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1.
PLoS Genet ; 18(2): e1010017, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35108269

RESUMO

Slash pine (Pinus elliottii Engelm.) is an important timber and resin species in the United States, China, Brazil and other countries. Understanding the genetic basis of these traits will accelerate its breeding progress. We carried out a genome-wide association study (GWAS), transcriptome-wide association study (TWAS) and weighted gene co-expression network analysis (WGCNA) for growth, wood quality, and oleoresin traits using 240 unrelated individuals from a Chinese slash pine breeding population. We developed high quality 53,229 single nucleotide polymorphisms (SNPs). Our analysis reveals three main results: (1) the Chinese breeding population can be divided into three genetic groups with a mean inbreeding coefficient of 0.137; (2) 32 SNPs significantly were associated with growth and oleoresin traits, accounting for the phenotypic variance ranging from 12.3% to 21.8% and from 10.6% to 16.7%, respectively; and (3) six genes encoding PeTLP, PeAP2/ERF, PePUP9, PeSLP, PeHSP, and PeOCT1 proteins were identified and validated by quantitative real time polymerase chain reaction for their association with growth and oleoresin traits. These results could be useful for tree breeding and functional studies in advanced slash pine breeding program.


Assuntos
Pinus/crescimento & desenvolvimento , Pinus/genética , Extratos Vegetais/genética , Brasil , China , Expressão Gênica/genética , Regulação da Expressão Gênica de Plantas/genética , Estudo de Associação Genômica Ampla/métodos , Melhoramento Vegetal/métodos , Polimorfismo de Nucleotídeo Único/genética , Transcriptoma/genética , Madeira/genética , Madeira/crescimento & desenvolvimento
2.
J Biol Chem ; 299(8): 104955, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37354973

RESUMO

Recovery from COVID-19 depends on the ability of the host to effectively neutralize virions and infected cells, a process largely driven by antibody-mediated immunity. However, with the newly emerging variants that evade Spike-targeting antibodies, re-infections and breakthrough infections are increasingly common. A full characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mechanisms counteracting antibody-mediated immunity is therefore needed. Here, we report that ORF8 is a virally encoded SARS-CoV-2 factor that controls cellular Spike antigen levels. We show that ORF8 limits the availability of mature Spike by inhibiting host protein synthesis and retaining Spike at the endoplasmic reticulum, reducing cell-surface Spike levels and recognition by anti-SARS-CoV-2 antibodies. In conditions of limited Spike availability, we found ORF8 restricts Spike incorporation during viral assembly, reducing Spike levels in virions. Cell entry of these virions then leaves fewer Spike molecules at the cell surface, limiting antibody recognition of infected cells. Based on these findings, we propose that SARS-CoV-2 variants may adopt an ORF8-dependent strategy that facilitates immune evasion of infected cells for extended viral production.


Assuntos
COVID-19 , Regulação Viral da Expressão Gênica , Evasão da Resposta Imune , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Humanos , Anticorpos Antivirais , COVID-19/imunologia , COVID-19/virologia , Evasão da Resposta Imune/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Regulação Viral da Expressão Gênica/genética , Células A549 , Células HEK293 , Retículo Endoplasmático/virologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-38961609

RESUMO

INTRODUCTION: Previous studies have indicated the association between smooth endoplasmic reticulum aggregates (SERa+) and poorer medically assisted reproduction outcomes. However, the link between SERa+ and neonatal outcomes remains controversial and open for debate. A comprehensive meta-analysis on the relation between SERa+ and the risk of birth defects is needed. MATERIAL AND METHODS: The literature search was conducted using the following databases: PubMed, Embase, Cochrane Libraries, Web of Science, and Chinese databases including China National Knowledge Infrastructure (CNKI) and Wan Fang from inception until July 2023. Risk ratio (RR) and 95% confidence interval (CI) were calculated by a fixed-effected model, while heterogeneity was assessed by forest plots and I2 statistic. Funnel plot was produced to assess publication bias. This meta-analysis has been registered on PROSPERO (CRD42022313387). RESULTS: The search resulted in 122 studies, 14 of which met the inclusion criteria. The analysis of birth defects revealed a higher risk (RR = 2.17, 95%CI 1.24 to 3.81, p = 0.007) in children derived from SERa+ cycle compared to SERa- cycles (711 vs. 4633). Meanwhile, in a subgroup analysis, the risk of birth defects was significantly increased in the SERa+ oocytes group as compared with the sibling SERa- oocytes group (RR = 3.53, 95%CI 1.21 to 10.24, p = 0.02). CONCLUSIONS: To conclude, our analysis indicated that SERa+ cycles/oocytes may have a potential risk of increased additional major birth defects comparing with SERa- cycles/oocytes. This conclusion may provide evidence-based support for clinicians in IVF clinical guidance and embryologists in prudent embryo selection strategy.

