Genomic regions influencing intramuscular fat in divergently selected rabbit lines

Intramuscular fat (IMF) is one of the main meat quality traits for breeding programmes in livestock species. The main objective of this study was to identify genomic regions associated with IMF content comparing two rabbit populations divergently selected for this trait, and to generate a list of putative candidate genes. Animals were genotyped using the Affymetrix Axiom OrcunSNP Array (200k). After quality control, the data involved 477 animals and 93 540 SNPs. Two methods were used in this research: single marker regressions with the data adjusted by genomic relatedness, and a Bayesian multiple marker regression. Associated genomic regions were located on the rabbit chromosomes (OCU) OCU1, OCU8 and OCU13. The highest value for the percentage of the genomic variance explained by a genomic region was found in two consecutive genomic windows on OCU8 (7.34%). Genes in the associated regions of OCU1 and OCU8 presented biological functions related to the control of adipose cell function, lipid binding, transportation and localisation (APOLD1, PLBD1, PDE6H, GPRC5D and GPRC5A) and lipid metabolic processes (MTMR2). The EWSR1 gene, underlying the OCU13 region, is linked to the development of brown adipocytes. The findings suggest that there is a large component of polygenic effect behind the differences in IMF content in these two lines, as the variance explained by most of the windows was low. The genomic regions of OCU1, OCU8 and OCU13 revealed novel candidate genes. Further studies would be needed to validate the associations and explore their possible application in selection programmes.     

Chemical constituents from Fallopia cynanchoides (Hemsl.) Harald. var. cynanchoides

Fifteen compounds were isolated and elucidated from the alcohol extract of Fallopia cynanchoides by modern phytochemical isolation and spectroscopic methods, and these compounds can be divided into four sterols, a phenol, anthraquinones, a chromone, two stilbenes and three flavonoids. All of these compounds were obtained from this plant for the first time. Chemotaxonomic studies indicated that F. cynanchoides has very close relationships with F. convolvulus and F. aubertii, and the genus Fallopia may have close relationships with the genera Rheum, Fagopyrum, Reynoutria and Polygonum.     

Bedtime hypertension chronotherapy best reduces cardiovascular disease risk as corroborated by the Hygia Chronotherapy Trial. Rebuttal to European Society of Hypertension officials.

ABSTRACT

Reinhold Kreutz and colleagues in a recent editorial claim the Hygia Chronotherapy Trial lacks credibility because of deficient methods, thereby dismissing both the plausibility and clinical significance of its reported findings. They misstate and misrepresent crucial information, findings and conclusions unambiguously detailed in the published report of the Hygia Chronotherapy Trial. The purpose of this communication is to provide a complete rebuttal to each and every one of the misleading and scientifically unsupported claims by Kreutz et al. that calls into question their expertise to decry the merits, advantages, limitations and validity of correctly designed and conducted ambulatory blood pressure monitoring-based chronotherapy trials.     

Design and synthesis of purine connected piperazine derivatives as novel inhibitors of Mycobacterium tuberculosis

A series of novel purine linked piperazine derivatives were synthesized to identify new, potent inhibitors of Mycobacterium tuberculosis. The compounds were designed to target MurB disrupting the biosynthesis of the peptidoglycan and exert antiproliferative effects. The first series of purine-2,6-dione linked piperazine derivatives were synthesized using an advanced intermediate 1-(3,4-difluorobenzyl)-7-(but-2-ynyl)-3-methyl-8-(piperazin-1-yl)-1H-purine-2,6(3H,7H)-dione hydrochloride (6) which was coupled with varied carboxylic acid chloride derivatives. Following this piperazine linked derivatives were also synthesized from 6 using diverse isocyanate partners. The anti-mycobacterial activity of the analogues was tested against Mycobacterium tuberculosis H37Rv which revealed a cluster of six analogues (11, 24, 27, 32, 33 and 34), possessed promising activity. In comparison, a set of these new compounds possessed greater potencies relative to current drugs used in the clinic such as Ethambutol. These results were also correlated with computational molecular docking analysis, providing models for strong interactions of the inhibitors with MurB providing a template for the future development of preclinical agents against Mycobacterium tuberculosis.     

