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1.
Steroids ; 177: 108949, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34896125

RESUMO

The species of Paris genus is a prolific source of structurally diverse steroidal saponins responsible for multivarious biological properties. The first phytochemical investigation on the steroidal saponin constituents from the rhizomes of Paris vaniotii Lévl. led to the discovery and structural characterization of four new spirostanol saponins, named parisvaniosides A-D (1-4), and one new furostanol glycoside, named parisvanioside E (5), along with eleven known analogues (6-16). Their structures were unambiguously established on the basis of extensive spectroscopic analysis and comparison with the reported spectroscopic data. Compound 1 is a rare spirostanol saponin sharing with a C-9/C-11 double bond and a peroxy group located between C-5 and C-8 of the aglycone, whereas 3 and 4 are unusual C-27 steroidal sapoins with hydroxyl/methoxyl at both C-5 and C-6. Furthermore, 5 is the first furostanol saponin with a unique aglycone featuring two trisubstituted double bonds in ring B. All isolated saponins were evaluated for their anti-inflammatory effects on a lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production model in RAW 264.7 macrophages.

2.
Innovation (N Y) ; : 100181, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34746904

RESUMO

Most COVID-19 convalescents can build effective anti-SARS-CoV-2 humoral immunity, but it remains unclear how long it can maintain and how efficiently it can prevent the reinfection of the emerging SARS-CoV-2 variants. Here, we tested the sera from 248 COVID-19 convalescents around one year post-infection in Wuhan, the earliest known epicenter. SARS-CoV-2 immunoglobulins G (IgG) were well maintained in most patients and potently neutralizes the infection of the original strain and the B.1.1.7 variant. However, varying degrees of immune escape was observed on the other tested variants in a patient-specific manner, with individuals showing remarkably broad neutralization potency. The immune escape can be largely attributed to several critical spike mutations. These results suggest that SARS-CoV-2 can elicit long-lasting immunity but escaped by the emerging variants.

3.
China CDC Wkly ; 3(46): 967-972, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34804629

RESUMO

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently emergent coronavirus of natural origin and caused the coronavirus disease (COVID-19) pandemic. The study of its natural origin and host range is of particular importance for source tracing, monitoring of this virus, and prevention of recurrent infections. One major approach is to test the binding ability of the viral receptor gene ACE2 from various hosts to SARS-CoV-2 spike protein, but it is time-consuming and labor-intensive to cover a large collection of species. Methods: In this paper, we applied state-of-the-art machine learning approaches and created a pipeline reaching >87% accuracy in predicting binding between different ACE2 and SARS-CoV-2 spike. Results: We further validated our prediction pipeline using 2 independent test sets involving >50 bat species and achieved >78% accuracy. A large-scale screening of 204 mammal species revealed 144 species (or 61%) were susceptible to SARS-CoV-2 infections, highlighting the importance of intensive monitoring and studies in mammalian species. Discussion: In short, our study employed machine learning models to create an important tool for predicting potential hosts of SARS-CoV-2 and achieved the highest precision to our knowledge in experimental validation. This study also predicted that a wide range of mammals were capable of being infected by SARS-CoV-2.

4.
Vaccine ; 39(48): 7001-7011, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34750014

RESUMO

COVID-19 pandemic has severely impacted the public health and social economy worldwide. A safe, effective, and affordable vaccine against SARS-CoV-2 infections/diseases is urgently needed. We have been developing a recombinant vaccine based on a prefusion-stabilized spike trimer of SARS-CoV-2 and formulated with aluminium hydroxide and CpG 7909. The spike protein was expressed in Chinese hamster ovary (CHO) cells, purified, and prepared as a stable formulation with the dual adjuvant. Immunogenicity studies showed that candidate vaccines elicited robust neutralizing antibody responses and substantial CD4+ T cell responses in both mice and non-human primates. And vaccine-induced neutralizing antibodies persisted at high level for at least 6 months. Challenge studies demonstrated that candidate vaccine reduced the viral loads and inflammation in the lungs of SARS-CoV-2 infected golden Syrian hamsters significantly. In addition, the vaccine-induced antibodies showed cross-neutralization activity against B.1.1.7 and B.1.351 variants. These data suggest candidate vaccine is efficacious in preventing SARS-CoV-2 infections and associated pneumonia, thereby justifying ongoing phase I/II clinical studies in China (NCT04982068 and NCT04990544).


