24 results on '"Yaohui Fang"'
Search Results
2. Interactome analysis of Crimean-Congo hemorrhagic fever virus glycoproteins reveals HAX1 as a host restriction factor against the virion packaging
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Shiyu Dai, Qi Li, Kuan Feng, Yuan-Qin Min, Zhenyu Jiang, Fuli Ren, Yaohui Fang, Jingyuan Zhang, Qiong Zhu, Manli Wang, Hualin Wang, Fei Deng, and Yun-Jia Ning
- Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is a biosafety level-4 and World Health Organization-recognized priority pathogen requiring urgent Research & Development attention. The glycoproteins of CCHFV, Gn and Gc, are considered to play multiple roles in the viral life cycle by interactions with host cells; however, these interactions remain largely unclear to date. Here, we analyzed the cellular interactomes of CCHFV glycoproteins by affinity purification-quantitative mass spectrometry and identified 45 host proteins as high-confidence Gn/Gc interactors. These host molecules are involved in transmembrane transport, metabolism, oxidative stress, protein folding and glycosylation, etc., in line with the potential physiological actions of the viral glycoproteins. As a proof of principle, we detailedly elucidated the role of an identified cellular protein, HAX1, and therefore uncovered an interesting host antiviral strategy. HAX1 interacts with Gn by its C-terminus, while its N-terminal region leads to mitochondrial localization. By the strong interaction, HAX1 sequestrates Gn to mitochondria, thus depriving Gn of its normal Golgi localization that is indispensable for functional glycoprotein-mediated progeny virion packaging. Consistently, the notable inhibitory activity of HAX1 against viral packaging and hence propagation was further elucidated in the contexts of pseudotyped and authentic CCHFV infections by series of loss/gain-of-function assays in cellular and animal infection models. Together, the findings not only provide a systematic CCHFV Gn/Gc-host protein-protein interaction map, but also unravel a novel cellular antiviral mechanism, which may facilitate further studies on CCHFV biology and therapeutic approaches.
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- 2023
3. Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases
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Shu, Shen, Yaxian, Zhang, Zhiyun, Yin, Qiong, Zhu, Jingyuan, Zhang, Tiantian, Wang, Yaohui, Fang, Xiaoli, Wu, Yuan, Bai, Shiyu, Dai, Xijia, Liu, Jiayin, Jin, Shuang, Tang, Jia, Liu, Manli, Wang, Yu, Guo, and Fei, Deng
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Mice ,Viral Proteins ,Antifungal Agents ,SARS-CoV-2 ,Virus Diseases ,Animals ,Receptor, Interferon alpha-beta ,General Medicine ,Anidulafungin ,Bunyaviridae Infections ,Antiviral Agents ,Clathrin - Abstract
Background The severe fever with thrombocytopenia syndrome disease (SFTS), caused by the novel tick-borne SFTS virus (SFTSV), was listed among the top 10 priority infectious disease by World Health Organization due to the high fatality rate of 5–30% and the lack of effective antiviral drugs and vaccines and therefore raised the urgent need to develop effective anti-SFTSV drugs to improve disease treatment. Methods The antiviral drugs to inhibit SFTSV infection were identified by screening the library containing 1340 FDA-approved drugs using the SFTSV infection assays in vitro. The inhibitory effect on virus entry and the process of clathrin-mediated endocytosis under different drug doses was evaluated based on infection assays by qRT-PCR to determine intracellular viral copies, by Western blot to characterize viral protein expression in cells, and by immunofluorescence assays (IFAs) to determine virus infection efficiencies. The therapeutic effect was investigated in type I interferon receptor defective A129 mice in vivo with SFTSV infection, from which lesions and infection in tissues caused by SFTSV infection were assessed by H&E staining and immunohistochemical analysis. Results Six drugs were identified as exerting inhibitory effects against SFTSV infection, of which anidulafungin, an antifungal drug of the echinocandin family, has a strong inhibitory effect on SFTSV entry. It suppresses SFTSV internalization by impairing the late endosome maturation and decreasing virus fusion with the membrane. SFTSV-infected A129 mice had relieving symptoms, reduced tissue lesions, and improved disease outcomes following anidulafungin treatment. Moreover, anidulafungin exerts an antiviral effect in inhibiting the entry of other viruses including SARS-CoV-2, SFTSV-related Guertu virus and Heartland virus, Crimean-Congo hemorrhagic fever virus, Zika virus, and Herpes simplex virus 1. Conclusions The results demonstrated that the antifungal drug, anidulafungin, could effectively inhibit virus infection by interfering with virus entry, suggesting it may be utilized for the clinical treatment of infectious viral diseases, in addition to its FDA-approved use as an antifungal. The findings also suggested to further evaluate the anti-viral effects of echinocandins and their clinical importance for patients with infection of viruses, which may promote therapeutic strategies as well as treatments and improve outcomes pertaining to various viral and fungal diseases.
