Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 364
Filtrar
1.
Biochem Pharmacol ; : 114538, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831397

RESUMO

Acute myeloid leukemia (AML) with FLT3 internal tandem duplication (FLT3-ITD) has a dismal prognosis. FLT3 inhibitors have been developed to treat patients with FLT3-ITD AML; however, when used alone, their efficacy is insufficient. FLT3 inhibitors combined with chemotherapy may be a promising treatment for FLT3-ITD AML. Homoharringtonine (HHT) is a classical anti-leukaemia drug with high sensitivity to FLT3-ITD AML cells. Here, we showed that HHT synergizes with a selective next-generation FLT3 inhibitor, quizartinib, to inhibit cell growth/viability and induce cell-cycle arrest and apoptosis in FLT3-ITD AML cells in vitro, significantly inhibit acute myeloid leukemia progression in vivo, and substantially prolong survival of mice-bearing human FLT3-ITD AML. Mechanistically, HHT and quizartinib cooperatively inhibit FLT3-AKT and its downstream targets GSK3ß, c-Myc, and cyclin D1, cooperatively up-regulate the pro-apoptosis proteins Bim and Bax, and down-regulate the anti-apoptosis protein Mcl1. Most strikingly, HHT and quizartinib cooperatively reduce the numbers of side-population (SP) and aldehyde dehydrogenase (ALDH)-positive cells, which reportedly are rich in LSCs. In conclusion, HHT combined with quizartinib may be a promising treatment strategy for patients with FLT3-ITD AML.

2.
Anal Chim Acta ; 1152: 338281, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648652

RESUMO

MicroRNAs (miRNAs) are a class of regulatory small RNA molecules that play critical roles in a wide variety of biological processes. Abnormally expressed miRNAs have been increasingly utilized as biomarkers for cancer diagnosis. Generally, a specific cancer is associated with expression alterations of several species of miRNAs and different types of cancers are related to different miRNA species. Therefore, a universal method for multiplexed detection of miRNA targets of interest is now desirable for cancer diagnosis. In this paper, by adding an enzymatic digestion step to reduce the nonspecific adaptor dimers, we firstly improved the method to construct cDNA library of all miRNAs, which greatly increased the cDNA yield. By specifically designing DNA probes to hybridize with the cDNAs at key positions and doubly encoding DNA probes with different lengths and different fluorophores during single-base extension, each miRNA could produce a unique product, which could be separated and detected by capillary electrophoresis. Thus, miRNA targets of interest could be simultaneously detected with great specificity at single-base resolution. By using seventeen randomly selected miRNAs as the model, as low as 1.0 fM of each miRNA target could be simultaneously determined. Furthermore, we had achieved accurate analysis of multiple miRNAs in real biological RNA samples and found that several miRNAs expressed differently between cancer cells and normal cells, indicating that the proposed method had the ability to pick out aberrant expression miRNAs in real biological samples. Compared with high-throughput sequencing methods, the proposed method is simpler and specific, and very suitable for the detection of specific miRNAs associated with a disease, which shows great potential for cancer diagnosis.

3.
J Biomol Struct Dyn ; : 1-12, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645467

RESUMO

Hydroxylated polychlorinated biphenyls (HO-PCBs), as the major metabolites of PCBs, have been reported to act as estrogen receptor ß (ERß) agonists. However, the chemical-biological interactions governing their activities toward ERß have not been elucidated. Therefore, three dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations, to the best of our knowledge, for the first time were performed to explore the correlation between the structures and activities. The best 3D-QSAR model presented higher predictive ability (R2cv=0.543, R2pred=0.5793/R2cv=0.543, R2pred=0.6795) based on comparative molecular field analysis (CoMFA) and comparative similarity indices analysis (CoMSIA), respectively. At the same time, the derived contour maps indicated the important structural features required for improving the activity. Furthermore, molecular docking studies and MD simulations predicted the binding mode and the interactions between the ligand and the receptor. All the results would lead to a better understanding of the specific mechanism of HO-PCBs on estrogen receptor ß (ERß).Communicated by Ramaswamy H. Sarma.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33534364

