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| 1 | Structural and functional properties of SARS-CoV-2 spike protein:potential antivirus drug development for COVID-19显示文摘Coronavirus disease 2019 is a newly emerging infectious disease currently spreading across the world.It is caused by a novel coronavirus,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The spike(S)protein of SARS-CoV-2,which plays a key role in the receptor recognition and cell membrane fusion process,is composed of two subunits,S1 and S2.The S1 subunit contains a receptor-binding domain that recognizes and binds to the host receptor angiotensin-converting enzyme 2,while the S2 subunit mediates viral cell membrane fusion by forming a six-helical bundle via the two-heptad repeat domain.In this review,we highlight recent research advance in the structure,function and development of antivirus drugs targeting the S protein. | Yuan Huang Chan Yang Xin-feng Xu Wei Xu Shu-wen Liu | 2020 | Acta Pharmacologica Sinica2020，41，9： | 25 |
| 2 | Mechanism of Anti-β-adrenoceptor Antibody Mediated Myocardial Damage in Dilated Cardiomyopathy显示文摘Antibodies against &-adrenoceptor can be detected in serum of patients with dilated cardiomyopathy (DCM), which have 5-agonist-like activity, and induce a positive chronotropic effect on cardiac myocytes by its persistence at full strength. Effects of the antibodies against Padrenoceptor from sera of patients with DCM on myocardial cytotoxicity and cytoplasmic free Ca2+-concentration (LCa2+ji) were observed in the cultured single layer SD rat ventricular cells by using the cytotoxicity assay and fluorescent Ca2+- indicat0r fura-2/AM. The positive sera of the anti-&adrenoceptor antibodies from patients with DCM markedly enhanced myocardial [Ca2+]i. Betaloc, a 5, -receptor blocker, might inhibit the increase of the antibody-mediated myocardial [Ca2+]i, and the sera from healthy donors had no effect on myocardial [Ca2+]i,. Our results suggest that the anti-β-adrenoceptor antibody might increase myocardial [Ca2+]i, and result in myocardial damage. The antibodies might activate receptor-gating Ca2+-channel, thereby causing myocardial [Ca2+]i, rise and calcium overload. Early use of betaloc is recommended in the treatment of dilated cardiomyopathy. | 廖玉华 程龙献 涂源淑 张金枝 董继华 李淑莉 田元 彭又红 | 1997 | Journal of Huazhong University of Science and Technology(Medical Sciences)1997，17，1： | 21 |
| 3 | Understanding p53 functions through p53 antibodies显示文摘TP53 is the most frequently mutated gene across all cancer types. Our understanding of its functions has evolved since its discovery four decades ago. Initially thought to be an oncogene, it was later realized to be a critical tumour suppressor. A significant amount of our knowledge about p53 functions have come from the use of antibodies against its various forms. The early anti-p53 antibodies contributed to the recognition of p53 accumulation as a common feature of cancer cells and to our understanding of p53 DNA-binding and transcription activities. They led to the concept that conformational changes can facilitate p53’s activity as a growth inhibitory protein. The ensuing p53 conformational-specific antibodies further underlined p53’s conformational flexibility, collectively forming the basis for current efforts to generate therapeutic molecules capable of altering the conformation of mutant p53. A subsequent barrage of antibodies against post-translational modifications on p53 has clarified p53’s roles further, especially with respect to the mechanistic details and context-dependence of its activity. More recently, the generation of p53 mutation-specific antibodies have highlighted the possibility to go beyond the general framework of our comprehension of mutant p53-and promises to provide insights into the specific properties of individual p53 mutants. This review summarizes our current knowledge of p53 functions derived through the major classes of anti-p53 antibodies, which could be a paradigm for understanding other molecular events in health and disease. | Kanaga Sabapathy David P.Lane | 2019 | Journal of Molecular Cell Biology2019，11，4： | 15 |
