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| 1 | Coronary artery anomalies overview: The normal and the abnormal显示文摘The aim of this review is to give a comprehensive and concise overview of coronary embryology and normal coronary anatomy, describe common variants of normal and summarize typical patterns of anomalous coronary artery anatomy. Extensive iconography supports the text, with particular attention to images obtained in vivo using non-invasive imaging. We have divided this article into three groups, according to their frequency in the general population: Normal, normal variant and anomaly. Although congenital coronary artery anomalies are relatively uncommon, they are the second most common cause of sudden cardiac death among young athletes and therefore warrant detailed review. Based on the functional relevance of each abnormality, coronary artery anomalies can be classified as anomalies with obligatory ischemia, without ischemia or with exceptional ischemia. The clinical symptoms may include chest pain, dyspnea, palpitations, syncope, cardiomyopathy, arrhythmia, myocardial infarction and sudden cardiac death. Moreover, it is important to also identify variants and anomalies without clinical relevance in their own right as complications during surgery or angioplasty can occur. | Adriana DM Villa Eva Sammut Arjun Nair Ronak Rajani Rodolfo Bonamini Amedeo Chiribiri | 2016 | World Journal of Radiology2016，8，6： | 14 |
| 2 | Core promoter: A critical region where the hepatitis B virus makes decisions显示文摘The core promoter(CP)of the viral genome plays an important role for hepatitis B virus(HBV)replication as it directs initiation of transcription for the synthesis of both the precore and pregenomic(pg)RNAs.The CP consists of the upper regulatory region and the basal core promoter(BCP).The CP overlaps with the 3’-end of the X open reading frames and the 5’-end of the precore region,and contains cis-acting elements that can independently direct transcription of the precore mRNA and pgRNA.Its transcription regulation is under strict control of viral and cellular factors.Even though this regulatory region exhibits high sequence conservation,when variations appear,they may contribute to the persistence of HBV within the host,leading to chronic infection and cirrhosis,and eventually,hepatocellular carcinoma.Among CP sequence variations,those occurring at BCP may dysregulate viral gene expression with emphasis in the hepatitis B e antigen,and contribute to disease progression.In this review these molecular aspects and pathologic topics of core promoter are deeply evaluated. | Jorge Quarleri | 2014 | World Journal of Gastroenterology2014，20，2： | 13 |
| 3 | Overview of coronary artery variants, aberrations and anomalies显示文摘Coronary artery anomalies and variants are relatively uncommon congenital disorders of the coronary artery anatomy and constitute the second most common cause of sudden cardiac death in young competitive athletes. The rapid advancement of imaging techniques, including computed tomography, magnetic resonance imaging, intravascular ultrasound and optical coherence tomography, have provided us with a wealth of new information on the subject. Anomalous origin of a coronary artery from the contralateral sinus is the anomaly most frequently associated with sudden cardiac death, in particular if the anomalous coronary artery has a course between the aorta and the pulmonary artery. However, other coronary anomalies, like anomalous origin of the left coronary artery from the pulmonary artery, atresia of the left main stem and coronary fistulae, have also been implicated in cases of sudden cardiac death. Patients are usually asymptomatic, and in most of the cases, coronary anomalies are discovered incidentally during coronary angiography or on autopsy following sudden cardiac death. However, in some cases, symptoms like angina, syncope, heart failure and myocardial infarction may occur. The aims of this article are to present a brief overview of the diverse coronary variants and anomalies, focusing especially on anatomical features, clinical manifestations, risk of sudden cardiac death and pathophysiologic mechanism of symptoms, as well as to provide valuable information regarding diagnostic workup, follow-up, therapeutic choices and timing of surgical treatment. | Stylianos Kastellanos Konstantinos Aznaouridis Charalambos Vlachopoulos Eleftherios Tsiamis Evangelos Oikonomou Dimitris Tousoulis | 2018 | World Journal of Cardiology2018，10，10： | 12 |