4.
Plant Physiol ; 188(1): 241-254, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34609517

RESUMO

Disulfide bonds play essential roles in the folding of secretory and plasma membrane proteins in the endoplasmic reticulum (ER). In eukaryotes, protein disulfide isomerase (PDI) is an enzyme catalyzing the disulfide bond formation and isomerization in substrates. The Arabidopsis (Arabidopsis thaliana) genome encodes diverse PDIs including structurally distinct subgroups PDI-L and PDI-M/S. It remains unclear how these AtPDIs function to catalyze the correct disulfide formation. We found that one Arabidopsis ER oxidoreductin-1 (Ero1), AtERO1, can interact with multiple PDIs. PDI-L members AtPDI2/5/6 mainly serve as an isomerase, while PDI-M/S members AtPDI9/10/11 are more efficient in accepting oxidizing equivalents from AtERO1 and catalyzing disulfide bond formation. Accordingly, the pdi9/10/11 triple mutant exhibited much stronger inhibition than pdi1/2/5/6 quadruple mutant under dithiothreitol treatment, which caused disruption of disulfide bonds in plant proteins. Furthermore, AtPDI2/5 work synergistically with PDI-M/S members in relaying disulfide bonds from AtERO1 to substrates. Our findings reveal the distinct but overlapping roles played by two structurally different AtPDI subgroups in oxidative protein folding in the ER.


Assuntos
Arabidopsis/genética , Arabidopsis/metabolismo , Catálise/efeitos dos fármacos , Dissulfetos/metabolismo , Oxirredução/efeitos dos fármacos , Isomerases de Dissulfetos de Proteínas/metabolismo , Dobramento de Proteína/efeitos dos fármacos , Variação Genética , Genótipo , Mutação , Isomerases de Dissulfetos de Proteínas/genética
5.
Reprod Biol Endocrinol ; 21(1): 82, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667331

RESUMO

BACKGROUND: Actin-like 7 A (ACTL7A) is essential for acrosome formation, fertilization and early embryo development. ACTL7A variants cause acrosome detachment responsible for male infertility and early embryonic arrest. In this study, we aim to explore the additional functions of ACTL7A beyond the process of acrosome biogenesis and investigate the possible underlying mechanisms. METHODS: Nuclear morphology analysis was used to observe the sperm head shape of ACTL7A-mutated patients. Actl7a knock-out (KO) mouse model was generated. Immunofluorescence and transmission electron microscopy (TEM) were performed to analyze the structure of spermatids during spermiogenesis. Tandem mass tags labeling quantitative proteomics strategy was employed to explore the underlying molecular mechanisms. The expression levels of key proteins in the pathway were analyzed by western blotting. Intracytoplasmic sperm injection (ICSI)-artificial oocyte activation (AOA) technology was utilized to overcome fertilization failure in male mice with a complete knockout of Actl7a. RESULTS: The new phenotype of small head sperm associated with loss of ACTL7A in patients was discovered, and further confirmed in Actl7a-KO mice. Immunofluorescence and TEM analyses revealed that the deletion of ACTL7A damaged the formation of acrosome-acroplaxome-manchette complex, leading to abnormalities in the shaping of sperm heads. Moreover, a proteomic analysis of testes from WT and Actl7a-KO mice revealed that differentially expressed genes were notably enriched in PI3K/AKT/mTOR signaling pathway which is strongly associated with autophagy. Inhibition of autophagy via PI3K/AKT/mTOR signaling pathway activation leading to PDLIM1 accumulation might elucidate the hindered development of manchette in Actl7a-KO mice. Remarkably, AOA successfully overcame fertilization failure and allowed for the successful production of healthy offspring from the Actl7a complete knockout male mice. CONCLUSIONS: Loss of ACTL7A causes small head sperm as a result of defective acrosome-acroplaxome-manchette complex via autophagy inhibition. ICSI-AOA is an effective technique to rescue male infertility resulting from ACTL7A deletion. These findings provide essential evidence for the diagnosis and treatment of patients suffering from infertility.


