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1.
Clin Transl Sci ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34755921

RESUMO

Steroid 5α-reductase type 2 deficiency (5α-RD2) and androgen insensitivity syndrome (AIS) are difficult to distinguish clinically and biochemically, and adrenal-derived androgens have not been investigated in these conditions using modern methods. The objective of the study was to compare Chinese patients with 5α-RD2, AIS, and healthy men. Sixteen patients with 5α-RD2, 10 patients with AIS, and 39 healthy men were included. Serum androgen profiles were compared in these subjects using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Based on clinical features and laboratory tests, 5α-RD2 and AIS were diagnosed and confirmed by genotyping. Dihydrotestosterone (DHT) and testosterone (T) were both significantly lower in patients with 5α-RD2 than AIS (p < 0.0001). The T/DHT ratio was higher in 5α-RD2 (4.5-88.6) than AIS (13.4-26.7) or healthy men (7.6-40.5). Using LC-MS/MS, a cutoff T/DHT value of 27.3 correctly diagnosed 5α-RD2 versus AIS with sensitivity 93.8% and specificity 100%. Among the adrenal-derived 11-oxygenated androgens, 11ß-hydroxyandrostenedione (11OHA4) and 11-ketoandrostenedione (11KA4) were also lower in patients with 5α-RD2 than those of patients with AIS. In contrast, 11ß-hydroxytestosterone (11OHT) was higher in 5α-RD2 than AIS. Furthermore, a 11OHT/11OHA4 cutoff value of 0.048 could also distinguish 5α-RD2 from AIS. Thus, both elevated T/DHT values above 27.3 and the unexpected 11-oxygenated androgen profile, with a 11OHT/11OHA4 ratio greater than 0.048, distinguished 5α-RD2 from AIS. These data suggest that the metabolism of both gonadal and adrenal-derived androgens is altered in 5α-RD2.

2.
J Anesth ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34738161

RESUMO

PURPOSE: To investigate the efficacy and safety of low-dose bolus plus continuous infusion of penehyclidine in preventing postoperative nausea and vomiting (PONV) following bimaxillary surgery. METHODS: Three hundred fifty-four patients were randomly allocated into three groups. In the Control group, placebo (normal saline) was injected before anesthesia and infused over 48 h after surgery; in the Bolus group, 0.5 mg penehyclidine was injected before anesthesia, whereas placebo was infused after surgery; in the Infusion group, 0.25 mg penehyclidine were injected before anesthesia, another 0.25 mg penehyclidine was infused after surgery. The primary endpoint was the incidence of PONV within 72 h. RESULTS: A total of 353 patients were included in intention-to-treat analysis. The PONV incidence was 61.0% (72/118) in the Control group, 40.2% (47/117) in the Bolus group, and 28.0% (33/118) in the Infusion group. The incidence was significantly lower in the Bolus group than in the Control group (RR 0.66; 95% CI 0.51-0.86; adjusted P = 0.003) and in the Infusion group than in the Control group (RR 0.46; 95% CI 0.33-0.63; adjusted P < 0.001); the difference between the Infusion and Bolus groups was not statistically significant (RR 0.70; 95% CI 0.48-1.00; adjusted P = 0.144). Emergence agitation occurred more frequently in the Bolus group than in the Control group (36.8% [43/117] vs. 21.2% [25/118], adjusted P = 0.027), but did not differ significantly between the Infusion and Control groups. CONCLUSIONS: A low-dose bolus plus continuous infusion of penehyclidine was effective in preventing PONV without increasing emergence agitation. TRIAL REGISTRATION: Clinicaltrials.gov. Identifier: NCT04454866.

3.
Hum Vaccin Immunother ; : 1-14, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34756160

RESUMO

Increased severity of diseases caused by Coxsackievirus A10 (CV-A10) as well as a large number of mutants and recombinants circulating in the population are a cause of concern for public health. A vaccine with broad-spectrum and homogenous protective capacity is needed to prevent outbreaks of CV-A10. Here, we evaluated cross-neutralization of prototype strain and 17 CV-A10 strains from related manufacturers in mainland China in vitro using 30 samples of plasma collected from naturally infected human adults and 18 sera samples from murine immunized with the above strains of CV-A10. Both human plasma and murine sera exhibited varying degrees of cross-neutralizing activities. Prototype A/Kowalik and sub-genotype C3/S113 were most difficult to neutralize. Among all strains tested, neutralization of S102 and S108 strains by 18 different sera was the most uniform, suggesting their suitability for detection of NtAb titers of different vaccines for avoiding biases introduced by detection strain. Furthermore, among all immune-sera, cross-neutralization of the 18 strains of CV-A10 by anti-S110 and anti-S102 was the most homogenous. Anti-S102 exhibiting higher geometric mean titer (GMT) in vitro was evaluated for its cross-protection capacity in vivo. Remarkably, administration of anti-S102 protected mice from lethal dosage of eight strains of CV-A10. These results provide a framework for formulating strategies for the R&D of vaccines targeting CV-A10 infections.

