共查询到20条相似文献，搜索用时 15 毫秒
1.
Fulvia Milena Cribi Roberta Erra Lorenza Pugni Carlota Rubio-Perez Lidia Alonso Sara Simonetti Giorgio Alberto Croci Garazi Serna Andrea Ronchi Carlo Pietrasanta Giovanna Lunghi Anna Maria Fagnani Maria Piana Matthias Matter Alexandar Tzankov Luigi Terracciano Andres Anton Enrico Ferrazzi Stefano Ferrero Enrico Iurlaro Joan Seoane Paolo Nuciforo 《The Journal of clinical investigation》2021,131(6)
2.
Wenjing Wang Yoichi Miyamoto Biaobang Chen Juanzi Shi Feiyang Diao Wei Zheng Qun Li Lan Yu Lin Li Yao Xu Ling Wu Xiaoyan Mao Jing Fu Bin Li Zheng Yan Rong Shi Xia Xue Jian Mu Zhihua Zhang Tianyu Wu Lin Zhao Weijie Wang Zhou Zhou Jie Dong Qiaoli Li Li Jin Lin He Xiaoxi Sun Ge Lin Yanping Kuang Lei Wang Qing Sang 《The Journal of clinical investigation》2023,133(2)
Preimplantation embryo arrest (PREMBA) is a common cause of female infertility and recurrent failure of assisted reproductive technology. However, the genetic basis of PREMBA is largely unrevealed. Here, using whole-exome sequencing data from 606 women experiencing PREMBA compared with 2,813 controls, we performed a population and gene–based burden test and identified a candidate gene, karyopherin subunit α7 (KPNA7). In vitro studies showed that identified sequence variants reduced KPNA7 protein levels, impaired KPNA7 capacity for binding to its substrate ribosomal L1 domain-containing protein 1 (RSL1D1), and affected KPNA7 nuclear transport activity. Comparison between humans and mice suggested that mouse KPNA2, rather than mouse KPNA7, acts as an essential karyopherin in embryonic development. Kpna2–/– female mice showed embryo arrest due to zygotic genome activation defects, recapitulating the phenotype of human PREMBA. In addition, female mice with an oocyte-specific knockout of Rsl1d1 recapitulated the phenotype of Kpna2–/– mice, demonstrating the vital role of substrate RSL1D1. Finally, complementary RNA (cRNA) microinjection of human KPNA7, but not mouse Kpna7, was able to rescue the embryo arrest phenotype in Kpna2–/– mice, suggesting mouse KPNA2 might be a homologue of human KPNA7. Our findings uncovered a mechanistic understanding for the pathogenesis of PREMBA, which acts by impairing nuclear protein transport, and provide a diagnostic marker for PREMBA patients. 相似文献
3.
Cyril Djari Isabelle Sahut-Barnola Amandine Septier Ingrid Plotton Nathanaëlle Montanier Damien Dufour Adrien Levasseur James Wilmouth Jr. Jean-Christophe Pointud Fabio R. Faucz Crystal Kamilaris Antoine-Guy Lopez Florian Guillou Amanda Swain Seppo J. Vainio Igor Tauveron Pierre Val Herv Lefebvre Constantine A. Stratakis Antoine Martinez Anne-Marie Lefranois-Martinez 《The Journal of clinical investigation》2021,131(23)
4.