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- 2022
4. A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes
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Dan Fu, Mingjie Chen, Yuhui Wang, Wei Zhang, Zihe Rao, Zhiming Yuan, Chen Zhang, Zhiyong Lou, Lisu Huang, W.J. Zhang, Chunjiang Pi, Shu Shen, Mingfang Feng, Yuan Wang, Xue Hu, Hongkai Zhang, Da Chen, Ge Gao, Minmin Lu, Feng Yu, Yun-Yueh Lu, Yu Guo, Francisco Adrian, Bingqing Shen, Yanfeng Yao, Liang Schweizer, Alexey Stepanov, Yarong Li, Junwei Liu, Qisheng Wang, Fei Deng, Xin Li, Jia Wu, Bo Li, Juan Min, He Zhou, Shanshan Wang, Kun Sun, Qian Zhang, Heyu Huang, X.Q. Zeng, Alexander G. Gabibov, Yun Peng, Xingdong Zhou, Chao Shan, Yan Cai, Yaohui Fang, and Guangshun Zhang
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Male ,0301 basic medicine ,medicine.drug_class ,Science ,Protein domain ,Mutant ,General Physics and Astronomy ,Plasma protein binding ,Biology ,Antibodies, Viral ,Monoclonal antibody ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,Protein Domains ,Antibody Specificity ,Cell Line, Tumor ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Neutralizing antibody ,skin and connective tissue diseases ,Pandemics ,Vero Cells ,Cells, Cultured ,Multidisciplinary ,SARS-CoV-2 ,fungi ,Wild type ,Antibodies, Monoclonal ,COVID-19 ,General Chemistry ,Antibodies, Neutralizing ,Macaca mulatta ,Virology ,COVID-19 Drug Treatment ,body regions ,Treatment Outcome ,030104 developmental biology ,Mutation ,Spike Glycoprotein, Coronavirus ,biology.protein ,Vero cell ,Female ,Antibody ,030217 neurology & neurosurgery ,Protein Binding - Abstract
COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against SARS-CoV-2 can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent antibodies binding to SARS-CoV-2 Spike protein were identified from COVID-19 convalescent patients. Among them, P4A1 interacts directly with and covers majority of the Receptor Binding Motif of the Spike Receptor-Binding Domain, shown by high-resolution complex structure analysis. We further demonstrate the binding and neutralizing activities of P4A1 against wild type and mutant Spike proteins or pseudoviruses. P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life. The engineered antibody exhibits an optimized pharmacokinetic and safety profile, and it results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection. These data suggest its potential against SARS-CoV-2 related diseases.
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- 2021
5. Next-generation Liquid Biopsy Instruments: Challenges and Opportunities
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Shu Zhu, Yaohui Fang, Kefan Guo, Zhonghua Ni, and Nan Xiang
- Abstract
Conventional cancer diagnosis needs to excise diseased tissue from the patient’s body for biopsy, causing severe injury to patients. Liquid biopsy with the superior advantage of minimal invasiveness has shown its ability to cancer diagnosis in real-time, and has been developing promising diagnostic instruments. However, until today, the developed instrument still cannot be an alternative to tissue biopsy in the majority of research and clinical settings. In this paper, we firstly summarize the challenges and limitations suffered by the existing liquid biopsy instrument. Then, the opportunities and future progression of the next-generation instrument are discussed in detail. In all, we hope that the future liquid biopsy instrument can be eventually integrated into the clinical workflow, and serve as a validated and reliable tool for cancer diagnosis.
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- 2022
6. Viromes and surveys of RNA viruses in camel-derived ticks revealing transmission patterns of novel tick-borne viral pathogens in Kenya
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Moses Masika, Jacqueline K Lichoti, Jun Wang, Bernard Agwanda, Shu Shen, Sheila C. Ommeh, Stephen Kuria, Zhengli Shi, Shuang Tang, Hualin Wang, Fei Deng, You Zhang, Ben Hu, Zhaojun Fan, Yaohui Fang, and Juan Yang
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tick-borne viruses ,Camelus ,Epidemiology ,viruses ,Immunology ,Genome, Viral ,Microbiology ,Ticks ,RNA Virus Infections ,Tick borne ,Virology ,parasitic diseases ,Drug Discovery ,camels ,Animals ,Humans ,RNA Viruses ,Human virome ,viral transmission correlation ,virome ,biology ,Transmission (medicine) ,RNA ,General Medicine ,bacterial infections and mycoses ,Serum samples ,biology.organism_classification ,Kenya ,Tick Infestations ,Infectious Diseases ,Tick-Borne Diseases ,RNA, Viral ,Parasitology ,Hyalomma ,Research Article - Abstract
Tick-borne viruses (TBVs) capable of transmitting between ticks and hosts have been increasingly recognized as a global public health concern. In this study, Hyalomma ticks and serum samples from camels were collected using recorded sampling correlations in eastern Kenya. Viromes of pooled ticks were profiled by metagenomic sequencing, revealing a diverse community of viruses related to at least 11 families. Five highly abundant viruses, including three novel viruses (Iftin tick virus, Mbalambala tick virus [MATV], and Bangali torovirus [BanToV]) and new strains of previously identified viruses (Bole tick virus 4 [BLTV4] and Liman tick virus [LMTV]), were characterized in terms of genome sequences, organizations, and phylogeny, and their molecular prevalence was investigated in individual ticks. Moreover, viremia and antibody responses to these viruses have been investigated in camels. MATV, BLTV4, LMTV, and BanToV were identified as viral pathogens that can potentially cause zoonotic diseases. The transmission patterns of these viruses were summarized, suggesting three different types according to the sampling relationships between viral RNA-positive ticks and camels positive for viral RNA and/or antibodies. They also revealed the frequent transmission of BanToV and limited but effective transmission of other viruses between ticks and camels. Furthermore, follow-up surveys on TBVs from tick, animal, and human samples with definite sampling relationships are suggested. The findings revealed substantial threats from the emerging TBVs and may guide the prevention and control of TBV-related zoonotic diseases in Kenya and in other African countries.