Assuntos
Acrossomo , Actinas , Infertilidade Masculina , Animais , Humanos , Masculino , Camundongos , Infertilidade Masculina/genética , Fosfatidilinositol 3-Quinases , Proteômica , Proteínas Proto-Oncogênicas c-akt/genética , Sêmen , Actinas/genética
6.
Acta Radiol ; 64(9): 2541-2551, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37312501

RESUMO

BACKGROUND: Accurate identification of the histopathological grade and the Ki-67 expression level is important in clinical cases of soft tissue sarcomas (STSs). PURPOSE: To explore the feasibility of a radiomics model based on intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and diffusion kurtosis imaging (DKI) MRI parameter maps in predicting the histopathological grade and Ki-67 expression level of STSs. MATERIAL AND METHODS: In total, 42 patients diagnosed with STSs between May 2018 and January 2020 were selected. The MADC software in Functool of GE ADW 4.7 workstation was used to obtain standard apparent diffusion coefficient (ADC), D, D*, f, mean diffusivity, and mean kurtosis (MK). The histopathological grade and Ki-67 expression level of STSs were identified. The radiomics features of IVIM and DKI parameter maps were used as the dataset. The area under the receiver operating characteristic curve (AUC) and F1-score were calculated. RESULTS: D-SVM achieved the best diagnostic performance for histopathological grade. The AUC in the validation cohort was 0.88 (sensitivity: 0.75 [low level] and 0.83 [high level]; specificity: 0.83 [low level] and 0.75 [high level]; F1-score: 0.75 [low level] and 0.83 [high level]). MK-SVM achieved the best diagnostic performance for Ki-67 expression level. The AUC in the validation cohort was 0.83 (sensitivity: 0.83 [low level] and 0.50 [high level; specificity: 0.50 [low level] and 0.83 [high level]; F1-score: 0.77 [low level] and 0.57 [high level]). CONCLUSION: The proposed radiomics classifier could predict the pathological grade of STSs and the Ki-67 expression level in STSs.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Antígeno Ki-67/metabolismo , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Movimento (Física) , Sarcoma/diagnóstico por imagem
7.
Res Nurs Health ; 46(2): 251-262, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36752308

RESUMO

Learned helplessness (LH) is an important concept in nursing. This study aimed to adapt and translate the Arthritis Helplessness Index scale into a Chinese version of an LH scale for maintenance hemodialysis patients in China (LHS-MHD-C), and to validate its psychometric properties. Data collected included LHS-MHD-C, as well as the Hospital Depression Scale (HADS-D), and the Beck Hopelessness Scale (BHS) for assessing LHS-MHD-C's criterion validity (predictive and concurrent, respectively). The expert consultation and the pilot study demonstrated semantic and conceptual equivalence and content validity (except for Item 3, the item content validity ranged from 0.82 to 1, and the scale content validity was 0.95). An exploratory factor analysis (n = 146) eliminated three items and accepted 11 items for the two factors, explaining 63.87% of the total variance. A CFA (n = 218) showed that the two-factors structure was consistent with the LH theory. The LHS-MHD-C can distinguish between maintenance hemodialysis (MHD) patients of different ages, education, working status, monthly income, and MHD duration. The scale had good concurrent validity with the BHS (r = .78, p < 0.01). Using the HADS-D as a criterion, the LHS-MHD-C showed a sensitivity of 86.2% and a specificity of 96.8%. A total score of 36.5 may be the best cut-off value for predicting MHD patients' depression. The scale showed good reliabilities (Cronbach's α value of .759, test-retest reliability of 0.772, and split-half reliability of 0.774). This study found that the LHS-MHD-C is a reliable and valid scale for assessing Chinese MHD patients' helplessness.


