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1.
Plant Cell ; 35(6): 2391-2412, 2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-36869655

RESUMO

Mitogen-activated protein kinase (MPK) cascades play vital roles in plant innate immunity, growth, and development. Here, we report that the rice (Oryza sativa) transcription factor gene OsWRKY31 is a key component in a MPK signaling pathway involved in plant disease resistance in rice. We found that the activation of OsMKK10-2 enhances resistance against the rice blast pathogen Magnaporthe oryzae and suppresses growth through an increase in jasmonic acid and salicylic acid accumulation and a decrease of indole-3-acetic acid levels. Knockout of OsWRKY31 compromises the defense responses mediated by OsMKK10-2. OsMKK10-2 and OsWRKY31 physically interact, and OsWRKY31 is phosphorylated by OsMPK3, OsMPK4, and OsMPK6. Phosphomimetic OsWRKY31 has elevated DNA-binding activity and confers enhanced resistance to M. oryzae. In addition, OsWRKY31 stability is regulated by phosphorylation and ubiquitination via RING-finger E3 ubiquitin ligases interacting with WRKY 1 (OsREIW1). Taken together, our findings indicate that modification of OsWRKY31 by phosphorylation and ubiquitination functions in the OsMKK10-2-mediated defense signaling pathway.


Assuntos
Resistência à Doença , Proteínas Quinases Ativadas por Mitógeno , Fosforilação , Resistência à Doença/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais , Ubiquitinação
2.
Cell Mol Life Sci ; 81(1): 402, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276234

RESUMO

The excessive inflammation caused by the prolonged activation of Toll-like receptor 4 (TLR4) and its downstream signaling pathways leads to sepsis. CD14-mediated endocytosis of TLR4 is the key step to control the amount of TLR4 on cell membrane and the activity of downstream pathways. The actin cytoskeleton is necessary for receptor-mediated endocytosis, but its role in TLR4 endocytosis remains elusive. Here we show that Tropomodulin 1 (Tmod1), an actin capping protein, inhibited lipopolysaccharide (LPS)-induced TLR4 endocytosis and intracellular trafficking in macrophages. Thus it resulted in increased surface TLR4 and the upregulation of myeloid differentiation factor 88 (MyD88)-dependent pathway and the downregulation of TIR domain-containing adaptor-inducing interferon-ß (TRIF)-dependent pathway, leading to the enhanced secretion of inflammatory cytokines, such as TNF-α and IL-6, and the reduced secretion of cytokines, such as IFN-ß. Macrophages deficient with Tmod1 relieved the inflammatory response in LPS-induced acute lung injury mouse model. Mechanistically, Tmod1 negatively regulated LPS-induced TLR4 endocytosis and inflammatory response through modulating the activity of CD14/Syk/PLCγ2/IP3/Ca2+ signaling pathway, the reorganization of actin cytoskeleton, and the membrane tension. Therefore, Tmod1 is a key regulator of inflammatory response and immune functions in macrophages and may be a potential target for the treatment of excessive inflammation and sepsis.


Assuntos
Endocitose , Inflamação , Lipopolissacarídeos , Macrófagos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Receptor 4 Toll-Like , Tropomodulina , Animais , Humanos , Camundongos , Citoesqueleto de Actina/metabolismo , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/patologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Citocinas/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Células RAW 264.7 , Receptor 4 Toll-Like/metabolismo , Tropomodulina/metabolismo , Tropomodulina/genética
3.
J Med Virol ; 96(4): e29602, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597349

RESUMO

China experienced severe epidemics of multiple respiratory pathogens in 2023 after lifting "Zero-COVID" policy. The present study aims to investigate the changing circulation and infection patterns of respiratory pathogens in 2023. The 160 436 laboratory results of influenza virus and respiratory syncytial virus (RSV) from February 2020 to December 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from June 2020 to December 2023, Mycoplasma pneumoniae, adenovirus, and human rhinovirus from January 2023 to December 2023 were analyzed. We observed the alternating epidemics of SARS-CoV-2 and influenza A virus (IAV), as well as the out-of-season epidemic of RSV during the spring and summer of 2023. Cocirculation of multiple respiratory pathogens was observed during the autumn and winter of 2023. The susceptible age range of RSV in this winter epidemic (10.5, interquartile range [IQR]: 5-30) was significantly higher than previously (4, IQR: 3-34). The coinfection rate of IAV and RSV in this winter epidemic (0.695%) was significantly higher than that of the last cocirculation period (0.027%) (p < 0.001). Similar trend was also found in the coinfection of IAV and SARS-CoV-2. The present study observed the cocirculation of multiple respiratory pathogens, changing age range of susceptible population, and increasing coinfection rates during the autumn and winter of 2023, in Beijing, China.