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- 2021
7. SARS-CoV-2 N protein antagonizes type I interferon signaling by suppressing phosphorylation and nuclear translocation of STAT1 and STAT2
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Fei Deng, An Wang, Yaohui Fang, Qi Yang, Muhan Huang, Xi Zhou, Jingfang Mu, Ting Shu, Liang Jin, and Yang Qiu
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2019-20 coronavirus outbreak ,biology ,Coronavirus disease 2019 (COVID-19) ,lcsh:Cytology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Cell Biology ,Biochemistry ,Nuclear translocation ,Cell biology ,Interferon ,Correspondence ,Genetics ,biology.protein ,medicine ,Phosphorylation ,STAT1 ,STAT2 ,lcsh:QH573-671 ,Molecular Biology ,medicine.drug - Published
- 2020
8. Evidence of Human Exposure to Tamdy Virus, Northwest China
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Yanfang Zhang, Abulimiti Moming, Yujiang Zhang, Surong Sun, Jingyuan Zhang, Hualin Wang, Fei Deng, Shuang Tang, Lin-Fa Wang, Tianxian Li, Yaohui Fang, Shu Shen, and Zhihong Hu
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Microbiology (medical) ,China ,human virus exposure ,Isolation (health care) ,Ixodidae ,Tamdy virus ,Epidemiology ,Virus isolation ,viruses ,Infectious and parasitic diseases ,RC109-216 ,Biology ,tickborne virus ,Virus ,Serology ,ticks ,Orthonairovirus ,Animals ,Humans ,virus isolation ,Dispatch ,Virology ,Hyalomma asiaticum ,Infectious Diseases ,Human exposure ,Evidence of Human Exposure to Tamdy Virus, Northwest China ,arboviruses ,Viruses ,Etiology ,Medicine - Abstract
We report the isolation of Tamdy virus from Hyalomma asiaticum ticks in northwest China and serologic evidence of human Tamdy virus infection in the same region. These findings highlight the need to further investigate a potential causal relationship between Tamdy virus and febrile illnesses of unknown etiology in that region.
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- 2021
9. Antibody neutralization to SARS-CoV-2 and variants after 1 year in Wuhan, China
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Ke Xu, Bing Hu, Shu Shen, Faxian Zhan, Xin Wang, Qianyun Liu, Yaohui Fang, Suhua Zhou, Yongzhong Jiang, Huan Yan, Ming Guo, Fei Deng, Yu Chen, Qing Xiong, Li Tao, Yingle Liu, Kun Cai, Li Zhou, Junqiang Xu, Zhen Zhang, Xianying Chen, Fanghua Mei, Chengbao Ma, Changwen Ke, Fang Liu, and Ke Lan
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B.1.617.2 ,2019-20 coronavirus outbreak ,Science (General) ,Multidisciplinary ,Coronavirus disease 2019 (COVID-19) ,biology ,SARS-CoV-2 ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,fungi ,convalescent ,Immune escape ,food and beverages ,biochemical phenomena, metabolism, and nutrition ,Virology ,Neutralization ,Q1-390 ,variant ,Immunity ,Report ,antibody ,Humoral immunity ,biology.protein ,Antibody - Abstract
Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulins G (IgG) were well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but escaped by the emerging variants., graphical Abstract
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- 2021
10. Tetrasubstituted imidazoles as incognito Toll-like receptor 8 a(nta)gonists
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Torey Jones, H. Tanji, Umeharu Ohto, Kentaro Sakaniwa, Toshiyuki Shimizu, Shuangshuang Jiang, Hang Yin, Jian Huang, Subada Soti, Fei Deng, Chengrui Shi, Adam Csakai, Yaohui Fang, Yi Yang, Christina Smith, Lindsey J. Broadwell, and Shu Shen
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Agonist ,genetic structures ,medicine.drug_class ,Science ,Inflammatory response ,General Physics and Astronomy ,Medicinal chemistry ,Inflammation ,Mechanism of action ,Calorimetry ,behavioral disciplines and activities ,01 natural sciences ,Article ,General Biochemistry, Genetics and Molecular Biology ,Structure-Activity Relationship ,03 medical and health sciences ,X-Ray Diffraction ,medicine ,Humans ,Drug discovery and development ,030304 developmental biology ,0303 health sciences ,Toll-like receptor ,Multidisciplinary ,Innate immune system ,010405 organic chemistry ,business.industry ,Small molecules ,Imidazoles ,General Chemistry ,TLR8 ,Tlr agonists ,Recombinant Proteins ,Toll-like receptors ,0104 chemical sciences ,Molecular Docking Simulation ,HEK293 Cells ,nervous system ,Toll-Like Receptor 8 ,Quinolines ,Cancer research ,RNA ,medicine.symptom ,business ,psychological phenomena and processes ,Signal Transduction - Abstract
Small-molecule modulators of TLR8 have drawn much interests as it plays pivotal roles in the innate immune response to single-stranded RNAs (ssRNAs) derived from viruses. However, their clinical uses are limited because they can invoke an uncontrolled, global inflammatory response. The efforts described herein culminate in the fortuitous discovery of a tetrasubstituted imidazole CU-CPD107 which inhibits R848-induced TLR8 signaling. In stark contrast, CU-CPD107 shows unexpected synergistic agonist activities in the presence of ssRNA, while CU-CPD107 alone is unable to influence TLR8 signaling. CU-CPD107’s unique, dichotomous behavior sheds light on a way to approach TLR agonists. CU-CPD107 offers the opportunity to avoid the undesired, global inflammation side effects that have rendered imidazoquinolines clinically irrelevant, providing an insight for the development of antiviral drugs., Toll-like receptor 8 (TLR8) plays essential roles in the innate immune response to viral single-stranded RNA (ssRNA), so small molecule modulators of TLR8 are of interest, however adverse effects limit their use. Here, the authors report a tetrasubstituted imidazole CU-CPD107 with dichotomous behaviour, which inhibits R848-induced TLR8 signaling, but shows synergistic activity in the presence of ssRNA, making it a potential antiviral agent.