RESUMO

OBJECTIVES: A group of short bowel syndrome (SBS) patients developed chronic intestinal inflammation while struggling weaning off parenteral nutrition (PN). They did not respond to standard management of SBS and food allergy. We treated them with glucocorticoids and described the outcome. METHODS: Our study is a retrospective descriptive study. We reviewed records from the intestinal rehabilitation program from 2006 to 2017. We identified 15 patients whose lab values, pathology results, and clinic notes were reviewed. RESULTS: We had more patients (n = 10) with diagnosis of gastroschisis, and more female patients (n = 9). Seven patients weaned off PN with median treatment duration of 5 months, five of which remained on budesonide for significant period of time (median: 7.5 months). One of these 7 patients relapsed, as the patient resumed glucocorticoids due to recurrence of chronic intestinal inflammation. Six of 15 children had significant eosinophils in their initial biopsy, 5 of these children weaned off PN while one's GI bleeding stopped. Four patients were not able to decrease PN calorie. Two of these patients'GI bleeding stopped, the other two had normalized histology. CONCLUSIONS: For SBS children with histologically confirmed chronic intestinal inflammation, glucocorticoids may help promote enteral feeding tolerance. Glucocorticoids regimen should be chosen individually. Patients are more likely to respond if initial histology has significant eosinophilic infiltration. Patients may need to remain on glucocorticoids for over six months.

6.
Materials (Basel) ; 14(4)2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33578898

RESUMO

Ferro-coke, as a new burden of blast furnace (BF), can not only greatly reduce the energy consumption and CO2 emission, but also promote the resource utilization by using the low-quality iron ore and low-grade coal. However, the strength of ferro-coke decreased with the increasing amount of iron ore powder. In order to maintain the strength of ferro-coke while increasing the amount of iron ore powder, it is necessary to add binder during the coking process to enhance the strength of ferro-coke. In this paper, phenolic resin, silicon metal powder, corn starch, and coal tar pitch were used as binder for the fabrication of ferro-coke. I-type drum machine (I 600), scanning electron microscope (SEM), and X-ray diffraction (XRD) were applied to test the crushing strength, morphology, and microcrystalline structure of the ferro-coke. The results showed that the increasing amount of iron ore powder resulted in lower crushing strength, higher porosity, and the worse macroscopic morphology of ferro-coke. When the amount of iron ore powder reached 40%, obvious cracks appeared on the surface of ferro-coke. When the amount of iron ore was 30%, the crushing strength of ferro-coke dropped to 18.15%. Among the four binders, coal tar pitch could significantly enhance the cold crushing strength of ferro-coke through decreasing the porosity of ferro-coke and improving the bonding effect between carbon matrix particles. In the case of the 10% coal tar pitch addition, the cold crushing strength of ferro-coke was increased from 18.15% to 76.41%; meanwhile, its hot compression strength during gasification improved by 100N.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33586808