Vincent Dupont Anders H. Berg Michifumi Yamashita Chengqun Huang Ambart E. Covarrubias Shafat Ali Aleksandr Stotland Jennifer E. Van Eyk Belinda Jim Ravi Thadhani S. Ananth Karumanchi 《The Journal of clinical investigation》2022,132(20)
To understand how kidney donation leads to an increased risk of preeclampsia, we studied pregnant outbred mice with prior uninephrectomy and compared them with sham-operated littermates carrying both kidneys. During pregnancy, uninephrectomized (UNx) mice failed to achieve a physiological increase in the glomerular filtration rate and during late gestation developed hypertension, albuminuria, glomerular endothelial damage, and excess placental production of soluble fms–like tyrosine kinase 1 (sFLT1), an antiangiogenic protein implicated in the pathogenesis of preeclampsia. Maternal hypertension in UNx mice was associated with low plasma volumes, an increased rate of fetal resorption, impaired spiral artery remodeling, and placental ischemia. To evaluate potential mechanisms, we studied plasma metabolite changes using mass spectrometry and noted that l-kynurenine, a metabolite of l-tryptophan, was upregulated approximately 3-fold during pregnancy when compared with prepregnant concentrations in the same animals, consistent with prior reports suggesting a protective role for l-kynurenine in placental health. However, UNx mice failed to show upregulation of l-kynurenine during pregnancy; furthermore, when UNx mice were fed l-kynurenine in drinking water throughout pregnancy, their preeclampsia-like state was rescued, including a reversal of placental ischemia and normalization of sFLT1 levels. In aggregate, we provide a mechanistic basis for how impaired renal reserve and the resulting failure to upregulate l-kynurenine during pregnancy can lead to impaired placentation, placental hypoperfusion, an antiangiogenic state, and subsequent preeclampsia. 相似文献
5.
Ali Abbara Pei Chia Eng Maria Phylactou Sophie A. Clarke Rachel Richardson Charlene M. Sykes Chayarndorn Phumsatitpong Edouard Mills Manish Modi Chioma Izzi-Engbeaya Debbie Papadopoulou Kate Purugganan Channa N. Jayasena Lisa Webber Rehan Salim Bryn Owen Paul Bech Alexander N. Comninos Craig A. McArdle Margaritis Voliotis Krasimira Tsaneva-Atanasova Suzanne Moenter Aylin Hanyaloglu Waljit S. Dhillo 《The Journal of clinical investigation》2020,130(12):6739
6.
Yidong Chen Yuan Gao Jialin Jia Liang Chang Ping Liu Jie Qiao Fuchou Tang Lu Wen Jin Huang 《The Journal of clinical investigation》2021,131(12)
The discovery of embryonic cell–free DNA (cfDNA) in spent embryo culture media (SECM) has brought hope for noninvasive preimplantation genetic testing. However, the cellular origins of SECM cfDNA are not sufficiently understood, and methods for determining maternal DNA contamination are limited. Here, we performed whole-genome DNA methylation sequencing for SECM cfDNA. Our results demonstrated that SECM cfDNA was derived from blastocysts, cumulus cells, and polar bodies. We identified the cumulus-specific differentially methylated regions (DMRs) and oocyte/polar body–specific DMRs, and established an algorithm for deducing the cumulus, polar body, and net maternal DNA contamination ratios in SECM. We showed that DNA methylation sequencing accurately detected chromosome aneuploidy in SECM and distinguished SECM samples with low and high false negative rates and gender discordance rates, after integrating the origin analysis. Our work provides insights into the characterization of embryonic DNA in SECM and provides a perspective for noninvasive preimplantation genetic testing in reproductive medicine. 相似文献
7.
Ravi Shankar Nita Radhakrishnan Seema Dua Satyam Arora Megha Rana Dinesh Kumar Sahu Sumit Rai Devendra Kumar Gupta 《Transfusion and apheresis science》2021,60(1):102956
The natural history of COVID-19 infection in children is still evolving as the pandemic unfolds. Few cases of severe and often fatal COVID-19 have been reported although the infection is mild in the large majority. Children with cancers are recognised as a high risk group for all infections. Since there aren’t any definite treatment guidelines established in children with severe COVID, treatment is guided by adult recommendations which too are often not evidence based. We report the case of a 4-year-old girl with severe COVID-19 associated pneumonia who presented to us as febrile neutropenia. The use of convalescent plasma along with steroids and IVIG showed dramatic results in this child and she recovered without the need for any specific treatment. This is highlighted as one of the earliest cases that is reporting the use of convalescent plasma in a child; the first ever in a child with underlying malignancy. 相似文献
9.
