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1.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-479221

RESUMO

The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein mediates viral entry into host cells through binding to the cell-surface receptor angiotensin-converting enzyme 2 (ACE2). It has been shown that SARS-CoV-2 RBD (RBDCoV2) has a higher binding affinity to human ACE2 than its highly homologous SARS-CoV RBD (RBDCoV), for which the mechanistic reasons still remain to be elucidated. Here, we used the multiple-replica molecular dynamics (MD) simulations, molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding free energy calculations, and interface residue contact network (IRCN) analysis approach to explore the mechanistic origin of different ACE2 binding affinities of these two RBDs. The results demonstrate that, when compared to the RBDCoV2-ACE2 complex, the RBDCoV-ACE2 complex features the enhanced overall structural fluctuations and inter-protein positional movements and increased conformational entropy and diversity. The inter-protein electrostatic attractive interactions are a dominant force in determining the high ACE2 affinities of both RBDs, while the significantly strengthened electrostatic forces of attraction of ACE2 to RBDCoV2 determine the higher ACE2 binding affinity of RBDCoV2 than of RBDCoV. Comprehensive comparative analyses of the residue binding free energy components and IRCNs reveal that, although any RBD residue substitution involved in the charge change can significantly impact the inter-protein electrostatic interaction strength, it is the substitutions at the RBD interface that lead to the overall stronger electrostatic attractive force of RBDCoV2-ACE2, which in turn not only tightens the interface packing and suppresses the dynamics of RBDCoV2-ACE2, but also enhances the ACE2 binding affinity of RBDCoV2 compared to that of RBDCoV. Since the RBD residue substitutions involving gain/loss of the positively/negatively charged residues, in particular those near/at the binding interfaces with the potential to form hydrogen bonds and/or salt bridges with ACE2, can greatly enhance the ACE2 binding affinity, the SARS-CoV-2 variants carrying such mutations should be paid special attention to.

2.
Mitochondrial DNA B Resour ; 6(3): 1162-1163, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33855174

RESUMO

Sinolimprichtia alpina var. dissecta is a plant variety which is characterized from S. alpina var. alpina in possessing characteristic, highly dissected bracteoles. In the current study, we have sequenced the complete chloroplast genome of S. alpina var. dissecta using the Illumina sequencing platform. The chloroplast genome is 156,719 bp in length, consisting of a LSC region of 95,625 bp, a SSC region of 10,500 bp, and a pair of inverted repeats (IR) regions of 25,297 bp. The GC content was 37.7%. A total of 126 unique genes were identified, including 81 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Phylogenetic analysis based on 28 chloroplast genomes indicates that S. alpina var. dissecta is most closely related to Pterygopleurum neurophyllum.

3.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-432373

RESUMO

The COVID-19 pandemic caused by the SARS-CoV-2 virus has created a global health and economic emergency. SARS-CoV-2 viruses hijack human proteins to promote their spread and virulence including the interactions involving the viral envelope (E) protein and human proteins. To understand the structural basis for SARS-CoV-2 viral-host recognition, we used cryo-electron microscopy to determine a structure for the human cell junction protein PALS1 and SARS-CoV-2 E protein complex. The structure shows that the E protein C-terminal DLLV motif recognizes a pocket formed exclusively by hydrophobic residues from the PDZ and SH3 domains in PALS1. Our structural analysis provides an explanation for the observation that the viral E protein recruits PALS1 from lung epithelial cell junctions resulting in vascular leakage, lung damage, viral spread, and virulence. In addition, our structure provides novel targets for peptide- and small-molecule inhibitors that could block the PALS1-E interactions to reduce the E-mediated damage to vascular structures.

4.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-267716

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes a tremendous threat to global health. Although vaccines against the virus are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulated the three-dimensional structures of SARS-CoV-2 proteins with high performance computer, predicted the B cell epitopes on spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches, and then validated the epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induced antibody production, six of which were immunodominant epitopes in patients identified via the binding of epitopes with the sera from domestic and imported COVID-19 patients, and 23 were conserved within SARS-CoV-2, SARS-CoV and bat coronavirus RaTG13. We also found that the immunodominant epitopes of domestic SARS-CoV-2 were different from that of the imported, which may be caused by the mutations on S (G614D) and N proteins. Importantly, we validated that eight epitopes on S protein elicited neutralizing antibodies that blocked the cell entry of both D614 and G614 pseudo-virus of SARS-CoV-2, three and nine epitopes induced D614 or G614 neutralizing antibodies, respectively. Our present study shed light on the immunodominance, neutralization, and conserved epitopes on SARS-CoV-2 which are potently used for the diagnosis, virus classification and the vaccine design tackling inefficiency, virus mutation and different species of coronaviruses.