| 4 | From targeting the tumor to targeting the immune system: Transversal challenges in oncology with the inhibition of the PD-1/PD-L1 axis显示文摘After that the era of chemotherapy in the treatment of solid tumors have been overcome by the 'translational era', with the innovation introduced by targeted therapies, medical oncology is currently looking at the dawn of a new 'immunotherapy era' with the advent of immune checkpoint inhibitors(CKI) antibodies.The onset of PD-1/PD-L1 targeted therapy has demonstrated the importance of this axis in the immune escape across almost all human cancers.The new CKI allowed to significantly prolong survival and to generate durable response, demonstrating remarkable efficacy in a wide range of cancer types.The aim of this article is to review the most up to date literature about the clinical effectiveness of CKI antibodies targeting PD-1/PD-L1 axis for the treatment of advanced solid tumors and to explore transversal challenges in the immune checkpoint blockade. | Melissa Bersanelli Sebastiano Buti | 2017 | World Journal of Clinical Oncology2017，8，1： | 15 |
| 5 | Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients显示文摘AIM:To investigate possible associations of anti-nuclear envelope antibody(ANEA)with disease severity and survival in Greek primary biliary cirrhosis(PBC)patients.METHODS:Serum samples were collected at diagnosis from 147 PBC patients(85%female),who were followed-up for a median 89.5 mo(range 1-240).ANEA were detected with indirect immunofluorescence on 1% formaldehyde fixed Hep2 cells,and anti-gp210 antibodies were detected using an enzyme linked immunosorbent assay.Findings were correlated with clinical data,histology,and survival.RESULTS:ANEA were detected in 69/147(46.9%) patients and 31/147(21%)were also anti-gp210 positive.The ANEA positive patients were at a more advanced histological stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ56.5%/43.5% vs 74.4%/25.6%,P=0.005)compared to the ANEA negative ones.They had a higher antimitochondrial antibodies(AMA)titer(≤1:160/>1:160 50.7%/49.3%vs 71.8%/28.2%,P=0.001)and a lower survival time(91.7 ±50.7 mo vs 101.8±55 mo,P=0.043).Moreover,they had more advanced fibrosis,portal inflammation,interface hepatitis,and proliferation of bile ductules(P =0.008,P=0.008,P=0.019,and P=0.027,respectively).They also died more frequently of hepatic failure and/or hepatocellular carcinoma(P=0.016).ANEA positive,anti-gp210 positive patients had a difference in stage(Ⅰ-Ⅱ/Ⅲ-Ⅳ54.8%/45.2%vs 74.4%/25.6%,P= 0.006),AMA titer(≤1:160/>1:160 51.6%/48.4%vs 71.8%/28.2%,P=0.009),survival(91.1±52.9 mo vs 101.8±55 mo,P=0.009),and Mayo risk score(5.5 ±1.9 vs 5.04±1.3,P=0.04)compared to the ANEA negative patients.ANEA positive,anti-gp210 negative patients had a difference in AMA titer(≤1:160/>1:160 50%/50%vs 71.8%/28.2%,P=0.002),stage(Ⅰ-Ⅱ/Ⅲ -Ⅳ57.9%/42.1%vs 74.4%/25.6%,P=0.033),fibrosis(P=0.009),portal inflammation(P=0.018),interface hepatitis(P=0.032),and proliferation of bile ductules(P=0.031).Anti-gp210 positive patients had a worse Mayo risk score(5.5±1.9 vs 4.9±1.7,P=0.038)than the anti-gp210 negative ones.CONCLUSION:The presence of ANEA and anti-gp210 identifies a subgroup of PBC patients with advanced disease severity and poor prognosis. | Ourania Sfakianaki Meri Koulentaki Maria Tzardi Elena Tsangaridou Panayotis A Theodoropoulos Elias Castanas Elias A Kouroumalis | 2010 | World Journal of Gastroenterology2010，16，39： | 11 |
| 6 | Autoantibodies in chronic hepatitis C: A clinical perspective显示文摘Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus(HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of glutenrelated seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon(IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmunedisease may be present or may be precipitated by IFNbased HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations. | Janaína Luz Narciso-Schiavon Leonardo de Lucca Schiavon | 2015 | World Journal of Hepatology2015，7，8： | 11 |