Wan-Chen Hsieh En-Yu Lai Yu-Ting Liu Yi-Fu Wang Yi-Shiuan Tzeng Lu Cui Yun-Ju Lai Hsiang-Chi Huang Jia-Hsin Huang Hung-Chih Ni Dong-Yan Tsai Jian-Jong Liang Chun-Che Liao Ya-Ting Lu Laurence Jiang Ming-Tsan Liu Jann-Tay Wang Sui-Yuan Chang Chung-Yu Chen Hsing-Chen Tsai Yao-Ming Chang Gerlinde Wernig Chia-Wei Li Kuo-I Lin Yi-Ling Lin Huai-Kuang Tsai Yen-Tsung Huang Shih-Yu Chen 《The Journal of clinical investigation》2021,131(21)
To explore how the immune system controls clearance of SARS-CoV-2, we used a single-cell, mass cytometry–based proteomics platform to profile the immune systems of 21 patients who had recovered from SARS-CoV-2 infection without need for admission to an intensive care unit or for mechanical ventilation. We focused on receptors involved in interactions between immune cells and virus-infected cells. We found that the diversity of receptor repertoires on natural killer (NK) cells was negatively correlated with the viral clearance rate. In addition, NK subsets expressing the receptor DNAM1 were increased in patients who more rapidly recovered from infection. Ex vivo functional studies revealed that NK subpopulations with high DNAM1 expression had cytolytic activities in response to target cell stimulation. We also found that SARS-CoV-2 infection induced the expression of CD155 and nectin-4, ligands of DNAM1 and its paired coinhibitory receptor TIGIT, which counterbalanced the cytolytic activities of NK cells. Collectively, our results link the cytolytic immune responses of NK cells to the clearance of SARS-CoV-2 and show that the DNAM1 pathway modulates host-pathogen interactions during SARS-CoV-2 infection. 相似文献
10.
Yanfang P. Zhu Isaac Shamie Jamie C. Lee Cameron J. Nowell Weiqi Peng Shiela Angulo Linh N.N. Le Yushan Liu Huilai Miao Hainan Xiong Cathleen J. Pena Elizabeth Moreno Eric Griffis Stephanie G. Labou Alessandra Franco Lori Broderick Hal M. Hoffman Chisato Shimizu Nathan E. Lewis John T. Kanegaye Adriana H. Tremoulet Jane C. Burns Ben A. Croker the Pediatric Emergency Medicine Kawasaki Disease Research Group Consortium 《The Journal of clinical investigation》2021,131(20)
BACKGROUNDMultisystem inflammatory syndrome in children (MIS-C) is a rare but potentially severe illness that follows exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Kawasaki disease (KD) shares several clinical features with MIS-C, which prompted the use of intravenous immunoglobulin (IVIG), a mainstay therapy for KD. Both diseases share a robust activation of the innate immune system, including the IL-1 signaling pathway, and IL-1 blockade has been used for the treatment of both MIS-C and KD. The mechanism of action of IVIG in these 2 diseases and the cellular source of IL-1β have not been defined.METHODSThe effects of IVIG on peripheral blood leukocyte populations from patients with MIS-C and KD were examined using flow cytometry and mass cytometry (CyTOF) and live-cell imaging.RESULTSCirculating neutrophils were highly activated in patients with KD and MIS-C and were a major source of IL-1β. Following IVIG treatment, activated IL-1β+ neutrophils were reduced in the circulation. In vitro, IVIG was a potent activator of neutrophil cell death via PI3K and NADPH oxidase, but independently of caspase activation.CONCLUSIONSActivated neutrophils expressing IL-1β can be targeted by IVIG, supporting its use in both KD and MIS-C to ameliorate inflammation.FUNDINGPatient Centered Outcomes Research Institute; NIH; American Asthma Foundation; American Heart Association; Novo Nordisk Foundation; NIGMS; American Academy of Allergy, Asthma and Immunology Foundation. 相似文献
11.
