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1.
Proc Natl Acad Sci U S A ; 120(11): e2221713120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36897979

RESUMO

The recently emerged Omicron subvariants XBB and BQ.1.1 have presented striking immune evasion against most monoclonal neutralizing antibodies and convalescent plasma. Therefore, it is essential to develop broad-spectrum COVID-19 vaccines to combat current and future emerging variants. Here, we found that the human IgG Fc-conjugated RBD of the original SARS-CoV-2 strain (WA1) plus a novel STING agonist-based adjuvant CF501 (CF501/RBD-Fc) could induce highly potent and durable broad-neutralizing antibody (bnAb) responses against Omicron subvariants, including BQ.1.1 and XBB in rhesus macaques with NT50s ranging from 2,118 to 61,742 after three doses. A decline of 0.9- to 4.7-fold was observed in the neutralization activity of sera in the CF501/RBD-Fc group against BA.2.2, BA.2.9, BA.5, BA.2.75, and BF.7 relative to D614G after three doses, while a significant decline of NT50 against BQ.1.1 (26.9-fold) and XBB (22.5-fold) relative to D614G. However, the bnAbs were still effective in neutralizing BQ.1.1 and XBB infection. These results suggest that the conservative but nondominant epitopes in RBD could be stimulated by CF501 to generate bnAbs, providing a proof-of-concept for using "nonchangeable against changeables" strategy to develop pan-sarbecovirus vaccines against sarbecoviruses, including SARS-CoV-2 and its variants.


Assuntos
COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Vacinas , Animais , Humanos , SARS-CoV-2 , Anticorpos Neutralizantes , Vacinas contra COVID-19 , Anticorpos Amplamente Neutralizantes , Macaca mulatta , Soroterapia para COVID-19 , Anticorpos Monoclonais , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus
2.
Nano Lett ; 24(25): 7757-7763, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38874303

RESUMO

Terahertz scattering scanning near-field optical microscopy is a robust spectral detection technique with a nanoscale resolution. However, there are still major challenges in investigating the heterogeneity of cell membrane components in individual cells. Here, we present a novel and comprehensive analytical approach for detecting and investigating heterogeneity in cell membrane components at the single-cell level. In comparison to the resolution of the topographical atomic force microscopy image, the spatial resolution of the terahertz near-field amplitude image is 3 times that of the former. This ultrafine resolution enables the compositional distribution in the cell membrane, such as the distribution of extracellular vesicles, to be finely characterized. Furthermore, via extraction of the near-field absorption images at specific frequencies, the visualization and compositional difference analysis of cell membrane components can be presented in detail. These findings have significant implications for the intuitive and visual analysis of cell development and disease evolutionary pathways.


Assuntos
Membrana Celular , Análise de Célula Única , Análise de Célula Única/métodos , Membrana Celular/química , Humanos , Imagem Terahertz/métodos , Microscopia de Força Atômica/métodos , Vesículas Extracelulares/química
3.
J Mol Recognit ; 37(4): e3091, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38773782

RESUMO

The development of effective therapeutics against COVID-19 requires a thorough understanding of the receptor recognition mechanism of the SARS-CoV-2 spike (S) protein. Here the multidomain collective dynamics on the trimer of the spike protein has been analyzed using normal mode analysis (NMA). A common nanomechanical profile was identified in the spike proteins of SARS-CoV-2 and its variants. The profile involves collective vibrations of the receptor-binding domain (RBD) and the N-terminal domain (NTD), which may mediate the physical interaction process. Quantitative analysis of the collective modes suggests a nanomechanical property involving large-scale conformational changes, which explains the difference in receptor binding affinity among different variants. These results support the use of intrinsic global dynamics as a valuable perspective for studying the allosteric and functional mechanisms of the S protein. This approach also provides a low-cost theoretical toolkit for screening potential pathogenic mutations and drug targets.


