Association between serum albumin levels and disease severity in adult patients with dengue: A 7-year retrospective cohort study in China's Mainland

Objective:To identify the association between serum albumin levels and disease severity among adult patients with dengue in China's Mainland.Methods:This retrospective cohort study analyzed the data of adult patients(aged≥18 years)hospitalized with laboratory-confirmed dengue in a tertiary center for infectious diseases from 2013 to 2019 in China's Mainland.Serum albumin levels were estimated and compared between patients with severe dengue and non-severe dengue.Additionally,the association between serum albumin levels and severe dengue was evaluated using a generalized linear model[relative risks(RR)].Multivariate logistic regression analysis was performed to identify the potential predictors of severe dengue.Results:Overall,1568 patients were included in this study.Of these patients,34(2.17%)developed severe dengue.The median serum albumin levels were significantly lower in patients with severe dengue than that in those with non-severe dengue(33 g/L vs.37 g/L,P<0.001).After adjustment for age,sex,and comorbidities,hypoalbuminemia(RR 4.877,95%CI 2.193-11.461,P<0.001)was found to be a predictor of severe dengue.Serum albumin levels(OR 1.303,95%CI 1.161-1.462,P<0.001)and age(OR 1.038,95%CI 1.017-1.061,P<0.001)were significant risk factors for severe dengue.The area under the curve for serum albumin levels to distinguish severe dengue was 0.787.Conclusions:Lower serum albumin levels were significantly associated with disease severity in adult patients with dengue.Hypoalbuminemia on admission resulted in at least a four-fold increased risk of severe dengue.

Application of Opening and Closing Morphology in Deep Learning-Based Brain Image Registration

In order to improve the registration accuracy of brain magnetic resonance images(MRI),some deep learning registration methods use segmentation images for training model.How-ever,the segmentation values are constant for each label,which leads to the gradient variation con-centrating on the boundary.Thus,the dense deformation field(DDF)is gathered on the boundary and there even appears folding phenomenon.In order to fully leverage the label information,the morphological opening and closing information maps are introduced to enlarge the non-zero gradi-ent regions and improve the accuracy of DDF estimation.The opening information maps supervise the registration model to focus on smaller,narrow brain regions.The closing information maps supervise the registration model to pay more attention to the complex boundary region.Then,opening and closing morphology networks(OC_Net)are designed to automatically generate open-ing and closing information maps to realize the end-to-end training process.Finally,a new registra-tion architecture,VM_(seg+oc),is proposed by combining OC_Net and VoxelMorph.Experimental results show that the registration accuracy of VM_(seg+oc) is significantly improved on LPBA40 and OASIS1 datasets.Especially,VM_(seg+oc) can well improve registration accuracy in smaller brain regions and narrow regions.

Salt-induced hydrogen peroxide is involved in modulation of antioxidant enzymes in cotton

Salt severely restricts cotton(Gossypium hirsutum) growth and production.The present study was undertaken to study the effect of salt-induced hydrogen peroxide(H_2O_2) on antioxidant enzymes in cotton.Na Cl treatment or exogenous H_2O_2 was used to investigate the relationship between H_2O_2 content and levels of antioxidant enzymes including superoxide dismutase(SOD),ascorbate peroxidase(APX),peroxidase(POD),and catalase(CAT),as well as the transcriptional levels of corresponding genes.H_2O_2 content increased within 24 h following 200 mmol L^(–1)Na Cl treatment.Both Na Cl-induced and exogenous H_2O_2 increased the activity of antioxidant enzymes including APX and SOD and upregulated the transcriptional levels of Ghc APX1,Gh Fe SOD,and Ghchl CSD.These increased activities and upregulated transcriptional levels were inhibited when the salt-induced H_2O_2 was scavenged by NAC.These results indicate that salt-induced H_2O_2 as a second signaling messenger modulates APX and SOD activities by regulating the transcription levels of corresponding genes,alleviating oxidative stress,and increasing salt tolerance in cotton.