Assuntos
Vacinas contra COVID-19 , COVID-19 , Compostos de Alúmen , Hidróxido de Alumínio , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Células CHO , Cricetinae , Cricetulus , Humanos , Camundongos , Pandemias , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
5.
BMC Psychiatry ; 21(1): 543, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732164

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) has increased the physical and psychological stress of medical workers. This study was designed to investigate the prevalence and risk factors of job burnout and its impact on work ability among Biosafety Laboratory (BSL) staffs during the COVID-19 epidemic in Xinjiang. METHODS: A total of 7911 qualified BSL staffs in Xinjiang were investigated by electronic questionnaires. The Maslach Burnout Inventory-General Survey (MBI-GS) was used for job burnout survey. Work Ability Index (WAI) was used for work ability survey. The prevalence and risk factors of job burnout in BSL staffs were analyzed through chi square test, t-test and one-way ANOVA. And then, the influence of demographic and job-related variables, i.e., confounding factors, were eliminated to the greatest extent by the propensity score analysis (PSA) method, to investigate the impact of job burnout on work ability in BSL staffs. RESULTS: A total of 67.6% BSL staffs experienced job burnout. There were significant differences in the detection rate of job burnout among demographic and job-related variables, including gender, age, ethnicity, education, working years, professional title, marital status, number of night shift per month and overall sleep condition (all P < 0.05). The detection rate of job burnout in female was higher than that in male. The detection rates of job burnout in 45-50 years old, Han ethnicity, education of postgraduate or above, 11-20 years of working, intermediate professional title, married, staff with many night shifts per month and poor overall sleep condition were higher than that of other groups. The average burnout scores of the Emotional Exhaustion (EE), Cynicism (CY), Reduced Personal Accomplishment (PA) scale were 10.00 ± 5.99, 4.64 ± 4.59 and 15.25 ± 8.16, respectively. Multiple logistic regression analysis showed that the three dimensions of job burnout, i.e., EE, CY, PE, were negatively correlated with work ability and significantly affected the work ability of BSL staffs (all P < 0.001). CONCLUSIONS: Our results suggest that the prevalence of job burnout is extremely common among BSL staffs. In addition, the work ability decreases with the increase of job burnout and the improvement of job burnout can enhance work ability among BSL staffs.


Assuntos
Esgotamento Profissional , COVID-19 , Epidemias , Esgotamento Profissional/epidemiologia , Contenção de Riscos Biológicos , Feminino , Humanos , Satisfação no Emprego , Laboratórios , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Inquéritos e Questionários , Avaliação da Capacidade de Trabalho
6.
Artigo em Inglês | MEDLINE | ID: mdl-34591255

RESUMO

This study aimed to explore an effective, simple, and time-saving method for astaxanthin accumulation. Wild-type Saccharomyces cerevisiae as a bioreactor, the SpcrtR gene was first ligated with the signal peptide S to construct pYES2/NT-A-S-SpcrtR plasmid in Saccharomyces cerevisiae. The detection of SDS-PAGE and Western blotting protein proved that SpCRTR was successfully extracellular expressed in Saccharomyces cerevisiae. The target product astaxanthin was produced by co-fermentation of Spirulina platensis and recombinant Saccharomyces cerevisiae. The test results showed that after 18 h of fermentation, the astaxanthin concentration was highest in the mixed fermentation broth with 4% Spirulina platensis and recombinant Saccharomyces cerevisiae, and the content of astaxanthin was 0.25 ± 0.02 µg/mL. In addition, the source of astaxanthin was explored. During the fermentation process of the Saccharomyces cerevisiae strain, SpCRTR enzyme catalyzed the Spirulina platensis canthaxanthin, which almost completely converted into astaxanthin, providing a simple method for astaxanthin synthesis. Compared with culture of Haematococcus pluvialis, this culture route not only shortens culture time, but also eliminates the limitation of the conditions in the culture process.