Assuntos
Comparação Transcultural , Desamparo Aprendido , Humanos , Psicometria , Reprodutibilidade dos Testes , Projetos Piloto , Inquéritos e Questionários , Diálise Renal , China
8.
Plant Physiol ; 180(4): 2022-2033, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31138621

RESUMO

Disulfide bonds are essential for the folding of the eukaryotic secretory and membrane proteins in the endoplasmic reticulum (ER), and ER oxidoreductin-1 (Ero1) and its homologs are the major disulfide donors that supply oxidizing equivalents in the ER. Although Ero1 homologs in yeast (Saccharomyces cerevisiae) and mammals have been extensively studied, the mechanisms of plant Ero1 functions are far less understood. Here, we found that both Arabidopsis (Arabidopsis thaliana) ERO1 and its homolog AtERO2 are required for oxidative protein folding in the ER. The outer active site, the inner active site, and a long-range noncatalytic disulfide bond are required for AtERO1's function. Interestingly, AtERO1 and AtERO2 also exhibit significant differences. The ero1 plants are more sensitive to reductive stress than the ero2 plants. In vivo, both AtERO1 and AtERO2 have two distinct oxidized isoforms (Ox1 and Ox2), which are determined by the formation or breakage of the putative regulatory disulfide. AtERO1 is mainly present in the Ox1 redox state, while more AtERO2 exists in the Ox2 state. Furthermore, AtERO1 showed much stronger oxidative protein-folding activity than AtERO2 in vitro. Taken together, both AtERO1 and AtERO2 are required to regulate efficient and faithful oxidative protein folding in the ER, but AtERO1 may serves as the primary sulfhydryl oxidase relative to AtERO2.


Assuntos
Arabidopsis/metabolismo , Retículo Endoplasmático/metabolismo , Proteínas de Arabidopsis/metabolismo , Oxirredução , Dobramento de Proteína , Isoformas de Proteínas/metabolismo , Saccharomyces cerevisiae/metabolismo
9.
Reprod Biol Endocrinol ; 18(1): 27, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32290842

RESUMO

BACKGROUND: The study aimed to investigate whether and how general and partial time intervals between processes, from human chorionic gonadotrophin (HCG) trigger to intracytoplasmic sperm injection (ICSI), affected the laboratory and reproductive outcomes in ICSI cycles. METHODS: This was a retrospective data analysis of 3602 women who underwent ICSI treatment cycles using partner or donor sperms, performed at Reproduction Medicine Center of Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology (Wuhan, China) between October 2016 and September 2018. The clinical pregnancy rate was the major outcome in the study. The fertilization and available embryo rates were secondary outcomes. RESULTS: Data from 3602 consecutive fresh ICSI cycles was analysed. Multivariate linear regression and logistic regression analysis of factors related to fertilization and clinical pregnancy rates showed that fertilization rate (P = 0.001) and clinical pregnancy rate (P = 0.037) were significantly associated with denudation (DN)-ICSI interval. Long DN-ICSI interval was associated with higher rate of fertilization than short DN-ICSI interval but significantly decreased clinical pregnancy rate when the interval is over 4 h (P < 0.05). CONCLUSIONS: DN-ICSI time interval can act as an independent predictor for clinical outcomes in ICSI cycles. The optimal time for ICSI is within 4 h after oocyte denudation for excellent laboratory and reproductive outcomes in ICSI cycles.


Assuntos
Fertilização in vitro/métodos , Recuperação de Oócitos/métodos , Oócitos/fisiologia , Adulto , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas , Fatores de Tempo , Adulto Jovem
10.
Biochem Biophys Res Commun ; 495(1): 1041-1047, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29162449

RESUMO

Protein disulfide isomerases (PDIs) can catalyze disulfide bond formation in nascent secretory proteins and membrane proteins and can introduce correct disulfide bonds into substrate proteins containing mispaired disulfides. The functions of mammalian PDIs have been extensively studied; however, relative to mammalian PDIs, the systematic characterization of PDIs for their oxidoreductase activity in plants is still lacking. Arabidopsis protein disulfide isomerases-11 (AtPDI11), with the structure of a-a'-D, has no ortholog in animals or yeast. In this study, we demonstrated that AtPDI11 has oxidoreductase activity in vitro using a GSSG/GSH-mediated oxidative protein folding system. Moreover, the active site in the a' domain of AtPDI11 is critical for its oxidative folding activity. AtPDI11 is present in four redox forms in vivo, which are determined by the active site cysteines (Cys52 and Cys55 in the a domain, and Cys171 and Cys174 in the a' domain). Genetic evidence suggests that AtPDI11 is required for plant growth under reducing conditions. Our work provides an example for studying the oxidoreductase function of other plant PDIs.