Assuntos
Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vibração , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , SARS-CoV-2/metabolismo , Humanos , COVID-19/virologia , COVID-19/metabolismo , Simulação de Dinâmica Molecular , Domínios Proteicos , Conformação Proteica
4.
BMC Plant Biol ; 23(1): 119, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36855097

RESUMO

BACKGROUND: Owing to successful cloning of wheat functional genes in recent years, more traits can be selected by diagnostic markers, and consequently, effective molecular markers will be powerful tools in wheat breeding programs. RESULTS: The present study proposed a cost-effective duplex Kompetitive Allele Specific PCR (dKASP) marker system that combined multiplex PCR and KASP™ technology to yield twice the efficiency at half the cost compared with the common KASP™ markers and provide great assistance in breeding selection. Three dKASP markers for the major genes controlling plant height (Rht-B1/Rht-D1), grain hardness (Pina-D1/Pinb-D1), and high-molecular-weight glutenin subunits (Glu-A1/Glu-D1) were successfully developed and applied in approved wheat varieties growing in the middle and lower reaches of the Yangtze River and advanced lines from our breeding program. Three markers were used to test six loci with high efficiency. In the approved wheat varieties, Rht-B1b was the most important dwarfing allele, and the number of accessions carrying Pinb-D1b was much greater than that of the accessions carrying Pina-D1b. Moreover, the number of accessions carrying favorable alleles for weak-gluten wheat (Null/Dx2) was much greater than that of the accessions carrying favorable alleles for strong-gluten wheat (Ax1 or Ax2*/Dx5). In the advanced lines, Rht-B1b and Pinb-D1b showed a significant increase compared with the approved varieties, and the strong-gluten (Ax1 or Ax2*/Dx5) and weak-gluten (Null/Dx2) types also increased. CONCLUSION: A cost-effective dKASP marker system that combined multiplex PCR and KASP™ technology was proposed to achieve double the efficiency at half the cost compared with the common KASP™ markers. Three dKASP markers for the major genes controlling PH (Rht-B1/Rht-D1), GH (Pina-D1/Pinb-D1), and HMW-GS (Glu-A1/Glu-D1) were successfully developed, which would greatly improve the efficiency of marker-assisted selection of wheat.


Assuntos
Melhoramento Vegetal , Triticum , Alelos , Triticum/genética , Análise Custo-Benefício , Reação em Cadeia da Polimerase , Glutens/genética
5.
J Med Virol ; 95(1): e28172, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36161303

RESUMO

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with high transmission rates and striking immune evasion have posed a serious challenge to the application of current first-generation SARS-CoV-2 vaccines. Other sarbecoviruses, such as SARS-CoV and SARS-related coronaviruses (SARSr-CoVs), have the potential to cause outbreaks in the future. These facts call for the development of variant-proof SARS-CoV-2, pan-sarbecovirus or pan-ß-CoV vaccines. Several novel vaccine platforms have been used to develop vaccines with broad-spectrum neutralizing antibody responses and protective immunity to combat the current SARS-CoV-2 and its variants, other sarbecoviruses, as well as other ß-CoVs, in the future. In this review, we discussed the major target antigens and protective efficacy of current SARS-CoV-2 vaccines and summarized recent advances in broad-spectrum vaccines against sarbecoviruses and ß-CoVs.


Assuntos
COVID-19 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Humanos , SARS-CoV-2/genética , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Glicoproteína da Espícula de Coronavírus
6.
Proteins ; 90(3): 881-888, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34792219