Ralf Duerr Dacia Dimartino Christian Marier Paul Zappile Guiqing Wang Jennifer Lighter Brian Elbel Andrea B. Troxel Adriana Heguy 《The Journal of clinical investigation》2021,131(18)
The efficacy of COVID-19 mRNA vaccines is high, but breakthrough infections still occur. We compared the SARS-CoV-2 genomes of 76 breakthrough cases after full vaccination with BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna), or JNJ-78436735 (Janssen) to unvaccinated controls (February–April 2021) in metropolitan New York, including their phylogenetic relationship, distribution of variants, and full spike mutation profiles. The median age of patients in the study was 48 years; 7 required hospitalization and 1 died. Most breakthrough infections (57/76) occurred with B.1.1.7 (Alpha) or B.1.526 (Iota). Among the 7 hospitalized cases, 4 were infected with B.1.1.7, including 1 death. Both unmatched and matched statistical analyses considering age, sex, vaccine type, and study month as covariates supported the null hypothesis of equal variant distributions between vaccinated and unvaccinated in χ2 and McNemar tests (P > 0.1), highlighting a high vaccine efficacy against B.1.1.7 and B.1.526. There was no clear association among breakthroughs between type of vaccine received and variant. In the vaccinated group, spike mutations in the N-terminal domain and receptor-binding domain that have been associated with immune evasion were overrepresented. The evolving dynamic of SARS-CoV-2 variants requires broad genomic analyses of breakthrough infections to provide real-life information on immune escape mediated by circulating variants and their spike mutations. 相似文献
12.
Bezawit A. Woldemeskel Arbor G. Dykema Caroline C. Garliss Saphira Cherfils Kellie N. Smith Joel N. Blankson 《The Journal of clinical investigation》2022,132(5)
Recent studies have shown that vaccinated individuals harbor T cells that can cross-recognize SARS-CoV-2 and endemic human common cold coronaviruses. However, it is still unknown whether CD4+ T cells from vaccinated individuals recognize peptides from bat coronaviruses that may have the potential of causing future pandemics. In this study, we identified a SARS-CoV-2 spike protein epitope (S815-827) that is conserved in coronaviruses from different genera and subgenera, including SARS-CoV, MERS-CoV, multiple bat coronaviruses, and a feline coronavirus. Our results showed that S815-827 was recognized by 42% of vaccinated participants in our study who received the Pfizer-BioNTech (BNT162b2) or Moderna (mRNA-1273) COVID-19 vaccines. Using T cell expansion and T cell receptor sequencing assays, we demonstrated that S815-827-reactive CD4+ T cells from the majority of responders cross-recognized homologous peptides from at least 6 other diverse coronaviruses. Our results support the hypothesis that the current mRNA vaccines elicit T cell responses that can cross-recognize bat coronaviruses and thus might induce some protection against potential zoonotic outbreaks. Furthermore, our data provide important insights that inform the development of T cell–based pan-coronavirus vaccine strategies. 相似文献
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Magdalena E. Sobieszczyk Jill Maaske Ann R. Falsey Stephanie Sproule Merlin L. Robb Robert W. Frenck Jr. Hong-Van Tieu Kenneth H. Mayer Lawrence Corey Kathleen M. Neuzil Tina Tong Margaret Brewinski Isaacs Holly Janes Himanshu Bansal Lindsay M. Edwards Justin A. Green Elizabeth J. Kelly Kathryn Shoemaker Therese Takas Tom White Prakash Bhuyan Tonya Villafana and Ian Hirsch 《The Journal of clinical investigation》2022,132(18)
15.