Assuntos
Arabidopsis/enzimologia , Arabidopsis/crescimento & desenvolvimento , Isomerases de Dissulfetos de Proteínas/química , Isomerases de Dissulfetos de Proteínas/metabolismo , Dobramento de Proteína , Arabidopsis/genética , Sítios de Ligação , Ativação Enzimática , Oxirredução , Ligação Proteica , Isomerases de Dissulfetos de Proteínas/ultraestrutura , Domínios Proteicos , Relação Estrutura-Atividade
11.
J Nurs Manag ; 26(8): 1091-1099, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30221422

RESUMO

AIMS: To explore the relationships between work environment, value congruence and nurses' work outcomes; as well as to test the moderating effects of value congruence. BACKGROUND: A poor nursing work environment in most of mainland China has negatively influenced nurses' job satisfaction, burnout and turnover intention. New insights such as improving nurses' value congruence should be proposed to better foster nurses. METHODS: Cross-sectional data were selected from the Chinese Nurses' Environment of Work Status study. In total, 19149 valid samples were collected. Hierarchical regression analyses and simple slope analyses were performed. RESULTS: The correlation coefficients of the variables were all significant (p < .01) and in the expected direction. Value congruence moderated the relationship between nursing work environment and burnout (emotional exhaustion: ß = 0.106, p < .01; depersonalization: ß = 0.111, p < .01). CONCLUSIONS: Nursing work environment and value congruence were positively related to job satisfaction, and negatively related to burnout and turnover intention. The adverse impact of poor work environment on nurses' burnout can be buffered if nurses' value congruence is compatible with that of the organisation. IMPLICATIONS FOR NURSING MANAGEMENT: Except for improving the organisational characteristics, value congruence is a useful concept that managers can leverage to improve positive outcomes for both the organisation and its nurses.


Assuntos
Esgotamento Profissional/complicações , Cuidados de Enfermagem/normas , Local de Trabalho/normas , Adulto , Esgotamento Profissional/psicologia , China , Estudos Transversais , Feminino , Humanos , Satisfação no Emprego , Masculino , Pessoa de Meia-Idade , Cuidados de Enfermagem/métodos , Psicometria/instrumentação , Psicometria/métodos , Valores Sociais , Inquéritos e Questionários , Local de Trabalho/psicologia
12.
J Ethnopharmacol ; 328: 117993, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38423408

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a multi-factorial degenerative disease, and multi-targeted therapies targeting multiple pathogenic mechanisms should be explored. Shenghui decoction (SHD) is an ancient traditional Chinese medicine (TCM) formula used clinically to alleviate AD. However, the precise mechanism of action of SHD as a therapeutic agent for AD remains unclear. AIM OF THE STUDY: This study investigated the neuroprotective properties and potential mechanisms of action of SHD in mitigating AD-like symptoms induced by AlCl3 in a zebrafish model. MATERIALS AND METHODS: Active components of SHD were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Zebrafish were exposed to AlCl3 (200 µg/L) for 30 days to establish an AD zebrafish model. AlCl3-exposed zebrafish were treated with SHD or donepezil. Behavioral tests were used to assess learning and memory, locomotor activity, and AD-related anxiety and aggression in AlCl3-exposed zebrafish. Nissl staining and transmission electron microscopy were used to evaluate histological alterations in brain neurons. The concentrations of pro-inflammatory cytokines (tumor necrosis factor-α, TNF-α; interleukin-1ß, IL-1ß) were quantified using Enzyme-linked immunosorbent assay (ELISA). Markers of oxidative stress and cholinergic activity (acetylcholinesterase, AChE) were detected using biochemical assays. Western blotting and immunofluorescence were used to detect the protein expression levels of Aß, p-tau, PSD-95, synaptophysin, TLR4, phosphorylation of NF-κB p65, p38, and JNK. RESULTS: Fifteen SHD compounds were identified by UPLC-MS/MS analysis. SHD improved AlCl3-induced dyskinesia, learning and memory impairment, anxiety-like behavior, and aggressive behavior in zebrafish. AlCl3-exposed zebrafish showed AD-like pathology, overexpression of Aß, hyperphosphorylated tau protein, marked neuronal damage, decreased expression of synaptic proteins, synaptophysin, and PSD-95, and impairment of synaptic structural plasticity. These effects were reversed by the SHD treatment. We also observed that SHD ameliorated oxidative stress and decreased AChE activity and inflammatory cytokine levels. These effects are similar to those observed for donepezil. Meanwhile, SHD could decrease the protein expression of TLR4 and inhibit phosphorylation of NF-κB, JNK, and p38 MAPK. These results demonstrate that SHD has the potential to exert neuroprotective effects, which may be partly mediated via inhibition of the JNK/p38 MAPK signaling pathway. CONCLUSIONS: Our findings revealed the therapeutic mechanism of SHD in mitigating AD progression and suggested that SHD is a potent neuroprotectant that contributes to the future development of TCM modernization and broader clinical applications.


