Identification of an LDLR variant in a Chinese familial hypercholesterolemia and its relation to ROS/NLRP3-Mediated pyroptosis in hepatic cells

BACKGROUND Familial hypercholesterolemia(FH)is a common autosomal dominant hereditary disease.Its early diagnosis and intervention significantly improve the patient’s quality of life.However,there are few types of research on the FH pathogenic genes in China.METHODS In this study,we recruited a family diagnosed with FH and used whole exome sequencing(WES)to analyze the proband variants.Intracellular cholesterol level,reactive oxygen species(ROS)level,and the expression of pyroptosis-related genes were detected after overexpression of wild-type or variant LDLR in L02 cells.RESULTS A heterozygous missense variant predicted to be deleterious to LDLR(c.1879G>A,p.Ala627Thr)was identified in the proband.Mechanistically,intracellular cholesterol level,ROS level,and the expression of pyroptosis-related genes,nucleotidebinding oligomerization domain-like receptor family protein 3(NLRP3)inflammasome and components(caspase 1,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC)and NLRP3),gasdermin D(GSDMD),interleukin(IL)-18,IL-1βwas elevated in the variant LDLR group,which was attenuated by inhibition of ROS.CONCLUSIONS FH is associated with a variant(c.1879G>A,p.Ala627Thr)in the LDLR gene.Regarding the mechanism,the ROS/NLRP3-mediated pyroptosis in hepatic cells may contribute to the pathogenesis of the LDLR variant.

Discoursing on Soxhlet extraction of ginseng using association analysis and scanning electron microscopy

Soxhlet extraction is a common method of sample preparation. However, there has been no discussion about the efficiency of Soxhlet extraction from different batches and the factors that cause content fluctuation. In this study, Panax ginseng was selected as a model sample. Soxhlet extraction by means of a water bath, which has always been neglected, was identified as a novel key factor in the poor repeat- ability in different batches of Soxhlet extraction, as it can affect the siphon times and reflux time, which have been positively correlated with the ginsenoside contents. By substituting round bottom flasks in the same column, the relative standard deviation of the most fluctuated compound, ginsenoside Rbl, was decreased from 24.6% to 5.02%. Scanning electron microscopy analysis confirmed that the breakdown of the surface of the ginseng powder in the Soxhlet extraction led to a better dissolution of ginsenosides, indicating that chloroform may promote the extraction of ginsenosides by disrupting the cell structure. Moreover, 70% methanol was regarded as the better solvent for extracting the ginsenosides. Overall, this work offers a practical and effective protocol for improving the accuracy and repeatability of Soxhlet extraction methodology for ginsenosides and other analytes.

Characterizing a large outbreak of dengue fever in Guangdong Province, China

Background:Dengue cases have been reported each year for the past 25 years in Guangdong Province,China with a recorded historical peak in 2014.This study aims to describe the epidemiological characteristics of this large outbreak in order to better understand its epidemic factors and to inform control strategies.Methods:Data for clinically diagnosed and laboratory-confirmed dengue fever cases in 2014 were extracted from the China Notifiable Infectious Disease Reporting System.We analyzed the incidence and characteristics of imported and indigenous cases in terms of population,temporal and spatial distributions.Results:A total of 45224 dengue fever cases and 6 deaths were notified in Guangdong Province in 2014,with an incidence of 47.3 per 100000 people.The elderly(65+years)represented 11.7%of total indigenous cases with the highest incidence(72.3 per 100000).Household workers and the unemployed accounted for 23.1%of indigenous cases.The majority of indigenous cases occurred in the 37th to 44th week of 2014(September and October)and almost all(20 of 21)prefecture-level cities in Guangdong were affected.Compared to the non-Pearl River Delta Region,the Pearl River Delta Region accounted for the majority of dengue cases and reported cases earlier in 2014.Dengue virus serotypes 1(DENV-1),2(DENV-2)and 3(DENV-3)were detected and DENV-1 was predominant(88.4%).Conclusions:Dengue fever is a serious public health problem and is emerging as a continuous threat in Guangdong Province.There is an urgent need to enhance dengue surveillance and control,especially for the high-risk populations in high-risk areas.

Facilitating fine-grained intra-urban dengue forecasting by integrating urban environments measured from street-view images

Background:Dengue fever(DF)is a mosquito-borne infectious disease that has threatened tropical and subtropical regions in recent decades.An early and targeted warning of a dengue epidemic is important for vector control.Current studies have primarily determined weather conditions to be the main factor for dengue forecasting,thereby neglecting that environmental suitability for mosquito breeding is also an important factor,especially in fine-grained intra-urban settings.Considering that street-view images are promising for depicting physical environments,this study proposes a framework for facilitating fine-grained intra-urban dengue forecasting by integrating the urban environments measured from street-view images.

蓝莓花青素对RAW264.7细胞的抗炎活性研究及其机理初探（英文）

目的:以园蓝为研究材料,鉴定园蓝花青素提取物(GBBAEs)中的功能性成分的结构,建立脂多糖(LPS)诱导的体外炎症模型,并评价其抗炎作用和初步机制。创新点:首次探究了蓝莓花青素对建立的LPS诱导体外炎症模型的营养干预作用,并初步探究了发挥抗炎机制的作用通路。方法:将RAW 264.7细胞分为对照组(不作处理)和实验组(1μg/ml LPS刺激建模)。实验组进一步分为3个不同浓度组:400μg/ml GBBAEs组、800μg/ml GBBAEs组和1200μg/ml GBBAEs组。用酶联免疫吸附测定(ELISA)试剂盒检测一氧化氮(NO)、前列腺素E2(PGE2)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、干扰素γ(INF-γ)等炎症因子的释放量;用实时定量聚合酶链反应(RT-PCR)分析IL-1β、IL-6、TNF-α、环氧合酶-2(COX-2)及单核细胞趋化蛋白-1(MCP-1)的炎症相关基因m RNA的表达水平;用蛋白质印迹法(Western blot法)测定相关炎症蛋白COX-2和NF-κBp65表达水平。结论:试验结果表明,通过ELISA法测定GBBAEs可以显著性抑制NO、PGE2、IL-1β、IL-6、INF-γ等炎症因子的释放;RT-PCR分析阐明在LPS诱导的单核-巨噬细胞RAW 264.7中,GBBAEs可以显著性抑制IL-1β、IL-6、TNF-α、COX-2及MCP-1的炎症相关基因m RNA的表达水平。此外,Western blot法进一步显示GBBAEs对相关炎症蛋白COX-2和NF-κBp65表达具有明显抑制作用,进一步证实GBBAEs通过NF-κB机制通路来发挥抗炎作用。

A New Periodic Solution to Jacobi Elliptic Functions of MKdV Equation and BBM Equation

Based on the homogeneous balance method, the Jacobi elliptic expansion method and the auxiliary equation method, the first elliptic function equation is used to get a new kind of solutions of nonlinear evolution equations. New exact solutions to the Jacobi elliptic function of MKdV equations and Benjamin-Bona-Mahoney （BBM） equations are obtained with the aid of computer algebraic system Maple. The method is also valid for other （l＋l）-dimensional and higher dimensional systems.

Thrombin induces ACSL4-dependent ferroptosis during cerebral ischemia/reperfusion

Ischemic stroke represents a significant danger to human beings,especially the elderly.Interventions are only available to remove the clot,and the mechanism of neuronal death during ischemic stroke is still in debate.Ferroptosis is increasingly appreciated as a mechanism of cell death after ischemia in various organs.