4.
Mol Psychiatry ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34686765

RESUMO

Drug exposure impairs cortical plasticity and motor learning, which underlies the reduced behavioral flexibility in drug addiction. Physical exercise has been used to prevent relapse in drug rehabilitation program. However, the potential benefits and molecular mechanisms of physical exercise on drug-evoked motor-cortical dysfunctions are unknown. Here we report that 1-week treadmill training restores cocaine-induced synaptic deficits, in the form of improved in vivo spine formation, synaptic transmission, and spontaneous activities of cortical pyramidal neurons, as well as motor-learning ability. The synaptic and behavioral benefits relied on de novo protein synthesis, which are directed by the activation of the mechanistic target of rapamycin (mTOR)-ribosomal protein S6 pathway. These findings establish synaptic functional restoration and mTOR signaling as the critical mechanism supporting physical exercise training in rehabilitating the addicted brain.

5.
Virol Sin ; 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34581960

RESUMO

Coxsackievirus B1 (CVB1) is a leading causative agent of severe infectious diseases in humans and has been reported to be associated with outbreaks of aseptic meningitis, myocarditis, and the development of chronic diseases such as type 1 diabetes mellitus (T1DM). There is no approved vaccine or effective antiviral therapy to treat CBV1 infection. And animal models to assess the effects of antiviral agents and vaccine remain limited. In this study, we established a neonatal mouse model of CVB1 using a clinically isolated strain to characterize the pathological manifestations of virus infection and to promote the development of vaccines and antiviral drugs against CVB1. One-day-old BALB/c mice were susceptible to CVB1 infection by intraperitoneal injection. Mice challenged with CVB1 at a low dose [10 median tissue culture infective dose (TCID50)] exhibited a series of clinical symptoms, such as inactivity, emaciation, limb weakness, hair thinning, hunching and even death. Pathological examination and tissue viral load analysis showed that positive signals of CVB1 were detected in the heart, spinal cord, limb muscle and kidney without pathological damage. Particularly, CVB1 had a strong tropism towards the pancreas, causing severe cellular necrosis with inflammatory infiltration, and was spread by viraemia. Notably, the monoclonal antibody (mAb) 6H5 and antisera elicited from CVB1-vaccinated mice effectively protected the mice from CVB1 infection in the mouse model. In summary, the established neonatal mouse model is an effective tool for evaluating the efficacy of CVB1 antiviral reagents and vaccines.

6.
Nat Prod Res ; : 1-9, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498966

RESUMO

A new highly oxygenated cycloheptane derivative crustane (1), along with fourteen known compounds (2-15) were isolated from Penicillium crustosum JT-8. The structure of compound 1 was determined by extensive spectroscopic data, DP4+ probability analyses and dimolybdenum CD method. Compound 1 exhibited moderate antibacterial activity against Staphylococcus aureus with MIC of 4.0 µg/mL.

7.
Nat Commun ; 12(1): 5652, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34580306

RESUMO

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses' receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.


Assuntos
Anticorpos Antivirais/imunologia , Anticorpos Amplamente Neutralizantes/imunologia , COVID-19/terapia , Imunização Passiva/métodos , SARS-CoV-2/imunologia , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Anticorpos Monoclonais/metabolismo , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/isolamento & purificação , Anticorpos Antivirais/metabolismo , Sítios de Ligação/genética , Sítios de Ligação/imunologia , Anticorpos Amplamente Neutralizantes/administração & dosagem , Anticorpos Amplamente Neutralizantes/isolamento & purificação , Anticorpos Amplamente Neutralizantes/metabolismo , Células CHO , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Chlorocebus aethiops , Cricetulus , Epitopos/imunologia , Células HEK293 , Humanos , Camundongos , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Testes de Neutralização , Pandemias/prevenção & controle , Multimerização Proteica , Receptores Virais/metabolismo , SARS-CoV-2/genética , Células Sf9 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Células Vero
8.
Emerg Microbes Infect ; 10(1): 1881-1889, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34490832