RESUMO

BACKGROUND AND AIM: Concerns regarding adverse events associated with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) for gastrointestinal bleeding (GIB) prophylaxis in the intensive care unit have increased in recent years. Few studies have focused on acid suppressant use in the cardiac care unit (CCU) setting exclusively. We performed a cohort study to determine the efficacy and safety of acid suppressants for GIB prophylaxis in CCU patients. METHODS: This retrospective cohort study included adults who were admitted directly to the CCU for more than 2 days from January 1, 2014, to April 30, 2019. The Crusade score was calculated to evaluate the risk of GIB. The primary outcomes were clinically important gastrointestinal bleeding (CIGIB), hospital-acquired pneumonia (HAP), and in-hospital mortality. RESULTS: Of the 3318 patients enrolled, 2284 (68.8%) patients received PPIs, 515 (15.5%) received H2RAs, and 519 (15.7%) received no acid suppressants. After adjusting for potential confounders, utilization of PPIs (2.69, 95% confidence interval [0.62-11.73]) and H2RAs (1.41, 95% confidence interval [0.19-10.36]) were not associated with a lower risk of CIGIB than the control. Sensitivity analyses revealed that PPI use was an independent risk factor for in-hospital mortality in patients over 75 years old, with an adjusted odds ratio of 4.08 (1.14-14.63). PPIs increased the risk of HAP in patients over 75 years old and in those with heart failure, with adjusted odds ratios of 2.38 (1.06-5.34) and 2.88 (1.34-7.28), respectively. CONCLUSIONS: Proton pump inhibitors and H2RAs for GIB prophylaxis in CCU patients were not associated with a lower risk of CIGIB than the controls. PPI therapy is associated with increased risks of HAP and in-hospital mortality in patients over 75 years old. PPIs may increase the risk of HAP in patients with heart failure.

8.
Am J Med Sci ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33600783

RESUMO

ß-thalassemia is a lethal inherited disease resulting from ß-globin gene mutations. Severe ß-thalassemia requires regular blood transfusions. Other active interventions, including iron chelating, stem cell transplantation and gene therapy, have remarkably improved the quality of life and prolonged the survival of patients with transfusion-dependent ß-thalassemia, but all with significant limitations and complications. MicroRNAs (miRNAs), encoded by a class of endogenous genes, are found to play important roles in regulating globin expression. Among the miRNAs of particular interest related to ß-thalassemia, miR-15a/16-1, miR-486-3p, miR-26b, miR-199b-5p, miR-210, miR-34a, miR-138, miR-326, let-7, and miR-17/92 cluster elevate γ-globin expression, while miR-96, miR-146a, miR-223-3p, and miR-144 inhibit γ-globin expression. A couple of miRNAs, miR-144 and miR-150, repress α-globin expression, whereas miR-451 induces α-, ß- and γ-globin expression. Single nucleotide polymorphism in miRNA genes or their targeted genes might also contribute to the abnormal expression of hemoglobin. Moreover, changes in the expression of miR-125b, miR-210, miR-451, and miR-609 reflect the severity of anemia and hemolysis in ß-thalassemia patients. These results suggest that miRNAs are potential biomarkers for the diagnosis and prognosis of ß-thalassemia, and miRNA-based therapeutic strategy might be used as a coordinated approach for effectively treating ß-thalassemia.

9.
Poult Sci ; 100(2): 603-614, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33518113

RESUMO

Pigeon paramyxovirus type 1 (PPMV-1) is a globally distributed, virulent member of the avian paramyxovirus type-1. The PPMV-1-associated disease poses a great threat to the pigeon industry. The innate immune response is crucial for antiviral infections and revealing the pathogenic mechanisms of PPMV-1. In this study, we evaluated the pathogenicity of a PPMV-1 strain LHLJ/110822 in one-month-old domestic pigeons, as well as the host immune responses in PPMV-1-infected pigeons. We observed typically clinical sign in infected pigeons by 3 dpi. The morbidity rate and the mortality in pigeons inoculated with the PPMV-1 strain were up to 100% and 30%, respectively. The virus could replicate in all of the examined tissues, namely trachea, lung, liver, spleen, and bursa of Fabricius. In addition, the infected pigeons had developed anti-PPMV-1 antibodies as early as 8 dpi; and the antibody level increased over the time in this study. The expression level of toll-like receptor (TLR) 2, TLR3 TLR15, IFN-γ, and IL-6 were significantly upregulated by the PPMV-1 infection in some tissues of pigeons. By contrast, PPMV-1 infection results in downregulation of IL-18 expression in most of investigated tissues except for bursa of Fabricius in this study. The current results confirmed that this virus could replicate in pigeons and induce host immune responses, then leading to produce serum antibody titers. Meanwhile, the PPMV-1 infection induces strong innate immune responses and intense inflammatory responses at early stage in pigeon which may associate with the viral pathogenesis.