| 7 | Targeted therapies in gastric cancer and future perspectives显示文摘Advanced gastric cancer(AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after firstline platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase Ⅰ-Ⅱ trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER(2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed. | Ozan Yazici M Ali Nahit Sendur Nuriye Ozdemir Sercan Aksoy | 2016 | World Journal of Gastroenterology2016，22，2： | 11 |
| 8 | Inflammatory bowel disease serology in Asia and the West显示文摘AIM:To study serological antibodies in Caucasians and Asians,in health and inflammatory bowel disease(IBD),in Australia and Hong Kong(HK).METHODS:Anti-glycan antibodies[anti-chitobioside(ACCA),anti-laminaribioside(ALCA)],and anti-mannobioside(AMCA),anti-Saccharomyces cervisiae(gASCA);and atypical perinuclear anti-neutrophil cytoplasmic antibody(pANCA)were tested in IBD patients,their unaffected relatives,and healthy controls in Australia and HK(China).Antibody status(positive or negative)and titre was compared between subjects of different geography,ethnicity and disease state.RESULTS:Ninety subjects were evaluated:21 Crohn’s disease(CD),32 ulcerative colitis(UC),29 healthy controls,and 8 IBD patient relatives.Forty eight subjects were Australian(29 Caucasian and 19 ethnic Han Chinese)and 42 were from HK(all Han Chinese).Caucasian CD patients had a significantly higher antibody prevalence of gASCA(67%vs 3%,P<0.001),ALCA(44%vs 6%,P=0.005),and AMCA(67%vs 15%,P=0.002),whereas HK CD patients had a higher prevalence of only AMCA(58%vs 25%,P=0.035),when compared with UC and healthy subjects in both countries.Caucasian CD had significantly higher gASCA prevalence(67%vs 0%,P<0.001)and titre(median59 vs 9,P=0.002)than HK CD patients.Prevalence and titres of ALCA,ACCA and AMCA did not differ between CD in the two countries.Presence of at least one antibody was higher in Caucasian than HK CD patients(100%vs 58%,P=0.045).pANCA did not differ between countries or ethnicity.CONCLUSION:Serologic CD responses differ between HK Asian and Australian Caucasian patients.Different genetic,environmental or disease pathogenic factors may account for these differences. | Lani Prideaux Michael A Kamm Peter De Cruz Daniel R van Langenberg Siew C Ng Iris Dotan | 2013 | World Journal of Gastroenterology2013，19，37： | 10 |
| 9 | Risk factors for hepatic decompensation in patients with primary biliary cirrhosis显示文摘AIM:To examine the clinical features and analyze prognostic factors in a prospective study of primary biliary cirrhosis(PBC) patients.METHODS:From 1995 to 2010,PBC patients without hepatic decompensation seen at the Peking Union Medical College Hospital were enrolled.Clinical signs and manifestations(pruritus,persistent fatigue,jaundice and pain in the right hypochondrium),laboratory parameters(auto-antibodies for autoimmune hepatic disease,biliary and hepatic enzymes,immunoglobulin,bilirubin,and albumin) and imaging findings were recorded at entry and at specific time points during follow-up.Cox regression and Kaplan-Meier analyses,respectively,assessed the risk factors for hepatic decompensation and survival.RESULTS:Two hundred and sixty-two PBC patients were enrolled with a median follow-up of 75.2 mo(range,21-201 mo).The 240 patients were aged 51.5 ± 10.2 years at diagnosis and 91.6% were female.Two hundred and forty-five(93.5%) were seropositive for anti-mitochondrial antibodies.At presentation,170 patients(64.9%) were symptomatic,while 96 patients(36.6%) had extra-hepatic autoimmune disease.During the follow-up period,62(23.7%) patients developed hepatic decompensation of whom four underwent liver transplantation and 17 died.The cumulative survival rate and median survival time were 83.9% and 181.7 mo,respectively.Cox regression analysis revealed that an incomplete ursodeoxycholic acid(UDCA) response or inconsistent treatment [P < 0.001;hazard risk(HR) 95%CI = 2.423-7.541],anti-centromere antibodies(ACA) positivity(P < 0.001;HR 95%CI = 2.516-7.137),alanine aminotransferase ratio(AAR) elevations(P < 0.001;HR 95%CI = 1.357-2.678),and histological advanced liver disease(P = 0.006;HR 95%CI = 1.481-10.847) were predictors of hepatic decompensation.The clinical features and survival of PBC in China are consistent with those described in Western countries.CONCLUSION:Incomplete UDCA response or inconsistent treatment,ACA positivity,AAR elevations,and advanced histological stage are predictors of decompensation. | Tian-Yan Shi Li-Na Zhang Hua Chen Li Wang Min Shen Xuan Zhang Feng-Chun Zhang | 2013 | World Journal of Gastroenterology2013，19，7： | 9 |
