Expanding the Structural Diversity of Tubulin-Targeting Agents: Development of Highly Potent Benzimidazoles for Treating Fungal Diseases.

Benzimidazoles, the representative pharmacophore of fungicides, have excellent antifungal potency, but their simple structure and single site of action have hindered their wider application in agriculture. In order to extend the structural diversity of tubulin-targeted benzimidazoles, novel benzimidazole derivatives were prepared by introducing the attractive pyrimidine pharmacophore. 2-((6-(4-(trifluoromethyl)phenoxy)pyrimidin-4-yl)thio)-1-benzo[]imidazole () exhibited optimal antifungal activity against (), affording an excellent half-maximal effective concentration (EC) of 0.

Identification of novel 4-substituted 7H-pyrrolo[2,3-d]pyrimidine derivatives as new FtsZ inhibitors: Bioactivity evaluation and computational simulation.

Bacterial infections and the consequent outburst of bactericide-resistance issues are fatal menace to both global health and agricultural produce. Hence, it is crucial to explore candidate bactericides with new mechanisms of action. The filamenting temperature-sensitive mutant Z (FtsZ) protein has been recognized as a new promising and effective target for new bactericide discovery.

The efficacy and safety of 5-fluorouracil/cisplatin/vincristine as a multi-agent chemotherapy regimen in gestational trophoblastic neoplasia.

Objective: To determine the efficacy and safety of the 5-fluorouracil (5-FU), cisplatin, and vincristine (FPV) chemotherapy regimen in patients with gestational trophoblastic neoplasia (GTN).

Methods: We performed a retrospective study of 96 GTN patients with International Federation of Gynecology and Obstetrics (FIGO) scores of 5 or greater in the Second Affiliated Hospital of Zhengzhou University from October 2013 to October 2019, including 54 patients who received FPV chemotherapy and 42 who received 5-FU/actinomycin D/vincristine (FAV) chemotherapy. A pulsed intravenous device was used to administer 5-FU.

Exploiting Natural Maltol for Synthesis of Novel Hydroxypyridone Derivatives as Promising Anti-Virulence Agents in Bactericides Discovery.

Anti-infection strategies based on suppression of bacterial virulence factors represent a crucial direction for the development of new antibacterial agents to address the resistance triggered by traditional drugs'/pesticides' bactericidal activity. To identify and obtain more effective and diverse molecules targeting virulence, we prepared a series of 3-hydroxy-2-methyl-1-pyridin-4-(1)-one derivatives and evaluated their antibacterial behaviors. Compound exhibited the highest bioactivity, with half-maximal effective concentration (EC) values ranging fro9m 10.

Dynamic of centromere associated RNAs and the centromere loading of DNA repair proteins in growing oocytes.

Mammalian centromeres are generally composed of dispersed repeats and the satellites such as α-satellites in human and major/minor satellites in mouse. Transcription of centromeres by RNA polymerase II is evolutionary conserved and critical for kinetochore assembly. In addition, it has been found that the transcribed satellite RNAs can bind DNA repair proteins such as MRE11 and PRKDC, and excessively expressed satellite RNAs could induce genome instability and facilitate tumorigenesis.

Design, Synthesis and Bioactivity Evaluation of Novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents.

Imidazole alkaloids, a common class of five-membered aromatic heterocyclic compounds, exist widely in plants, animals and marine organisms. Because of imidazole's extensive and excellent biological and pharmacological activities, it has always been a topic of major interest for researchers and has been widely used as an active moiety in search of bioactive molecules. To find more efficient antibacterial compounds, a series of novel imidazole-fragment-decorated 2-(pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized based on our previous works via the active substructure splicing principle, and their bioactivities were systematically evaluated both in vitro and in vivo.

Development of thermostable sucrose phosphorylase by semi-rational design for efficient biosynthesis of alpha-D-glucosylglycerol.

Sucrose phosphorylase (SPase) can specifically catalyze transglycosylation reactions and can be used to enzymatically synthesize α-D-glycosides. However, the low thermostability of SPase has been a bottleneck for its industrial application. In this study, a SPase gene from Leuconostoc mesenteroides ATCC 12,291 (LmSPase) was synthesized with optimized codons and overexpressed successfully in Escherichia coli.

Garcinone-E exhibits anticancer effects in HeLa human cervical carcinoma cells mediated via programmed cell death, cell cycle arrest and suppression of cell migration and invasion.

Xanthones are an important class of natural compounds bearing huge bioactivity profiles. Garcinone-E is one among most active xanthones showing potential anticancer activity against various human cancer cell lines. Therefore, the current study was performed to explore the anticancer potency of naturally occurring garcinone-E xanthone against human HeLa cervical cancer cells.

Activation of BK Channels Prevents Hepatic Stellate Cell Activation and Liver Fibrosis Through the Suppression of TGFβ1/SMAD3 and JAK/STAT3 Profibrotic Signaling Pathways.

