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1.
J Pain Res ; 14: 3047-3055, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34611435

RESUMO

Purpose: The Nuss procedure is a recognized treatment for adolescent pectus excavatum that results in severe postoperative pain. Erector spinae plane block (ESPB) is a novel technique that provides postoperative analgesia and reduces opioid consumption. Our aim is to explore whether ESPB produces analgesia similar to thoracic epidural anaesthesia (TEA) in paediatric patients undergoing Nuss procedure. Study Design and Methods: This randomized, controlled, non-inferiority trial will enrol 300 paediatric patients undergoing Nuss surgery. Participants will be randomly assigned 1:1 to receive ESPB or TEA preoperatively. The primary, joint endpoint is the average numeric rating scale (NRS) score and cumulative sufentanil consumption. The secondary endpoints are pain scores and sufentanil consumption at different time points after surgery, analgesia-related side effects, and other postoperative complications. Data will be analysed by the intention-to-treat principle. Discussion: This study investigates the effect of ESPB on postoperative opioid consumption and pain scores and intend to provide a new strategy of analgesia management for Nuss procedure in paediatric patients.

2.
Opt Express ; 29(17): 27661-27673, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615178

RESUMO

Quantum digital signatures (QDSs) promise information-theoretic security against repudiation and forgery of messages. Compared with currently existing three-party QDS protocols, multiparty protocols have unique advantages in the practical case of more than two receivers when sending a mass message. However, complex security analysis, numerous quantum channels and low data utilization efficiency make it intractable to expand three-party to multiparty scenario. Here, based on six-state non-orthogonal encoding protocol, we propose an effective multiparty QDS framework to overcome these difficulties. The number of quantum channels in our protocol only linearly depends on the number of users. The post-matching method is introduced to enhance data utilization efficiency and make it linearly scale with the probability of detection events even for five-party scenario. Our work compensates for the absence of practical multiparty protocols, which paves the way for future QDS networks.

3.
Opt Express ; 29(20): 32244-32255, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34615300

RESUMO

Quantum secret sharing (QSS) is an essential primitive for the future quantum internet, which promises secure multiparty communication. However, developing a large-scale QSS network is a huge challenge due to the channel loss and the requirement of multiphoton interference or high-fidelity multipartite entanglement distribution. Here, we propose a three-user QSS protocol without monitoring signal disturbance, which is capable of ensuring the unconditional security. The final key rate of our protocol can be demonstrated to break the Pirandola-Laurenza-Ottaviani-Banchi bound of quantum channel and its simulated transmission distance can approach over 600 km using current techniques. Our results pave the way to realizing high-rate and large-scale QSS networks.

4.
Front Psychiatry ; 12: 731378, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650455

RESUMO

There is little empirical research on the effect of working after retirement on the mental health of the older adults in China. To fill this gap in the literature, this study examines the effects of working after retirement on the mental health of the older adults using data from the China Family Panel Studies. We employed the methods of ordinary least squares, ordered logit, and propensity score matching-difference in differences (PSM-DID). Results show that working after retirement is negatively related to mental health of the older adults in China. The deterioration effect of post-retirement work mainly impacts those aged over 60 years, women, and those with lower education background, urban household registration, higher pension, and higher social status. Working after retirement is negatively related to mental health through the mediating effects of deteriorating interpersonal relationships and lower positive attitude. It is necessary to consider mental health effects and their population differences to evaluate the impact and improve the quality of policies of active aging.

6.
Phys Rev Lett ; 127(11): 112501, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34558921

RESUMO

High-accuracy mass measurements of neutron-deficient Yb isotopes have been performed at TRIUMF using TITAN's multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS). For the first time, an MR-TOF-MS was used on line simultaneously as an isobar separator and as a mass spectrometer, extending the measurements to two isotopes further away from stability than otherwise possible. The ground state masses of ^{150,153}Yb and the excitation energy of ^{151}Yb^{m} were measured for the first time. As a result, the persistence of the N=82 shell with almost unmodified shell gap energies is established up to the proton drip line. Furthermore, the puzzling systematics of the h_{11/2}-excited isomeric states of the N=81 isotones are unraveled using state-of-the-art mean field calculations.