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- 2021
11. Antibody neutralization to SARS-CoV-2 and variants after one year in Wuhan
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Qing Xiong, Chengbao Ma, Bing Hu, Yingle Liu, Kun Cai, Zhen Zhang, Huan Yan, Qianyun Liu, Yongzhong Jiang, Faxian Zhan, Xianying Chen, Fang Liu, Ming Guo, Fanghua Mei, Changwen Ke, Shu Shen, Ke Lan, Xin Wang, Li Zhou, Fei Deng, Yu Chen, Junqiang Xu, Yaohui Fang, and Ke Xu
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Vaccination ,Mutation ,Humoral immunity ,biology.protein ,medicine ,Potency ,Biology ,Antibody ,medicine.disease_cause ,Virology ,Epitope ,Immunoglobulin G ,Neutralization - Abstract
Most COVID-19 patients can build effective humoral immunity against SARS-CoV-2 after recovery(1, 2). However, it remains unknown how long the protection can maintain and how efficiently it can protect people from the reinfection of the emerging SARS-CoV-2 variants. Here we evaluated the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest epicenter of SARS-CoV-2. We demonstrated that the SARS-CoV-2 immunoglobulin G (IgG) maintains at a high level and potently neutralizes the infection of the original strain (WT) and the B.1.1.7 variant in most patients. However, they showed varying degrees of efficacy reduction against the other variants of concern (P.1, B.1.525, and especially B.1.351) in a patient-specific manner. Mutations in RBD including K417N, E484K, and E484Q/L452R (B.1.617) remarkably impair the neutralizing activity of the convalescents’ sera. Encouragingly, we found that a small fraction of patients’ sera showed broad neutralization potency to multiple variants and mutants, suggesting the existence of broadly neutralizing antibodies recognizing the epitopes beyond the mutation sites. Our results suggest that the SARS-CoV-2 vaccination effectiveness relies more on the timely re-administration of the epitope-updated vaccine than the durability of the neutralizing antibodies.
- Published
- 2021
12. Declining Levels of Neutralizing Antibodies Against SARS-CoV-2 in Convalescent COVID-19 Patients One Year Post Symptom Onset
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Tiandan Xiang, Boyun Liang, Yaohui Fang, Sihong Lu, Sumeng Li, Hua Wang, Huadong Li, Xiaoli Yang, Shu Shen, Bin Zhu, Baoju Wang, Jun Wu, Jia Liu, Mengji Lu, Dongliang Yang, Ulf Dittmer, Mirko Trilling, Fei Deng, and Xin Zheng
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SARS-CoV-2 ,humoral immunity ,COVID-19 ,spike ,Immunologic diseases. Allergy ,RC581-607 ,antibody responses - Abstract
Major advances have been made in understanding the dynamics of humoral immunity briefly after the acute coronavirus disease 2019 (COVID-19). However, knowledge concerning long-term kinetics of antibody responses in convalescent patients is limited. During a one-year period post symptom onset, we longitudinally collected 162 samples from 76 patients and quantified IgM and IgG antibodies recognizing the nucleocapsid (N) protein or the receptor binding domain (RBD) of the spike protein (S). After one year, approximately 90% of recovered patients still had detectable SARS-CoV-2-specific IgG antibodies recognizing N and RBD-S. Intriguingly, neutralizing activity was only detectable in ~43% of patients. When neutralization tests against the E484K-mutated variant of concern (VOC) B.1.351 (initially identified in South Africa) were performed among patients who neutralize the original virus, the capacity to neutralize was even further diminished to 22.6% of donors. Despite declining N- and S-specific IgG titers, a considerable fraction of recovered patients had detectable neutralizing activity one year after infection. However, neutralizing capacities, in particular against an E484K-mutated VOC were only detectable in a minority of patients one year after symptomatic COVID-19. Our findings shed light on the kinetics of long-term immune responses after natural SARS-CoV-2 infection and argue for vaccinations of individuals who experienced a natural infection to protect against emerging VOC.