Large-conductance and Ca-activated K (BK) channels are expressed in human hepatic stellate cells (HSCs), where they have roles in normal hepatic microcirculation, as well as in portal hypertension in liver cirrhosis through the regulation of contractility in activated HSCs. Nevertheless, whether BK channel activity exerts protective effects against aberrant HSC activation and hepatic fibrosis is unknown. Here, we report that BK channels are expressed in activated primary rat HSCs as well as in a human HSC line.

[A cohort study of serum leptin level in Zhejiang Province middle and old age residents on blood pressure and hypertension from 2014 to 2017].

Objective: To investigate the association between serum leptin concentration with blood pressure and hypertension in different gender.

Methods: A total of 343 non-hypertensive residents aged 30 to 65 were randomly selected from Zhejiang Province in 2014. Parameters including height, weight, waist, blood pressure, serum lipid and serum leptin concentration of participants were measured and determined by physical examination and laboratory detection in 2014 and 2017.

[Effects of isocaloric diets with different percentage energy from fat on blood glucose and lipids in rats].

Objective: To investigate the effects of isocaloric diets with different percentage energy from fat on blood glucose and lipids in rats.

Methods: Forty male SD rats were assigned to low fat group, normal fat group, medium fat group and high fat group using randomized blocks method. Rats in four groups were fed with isocaloric diets whose percentage energy from fat were 5%, 15%, 25% and 40% respectively for 10 weeks.

[Effects of marginal zinc deficiency on obesity].

Objective: To investigate the influence of marginal zinc deficiency on obesity and provide the theory basis for the prevention and treatment of obesity.

Methods: Thirty two male SPF SD rats were randomly divided into four groups. Four groups were supplied different doses of zinc.

[Effect of body mass index, waist-to-height ratio and dietary fat on serum leptin level of middle-age adult in Zhejiang Province].

Objective: To investigate the association between body mass index(BMI), waist-to-height ratio(WHtR) and dietary fat with serum leptin concentration.

Methods: A three-day 24-h dietary recall method was conducted on 513 participants aged30-65 years who were randomly selected from Zhejiang Province in 2014 to investigate usual fat intake. In addition, parameters including height, weight, waist and serum leptinconcentration of participants were measured and determined by physical examination and laboratory detection.

Chemotherapy-induced uridine diphosphate release promotes breast cancer metastasis through P2Y6 activation.

Although purinergic signaling is important in regulation of immune responses, the therapeutic potential of it in the tumor microenvironment is little defined. In this study, we demonstrate that UDP/P2Y6 signaling facilitates breast cancer metastasis both in vitro and in vivo. We found that P2Y6 is not only aberrantly expressed and mutated in most tumor types, but also highly correlated with poor prognosis in breast cancer patients.

Human EAG channels are directly modulated by PIP2 as revealed by electrophysiological and optical interference investigations.

Voltage-gated ether à go-go (EAG) K(+) channels are expressed in various types of cancer cells and also in the central nervous system. Aberrant overactivation of human EAG1 (hEAG1) channels is associated with cancer and neuronal disorders such as Zimmermann-Laband and Temple-Baraitser syndromes. Although hEAG1 channels are recognized as potential therapeutic targets, regulation of their functional properties is only poorly understood.

[Construction of P2Y6 constitutive knock down breast cancer cell line and evaluation of its proliferation].

Aim: To construct the constitutive P2Y6 knock down breast cancer cell line with shRNA technology and provide a basis for discovering how P2Y6 regulates tumorigenesis and progression in breast cancer.

Methods: The paired oligo nucleotides targeting human P2Y6 gene were synthesized and annealed into linear PLKO lentiviral vector digested by EcoRI and AgeI. The recombined vector which was identified by double digest with EcoRI and NdeI and DNA sequencing was packaged in 293T cells together with psPAX2 and pMD2.

Nitidine Chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling pathway.

Nitidine is a benzophenanthridine alkaloid, which has been shown to have anti-tumor properties. Here, we demonstrated that Nitidine Chloride (NC) could inhibit breast cancer cells migration and invasion both in vitro and in vivo. Meanwhile, the protrusion formation and partial proteolytic activity of MMP-9 and MMP-2 were attenuated by NC in a dose-dependent manner in MDA-MB-231 cells.

Evaluation of the expert patient program in a Chinese population with permanent colostomy.

Background: A colostomy can negatively impact patients' quality of life. Recent research findings suggest that self-efficacy and psychosocial adjustment are positively associated with quality of life, but there are few research reports about the self-efficacy and psychosocial adjustment of patients with a permanent colostomy.

Objectives: The objective of the study was to evaluate the effect of a 3-week Expert Patient Program (EPP) on colostomy knowledge, stoma care self-efficacy, self-management, and psychosocial adjustment in Chinese patients who had a permanent colostomy.