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1.
Chem Asian J ; 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35575910

RESUMO

Despite the continuous efforts, the current repertoire of detergents is still far from sufficient for the biophysics studies of membrane proteins (MPs). Toward the rapid expansion of detergent diversity, we herein report a new strategy based on Ugi reaction mediated modular assembly. Structural varieties, including hydrophobic tails and hydrophilic heads, could be conveniently introduced from the multiple reaction components. New detergents then were comprehensively evaluated in the physical properties and preliminarily screened by the thermal stabilization for a transporter MsbA and a spectrum of G protein-coupled receptors (GPCRs). For the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR, detergent M-23-M finally stood out in a second evaluation for the maintenance of homogeneity and was further illustrated its application in the improvement of NMR study. Besides the promising utility in the MP study, the current results exhibit intriguing structural-physical relationship that would allow the guidance in the tuning of detergent properties in the future.

2.
Chemistry ; 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608006

RESUMO

Detergents are the most frequently applied reagents in membrane protein (MP) studies. The limited diversity of one-head-one-tailed traditional detergents however, is far from sufficient for structurally distinct MPs. Expansion of detergent repertoire has a continuous momentum. In line with the speculation that detergent pre-assembly exerts superiority, herein we for the first time report cross-conjugation of two series of monomeric detergents for constructing a two-dimensional library of dimeric detergents. Optimum detergents stood out with unique preferences in the systematic evaluation of individual MPs. Furthermore, unprecedented hybrid detergents 14M8G and 14M9G enabled high-quality EM study of transporter MsbA and NMR study of G protein-coupled receptor A 2A AR, respectively. Given the abundance of cross-coupling chemistries, comprehensive diversity could be readily covered that would facilitate the finding of new detergents for the manipulation of thorny MPs and innovation of the functional and structural study in future.

3.
Int J Audiol ; : 1-9, 2022 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-35608224

RESUMO

OBJECTIVE: To explore trajectories of receptive and expressive vocabulary in Mandarin-speaking children under the age of 4 years, fitted with cochlear implants (CIs). DESIGN: Vocabulary trajectories were measured at baseline, 3, 6, and 12 months after implantation using the Chinese version of the MacArthur-Bates Communicative Development Inventory. STUDY SAMPLE: There were 216 children with CIs in West China Hospital who took part and were divided into three groups based on age at first CI. RESULTS: Receptive and expressive vocabulary scores of the younger implantation group were significantly different from the older groups at baseline. After 12 months of implant use, there were no significant differences between all groups. Furthermore receptive vocabulary trajectories for all children with CIs were not significantly different from those of children with normal hearing. However, expressive vocabulary trajectories were poorer when compared to children with normal hearing. Significant differences were seen between receptive and expressive vocabulary in all age groups. CONCLUSIONS: This study suggests no differences in vocabulary trajectories in Mandarin-speaking children whether they received their first CI at 1, 2, or 3 years of age. It is important that clinicians convey realistic expectations about potential differences in receptive vs. expressive trajectories for Mandarin-speaking children fitted with CIs.

4.
Lupus ; : 9612033221097812, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35499216

RESUMO

OBJECTIVE: To observe the efficacy and safety of telitacicept in refractory childhood-onset systemic lupus erythematosus (cSLE). METHODS: A self-controlled before-after trial. Children with active SLE, aged 5-18 years, who cannot tolerate side effects of glucocorticoid, were enrolled in our study. Patients received subcutaneous injection of telitacicept weekly based on the standard treatment. SLE responder index-4 (SRI-4) was assessed before the first administration and at least 4 weeks after the first administration. RESULTS: Among the 15 cases of refractory cSLE, three were males (20%) and 12 were females (80%). The median age and weight were 13 years old and 52 kg, respectively. The median duration of disease was 30 months. 5-26 weeks (80 or 160 mg per week) after administration of telitacicept, 66.7% (n=10) reached SRI-4 response. 12 cases reduced their glucocorticoid intake from 40 mg/d to 17.5 mg/d. The urinary protein after treatment declined in 8 cases whose 24-h proteinuria was >0.5 g at baseline. The urinary protein in two of the eight cases turned negative and plasma albumin in five of the eight cases rose to normal. In addition, three of these eight cases demonstrated varying degrees of improvement in renal impairment, whose estimated glomerular filtration rate (eGFR, ml/min·1.73 m2) rose from 17.4 to 26.6, 40.7 to 48.2, and 63.2 to 146.0, respectively. There were mild to moderate adverse events after treatment. CONCLUSION: Telitacicept combined with the standard treatment may significantly increase the SRI-4 response rate and reduce the glucocorticoid dosage in refractory cSLE, and also shown efficacy on lupus nephritis. The related adverse drug events were controllable.