| 4 | PCR restriction fragment length polymorphism in detection of YMDD variants of viral polymerase in hepatitis B virus patients treated with lamivudine显示文摘Objective: To analyse the emergence of YMDD motif(tyrosine-methionine-aspartate-aspartate) variants inpatients with hepatitis B treated with lamivudine.Methods: The amino acid substitution from methio-nine or isoleucine at the YMDD motif at the HBVpolymerase gene is a main mutation resistant to lami-vudine treatment. Generated from a fragment of do-main C of the polymerase gene, patients HBV DNA,which had been positive previously became positive a-gain ever since it had been negative during lamivudi-ne therapy. Variants were detected by cleavage of theproducts of the three PCRs with following enzymes:FokI, SspI, Alw441. The results of PCR-RELP wereanalysed by 8. 4% polypropylene acidemide gel elec-trophoresis. PCR-RFLP assay was compared to di-rect sequencing.Results: HBV DNA was positive again in 33 patientsand positive for one year in 2 patients. YMDD vari-ants were detected in serum 14 of 35 patients, YIDDvariants in 4, YVDD variants in 6, and YI/MDD va-riants in 1; all were in concordance with the resultsof direct sequencing. The samples of other 3 patientsshowed YI/VDD mutations, as shown by direct se-quencing. The results of PCR-RFLP assay of themixed sera of YIDD and YVDD variants were similarto those sera of YI/VDD variants.Conclusion: PCR-RFLP is suitable for rapid detec-tion of YMDD variants of viral polymerase in hepati-tis B virus patients treated with lamivudine. | | 2002 | Hepatobiliary & Pancreatic Diseases International2002，1，2： | 7 |
| 5 | Pharmacogenetic studies update in type 2 diabetes mellitus显示文摘Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment. | Shalini Singh Kauser Usman Monisha Banerjee | 2016 | World Journal of Diabetes2016，7，15： | 5 |
| 6 | PXR variants:the impact on drug metabolism and therapeutic responses显示文摘The pregnane X receptor(PXR) plays an important and diverse role in mediating xenobiotic induction of drug-metabolizing enzymes and transporters.Several protein isoforms of PXR exist,and they have differential transcriptional activity upon target genes; transcript variants 3(PXR3) and 4(PXR4) do not induce target gene expression,whereas transcript variants 1(PXR1) and 2(PXR2) respond to agonist by activating target gene expression.PXR protein variants also display differences in protein–protein interactions; PXR1 interacts with p53,whereas PXR3 does not.Furthermore,the transcript variants of PXR that encode these protein isoforms are differentially regulated by methylation and deletions in the respective promoters of the variants,and their expression differs in various human cancers and also in cancerous tissue compared to adjacent normal tissues.PXR1 and PXR4 m RNA are downregulated by methylation in cancerous tissue and have divergent effects on cellular proliferation when ectopically overexpressed.Additional detailed and comparative mechanistic studies are required to predict the effect of PXR transcript variant expression on carcinogenesis,therapeutic response,and the development of toxicity. | C.Trent Brewer Taosheng Chen | 2016 | Acta Pharmaceutica Sinica B2016，6，5： | 5 |