| 10 | Effects of autoantibodies against AT1-receptor and angiotensin Ⅱ on refractory hypertension显示文摘Objective The study will explore effects of the autoantibodies against AT1 receptor and angiotensin Ⅱ on the refractory hypertension. Methods Seventy-seven patients (46 men and 31 women) with essential hypertension were divided into groups of refractory hypertension (RH) and hypertension (HT) according to the 1999 WHO - ISH Guidelines for the Management of Hypertension. Forty normotensives (22 men) were recruited as controls. The mean age was 54. 3±13 years old in RH group, 53. 5±9 years old in HT group and 51. 2 ±11. 9 years old in normotensives (NT) group. The mean blood pressure was 154. 2±9. 4/98. 4 ± 8. 2 mmHg in RH group and 130. 1±7. 6/80. 5±6. 7 mmHg in HT group after combination drug therapy of hypertension for 4 weeks. Blood pressure in NT group was 120. 8±11. 7/76. 4±7. 2 mmHg. The epitope of the 2nd extracellular loops of AT1 receptor was synthesized and used as antigens to screen the autoantibodies by ELISA. Plasma angiotensin (Ang) II were examined by a radioimmunoassay. Results | 廖玉华 魏宇淼 王敏 董继华 王朝晖 苑海涛 | 2001 | South China Journal of Cardiology2001，2，2： | 9 |
| 11 | Seeing is believing:anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy显示文摘Structural immunology,focusing on structures of host immune related molecules,enables the immunologists to see what the molecules look like,and more importantly,how they work together.Antibody-based PD-1/PD-L1 blockade therapy has achieved brilliant successes in clinical applications.The recent breakthrough of the complex structures of checkpoint blockade antibodies with their counterparts,pembrolizumab with PD-1 and avelumab with PD-L1,have made it clear how these monoclonal antibodies compete the binding of PD-1/PD-L1 and function to blockade the receptor-ligand interaction.Herein,we summarize the structural findings of these two reports and look into the future for how this information would facilitate the development of more efficient PD-1/PD-L1 targeting antibodies,small molecule drugs,and other protein or non-protein inhibitors. | Shuguang Tan Catherine W-H Zhang George F Gao | 2016 | Signal Transduction and Targeted Therapy2016，1，1： | 8 |
| 12 | Primary biliary cirrhosis in HBV and HCV patients:Clinical characteristics and outcome显示文摘AIM: To present the characteristics, management and outcome of patients with hepatitis B virus(HBV) or hepatitis C virus(HCV) infections concurrent with primary biliary cirrhosis(PBC).METHODS: Since January 2001 to September 2009,we retrospectively evaluated the medical records of all HBV(n = 1493) and HCV patients(n = 526) who are followed in our center for the presence of concurrent PBC. Seventeen patients identified with concurrent viral hepatitis and PBC(8 HCV and PBC; follow-up: 61 ± 37 mo and 9 HBV and PBC; follow-up: 57 ± 38 mo). PBC diagnosis was established if the patients met at least two of the following criteria: positivity for antimitochondrial antibody, elevated cholestatic enzymes and histological lesions of PBC.RESULTS: HCV or HBV diagnosis preceded that of PBC in most patients by many years. PBC diagnosis was based on the presence of antimitochondrial antibody and elevated cholestatic enzymes in all 17 patients,while one third(5/17; 29.4%) experienced severe pruritus many years before diagnosis. Patients with PBC and HBV were significantly younger at diagnosis of PBC compared to patients with PBC and HCV(56.1 ± 11.2vs 68.5 ± 10.3, respectively, P < 0.05). At initial clinical and histological assessment the majority of patients were cirrhotics(10/17; 58.8%) with the group of PBC and HCV carrying the highest frequency(87.5% vs33.3% in PBC and HBV; P < 0.05). The patients with HBV and concomitant PBC seem to have better outcome compared to those with HCV and PBC since none of the 6 non-cirrhotics with HBV and PBC developed cirrhosis during follow-up.CONCLUSION: PBC diagnosis in HBV or HCV patients is very difficult and usually delayed. Therefore, in any case, cholestasis should alert physicians to further search for PBC. | Eirini I Rigopoulou Kalliopi Zachou Nikolaos K Gatselis Georgia Papadamou George K Koukoulis George N Dalekos | 2013 | World Journal of Hepatology2013，5，10： | 7 |