- Published
- 2021
13. Observation of topological superconductivity in a stoichiometric transition metal dichalcogenide 2M-WS2
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Yiwei Li, Jinliang Pan, Huakun Zheng, Yaohui Fang, D. Q. Zhang, Huichao Zhang, Cephise Cacho, S. W. Jung, Yujie Chen, Cheng Chen, Fuqiang Huang, Suning Liu, Longyong Xu, Wujun Shi, Aiji Liang, Yudou He, Alexei Barinov, Donghui Lu, Yulin Chen, Makoto Hashimoto, Ding Pei, Liang Fu, Meixiao Wang, Zhongkai Liu, and Lexian Yang
- Subjects
cond-mat.supr-con ,Materials science ,Photoemission spectroscopy ,Science ,FOS: Physical sciences ,General Physics and Astronomy ,02 engineering and technology ,Topology ,01 natural sciences ,Article ,General Biochemistry, Genetics and Molecular Biology ,Superconducting properties and materials ,Superconductivity (cond-mat.supr-con) ,symbols.namesake ,Condensed Matter::Superconductivity ,0103 physical sciences ,Topological insulators ,010306 general physics ,Surface states ,Quantum computer ,Superconductivity ,Condensed Matter - Materials Science ,Multidisciplinary ,Condensed Matter - Superconductivity ,Materials Science (cond-mat.mtrl-sci) ,Heterojunction ,General Chemistry ,021001 nanoscience & nanotechnology ,cond-mat.mtrl-sci ,MAJORANA ,Qubit ,symbols ,van der Waals force ,0210 nano-technology - Abstract
Topological superconductors (TSCs) are unconventional superconductors with bulk superconducting gap and in-gap Majorana states on the boundary that may be used as topological qubits for quantum computation. Despite their importance in both fundamental research and applications, natural TSCs are very rare. Here, combining state of the art synchrotron and laser-based angle-resolved photoemission spectroscopy, we investigated a stoichiometric transition metal dichalcogenide (TMD), 2M-WS2 with a superconducting transition temperature of 8.8 K (the highest among all TMDs in the natural form up to date) and observed distinctive topological surface states (TSSs). Furthermore, in the superconducting state, we found that the TSSs acquired a nodeless superconducting gap with similar magnitude as that of the bulk states. These discoveries not only evidence 2M-WS2 as an intrinsic TSC without the need of sensitive composition tuning or sophisticated heterostructures fabrication, but also provide an ideal platform for device applications thanks to its van der Waals layered structure., Accepted by Nature Communications
- Published
- 2021
14. SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism
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Fei Deng, Xin Zheng, Jun Wu, Yaohui Fang, Jingyuan Zhang, Sihong Lu, and Shu Shen
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Blood Platelets ,Platelets ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Transcription, Genetic ,Receptor expression ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Virus Attachment ,ACE2 ,030204 cardiovascular system & hematology ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Thrombophilia ,Diseases of the blood and blood-forming organs ,Platelet ,RNA, Messenger ,Platelet activation ,Receptor ,Letter to the Editor ,Molecular Biology ,RC254-282 ,Hematology ,SARS-CoV-2 ,Chemistry ,Mechanism (biology) ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,COVID-19 ,Virus Internalization ,Alternative receptors ,Cell biology ,030104 developmental biology ,Oncology ,Coagulation ,Organ Specificity ,RNA, Viral ,Receptors, Virus ,Angiotensin-Converting Enzyme 2 ,RC633-647.5 ,Megakaryocytes - Abstract
Evidence suggests that platelets may directly interact with SARS-CoV-2, raising the concern whether ACE2 receptor plays a role in this interaction. The current study showed that SARS-CoV-2 interacts with both platelets and megakaryocytes despite the limited efficiency. Abundance of the conventional receptor ACE2 and alternative receptors or co-factors for SARS-CoV-2 entry was characterized in platelets from COVID-19 patients and healthy persons as well as human megakaryocytes based on laboratory tests or previously reported RNA-seq data. The results suggest that SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism and may regulate alternative receptor expression associated with COVID-19 coagulation dysfunction. Supplementary Information The online version contains supplementary material available at 10.1186/s13045-021-01082-6.
- Published
- 2021
15. Reviving chloroquine for anti-SARS-CoV-2 treatment with cucurbit[7]uril-based supramolecular formulation
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Shengke Li, Cheryl H. T. Kwong, Simon Ming-Yuen Lee, Yaohui Fang, Fei Deng, Hiotong Kam, Ruibing Wang, Jingfang Mu, Qianyun Liu, Xiangjun Zhang, Xi Zhou, and Yu Chen
- Subjects
viruses ,02 engineering and technology ,010402 general chemistry ,medicine.disease_cause ,01 natural sciences ,Virus ,Mouse hepatitis virus ,In vivo ,Chloroquine ,medicine ,Cytotoxicity ,Curcurbit[7]uril ,Coronavirus ,biology ,Chemistry ,SARS-CoV-2 ,Communication ,COVID-19 ,Host-guest ,General Chemistry ,021001 nanoscience & nanotechnology ,biology.organism_classification ,Virology ,In vitro ,0104 chemical sciences ,Vero cell ,0210 nano-technology ,medicine.drug - Abstract
Graphical abstract Chloroquine (CQ), an antimalarial drug, was found to exhibit promising antiviral activity in vitro and in vivo at a high dosage, thus CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity. Herein, we show that supramolecular formulation of CQ by a macrocyclic host, curcurbit[7]uril (CB[7]), reduced its non-specific toxicity and improved its antiviral activity against coronavirus, working in synergy with CB[7]., The wide-spreading SARS-CoV-2 virus has put the world into boiling water for more than a year, however pharmacological therapies to act effectively against coronavirus disease 2019 (COVID-19) remain elusive. Chloroquine (CQ), an antimalarial drug, was found to exhibit promising antiviral activity in vitro and in vivo at a high dosage, thus CQ was approved by the FDA for the emergency use authorization (EUA) in the fight against COVID-19 in the US, but later was revoked the EUA status due to the severe clinical toxicity. Herein, we show that supramolecular formulation of CQ by a macrocyclic host, curcurbit[7]uril (CB[7]), reduced its non-specific toxicity and improved its antiviral activity against coronavirus, working in synergy with CB[7]. CB[7] was found to form 1:1 host-guest complexes with CQ, with a binding constant of ∼104 L/mol. The CQ-CB[7] formulation decreased the cytotoxicity of CQ against Vero E6 and L-02 cell lines. In particular, the cytotoxicity of CQ (60 µmol/L) against both Vero E6 cell line and L-02 cell lines was completely inhibited in the presence of 300 µmol/L and 600 µmol/L CB[7], respectively. Furthermore, the CB[7] alone showed astonishing antiviral activity in SARS-CoV-2 infected Vero E6 cells and Mouse hepatitis virus strain A59 (MHV-A59) infected N2A cells, and synergistically improved the antiviral activity of CQ-CB[7], suggesting that CB[7]-based CQ formulation has a great potential as a safe and effective antiviral agent against SARS-CoV-2 and other coronavirus.