Assuntos
Coinfecção , Vírus da Influenza A , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Estudos Retrospectivos , Infecções Respiratórias/epidemiologia , Pequim/epidemiologia , Estações do Ano , Coinfecção/epidemiologia , China/epidemiologia , SARS-CoV-2 , Influenza Humana/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia
4.
Chemistry ; 30(58): e202402602, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39112402

RESUMO

Mild and inexpensive copper-catalyzed aromatization-driven ring-opening amination and oxygenation of spiro dihydroquinazolinones are presented, respectively. These protocols provide facile and atom-economical access to the aminated and the carbonyl-containing quinazolin-4(3H)-ones in good yields with good functional group compatibility, which are difficult to obtain by conventional methods. Remarkably, a telescoped procedure involving the condensation and the ring-opening/functionalization for simple cycloalkanone was found to be accessible. Mechanistic studies suggest a radical pathway for this transformation.

5.
Glycoconj J ; 41(4-5): 241-254, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39046578

RESUMO

Pertussis vaccines have been very effective in controlling whooping-cough epidemics but are ineffective in controlling circulation in older children and adults, thus facilitating the onset of future outbreaks. Antibodies against the lipopolysaccharide could reduce the carriage of the bacteria, its circulation, and transmission. The oligosaccharide fragments from the lipopolysaccharide may become a potential complement to existing vaccines in the form of protein glycoconjugates. An important step in the development of this type of vaccine is defining the minimal oligosaccharide epitope recognized by B. pertussis anti-lipopolysaccharide antibodies. This paper describes the complete synthesis of oligosaccharides containing two to five monosaccharide units corresponding to the pentasaccharide at the nonreducing end of the lipooligosaccharide and their recognition by mice and rabbit antibodies elicited against whole-cell B. pertussis. For the first time, we report that the terminal disaccharide, α-D-GlcNAcp-(1 → 4)-(2,3-di-NAc)-D-ManAp acid is the minimal structure recognized by antibodies induced by B. pertussis.


Assuntos
Anticorpos Antibacterianos , Bordetella pertussis , Epitopos , Lipopolissacarídeos , Oligossacarídeos , Animais , Bordetella pertussis/imunologia , Bordetella pertussis/química , Oligossacarídeos/imunologia , Oligossacarídeos/química , Lipopolissacarídeos/imunologia , Lipopolissacarídeos/química , Camundongos , Epitopos/imunologia , Epitopos/química , Coelhos , Anticorpos Antibacterianos/imunologia , Coqueluche/imunologia , Coqueluche/prevenção & controle , Sequência de Carboidratos , Vacina contra Coqueluche/imunologia , Vacina contra Coqueluche/química
6.
Bioorg Chem ; 150: 107612, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38986418

RESUMO

The high level of tyrosinase leads to the generation of neuromelanin, further causing the abnormality of redox-related protein level and mediating the occurrence and development of Parkinson's disease (PD). However, the existing tyrosinase inhibitors are mostly natural product extracts or polyphenolic derivatives, which hindered them from penetrating the blood-brain barrier (BBB). Herein, we obtained a novel tyrosinase inhibitor, 2-06 (tyrosinase: monophenolase IC50 = 70.44 ± 22.69 µM, diphenolase IC50 = 1.89 ± 0.64 µM), through the structure-based screening method. The compound 2-06 presented good in vitro and in vivo safety, and can inhibit the tyrosinase and melanogenesis in B16F10. Moreover, this compound showed neuroprotective effects and Parkinsonism behavior improving function. 2-06 was proved to penetrate the BBB and enter the central nervous system (CNS). The exploration of the binding mode between 2-06 and tyrosinase provided the foundation for the subsequent structural optimization. This is the first research to develop a central-targeting tyrosinase inhibitor, which is crucial for in-depth study on the new strategy for utilizing tyrosinase inhibitors to treat PD.