| 13 | High tacrolimus intra-patient variability is associated with graft rejection,and de novo donor-specific antibodies occurrence after liver transplantation显示文摘AIM To investigate the role of tacrolimus intra-patient variability(IPV) in adult liver-transplant recipients.METHODS We retrospectively assessed tacrolimus variability in a cohort of liver-transplant recipients and analyzed its effect on the occurrence of graft rejection and de novo donor-specific antibodies(dn DSAs), as well as graft survival during the first 2 years posttransplantation. Between 02/08 and 06/2015, 116 patients that received tacrolimus plus mycophenolate mofetil(with or without steroids) were included. RESULTS Twenty-two patients(18.5%) experienced at least one acute-rejection episode(BPAR). Predictive factors for a BPAR were a tacrolimus IPV of > 35% [OR = 3.07 95%CI(1.14-8.24), P = 0.03] or > 40% [OR = 4.16(1.38-12.50), P = 0.01), and a tacrolimus trough level of < 5 ng/mL [OR=3.68(1.3-10.4), P =0.014]. Thirteen patients(11.2%) developed at least one dn DSA during the follow-up. Tacrolimus IPV [coded as a continuous variable: OR = 1.1, 95%CI(1.0-1.12), P = 0.006] of > 35% [OR = 4.83, 95%CI(1.39-16.72), P = 0.01] and > 40% [OR = 9.73, 95%CI(2.65-35.76), P = 0.001] were identified as predictors to detect dn DSAs. IPV did not impact on patient-or graft-survival rates during the follow-up. CONCLUSION Tacrolimus-IPV could be a useful tool to identify patients with a greater risk of graft rejection and of developing a de novo DSA after liver | Arnaud Del Bello Nicolas Congy-Jolivet Marie Danjoux Fabrice Muscari Laurence Lavayssière Laure Esposito Anne-Laure Hebral Julie Bellière Nassim Kamar | 2018 | World Journal of Gastroenterology2018，24，16： | 7 |
| 14 | Impact of donor-specific antibodies on the outcomes of kidney graft:Pathophysiology, clinical, therapy显示文摘Allo-antibodies, particularly when donor specific, are one of the most important factors that cause both early and late graft dysfunction. The authors review the current state of the art concerning this important issue in renal transplantation. Many antibodies have been recognized as mediators of renal injury. In particular donorspecific-Human Leukocyte Antigens antibodies appear to play a major role. New techniques, such as solid phase techniques and Luminex, have revealed these antibodies from patient sera. Other new techniques have uncovered alloantibodies and signs of complement activation in renal biopsy specimens. It has been acknowledged that the old concept of chronic renal injury caused by calcineurine inhibitors toxicity should be replaced in many cases by alloantibodies acting against the graft. In addition, the number of patients on waiting lists with preformed anti-human leukocyte antigens(HLA) antibodies is increasing, primarily from patients with a history of renal transplant failure already been sensitized. We should distinguish early and late acute antibody-mediated rejection from chronic antibody-mediated rejection. The latter often manifets late during the course of the posttransplant period and may be difficult to recognize if specific techniques are not applied. Different therapeutic strategies are used to control antibody-induced damage.These strategies may be applied prior to transplantation or, in the case of acute antibody-mediated rejection, after transplantation. Many new drugs are appearing at the horizon; however, these drugs are far from the clinic because they are in phase Ⅰ-Ⅱ of clinical trials. Thus the pipeline for the near future appears almost empty. | Maurizio Salvadori Elisabetta Bertoni | 2014 | World Journal of Transplantation2014，4，1： | 6 |