7.
Int J Womens Health ; 13: 829-840, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34552355

RESUMO

Objective: The growth of oviduct mucosa in the uterine cavity was observed by co-culture of oviduct mucosa cells and endometrial cells in different proportions to study the possibility and function of the growth of oviduct mucosa in the uterine cavity. Methods: The extracted cells were identified by immunofluorescence with cytokeratins 19 (CK19) and vimentin. A Cell Counting Kit-8 (CCK8) experiment, cell decidualization induction, and HE staining were performed after the co-culture of two kinds of cells in different proportions. Results: 1) The cells could grow normally when the two cells were co-cultured indirectly. 2) A CCK8 test of oviduct mucosa cells showed that the growth rate of each group was similar after the indirect co-culture of two kinds of cells in different proportions, which was in line with the growth law of normal cells. 3) Immunofluorescence identification of the cells showed that most of the two kinds of cells in the second passage were CK19 positive and were epithelial cells, while most of the cells in the fifth passage expressed positive vimentin antibody and were stroma cells. 4) After cell decidualization induction, the cell morphology of each group showed deciduation-like changes. 5) After decidualization, the cell morphology of each group was similar after HE staining. Conclusion: Oviduct mucosa cells can grow normally in the uterine environment. In the uterine environment with different degrees of endometrial loss, the growth rate of oviduct mucosa cells is not inhibited. Its morphology does not change, and it can undergo decidualization in vitro.

8.
ACS Omega ; 6(37): 24016-24026, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34568680

RESUMO

The aim of this study is to investigate mRNA expression profiling by RNA sequencing (RNA-seq) in patients with coronary artery disease (CAD) and validate differentially expressed genes (DEGs) as novel biomarkers for CAD. Transcriptome-wide mRNA expression analysis of peripheral blood mononuclear cells was performed in five CAD patients and five controls. Functional enrichment analyses, protein-protein interaction network construction, and hub gene selection were further conducted. Relative expression levels of hub genes were validated by quantitative reverse transcription PCR in larger cohorts. Spearman correlation test and multiple linear regression analysis were applied to examine the relationship between confounding factors with severity of coronary artery atherosclerosis. Receiver operating characteristic (ROC) curve analysis was adopted to identify potentially diagnostic biomarkers for CAD. A total of 527 upregulated and 653 downregulated mRNAs were identified as DEGs in CAD patients. The relative expression levels of beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), F-box and leucine-rich repeat protein 4 (FBXL4), ubiquitin conjugating enzyme E2 D2 (UBE2D2), and ankyrin repeat and SOCS box containing 1 (ASB1) were significantly different between two groups (all p ≤ 0.05). The severity of coronary artery atherosclerosis was negatively associated with the BTRC gene relative expression level (r = -0.323, p < 0.001) and positively with UBE2D2 (r = 0.285, p < 0.001). ROC analysis of BTRC and UBE2D2 genes showed that the areas under the curve were 0.782 (95% CI: 0.720-0.845, p < 0.001) and 0.753 (95% CI: 0.681-0.824, p < 0.001), respectively. We described the characteristics of mRNA expression in the peripheral blood of CAD patients and controls by RNA-seq. Combined with Spearman correlation analysis and ROC analyses, BTRC and UBE2D2 genes had significantly diagnostic values, which may have potential to act as novel diagnostic biomarkers and therapeutic targets for CAD.

