Meta-analysis of the effect of KCNQ1 gene polymorphism on the risk of type 2 diabetes

The potassium voltage-gated channel, KQT-like subfamily member 1 (KCNQ1) is a member of 11 mammalian Kv channel families that plays a key role for the repolarization of the cardiac action potential as well as water and salt transport. Genome-wide association studies have identified KCNQ1 as a type 2 diabetes (T2D) susceptibility gene in populations of Asian descent. After that, a number of studies reported that the rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 polymorphism in KCNQ1 has been implicated in T2D risk. However, studies on the association between these polymorphism and T2D remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis of 114,140 patients and 167,322 controls from 30 published case–control studies was performed. Overall, significantly elevated T2D risk was associated with rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 risk allele when all studies were pooled into the meta-analysis. In the subgroup analysis by ethnicity, sample size, and Hardy–Weinberg equilibrium status of controls, significantly increased risks were found for these polymorphisms. In conclusion, this meta-analysis suggests that rs2237892, rs2237895, rs2237897, rs2283228, and rs231362 polymorphisms in KCNQ1 are associated with elevated T2D risk.     

ONTD induces apoptosis of human hepatoma Bel-7402 cells via a MAPK-dependent mitochondrial pathway and the depletion of intracellular glutathione

3-Oxo-29-noroleana-1,9(11),12-trien-2,20-dicarbonitrile (ONTD) is a novel synthetic derivative of glycyrrhetinic acid (GA), which has the ability to inhibit the proliferation of human hepatocellular carcinoma (HCC) cells. However, the mechanisms by which ONTD exerts its inhibitory effects remain elusive. The present study was conducted to investigate the cytotoxicity of ONTD in Bel-7402 cells and its molecular mechanisms. We found that ONTD depleted intracellular GSH, increased the level of ROS, and consequently induced mitochondrial permeability transition (MPT) leading to the release of apoptosis-inducing factor (AIF) and cytochrome c (Cyt c) to the cytosol. Mitochondrial alteration and subsequent apoptotic cell death in ONTD-treated Bel-7402 cells could be blocked by addition of exogenous antioxidants N-acetylcystein (NAC), GSH and the MTP inhibitor cyclosporin A (CsA). In addition, ONTD activated the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (MAPK) but not extracellular signal-regulated protein kinases (ERK 1/2). When the cells were exposed to SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), the deregulation of the expression of apoptotic proteins was attenuated. Furthermore, 40 mg/kg ONTD significantly reduced tumor weight (?70.62%, p < 0.01) in the H22 tumor-bearing mouse model in vivo. Taken together, these findings provide the first experimental evidence supporting that ONTD could induce apoptosis of Bel-7402 cells via MAPK-mediated mitochondrial pathway and ONTD has the potential to be developed as a therapeutic agent for the treatment of HCC.     

First synthesis of 12-oxosoladulcidine and its derivatives as potential antitumor steroidal alkaloids

The first synthesis of 12-oxosoladulcidine (= (3beta,5alpha,22alpha,25R)-3-hydroxyspirosolan-12-one; 4) is reported, and its structure was confirmed by single-crystal X-ray diffraction analysis. Compound 4 was readily obtained in five steps in an overall yield of 31%, starting from hecogenin (5). By slightly modifying the synthetic protocol, eight analogues of 4 were also prepared. The title compound and its derivatives are expected to be potent antitumor alkaloids, since structurally closely related to the known antitumor agents soladulcidine (2) and hecogenin (5).     

Reducing Staphylococcus aureus resistance to lysostaphin using CRISPR-dCas9

Bacteriolytic enzymes (cell lytic enzymes) are promising alternatives to antibiotics especially in killing drug-resistant bacteria. However, some bacteria slowly become resistant to various classes of peptidoglycan hydrolases, for reasons not well studied, in the presence of growth-supporting nutrients, which are prevalent at sites of infection. Here, we show that Staphylococcus aureus, a human and animal pathogen, while susceptible to the potent staphylolytic enzyme lysostaphin (Lst) in buffered saline, is highly resistant in the rich medium tryptic soy broth (TSB). Through a series of biochemical analysis, we identified that the resistance was due to prevention of Lst-cell binding mediated by the wall teichoic acids (WTAs) present on the cell surface. Inhibition or deletion of the gene tarO responsible for the first step of WTA biosynthesis greatly reduced S. aureus resistance to Lst in TSB. To overcome the resistance, we took advantage of the gene regulation potential of CRISPR-dCas9 and demonstrated that downregulation of tarO, tarH, and/or tarG gene expression, the latter two encoding enzymes that anchor WTAs in the outer layer of cell wall peptidoglycan, sensitized S. aureus to Lst and enabled eradication of the bacterium in TSB in 24 hr. As a result, we elucidate a key mechanism of Lst resistance in metabolically active S. aureus and provide a potential approach for treating life-threatening or hard-to-treat infections caused by Gram-positive pathogens.     

Integrated RNA-seq and RNAi Analysis of the Roles of the Hsp70 and SP Genes in Red-Shell Meretrix meretrix Tolerance to the Pathogen Vibrio parahaemolyticus

Marine Biotechnology - The “Wanlihong” Meretrix meretrix (WLH-M) clam is a new variety of this species that has a red shell and stronger Vibrio tolerance than ordinary M. meretrix...     

Diterpenoids and a Diarylheptanoid from Hedychium coronarium with Significant Anti‐Angiogenic and Cytotoxic Activities

Two new labdane diterpenoids, namely hedycoronals A and B ( 1 and 2 , resp.), were isolated from the rhizomes of Hedychium coronarium, together with eight known diterpenoids, 4 – 11 , and a known diarylheptanoid, 3 . The structures of 1 and 2 were established by detailed interpretation of their 1D‐ and 2D‐NMR spectra and HR‐ESI‐MS data. Inhibitory activities against human umbilical vein endothelial cells (HUMECs) proliferation and cytotoxic activities against four cancer cell lines were assessed for all the isolates. Most of these metabolites showed moderate or potent cytotoxic activities against four cancer cell lines. Moreover, compounds 3 and 8 exhibited promising inhibitory activities against HUMECs with the IC₅₀ values of 6.4 to 3.3 μM .     

不同株型玉米物质生产和群体库源特征的研究

玉米产量与吐丝期至成热期干物质积累量和这一阶段群体库源特征密切相关。紧凑型玉米比平展型玉米，吐丝至成熟期的于物质积累量高３０８７．６－４５２５．５ｋｇ／ｈｍ￣２，群体库容量大（１３２２．６－１５１６．８ｇ／ｍ￣２），源供应能力强（１０７３．０－１１６８．８ｇ／ｍ￣２），库源比值适宜（１．４５左右），因而籽粒产量相戍提高了２２１４．０－２７１６．５ｋｇ／ｈｍ￣２。玉米品种改良的关键是提高吐丝后群体物质生产效率和光合生产效率，同时使群体库源关系协调发展，相对平衡.