5.
Genes Brain Behav ; : e12806, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35535862

RESUMO

To explore the role of intestinal microbiota on the occurrence of depression-like behavior. Twenty male adult Wistar rats were randomly divided into control and experimental groups. Depression-like behavior of the rats was validated using sucrose preference test (SPT) and forced swimming test (FST) after chronic unpredictable mild stress (CUMS) for 3 weeks. Fecal microbiota was analyzed through 16S rRNA sequence analysis. The levels of 5-HT and inflammatory factors in the colon, brain and sera were measured using enzyme-linked immunosorbent assay (ELISA), quantitative PCR (qPCR) and western blotting analyses. The percentage of different types of immune cells in the peripheral blood was determined through flow cytometry. CUMS caused depression-like symptoms, including anhedonia and desperate behavior. Significant differences were found in the structure and abundance of intestinal microbiota. CUMS intervention significantly increased the levels of 5-HT and Tph1 in the colon and decreased the level of Scl6a4. The concentrations of 5-HT and Tph2 in the prefrontal and hippocampal tissues were lower, while IDO1 was higher. Certain cytokines, such as IL-6, IL-1 and TNF-ɑ, were significantly elevated in peripheral blood, while the percentage of CD3+ CD4+ double-positive cells and CD4+ /CD8+ ratio were downregulated in the CUMS group. Pearson correlation analysis showed that intestinal microbiota was significantly associated with not only the metabolism of 5-HT in intestinal and brain tissues, but also with the proportion of immune cells and certain cytokines. Stress can lead to disturbances in the intestinal microbial structure, which may contribute to depression by interfering with 5-HT metabolism and immune inflammatory responses.

6.
Plant Commun ; : 100304, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35605195

RESUMO

Triticeae species, including wheat, barley, and rye, are critical for global food security. Mapping agronomically important genes is crucial for elucidating molecular mechanisms and improving crops. However, Triticeae includes many wild relatives with desirable agronomic traits, and frequent introgressions occurred during Triticeae evolution and domestication. Thus, Triticeae genomes are generally large and complex, making the localization of genes or functional elements that control agronomic traits challenging. Here, we developed Triti-Map, which contains a suite of user-friendly computational packages specifically designed and optimized to overcome the obstacles of gene mapping in Triticeae, as well as a web interface integrating multi-omics data from Triticeae for the efficient mining of genes or functional elements that control particular traits. The Triti-Map pipeline accepts both DNA and RNA bulk-segregated sequencing data as well as traditional QTL data as inputs for locating genes and elucidating their functions. We illustrate the usage of Triti-Map with a combination of bulk-segregated ChIP-seq data to detect a wheat disease-resistance gene with its promoter sequence that is absent from the reference genome and clarify its evolutionary process. We hope that Triti-Map will facilitate gene isolation and accelerate Triticeae breeding.

7.
Environ Pollut ; : 119510, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35605830

RESUMO

Atmospheric nitrogen dioxide (NO2) is an important reactive gas pollutant harmful to human health. The spatiotemporal coverage provided by traditional NO2 monitoring methods is insufficient, especially in the suburban and rural areas of north China, which have a high population density and experience severe air pollution. In this study, we implemented a spatiotemporal neural network (STNN) model to estimate surface NO2 from multiple sources of information, which included satellite and in situ measurements as well as meteorological and geographical data. The STNN predicted NO2 with high accuracy, with a coefficient of determination (R2) of 0.89 and a root mean squared error of 5.8 µg/m3 for sample-based 10-fold cross-validation. Based on the surface NO2 concentration determined by the STNN, we analyzed the spatial distribution and temporal trends of NO2 pollution in north China. We found substantial drops in surface NO2 concentrations ranging between 9.1% and 33.2% for large cities during the 2020 COVID-19 lockdown when compared to those in 2019. Moreover, we estimated the all-cause deaths attributed to NO2 exposure at a high spatial resolution of about 1 km, with totals of 6082, 4200, and 18,210 for Beijing, Tianjin, and Hebei Provinces in 2020, respectively. We observed remarkable regional differences in the health impacts due to NO2 among urban, suburban, and rural areas. Generally, the STNN model could incorporate spatiotemporal neighboring information and infer surface NO2 concentration with full coverage and high accuracy. Compared with machine learning regression techniques, STNN can effectively avoid model overfitting and simultaneously consider both spatial and temporal correlations of input variables using deep convolutional networks with residual blocks. The use of the proposed STNN model, as well as the surface NO2 dataset, can benefit air quality monitoring, forecasting, and health burden assessments.