9.
Pathol Oncol Res ; 27: 1609809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512202

RESUMO

Traditionally, clear cell papillary renal cell carcinoma (ccpRCC) was considered to share similar molecular and histological characteristics with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC). Here we aimed to identify somatic and germline variants of ccpRCC. For this purpose, we conducted whole-exome sequencing to detect somatic variants in the tissues of 18 patients with pathologically confirmed ccpRCC, who underwent surgical treatment at Fudan University Shanghai Cancer Center. Targeted sequencing was conducted to detect germline variants in paired tumor or normal tissues or blood. Somatic and germline variants of ccRCC and Renal cell carcinoma included in The Cancer Genome Atlas data and other published data were analyzed as well. The molecular profiles of ccpRCC, ccRCC and pRCC were compared. Among the 387 somatic variants identified, TCEB1 (3/18) and VHL (3/18) variants occurred at the highest frequencies. Germline mutation detection showed that nine variants associated with Fanconi anemia (VAFAs) pathway (FANCA, 6/18; FANCI, 3/18) were identified in 18 ccpRCC patients. Among ccpRCC patients with VAFAs, five out of eight patients had second primary malignancy or family history of cancer. Somatic variants characteristics may distinguish ccpRCC from ccRCC or pRCC and germline VAFAs may be a molecular characterization of ccpRCC. Compared with ccRCC or pRCC, ccpRCC patients may be significantly correlated with higher risk of developing second primary malignancy.

10.
Talanta ; 235: 122722, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517590

RESUMO

In-vehicle air pollution has become a major concern to public health in recent years. The traditional analytical methods for detection of volatile organic compounds (VOCs) pollutants in air are based on gas chromatography - mass spectrometry (GC-MS) or high-performance liquid chromatography (HPLC), including complicated pretreatment and separation procedures, which are not only time-consuming and labor-intensive, but also incapable of simultaneously measuring both aldehydes and benzenes. In this work, a new photoionization-induced NO+ chemical ionization time-of-flight mass spectrometry (PNCI-TOFMS) was developed for real-time and continuous measurement of aldehydes and benzenes in vehicles. High-intensity NO+ reactant ions could be generated by photoionization of NO reagent gas, and efficient chemical ionization between NO+ reactant ions and analyte molecules occurred to produce adduct ions M·NO+ at an elevated ion source pressure of 800 Pa. Consequently, the achieved LODs for aldehydes and benzenes were down to sub-ppbv within 60 s. The analytical capacity of this system was demonstrated by continuous and online monitoring of in-vehicle VOCs in a used car, exhibiting broad potential applications of the PNCI-TOFMS in air pollutants monitoring and in-vehicle air quality analysis.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Poluentes Atmosféricos/análise , Aldeídos , Benzeno , Cromatografia Gasosa-Espectrometria de Massas , Compostos Orgânicos Voláteis/análise
11.
Front Cardiovasc Med ; 8: 700630, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513945

RESUMO

Background: Proliferation and migration of smooth muscle cells in the coronary artery contribute to the deterioration of coronary artery disease (CAD). Aim: This research was designed to study the function of Shexiang Baoxin pills (SBPs) on the proliferation and migration of human coronary artery smooth muscle cells (HCASMCs) and their mechanism. Methods: Oxidized low-density lipoprotein (ox-LDL) was applied to stimulate the proliferation and migration of HCASMCs. The function of ox-LDL and SBP on HCASMCs was evidenced by the cell counting kit-8 assay, cell cycle, and Transwell assay. Network pharmacology was employed to predict the potential targets and pathways of SBP on CAD. Western blot assay and molecular docking were conducted to validate the potential targets and pathways. Results: The current research revealed that 2.5 mg/L SBP significantly inhibited the proliferation and migration of HCASMCs. Besides, network pharmacology revealed 11 candidate targets. Molecular docking and Western blot assay validated that the activation of the top 2 targets STAT3 and MAPK14 was associated with the inhibition of HCASMCs. Moreover, the Western blot assay also detected that HCASMCs treated with ox-LDL promoted the phosphorylation of the PI3K/AKT/mTOR pathway, and SBP inhibited the activation of the PI3K/AKT/mTOR pathway in HCASMCs stimulated by ox-LDL. Conclusion: This study demonstrated that the treatment of CAD using SBP may result from the suppression of the proliferation and migration of HCASMCs. The mechanism of this function partly resulted from relieving the phosphorylation of targets STAT3 and MAPK14 and the PI3K/AKT/mTOR pathway. This study enhanced our comprehension of SBP and provides new targets for the treatment of CAD.