10.
Plant Cell Rep ; 40(3): 491-506, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33388892

RESUMO

KEY MESSAGE: StMAPK11 overexpression promotes potato growth, physiological activities and photosynthesis under drought conditions. Mitogen-activated protein kinases (MAPKs) are import regulators of MAPK pathway in plants under drought condition. However, the critical role in potato (Solanum tuberosum L.) drought resistance is not fully understood. In this study, we aimed to explore the role of StMAPK11 under drought stress. The result of RT-qPCR for assay of StMAPKs expression demonstrated that 15 StMAPKs were differentially expressed in leaves, flowers, petioles, stamens, pistils, stems, stolons, roots, tubers and tuber peels of potato. StMAPKs was dynamically modulated by abiotic stresses and plant hormone treatments, and StMAPK11 was apparently up-regulated under drought conditions. Therefore, the vectors pCPB-StMAPK11 and pCPBI121-miRmapk11 for over-expression and down-regulation of StMAPK11 were constructed, respectively, and introduced into potato cultivar Atlantic. The result showed that StMAPK11 promoted potato growth under drought conditions, as well as the physiological activities evidenced by changes in SOD, CAT and POD activity and H2O2, proline and MDA content. StMAPK11 up-regulation intensified drought resistance of potato plant by elevating antioxidant activities and photosynthesis. Moreover, we consolidated the protective role of StMAPK11 in tobacco and Arabidopsis against drought stress. The result could provide new insights into the function of StMAPK11 in drought response and its possible mechanisms.

11.
BMC Complement Med Ther ; 21(1): 16, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413274

RESUMO

BACKGROUND: Traditional Chinese medicine (TCM) has gained increasing acceptance and popularity by the global community. The current study aimed to investigate self-reported evaluations of learning TCM and opinions about TCM courses among undergraduate international students majoring in conventional medicine at a university in China. METHODS: A cross-sectional survey was conducted at the Zhejiang University School of Medicine. A self-reported questionnaire was administered to international undergraduates who were enrolled in the TCM course during the 2018 and 2019 academic years (n = 157). The course employed a student-centered, multiform learning model. Demographic data and self-reported evaluations of TCM learning background and TCM learning course were obtained to conduct the analysis. RESULTS: A total of 133 students responded to the questionnaire. Among the respondents, 21.0% had some TCM-related knowledge, and 51.1% were interested in learning TCM before the course. Ninety-six students (85.7%) were from Asia. Students from Thailand showed significantly more interest in learning TCM than did students from other Asian countries (p = 0.025). After the course, 77.2% of students agreed that the course had brought about many benefits, 86.4% were satisfied with the course content, and 77.3% were satisfied with the teaching method. Students expressed their willingness to further learn acupuncture and to obtain more skilled practice through more visualized learning methods. CONCLUSIONS: The majority of the international students we surveyed agreed that the TCM course improved their interest in and understanding of TCM. It is thus suggested that TCM education should be directed toward students' learning barriers and needs.

13.
Cell Rep ; 34(1): 108551, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33406431

RESUMO

Recent studies reveal great diversity in the structure, function, and efferent innervation of afferent synaptic connections between the cochlear inner hair cells (IHCs) and spiral ganglion neurons (SGNs), which likely enables audition to process a wide range of sound pressures. By performing an extensive electron microscopic (EM) reconstruction of the neural circuitry in the mature mouse organ of Corti, we demonstrate that afferent SGN dendrites differ in abundance and composition of efferent innervation in a manner dependent on their afferent synaptic connectivity with IHCs. SGNs that sample glutamate release from several presynaptic ribbons receive more efferent innervation from lateral olivocochlear projections than those driven by a single ribbon. Next to the prevailing unbranched SGN dendrites, we found branched SGN dendrites that can contact several ribbons of 1-2 IHCs. Unexpectedly, medial olivocochlear neurons provide efferent innervation of SGN dendrites, preferring those forming single-ribbon, pillar-side synapses. We propose a fine-tuning of afferent and efferent SGN innervation.