| 15 | Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy显示文摘It remains unclear why the clinically used anti-CTLA-4 antibodies, popularly called checkpoint inhibitors, have severe immunotherapy-related adverse effects (irAEs) and yet suboptimal cancer immunotherapeutic effects (CITE). Here we report that while irAE-prone Ipilimumab and TremeIgG1 rapidly direct cell surface CTLA-4 for lysosomal degradation, the non-irAE-prone antibodies we generated, HL12 or HL32, dissociate from CTLA-4 after endocytosis and allow CTLA-4 recycling to cell surface by the LRBA-dependent mechanism. Disrupting CTLA-4 recycling results in robust CTLA-4 downregulation by all anti-CTLA-4 antibodies and confers toxicity to a non-irAE-prone anti-CTLA-4 mAb. Conversely, increasing the pH sensitivity of TremeIgG1 by introducing designed tyrosine-to-histidine mutations prevents antibody-triggered lysosomal CTLA-4 downregulation and dramatically attenuates irAE. Surprisingly, by avoiding CTLA-4 downregulation and due to their increased bioavailability, pH-sensitive anti-CTLA-4 antibodies are more effective in intratumor regulatory T-cell depletion and rejection of large established tumors. Our data establish a new paradigm for cancer research that allows for abrogating irAE while increasing CITE of anti-CTLA-4 antibodies. | Yan Zhang Xuexiang Du Mingyue Liu Fei Tang Peng Zhang Chunxia Ai James K. Fields Eric J. Sundberg Olga S. Latinovic Martin Devenport Pan Zheng Yang Liu | 2019 | Cell Research2019，29，8： | 6 |
| 16 | Relationship between serum antisperm antibodies and anticardiolipin antibodies and clinical pregnancy outcome in an in vitro fertilization and embryo transfer program显示文摘Inrecentyearsanimmunecomponenthasbeenrecognizedinseveraltypesofreproductivefailure,includinginfertility.Thepathogenicmechanis... | 田秀珠 张丽珠 吴燕 杨池荪 刘平 | 1999 | Chinese Medical Journal1999，，1： | 6 |
| 17 | Monoclonal neutralizing antibodies against EV71 screened from mice immunized with yeast-produced virus-like particles显示文摘Periodic outbreaks of hand, foot and mouth disease(HFMD) occur in children under 5 years old, and can cause death in some cases. The C4 strain of enterovirus 71(EV71) is the main pathogen that causes HFMD in China. Although no drugs against EV71 are available, some studies have shown that candidate vaccines or viral capsid proteins can produce anti-EV71 immunity. In this study, female BABL/c mice(6–8 weeks old) were immunized with virus-like particles(VLPs) of EV71 produced in yeast to screen for anti-EV71 antibodies. Two hybridomas that could produce neutralizing antibodies against EV71 were obtained. Both neutralizing m Abs(D4 and G12) were confirmed to bind the VP1 capsid protein of EV71, and could protect > 95% cells from 100 TCID50 EV71 infection at 25 μg/m L solution(lowest concentration). Those two neutralizing m Abs identified in the study may be promising candidates in development for m Abs to treat EV71 infection, and utilized as suitable reagents for use in diagnostic tests and biological studies. | Tao Lin Lingzhi Xianyu Songya Lyu | 2015 | Virologica Sinica2015，30，3： | 6 |
| 18 | Broadly neutralizing antibodies and vaccine design against HIV-1 infection显示文摘Remarkable progress has been achieved for prophylactic and therapeutic interventions against human immunodeficiency virus type I(HIV-1)through antiretroviral therapy.However,vaccine development has remained challenging.Recent discoveries in broadly neutralizing monoclonal antibodies(bNAbs)has led to the development of multiple novel vaccine approaches for inducing bNAbs-like antibody response.Structural and dynamic studies revealed several vulnerable sites and states of the HIV-1 envelop glycoprotein(Env)during infection.Our review aims to highlight these discoveries and rejuvenate our endeavor in HIV-1 vaccine design and development. | Qian Wang Linqi Zhang | 2020 | Frontiers of Medicine2020，14，1： | 4 |