5.
Biomed Pharmacother ; 125: 109962, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32106373

RESUMO

Chemoresistance is still a major obstacle for lung cancer treatment. Increasing studies have demonstrated that microRNAs (miRNAs) are essential meditators of chemoresistance during cancer progression. MiR-451a is reported to be a tumor suppressor during cancer development. However, its effects on lung cancer and drug resistance in lung cancer are still unclear. In the study, the results showed that miR-451a exhibited a significant role in suppressing the drug resistance in lung cancer cells when treated with doxorubicin (DOX) through alleviating epithelialmesenchymal transition (EMT), as evidenced by the markedly reduced expression of N-cadherin and Vimentin, while the enhanced expression of E-cadherin. In addition, miR-451a over-expression markedly promoted the sensitivity of lung cancer cells to DOX treatments, and also disrupted the EMT of lung cancer cells. Mechanistically, miR-451a was found to directly target c-Myc to affect the EMT and drug resistance in lung cancer cells in response to DOX incubation. Furthermore, c-Myc knockdown markedly elevated the sensitivity of lung cancer cells to DOX, whereas over-expressing c-Myc markedly reversed the anti-tumor role of DOX, which was slightly diminished by miR-451a mimic. The in vivo experiments confirmed that miR-451a promoted the sensitivity of lung cancer cells-derived tumors to DOX treatment by reducing c-Myc. Therefore, our results revealed a new insight into DOX resistance of lung cancer cells and miR-451a could be considered as a potential therapeutic target to overcome drug resistance in lung cancer.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/metabolismo , Fatores de Transcrição/metabolismo , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Neoplasias Experimentais/tratamento farmacológico , Fatores de Transcrição/genética
6.
World J Surg Oncol ; 13: 110, 2015 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-25885660

RESUMO

BACKGROUND: Cervical cancer is one of the commonest causes of cancer-related deaths worldwide. The prevalence rate of cervical cancer in Uyghur women in Xinjiang Autonomous Region of China has been remarkably higher than the ethnic groups living in the same region. This study aimed to assess the knowledge level and attitude of cervical cancer and its issues among the Uyghur women in Xinjiang province of China. METHODS: A cross-sectional interview-based survey of 5,000 Uyghur women was developed from 2013 to 2014 in Xinjiang autonomous region, to assess their knowledge and perception of cervical cancer and its issues. The collection of data was based on the questionnaire items. RESULTS: According to the questionnaire items, we collected a data for 5,000 participants. A very small proportion of participants had heard of the cervical cancer, human papillomavirus (HPV), and HPV vaccine, that is, 27.0%, 13.0% and, 6.0%, respectively. According to the demographic characteristics, women aged 31 to 40 years were more aware of the knowledge of cervical cancer (32.9%), HPV (17.8%), and HPV vaccine (9.1%), and women with undergraduate or higher educational level had more knowledge of cervical cancer (30.0%), HPV (21.0%), and HPV vaccine (9.7%). CONCLUSIONS: From our study, we concluded that Uyghur women need more information about cervical cancer and its risk factors. Lack of the related knowledge about cervical cancer may be one of the important factors for high incidence rate of cervical cancer in Uyghur population. In order to reduce the incidence rate and mortality of cervical cancer in Uyghur women and to make extensive health education to raise awareness of cervical cancer and HPV is strongly needed than prophylactic vaccination.


Assuntos
Atitude Frente a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Estudos Transversais , Detecção Precoce de Câncer , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/psicologia , Infecções por Papillomavirus/virologia , Percepção , Prognóstico , Inquéritos e Questionários , Neoplasias do Colo do Útero/psicologia , Neoplasias do Colo do Útero/virologia , Adulto Jovem
7.
Carbohydr Polym ; 107: 25-30, 2014 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-24702914

RESUMO

The kinetics and mechanism of depolymerisation of solid sodium hyaluronate at elevated temperatures and various pH have been investigated. Depolymerisation was found to be governed by random chain scission. The activation energy at neutral pH was found to be 127 kJ/mol. The solid polymer was most stable at neutral pH. Results suggest the depolymerisation mechanism in solid- and solution state to be the same. Correlation of log intrinsic viscosity to log weight-average molecular weight was investigated to ensure high quality data for polymer size. Based on more than sixty hyaluronate samples spanning from 0.4 to 2.3 MDa, it was concluded that a second order polynomial regression gives a better fit than the linear regression offered by classical Mark-Houwink-Kuhn-Sakurada description. This finding was supported by literature data and could be expanded to other simple, well behaving linear polymers, such as polystyrene and polyethylene.


Assuntos
Ácido Hialurônico/química , Temperatura , Estabilidade de Medicamentos , Cinética , Peso Molecular , Polimerização , Viscosidade
8.
J Environ Health Sci Eng ; 12(1): 34, 2014 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-24423063

RESUMO

Environmental pollution and greenhouse gas emissions are becoming significant environmental issues in China, thus the sustainable development and revival of the country is impossible using the conventional path of encouraging economic growth at the expense of the environment. In response to the global warming, the prices of the traditional energy rise considerably, and a series of environmental problems, China must improve its own mode of economic development. Hundreds of Chinese cities have billions of square meters of buildings and most industry and the annual energy demand is an astronomical figure. China's government is facing increasing pressure in the low carbon international backdrop, and the low carbon city becomes the inevitable developmental direction of Chinese city in the foreseeable future. The description is first centered on energy structure/energy consumption per unit/urbanized status, and urban energy consumption status, and then concerned with the efforts and measures of Chinese government, to realize the energy saving. Finally, we present the developmental prospect and barriers and the promotion measures related to the low carbon city under the government policy, financial incentives and funding supports, etc.