14.
Nat Commun ; 12(1): 264, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431876

RESUMO

The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , Anticorpos Antivirais/química , Anticorpos Antivirais/farmacologia , /efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Microscopia Crioeletrônica , Mapeamento de Epitopos , Epitopos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Ligação Proteica/efeitos dos fármacos , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia
15.
Fertil Steril ; 115(3): 771-781, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33358334

RESUMO

OBJECTIVE: To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs). DESIGN: Multicenter questionnaire-based survey, in vivo and ex vivo studies. SETTING: Twelve hospitals in China, animal research center, and research laboratory of a women's hospital. PATIENTS/ANIMALS: A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects. INTERVENTION(S): The PCOS rat model was established with the use of testosterone propionate. MAIN OUTCOME MEASURE(S): Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis. RESULT(S): There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle. CONCLUSION(S): There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.

16.
Anal Chem ; 93(3): 1702-1708, 2021 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-33369382

RESUMO

This paper introduces a novel potential-resolved paper-based biosensor for simultaneous detection of multiple microRNAs (miRNAs) (taking miRNA-155 and miRNA-126 as examples) based on the bipolar electrode (BPE) electrochemiluminescence (ECL) strategy. The proposed multiple-channel paper-based sensing microfluidic platform was prepared by wax-printing technology, screen-printing method, and in situ Au nanoparticles (AuNPs) growth to form hydrophilic areas, hydrophobic boundaries, waterproof electronic bridge, driving electrode regions, and parallel bipolar electrode regions. CdTe quantum dots (QDs)-H2 and Au@g-C3N4 nanosheets (NSs)-DNA1 were used as dual electrochemiluminescence signal probes, and carboxylated Fe3O4 magnetic nanoparticles existed as carriers. CdTe QDs-H2/S2O82- and Au@g-C3N4 NSs-DNA1/S2O82- could exhibit two strong and stable ECL emissions at a drive voltage of 9 and 12 V, respectively, which can be used as effective potential-resolved signal tags. In addition, the proposed three-dimensional (3D) DNA nanomachine model and the target miRNA cycle strategy were used to achieve double amplification of electrochemiluminescence intensity. More importantly, the combination of the bipolar electrode system and the potential-resolved multitarget electrochemiluminescence method can greatly reduce the spatial interference between substances. The prepared ECL biosensor showed a favorable linear response for the detection of miRNA-155 and miRNA-126 with relatively low detection limits of 5.7 and 4.2 fM, respectively. With excellent sensitivity, the strategy may provide an efficient method for clinical application, especially in detection of trace multiple targets.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , MicroRNAs/análise , Papel , Compostos de Cádmio/química , Eletrodos , Corantes Fluorescentes/química , Ouro/química , Grafite/química , Humanos , Compostos de Nitrogênio/química , Pontos Quânticos/química , Telúrio/química
17.
Meat Sci ; 171: 108292, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32896773

RESUMO

Beef rolls for hot pot are usually stored and transported in a frozen state, and the beef color deteriorates quickly. This paper reports on an investigation into the effect of packaging method, freezing temperature and storage time on instrumental color, pH, myoglobin state, lipid oxidation (TBARS) and total volatile basic nitrogen (TVB-N) of beef rolls. It was shown that the color of beef rolls at -18 °C was better than that at -12 °C overall, and the OxyMb% and pH values were higher, while the MetMb% and TBARS were lower with storage at -18 °C. With the extension of storage time, the instrumental color, OxyMb% and pH values of beef rolls decreased. Correspondingly, the MetMb% and TBARS showed an upward trend. However, the TVB-N of all treatments did not exceed the Chinese standard during 180d of storage. The results of this paper provide a number of recommendations for the storage of frozen beef rolls to extend color-shelf life.