人精氨酸酶Ⅰ基因克隆及生物信息学分析

[目的]克隆人精氨酸酶Ⅰ(human-ARGⅠ)基因并分析其生物学特性。[方法]根据NCBI数据库提供的人精氨酸酶Ⅰ基因序列设计其特异性引物,利用PCR扩增目的基因,并将其连接到pCMV-MYC载体上并利用生物信息学工具分析人精氨酸酶Ⅰ蛋白的生物学特性。[结果]酶切鉴定与DNA测序结果显示人精氨酸酶Ⅰ基因全长969bp,编码322个氨基酸残基;人精氨酸酶Ⅰ蛋白属于精氨酸酶———组蛋白去乙酰化酶超家族,是位于细胞质中的稳定亲水性蛋白,无信号肽,不含跨膜结构域,其二级结构由无规则卷曲,α-螺旋和延伸链构成,并且三级结构与二级结构预测结果高度一致,建模结果准确可靠。[结论]人精氨酸酶Ⅰ基因全长969bp,编码322个氨基酸残基,分子量为34734.94,pI6.72,其氨基酸序列中无信号肽,无跨膜结构域,是非分泌型及亲水性蛋白,是属于精氨酸酶-组蛋白去乙酰化酶超家族,无规则卷曲为二级结构中最主要的结构元件,并且三级结构与二级结构预测结果高度一致,建模结果准确可靠。

Phylogenetic and genetic characterization of a 2017 clinical isolate of H7N9 virus in Guangzhou,China during the fifth epidemic wave

Pathogenic H7N9 influenza viruses continue to pose a public health concern. The H7N9 virus has caused five outbreak waves of human infections in China since 2013. In the present study, a novel H7N9 strain(A/Guangdong/8 H324/2017) was isolated from a female patient with severe respiratory illness during the fifth wave of the 2017 H7N9 epidemic. Phylogenetic analysis showed that the H7N9 viruses collected during the fifth wave belong to two different lineages: the Pearl River Delta lineage and the Yangtze River Delta lineage. The novel isolate is closely related to the Pearl River Delta H7N9 viruses, which were isolated from patients in Guangdong Province. The novel H7N9 isolate has an insertion of three basic amino acids in the cleavage site of hemagglutinin(HA), which may enhance virulence in poultry. The 2017 isolate also possesses an R292 K substitution in the neuraminidase(NA)protein, which confers oseltamivir resistance. This study highlights the pandemic potential of the novel H7N9 virus in mammals;thus, future characterization and surveillance is warranted.

Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis

Publications>Journals>Journal of Clinical and Translational Hepatology>Article Full Text ORIGINAL ARTICLE OPEN ACCESS Efficacy and Safety of All-oral Emitasvir and Sofosbuvir in Patients with Genotype 1b HCV Infections without Cirrhosis Huiying Rao1,Xingxiang Yang2,Youwen Tan3,Qin Ning4,Daokun Yang5,Jiefei Wang6,Yongfeng Yang7,Sujun Zheng8,Dongliang Yang9,Jinlin Hou10,Qing Xie11,Caiyan Zhao12,Lunli Zhang13,Xiaorong Mao14,Tong Sun15,Lang Bai16,Fuchun Zhang17,Jinglan Jin18,Yingren Zhao19,Maorong Wang20,Wen Xie21,Yingjie Ma22,Jun Quan23,Xuebing Yan24,Ping An25,Feng Lin26,Jidong Jia27,Xiaoxuan Hu28,Zuojiong Gong29,Jie Wu30,Yongping Chen31,Zhansheng Jia32,Minghua Lin33,Guiqiang Wang34,Yueyong Zhu35,Yingjun Zhang*,36,Hongming Xie36,Lin Luo36,Qingyun Ren36,Rui Huang1 and Lai Wei*,37 Author information Journal of Clinical and Translational Hepatology 2020;8(3):255-261DOI:10.14218/JCTH.2020.00031 Abstract Background and Aims:Emitasvir is a new type of hepatitis C virus(HCV)nonstructural protein 5A(NS5A)inhibitor,and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance.We conducted this phase 3 trial to further verify the efficacy and safety.Methods:We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate(100 mg)combined with sofosbuvir(400 mg)once daily in non-cirrhotic patients with genotype 1 HCV infection.The primary endpoint was a sustained virological response at 12 weeks(SVR12)after the end of treatment.Results:Of the 362 patients enrolled in the trial,39.8%were male,99.2%had HCV genotype 1b,0.8%had genotype 1a and 79.8%were treatment-naïve.The average age was 47.2 years.All patients completed the treatment and follow-up.All 3 patients with genotype 1a achieved SVR.Two genotype 1b treatment-naïve patients experienced virologic relapse.The rate of SVR12 was 99.7%(358/359),and SVR24 was 99.4%(357/359)in genotype 1b.Overall,36.2%had resistance-associated substitutions(RASs)in NS5A and 98.3%had RASs in NS5B at baseline.The RASs at baseline had no effect on the rates of response.Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir.Most adverse events did not require therapy.Conclusions:The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis,who had not been treated or who had been treated with interferon-based regimen previously.