| 7 | Identification of yak lactate dehydrogenase B gene variants by gene cloning显示文摘Native polyacrylamide gel electrophoresis showed that two types of lactate dehydrogenase (LDH) existed in yaks. Based on the electrophoresis characteristics of LDH isoenzymes, yak LDH variants were speculated to be the gene mutation on H subunit encoded by B gene. According to the mobility in electrophoresis, the fast-band LDH type was named LDH-Hf and the slow-band LDH type LDH-Hs. In order to reveal the gene alteration in yak LDH variants, total RNA was extracted from heart tissues of yaks with different LDH variants, and cDNAs of the two variants were reverse transcripted. Two variants of B genes were cloned by RT-PCR. Sequence analysis revealed that four nucleotides differed between LDH-Bf and LDH-Bs, which resulted in two amino acids alteration. By Deepview software analysis of the conformation of yak LDH1 variants and H subunit, these four nucleotides altered two amino acids that generated new hydrogen bonds to change the hydrogen bonds network, and further caused subtle conformational changes between the two LDH variants. | ZHENG YuCai1, ZHAO XingBo2, ZHOU Jing1, PIAO Ying1, JIN SuYu1, HE QingHua1, HONG Jian1, LI Ning2 & WU ChangXin2 1 College of Life Science and Technology, Southwest University for Nationalities, Chengdu 610041, China 2 State Key Laboratory for Agrobiotechnology and Ministry of Agriculture Key Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100094, China | 2008 | Science China(Life Sciences)2008，51，5： | 5 |
| 8 | De novo assembly of a Tibetan genome and identification of novel structural variants associated with high-altitude adaptation显示文摘Structural variants(SVs) may play important roles in human adaptation to extreme environments such as high altitude but have been under-investigated. Here, combining long-read sequencing with multiple scaffolding techniques, we assembled a high-quality Tibetan genome(ZF1), with a contig N50 length of 24.57 mega-base pairs(Mb) and a scaffold N50 length of 58.80 Mb. The ZF1 assembly filled 80 remaining N-gaps(0.25 Mb in total length) in the reference human genome(GRCh38). Markedly, we detected17 900 SVs, among which the ZF1-specific SVs are enriched in GTPase activity that is required for activation of the hypoxic pathway. Further population analysis uncovered a 163-bp intronic deletion in the MKL1 gene showing large divergence between highland Tibetans and lowland Han Chinese. This deletion is significantly associated with lower systolic pulmonary arterial pressure, one of the key adaptive physiological traits in Tibetans. Moreover, with the use of the high-quality de novo assembly, we observed a much higher rate of genome-wide archaic hominid(Altai Neanderthal and Denisovan) shared non-reference sequences in ZF1(1.32%–1.53%) compared to other East Asian genomes(0.70%–0.98%),reflecting a unique genomic composition of Tibetans. One such archaic hominid shared sequence-a662-bp intronic insertion in the SCUBE2 gene-is enriched and associated with better lung function(the FEV1/FVC ratio) in Tibetans. Collectively, we generated the first high-resolution Tibetan reference genome, and the identified SVs may serve as valuable resources for future evolutionary and medical studies. | Ouzhuluobu Yaoxi He Haiyi Lou Chaoying Cui Lian Deng Yang Gao Wangshan Zheng Yongbo Guo Xiaoji Wang Zhilin Ning Jun Li Bin Li Caijuan Bai Baimakangzhuo Gonggalanzi Dejiquzong Bianba Duojizhuoma Shiming Liu Tianyi Wu Shuhua Xu Xuebin Qi Bing Su | 2020 | National Science Review2020，7，2： | 4 |
| 9 | Novel MSX1 variants identified in families with nonsyndromic oligodontia显示文摘The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants.Whole-exome sequencing(WES)and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia,and a series of bioinformatics databases were used for variant confirmation and functional prediction.Phenotypic characterization of the members of these families was described,and an in vitro analysis was performed for functional evaluation.Five novel MSX1 heterozygous variants were identified:three missense variants[c.662A>C(p.Q221P),c.670C>T(p.R224C),and c.809C>T(p.S270L)],one nonsense variant[c.364G>T(p.G122*)],and one frameshift variant[c.277delG(p.A93Rfs*67)].Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P,p.R224C,p.G122*,and p.A93Rfs*67 variants compared to the wild type.Three variants(p.Q221P,p.G122*,and p.A93Rfs*67)were classified as pathogenic or likely pathogenic,while p.S270L and p.R224C were of uncertain significance in the current data.Moreover,we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss.Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling. | Jinglei Zheng Miao Yu Haochen Liu Tao Cai Hailan Feng Yang Liu Dong Han | 2021 | International Journal of Oral Science2021，13，1： | 4 |