RESUMO

SARS-CoV-2 has been the causative pathogen of the pandemic of COVID-19, resulting in catastrophic health issues globally. It is important to develop human-like animal models for investigating the mechanisms that SARS-CoV-2 uses to infect humans and cause COVID-19. Several studies demonstrated that the non-human primate (NHP) is permissive for SARS-CoV-2 infection to cause typical clinical symptoms including fever, cough, breathing difficulty, and other diagnostic abnormalities such as immunopathogenesis and hyperplastic lesions in the lung. These NHP models have been used for investigating the potential infection route and host immune response to SARS-CoV-2, as well as testing vaccines and drugs. This review aims to summarize the benefits and caveats of NHP models currently available for SARS-CoV-2, and to discuss key topics including model optimization, extended application, and clinical translation.


Assuntos
COVID-19/virologia , Modelos Animais de Doenças , Primatas/virologia , SARS-CoV-2/fisiologia , Animais , Antivirais/administração & dosagem , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/patologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Humanos , Primatas/imunologia , SARS-CoV-2/genética
10.
Front Microbiol ; 12: 670488, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539594

RESUMO

Foodbone norovirus (NoV) is the leading cause of acute gastroenteritis worldwide. Candidate vaccines are being developed, however, no licensed vaccines are currently available for managing NoV infections. Screening for stimulated antibodies with broad-spectrum binding activities can be performed for the development of NoV polyvalent vaccines. In this study, we aimed to develop an indirect enzyme-linked immunosorbent assay (ELISA) for testing the broad spectrum of anti-NoV antibodies. Capsid P proteins from 28 representative NoV strains (GI.1-GI.9 and GII.1-GII.22 except GII.11, GII.18, and GII.19) were selected, prepared, and used as coating antigens on one microplate. Combined with incubation and the horseradish peroxidase chromogenic reaction, the entire process for testing the spectrum of unknown antibodies required 2 h for completion. The intra-assay and inter-assay coefficients of variation were less than 10%. The new method was successfully performed with monoclonal antibodies and polyclonal antibodies induced by multiple antigens. In conclusion, the indirect ELISA assay developed in this study had a good performance of reliability, convenience, and high-throughput screening for broad-spectrum antibodies.

11.
Plant Biotechnol J ; 19(11): 2362-2379, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34265872

RESUMO

Soybean is an important crop worldwide, but its production is severely affected by salt stress. Understanding the regulatory mechanism of salt response is crucial for improving the salt tolerance of soybean. Here, we reveal a role for nuclear factor Y subunit GmNFYA in salt tolerance of soybean likely through the regulation of histone acetylation. GmNFYA is induced by salt stress. Overexpression of GmNFYA significantly enhances salt tolerance in stable transgenic soybean plants by inducing salt-responsive genes. Analysis in soybean plants with transgenic hairy roots also supports the conclusion. GmNFYA interacts with GmFVE, which functions with putative histone deacetylase GmHDA13 in a complex for transcriptional repression possibly by reducing H3K9 acetylation at target loci. Under salt stress, GmNFYA likely accumulates and competes with GmHDA13 for interaction with GmFVE, leading to the derepression and maintenance of histone acetylation for activation of salt-responsive genes and finally conferring salt tolerance in soybean plants. In addition, a haplotype I GmNFYA promoter is identified with the highest self-activated promoter activity and may be selected during future breeding for salt-tolerant cultivars. Our study uncovers the epigenetic regulatory mechanism of GmNFYA in salt-stress response, and all the factors/elements identified may be potential targets for genetic manipulation of salt tolerance in soybean and other crops.

12.
Sci Transl Med ; 13(606)2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34285130

RESUMO

Multiple safe and effective vaccines that elicit immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are necessary to respond to the ongoing coronavirus disease 2019 (COVID-19) pandemic. Here, we developed a protein subunit vaccine composed of spike ectodomain protein (StriFK) plus a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH002C). StriFK-FH002C generated substantially higher neutralizing antibody titers in mice, hamsters, and cynomolgus monkeys than those observed in plasma isolated from COVID-19 convalescent individuals. StriFK-FH002C also induced both TH1- and TH2-polarized helper T cell responses in mice. In hamsters, StriFK-FH002C immunization protected animals against SARS-CoV-2 challenge, as shown by the absence of virus-induced weight loss, fewer symptoms of disease, and reduced lung pathology. Vaccination of hamsters with StriFK-FH002C also reduced within-cage virus transmission to unvaccinated, cohoused hamsters. In summary, StriFK-FH002C represents an effective, protein subunit-based SARS-CoV-2 vaccine candidate.