A unified global genotyping framework of dengue virus serotype-1 for a stratified coordinated surveillance strategy of dengue epidemics

Background: Dengue is the fastest spreading arboviral disease, posing great challenges on global public health. A reproduceable and comparable global genotyping framework for contextualizing spatiotemporal epidemiological data of dengue virus (DENV) is essential for research studies and collaborative surveillance.Methods: Targeting DENV-1 spreading prominently in recent decades, by reconciling all qualified complete E gene sequences of 5003 DENV-1 strains with epidemiological information from 78 epidemic countries/areas ranging from 1944 to 2018, we established and characterized a unified global high-resolution genotyping framework using phylogenetics, population genetics, phylogeography, and phylodynamics.Results: The defined framework was discriminated with three hierarchical layers of genotype, subgenotype and clade with respective mean pairwise distances 2-6%, 0.8-2%, and ≤ 0.8%. The global epidemic patterns of DENV-1 showed strong geographic constraints representing stratified spatial-genetic epidemic pairs of Continent-Genotype, Region-Subgenotype and Nation-Clade, thereby identifying 12 epidemic regions which prospectively facilitates the region-based coordination. The increasing cross-transmission trends were also demonstrated. The traditional endemic countries such as Thailand, Vietnam and Indonesia displayed as persisting dominant source centers, while the emerging epidemic countries such as China, Australia, and the USA, where dengue outbreaks were frequently triggered by importation, showed a growing trend of DENV-1 diffusion. The probably hidden epidemics were found especially in Africa and India. Then, our framework can be utilized in an accurate stratified coordinated surveillance based on the defined viral population compositions. Thereby it is prospectively valuable for further hampering the ongoing transition process of epidemic to endemic, addressing the issue of inadequate monitoring, and warning us to be concerned about the cross-national, cross-regional, and cross-continental diffusions of dengue, which can potentially trigger large epidemics.Conclusions: The framework and its utilization in quantitatively assessing DENV-1 epidemics has laid a foundation and re-unveiled the urgency for establishing a stratified coordinated surveillance platform for blocking global spreading of dengue. This framework is also expected to bridge classical DENV-1 genotyping with genomic epidemiology and risk modeling. We will promote it to the public and update it periodically.

Both structure and function of human monoclonal antibodies contribute to enhancement of Zika virus infectivity in vitro

Dear Editor,Antibody-dependent enhancement（ADE）has long been recognized for dengue virus（DENV）in vitro and in vivo.It is now clear that antibodies to DENV can also enhance Zika virus（ZIKV）infection in vitro,and vice versa（Dejnirattisai et al.,2016;Stettler et al.,2016）.The characteristics of enhancing antibodies,however,remain elusive.