Assuntos
Relação Dose-Resposta a Droga , Descoberta de Drogas , Inibidores Enzimáticos , Monofenol Mono-Oxigenase , Doença de Parkinson , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/síntese química , Animais , Relação Estrutura-Atividade , Camundongos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/síntese química , Humanos , Masculino , Simulação de Acoplamento Molecular , Barreira Hematoencefálica/metabolismo
7.
Environ Res ; 252(Pt 4): 119151, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38754608

RESUMO

The aim of this study was to assess effects of MnO2 addition (CK-0%, T1-2% and T2-5%) on humification and bacterial community during municipal sludge (MS) composting. The results suggested that MnO2 addition inhibited the growth of Nitrospira but stimulated Nonomuraea, Actinomadura, Streptomyces and Thermopolyspora, facilitating the lignocellulose degradation and humification with the increase in organic matter degradation by 13.8%-19.2% and humic acid content by 10.9%-20.6%. Compared to CK, the abundances of exoglucanase (EC:3.2.1.91), endo-1,4-beta-xylanase (EC:3.2.1.136) and endomannanase (EC:3.2.1.78) increased by 88-99, 52-66 and 4-15 folds, respectively. However, 5%-MnO2 induced the enrichment of Mizugakiibacter that harms the environment of agricultural production. The addition of 2%-MnO2 was recommended for MS composting. Furthermore, metabolic function analysis indicated that MnO2 addition altered amino acid and carbohydrate metabolism, especially enhancing propanoate metabolism and butanoate metabolism but inhibiting citrate cycle. Structural equation modeling revealed that Nonomuraea and Actinomadura were the main drivers for lignocellulose degradation. This study provided theoretical guidance in regulating humification via MnO2 for MS composting.


Assuntos
Compostagem , Eliminação de Resíduos Líquidos , Compostagem/métodos , Eliminação de Resíduos Líquidos/métodos , Microbiologia do Solo , Biodegradação Ambiental , Solo , Actinobacteria , Actinomadura , Streptomyces , Substâncias Húmicas
8.
BMC Psychiatry ; 24(1): 517, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039478

RESUMO

BACKGROUND: Depression and anxiety symptoms among medical students are often a concern. The Patient Health Questionnaire-Four (PHQ-4), an important tool for depression and anxiety screening, is commonly used and easy to administer. This study aimed to assess and update the longitudinal measurement invariance and psychometric properties of the simplified Chinese version. METHODS: A three-wave longitudinal survey was conducted among healthcare students using the PHQ-4. Structural validity was based on one-factor, two-factor, and second-order factor models, construct validity was based on the Self-Rated Health Questionnaire (SRHQ), Sleep Quality Questionnaire (SQQ), and Rosenberg Self-Esteem Scale (RSES), and longitudinal measurement invariance (LMI), internal consistency, and test-retest reliability were based on structural consistency across three time points. RESULTS: The results of the confirmatory factor analysis indicated that two-factor model was the best fit, and LMI was supported at three time points. Inter-factor, factor-total, and construct validity correlations of the PHQ-4 were acceptable. Additionally, Cronbach's alpha, McDonald's omega, and the intraclass correlation coefficient demonstrated acceptable/moderate to excellent reliability of the PHQ-4. CONCLUSIONS: This study adds new longitudinal evidence that the Chinese version of the PHQ-4 has promising LMI and psychometric properties. Such data lends confidence to the routine and the expanded use of the PHQ-4 for routine screening of depression and anxiety in Chinese healthcare students.