Paula Sa Rebecca V. Fink Sonia Bakkour Jing Jin Graham Simmons Marcus O. Muench Hina Dawar Clara Di Germanio Alvin J. Hui David J. Wright David E. Krysztof Steven H. Kleinman Angela Cheung Theresa Nester Debra A. Kessler Rebecca L. Townsend Bryan R. Spencer Hany Kamel Jacquelyn M. Vannoy Honey Dave Michael P. Busch Susan L. Stramer Mars Stone Rachael P. Jackman Philip J. Norris for the NHLBI Recipient Epidemiology Donor Evaluation Study-IV-Pediatric 《The Journal of clinical investigation》2022,132(17)
Respiratory viruses such as influenza do not typically cause viremia; however, SARS-CoV-2 has been detected in the blood of COVID-19 patients with mild and severe symptoms. Detection of SARS-CoV-2 in blood raises questions about its role in pathogenesis as well as transfusion safety concerns. Blood donor reports of symptoms or a diagnosis of COVID-19 after donation (post-donation information, PDI) preceded or coincided with increased general population COVID-19 mortality. Plasma samples from 2,250 blood donors who reported possible COVID-19–related PDI were tested for the presence of SARS-CoV-2 RNA. Detection of RNAemia peaked at 9%–15% of PDI donors in late 2020 to early 2021 and fell to approximately 4% after implementation of widespread vaccination in the population. RNAemic donors were 1.2- to 1.4-fold more likely to report cough or shortness of breath and 1.8-fold more likely to report change in taste or smell compared with infected donors without detectable RNAemia. No infectious virus was detected in plasma from RNAemic donors; inoculation of permissive cell lines produced less than 0.7–7 plaque-forming units (PFU)/mL and in susceptible mice less than 100 PFU/mL in RNA-positive plasma based on limits of detection in these models. These findings suggest that blood transfusions are highly unlikely to transmit SARS-CoV-2 infection. 相似文献
16.
《The Journal of clinical investigation》2021,131(13)
BACKGROUNDAlthough convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.METHODSWe conducted a randomized, double-blind, controlled trial among adults hospitalized with severe and critical COVID-19 at 5 sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized 2:1 to receive a single transfusion of either convalescent plasma or normal control plasma. The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.RESULTSOf 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to receive normal control plasma. At 28 days, no significant improvement in the clinical scale was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval [CI] 0.83–2.68, P = 0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 [12.6%] versus 18/73 [24.6%], OR 0.44, 95% CI 0.22–0.91, P = 0.034). The median titer of anti–SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80–1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.CONCLUSIONIn adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in day 28 clinical status. However, convalescent plasma was associated with significantly improved survival. A possible explanation is that survivors remained hospitalized at their baseline clinical status.TRIAL REGISTRATIONClinicalTrials.gov, NCT04359810.FUNDINGAmazon Foundation, Skoll Foundation. 相似文献
17.
Astrid Herzum Martina Burlando Mattia F. Molle Claudia Micalizzi Emanuele Cozzani Aurora Parodi 《Clinical Case Reports》2021,9(12):e05092
We report the third case of cutaneous lichen planus (LP) following COVID-19 BNT162b2 vaccination in a 59-year-old woman with previous LP. The reactivation of LP in patients with dormant LP suggests a possible vaccine-induced immune dysregulation. We suggest that the already described vaccine-induced upregulation of Th1 response may play a relevant role in LP reactivation, through an increase in inflammatory cytokines involved in the pathogenesis of LP. Interestingly, LP has already been associated with vaccinations and viral infections including COVID-19 disease. However, the exact mechanism underlying LP (re)activation after Pfizer-BiotNtech COVID-19 vaccination is still widely unknown and needs to be further investigated. 相似文献
18.