RESUMO

Most mutations in the DNA-binding domain (DBD) of p53 inactivate or rescue the protein function interacting with the minor groove of DNA. However, how the conformation changes propagating from the mutation sites result in distinct molecular recognition is still not well understood. As the protein mobility is an intrinsic property encrypted in its primary structure, we examined if different structures of wild-type and mutant p53 core domains display any unique patterns of intrinsic mobility. Normal mode calculation was employed to characterize the collective dynamics of DBD in p53 monomer and tetramer as well as their mutants. Intriguingly, the low-frequency collective motions of DBD show similar patterns between the wild-type protein and the rescued mutants. The analysis on atomic backbone fluctuations and low-frequency vibration mode statistics does further support the correlation between the intrinsic collective motion of DBD and the p53 protein function. The mutations in the DBD influence the low-frequency vibration of the p53 tetramer via the change of the collective motions among its four monomers. These findings thus provide new insights for understanding the physical mechanism of p53 protein structure-function relationship and help find the small molecule drug to modulate protein dynamic for disease therapy.


Assuntos
Proteínas Mutantes/química , Proteína Supressora de Tumor p53/química , Sequência de Aminoácidos , Sítios de Ligação , DNA/química , Humanos , Modelos Moleculares , Proteínas Mutantes/genética , Mutação , Ligação Proteica , Domínios Proteicos , Relação Estrutura-Atividade , Proteína Supressora de Tumor p53/genética
7.
BMC Plant Biol ; 22(1): 129, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313801

RESUMO

BACKGROUND: Wheat processing quality is an important factor in evaluating overall wheat quality, and dough characteristics are important when assessing the processing quality of wheat. As a notable germplasm resource, semi-wild wheat has a key role in the study of wheat processing quality. RESULTS: In this study, four dough rheological characteristics were collected in four environments using a nested association mapping (NAM) population consisting of semi-wild and domesticated wheat varieties to identify quantitative trait loci (QTL) for wheat processing quality. A total of 49 QTL for wheat processing quality were detected, explaining 0.36-10.82% of the phenotypic variation. These QTL were located on all wheat chromosomes except for 2D, 3A, 3D, 6B, 6D and 7D. Compared to previous studies, 29 QTL were newly identified. Four novel QTL, QMlPH-1B.4, QMlPH-3B.4, QWdEm-1B.2 and QWdEm-3B.2, were stably identified in three or more environments, among which QMlPH-3B.4 was a major QTL. Moreover, eight important genetic regions for wheat processing quality were identified on chromosomes 1B, 3B and 4D, which showed pleiotropy for dough characteristics. In addition, out of 49 QTL, 15 favorable alleles came from three semi-wild parents, suggesting that the QTL alleles provided by the semi-wild parent were not utilized in domesticated varieties. CONCLUSIONS: The results show that semi-wild wheat varieties can enrich the existing wheat gene pool and provide broader variation resources for wheat genetic research.


Assuntos
Pão , Mapeamento Cromossômico , Produtos Agrícolas/genética , Qualidade dos Alimentos , Locos de Características Quantitativas , Reologia , Triticum/genética , China , Cromossomos de Plantas , Genes de Plantas , Variação Genética , Estudo de Associação Genômica Ampla , Genótipo , Fenótipo
8.
Proc Biol Sci ; 289(1986): 20221623, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36321492

RESUMO

Exoskeletal dwelling tubes are widespread among extant animals and early fossil assemblages. Exceptional fossils from the Cambrian reveal independent origins of tube dwelling by several clades including cnidarians, lophophorates, annelids, scalidophorans, panarthropods and ambulacrarians. However, most fossil tubes lack preservation of soft parts, making it difficult to understand their affinities and evolutionary significance. Gangtoucunia aspera (Wulongqing Formation, Cambrian Stage 4) was an annulated, gradually expanding phosphatic tube, with occasional attachments of multiple, smaller juveniles and has previously been interpreted as the dwelling tube of a 'worm' (e.g. a scalidophoran), lophophorate or problematicum. Here, we report the first soft tissues from Gangtoucunia that reveal a smooth body with circumoral tentacles and a blind, spacious gut that is partitioned by septa. This is consistent with cnidarian polyps and phylogenetic analysis resolves Gangtoucunia as a total group medusozoan. The tube of Gangtoucunia is phenotypically similar to problematic annulated tubular fossils (e.g. Sphenothallus, Byronia, hyolithelminths), which have been compared to both cnidarians and annelids, and are among the oldest assemblages of skeletal fossils. The cnidarian characters of G. aspera suggest that these early tubular taxa are best interpreted as cnidarians rather than sessile bilaterians in the absence of contrary soft tissue evidence.