Assuntos
Ansiedade , Depressão , Questionário de Saúde do Paciente , Psicometria , Humanos , China , Feminino , Masculino , Estudos Longitudinais , Reprodutibilidade dos Testes , Depressão/psicologia , Depressão/diagnóstico , Ansiedade/psicologia , Ansiedade/diagnóstico , Adulto , Adulto Jovem , Estudantes de Medicina/psicologia , Análise Fatorial , Inquéritos e Questionários/normas
9.
Mycopathologia ; 189(3): 35, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637433

RESUMO

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/farmacologia , Candidíase/microbiologia , Candida auris , Candida , Anfotericina B/farmacologia , Farmacorresistência Fúngica/genética , Testes de Sensibilidade Microbiana
10.
J Clin Nurs ; 33(6): 2138-2152, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38590015

RESUMO

AIMS: To identify factors associated with health behaviours among stroke survivors, through a multi-centre study. DESIGN: A sequential mixed methods design. METHODS: In the quantitative research phase, a total of 350 participants were recruited through multi-stage sampling from December 2022 to June 2023. General information questionnaires, The Stroke Prevention Knowledge Questionnaire (SPKQ), Short Form Health Belief Model Scale (SF-HBMS), Health Promoting Lifestyle Profile (HPLPII), and the WHOQOL-BREF (World Health Organization Quality of Life Questionnaire, Brief Version) were distributed across five tertiary hospitals in Henan province, China. For the qualitative research component, semi-structured interviews were conducted to explore the barriers and facilitators of health behaviour. This study adheres to the GRAMMS guidelines. RESULTS: A total of 315 participants (90.0%) completed the survey. Identified barriers to health behaviour included residing in rural areas, higher scores on the Charlson Comorbidity Index (CCI) and mRS, as well as lower scores on SPKQ, SF-HBMS and WHOQOL-BREF. Twenty-four individuals participated in qualitative interviews. Twenty-eight themes were identified and categorised by frequency, covering areas such as knowledge, skills, intentions, social influences, social/professional role and identity, environmental context and resources, beliefs about capabilities, beliefs about consequences and behavioural regulation. Both quantitative and qualitative data suggested that health behaviour among stroke survivors is at a moderate level, and the identified barrier factors can be mapped into the COM-B model (Capability, Opportunity, Motivation and Behaviour). CONCLUSION: The study indicates that key barriers to health behaviour among stroke survivors align with the COM-B model. These identified factors should be carefully considered in the planning of future systematic interventions aimed at improving health behaviours among stroke survivors. PATIENT OR PUBLIC CONTRIBUTION: Patients were invited to completed questionnaires in the study and semi-structured interviews. The investigators provided explanation of this study' content, purpose and addressed issues during the data collection.


Assuntos
Comportamentos Relacionados com a Saúde , Acidente Vascular Cerebral , Sobreviventes , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Sobreviventes/psicologia , Sobreviventes/estatística & dados numéricos , Acidente Vascular Cerebral/psicologia , Inquéritos e Questionários , China , Idoso , Pesquisa Qualitativa , Adulto , Modelo de Crenças de Saúde , Conhecimentos, Atitudes e Prática em Saúde , Qualidade de Vida/psicologia
11.
Int J Nurs Pract ; : e13278, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862421

RESUMO

BACKGROUND: Illness perceptions are an important factor affecting the prognosis of stroke patients. Evaluating the illness perceptions of stroke patients is of great importance for predicting their health behaviour and rehabilitation outcomes. However, there is no specific tool for assessing illness perceptions in stroke patients in China. OBJECTIVES: The objective of this study is to translate the Stroke Illness Perception Questionnaire-Revised (SIPQ-R) into Chinese and to psychometrically test the Chinese version of the scale in the population of Chinese stroke patients. METHODS: This was a methodological study. We investigated 593 stroke patients in the neurology department of a hospital in China from March to September 2021. We translated the SIPQ-R and adapted it to the cultural context, after which we evaluated the reliability and validity of the Chinese version of SIPQ-R. RESULTS: Exploratory factor analysis identified eight common factors that accounted for 71.74% of the total variance, and the factor loadings ranged from 0.530 to 0.933. Confirmatory factor analysis confirmed the eight-factor structure (χ2/df = 1.765, root mean square error of approximation = 0.053, incremental fit index = 0.906, comparative fit index = 0.905 and Tucker-Lewis index = 0.900). Internal consistency was confirmed by a Cronbach's alpha coefficient of 0.982. The test-retest reliability was 0.762. The results showed good content validity (the scale level content validity index was 0.940, and the item level content validity index values ranged from 0.860 to 0.960). There were no missing responses and floor or ceiling effects. The standard error of measurement and the smallest detectable change for the SIPQ-R were 45.49 and 126.10, respectively. CONCLUSIONS: The results of this study provide empirical evidence for the reliability and validity of the Chinese version of the SIPQ-R for stroke patients.