- Published
- 2021
16. Occurrence of COVID-19 symptoms during SARS-CoV-2 infection defines waning of humoral immunity
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Liangkai Chen, Tiandan Xiang, Hua Wang, Dongliang Yang, Sihong Lu, Boyun Liang, Yaohui Fang, Jun Wu, Jia Liu, Ulf Dittmer, Mengji Lu, Fei Deng, Vu Thuy Khanh Le-Trilling, Sumeng Li, Mirko Trilling, Xin Zheng, Shu Shen, and Xiaoli Yang
- Subjects
biology ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Asymptomatic ,Immunoglobulin G ,Antigen ,Immunization ,Immunity ,Immunology ,Humoral immunity ,medicine ,biology.protein ,medicine.symptom ,Antibody ,business - Abstract
Approximately half of the SARS-CoV-2 infections occur without apparent symptoms, raising questions regarding long-term humoral immunity in asymptomatic individuals. Plasma levels of immunoglobulin G (IgG) and M (IgM) against the viral spike or nucleoprotein were determined for 25,091 individuals enrolled in a surveillance program in Wuhan, China. We compared 405 asymptomatic individuals with 459 symptomatic COVID-19 patients. The well-defined duration of the SARS-CoV-2 endemic in Wuhan allowed a side-by-side comparison of antibody responses following symptomatic and asymptomatic infections without subsequent antigen re-exposure. IgM responses rapidly declined in both groups. However, both the prevalence and durability of IgG responses and neutralizing capacities correlated positively with symptoms. Regardless of sex, age, and body weight, asymptomatic individuals lost their SARS-CoV-2-specific IgG antibodies more often and rapidly than symptomatic patients. These findings have important implications for immunity and favour immunization programs including individuals after asymptomatic infections.One-Sentence SummaryPrevalence and durability of SARS-CoV-2-specific IgG responses and neutralizing capacities correlate with COVID-19 symptoms.
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- 2021
17. SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19
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Hua Wang, Xin Zheng, Xuecheng Yang, Fei Deng, Bin Zhu, Yang Wu, Boyun Liang, Xiaoli Yang, Adalbert Krawczyk, Jun Wu, Baoju Wang, Cunrong Chen, Shumeng Li, Huadong Li, Yaohui Fang, Huan Wang, Mengji Lu, Mirko Trilling, Liangkai Chen, Di Liu, Ulf Dittmer, Dongliang Yang, Shu Shen, Chen Qi, Wenqing Zhou, Jia Liu, Sihong Lu, and Wei Li
- Subjects
Adult ,Male ,0301 basic medicine ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Medizin ,General Physics and Astronomy ,Antibodies, Viral ,medicine.disease_cause ,Severity of Illness Index ,Article ,Antibodies ,General Biochemistry, Genetics and Molecular Biology ,Virus ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Immunity ,medicine ,Humans ,030212 general & internal medicine ,Aged ,Coronavirus ,Multidisciplinary ,biology ,SARS-CoV-2 ,business.industry ,COVID-19 ,General Chemistry ,Middle Aged ,Antibodies, Neutralizing ,Immunity, Humoral ,Titer ,030104 developmental biology ,Immunoglobulin M ,Viral infection ,Immunoglobulin G ,Spike Glycoprotein, Coronavirus ,Immunology ,Humoral immunity ,biology.protein ,Female ,Antibody ,business - Abstract
Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of 6 months from COVID-19 disease onset in 349 symptomatic COVID-19 patients who were among the first be infected world-wide. The positivity rate and magnitude of IgM-S and IgG-N responses increase rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset are associated with virus control and IgG-S titers correlate closely with the capacity to neutralize SARS-CoV-2. Although specific IgM-S/N become undetectable 12 weeks after disease onset in most patients, IgG-S/N titers have an intermediate contraction phase, but stabilize at relatively high levels over the 6 month observation period. At late time points, the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies are still >70%. These data indicate sustained humoral immunity in recovered patients who had symptomatic COVID-19, suggesting prolonged immunity., A better understanding of longitudinal changes in antibody responses in COVID-19 patients is needed. Here the authors analyze anti-spike and anti-nucleocapsid antibody responses to Sars-CoV-2 over a course of 6 months in a large cohort of patients with COVID-19, showing that IgM is mostly not detectable after 3 months, whereas IgG responses contract, yet remain at high levels at 6 months.
- Published
- 2021
18. Additional file 1 of SARS-CoV-2 interacts with platelets and megakaryocytes via ACE2-independent mechanism
- Author
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Shen, Shu, Jingyuan Zhang, Yaohui Fang, Sihong Lu, Wu, Jun, Zheng, Xin, and Deng, Fei
- Abstract
Additional file 1. Detailed materials and methods, and supplementary tables and figure.