Tetrahydroquinoline units in flexible heteroarotinoids (Flex-Hets) convey anti-cancer properties in A2780 ovarian cancer cells

SHetA2 (NSC 721689), our lead Flex-Het anti-cancer agent, consists of a thiochroman (Ring A) and a 4-nitrophenyl (Ring B) linked by a thiourea bridge. In this work, several series of new analogs having a tetrahydroquinoline (THQ, Ring A) unit connected by a urea or thiourea linker to a 4-substituted phenyl (Ring B) have been prepared and evaluated relative to SHetA2 in terms of binding affinity with mortalin and inhibition of A2780 ovarian cancer cells. Six of the derivatives equaled or exceeded the efficacy shown by SHetA2. Compounds 1a-d (series 1), lacking a methyl on the Ring A nitrogen and the gem-dimethyls on the adjacent carbon, showed only weak activity. Salt 2, the quaternized N,N-dimethyl iodide salt analog of 1a, also possessed very modest growth inhibition in the cell line studied. Series 3 compounds, which had a C3 ketone and an N-methyl replacing the sulfur in Ring A, were most successful. Compound 3a [Ring A = 1,2,2,4,4-pentamethyl-3-oxo-1,2,3,4-tetrahydroquinolin-6-yl; urea linker; Ring B = 4-nitrophenyl] had slightly lower potency (IC₅₀ 3.8 μM), but better efficacy (94.8%) than SHetA2 (IC₅₀ 3.17 μM, efficacy 84.3%). In addition, 3c and 3d [urea and thiourea linkers, respectively; Ring B = 4-(trifluoromethyl)phenyl] and 3e and 3f [urea and thiourea linkers, respectively; Ring B = 4-(trifluoromethoxy)phenyl] were also evaluated since these agents possessed electron-withdrawing groups with H-bonding capability. All displayed good activity. Compounds 3c and 3e showed improvement in both potency and efficacy compared to SHetA2. In general, when the linker group between Rings A and B was a urea, efficacy values slightly exceeded those with a thiourea linker in the carbonyl-containing THQ systems 3a-g. In contrast, when Ring A possessed the 1,2,2,4,4-pentamethyl-3-hydroxytetrahydroquinolin-6-yl unit (4a-f, series 4), very modest potency and efficacy was observed. Model compound 5, an exact N-methyl THQ analog of SHetA2, demonstrated less potency (IC₅₀ 4.5 μM), but improved efficacy (91.7%). Modeling studies were performed to rationalize the observed results.     

2型糖尿病患者心率变异性与心率减速力的相关性及其对自主神经功能的评估价值

目的:探讨2型糖尿病(T2DM)患者心率变异性(HRV)与心率减速力(DC)的相关性及其对自主神经功能的评估价值。方法:选取2018年1月～2019年12月期间合肥市第一人民医院收治的120例T2DM患者为研究对象,纳入实验组,其中单纯T2DM患者69例(单纯T2DM组),T2DM伴周围神经病变(DPN)患者51例(DPN组),另选同期在我院进行心功能检查的健康志愿者120例作为对照组。所有受试者均进行24h动态心电图检查,根据检查结果计算HRV值[总标准差(SDNN)、两个相邻RR间期互差(PNN50)、差值均方根(RMSSD)]和DC值,根据各组受试者的DC值,统计对比各组的猝死风险,并分析T2DM患者DC值与HRV各项指标的相关性。结果:对照组、单纯T2DM组、DPN组的SDNN、PNN50、RMSSD、DC值依次降低(均P0.05)。对照组、单纯T2DM组、DPN组各猝死风险等级分布整体比较差异有统计学意义(P0.05),单纯T2DM组、DPN组猝死高危比例显著高于对照组,且DPN组猝死高危比例高于单纯T2DM组(均P0.05)。经Pearson相关分析,T2DM患者的DC值与SDNN、PNN50、RMSSD呈明显的正相关(P0.05)。结论:T2DM患者的DC值、HRV指标均低于正常人群,合并DPN的T2DM患者猝死风险明显提高,DC值与HRV指标间存在明显的正相关,可作为T2DM患者自主神经功能状态评估的重要指标。     