8.
Artigo em Inglês | MEDLINE | ID: mdl-35576553

RESUMO

Chiral ß-hydroxysulfides are an important class of organic compounds which find broad application in organic and pharmaceutical chemistry. Herein we describe the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of ß-hydroxysulfides by exploiting ketoreductase (KRED) enzymes. Four KREDs were discovered from a pool of 384 enzymes identified and isolated through a metagenomic approach. KRED311 and KRED349 catalysed the synthesis of ß-hydroxysulfides bearing a stereocentre at the C-O bond with opposite absolute configurations and excellent ee values by novel chemoenzymatic and biocatalytic-chemical-biocatalytic (bio-chem-bio) cascades starting from commercially available thiophenols/thiols and α-haloketones/alcohols. KRED253 and KRED384 catalysed the enantioselective synthesis of ß-hydroxysulfides bearing a stereocentre at the C-S bond with opposite enantioselectivities by dynamic kinetic resolution (DKR) of racemic α-thioaldehydes.

9.
Bioengineered ; 13(5): 12275-12288, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35603354

RESUMO

Diabetic nephropathy (DN) is a complication of diabetes. This study sought to explore the mechanism of triptolide (TP) in podocyte injury in DN. DN mice were induced by high-fat diet&streptozocin and treated with TP. Fasting blood glucose, 24 h urine microalbumin (UMA), the pathological changes of renal tissues, and ultrastructure of renal podocytes were observed. Podocytes (MPC5) were induced by high-glucose (HG) in vitro and treated with TP or microRNA (miR)-155-5p mimics, with Irbesartan as positive control. Reactive oxygen species (ROS) and levels of oxidative stress (OS) and inflammatory factors in MPC5 were detected. The levels of miR-155-5p, podocyte marker protein Nephrin, and inflammatory factors in mice and MPC5 were detected. The targeting relationship between miR-155-5p and brain-derived neurotrophic factor (BDNF) was verified. The expression levels of BDNF were detected. miR-155-5p mimics and overexpressed (oe)-BDNF plasmids were co-transfected into mouse podocytes treated with HG and TP. TP reduced fasting glucose and 24 h UMA of DN mice, alleviated the pathological damage and podocyte injury, up-regulated Nephrin level, and down-regulated miR-155-5p. TP down-regulated the high expression of miR-155-5p in HG-induced MPC5 cells and inhibited HG-induced OS and inflammatory injury, and the improvement effect of TP was better than Irbesartan. Overexpression of miR-155-5p reversed the protective effect of TP on injured mouse podocytes. miR-155-5p targeted BDNF. oe-BDNF reversed the inhibitory effect of oe-miR-155-5p on TP protection on podocyte injury in mice. Overall, TP up-regulated BDNF by inhibiting miR-155-5p, thus inhibiting OS and inflammatory damage and alleviating podocyte injury in DN mice.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , Podócitos , Animais , Apoptose/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Diabetes Mellitus/patologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Diterpenos , Compostos de Epóxi , Glucose/metabolismo , Inflamação/metabolismo , Irbesartana/farmacologia , Camundongos , MicroRNAs/metabolismo , Estresse Oxidativo , Fenantrenos , Podócitos/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-35428408