12.
Ann Clin Lab Sci ; 51(4): 470-486, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34452885

RESUMO

OBJECTIVE: Epithelium-specific ETS protein 3 (Ese-3) is a member of the ETS family that is associated with tumor progression. However, there is little knowledge about Ese-3 in skin cancer. This study was conducted to explore the effects of Ese-3 on clinical prognosis in skin cancer and the functions of HaCaT cells. MATERIALS AND METHODS: Gene expression and clinical data were collected from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and three GSE datasets (GSE15605, GSE46517, and GSE114445). Comparison of data between groups was performed by Student's t-test and chi square test. Survival analysis was performed using log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models. Enrichment analysis was used to predict Ese-3 related functions. Cell proliferation assays, colony formation assays, and flow cytometry were used to assess cell proliferation, while Transwell assays analyzed cell migration and invasion. RESULTS: Compared with normal tissues, the Ese-3 mRNA in cutaneous malignant melanoma (CMM) patients was downregulated (P<0.0001). Ese-3 mRNA was associated with the T stage (χ 2=10.015, P=0.018), clinical stage (χ 2=4.122, P=0.042), and prognosis in CMM patients (P=0.0219) and was an independent prognostic predictor in CMM (HR=1.878, P=0.048). Enrichment analysis showed that differentially expressed proteins were associated with "protein kinase B (AKT) binding." CONCLUSION: Ese-3 inhibited the proliferation, migration, and invasion of HaCaT cells by downregulating PSIP1 and NUCKS1 expression levels to inactivate the phosphorylation of AKT.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/antagonistas & inibidores , Fosfoproteínas/antagonistas & inibidores , Neoplasias Cutâneas/patologia , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Apoptose , Biomarcadores Tumorais/genética , Movimento Celular , Proliferação de Células , Feminino , Células HaCaT , Humanos , Masculino , Invasividade Neoplásica , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Taxa de Sobrevida , Fatores de Transcrição/genética
13.
Front Public Health ; 9: 679429, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34458220

RESUMO

Background: By implementing aggressive control measures, China has rapidly and effectively controlled the Coronavirus disease 2019 (COVID-19) pandemic. However, the neglected homeless population may become victims of that perceived success. Due to political sensitivity, we know little about them. Aims: This study aimed to investigate how the pandemic and the pandemic control strategies of the government affected the lives of the homeless people in mainland China. Methods: A total of 103 eligible participants experiencing absolute homelessness were recruited from Guangzhou City during July and August 2020. Surveys measured demographic characteristics including health status, changes in daily living, and actions of the government toward the homeless during the pandemic. Sankey diagrams and ordered logit regression models were used to examine the impact on the homeless of inhumane government efforts to drive the homeless away. Qualitative materials were analyzed by using an inductive approach to provide more details. Results: First, the homeless people in Guangzhou tended to be male, aged 40 to 64 years, less well-educated, and they originated from outside Guangdong although they were living in the city center. Most had little connection with their families. After a long period of homelessness, almost half of the participants were in poor health with various conditions, which made them extremely vulnerable to COVID-19. Second, the pandemic caused a substantial decline in incomes of homeless people, had less of a negative impact on their food intake, and affected sleep time in different ways. Third, during the COVID-19 pandemic, humanitarian aid from local governments of China decreased, whereas inhumane efforts to drive the homeless away intensified. Fourth, quantitative models and qualitative materials demonstrate the devastating effect of the strict pandemic control strategy of the government on the lives of homeless people, which may further cause their health problems. Conclusion: This study for the first time illustrated the characteristic features of the street homeless population in mainland China and their living situation during the COVID-19 pandemic, and most importantly demonstrated the devastating effect of the strict pandemic control of the government, which has been considered a great success in previous studies, on lives of homeless people. Urgent measures should be taken to ensure the protection of the homeless population and prevent an impending humanitarian crisis.