18.
Talanta ; 223(Pt 1): 121719, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303165

RESUMO

In this report, 4-mercaptophenylboronic acid (MBA) and dithiobis (succinimidyl propionate) (DSP) were used as DA molecular recognizer, which bounded onto the prepared Pt@CeO2 nanomaterial and the electrode surface. A sandwich-like electrochemical biosensor was constructed for sensitive detection of dopamine (DA) based on double molecular recognition and Pt@CeO2 (MBA-DSP- Pt@CeO2) as an electrochemical probe for signal amplification. It is worth noting that the diol and amine groups of DA were reacted by the boronic acid of MBA and the succinimide residue of DSP, respectively. This sandwich-like double molecular interaction can efficiently and accurately identify DA. The uniform Pt@CeO2 multicore@shell nanospheres as signal tags and signal amplifiers in electrochemical biosensor were synthesized by hydrothermal, which has excellent catalytic activity for H2O2. Interestingly, more oxygen vacancies were produced in the lattice structure of CeO2 doped with Pt, so that the catalytic and redox performance of the obtained Pt@CeO2 was much better than that of pure CeO2, thus greatly improving the performance of the proposed sensor. The proposed electrochemical biosensor provided a wide detection range of 2-180 nM and a low detection limit (0.71 nM) by the electrochemical measurement. And it also showed ultra-high sensitivity, accuracy and broad application prospect, which developed a new research method for early clinical diagnosis.

19.
Sci Adv ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33277323

RESUMO

The recent outbreaks and rapid international spread of SARS-CoV-2 pose a global health emergency. Its trimeric spike (S) glycoprotein interacts with human ACE2-receptor to mediate viral entry into host-cells. Here we present cryo-EM structures of a tightly closed SARS-CoV-2 S-trimer with packed fusion peptide, and an ACE2-bound S-trimer at 2.7 Å and 3.8 Å resolution, respectively. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing-motions within the S-trimer. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer regarding receptor-triggered transformation from the closed prefusion state to fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Our findings depict the mechanism of ACE2-induced S-trimer conformational transitions from ground prefusion state toward postfusion state, facilitating development of anti-SARS-CoV-2 vaccines and therapeutics.

20.
Medicine (Baltimore) ; 99(50): e23643, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33327344

RESUMO

BACKGROUND AND AIM: Intraabdominal infection (IAI) is a common and important disease worldwide. An increasing number of related guidelines/consensuses have been published in recent years, the quality evaluation for these guidelines/consensuses is necessary to identify lower-quality documents and explore the quality distribution in different time range and areas in this field. METHODS: The Appraisal of Guidelines for Research & Evaluation Instrument tool was adopted to assess the quality of IAI guidelines/consensuses by 3 researchers independently. Intraclass correlation coefficients (ICCs) among the researchers were retrieved to reflect reliability. The quality differences of these guidelines/consensuses issued before and after May 2009, both international and non-international, were compared by a Mann-Whitney U test. RESULTS: Fourteen IAI guidelines/consensuses published in English were obtained following a literature search. The ICCs among the researchers were all above 0.75, indicating satisfactory reliability. This outcome showed that the overall quality of these guidelines/consensuses was mediocre and considered acceptable in all items. A few guidelines/consensuses were better in their scientific and methodological characteristics than the others. Moreover, there were no significant differences in the scores between the guidelines/consensuses issued before and after May 2009 or between international vs regional guidelines/consensuses. CONCLUSIONS: Overall, the quality of the IAI guidelines/consensuses was generally acceptable and applicable, with a few deficiencies. Therefore, continuous improvement is essential. The guideline assessment tools should be applied in guideline/consensus development both widely and strictly to improve the methodological quality.


Assuntos
Infecções Intra-Abdominais/terapia , Guias de Prática Clínica como Assunto/normas , Consenso , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...