RESUMO

Investigations on the effects of newly constructed glucose-PEG2000-DSPE modified carbamazepine nano system on oxidative stress damage and cell apoptosis in epilepsy. The nano system was constructed by egg yolk lecithin, cholesterol, GLUPEG2000-DSPE, and carbamazepine as per the molar ratio of 95:20:5:6.35. The particle size, zeta potential, and release rate of carbamazepine was determined using a microscope and a microplate reader. The cells toxicity was detected for determine the optimal concentration of carbamazepine nano system. Cell uptake, cell apoptosis ratio and ROS level was determined by flow cytometry analysis. The in vivo studies were performed using male Wistar rats. H&E staining was employed for histological evaluation. Immunofluorescence was utilized for measure the expression level of GLUT1. ELISA assay was obtained for detecting the levels of SOD, GSH-Px and MDA. The results shown the average particle size was 108.57 ± 3.42 nm, and the mean zeta potential was -52.75 ± 1.48 mV. The modified carbamazepine liposomes exhibited higher release rate. Cell uptake indicated that carbamazepine nano system could be successfully internalized into cells. Flow cytometry analysis revealed the carbamazepine nano system dramatically decreased cell apoptosis rate and downregulated ROS level. Moreover, carbamazepine nano system improved histological status, increased GLUT1 expression and decreased oxidative stress in vivo. In conclusion, glucose-PEG2000-DSPE modified carbamazepine nano system ameliorated cell apoptosis and oxidative stress damage in epilepsy.

11.
Insects ; 13(4)2022 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-35447751

RESUMO

Daily temperature amplitudes (DTAs) significantly affect the ecological and physiological traits of insects. Most studies in this field are based on laboratory experiments, while there is limited research on the effects of changes in DTA on insect phenotypic plasticity under natural conditions. Therefore, we studied the acclimation effects of DTA on the longevity, total fecundity, early fecundity, and the thermal tolerance of adult diamondback moths (Plutella xylostella L.) under naturally occurring environmental conditions. As DTAs increased, male longevity and total fecundity decreased, and early fecundity increased. An increase in DTA was significantly associated with the increased heat coma temperature (CTmax) of both males and females, but had no significant effect on their cold coma temperature (CTmin). Our findings highlight the effects of DTA on the acclimation response of P. xylostella and emphasize the importance of considering DTA in predicting models for assessing insect populations and the effects of climate change.

12.
Front Surg ; 9: 872112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478726

RESUMO

Objective: To investigate the efficacy of bevacizumab combined with chemotherapy in the treatment of colorectal cancer (CRC) and to analyze the effects on brain peptides, intestinal flora, and oxidative stress in CRC patients. Methods: Eighty two patients with CRC who were admitted to our hospital from March 2018 to June 2021 were selected as the research subjects and divided into the control group (n = 41) and the observation group (n = 41). The control group was treated with XELOX chemotherapy, and the observation group was additionally treated with bevacizumab, which was repeated every 3 weeks for a total of two treatments. The therapeutic effects of the two groups were evaluated after treatment. The brain-gut peptide index, intestinal flora index and oxidative stress index were detected, and the adverse reactions of the two groups were recorded. Results: In the control group, ER was 36.59% (15/41) and DCR was 73.17% (30/41). In the observation group, ER was 63.41% (26/41) and DCR was 90.24% (37/41). ER and DCR in the observation group were higher than those in the control group (P < 0.05). After treatment, the levels of motilin and gastrin in the observation group were lower than those in the control group, and ghrelin was higher than that in the control group (P < 0.05). After treatment, the levels of Bifidobacterium, Lactobacilli and Enterococcus in the observation group were higher than those in the control group, and the level of Escherichia coli was lower than that in the control group (P < 0.05). After treatment, the SOD level of the observation group was lower than that of the control group, and the MDA level was higher than that of the control group. Conclusion: Bevacizumab combined with chemotherapy has good efficacy in the treatment of colorectal cancer patients, which can effectively improve the gastrointestinal motility of patients, regulate the intestinal flora of the body, rebuild the microecological balance, effectively reduce the oxidative stress response of patients, and reduce the incidence of adverse reactions.