The Limitation of Rapid Tests for DENV2 Infection in Host with Unique Immune Status:Low NS1 Antigenemia and Deficient Antibody Responses

Dear Editor,Dengue infections are caused by all four serotypes of dengue virus(DENV1–4).In recent years it has been confirmed that DENV-1 and DENV-2 are co-circulated in Guangzhou,Guangdong,China(Lai et al.2015;Luo et al.2017).DENV-2 strains were imported from Thailand and Indonesia(Luo et al.2017;Zhao et al.2014,2016),and had become the second local circulated serotype in Guangzhou.

An anti-drone device based on capture technology

In this paper,we design a device based on capture technology to solve the problems caused by hacking drones.We introduce the design,simulation,control scheme,and implementation of a capture device.A protective cover is designed to prevent the capture net from scattering.A high-power driver is selected to drive the motor motion simultaneously,which ensures the simultaneity of the surrounding six launch mechanisms.Finally,we conduct experiments to confirm the design feasibility.After capturing the target,we conduct a pull-off force test to confirm the stability of the capture net.Compared to the existing capture method,the proposed device is adjustable,rapid,reliable,environmentally friendly,and can capture the target without damage.

Expert Consensus on the Prevention and Treatment of Hemorrhagic Fever with Renal Syndrome

Hemorrhagic fever with renal syndrome(HFRS)is an acute zoonosis with a global distribution.China is one of the countries with a high incidence of HFRS,which has long endangered the lives and health of the Chinese people.The Infectious Disease Branch of the Chinese Preventive Medicine Association and the Infectious Diseases Branch of the Chinese Medical Association organized national multidisciplinary experts,based on domestic and international research results combined with experts’practical experiences,to reach this consensus after thorough discussion.This consensus contains 17 recommendations aimed at prevention and identification of important clinical issues to further standardize the prevention,diagnosis,and treatment of HFRS.

Guidelines for the Diagnosis and Treatment of Dengue in China

Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease.As a dengue non-endemic country,China has experienced several dengue outbreaks in recent years.However,dengue patients in China display clinical characteristics that are distinct from those of patients in dengue-endemic countries.To standardize the diagnosis and treatment of dengue fever,the experts at the Society of Infectious Diseases,Society of Tropical Medicine and Parasitology of the Chinese Medical Association,and the Society of Emergency Medicine of China Association of Chinese Medicine have developed a guideline after reviewing the following guidelines and data:guidelines for diagnosis,treatment,prevention,and control of dengue(World Health Organization,2009);the guidelines for diagnosis and treatment of dengue(National Health and Family Planning Commission of the People’s Republic of China,2014,Edition 2);health industry standard of the People’s Republic of China“diagnosis for dengue fever(WS216-2018)”;and systemic reports on dengue.The new guideline includes eight aspects:introduction,terminology,epidemiology and prevention,etiology and pathogenesis,clinical features,diagnosis,treatment,and problems to be solved.

Exact solution to a class of generalized Kitaev spin-1/2 models in arbitrary dimensions

We construct a class of exactly solvable generalized Kitaev spin-1/2 models in arbitrary dimensions, which is beyond the category of quantum compass models. The Jordan-Wigner transformation is employed to prove the exact solvability. An exactly solvable quantum spin-1/2 model can be mapped to a gas of free Majorana fermions coupled to static Z2 gauge fields. We classify these exactly solvable models according to their parent models. Any model belonging to this class can be generated by one of the parent models. For illustration, a two dimensional(2D) tetragon-octagon model and a three dimensional(3D) xy bond model are studied.