Assuntos
Cnidários , Animais , Filogenia , Fosfatos , Fósseis , Evolução Biológica , Preservação de Tecido
9.
Soft Matter ; 18(11): 2203-2210, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35226022

RESUMO

Phospholipase A2 (PLA2) is a peripheral membrane protein that plays an essential role in many inflammatory responses. However, the activation mechanisms of PLA2 on the membrane surface have not been fully understood. Herein, we have combined experimental techniques and theoretical approaches to investigate the activation and association of the PLA2 protein on an artificial phospholipid membrane. Using a phosphatidylserine (PS) nanodomain containing membrane to mimic the inflammatory conditions, we found that the activity of cytosolic PLA2s (cPLA2s) increases with higher ratios of PS in the membrane. Molecular dynamics simulations reveal that significant changes in the protein structure are related to negatively charged membranes. In particular, the alteration of negatively charged residues in the C2 domain brings about an opened binding pocket and the catalytic site access to the substrate phospholipid. Meanwhile, the negative residues in the loop 650-665 facilitate the optimal interfacial orientation of the protein with a closed binding pocket on the membrane surface. These results lead us to suggest an electrostatic-switch allosteric mechanism for cPLA2 activation on the cell membrane surface under the inflammatory state.


Assuntos
Fosfatidilserinas , Fosfolipídeos , Membranas , Fosfolipases A2/química , Fosfolipases A2/metabolismo , Fosfolipídeos/metabolismo , Eletricidade Estática
10.
J Gen Virol ; 102(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151142

RESUMO

The emerging pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused social and economic disruption worldwide, infecting over 9.0 million people and killing over 469 000 by 24 June 2020. Unfortunately, no vaccine or antiviral drug that completely eliminates the transmissible disease coronavirus disease 2019 (COVID-19) has been developed to date. Given that coronavirus nonstructural protein 1 (nsp1) is a good target for attenuated vaccines, it is of great significance to explore the detailed characteristics of SARS-CoV-2 nsp1. Here, we first confirmed that SARS-CoV-2 nsp1 had a conserved function similar to that of SARS-CoV nsp1 in inhibiting host-protein synthesis and showed greater inhibition efficiency, as revealed by ribopuromycylation and Renilla luciferase (Rluc) reporter assays. Specifically, bioinformatics and biochemical experiments showed that by interacting with 40S ribosomal subunit, the lysine located at amino acid 164 (K164) was the key residue that enabled SARS-CoV-2 nsp1 to suppress host gene expression. Furthermore, as an inhibitor of host-protein expression, SARS-CoV-2 nsp1 contributed to cell-cycle arrest in G0/G1 phase, which might provide a favourable environment for virus production. Taken together, this research uncovered the detailed mechanism by which SARS-CoV-2 nsp1 K164 inhibited host gene expression, laying the foundation for the development of attenuated vaccines based on nsp1 modification.


Assuntos
Interações Hospedeiro-Patógeno/genética , Lisina/genética , Proteínas Ribossômicas/genética , Subunidades Ribossômicas Menores de Eucariotos/genética , SARS-CoV-2/genética , Proteínas não Estruturais Virais/genética , Sequência de Aminoácidos , Substituição de Aminoácidos , Biologia Computacional/métodos , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Regulação da Expressão Gênica , Genes Reporter , Células HEK293 , Humanos , Luciferases/genética , Luciferases/metabolismo , Lisina/metabolismo , Mutação , Proteínas Ribossômicas/antagonistas & inibidores , Proteínas Ribossômicas/metabolismo , Subunidades Ribossômicas Menores de Eucariotos/metabolismo , Subunidades Ribossômicas Menores de Eucariotos/virologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/metabolismo , SARS-CoV-2/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Proteínas não Estruturais Virais/metabolismo
11.
Theor Appl Genet ; 133(3): 917-933, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31897512