Assuntos
COVID-19 , Pessoas em Situação de Rua , China/epidemiologia , Governo , Humanos , Masculino , Pandemias/prevenção & controle , SARS-CoV-2
14.
Front Public Health ; 9: 673368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336769

RESUMO

Purpose: The Internet has become an important part of daily life. However, older adults in China remain digital refugees amid the rapid development of digital information technology. This study attempts to scientifically answer how Internet use affects the subjective welfare of older adults. Method: Using data from the 2014 and 2016 China Longitudinal Aging Social Survey (CLASS), a combination of ordinary least squares, ordered logit regression models, and propensity score matching (PSM) models were used to analyze the effects of Internet use on the mental health of Chinese older adults. Results: Our findings suggest that Internet use affects the mental health of older adults and increases the incidence of their depressive symptoms. These findings are robust to changing the key indicators, research method, and sample. Further heterogeneity analysis reveals that the negative effects on mental health are more evident for specific groups of older adults, such as those who are women, younger and middle-aged, high-income, non-rural Hukou, less educated, and living with others. Conclusions: Cultivating the ability of older adults to use the Internet and maintain a rational attitude while doing so can prevent its negative impact on their life satisfaction. Moreover, it can improve their attitudes toward using the technology and reduce their anxiety.


Assuntos
Uso da Internet , Saúde Mental , Idoso , Envelhecimento , Atitude , China/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade
15.
Adv Sci (Weinh) ; 8(18): e2101326, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34313017

RESUMO

The state-of-the-art luminescent materials are gained widely by utilizing thermally activated delayed fluorescence (TADF) mechanism. However, the feasible molecular designing strategy of fully exploiting triplet excitons to enhance TADF properties is still in demand. Herein, TADF emitters with multiple conversion channels of triplet excitons are designed by concisely halogenating the electron acceptors containing carbonyl moiety. Compared with the chlorinated and brominated analogues, the fluorinated emitter exhibits distinguishing molecular stacking structures, participating in the formation of trimers through integrating CH···F and C═O···H hydrogen bonds together. It is also demonstrated that the multiple channels can be involved synergistically to accelerate the spin-flip of triplet excitons, and to take charge of the relatively superior reverse intersystem crossing constant rate of 6.20 × 105 s-1 , and thus excellent photoluminescence quantum yields over 90% can easily be achieved. Then the solution-processable organic light emitting diode based on fluorinated emitter can achieve a record-high external quantum efficiency value of 27.13% and relatively low efficiency roll-off with remaining 24.74% at 1000 cd m-2 . This result manifests the significance of enhancing photophysical properties through constructing multiple conversion channels of triplets excitons for high-efficiency TADF emitters and provides a guideline for the future study.

16.
Plant Biotechnol J ; 19(11): 2291-2303, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34328250

RESUMO

The engineering of C4 photosynthetic activity into the C3 plant rice has the potential to nearly double rice yields. To engineer a two-cell photosynthetic system in rice, the rice bundle sheath (BS) must be rewired to enhance photosynthetic capacity. Here, we show that BS chloroplast biogenesis is enhanced when the transcriptional activator, Oryza sativa Cytokinin GATA transcription factor 1 (OsCGA1), is driven by a vascular specific promoter. Ectopic expression of OsCGA1 resulted in increased BS chloroplast planar area and increased expression of photosynthesis-associated nuclear genes (PhANG), required for the biogenesis of photosynthetically active chloroplasts in BS cells of rice. A further refinement using a DNAse dead Cas9 (dCas9) activation module driven by the same cell-type specific promoter, directed enhanced chloroplast development of the BS cells when gRNA sequences were delivered by the dCas9 module to the promoter of the endogenous OsCGA1 gene. Single gRNA expression was sufficient to mediate the transactivation of both the endogenous gene and a transgenic GUS reporter fused with OsCGA1 promoter. Our results illustrate the potential for tissue-specific dCas9-activation and the co-regulation of genes needed for multistep engineering of C4 rice.