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- 2021
- Full Text
- View/download PDF
19. A SARS-CoV-2 neutralizing antibody with exceptional spike binding coverage and optimized therapeutic potentials
- Author
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Yaohui Fang, Xin Li, Jia Wu, Yu Guo, Fei Deng, Xue Hu, Shu Shen, Lisu Huang, Yun Peng, W.J. Zhang, Bingqing Shen, Liang Schweizer, Feng Yu, Alexey Stepanov, Yun-Yueh Lu, Junwei Liu, Francisco Adrian, Qisheng Wang, Bo Li, Xingdong Zhou, Chen Zhang, Juan Min, He Zhou, Mingfang Feng, Chao Shan, Qian Zhang, Wei Zhang, Chunjiang Pi, Minmin Lu, Ge Gao, Zhiming Yuan, X.Q. Zeng, Da Chen, Hongkai Zhang, Zhiyong Lou, Yuan Wang, Mingjie Chen, Yuhui Wang, Dan Fu, Yan Cai, Guangshun Zhang, Yanfeng Yao, Zihe Rao, Shanshan Wang, Alexander G. Gabibov, Kun Sun, and Heyu Huang
- Subjects
biology ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,biology.protein ,Spike (software development) ,Neutralizing antibody ,Virology - Abstract
The Coronavirus Disease of 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health and economy. Therapeutic options such as monoclonal antibodies (mAbs) against SARS-CoV-2 are in urgent need. We have identified potent monoclonal antibodies binding to SARS-CoV-2 Spike protein from COVID-19 convalescent patients and one of these antibodies, P4A1, interacts directly and covers the majority of the Receptor Binding Motif (RBM) of Spike receptor-binding domain (RBD), shown by high-resolution complex structure analysis. We further demonstrated P4A1 binding and neutralizing activities against wild type and mutant spike proteins. P4A1 was subsequently engineered to reduce the potential risk for antibody-dependent enhancement (ADE) of infection and to extend its half-life. The engineered mAb exhibits optimized pharmacokinetic and safety profile, and results in complete viral clearance in a rhesus monkey model of COVID-19 following a single injection.
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- 2020
20. Stackable micromixer with modular design for efficient mixing over wide Reynold numbers
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Yu Han, Shu Zhu, Yao Chen, Zhonghua Ni, Yaohui Fang, Nan Xiang, and Peiwen Yu
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Fluid Flow and Transfer Processes ,Computer simulation ,business.industry ,Computer science ,Mechanical Engineering ,Micromixer ,Reynolds number ,Modular design ,Condensed Matter Physics ,Micromixing ,symbols.namesake ,Planar ,symbols ,Electronic engineering ,business ,Mixing (physics) ,Communication channel - Abstract
Fast and efficient micromixing of different species is crucial in many fields. However, most previous micromixers can only achieve well mixing effects in a narrow Reynold number (Re) range, and the 3D micromixers for improved mixing efficiency are difficult to fabricate. To overcome these limitations, we report here a modular designed micromixer that contains an input module (IM), several stackable enhancement modules (EMs), and an output module (OM). Special structures including planar split-and-recombine (P-SAR) channel used for working at low Re, as well as planar and easily-fabricated 3D concave–convex channels used for working at high Re are employed in these modules. Moreover, the numbers of EMs can be increased or decreased flexibly for accomplishing well mixing effect over wide Re numbers. To verify our devices, numerical simulation and experiments are conducted. Under low Re ( 30), our micromixer with only 1 EM can achieve well mixing effect. Therefore, our micromixer can be worked over a wide Re range for efficient mixing than those of previous micromixers. Besides, as each module of our micromixers is made of cheap materials using well-established technologies, our micromixer can be produced massively. We envision the wide application of our micromixer in various fields of material synthesis, chemical, and biological analysis.
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- 2022
21. Immunological detection of serum antibodies in pediatric medical workers exposed to varying levels of SARS-CoV-2
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Fei Deng, Danna Tu, Yanfang Zhang, Junhua Shu, Wuxiang Guan, Hualin Wang, Xiaoqin Zhou, Shu Shen, Guirong Wang, Heng Li, Zhaoxuan Huang, Xiaoli Wu, Zhi Xia, and Yaohui Fang
- Subjects
0301 basic medicine ,Microbiology (medical) ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,viruses ,030106 microbiology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,030212 general & internal medicine ,skin and connective tissue diseases ,biology ,business.industry ,Transmission (medicine) ,fungi ,Infection rate ,respiratory tract diseases ,body regions ,Infectious Diseases ,Immunology ,biology.protein ,Antibody ,business ,Antibody detection - Abstract
Highlights • Pediatric healthcare workers are at risk for SARS-CoV-2 transmission from children and aerosols increase SARS-CoV-2 infection rate. • ELISA and dual-target fluorescence accurately detect SARS-CoV-2 antibodies indicated that antibody detection should be considered as an auxiliary diagnosis of COVID-19. • Antibody positive subjects tested negative for SARS-CoV-2 neutralizing antibodies and SARS-CoV-2 antibodies diminish to near undetectable levels within two months.