Assuntos
Doença de Alzheimer , Fármacos Neuroprotetores , Animais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Peixe-Zebra , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/química , Donepezila/uso terapêutico , Sinaptofisina/metabolismo , NF-kappa B/metabolismo , Acetilcolinesterase/metabolismo , Cromatografia Líquida , Receptor 4 Toll-Like/metabolismo , Espectrometria de Massas em Tandem , Citocinas/metabolismo , Sistema de Sinalização das MAP Quinases , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
13.
Adv Mater ; : e2405277, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877545

RESUMO

Replacing flammable organic liquid electrolytes with nonflammable solid electrolytes (SEs) in lithium batteries is crucial for enhancing safety across various applications, including portable electronics, electric vehicles, and scalable energy storage. Since typical cathode materials do not possess superionic conductivity, Li-ion conduction in the cathode predominantly relies on incorporating a significant number of SEs as additives to form a composite cathode, which substantially compromises the energy density of solid-state lithium batteries. Here, a halide SE, Li3VCl6 is demonstrated, which not only exhibits a decent Li+ conductivity, but more importantly, delivers a highly reversible capacity of approximately 80 mAh g-1 with an average voltage of 3 V versus Li+/Li. The ionic conductivity of Li3VCl6 experiences marginal fluctuations upon electrochemical lithiation/delithiation, as its prototypical solid-solution reaction results solely in a reduction of lithium vacancy. When combined with the traditional LiFePO4 cathode, the active Li3VCl6 catholyte enables an impressive capacity of 217.1 mAh g-1 LFP and about 50% increase in energy density compared with inactive catholytes. Harnessing the integrated mass of the catholyte-which can serve as an active material-presents an opportunity to boost the extra capacity, rendering it feasible in applications.

14.
Cell Chem Biol ; 31(3): 452-464.e10, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-37913771

RESUMO

Various biological agents have been developed to target tumor necrosis factor alpha (TNF-α) and its receptor TNFR1 for the rheumatoid arthritis (RA) treatment, whereas small molecules modulating such cytokine receptors are rarely reported in comparison to the biologicals. Here, by revealing the mechanism of action of vinigrol, a diterpenoid natural product, we show that inhibition of the protein disulfide isomerase (PDI, PDIA1) by small molecules activates A disintegrin and metalloprotease 17 (ADAM17) and then leads to the TNFR1 shedding on mouse and human cell membranes. This small-molecule-induced receptor shedding not only effectively blocks the inflammatory response caused by TNF-α in cells, but also reduces the arthritic score and joint damage in the collagen-induced arthritis mouse model. Our study indicates that targeting the PDI-ADAM17 signaling module to regulate the shedding of cytokine receptors by the chemical approach constitutes a promising strategy for alleviating RA.


Assuntos
Artrite Reumatoide , Diterpenos , Camundongos , Humanos , Animais , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteômica , Artrite Reumatoide/tratamento farmacológico , Proteína ADAM17
15.
Nat Commun ; 15(1): 1481, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368426