| 10 | Mechanism underlying the retarded nuclear translocation of androgen receptor splice variants显示文摘As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process. | Ye Liu Yinyu Wang Fangfang Wang Jiexue Pan Jingjing Xu Jingyi Li Chengliang Zhou Guolian Ding Yanting Wu Xinmei Liu Jianzhong Sheng Hefeng Huang | 2019 | Science China(Life Sciences)2019，62，2： | 4 |
| 11 | Magnetic resonance imaging of the spinal marrow:Basic understanding of the normal marrow pattern and its variant显示文摘For now, magnetic resonance(MR) is the best noninvasive imaging modality to evaluate vertebral bone marrow thanks to its inherent soft-tissue contrast andnon-ionizing nature. A daily challenging scenario for every radiologist interpreting MR of the vertebral column is discerning the diseased from normal marrow. This requires the radiologist to be acquainted with the used MR techniques to judge the spinal marrow as well as its normal MR variants. Conventional sequences used basically to image marrow include T1 W, fat-suppressed T2 W and short tau inversion recovery(STIR) imaging provides gross morphological data. Interestingly, using non-routine MR sequences; such as opposed phase, diffusion weighted, MR spectroscopy and contrastedenhanced imaging; may elucidate the nature of bone marrow heterogeneities; by inferring cellular and chemical composition; and adding new functional prospects. Recalling the normal composition of bone marrow elements and the physiologic processes of spinal marrow conversion and reconversion eases basic understanding of spinal marrow imaging. Additionally, orientation with some common variants seen during spinal marrow MR imaging as hemangiomas and bone islands is a must. Moreover, awareness of the age-associated bone marrow changes as well as changes accompanying different variations of the subject's health state is essential for radiologists to avoid overrating normal MR marrow patterns as pathologic states and metigate unnecessary further work-up. | Mohamed Ragab Nouh Ahmed Fathi Eid | 2015 | World Journal of Radiology2015，7，12： | 4 |
| 12 | Genetic polymorphisms and gastric cancer risk: a comprehensive review synopsis from meta-analysis and genome-wide association studies显示文摘Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.Methods: We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30 th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability(FPRP) test.Results: Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1(rs1760944), DNMT1(rs16999593), ERCC5(rs751402), GSTT1(null/presence), MDM2(rs2278744), PPARG(rs1801282), TLR4(rs4986790), IL-17 F(rs763780), and CASP8(rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.Conclusions: Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk;however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC. | Jie Tian Guanchu Liu Chunjian Zuo Caiyang Liu Wanlun He Huanwen Chen | 2019 | Cancer Biology & Medicine2019，16，2： | 4 |
| 13 | Technical tailoring of pancreaticoduodenectomy in patients with hepatic artery anatomic variants显示文摘BACKGROUND:Pancreaticoduodenectomy is the treatment of choice for periampullary and pancreatic head tumors.In case of hepatic artery abnormalities,early pancreatic transection during pancreaticoduodenectomy may prove inappropriate Early retroportal lamina dissection improves exposure of the superior mesenteric vessels and anatomic variants of the hepatic artery,where safeguarding is mandatory.METHOD:We describe our early retroportal lamina approach in patients with anatomic variants of the hepatic artery before pancreatic transection.RESULTS:This approach was used during 42 pancreatico duodenectomies with a hepatic artery anatomic variant which was spared in 40 