13.
Bioorg Med Chem Lett ; 68: 128761, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35483593

RESUMO

Resistance to telithromycin and off-target effects associated with the metabolic instability present serious and challenging problems for the development of novel macrolides. Herein, studies of hybrids of macrolides and quinolones (termed macrolones) bridged with linkers from 11,12-cyclic carbamate of macrolides revealed different structure-activity relationships from the previously reported macrolones bridged with linkers derived from 6-, 9- and 4''-positions of macrolides. The optimized macrolone 34 g with a longer and rigid sidechain than telithromycin had improved metabolic stability compared to telithromycin (t1/2: 110 vs 32 min), whose future has been heavily clouded by metabolic issues. Moreover, 34 g was 38-fold more potent than telithromycin against A2058/2059-mutated Mycoplasma pneumoniae (8 vs 315 µM), which may be attributed to a novel mode of action between the carboxylic acid of quinolone moiety and the bacterial ribosome. This work increases the prospect for discovery of novel and safe antibacterial agents to combat serious human infectious diseases.


Assuntos
Cetolídeos , Quinolonas , Antibacterianos/farmacologia , Humanos , Cetolídeos/farmacologia , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Mycoplasma pneumoniae , Quinolonas/farmacologia , Relação Estrutura-Atividade
14.
Int J Mol Sci ; 23(8)2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35456943

RESUMO

Plant growth and development are greatly affected by the environment. Many genes have been identified to be involved in regulating plant development and adaption of abiotic stress. Apart from protein-coding genes, more and more evidence indicates that non-coding RNAs (ncRNAs), including small RNAs and long ncRNAs (lncRNAs), can target plant developmental and stress-responsive mRNAs, regulatory genes, DNA regulatory regions, and proteins to regulate the transcription of various genes at the transcriptional, posttranscriptional, and epigenetic level. Currently, the molecular regulatory mechanisms of sRNAs and lncRNAs controlling plant development and abiotic response are being deeply explored. In this review, we summarize the recent research progress of small RNAs and lncRNAs in plants, focusing on the signal factors, expression characters, targets functions, and interplay network of ncRNAs and their targets in plant development and abiotic stress responses. The complex molecular regulatory pathways among small RNAs, lncRNAs, and targets in plants are also discussed. Understanding molecular mechanisms and functional implications of ncRNAs in various abiotic stress responses and development will benefit us in regard to the use of ncRNAs as potential character-determining factors in molecular plant breeding.


Assuntos
RNA Longo não Codificante , Regulação da Expressão Gênica de Plantas , Desenvolvimento Vegetal/genética , Plantas/genética , Plantas/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA de Plantas/genética , RNA de Plantas/metabolismo , RNA não Traduzido/genética , Estresse Fisiológico/genética
15.
Front Immunol ; 13: 791799, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401532

RESUMO

Yersinia pestis, the cause of plague, is a newly evolved Gram-negative bacterium. Through the acquisition of the plasminogen activator (Pla), Y. pestis gained the means to rapidly disseminate throughout its mammalian hosts. It was suggested that Y. pestis utilizes Pla to interact with the DEC-205 (CD205) receptor on antigen-presenting cells (APCs) to initiate host dissemination and infection. However, the evolutionary origin of Pla has not been fully elucidated. The PgtE enzyme of Salmonella enterica, involved in host dissemination, shows sequence similarity with the Y. pestis Pla. In this study, we demonstrated that both Escherichia coli K-12 and Y. pestis bacteria expressing the PgtE-protein were able to interact with primary alveolar macrophages and DEC-205-transfected CHO cells. The interaction between PgtE-expressing bacteria and DEC-205-expressing transfectants could be inhibited by the application of an anti-DEC-205 antibody. Moreover, PgtE-expressing Y. pestis partially re-gained the ability to promote host dissemination and infection. In conclusion, the DEC-205-PgtE interaction plays a role in promoting the dissemination and infection of Y. pestis, suggesting that Pla and the PgtE of S. enterica might share a common evolutionary origin.


Assuntos
Escherichia coli K12 , Salmonella enterica , Yersinia pestis , Animais , Proteínas de Bactérias/genética , Cricetinae , Cricetulus , Ativadores de Plasminogênio
16.
Sci Signal ; 15(729): eabg8744, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412852