17.
Acta Histochem ; 123(6): 151748, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34271280

RESUMO

Heart failure (HF) is a major cause of death in cardiovascular diseases worldwide, and its molecular mechanisms and effective prevention strategies remain to be further studied. The myocardial cytoskeleton plays a pivotal role in many heart diseases. However, little is known about the function of the membrane cytoskeleton 4.1 protein family and related regulatory mechanisms in the pathogenesis of HF. In this study, we detected the localization and expression of the protein 4.1 family and ion channel proteins in a rat HF model induced by doxorubicin (DOX), and studied the interactions between them. Our results showed that compared with the control group, the HF group displayed an increased expression level of protein 4.1R and decreased levels of protein 4.1 G and 4.1 N. The Nav1.5 protein levels were significantly increased, while the SERCA2a and Cav1.2 protein levels were significantly decreased in the HF group. Furthermore, there is co-localization and interaction between protein 4.1R and Nav1.5, protein 4.1 G and SERCA2a, protein 4.1 N and Cav1.2, respectively. Taken together, the results indicated that the protein 4.1 family might be involved in the occurrence and development of HF through its interaction with ion channel proteins, suggesting that 4.1 proteins may serve as a novel therapeutic target for HF.

18.
Entropy (Basel) ; 23(6)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199849

RESUMO

As an essential application of quantum mechanics in classical cryptography, quantum secret sharing has become an indispensable component of quantum internet. Recently, a differential phase shift quantum secret sharing protocol using a twin field has been proposed to break the linear rate-distance boundary. However, this original protocol has a poor performance over channels with asymmetric transmittances. To make it more practical, we present a differential phase shift quantum secret sharing protocol with asymmetric source intensities and give the security proof of our protocol against individual attacks. Taking finite-key effects into account, our asymmetric protocol can theoretically obtain the key rate two orders of magnitude higher than that of the original protocol when the difference in length between Alice's channel and Bob's is fixed at 14 km. Moreover, our protocol can provide a high key rate even when the difference is quite large and has great robustness against finite-key effects. Therefore, our work is meaningful for the real-life applications of quantum secret sharing.

19.
Front Public Health ; 9: 677643, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34268289

RESUMO

Purpose: The research objectives of this study are to test the scientific propositions of whether Internet use promotes life satisfaction among the elderly, whether there is variability in the effect of Internet use on the well-being of the elderly, and through what channels Internet use affects the elderly's life satisfaction. Method: Using data from the 2017 Chinese General Social Survey (CGSS), this paper employed linear regression, ordered logit model, and the propensity score matching (PSM) approach to investigate the association of Internet use with life satisfaction among the elderly in China. Results: The results show that Internet use was significantly and negatively associated with the life satisfaction of the Chinese elderly. Further analysis on group heterogeneity demonstrates that the negative association was more prominent among the participants who were males, at a lower age, had lower income and education, non-agricultural registered, and relatively healthy. Finally, the mediating effect indicates that Internet use may affect life satisfaction among the elderly through the channel of reducing their perceptions of social justice. Conclusions: In order to avoid the negative effects of using the Internet, the following policy suggestions are put forward: Improve the elderly's attitudes toward Internet use; pay attention to the sense of fairness of the elderly to improve life satisfaction; guide the elderly to reduce the time of using the Internet.


Assuntos
Uso da Internet , Satisfação Pessoal , Idoso , Atitude , China/epidemiologia , Humanos , Renda , Masculino
20.
Preprint em Inglês | bioRxiv | ID: ppbiorxiv-448958

RESUMO

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.

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