patients.Arterial reconstruction was performed in 2 patients.Five patients with a hepatic artery variant and adenocarcinoma involving the portomesenteric junction required venous resection and reconstruction.CONCLUSIONS:Early retroportal lamina dissection during pancreaticoduodenectomy in patients with hepatic artery anatomic variants enables easier exposure,avoiding injuries that might compromise the liver arterial supply.When the portomesenteric vein is involved,this approach facilitates en bloc 'no touch' venous resection and reconstruction. | Cristian Lupascu Dan Andronic Corina Ursulescu Ciprian Vasiluta Nutu Vlad | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，6： | 3 |
| 14 | A recombinant receptor-binding domain in trimeric form generates protective immunity against SARSCoV-2 infection in nonhuman primates显示文摘A safe and effective vaccine is critical to combat the COVID-19 pandemic.Here,we developed a trimeric SARS-CoV-2 receptor-binding domain(RBD)subunit vaccine candidate that simulates the natural structure of the spike(S)trimer glycoprotein.Immunization with the RBD trimer-induced robust humoral and cellular immune responses,and a high level of neutralizing antibodies was maintained for at least 4.5 months.Moreover,the antibodies that were produced in response to the vaccine effectively cross-neutralized the SARS-CoV-2501Y.V2 variant(B.1.351).Of note,when the vaccine-induced antibodies dropped to a sufficiently low level,only one boost quickly activated the anamnestic immune response,conferring full protection against a SARSCoV-2 challenge in rhesus macaques without typical histopathological changes in the lung tissues.These results demonstrated that the SARS-CoV-2 RBD trimer vaccine candidate is highly immunogenic and safe,providing long-lasting,broad,and significant immunity protection in nonhuman primates,thereby offering an optimal vaccination strategy against COVID-19. | Limin Yang Deyu Tian Jian-bao Han Wenhui Fan Yuan Zhang Yunlong Li Wenqiang Sun Yanqiu Wei Xiaodong Tian Dan-dan Yu Xiao-li Feng Gong Cheng Yuhai Bi Yong-tang Zheng Wenjun Liu | 2021 | The Innovation2021，2，3： | 3 |
| 15 | Association of gene variants with susceptibility to type 2 diabetes among Omanis显示文摘AIM:To investigate the association of 10 known common gene variants with susceptibility to type 2diabetes mellitus(T2D)among Omanis.METHODS:Using case-control design,a total of992 diabetic patients and 294 normoglycemic Omani Arabs were genotyped,by an allelic discrimination assay-by-design TaqMan method on fast real time polymerase chain reaction system,for the following gene variants:KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398),CDKN2A/B(rs10811661),FTO(rs9939609 and rs8050136),IGF2BP2(rs4402960),SLC30A8(rs13266634)CAPN10(rs3792267)and HHEX(rs1111875).T2D patients were recruited from the Diabetes Clinic(n=243)and inpatients(n=749)at Sultan Qaboos Univesity Hospital(SQUH),Muscat,Oman.Adult control participants(n=294)were volunteers from the community and from those visiting Family Medicine Clinic at SQU,for regular medical checkup.The difficulty in recruiting Omani participants with no family history of diabetes was the main reason behind the small number of control participants in this study.Almost all volunteers questioned had a relativewith diabetes mellitus.Inspite of the small number of normoglycemic controls in this study,this sample was sufficient for detection of genes and loci for common alleles influencing T2D with an odds ratio of≥1.3reaching at least 80%power.Data was collected from June 2010 to February 2012.RESULTS:Using binary logistic regression analysis,four gene variants showed significant association with T2D risk:KCNJ11(rs5219,P=5.8×10^(-6),OR=1.74),TCF7L2(rs7903146,P=0.001,OR=1.46),CDKAL1(rs10946398,P=0.002,OR=1.44)and CDKN2A/B(rs10811661,P=0.020,OR=1.40).The fixation index analysis of these four gene variants indicated significant genetic differentiation between diabetics and controls{[KCNJ11(rs5219),P<0.001],[TCF7L2(rs7903146),P<0.001],[CDKAL1(rs10946398),P<0.05],[CDKN2A/B(rs10811661),P<0.05]}.The