12.
Molecules ; 29(4)2024 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-38398644

RESUMO

Corn silk (Zea mays L.) is the stigma of an annual gramineous plant named corn, which is distributed in many regions worldwide and has a long history of medicinal use. In recent years, with the sustainable development of traditional Chinese medicine, studies of corn silk based on modern technologies, such as GC-MS, LC-MS, and other analytical means, have offered more comprehensive analyses. Phytochemistry studies have shown that the main bioactive components in corn silk include flavonoids, polyphenols, phenolic acids, fatty acids, and terpenoids. Pharmacological studies have shown that corn silk extract has various pharmacological effects, such as reducing blood lipids, lowering blood pressure, regulating blood sugar levels, anti-inflammatory effects, and anti-oxidation effects. In this paper, the related research on corn silk from the past few years is summarized to provide a theoretical reference for the further development and utilization of corn silk.


Assuntos
Extratos Vegetais , Zea mays , Pressão Sanguínea , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia
13.
J Sci Food Agric ; 104(10): 6242-6251, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38456730

RESUMO

BACKGROUND: The pickling process with NaCl is an essential step for pork preservation. This study aimed to investigate the effect of different ultrasonic intensities of tri-frequency simultaneous ultrasound (TSIU) pickling on the NaCl content and quality of pork (longissimus dorsi). After 30 min pickling, the NaCl content, moisture content, pickling yield, cooking loss, textural properties, color, pH, moisture migration and distribution as well as microstructure of pork were assessed. RESULTS: Results showed that among all the ultrasonic treatment intensities (85-150 W L-1), the NaCl content of the sample pickled by an intensity of 101.3 W L-1 was higher than that of other intensities. TSIU 101.3 W L-1 showed 59.95% higher NaCl content than the control sample. In addition, the sample treated with TSIU of 101.3 W L-1 had higher pickling yield and moisture content, better textural properties of pork (including hardness and chewiness), and less cooking loss. The results of the low-field nuclear magnetic resonance showed that, compared with the control group, the relaxation time T21 of the ultrasound-assisted pickling samples increased, while the proportion of T22 (A22) reduction ranged from 175.0% to 379.9%. The microstructure designated that the ultrasonic treatment could facilitate changes in meat texture. CONCLUSION: Ultrasound marination of different intensities promoted the diffusion of NaCl and affected the quality of pork tenderloins. The TSIU at 101.3 W L-1 could better accelerate NaCl transport and homogeneous distribution on meat, thereby improving the sample quality. © 2024 Society of Chemical Industry.


Assuntos
Culinária , Manipulação de Alimentos , Cloreto de Sódio , Animais , Cloreto de Sódio/química , Cloreto de Sódio/análise , Suínos , Manipulação de Alimentos/métodos , Culinária/métodos , Melhoria de Qualidade , Ultrassom/métodos , Produtos da Carne/análise , Conservação de Alimentos/métodos , Cor , Músculo Esquelético/química , Músculo Esquelético/efeitos da radiação
14.
Angew Chem Int Ed Engl ; : e202419082, 2024 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-39479975

RESUMO

Because of the unique and superior optoelectronic properties, metal halide perovskites (MHPs) have attracted great interests in photocatalysis. Element doping strategy is adopted to modify perovskite materials to improve their photocatalytic performance. However, the contribution of bare doping-site onto photocatalytic efficiency, and the correlation between doping locations and activity have not yet to be demonstrated. This promoted us to explore the potential of A-site-doped MHPs for photocatalysis. Herein, we dope potassium (K+) into CsPbBr3 and first reveal that the occupied locations of K+ in CsPbBr3 is lattice incorporation rather than surface segregation, which would change from A-site substitution to interstitial site in lattice with the increase of K+ concentrations. Taking H2 evolution as a model reaction, photocatalytic activity of CsPbBr3 after K+ doping could be significantly improved ~11-fold with A-site substitution, which is superior to that of interstitial site doping. Moreover, other alkali metals including Li, Na, and Rb doping give the same results. The structure of photocatalysts during reaction confirmed the contribution of A-site doping onto enhanced photocatalytic activity. Mechanistic insights show it is a result of the relaxed residual lattice strain induced promoted charge-carriers dynamics and formed upward shifting of band after K+ A-site doping.