7.
Chem Commun (Camb) ; 57(59): 7272-7275, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34195708

RESUMO

The first copper-catalyzed [3+2]-type condensation reaction of α,ß-unsaturated ketoximes with activated ketones has been described for the synthesis of dihydrooxazoles, especially trifluoromethyl-decorated dihydrooxazoles. Notable features of this method include its broad substrate scope, good functional group tolerance, and simple operation.

8.
Dis Markers ; 2021: 6639366, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239621

RESUMO

Background: Nowadays, PD-1/PD-L1 inhibitors are widely used to treat various malignant tumors. However, during the immunotherapy in a few patients, a flare-up of tumor growth occurred. This new pattern of progression is called hyperprogressive disease (HPD). Patients and Methods. The retrospective study included 377 patients with various malignant tumors treated with PD-1 inhibitors (nivolumab or pembrolizumab) in the Chinese PLA General Hospital from January 2015 to January 2019. Clinicopathologic variables, tumor growth rate (TGR), and treatment outcomes were analyzed in patients with pan-cancer treated with PD-1 inhibitors. HPD was defined as the difference of TGR before and during immunotherapy exceeding 50%. Results: In 38 of 377 patients (10.08%), HPD occurred after treatment with PD-1 inhibitors. Patients with HPD had lower overall survival (OS) than those without HPD (median OS, 3.6months (95% CI, 3.0-4.2) vs. 7.3 months (95% CI, 5.9-8.7); P < 0.01). Factors related to HPD include more than 2 metastatic sites, ECOG performance status ≥ 2, hepatic metastases, and lactate dehydrogenase level greater than normal upper limit. KRAS status was significantly associated with HPD in patients with colorectal cancer. In the exploratory predictors' analysis, the rapid increase of characteristic tumor markers (such as CEA in colorectal cancer, CA199 in pancreatic cancer and cholangiocarcinoma) within one month was found to be associated with the occurrence of HPD. Conclusions: HPD was developed with different rates in a variety of malignant tumor patients treated with PD-1 inhibitors and related to some clinicopathological features and poor prognosis. Tumor markers, especially CA199, might be served as early predictors of HPD.

9.
Front Genet ; 12: 639872, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262591

RESUMO

Motivation: Long non-coding RNAs (lncRNAs) play important roles in cancer development. Prediction of lncRNA-cancer association is necessary for efficiently discovering biomarkers and designing treatment for cancers. Currently, several methods have been developed to predict lncRNA-cancer associations. However, most of them do not consider the relationships between lncRNA with other molecules and with cancer prognosis, which has limited the accuracy of the prediction. Method: Here, we constructed relationship matrices between 1,679 lncRNAs, 2,759 miRNAs, and 16,410 genes and cancer prognosis on three types of cancers (breast, lung, and colorectal cancers) to predict lncRNA-cancer associations. The matrices were iteratively reconstructed by matrix factorization to optimize low-rank size. This method is called detecting lncRNA cancer association (DRACA). Results: Application of this method in the prediction of lncRNAs-breast cancer, lncRNA-lung cancer, and lncRNA-colorectal cancer associations achieved an area under curve (AUC) of 0.810, 0.796, and 0.795, respectively, by 10-fold cross-validations. The performances of DRACA in predicting associations between lncRNAs with three kinds of cancers were at least 6.6, 7.2, and 6.9% better than other methods, respectively. To our knowledge, this is the first method employing cancer prognosis in the prediction of lncRNA-cancer associations. When removing the relationships between cancer prognosis and genes, the AUCs were decreased 7.2, 0.6, and 5% for breast, lung, and colorectal cancers, respectively. Moreover, the predicted lncRNAs were found with greater numbers of somatic mutations than the lncRNAs not predicted as cancer-associated for three types of cancers. DRACA predicted many novel lncRNAs, whose expressions were found to be related to survival rates of patients. The method is available at https://github.com/Yanh35/DRACA.