Assuntos
COVID-19 , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , Cricetinae , Humanos , Camundongos , Subunidades Proteicas , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
13.
Anesthesiology ; 135(2): 233-245, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34195784

RESUMO

BACKGROUND: Experimental and observational research suggests that combined epidural-general anesthesia may improve long-term survival after cancer surgery by reducing anesthetic and opioid consumption and by blunting surgery-related inflammation. This study therefore tested the primary hypothesis that combined epidural-general anesthesia improves long-term survival in elderly patients. METHODS: This article presents a long-term follow-up of patients enrolled in a previous trial conducted at five hospitals. Patients aged 60 to 90 yr and scheduled for major noncardiac thoracic and abdominal surgeries were randomly assigned to either combined epidural-general anesthesia with postoperative epidural analgesia or general anesthesia alone with postoperative intravenous analgesia. The primary outcome was overall postoperative survival. Secondary outcomes included cancer-specific, recurrence-free, and event-free survival. RESULTS: Among 1,802 patients who were enrolled and randomized in the underlying trial, 1,712 were included in the long-term analysis; 92% had surgery for cancer. The median follow-up duration was 66 months (interquartile range, 61 to 80). Among patients assigned to combined epidural-general anesthesia, 355 of 853 (42%) died compared with 326 of 859 (38%) deaths in patients assigned to general anesthesia alone: adjusted hazard ratio, 1.07; 95% CI, 0.92 to 1.24; P = 0.408. Cancer-specific survival was similar with combined epidural-general anesthesia (327 of 853 [38%]) and general anesthesia alone (292 of 859 [34%]): adjusted hazard ratio, 1.09; 95% CI, 0.93 to 1.28; P = 0.290. Recurrence-free survival was 401 of 853 [47%] for patients who had combined epidural-general anesthesia versus 389 of 859 [45%] with general anesthesia alone: adjusted hazard ratio, 0.97; 95% CI, 0.84 to 1.12; P = 0.692. Event-free survival was 466 of 853 [55%] in patients who had combined epidural-general anesthesia versus 450 of 859 [52%] for general anesthesia alone: adjusted hazard ratio, 0.99; 95% CI, 0.86 to 1.12; P = 0.815. CONCLUSIONS: In elderly patients having major thoracic and abdominal surgery, combined epidural-general anesthesia with epidural analgesia did not improve overall or cancer-specific long-term mortality. Nor did epidural analgesia improve recurrence-free survival. Either approach can therefore reasonably be selected based on patient and clinician preference.


Assuntos
Analgesia Epidural/mortalidade , Anestesia Geral/mortalidade , Avaliação Geriátrica/métodos , Procedimentos Cirúrgicos Operatórios/mortalidade , Idoso , Idoso de 80 Anos ou mais , Analgesia Epidural/métodos , Anestesia Geral/métodos , China/epidemiologia , Quimioterapia Combinada , Feminino , Seguimentos , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Sobrevida
14.
Theranostics ; 11(13): 6607-6615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995679

RESUMO

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo. Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.


Assuntos
COVID-19/imunologia , Modelos Animais de Doenças , Pulmão/patologia , Mucosa Respiratória/citologia , SARS-CoV-2/imunologia , Feto Abortado , Animais , COVID-19/patologia , COVID-19/virologia , Células Cultivadas , Células Epiteliais/virologia , Xenoenxertos , Humanos , Pulmão/imunologia , Pulmão/virologia , Transplante de Pulmão , Masculino , Camundongos , Camundongos SCID , Cultura Primária de Células , SARS-CoV-2/patogenicidade , Replicação Viral
15.
New Phytol ; 231(2): 661-678, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33864683

RESUMO

Soybean (Glycine max) is one of the most important oilseed crops. However, the regulatory mechanism that governs the process of oil accumulation in soybean remains poorly understood. In this study, GmZF392, a tandem CCCH zinc finger (TZF) protein which was identified in our previous RNA-seq analysis of seed-preferred transcription factors, was found to function as a positive regulator of lipid production. GmZF392 promotes seed oil accumulation in both transgenic Arabidopsis and stable transgenic soybean plants by binding to a bipartite cis-element, containing TG- and TA-rich sequences, in promoter regions, activating the expression of genes in the lipid biosynthesis pathway. GmZF392 physically interacts with GmZF351, our previously identified transcriptional regulator of lipid biosynthesis, to synergistically promote downstream gene expression. Both GmZF392 and GmZF351 are further upregulated by GmNFYA, another transcription factor involved in lipid biosynthesis, directly (in the former case) and indirectly (in the latter case). Promoter sequence diversity analysis showed that the GmZF392 promoter may have been selected at the origin of the Glycine genus and further mildly selected during domestication from wild soybeans to cultivated soybeans. Our study reveals a regulatory module containing three transcription factors in the lipid biosynthesis pathway, and manipulation of the module may improve oil production in soybean and other oilseed crops.