15.
Hepatology ; 75(6): 1446-1460, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34662438

RESUMO

BACKGROUND AND AIMS: Ischemia-reperfusion (I/R) injury is an inevitable complication of liver transplantation (LT) and compromises its prognosis. Glycosyltransferases have been recognized as promising targets for disease therapy, but their roles remain open for study in hepatic I/R (HIR) injury. Here, we aim to demonstrate the exact function and molecular mechanism of a glycosyltransferase, N-acetylgalactosaminyltransferase-4 (GALNT4), in HIR injury. APPROACH AND RESULTS: By an RNA-sequencing data-based correlation analysis, we found a close correlation between GALNT4 expression and HIR-related molecular events in a murine model. mRNA and protein expression of GALNT4 were markedly up-regulated upon reperfusion surgery in both clinical samples from subjects who underwent LT and in a mouse model. We found that GALNT4 deficiency significantly exacerbated I/R-induced liver damage, inflammation, and cell death, whereas GALNT4 overexpression led to the opposite phenotypes. Our in-depth mechanistic exploration clarified that GALNT4 directly binds to apoptosis signal-regulating kinase 1 (ASK1) to inhibit its N-terminal dimerization and subsequent phosphorylation, leading to a robust inactivation of downstream c-Jun N-terminal kinase (JNK)/p38 and NF-κB signaling. Intriguingly, the inhibitory capacity of GALNT4 on ASK1 activation is independent of its glycosyltransferase activity. CONCLUSIONS: GALNT4 represents a promising therapeutic target for liver I/R injury and improves liver surgery prognosis by inactivating the ASK1-JNK/p38 signaling pathway.


Assuntos
Fígado , MAP Quinase Quinase Quinase 5 , N-Acetilgalactosaminiltransferases , Traumatismo por Reperfusão , Animais , Apoptose , Fígado/patologia , MAP Quinase Quinase Quinase 5/metabolismo , Camundongos , N-Acetilgalactosaminiltransferases/genética , Multimerização Proteica , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/prevenção & controle , Polipeptídeo N-Acetilgalactosaminiltransferase
16.
J Org Chem ; 88(14): 9927-9940, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37432753

RESUMO

An array of redox-neutral alkylation/cyclization cascade reactions of N-functionalized acrylamides with cycloalkyl hydroperoxides were achieved via the alkoxyl radical-triggered C-C bond cleavage. Through adjusting the radical acceptors on the N atom, a variety of keto-alkylated chain-containing azaheterocycles, including indolo[2,1-a]isoquinolin-6(5H)-ones, quinoline-2,4-diones, and pyrido[4,3,2-gh]phenanthridines were constructed by a one-pot procedure with good yields and excellent functional group tolerance.

17.
Org Biomol Chem ; 21(28): 5855-5860, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37401815

RESUMO

An efficient iron-catalyzed alkoxyl radical-mediated C-C bond cleavage/phosphorothiolation cascade is presented. This protocol features mild and redox neutral conditions, wide substrate scope and easy scalability, allowing straightforward access to functionalized S-alkyl organophosphorus compounds in moderate to good yields.