10.
Int J Phytoremediation ; : 1-7, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34292800

RESUMO

This study investigated the effect of Ca(H2PO4)2 on pH, leaching toxicity and speciations of soil before and after leaching on it. Different amounts of Ca(H2PO4)2 were added to Pb-contaminated soil and stabilized for 30 days. The changes of pH and leaching toxicity of Pb-contaminated soil were tracked during that period. The content of Pb in soil before and after leaching was also determined after 30 days of stabilization. Results showed that the pH of the Pb-contaminated soil didn't change much with the addition of-Ca(H2PO4)2. When the amount of Ca(H2PO4)2 reached to 3 wt%, the leaching toxicity met the standard limiting level of groundwater class III of China. The change of leaching toxicity was found to be mainly affected by the water-soluble fraction and mild acid-soluble fraction of lead. The speciation experiments revealed that the changes on reducible, oxidizable, and residual fractions are significant, while there are only minor changes on the water-soluble and mild acid-soluble fractions. X-ray diffractometry (XRD) analysis showed that Pb9(PO4)6 and Pb2P2O7 substances were generated in the stabilized soil. The stabilization mechanism of Ca(H2PO4)2 was mainly attributed to the formation of insoluble Pb phosphate precipitates through interactions between the heavy metal Pb and the Ca(H2PO4)2. In such a way the active species of Pb in the soil can be successfully stabilized. Novelty statementAt present, the leaching toxicity is currently used for the evaluation of stabilization effect of heavy metal contaminated soil. The speciation distribution of stabilized contaminated soil before and after leaching has rarely been studied, and the research on stabilizing contaminated soil after leaching is less.Therefore, this paper mainly studies the stabilization effect through the speciation changes of contaminated soil before and after leaching, providing a new idea and method for the evaluation of the stabilization effect of contaminated soil remediation.Ca(H2PO4)2 has no significance in pH of contaminated soil: 5.05<pH<5.5.The content of the water-soluble fraction and the mild acid-soluble fraction of Pb were availably reduced by Ca(H2PO4)2.The content of the water-soluble fraction and the mild acid-soluble fraction of Pb has no marked change before and after leaching.The stabilization mechanism of Ca(H2PO4)2 is through interaction between the Pb in the soil and phosphate to form insoluble substances of lead phosphate.Ca(H2PO4)2 has a good effect on the stabilization of lead-contaminated soil.

11.
Front Oncol ; 11: 648068, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34221968

RESUMO

Background: There are limited treatment options for advanced biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, gallbladder cancer. We compared the efficacy and safety of PD-1 inhibitors plus chemotherapy and chemotherapy alone as first-line treatment in patients with advanced BTC. Methods: We retrospectively reviewed patients with BTC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor with chemotherapy (anti-PD-1+C group) or chemotherapy alone (C group). Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) was analyzed using Kaplan-Meier survival curves with log-rank tests. Objective response rate (ORR), disease control rate (DCR), and safety were also analyzed. Results: This study included 75 patients who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) plus chemotherapy and 59 patients who received chemotherapy alone. After matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 5.8m in the anti-PD-1+C group, which was significantly longer than the C group, at 3.2m (HR: 0.47, 95% CI 0.29 to 0.76, P = 0.004). The ORR was 21.7% and DCR was 80.4% in the anti-PD-1+C group, while the ORR was 15.2% and DCR was 69.6% in the C group. No significant differences were found in the ORR and DCR between the two groups (P=0.423, P=0.231). Grade 3 or 4 treatment was related to adverse events (AEs) that occurred in the anti-PD-1+C group, namely hypothyroidism (n=3, 6.5%), rash (n=2, 4.2%), and hepatitis (n=1, 2.2%). There was no AE-related death. The grade 3-4 leukopenia rate was similar in the two groups (4.3% vs. 6.5%). Conclusions: Anti-PD-1 therapy plus chemotherapy prolonged the PFS compared with chemotherapy alone in advanced BTC with controllable AEs. Further clinical trials are needed to confirm this result.