highest genotype variation%between diabetics and controls was found at KCNJ11(2.07%)and TCF7L2(1.62%).This study was not able to detect an association of T2D risk with gene variants of IGF2BP2(rs4402960),SLC30A8(rs13266634),CAPN10(rs3792267)and HHEX(rs1111875).Moreover,no association was found between FTO gene variants(rs9939609 and rs8050136)and T2D risk.However,T2D risk was found to be significantly associated with obesity(P=0.002,OR=2.22);and with the Waist-to-Hip ratio(n=532,P=1.9×10^(-7),OR=2.4),[among males(n=234,P=1.2×10^(-4),OR=2.0)and females(n=298,P=0.001,OR=6.3)].CONCLUSION:Results confirmed the association of KCNJ11(rs5219),TCF7L2(rs7903146),CDKAL1(rs10946398)and CDKN2A/B(rs10811661)gene variants with susceptibility to T2D among Omani Arabs. | Sawsan Al-Sinani Nicolas Woodhouse Ali Al-Mamari Omaima Al-Shafie Mohammed Al-Shafaee Said Al-Yahyaee Mohammed Hassan Deepali Jaju Khamis Al-Hashmi Mohammed Al-Abri Khalid Al-Rassadi Syed Rizvi Yengo Loic Philippe Froguel Riad Bayoumi | 2015 | World Journal of Diabetes2015，6，2： | 3 |
| 16 | High throughput sequencing reveals Drosophila suzukiiresponses to insecticides显示文摘Global climate change and acquired resistance to insecticides are threats to world food security.Drosophila suzukii,a devastating invasive pest in many parts of the world,causes substantial economic losses to fruit production industries,forcing farmers to apply broad-spectrum insecticides frequently,This could lead to the development of insecticide resistance.We determined the Lethal Concentration 50 (median lethal concen- tration,LC50)values of zeta-cypermethrin,spinosad,and malathion insecticides against D.suzukii colonies established from Clarke and Pierce county Georgia,United States. The LC50 values were 3 fold higher in the Pierce county population for all insecticide treatments.We then used RNA sequencing to analyze the responses of Pierce and Clarke population flies surviving a LC50 treatment of the 3 insecticides.We identified a high num- ber of differentially expressed genes that are likely involved in detoxification and reduced cuticular penetration,especially in the Pierce population,with extensive overlap in differ- entially expressed genes between the 3 insecticide treatments.Finally,we predicted fewer nonsynonymous single nucleotide variants having deleterious effects on protein function among detoxification,insecticide target,and cuticular protein encoding genes in Pierce flies.Thus a combination of increased gene expression and fewer deleterious single nu- cleotide variants highlights molecular mechanisms underlying the higher LC50 values for Pierce population flies. | Ruchir Mishra Joanna C.Chiu Gang Hua Nilesh R.Tawari Michael J.Adang Ashfaq A.Sial | 2018 | Insect Science2018，25，6： | 2 |
| 17 | Exome sequencing reveals genetic architecture in patients with isolated or syndromic short stature显示文摘Short stature is among the most common endocrinological disease phenotypes of childhood and may occur as an isolated finding or in conjunction with other clinical manifestations.Although the diagnostic utility of clinical genetic testing in short stature has been implicated,the genetic architecture and the utility of genomic studies such as exome sequencing(ES)in a sizable cohort of patients with short stature have not been investigated systematically.In this study,we recruited 561 individuals with short stature from two centers in China during a 4-year period.We performed ES for all patients and available parents.All patients were retrospectively divided into two groups:an isolated short stature group(group I,n=257)and an apparently syndromic short stature group(group II,n=304).Causal variants were identified in 135 of 561(24.1%)patients.In group I,29 of 257(11.3%)of the patients were solved by variants in 24 genes.In group II,106 of 304(34.9%)patients were solved by variants in 57 genes.Genes involved in fundamental cellularprocess played an important role in the genetic architecture of syndromic short stature.Distinct genetic architectures and pathophysiological processes underlie isolated and syndromic short stature. | Xin Fan Sen Zhao Chenxi Yu Di Wu Zihui Yan Lijun Fan Yanning Song Yi Wang Chuan Li Yue Ming Baoheng Gui Yuchen Niu Xiaoxin Li Xinzhuang Yang Shiyu Luo Qiang Zhang Xiuli Zhao Hui Pan Mei Li Weibo Xia Guixing Qiu Pengfei Liu Shuyang Zhang Jianguo Zhang Zhihong Wu James R.Lupski Jennifer E.Posey Shaoke Chen Chunxiu Gong Nan Wu | 2021 | Journal of Genetics and Genomics2021，48，5： | 2 |