RESUMO

KEY MESSAGE: Eight environmentally stable QTL for grain yield-related traits were detected by four RIL populations, and two of them were validated by a natural wheat population containing 580 diverse varieties or lines. Yield and yield-related traits are important factors in wheat breeding. In this study, four RIL populations derived from the cross of one common parent Yanzhan 1 (a Chinese domesticated cultivar) and four donor parents including Hussar (a British domesticated cultivar) and three semi-wild wheat varieties in China were phenotyped for 11 yield-related traits in eight environments. An integrated genetic map containing 2009 single-nucleotide polymorphism (SNP) markers generated from a 90 K SNP array was constructed to conduct quantitative trait loci (QTL) analysis. A total of 161 QTL were identified, including ten QTL for grain yield per plant (GYP) and yield components, 49 QTL for spike-related traits, 43 QTL for flag leaf-related traits, 22 QTL for plant height (PH), and 37 QTL for heading date and flowering date. Eight environmentally stable QTL were validated in individual RIL population where the target QTL was notably detected, and six of them had a significant effect on GYP. Furthermore, Two QTL, QSPS-2A.4 and QSL-4A.1, were also validated in a natural wheat population containing 580 diverse varieties or lines, which provided valuable resources for further fine mapping and genetic improvement in yield in wheat.


Assuntos
Grão Comestível/genética , Locos de Características Quantitativas , Triticum/genética , Alelos , China , Mapeamento Cromossômico , Cromossomos de Plantas , Grão Comestível/crescimento & desenvolvimento , Flores/genética , Flores/crescimento & desenvolvimento , Flores/fisiologia , Ligação Genética , Genoma de Planta , Genótipo , Fenótipo , Melhoramento Vegetal , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Polimorfismo de Nucleotídeo Único , Triticum/crescimento & desenvolvimento
12.
J Immunol ; 196(4): 1790-8, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26783339

RESUMO

Extracellular UDP (eUDP), released as a danger signal by stressed or apoptotic cells, plays an important role in a series of physiological processes. Although the mechanism of eUDP release in apoptotic cells has been well defined, how the eUDP is released in innate immune responses remains unknown. In this study, we demonstrated that UDP was released in both Escherichia coli-infected mice and LPS- or Pam3CSK4-treated macrophages. Also, LPS-induced UDP release could be significantly blocked by selective TLR4 inhibitor Atractylenolide I and selective gap junction inhibitors carbenoxolone and flufenamic acid (FFA), suggesting the key role of TLR signaling and gap junction channels in this process. Meanwhile, eUDP protected mice from peritonitis by reducing invaded bacteria that could be rescued by MRS2578 (selective P2Y6 receptor inhibitor) and FFA. Then, connexin 43, as one of the gap junction proteins, was found to be clearly increased by LPS in a dose- and time-dependent manner. Furthermore, if we blocked LPS-induced ERK signaling by U0126, the expression of connexin 43 and UDP release was also inhibited dramatically. In addition, UDP-induced MCP-1 secretion was significantly reduced by MRS2578, FFA, and P2Y6 mutation. Accordingly, pretreating mice with U0126 and Gap26 increased invaded bacteria and aggravated mice death. Taken together, our study reveals an internal relationship between danger signals and TLR signaling in innate immune responses, which suggests a potential therapeutic significance of gap junction channel-mediated UDP release in infectious diseases.