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- 2020
22. Novel SFTSV Phylogeny Reveals New Reassortment Events and Migration Routes
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Yanfang Zhang, Junming Shi, Cheng Peng, Shu Shen, Boyun Liang, Ling Xu, Hualin Wang, Tao Zhang, Jun Wang, Wenjing Zhang, Shuang Tang, Fei Deng, Zhengyuan Su, Qiaoli Wu, Mingyue Li, Yaohui Fang, Xin Zheng, Xiaoli Wu, and Mengmeng Li
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0301 basic medicine ,Genetics ,Male ,Phlebovirus ,China ,Future studies ,Phylogenetic tree ,030106 microbiology ,Immunology ,Reassortment ,Biology ,Bunyaviridae Infections ,Sequence identity ,03 medical and health sciences ,030104 developmental biology ,Human disease ,Phylogenetics ,Virology ,Genotype ,Republic of Korea ,Molecular Medicine ,Humans ,Female ,Phylogeny ,Research Articles - Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent of a febrile human disease, was first identified from central and eastern provinces in China, and later in Japan and South Korea. Hubei Province is one of the major SFTS epidemic areas in the central part of China. This study reported the isolation of 11 new SFTSV strains from patients in Hubei Province collected in 2017. Extensive phylogenetic analyses were conducted based on the complete coding sequences of SFTSV segments including the new strains. It was suggested that five different SFTSV genotypes were circulating in Hubei, and 15 reassortment patterns and migration pathways correlated with each genotype were identified, which was more than previously recognized. Hubei Province was more involved in the evolutionary events of SFTSV than that previously thought in which the evolutionary events of SFTSV were reported to be independent from those in other epidemic regions. Further divergence of SFTSV strains was suggested by pairwise comparison of SFTSV sequences from each genotype and sequence identity normalized to representative strain in genotype C1. Subsequently, amino acid variations specific for genotype(s), strain(s), or cluster(s) were inspected, which may be related to differential biological activity of SFTSV strains/genotypes. In conclusion, we analyzed the current status of SFTSV phylogeny in Hubei Province and discussed the possible events correlated to SFTSV evolution. It provided an in-depth insight into SFTSV evolution, raising concerns for the use of proper SFTSV strains in future studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-020-00289-0) contains supplementary material, which is available to authorized users.
- Published
- 2020
23. Isolation, Characterization, and Phylogenetic Analysis of Two New Crimean-Congo Hemorrhagic Fever Virus Strains from the Northern Region of Xinjiang Province, China
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Zhong Zhang, Abulikemu Abudurexiti, Yanfang Zhang, Jinliang Liu, Yaohui Fang, Zhengyuan Su, Yujiang Zhang, Wang Cheng, Qiaoli Wu, Jinhao Liang, Shu Shen, Zhihong Hu, and Fei Deng
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0301 basic medicine ,Veterinary medicine ,China ,Genotype ,Ixodidae ,Immunology ,Sequence Homology ,Biology ,03 medical and health sciences ,Virology ,Animals ,Cluster Analysis ,CCHF VIRUS ,Phylogenetic tree ,Reverse Transcriptase Polymerase Chain Reaction ,Outbreak ,Sequence Analysis, DNA ,Isolation (microbiology) ,Hyalomma asiaticum ,Phylogeography ,030104 developmental biology ,Hemorrhagic Fever Virus, Crimean-Congo ,Molecular Medicine ,Metagenomics ,Crimean Congo hemorrhagic fever virus ,Research Article - Abstract
Crimean-Congo hemorrhagic fever (CCHF) caused by the CCHF virus (CCHFV) is a tick-borne natural focal disease with a mortality rate of approximately 50%. CCHFV is widely prevalent in Africa, southern Asia, the Middle East, and southeast Europe. CCHF outbreaks have been reported previously in Xinjiang province, China, especially in its southern region. Epidemiological surveys conducted on ticks and animals have revealed the presence of CCHFV strains in ticks, rodents, and infected individuals from cities and counties in southern Xinjiang. Phylogenetic analyses revealed that the Chinese CCHFV strains belong to one genotype, based on complete sequences of the S segments of its negative-stranded RNA genome. The present study reports two new CCHFV strains isolated from Hyalomma asiaticum asiaticum ticks collected from Fukang City and Wujiaqu City in the northern region of Xinjiang. Viral characteristics and their evolutionary relationships were analyzed through metagenomic and reverse-transcription PCR analyses; these analyses indicated that the genotype of both strains was different from that of other Chinese strains. Furthermore, previous reports of CCHFV in Xinjiang were reviewed and phylogenetic analyses were performed. CCHFV was found to prevail in Fukang City in Junggar Basin for more than 20 years, and that Fukang City and Wujiaqu City are considered natural reservoirs of different genotypes of CCHFV strains. Our findings facilitate the understanding of CCHFV distribution in Xinjiang province and provide insights into the evolutionary relationships among Chinese CCHFV strains. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12250-018-0020-7) contains supplementary material, which is available to authorized users.
- Published
- 2018
24. Two new kalligrammatids (Insecta, Neuroptera) from the Middle Jurassic of Daohugou, Inner Mongolia, China
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郑大燃) Zheng, Haichun Zhang, Yaohui Fang, Bo (王博) Wang, Qing Huo Liu, and Qingqing Zhang
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Paleontology ,biology ,Neuroptera ,Genus ,Inner mongolia ,biology.organism_classification ,Entire wing ,Ecology, Evolution, Behavior and Systematics - Abstract
A new genus and two new species of kalligrammatid lacewings (Insecta, Neuroptera), Kalligramma paradoxum sp. nov. and Huiyingogramma formosum gen. et sp. nov., are described and figured, based on two well-preserved forewings from the Middle Jurassic of Daohugou, Inner Mongolia, China. Kalligramma paradoxum sp. nov. can be distinguished from other known Kalligramma species based on forewing characters (e.g., wing shape, costal space, branches of Rs, eye-spot). Huiyingogramma gen. nov. is characterized by a distinct humeral recurrent vein, relatively broad costal space with well-forked costal veinlets, well-developed eye-spot and dense crossveins over the entire wing.
- Published
- 2013
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