18.
J Clin Nurs ; 32(13-14): 3787-3796, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36717977

RESUMO

BACKGROUND: There are an increasing number of evidence-based recommendations for managing dysphagia in post-stroke patients. However, it is unclear whether nurses adopt these recommendations in their daily nursing practices. AIMS: This study aimed to explore nurses' adherence, barriers, facilitators and views on dysphagia screening and assessment of post-stroke dysphagia. METHODS: In this study, multiple methods were adopted. In Phase 1, a general information questionnaire and a knowledge-attitude-practice and barriers/facilitators questionnaire for dysphagia screening and assessment were distributed in 55 hospitals online. In Phase 2, semi-structured interviews were conducted to explore nurses' views on barriers. Descriptive and one-way variance analyses were used to analyse the quantitative data, while content analysis was used to analyse the qualitative data. This study adheres to STROBE and COREQ guidelines. RESULTS: Nine hundred and forty-two completed questionnaires were collected. Only 36.52% of the nurses screened for swallow function in patients as a guideline. The biggest barrier was 'memory, attention and decision process', with an average score of 3.22 (.74). The different stages of implementation had various types and degrees of barriers (p < .001). Five themes were extracted after interviews, namely 'Inadequate environment and resource support', 'Increased workload', 'Professional value perception', 'Organisational culture', and 'Poor knowledge and skill'. CONCLUSIONS: Nurses' practice of dysphagia screening and assessment of patients with dysphagia after stroke were inadequate, and the barriers originated from patients, leadership and the nurses themselves. RELEVANCE TO CLINICAL PRACTICE: This research extracted five barriers of guidance adherence for post-stroke dysphagia screening and assessment and identified the different kinds and degrees of barriers in five implementation stages, providing a basis for nursing managers to break through the bottleneck of guideline implementation. PATIENT OR PUBLIC CONTRIBUTION: The nurses recruited in this study completed validated questionnaires in the survey and suggestive answers in interviews.


Assuntos
Transtornos de Deglutição , Fidelidade a Diretrizes , Padrões de Prática em Enfermagem , Humanos , Acidente Vascular Cerebral , Reabilitação do Acidente Vascular Cerebral , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/reabilitação , Estudos Transversais , Pesquisa Qualitativa , Programas de Rastreamento , Conhecimentos, Atitudes e Prática em Saúde
19.
Int J Nurs Pract ; 29(2): e13060, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35581746

RESUMO

AIM: This study aimed to explore and confirm the factor structure and item distribution of the Chinese version of Self-care Ability Scale for the Elderly among older Chinese people. METHODS: A cluster random sampling method was used to collect 2856 older people from five different cities of China from July 2018 to July 2019. A questionnaire comprised of socio-demographic information and the Chinese version of the Self-care Ability Scale for the Elderly was administered, and SPSS 21.0 and Mplus 7.4 were used for analyses. RESULTS: Participants were aged 60 to 92 years, with a mean age of 71.52 (SD = 7.68) years. In the Exploratory Factor Analysis, the three-factor structure and item distribution of the Chinese version of the Self-care Ability Scale for the Elderly were verified to be better than other options. The factor loadings varied from 0.428 to 0.800, and the communality values ranged from 0.426 to 0.792. The modified model showed a good fit in the Confirmatory Factor Analysis. CONCLUSION: The Chinese version of the Self-care Ability Scale for the Elderly has a clear three-factor structure and a good item distribution. It serves as a convenient and accurate assessment tool to assess the self-care ability of older Chinese people.


Assuntos
Comparação Transcultural , Autocuidado , Idoso , Humanos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários , China , Análise Fatorial
20.
J Environ Sci (China) ; 125: 319-331, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36375917

RESUMO

Oxidation-absorption technology is a key step for NOx removal from low-temperature gas. Under the condition of low O3 concentration (O3/NO molar ratio = 0.6), F-TiO2 (F-TiO2), which is cheap and environmentally friendly, has been prepared as ozonation catalysts for NO oxidation. Catalytic activity tests performed at 120°C showed that the NO oxidation efficiency of F-TiO2 samples was higher than that of TiO2 (about 43.7%), and the NO oxidation efficiency of F-TiO2-0.15 was the highest, which was 65.3%. Combined with physicochemical characteristics of catalysts and the analysis of active species, it was found that there was a synergistic effect between F sites and oxygen vacancies on F-TiO2, which could accelerate the transformation of monomolecular O3 into multi-molecule singlet oxygen (1O2), thus promoting the selective oxidation of NO to NO2. The oxidation reaction of NO on F-TiO2-0.15 follows the Eley-Rideal mechanism, that is, gaseous NO reacts with adsorbed O3 and finally form NO2.


Assuntos
Dióxido de Nitrogênio , Oxigênio , Catálise , Oxirredução , Oxigênio/química , Titânio/química , Ozônio/química , Óxido Nítrico/química
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