Assuntos
Conexina 43/imunologia , Infecções por Escherichia coli/imunologia , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/imunologia , Difosfato de Uridina/imunologia , Difosfato de Uridina/metabolismo , Animais , Western Blotting , Conexina 43/metabolismo , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Feminino , Junções Comunicantes/imunologia , Imunidade Inata , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Receptor 4 Toll-Like/metabolismo , Receptores Toll-Like/imunologia , Receptores Toll-Like/metabolismo
13.
Neuroradiology ; 58(4): 391-400, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26801480

RESUMO

INTRODUCTION: Treatment of complex anterior circulation aneurysms with flow diverters (FDs) has become common practice in neurovascular centers. However, this treatment method for posterior circulation aneurysms (PCAs) still remains controversial. METHODS: Through searches for reports on the treatment of PCAs with FDs, we conducted a systematic review of the literature on its clinical efficacy and safety using random-effect binomial meta-analysis. RESULTS: We included 14 studies, which reported on a total of 225 PCAs in 220 patients. Procedure-related good outcome rate was 79% (95% confidence interval (CI), 72-84), with significantly lower odds among patients with ruptured aneurysms and basilar artery aneurysms. Procedure-related mortality rate was 15% (95% CI 10-21), with significantly higher rates among patients with giant aneurysms and basilar artery aneurysms. The rate of complete aneurysm occlusion at 6-month digital subtraction angiography (DSA) was 84%. Ischemic stroke rate was 11%. Perforator infarction rate was 7%. Postoperative subarachnoid hemorrhage (SAH) rate was 3%. Intraparenchymal hemorrhage (IPH) rate was 4%. CONCLUSIONS: Flow diverter treatment of PCAs is an effective method, which provides a high rate of complete occlusion at 6-month DSA. However, compared with anterior circulation aneurysms, patients with PCAs are at significantly higher risk of mortality, ischemic stroke and perforator infarction. Our findings indicate that, in most clinical centers, flow diverter treatment of PCAs should be conducted in carefully selected patients with poor natural history and no optimal treatment strategy. For ruptured and giant basilar artery aneurysms, there is still no good treatment option.


Assuntos
Prótese Vascular , Procedimentos Endovasculares , Aneurisma Intracraniano/terapia , Stents , Humanos
14.
Artif Intell Med ; 149: 102812, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38462270

RESUMO

Mental and physical disorders (MPD) are inextricably linked in many medical cases; psychosomatic diseases can be induced by mental concerns and psychological discomfort can ensue from physiological diseases. However, existing medical informatics studies focus on identifying mental or physical disorders from a unilateral perspective. Consequently, no existing domain knowledge base, corpus, or detection modeling approach considers mental as well as physical aspects concurrently. This paper proposes a joint modeling approach to detect MPD. First, we crawl through online medical consultation records of patients from websites and build an MPD knowledge ontology by extracting the core conceptual features of the text. Based on the ontology, an MPD knowledge graph containing 12,673 nodes and 82,195 relations is obtained using term matching with a domain thesaurus of each concept. Subsequently, an MPD corpus with fine-grained severities (None, Mild, Moderate, Severe, Dangerous) and 8909 records is constructed by formulating MPD classification criteria and a data annotation process under the guidance of domain experts. Taking the knowledge graph and corpus as the dataset, we design a multi-task learning model to detect the MPD severity, in which a knowledge graph attention network (KGAT) is embedded to better extract knowledge features. Experiments are performed to demonstrate the effectiveness of our model. Furthermore, we employ ontology-based and centrality-based methods to discover additional potential inferred knowledge, which can be captured by KGAT so as to improve the prediction performance and interpretability of our model. Our dataset has been made publicly available, so it can be further used as a medical informatics reference in the fields of psychosomatic medicine, psychiatrics, physical co-morbidity, and so on.