Computational exploration and screening of novel Janus MA2Z4 (M = Sc–Zn, Y–Ag, Hf–Au;A=Si, Ge;Z=N, P) monolayers and potential application as a photocatalyst

By high-throughput calculations,13 thermally and environmentally stable Janus MA_(2)Z_(4) monolayers were screened from 104 types of candidates.The 13 stable monolayers have very high charge carrier concentrations(×10^(15) cm^(–2)),which are better than those of the well-known graphene and TaS_(2).Because of their excellent conductivity,the 6 monolayers with band gaps less than 0.5 eV are identified as potential electrode materials for hydrogen evolution reaction applications.For potential applications as photoelectric or photocatalytic materials,bandgaps(Eg-HSE)higher than 0.5 eV remained,which resulted in 7 potential candidates.Based on optical absorption analysis in the visible-light range,H-HfSiGeP_(4) and HMoSiGeP_(4) have higher absorption ability and optical conductivity,which is quite impressive for optoelectronic,solar cell device,and photocatalysis applications.Additionally,the transmittance coefficient of Janus MA_(2)Z_(4) monolayers is approximately 70%–80%in the visible-light range,which implies that these monolayers show good light transmittance.For potential applications as photocatalysts,the redox potential and charge effective mass analysis indicate that H-HfSiGeP_(4),HMoSiGeP_(4),T-ScSiGeN_(4),and T-ZrSiGeN_(4) are suitable photocatalysts for CO_(2) reduction reactions.Using high-throughput identification,13 types of new and stable Janus MA2Z4 monolayers were explored,and the basic properties and potential applications were investigated,which can reduce the time for experiments and provide basic data for the material genome initiative.

Cloning,sequencing and prokaryotic expression of cDNAs for antifreeze protein family from Beetle Tenebrio molitor

Partial cDNA sequences coding for antifreeze proteins in Tenebrio molitor were obtained by RT-PCR.Sequence analysis revealed nine putative cDNAs with a high degree of homology to Tenebrio molitor antifreeze protein genes published in GenBank.The recombinant pGEX-4T-1-tmafp-XJ430 was introduced into E.coli BL21 to induce a GST fusion protein by IPTG.SDS-PAGE analysis for the fusion protein shows a band of 38 kDa.pCDNA3-tmafp-XJ430 was injected into mice to generate antiserum which was later detected by indirect ELISA.The titer of the antibody was 1:2000.Western blotting analysis shows that the antiserum was specifically against the antifreeze protein.Our results laid the foundation for further studies on the properties and functions of insect antifreeze proteins.

COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.

Genetic and pathogenicity diversity of dengue virus type 2 strains circulating in Guangdong,China

Dengue fever is a mosquito-borne viral disease spread in tropical and subtropical regions caused by the dengue virus(DENV).DENV causes a febrile illness,severe forms including hemorrhagic fevers and shock with fatalities in humans.DENV-2 is frequently associated with severe dengue infections and epidemics.DENV-2 strains from Guangdong,China,have not been characterized to compare the phylogenetics and pathogenicity of different DENV-2 subgenotype strains in both vitro and vivo.A total of 22 patients tested to be DENV-2 positive and were enrolled in this study,22 complete genomes were obtained by virus isolation and high-throughput sequencing.Phylogenetic and single amino polymorphism(SAP)analysis indicated that two major subgenotypes(A and C)of DENV-2 Cosmopolitan were prevalent in Guangdong in 2018.The apparent change of major subgenotypes of DENV-2 circulating in Guangdong indicated the diversity of DENV-2 strains,including endemic genotype and imported genotype.It alerted the risk of cross-border transmission of DENV.A significant difference in replication rate was observed in C6/36 between different DENV-2 strains,although growth kinetics comparison of different DENV-2 Cosmopolitan subgenotypes showed similar profiles.DENV-2 subgenotypes(A and C)replicated efficiently in IFNAR−/−C57BL/6 mice,and subgenotype A of Cosmopolitan infected mice showed increased weight loss and delayed viral clearance compared with the subgenotype C group.DENV-2 prevalent in Guangdong in 2018 showed apparent genetic and pathogenicity diversity in both vitro and vivo,indicating the necessity of molecular surveillance and exploration of the relationship between its pathogenicity and clinical characteristics.