12.
Front Oncol ; 11: 655716, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211839

RESUMO

Background: Biomarkers such as prevailing PD-L1 expression and TMB have been proposed as a way of predicting the outcome of immunotherapy in patients with advanced gastric cancer (AGC) and metastatic gastric cancer (MGC). Our study aims to investigate whether there is a link between pretreatment hemoglobin (Hb) levels and survival to immunotherapy in patients with AGC and MGC. Methods: We retrospectively reviewed patients with AGC or MGC treated at the oncology department of the Chinese PLA general hospital receiving PD-1 inhibitor. The Propensity Score Matching (PSM) (1:1) was performed to balance potential baseline confounding factors. Progression-free survival (PFS) and overall survival (OS) was analyzed among different Hb level (normal Hb group and decreased Hb group). Objective response rate (ORR), disease control rate (DCR) were also analyzed. Univariate analysis and multivariate analysis were performed further to validate the prognostic value of Hb level. Results: We included 137 patients with AGC and MGC who received PD-1 inhibitors (including Pembrolizumab, Nivolumab, Sintilimab, Toripalimab) in this study. After PSM matching, there were no significant differences between the two groups for baseline characteristics. Within the matched cohort, the median PFS was 7.8 months in the normal Hb level group and 4.3 months in the decreased Hb group (HR 95% CI 0.5(0.31, 0.81), P=0.004). The OS was 14.4 months with normal Hb level as compared with 8.2 months with decreased Hb level(HR 95% CI 0.59(0.37, 0.94), P=0.024). The ORR was 40.7% and DCR was 83.0% in the normal Hb group, while the ORR was 25.5% and DCR was 85.1% in the decreased Hb group. No significant differences were found in the ORR and DCR between the two groups (P=0.127, P=0.779). Univariate analysis and multivariate analysis showed that Hb level was only independent predictor for PFS and baseline Hb level was significant prognostic factor influencing the OS. Only when patients had normal Hb level, anti-pd-1 monotherapy or combined with chemotherapy was superior to anti-pd-1 plus anti-angiogenic therapy with respect to PFS (10.3 m vs 2.8 m, HR 95% CI 0.37(0.15, 0.95), P=0.031) and OS(15 m vs 5.7 m, HR 95% CI 0.21 (0.08, 0.58), P=0.001). Conclusions: Our study have demonstrated that pretreatment Hb level was an independent prognostic biomarker in term of PFS and OS with immunotherapy for AGC and MGC patients. Correction of anemia for GC patients as immunotherapy would be a strategy to improve the survival. More data was warranted to further influence this finding.

13.
mBio ; 12(3): e0145721, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34154409