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the unprecedented coronavirus disease 2019 (COVID-19) pandemic. Critical cases of COVID-19 are characterized by the production of excessive amounts of cytokines and extensive lung damage, which is partially caused by the fusion of SARS-CoV-2-infected pneumocytes. Here, we found that cell fusion caused by the SARS-CoV-2 spike (S) protein induced a type I interferon (IFN) response. This function of the S protein required its cleavage by proteases at the S1/S2 and the S2' sites. We further showed that cell fusion damaged nuclei and resulted in the formation of micronuclei that were sensed by the cytosolic DNA sensor cGAS and led to the activation of its downstream effector STING. Phosphorylation of the transcriptional regulator IRF3 and the expression of IFNB, which encodes a type I IFN, were abrogated in cGAS-deficient fused cells. Moreover, infection with VSV-SARS-CoV-2 also induced cell fusion, DNA damage, and cGAS-STING-dependent expression of IFNB. Together, these results uncover a pathway underlying the IFN response to SARS-CoV-2 infection. Our data suggest a mechanism by which fused pneumocytes in the lungs of patients with COVID-19 may enhance the production of IFNs and other cytokines, thus exacerbating disease severity.


Assuntos
COVID-19 , Interferon Tipo I , COVID-19/genética , Fusão Celular , Citocinas , Humanos , Interferon Tipo I/genética , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
17.
Value Health Reg Issues ; 31: 53-60, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35436633

RESUMO

OBJECTIVES: This study evaluated the psychometric properties of the Mandarin version of the HeartQoL questionnaire, a core ischemic heart disease (IHD) health-related quality of life (HRQL) instrument, in patients with angina, myocardial infarction (MI), and ischemic heart failure (IHF). METHODS: The English version of HeartQoL was translated into Mandarin. A cross-sectional study was then conducted in mainland China using the Mandarin HeartQoL, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale. Factor analysis was used to establish the HeartQoL structure and internal consistency reliability and construct validity were assessed. RESULTS: Patients with IHD (n = 412; angina = 112, MI = 151, and IHF = 149) were enrolled. Significantly higher HeartQoL HRQL scores were reported by patients with either angina or MI than by patients with IHF. The 2-factor structure was confirmed by Mokken scale analysis in the total group with strong H coefficients on the global scale (0.64) and both the physical (0.70) and emotional (0.80) subscales. Internal consistency reliability was strong with Cronbach's α ranging from 0.90 to 0.95. Convergent validity was confirmed with strong correlations between similar physical and mental HeartQoL and Short Form-12 Health Survey subscales ranging from 0.77 to 0.82 with divergent validity confirmed with significantly lower correlations between dissimilar constructs. Discriminative validity was confirmed for 72% of the a priori sociodemographic and clinical hypotheses. CONCLUSIONS: The Mandarin version of the HeartQoL HRQL questionnaire demonstrates acceptable internal consistency reliability and convergent, divergent, and discriminative validity in patients with IHD and in each diagnostic subgroup. The data support the use of the HeartQoL to assess and compare HRQL in Mandarin-speaking patients with IHD.

18.
Front Immunol ; 13: 859380, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444666

RESUMO

Objective: This study aimed to compare the efficacy and safety (infection events) between rituximab (RTX), tacrolimus (TAC), mycophenolate mofetil (MMF), and cyclophosphamide (CYC) as induction therapies in lupus nephritis (LN). Methods: Electronic databases, including PubMed, EMBASE, and the Cochrane Library, were searched from inception up to December 9, 2021. Bayesian network meta-analysis was used to combine the direct and indirect evidence of different drugs for LN patients. The pooled relative effects were shown using odds ratios (ORs) and 95% credible intervals (CrIs). Results: Nineteen studies (1,566 patients) met the inclusion criteria and were selected in the present study. The network meta-analysis reported that no statistically significant differences were found in partial remission (PR) and infection among the four drugs. RTX showed a significantly higher complete remission (CR) than MMF (OR = 2.60, 95% CrI = 1.00-7.10) and seemed to be more effective than CYC (OR = 4.20, 95% CrI = 1.70-14.00). MMF had a better CR than CYC (OR = 1.60, 95% CrI = 1.00-3.20). TAC presented a better overall response than CYC (OR = 3.70, 95% CrI = 1.20-12.00). Regarding CR and overall response, the maximum surface under the cumulative ranking curve (SUCRA) values were 96.94% for RTX and 80.15% for TAC. The maximum SUCRA value of infection reaction was 74.98% for RTX and the minimum value was 30.17% for TAC, respectively. Conclusions: RTX and TAC were the most effective drugs for induction remission in LN. Among the four drugs, TAC had the lowest probability of infection, and RTX showed the highest probability of experiencing an infection. This meta-analysis could not conclude about other adverse events.


