. Regarding co-occurrence, Alistipes and the Family_XIII_AD3011_group that rejected each other were found in Ruminiclostridium_6 and Tyzzerella. Metabolomics analysis produced a total of three different metabolites that included one up-regulated (glutamine) and two down-regulated (unsaturated acids, UFA [CH=CH] and glucose) metabolites, as well as 22 pathways (including type 2 diabetes mellitus, 2-component system, and streptomycin biosynthesis). We subsequently screened those with a significance level of less than 0.05. Integrational analysis results showed that Lachnospiraceae_NC2004_group, Flavonifractor, Parasutterella, glucose, and glutamine were directly regulated. A literature search revealed that the Lacchinospiraceae_NC2004_group, glucose, and glutamine were affected by berberine and exerted a treatment/amelioration effect on IR associated with PCOS. Akkermansia, Bacteroides, and glucose were also associated with IR. Conclusion: Our results suggest that berberine plays a positive role in the treatment/amelioration of PCOS by affecting gut microbiota, and can therefore modulate metabolism.

The purpose of this study was to investigate the effect of Huaier on autophagy of human hepatoma SK-HEP-1 cells and the effect of autophagy on the proliferation of SK-HEP-1 cells. CCK-8 assay was used to evaluate the effect of Huaier on the proliferation of SK-HEP-1 cells under different concentrations and different times. Acridine orange staining was used to measure the effect of Huaier on the autolysosome formation in SK-HEP-1 cells. Immunofluorescence assay was applied to examine the effect of Huaier on the expression and distribution of autophagy marker LC3 in SK-HEP-1 cells. In addition， LC3 expression was also checked by immunoblot analysis in the presence of Huaier. At last， the effects of Huaier in combination with autophagy inhibitor bafilomycin A1 on the proliferation of SK-HEP-1 cells was detected by CCK-8 assay. The results showed that Huaier aqueous extract significantly inhibited the proliferation of human hepatoma SK-HEP-1 cells in a dose- and time-dependent manner. Huaier aqueous extract dramatically promoted the formation of autolysosome in SK-HEP-1 cells. Moreover， Huaier markedly increased the number and intensity of intracellular LC3 fluorescent puncta and up-regulated LC3-Ⅱ expression. These data indicated that Huaier evidently activated autophagy of SK-HEP-1 cells. Additionally， autophagy inhibition significantly attenuated the sensitivity of SK-HEP-1 cells to Huaier treatment. Therefore， autophagy activation is involved in the inhibitory effects of Huaier on the proliferation of human hepatoma SK-HEP-1 cells.

Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after induction with TGF-β1 were examined. Synthesis and degradation of collagens, secretion of IL-10, and expression of ALK-5 and p-Smad2/3 of TGF-β1-induced cells were assessed after treatment with serelaxin. Serelaxin inhibited differentiation of TGF-β1-induced CFs towards MFs, and reduced proliferation and migration of the induced cells. Moreover, serelaxin down-regulated expression of collagen I/III and TIMP-2, and up-regulated expression of MMP-2 and MMP-9 in the cells. After treatment with serelaxin, activity of MMP-2 and MMP-9 and secretion of IL-10 increased, expression of ALK-5 and the level of Smad2/3 phosphorylation was reduced significantly. These results suggest that serelaxin can inhibit differentiation of TGF-β1-induced CFs towards MFs, reduce production of collagens by suppressing ALK-5/Smad2/3 signaling pathway, and enhance extracellular matrix degradation by increasing MMP-2/TIMP-2 ratio and IL-10 secretion. Serelaxin may be a potential therapeutic drug for inhibiting cardiac fibrosis.

In order to analyze the control strategy of the low voltage ride through (LVRT) of DFIG during the asymmetric voltage sag, it is necessary to analyze the transient performance of a DFIG during the asymmetric voltage sag. In this paper, analyzed the influence of the asymmetric grid voltage to DFIG and the analysis method of the asymmetric voltage sag, and on the basis of positive and negative sequence mathematical model, analyzed the composition of stator output active and reactive power under the condition of asymmetric grid voltage. And built a DFIG asymmetric voltage drop simulation model of 1.5MW in MATLAB/Simulink, the simulation results shows that the stator voltage, current, active power and reactive power all present a double frequency ripple during the asymmetric voltage sag, consistent with theoretical analysis. It can provide theoretical basis for double-fed motor control strategy of asymmetric LVRT.

In order to analyze the operational capability of the low voltage ride through ( LVRT) of a gird-connected wind turbine with doubly fed induction generator (DFIG) effectively, it is necessary to evaluate operation characteristics of DFIG under a grid fault.By using the transient principle of the flux of stator and rotor, the expressions of transient currents of stator and rotor of DFIG are derived under the grid voltage sag. The transient process is analyzed by using the Matlab to derive the correctness of the expression. A control strategy is presented to eliminate harmonic currents by proposing the essential factors of over-current of stator and rotor. The output active power and reactive power are calculated by using the derived expression with different voltage sags. Based on the theoretical analysis, a DFIG is established to analysis the model of LVRT. Simulation results show that the control strategy is able to eliminate the harmonic currents and achieve the requirements of LVRT.