RESUMO

Human-pathogenic Yersinia species employ a plasmid-encoded type III secretion system (T3SS) to negate immune cell function during infection. A critical element in this process is the coordinated regulation of T3SS gene expression, which involves both transcriptional and posttranscriptional mechanisms. LcrQ is one of the earliest identified negative regulators of Yersinia T3SS, but its regulatory mechanism is still unclear. In a previous study, we showed that LcrQ antagonizes the activation role played by the master transcriptional regulator LcrF. In this study, we confirm that LcrQ directly interacts with LcrH, the chaperone of YopD, to facilitate the negative regulatory role of the YopD-LcrH complex in repressing lcrF expression at the posttranscriptional level. Negative regulation is strictly dependent on the YopD-LcrH complex, more so than on LcrQ. The YopD-LcrH complex helps to retain cytoplasmic levels of LcrQ to facilitate the negative regulatory effect. Interestingly, RNase E and its associated protein RhlB participate in this negative regulatory loop through a direct interaction with LcrH and LcrQ. Hence, we present a negative regulatory loop that physically connects LcrQ to the posttranscriptional regulation of LcrF, and this mechanism incorporates RNase E involved in mRNA decay. IMPORTANCE All three human-pathogenic Yesinia species, Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis, employ a plasmid-encoded T3SS to target immunomodulatory effectors into host immune cells. Several plasmid-encoded regulators influence T3SS control, including the master transcriptional activator LcrF, the posttranscriptional repressor YopD, and the unassigned negative regulatory factor LcrQ. Since LcrQ lacks any obvious DNA or RNA binding domains, its regulatory mechanism might be special. In this study, we screened for proteins that directly engaged with LcrQ. We found that LcrQ cooperates with LcrH of the YopD-LcrH complex to aid in the posttranscriptional repression of lcrF expression. This negative-control loop also involved the mRNA decay factor RNase E and its associated RhlB protein, which were recruited to the regulatory complex by both LcrQ and LcrH. Hence, we identify interacting components of LcrQ that shed new light on a mechanism inhibiting T3SS production and biogenesis.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Regulação Bacteriana da Expressão Gênica , Chaperonas Moleculares/genética , Sistemas de Secreção Tipo III/genética , Yersinia pseudotuberculosis/genética , Yersinia pseudotuberculosis/metabolismo , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo , Endorribonucleases/metabolismo , Humanos , Chaperonas Moleculares/metabolismo , Sistemas de Secreção Tipo III/metabolismo
14.
Malays J Med Sci ; 28(2): 161-170, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33958970

RESUMO

Background: Specific language impairment (SLI) diagnosis is inconvenient due to manual procedures and hardware cost. Computer-aided SLI diagnosis has been proposed to counter these inconveniences. This study focuses on evaluating the feasibility of computer systems used to diagnose SLI. Methods: The accuracy of Webgazer.js for software-based gaze tracking is tested under different lighting conditions. Predefined time delays of a prototype diagnosis task automation script are contrasted against with manual delays based on human time estimation to understand how automation influences diagnosis accuracy. SLI diagnosis binary classifier was built and tested based on randomised parameters. The obtained results were cross-compared to Singlims_ES.exe for equality. Results: Webgazer.js achieved an average accuracy of 88.755% under global lighting conditions, 61.379% under low lighting conditions and 52.7% under face-focused lighting conditions. The diagnosis task automation script found to execute with actual time delays with a deviation percentage no more than 0.04%, while manually executing time delays based on human time estimation resulted in a deviation percentage of not more than 3.37%. One-tailed test probability value produced by both the newly built classifier and Singlims_ES were observed to be similar up to three decimal places. Conclusion: The results obtained should serve as a foundation for further evaluation of computer tools to help speech language pathologists diagnose SLI.

15.
J Med Chem ; 64(9): 5973-6007, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33906348

RESUMO

Dimeric bile acid derivatives (DBADs) were developed and tested for their anti-HBV and anti-HDV activities as sodium taurocholate cotransporting polypeptide (NTCP) inhibitors. DBADs exhibited strong and persistent potency of NTCP inhibition, whereas diverse linkers and constitutions showed distinct inhibition features. Motif aa157-165 on NTCP was shown to be a possible binding site of DBADs; therefore, we determined DBADs' selectivity among NTCPs from different species. A cyclized DBAD scaffold DBA-41 exhibited a high affinity to human NTCP (hNTCP). Intraperitoneal administration of DBA-41 to hNTCP-tg mice induced serum total bile acid elevation. DBA-41 may serve as a biological tool to study NTCP physiological function.