Assuntos
Nefrite Lúpica , Teorema de Bayes , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Imunossupressores/uso terapêutico , Nefrite Lúpica/induzido quimicamente , Nefrite Lúpica/tratamento farmacológico , Masculino , Ácido Micofenólico/uso terapêutico , Metanálise em Rede , Rituximab/uso terapêutico , Tacrolimo , Resultado do Tratamento
19.
Dalton Trans ; 51(16): 6226-6234, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35362491

RESUMO

Constructing chiral luminescent systems with both large luminescence dissymmetry factor (glum) and high luminous efficiency has been considered a great challenge. We herein describe a highly efficient approach to sterically stabilize the helical configurations of carbo[5]helicenes for improved CPL properties in a series of π-donor and π-acceptor substituted [5]helicenes (1, 2, 3, 4 and 5). Enabled by the ortho-installation of methyl groups as well as the steric effects of triarylamine (Ar3N) and triarylborane (Ar3B) handles in meta-substituted [5]helicenes, their optical resolution into enantiomers has been accomplished using preparative chiral HPLC. The molecular chirality of [5]helicenes can be transferred to Ar3B and Ar3N as light emitters, which allowed further investigations of their chiroptics, including optical rotation, circular dichroism (CD) and circularly polarized luminescence (CPL). Remarkably, 4 has been demonstrated to display dramatically enhanced CPL performance with a much larger glum (>1.2 × 10-2) and an increased emission quantum efficiency (ΦS = 0.75) compared with the other analogues, as a result of the isomeric tuning of substitutions with differential steric and electronic effects. These experimentally observed CPL activities were rationalized by TD-DFT computations for the angle (θµ,m) between electric and magnetic transition dipole moments in the excited states. In addition, the conspicuous intramolecular donor-acceptor charge transfer led to thermal responses in the emissions of 2 and 4 over a broad temperature range.

20.
Fish Shellfish Immunol ; 123: 207-217, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35278639

RESUMO

Interleukin-21 (IL-21), a crucial immune regulatory molecule, belongs to the common γ-chain family of type I cytokines, and exerts pleiotropic effects on multiple immune cell types in mammals. However, the characteristics and functions of fish IL-21 remain unclear. To further investigate the molecular mechanism of IL-21 in teleosts, we first cloned and identified the IL-21 gene (designated shIL-21) of the snakehead (Channa argus). The full-length open reading frame of shIL-21 is 438 bp in length, and encodes a predicted protein of 145 amino acid residues. A sequence analysis showed that shIL-21 has the typical structural characteristics of other IL-21 proteins, containing four α-helices and four conserved cysteine residues. In a phylogenetic analysis, shIL-21 clustered within a subgroup of IL-21 proteins from other teleost species and shared its closest evolutionary relationship with that of Lates calcarifer. The expression analysis showed that shIL-21 was ubiquitously expressed in all the healthy snakehead tissues tested, albeit at different levels. After infection with Nocardia seriolae or Aeromonas schubertii, the relative expression of shIL-21 was mainly upregulated in the head kidney and spleen in vivo. Similarly, after stimulation with the three pathogen analogues lipoteichoic acid, lipopolysaccharides, and polyinosinic-polycytidylic acid, the expression of shIL-21 was also induced in head kidney leukocytes in vitro. A recombinant shIL-21 protein was expressed and purified, and promoted the proliferation of head kidney leukocytes, induced the expression of genes encoding critical signaling molecules in the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway, including JAK1, JAK3, STAT1, and STAT3, and induced the expression of endogenous shIL-21 and genes encoding several key proinflammatory cytokines (tumor necrosis factor-α, interferon-γ, and IL-1ß). Taken together, these preliminary findings suggest that shIL-21 is involved in the immune defense against bacterial infection, in leukocyte proliferation, and in the activation of the JAK-STAT pathway. They thus extend the functional studies of IL-21 in teleosts.


Assuntos
Doenças dos Peixes , Janus Quinases , Animais , Proliferação de Células , Peixes/genética , Interleucinas/genética , Interleucinas/metabolismo , Janus Quinases/genética , Leucócitos/metabolismo , Mamíferos/metabolismo , Filogenia , Fatores de Transcrição STAT/genética , Transdução de Sinais
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