RESUMO

Stable solid electrolytes are essential to high-safety and high-energy-density lithium batteries, especially for applications with high-voltage cathodes. In such conditions, solid electrolytes may experience severe oxidation, decomposition, and deactivation during charging at high voltages, leading to inadequate cycling performance and even cell failure. Here, we address the high-voltage limitation of halide solid electrolytes by introducing local lattice distortion to confine the distribution of Cl-, which effectively curbs kinetics of their oxidation. The confinement is realized by substituting In with multiple elements in Li3InCl6 to give a high-entropy Li2.75Y0.16Er0.16Yb0.16In0.25Zr0.25Cl6. Meanwhile, the lattice distortion promotes longer Li-Cl bonds, facilitating favorable activation of Li+. Our results show that this high-entropy halide electrolyte boosts the cycle stability of all-solid-state battery by 250% improvement over 500 cycles. In particular, the cell provides a higher discharge capacity of 185 mAh g-1 by increasing the charge cut-off voltage to 4.6 V at a small current rate of 0.2 C, which is more challenging to electrolytes|cathode stability. These findings deepen our understanding of high-entropy materials, advancing their use in energy-related applications.

16.
Nat Metab ; 6(3): 550-566, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448615

RESUMO

The post-translational modification lysine succinylation is implicated in the regulation of various metabolic pathways. However, its biological relevance remains uncertain due to methodological difficulties in determining high-impact succinylation sites. Here, using stable isotope labelling and data-independent acquisition mass spectrometry, we quantified lysine succinylation stoichiometries in mouse livers. Despite the low overall stoichiometry of lysine succinylation, several high-stoichiometry sites were identified, especially upon deletion of the desuccinylase SIRT5. In particular, multiple high-stoichiometry lysine sites identified in argininosuccinate synthase (ASS1), a key enzyme in the urea cycle, are regulated by SIRT5. Mutation of the high-stoichiometry lysine in ASS1 to succinyl-mimetic glutamic acid significantly decreased its enzymatic activity. Metabolomics profiling confirms that SIRT5 deficiency decreases urea cycle activity in liver. Importantly, SIRT5 deficiency compromises ammonia tolerance, which can be reversed by the overexpression of wild-type, but not succinyl-mimetic, ASS1. Therefore, lysine succinylation is functionally important in ammonia metabolism.


Assuntos
Lisina , Sirtuínas , Camundongos , Animais , Lisina/química , Lisina/metabolismo , Amônia , Sirtuínas/metabolismo , Camundongos Knockout , Ureia
17.
BMJ Open ; 13(8): e068601, 2023 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-37640465

RESUMO

OBJECTIVES: To explore the multiple mediating roles of the learned helplessness's core system in the relationship between health literacy/social support and self-management. DESIGN: Cross-sectional survey design. SETTING: Changsha, China. PARTICIPANTS: 239 Chinese maintenance haemodialysis (MHD) patients. METHODS: Two multiple mediator models were constructed based on the COM-B (Capacity, Opportunity, Motivation - Behaviour) model. A total of 239 Chinese MHD patients participated in a cross-sectional study, which included surveys on the Learned Helplessness Scale for MHD patients, Dialysis Knowledge Questionnaire, Social Support Scale and Self-Management Scale for Haemodialysis. The PROCESS macro in SPSS was used for mediated effects analysis. RESULTS: Helplessness and internality partially mediated the relationship between health literacy/social support and self-management ((ß=-0.212, p<0.01; ß=0.240, p<0.01)/(ß=-0.331, p<0.001; ß=0.376, p<0.001)). The mediation effect size was 0.780 (95% CI (0.373 to 1.218)) in the health literacy model, accounting for 45.29% of the total effect, and 0.286 (95% CI (0.207 to 0.377)) in the social support model, accounting for 57.88% of the total effect. The differences in effect sizes for helplessness and internality in the two models were -0.080 (95% CI (-0.374 to 0.216)) and -0.041 (95% CI (-0.127 to 0.043)), respectively. CONCLUSION: Health literacy/social support directly affects MHD patients' self-management and indirectly affects it by changing learned helplessness, such as increasing internality while reducing helplessness.