| 18 | Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia显示文摘Three members of the angiopoietin-like(ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8-are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function(LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia(FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides. | Patrizia Tarugi Stefano Bertolini Sebastiano Calandra | 2019 | The Journal of Biomedical Research2019，33，2： | 2 |
| 19 | Engineering SpyCatcher Variants with Proteolytic Sites for Less-Trace Ligation显示文摘Summary of main observation and conclusion The SpyTag/SpyCatcher reaction is a powerful tool for bioconjugation, but it leaves a complex of considerable size after ligation. To facilitate removal of the catalytic fragment, proteolytic recog nit ion sites (such as DDDDK, AVLQ, and WELQ) were directly engineered into the first or second loop of SpyCatcher at locations after the reactive lysine to give a set of cleavable SpyCatcher variants. Among them, SpyCatcherDDDDK exhibits excellent reactivity with SpyTag and could still be cleaved proteolytically by enterokinase after ligation. Notably, SpyCatcherDDDDK is disordered in solution and forms an ordered complex upon reaction with SpyTag with a second order rate constant of 99.2 ± 0.1M^-1·S^-1 which is comparable to, if not faster than, most click reactions. The results demonstrate the high sequence plasticity of SpyCatcher and suggest that covalent bond formation may confer robustness on the folded structure against extensive mutation. These variants add to the expanding toolbox of genetically-encoded peptide-protein chemistry with diverse features. | Xue-Jian Zhang Xia-Ling Wu Dong Liu Xiao-Di Da Xiao-Wei Wang Shuguang Yang Wen-Bin Zhang | 2019 | Chinese Journal of Chemistry2019，37，2： | 2 |
| 20 | Differential expression of glial cell line-derived neurotrophic factor splice variants in the mouse brain显示文摘Glial cell line-derived neurotrophic factor(GDNF) plays a critical role in neuronal survival and function. GDNF has two major splice variants in the brain,α-pro-GDNF and β-pro-GDNF, and both isoforms have strong neuroprotective effects on dopamine neurons. However, the expression of the GDNF splice variants in dopaminergic neurons in the brain remains unclear. Therefore, in this study, we investigated the mRNA and protein expression of α-and β-pro-GDNF in the mouse brain by real-time quantitative polymerase chain reaction, using splice variant-specific primers, and western blot analysis. At the mRNA level,β-pro-GDNF expression was significantly greater than that of α-pro-GDNF in the mouse brain. In contrast, at the protein level,α-pro-GDNF expression was markedly greater than that of β-pro-GDNF. To clarify the mechanism underlying this inverse relationship in mRNA and protein expression levels of the GDNF splice variants, we analyzed the expression of sorting protein-related receptor with A-type repeats(SorLA) by real-time quantitative polymerase chain reaction. At the mRNA level, SorLA was positively associated with β-pro-GDNF expression, but not with α-pro-GDNF expression. This suggests that the differential expression of α-and β-pro-GDNF in the mouse brain is related to SorLA expression. As a sorting protein, SorLA could contribute to the inverse relationship among the mRNA and protein levels of the GDNF isoforms. This study was approved by the Animal Ethics Committee of Xuzhou Medical University, China on July 14, 2016. | Xiao-He Gu Heng Li Lin Zhang Tao He Xiang Chai He Wei Dian-Shuai Gao | 2020 | Neural Regeneration Research2020，15，2： | 1 |
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