Assuntos
Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/farmacologia , Dimerização , Desenho de Fármacos , Transportadores de Ânions Orgânicos Dependentes de Sódio/antagonistas & inibidores , Simportadores/antagonistas & inibidores , Animais , Ácidos e Sais Biliares/sangue , Humanos , Camundongos , Relação Estrutura-Atividade
16.
Nat Ecol Evol ; 5(5): 600-608, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33649547

RESUMO

Bats are the suggested natural hosts for severe acute respiratory syndrome coronavirus (SARS-CoV) and the causal agent of the coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2. The interaction of viral spike proteins with their host receptor angiotensin-converting enzyme 2 (ACE2) is a critical determinant of potential hosts and cross-species transmission. Here we use virus-host receptor binding and infection assays to examine 46 ACE2 orthologues from phylogenetically diverse bat species, including those in close and distant contact with humans. We found that 24, 21 and 16 of them failed to support infection by SARS-CoV, SARS-CoV-2 or both viruses, respectively. Furthermore, we confirmed that infection assays in human cells were consistent with those in two bat cell lines. Additionally, we used genetic and functional analyses to identify critical residues in bat ACE2 receptors associated with viral entry restrictions. Our results suggest that many bat species may not be the potential hosts of one or both viruses and that no correlation was identified between proximity to humans and probability of being natural hosts of SARS-CoV or SARS-CoV-2. This study demonstrates dramatic variation in susceptibility to SARS-CoV and SARS-CoV-2 infection among bat species and adds knowledge towards a better understanding of coronavirus-bat interaction.


Assuntos
COVID-19 , Quirópteros , Enzima de Conversão de Angiotensina 2 , Animais , Humanos , Peptidil Dipeptidase A/genética , Receptores Virais/genética , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
17.
Science ; 371(6535): 1257-1260, 2021 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-33737487

RESUMO

Tandem catalysis couples multiple reactions and promises to improve chemical processing, but precise spatiotemporal control over reactive intermediates remains elusive. We used atomic layer deposition to grow In2O3 over Pt/Al2O3, and this nanostructure kinetically couples the domains through surface hydrogen atom transfer, resulting in propane dehydrogenation (PDH) to propylene by platinum, then selective hydrogen combustion by In2O3, without excessive hydrocarbon combustion. Other nanostructures, including platinum on In2O3 or platinum mixed with In2O3, favor propane combustion because they cannot organize the reactions sequentially. The net effect is rapid and stable oxidative dehydrogenation of propane at high per-pass yields exceeding the PDH equilibrium. Tandem catalysis using this nanoscale overcoating geometry is validated as an opportunity for highly selective catalytic performance in a grand challenge reaction.

18.
J Food Biochem ; 45(4): e13685, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33682148

RESUMO

Date plum persimmon (Diospyros lotus L.) is a fruit crop from the Ebenaceae family. Its microorganism-fermented extract (DPEML) was shown to exhibit a hypoglycemic effect in our previous work. Here, we investigated the effects of DPEML fermented by Microbacterium flavum YM18-098 and Lactobacillus plantarum B7 on the high glucose-induced apoptosis of MIN6 cells and explored its potential cell protective mechanisms. DPEML ameliorated the apoptosis of MIN6 cells cultured under high glucose conditions, thereby improving cell viability. DPEML upregulated the Bcl-2/Bax mRNA ratio to obstruct an intrinsic apoptotic pathway and concomitantly downregulated the expression of the apoptosis-linked proteins, AIF, and Cyt-C, in high glucose-induced MIN6 cells. Furthermore, DPEML promoted the insulin secretion of MIN6 cells grown under chronically high-glucose conditions by upregulating Ins mRNA expression. In summary, our study suggested that DPEML is a promising functional food for the development of therapeutics for the treatment of Type 2 diabetes mellitus. PRACTICAL APPLICATIONS: We investigated the effects of DPEML fermented by Microbacterium flavum YM18-098 and Lactobacillus plantarum B7 on the high glucose-induced apoptosis of MIN6 cells and explored its potential cell protective mechanisms. DPEML ameliorated the apoptosis of MIN6 cells cultured under high glucose conditions, thereby improving cell viability. DPEML upregulated the Bcl-2/Bax mRNA ratio to obstruct an intrinsic apoptotic pathway and concomitantly downregulated the expression of the apoptosis-linked proteins, AIF and Cyt-C, in high glucose-induced MIN6 cells. Furthermore, DPEML promoted the insulin secretion of MIN6 cells grown under chronically high-glucose conditions by upregulating Ins mRNA expression. We suggested that DPEML is a promising functional food for the development of therapeutics for the treatment of Type 2 diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 2 , Diospyros , Células Secretoras de Insulina , Apoptose , Glucose , Extratos Vegetais/farmacologia
19.
Cell Res ; 31(4): 395-403, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33603116