Assuntos
Letramento em Saúde , Autogestão , Humanos , Desamparo Aprendido , Estudos Transversais , Diálise Renal , China , Apoio Social
18.
Artigo em Inglês | MEDLINE | ID: mdl-36981585

RESUMO

Shigella flexneri (S. flexneri), a major intestinal pathogen, is a global public health concern. The biofilms formed by S. flexneri threaten environmental safety, since they could promote the danger of environmental contamination and strengthen the disease-causing properties of bacteria. Epigallocatechin gallate (EGCG) is an important catechin in tea, which has a high antibacterial activity. However, its antibacterial mechanism is still unclear. This research aims to quantify the antibacterial function and investigate the possible mechanism of EGCG inhibition of S. flexneri. The minimum inhibitory concentration (MIC) of EGCG against planktonic S. flexneri in the investigation was measured to be 400 µg/mL. Besides, SDS-PAGE and field emission scanning electron microscopy showed that EGCG interfered with protein synthesis and changed bacteria morphology. Through controlling the expression of the mdoH gene, EGCG was found to be able to prevent an S. flexneri biofilm extracellular polysaccharide from forming, according to experiments utilizing the real-time PCR test. Additional research revealed that EGCG might stimulate the response of S. flexneri to oxidative stress and prevent bacterial growth. These findings suggest that EGCG, a natural compound, may play a substantial role in S. flexneri growth inhibition.


Assuntos
Catequina , Catequina/farmacologia , Shigella flexneri , Antibacterianos/farmacologia , Biofilmes
19.
Turk J Gastroenterol ; 34(5): 463-471, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37158532

RESUMO

BACKGROUND: Vitamin D has anti-inflammatory properties and is involved in immune function, making it a potential therapy for Crohn's disease. This study aimed to investigate the effects of vitamin D supplementation on immune function and the clinical efficacy of patients with Crohn's disease. METHODS: From September 2017 to September 2021, patients with Crohn's disease were recruited and randomly divided into 2 groups: the routine treatment group (n = 52) and the vitamin D supplement group (n = 50). In addition to routine treatment, the vitamin D group received oral calcitriol capsule supplementation, while the routine treatment group did not receive any additional intervention. T helper 17/T-regulatory cell level, inflammatory indicators, and nutritional status were compared between the 2 groups, as well as mucosal healing under endoscopy and the life quality of patients. RESULTS: C-reactive protein was significantly lower in the vitamin D treatment group compared to the routine treatment group (6.08 ± 2.72 vs. 18.91 ± 2.66, P < .05). Compared to the routine treatment group, the ratio of T helper 17/T-regulatory cells was significantly lower in the vitamin D group (0.26 ± 0.12 vs. 0.55 ± 0.11, P < .05). After vitamin D treatment, both of the average Crohn's disease activity index score (from 319.7 ± 72.7 to 179.6 ± 48.5, P < .05) and simple endoscopic score for Crohn's disease score (from 7.9 ± 2.3 to 3.9 ± 0.6, P < .05) were significantly decreased, while the Inflammatory Bowel Disease Questionnaire score was significantly increased (from 137.8 ± 21.2 to 158.1 ± 25.1, P < .05). CONCLUSIONS: Vitamin D has the potential to improve the inflammatory status and immune environment of patients with Crohn's disease, which can reduce the level of inflammatory factors and help the recovery of symptoms, thus improving the clinical course and quality of life in Crohn's disease patients.


Assuntos
Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Qualidade de Vida , Vitamina D , Vitaminas/uso terapêutico , Suplementos Nutricionais , Progressão da Doença
20.
Artigo em Inglês | MEDLINE | ID: mdl-36767307

RESUMO

Coronavirus Disease 2019 (COVID-19) has been a global public health concern for almost three years, and the transmission characteristics vary among different virus variants. Previous studies have investigated the relationship between air pollutants and COVID-19 infection caused by the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is unclear whether individuals might be more susceptible to COVID-19 due to exposure to air pollutants, with the SARS-CoV-2 mutating faster and faster. This study aimed to explore the relationship between air pollutants and COVID-19 infection caused by three major SARS-CoV-2 strains (the original strain, Delta variant, and Omicron variant) in China. A generalized additive model was applied to investigate the associations of COVID-19 infection with six air pollutants (PM2.5, PM10, SO2, CO, NO2, and O3). A positive correlation might be indicated between air pollutants (PM2.5, PM10, and NO2) and confirmed cases of COVID-19 caused by different SARS-CoV-2 strains. It also suggested that the mutant variants appear to be more closely associated with air pollutants than the original strain. This study could provide valuable insight into control strategies that limit the concentration of air pollutants at lower levels and would better control the spread of COVID-19 even as the virus continues to mutate.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/epidemiologia , Dióxido de Nitrogênio , Material Particulado/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Poluentes Atmosféricos/análise , China/epidemiologia
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