Assuntos
Transtornos Mentais , Psiquiatria , Humanos , Reconhecimento Automatizado de Padrão , Aprendizagem , Transtornos Mentais/diagnóstico , Bases de Conhecimento
15.
Curr Res Microb Sci ; 6: 100208, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38149085

RESUMO

The unceasing global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls for the development of novel therapeutics. Although many newly developed antivirals and repurposed antivirals have been applied to the treatment of coronavirus disease 2019 (COVID-19), antivirals showing satisfactory clinical efficacy are few in number. In addition, the loss of sensitivity to variants of concern (VOCs) and lack of oral bioavailability have also limited the clinical application of some antivirals. These facts remind us to develop more potent and broad-spectrum antivirals with better pharmacokinetic/pharmacodynamic properties to fight against infections from SARS-CoV-2, its variants, and other human coronaviruses (HCoVs). In this review, we summarize the latest advancements in the clinical development of antivirals against infections by SARS-CoV-2 and its variants.

16.
Cell Rep Med ; 5(3): 101445, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38428429

RESUMO

The emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariants BA.2.86 and JN.1 raise concerns regarding their potential to evade immune surveillance and spread globally. Here, we test sera from rhesus macaques immunized with 3 doses of wild-type SARS-CoV-2 receptor-binding domain (RBD)-Fc adjuvanted with the STING agonist CF501. We find that the sera can potently neutralize pseudotyped XBB.1.5, XBB.1.16, CH.1.1, EG.5, BA.2.86, and JN.1, with 50% neutralization titers ranging from 3,494 to 7,424. We also demonstrate that CF501, but not Alum, can enhance immunogenicity of the RBD from wild-type SARS-CoV-2 to improve induction of broadly neutralizing antibodies (bnAbs) with binding specificity and activity similar to those of SA55, BN03, and S309, thus exhibiting extraordinary broad-spectrum neutralizing activity. Overall, the RBD from wild-type SARS-CoV-2 also contains conservative epitopes. The RBD-Fc adjuvanted by CF501 can elicit potent bnAbs against JN.1, BA.2.86, and other XBB subvariants. This strategy can be adopted to develop broad-spectrum vaccines to combat future emerging and reemerging viral infectious diseases.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , SARS-CoV-2/genética , Anticorpos Amplamente Neutralizantes , Macaca mulatta , Epitopos/genética
17.
Innovation (Camb) ; 4(4): 100465, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37448741

RESUMO

Further applications of electric vehicles (EVs) and energy storage stations are limited because of the thermal sensitivity, volatility, and poor durability of lithium-ion batteries (LIBs), especially given the urgent requirements for all-climate utilization and fast charging. This study comprehensively reviews the thermal characteristics and management of LIBs in an all-temperature area based on the performance, mechanism, and thermal management strategy levels. At the performance level, the external features of the batteries were analyzed and compared in cold and hot environments. At the mechanism level, the heat generation principles and thermal features of LIBs under different temperature conditions were summarized from the perspectives of thermal and electrothermal mechanisms. At the strategy level, to maintain the temperature/thermal consistency and prevent poor subzero temperature performance and local/global overheating, conventional and novel battery thermal management systems (BTMSs) are discussed from the perspective of temperature control, thermal consistency, and power cost. Moreover, future countermeasures to enhance the performance of all-climate areas at the material, cell, and system levels are discussed. This study provides insights and methodologies to guarantee the performance and safety of LIBs used in EVs and energy storage stations.

18.
Int J Biol Macromol ; 227: 285-296, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36549029

RESUMO

Flowering time is a critical agronomic trait that has strong effects on crop yields. Auxin signaling pathway plays an important role in various development processes, such as flowering, grain development. However, no Aux/IAA gene had been reported to have functions involving in wheat flowering time. Here, we systematically performed genome-wide identification, classification, domain distribution, exon-intron structure, chromosome locations and global expression pattern of Aux/IAA gene family in 14 plant genomes (including Triticum aestivum). A phylogenetic model was proposed to infer the Aux/IAA evolutionary history involving in a central exon-intron structure "2121" during evolution. Overexpression of TaIAA15-1A caused an early flowering time in Brachypodium. RNA-seq analysis showed that TaIAA15-1A overexpression alters various pathways including phytohormone signaling pathway, flowering-related pathway, and polyamine biosynthesis pathway. Screening of auxin response factor (ARF) genes identified BdARF16 that interacted with TaIAA15-1A. Exogenous polyamine (spermidine and spermine) treatments promoted early flowering and (putrescine and DCHA) delayed flowering time of WT plants. Our finding will provide insights on mechanisms of Aux/IAAs gene family and TaIAA15-1A, illustrating the potential during crop improvement programs.