Assuntos
Regulação da Expressão Gênica de Plantas , Soja , Lipídeos , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Sementes/metabolismo , Soja/genética , Soja/metabolismo
16.
Cereb Cortex ; 31(9): 4398-4410, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-33895811

RESUMO

While social interaction between a mother and her child has been found to play an important role in the child's committed compliance, the underlying neurocognitive process remains unclear. To investigate this process, we simultaneously recorded and assessed brain activity in 7-year-old children and in children's mothers or strangers during a free-play task using functional near-infrared spectroscopy-based hyperscanning. The results showed that a child's committed compliance was positively associated with the child's responsiveness but was negatively associated with mutual responsiveness and was not associated with the mother's responsiveness during mother-child interactions. Moreover, interpersonal neural synchronization (INS) at the temporoparietal junction mediated the relationship between the child's responsiveness and the child's committed compliance during mother-child interactions when the child's brain activity lagged behind that of the mother. However, these effects were not found during stranger-child interactions, nor were there significant effects in the mother-child pair when no real interactions occurred. Finally, we found a transfer effect of a child's committed compliance from mother-child interactions to stranger-child interactions via the mediation of mother-child INS, but the opposite did not occur. Together, these findings suggest that a child's responsiveness during mother-child interactions can significantly facilitate her or his committed compliance by increasing mother-child INS.

17.
Signal Transduct Target Ther ; 6(1): 136, 2021 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-33790236

RESUMO

Epidemiological studies of the COVID-19 patients have suggested the male bias in outcomes of lung illness. To experimentally demonstrate the epidemiological results, we performed animal studies to infect male and female Syrian hamsters with SARS-CoV-2. Remarkably, high viral titer in nasal washings was detectable in male hamsters who presented symptoms of weight loss, weakness, piloerection, hunched back and abdominal respiration, as well as severe pneumonia, pulmonary edema, consolidation, and fibrosis. In contrast with the males, the female hamsters showed much lower shedding viral titers, moderate symptoms, and relatively mild lung pathogenesis. The obvious differences in the susceptibility to SARS-CoV-2 and severity of lung pathogenesis between male and female hamsters provided experimental evidence that SARS-CoV-2 infection and the severity of COVID-19 are associated with gender.


Assuntos
COVID-19 , SARS-CoV-2/metabolismo , Caracteres Sexuais , Animais , COVID-19/metabolismo , COVID-19/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Masculino , Mesocricetus
19.
Nat Commun ; 12(1): 1383, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33654063

RESUMO

In this study, we investigate the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang in China. From January to April 2020, 38,144 healthy blood donors in the three cities were tested for total antibody against SARS-CoV-2 followed by pseudotype SARS-CoV-2 neutralization tests, IgG, and IgM antibody testing. Finally, a total of 398 donors were confirmed positive. The age- and sex-standardized SARS-CoV-2 seroprevalence among 18-60 year-old adults (18-65 year-old in Shenzhen) was 2.66% (95% CI: 2.24%-3.07%) in Wuhan, 0.033% (95% CI: 0.0029%-0.267%) in Shenzhen, and 0.0028% (95% CI: 0.0001%-0.158%) in Shijiazhuang, respectively. Female sex and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among blood donors in Wuhan. As most of the population of China remained uninfected during the early wave of the COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.


Assuntos
SARS-CoV-2/patogenicidade , Anticorpos Antivirais/sangue , Doadores de Sangue/estatística & dados numéricos , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/imunologia , China/epidemiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Testes de Neutralização , Prevalência , Fatores de Risco , SARS-CoV-2/imunologia
20.
Cell Host Microbe ; 29(3): 448-462.e5, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33539764

RESUMO

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization.


Assuntos
Microscopia Crioeletrônica , Enterovirus/metabolismo , Enterovirus/ultraestrutura , Animais , Anticorpos Neutralizantes , Capsídeo/metabolismo , Proteínas do Capsídeo/ultraestrutura , Enterovirus Humano B/metabolismo , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/metabolismo , Infecções por Enterovirus/virologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Domínios e Motivos de Interação entre Proteínas , Receptores Virais , Vírion/metabolismo , Vírion/ultraestrutura , Desenvelopamento do Vírus
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