《The Journal of clinical investigation》2023,133(3)
BACKGROUNDThe presence and reactivation of chronic viral infections, such as EBV, CMV, and HIV, have been proposed as potential contributors to long COVID (LC), but studies in well-characterized postacute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited.METHODSIn a cohort of 280 adults with prior SARS-CoV-2 infection, we assessed the presence and types of LC symptoms and prior medical history (including COVID-19 history and HIV status) and performed serological testing for EBV and CMV using a commercial laboratory. We used covariate-adjusted binary logistic regression models to identify independent associations between variables and LC symptoms.RESULTSWe observed that LC symptoms, such as fatigue and neurocognitive dysfunction, at a median of 4 months following initial diagnosis were independently associated with serological evidence suggesting recent EBV reactivation (early antigen–diffuse IgG positivity) or high nuclear antigen (EBNA) IgG levels but not with ongoing EBV viremia. Serological evidence suggesting recent EBV reactivation (early antigen–diffuse IgG positivity) was most strongly associated with fatigue (OR = 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR = 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR = 0.52).CONCLUSIONOverall, these findings suggest differential effects of chronic viral coinfections on the likelihood of developing LC and association with distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted.TRIAL REGISTRATIONLong-term Impact of Infection with Novel Coronavirus; ClinicalTrials.gov NCT04362150.FUNDINGThis work was supported by NIH/National Institute of Allergy and Infectious Diseases grants (3R01AI141003-03S1, R01AI158013, and K24AI145806); the Zuckerberg San Francisco General Hospital Department of Medicine and Division of HIV, Infectious Diseases, and Global Medicine; and the UCSF-Bay Area Center for AIDS Research (P30-AI027763). 相似文献
19.
《The Journal of clinical investigation》2021,131(20)
BACKGROUNDPassive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19. Evidence from controlled clinical trials is inconclusive.METHODSWe conducted a randomized, open-label, controlled clinical trial at 27 hospitals in Spain. Patients had to be admitted for COVID-19 pneumonia within 7 days from symptom onset and not on mechanical ventilation or high-flow oxygen devices. Patients were randomized 1:1 to treatment with CP in addition to standard of care (SOC) or to the control arm receiving only SOC. The primary endpoint was the proportion of patients in categories 5 (noninvasive ventilation or high-flow oxygen), 6 (invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), or 7 (death) at 14 days. Primary analysis was performed in the intention-to-treat population.RESULTSBetween April 4, 2020, and February 5, 2021, 350 patients were randomly assigned to either CP (n = 179) or SOC (n = 171). At 14 days, proportion of patients in categories 5, 6, or 7 was 11.7% in the CP group versus 16.4% in the control group (P = 0.205). The difference was greater at 28 days, with 8.4% of patients in categories 5–7 in the CP group versus 17.0% in the control group (P = 0.021). The difference in overall survival did not reach statistical significance (HR 0.46, 95% CI 0.19–1.14, log-rank P = 0.087).CONCLUSIONCP showed a significant benefit in preventing progression to noninvasive ventilation or high-flow oxygen, invasive mechanical ventilation or ECMO, or death at 28 days. The effect on the predefined primary endpoint at 14 days and the effect on overall survival were not statistically significant.TRIAL REGISTRATIONClinicaltrials.gov, NCT04345523.FUNDINGGovernment of Spain, Instituto de Salud Carlos III. 相似文献
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Jia Zou Li Li Peiyi Zheng Wenhua Liang Siyi Hu Shuaixiang Zhou Yanqun Wang Jincun Zhao Daopeng Yuan Lu Liu Dongdong Wu Mengqiu Xu Fangfang Zhang Mengzhu Zhu Zhihai Wu Xiaochao Cao Meng Ni Xiaomin Ling Yue Wu Zhihui Kuang Moyan Hu Jianfeng Li Xue Li Xiling Guo Tianmin Xu Haiping Jiang Changshou Gao Michael Yu Junjian Liu Nanshan Zhong Jianfeng Zhou Jian-an Huang Tengchuan Jin Jianxing He 《The Journal of clinical investigation》2022,132(4)
Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22’s only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2. 相似文献