Assuntos
Ácidos Indolacéticos , Triticum , Ácidos Indolacéticos/metabolismo , Triticum/genética , Triticum/metabolismo , Proteínas de Plantas/química , Filogenia , Reguladores de Crescimento de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
19.
ACS Omega ; 7(49): 44733-44742, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36530310

RESUMO

High-temperature aging has a serious impact on the safety and performance of lithium-ion batteries. This work comprehensively investigates the evolution of heat generation characteristics upon discharging and electrochemical performance and the degradation mechanism during high-temperature aging. Post-mortem characterization analysis revealed that lithium plating is the main degradation mechanism. The occurrence of side reactions leads to cell capacity fading and electrochemical performance degradation. The DC resistance and AC impedance increase significantly, and the severe internal polarization makes the incremental capacity curve shift to lower voltage. In the early aging stage, the cell degrades slightly, and the temperature rise rate has not changed significantly upon discharging. The cell capacity plays a leading role, whose degradation makes the temperature rise decrease. With the aging deepening, the severe cell degradation makes the temperature rise rate increase significantly. Even if the capacity fading, the temperature rise still increases significantly compared to the fresh state. Furthermore, irreversible heat and reversible heat increase significantly with the aging deepening and current rate increasing.

20.
Front Neurol ; 13: 796339, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35557625

RESUMO

Background: Caveolin-1 (Cav-1) plays pivotal roles in the endothelial function and angiogenesis postischemia. Moyamoya disease (MMD) is characterized by progressive artery stenosis with unknown etiology. We aim to determine whether serum Cav-1 levels of patients with MMD were associated with collateral vessel formation after bypass surgery. Methods: We studied serum Cav-1 levels of 130 patients with MMD (16 with RNF213 p.R4810K mutation and 114 without RNF213 p.R4810K mutation), 15 patients with acute stroke, and 33 healthy controls. Cerebral perfusion and collateral circulation were evaluated preoperation and at 6 months after operation using pseudocontinuous arterial spin labeling MRI (pCASL-MRI) and digital subtraction angiography (DSA), respectively. Endothelial expression of Cav-1 was verified in the superficial temporal artery (STA) wall of patients with MMD by immunofluorescence double staining. We also investigated whether overexpression of Cav-1 affects cell migration and tube formation using human microvascular endothelial cells (HMECs). Results: The serum Cav-1 level of patients with MMD intermediated between the stroke group and healthy controls and it was enhanced after the bypass surgery (681.87 ± 311.63 vs. 832.91 ± 464.41 pg/ml, p = 0.049). By 6 months after bypass surgery, patients with MMD with better collateral compensation manifested higher postoperative/preoperative Cav-1 ratio (rCav-1) than bad compensation patients. Consistently, cerebral blood flow (CBF) determined by pCASL-MRI (nCBFMCA ratio) was positively in line with rCav-1 ratio (r = 0.8615, p < 0.0001). Cav-1 was expressed in the endothelial cells of the STA vessels of patients with MMD. Overexpression of Cav-1 by plasmid transfection in HMECs promoted tube formation and cell migration. Conclusion: This study indicated that Cav-1 may be a potential driver to promote angiogenesis and collateral formation after bypass surgery in patients with MMD, providing a better understanding of MMD pathophysiology and potential non-surgical targets of MMD.

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