| 19 | Recurrent headaches may be caused by cerebral toxoplasmosis显示文摘AIM: To establish seroprevalence and provide characteristics of Toxoplasma gondii(TG) infection in children with recurrent headaches. METHODS: The study was performed in 178 children aged 7-17 years admitted consecutively to the Department of Pediatric Neurology from November 2009 to July 2011. The children were surveyed with a questionnaire with the help and assistance of their parents and blood samples taken on admission were studied for the presence of specific anti-TG Ig M, Ig G antibodies and Ig G avidity using enzyme immunoassay Platelia Toxo Ig M, Ig G. RESULTS: The study showed that 19 children(8 boys, 11 girls; 8-17 years old, mean age 14.36 years) hadhigh serum anti-TG Ig G antibody levels(range: 32.2 > 240 UI/m L, mean 120.18 UI/m L; positive value for Ig G was ≥ 9 UI/m L). The avidity index(AI) ranged from 0.202 to 0.925(scale: ≥ 0.5 high AI). The results for Ig M antibodies were all negative and the obtained results ranged from 0.113 to 0.25 U/m L(mean = 0.191 IU/m L) and all values below 0.8 IU/m L were considered negative. The most frequent complaints found in the seropositive patients were headaches that affected the frontal(13 children), occipital(4) and parietal areas(5). Headaches usually had a pulsating(in 7 patients) and squeezing(6) character and rarely were piercing, dull or expanding. Interestingly, 8 children did not feel discomfort during the headaches, probably because they did not have sufficiently increased intracranial pressure yet. The headaches usually appeared 1-2 times/mo, lasted for 2-6 h, and had a mean intensity of 5.5 points in a 10 point subjective scale. The comorbidities included epilepsy(5 patients), various infections in 3 children(chronic eustachitis, chronic rhinitis, chronic purulent tonsillitis, streptococcal pharyngitis, meningitis, allergic diseases), disturbances of behavior, deficits of attention, and ocular and motor concentration disorders in 1 child. The electroencephalographic and neuroimaging studies performed in our patients had a very limited value in establishing cerebral toxoplasmosis.CONCLUSION: Ten point six seven percent of the studied children had markedly increased serum anti-TG Ig G antibodies and high AI indicated chronic infestation. It is suggested that tests for TG infection should be introduced to routine diagnostics in patients with recurrent headaches. | Joseph Prandota Anna Gryglas Aleksander Fuglewicz Agata Zesawska-Faleńczyk Barbara Ujma-Czapska Leszek Szenborn Janusz Mierzwa | 2014 | World Journal of Clinical Pediatrics2014，3，3： | 4 |
| 20 | Structural basis for bivalent binding and inhibition of SARS-CoV-2 infection by human potent neutralizing antibodies显示文摘Neutralizing monoclonal antibodies(nAbs)to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)represent promising candidates for clinical intervention against coronavirus disease 2019(COVID-19).We isolated a large number of nAbs from SARS-CoV-2-infected individuals capable of disrupting proper interaction between the receptor binding domain(RBD)of the viral spike(S)protein and the receptor angiotensin converting enzyme 2(ACE2).However,the structural basis for their potent neutralizing activity remains unclear.Here,we report cryo-EM structures of the ten most potent nAbs in their native full-length IgG-form or in both IgG-form and Fab-form bound to the trimeric S protein of SARS-CoV-2.The bivalent binding of the full-length IgG is found to associate with more RBDs in the“up”conformation than the monovalent binding of Fab,perhaps contributing to the enhanced neutralizing activity of IgG and triggering more shedding of the S1 subunit from the S protein.Comparison of a large number of nAbs identified common and unique structural features associated with their potent neutralizing activities.This work provides a structural basis for further understanding the mechanism of nAbs,especially through revealing the bivalent binding and its correlation with more potent neutralization and the shedding of S1 subunit. | Renhong Yan Ruoke Wang Bin Ju Jinfang Yu Yuanyuan Zhang Nan Liu Jia Wang Qi Zhang Peng Chen Bing Zhou Yaning Li Yaping Shen Shuyuan Zhang Long Tian Yingying Guo Lu Xia Xinyue Zhong Lin Cheng Xiangyang Ge Juanjuan Zhao Hong-Wei Wang Xinquan Wang Zheng Zhang Linqi Zhang Qiang Zhou | 2021 | Cell Research2021，31，5： | 4 |
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