RESUMO

The upcoming flu season in the Northern Hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental coinfection with influenza A virus (IAV) and either pseudotyped or live SARS-CoV-2 virus, we found that IAV preinfection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, in vivo, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice coinfected with IAV. Moreover, such enhancement of SARS-CoV-2 infectivity was not observed with several other respiratory viruses, likely due to a unique feature of IAV to elevate ACE2 expression. This study illustrates that IAV has a unique ability to aggravate SARS-CoV-2 infection, and thus, prevention of IAV infection is of great significance during the COVID-19 pandemic.


Assuntos
COVID-19/patologia , Coinfecção/patologia , Vírus da Influenza A/fisiologia , Infecções por Orthomyxoviridae/patologia , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/deficiência , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Animais , COVID-19/virologia , Catepsina L/genética , Catepsina L/metabolismo , Linhagem Celular , Coinfecção/virologia , Humanos , Vírus da Influenza A/isolamento & purificação , Pulmão/patologia , Camundongos , Camundongos Transgênicos , Infecções por Orthomyxoviridae/virologia , RNA Guia/metabolismo , SARS-CoV-2/isolamento & purificação , Serina Endopeptidases/genética , Serina Endopeptidases/metabolismo , Índice de Gravidade de Doença , Carga Viral , Internalização do Vírus
20.
Eur J Obstet Gynecol Reprod Biol ; 257: 138-143, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33419589

RESUMO

OBJECTIVES: Our aim was to generalize the available evidence and evaluate the effectiveness of acupuncture for urinary incontinence in middle-aged and elderly women. METHODS: Six databases including VIP, CNKI, Wan Fang, Web of Science, PubMed and The Cochrane Library were systematically searched to retrieve similar studies updated to December 2019 to gather RCTs regarding the effectiveness of acupuncture for middle-aged and elderly women with urinary incontinence. Two researchers independently performed the whole process of retrieving the studies, extracting the data and assessing the risk of bias of the included studies. The current meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of eight studies with 607 patients were included in the evaluation. The current meta-analysis showed that Compared with rehabilitation exercise or medication, acupuncture intervention significantly improved the clinical effectiveness (OR = 5.52, 95 % CI, 3.13-9.73), reduced the urine leakage in pad test (SMD = -2.67, 95 % CI, -4.05 to -1.29) and decrease the ICIQ-SF score (MD = -3.46, 95 % CI, -3.69 to -3.22). The results indicated that acupuncture intervention can help the patients alleviate the symptoms effectively. CONCLUSION: Based on this study, acupuncture intervention of stress urinary incontinence in middle-aged and elderly women can improve the clinical effectiveness, reduce the urine leakage in pad test and ICIQ-SF score. More high-quality studies with large sample size are required for further verification.


Assuntos
Terapia por Acupuntura , Incontinência Urinária por Estresse , Incontinência Urinária , Idoso , Terapia por Exercício , Feminino , Humanos , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Incontinência Urinária/terapia
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