9.
Iran J Reprod Med ; 11(11): 905-12, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24639715

RESUMO

BACKGROUND: Creation of artificial gametes may provide a universal solution for these patients with no gametes. Stem cell technology may provide a way to obtain fully functional gametes. Retinoic acid (RA) can initiate meiosis. Several studies have demonstrated that RA can promote sperm cells differentiation from mouse embryonic stem cells (mESCs) and other cells from human embryonic stem cells (hESCs). OBJECTIVE: We sought to determine whether RA could promote differentiation of germ cells from hESCs. MATERIALS AND METHODS: hESCs were differentiated as embryoid bodies (EBs) in suspension with all-trans RA (atRA) or without atRA for 0, 1, 3, 5 and 7 days, and then the expression of VASA, SCP3, GDF9 and TEKT1 were compared by real-time PCR. The statistical differences were evaluated by one way ANOVA. RESULTS: The expression of germ cell-specific markers including the gonocyte marker VASA, the meiotic marker SCP3, and post meiotic markers, GDF9 and TEKT1, all increased in the presence and absence of RA as EB differentiation progressed. In addition, the expression of these markers increased an average of 9.3, 6.9, 7.2 and 11.8 fold respectively in the presence of RA, compared to the absence of RA, over 5 days differentiation. CONCLUSION: Our results indicate that hESCs may have the potential to differentiate to primordial germ cells (PGCs) and early gametes. RA can improve germ cells differentiation from hESCs.

10.
J Surg Oncol ; 100(5): 396-400, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19582795

RESUMO

BACKGROUND: Myeloid cell leukemia-1 protein (Mcl-1), an anti-apoptotic member of Bcl-2 family, has been reported to be correlated with tumor progression. The purpose of this study was to establish the prognostic value of Mcl-1 expression in human gastric cancer. METHODS: Western blot assay was performed to detect the expression of Mcl-1 protein in human gastric cancer cell lines and tissues, while Mcl-1 expression in resected gastric cancer tissue samples was analysed by immunohistochemistry. RESULTS: The level of Mcl-1 protein expression in gastric cancer cell lines was significantly higher than that in gastric mucosa epithelial cell line. Moreover, the expression level of Mcl-1 protein was significantly higher in gastric cancer tissues than corresponding noncancerous tissues. Expression was correlated with T classification (P = 0.003), metastasis (P = 0.001), clinical stage (P = 0.010), and venous invasion (P = 0.004). Patients with high Mcl-1 expression showed poorer 5-year overall survival than patients with low Mcl-1 expression (P = 0.012; log-rank test). Further univariate and multivariate analysis suggested that high Mcl-1 expression was an independent prognostic marker for the disease. CONCLUSION: Mcl-1 is highly upregulated in gastric cancer and high Mcl-1 expression is correlated with a poor prognosis in gastric cancer patients. Thus, Mcl-1 can be utilized as an independent prognostic factor.


Assuntos
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidade , Biomarcadores Tumorais/metabolismo , Western Blotting , Linhagem Celular Tumoral , Feminino , Mucosa Gástrica/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Proteína de Sequência 1 de Leucemia de Células Mieloides , Invasividade Neoplásica , Prognóstico , Neoplasias Gástricas/patologia , Taxa de Sobrevida
11.
Health Promot Int ; 23(3): 220-30, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18728109

RESUMO

In 2003, after three pilot projects successfully implemented WHO's Health-Promoting Schools (HPS) concept, officials in Zhejiang Province, China, expanded to additional 51 schools (93,000 students and their families and 6800 school personnel). Each school identified a health issue to begin HPS development, followed by conceptual orientation, resource mobilization, teacher training, surveys, interventions, outreach and evaluation. This study focused on the extent to which participating schools implemented the HPS concept and improved their psycho-social environments (PSEs). Forty-nine of the 51 schools met China's HPS criteria. Schools with fewer resources and with substantial resources, i.e. schools in both rural and urban areas, met the criteria. Schools' PSEs, as measured by the PSE Profile, improved as they became HPS. Findings from interviews and observations identified strong encouragement and support from officials, school personnel, students, parents and community leaders, and consistency of HPS with the national policy on quality education, as success factors.


Assuntos
Difusão de Inovações , Promoção da Saúde/organização & administração , Serviços de Saúde Escolar , China , Entrevistas como Assunto , Psicologia , Organização Mundial da Saúde
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