糖尿病肾病(DN)患者血清脂肪特异性丝氨酸蛋白酶抑制剂(Vaspin)水平的变化及其与炎症因子的关系研究

目的:分析糖尿病肾病(Diabetic Nephropthy,DN)患者血清脂肪特异性丝氨酸蛋白酶抑制剂(Vaspin)水平的变化及其与炎症因子的关系。方法:将我院近期(2016年10月-2019年10月)收治100例DN患者设置为DN组,依据DN临床进展分期分组,39例白蛋白尿正常者设置为A组、40例早期DN微量蛋白尿者设置为B组、21例临床DN大量蛋白尿者设为C组,并选取同期于我院的健康体检健康者50例设置为健康组。检测和比价各组糖脂代谢水平、血清Vaspin、炎性因子水平,并进行相关性分析。结果:四组入组者脂代谢各项指标水平相比差异无统计学意义(P0.05)。而DN组中A组、B组、C组患者血清糖代谢水平均明显高于健康组(P0.05)。DN组各组Vaspin、TNF-α、IL-6、MCP-1水平均高于健康组(P0.05)。C组、B组、A组IL-6、TNF-α、MCP-1升高,Vaspin降低(P0.05)。A组IL-10水平高于健康组(P0.05)。其余各组间比较(P0.05)。各组Vaspin水平与促炎因子IL-6、TNF-α、MCP-1水平呈负相关(P0.05),与抗炎因子IL-10水平无关(P0.05)。结论:随着疾病的严重程度增加,DN患者血清vaspin呈上升趋势,且与患者的炎症因子呈负相关。检测vaspin水平的变化有助于临床对该病的防治。     

手臂早期重复刺激有助于脑卒中患者运动功能恢复

为了探究脑卒中患者手臂进行重复感觉运动训练后5年的效果,本研究将100名脑卒中患者随机分配到实验组与对照组,进行为期6周的治疗。使用Brunnstrom-Fugl-Meyer (BFM)测试、上肢动作研究(ARA)和Barthel指数(BI)对脑卒中患者进行治疗前、中途和治疗后以及治疗后6个月和12个月评估,并对62位患者治疗后第5年重新评估。第5年随访结果显示,实验组BFM测试和ARA具有显著性差异,从初始评估到第5年评估各组间改善平均差为BFM17分和ARA17.4分,在BI指数中未发现效果。干预治疗对运动缺陷严重的患者治疗效果最佳。卒中急性期对患者手臂进行特定干预措施,对运动功能具有临床意义及长期效应,该结果归功于早期,重复和有针对性的手臂刺激。     

Minimum sample sizes for invasion genomics: Empirical investigation in an invasive whitefly

Analysis of population genetics provides insights into the evolutionary processes, among which the sample size choice is per se a crucial issue in the analysis. Genome‐wide high‐throughput techniques based on RADseq have been increasingly used in studies on the population genomics of invasive species. However, there is little information available regarding optimal sample sizes for analyzing population genomics of invasive species. In this study, we first use type IIB endonucleases restriction site‐associated DNA (2b‐RAD) to mine thousands of single nucleotide polymorphisms (SNPs) for native and introduced populations in Q1 clade (SPB and 17JN) and Q2 clade (ISQ and UAS0601) of the whitefly, Bemisia tabaci (Gennadius) MED (also known as B. tabaci biotype Q). Then, we used resampling techniques to create simulated populations with a random subset of individuals and 3,000 SNPs to determine how many individuals should be sampled for accurate estimates of intra‐ and interpopulation genetic diversity. We calculated the intrapopulation genetic diversity parameters (unbiased expected heterozygosity, observed heterozygosity, and the number of effect alleles) and pairwise genetic differentiation F_ST; finally, an ad hoc statistic, ΔK, was used to determine the optimal value. Our results showed that a sample size greater than four individuals (n ≥ 4) has little impact on estimates of genetic diversity within whitefly populations; moreover, precise estimate of F_ST can be easily achieved at a very small simple size (n = 3 or 4). Our results will provide in‐depth understanding of the optimization of sampling schemes in population genomics of invasive species.