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1.
Plant J ; 118(5): 1413-1422, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38341804

RESUMO

Mung bean (Vigna radiata) stands as a crucial legume crop in Asia, contributing to food security. However, our understanding of the underlying genetic foundation governing domesticated agronomic traits, especially those linked to pod architecture, remains largely unexplored. In this study, we delved into the genomic divergence between wild and domesticated mung bean varieties, leveraging germplasm obtained from diverse sources. Our findings unveiled pronounced variation in promoter regions (35%) between the two mung bean subpopulations, suggesting substantial changes in gene expression patterns during domestication. Leveraging transcriptome analysis using distinct reproductive stage pods and subpopulations, we identified candidate genes responsible for pod and seed architecture development, along with Genome-Wide Association Studies (GWAS) and Quantitative Trait Locus (QTL) analysis. Notably, our research conclusively confirmed PDH1 as a parallel domesticated gene governing pod dehiscence in legumes. This study imparts valuable insights into the genetic underpinnings of domesticated agronomic traits in mung bean, and simultaneously highlighting the parallel domestication of pivotal traits within the realm of legume crops.


Assuntos
Produtos Agrícolas , Domesticação , Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Vigna , Vigna/genética , Locos de Características Quantitativas/genética , Produtos Agrícolas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes/genética , Genoma de Planta/genética , Regulação da Expressão Gênica de Plantas , Genômica , Fenótipo
2.
J Proteome Res ; 23(7): 2532-2541, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38902972

RESUMO

Metabolic dysfunction is recognized as a contributing factor in the pathogenesis of wet age-related macular degeneration (wAMD). However, the specific metabolism-related proteins implicated in wAMD remain elusive. In this study, we assessed the expression profiles of 92 metabolism-related proteins in aqueous humor (AH) samples obtained from 44 wAMD patients and 44 cataract control patients. Our findings revealed significant alterations in the expression of 60 metabolism-related proteins between the two groups. Notably, ANGPTL7 and METRNL displayed promising diagnostic potential for wAMD, as evidenced by area under the curve values of 0.88 and 0.85, respectively. Subsequent validation studies confirmed the upregulation of ANGPTL7 and METRNL in the AH of wAMD patients and in choroidal neovascularization (CNV) models. Functional assays revealed that increased ANGPTL7 and METRNL played a pro-angiogenic role in endothelial biology by promoting endothelial cell proliferation, migration, tube formation, and spouting in vitro. Moreover, in vivo studies revealed the pro-angiogenic effects of ANGPTL7 and METRNL in CNV formation. In conclusion, our findings highlight the association between elevated ANGPTL7 and METRNL levels and wAMD, suggesting their potential as novel predictive and diagnostic biomarkers for this condition. These results underscore the significance of ANGPTL7 and METRNL in the context of wAMD pathogenesis and offer new avenues for future research and therapeutic interventions.


Assuntos
Proteína 7 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina , Humor Aquoso , Biomarcadores , Degeneração Macular Exsudativa , Humor Aquoso/metabolismo , Humanos , Biomarcadores/metabolismo , Masculino , Degeneração Macular Exsudativa/metabolismo , Degeneração Macular Exsudativa/genética , Feminino , Proteínas Semelhantes a Angiopoietina/metabolismo , Proteínas Semelhantes a Angiopoietina/genética , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Idoso , Proliferação de Células , Animais , Movimento Celular , Camundongos
3.
Plant J ; 116(6): 1717-1736, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37751381

RESUMO

Wheat yellow mosaic virus (WYMV) causes severe wheat viral disease in Asia. However, the viral suppressor of RNA silencing (VSR) encoded by WYMV has not been identified. Here, the P1 protein encoded by WYMV RNA2 was shown to suppress RNA silencing in Nicotiana benthamiana. Mutagenesis assays revealed that the alanine substitution mutant G175A of P1 abolished VSR activity and mutant Y10A VSR activity remained only in younger leaves. P1, but not G175A, interacted with gene silencing-related protein, N. benthamiana calmodulin-like protein (NbCaM), and calmodulin-binding transcription activator 3 (NbCAMTA3), and Y10A interacted with NbCAMTA3 only. Competitive Bimolecular fluorescence complementation and co-immunoprecipitation assays showed that the ability of P1 disturbing the interaction between NbCaM and NbCAMTA3 was stronger than Y10A, Y10A was stronger than G175A. In vitro transcript inoculation of infectious WYMV clones further demonstrated that VSR-defective mutants G175A and Y10A reduced WYMV infection in wheat (Triticum aestivum L.), G175A had a more significant effect on virus accumulation in upper leaves of wheat than Y10A. Moreover, RNA silencing, temperature, and autophagy have significant effects on the accumulation of P1 in N. benthamiana. Taken together, WYMV P1 acts as VSR by interfering with calmodulin-associated antiviral RNAi defense to facilitate virus infection in wheat, which has provided clear insights into the function of P1 in the process of WYMV infection.


Assuntos
Vírus do Mosaico , Viroses , Interferência de RNA , Triticum/genética , Calmodulina/genética , Viroses/genética , Vírus do Mosaico/genética , Doenças das Plantas/genética
4.
Small ; 20(27): e2311124, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38258393

RESUMO

The electrochemical nitrogen oxidation reaction (NOR) holds significant potential to revolutionize the traditional nitrate synthesis processes. However, the progression in NOR has been notably stymied due to the sluggish kinetics of initial N2 adsorption and activation processes. Herein, the research embarks on the development of a CeO2-Co3O4 heterostructure, strategically engineered to facilitate the electron transfer from CeO2 to Co3O4. This orchestrated transfer operates to amplify the d-band center of the Co active sites, thereby enhancing N2 adsorption and activation dynamics by strengthening the Co─N bond and diminishing the resilience of the N≡N bond. The synthesized CeO2-Co3O4 manifests promising prospects, showcasing a significant HNO3 yield of 37.96 µg h-1 mgcat -1 and an elevated Faradaic efficiency (FE) of 29.30% in a 0.1 m Na2SO4 solution at 1.81 V versus RHE. Further substantiating these findings, an array of in situ methodologies coupled with DFT calculations vividly illustrate the augmented adsorption and activation of N2 on the surface of CeO2-Co3O4 heterostructure, resulting in a substantial reduction in the energy barrier pertinent to the rate-determining step within the NOR pathway. This research carves a promising pathway to amplify N2 adsorption throughout the electrochemical NOR operations and delineates a blueprint for crafting highly efficient NOR electrocatalysts.

5.
J Transl Med ; 22(1): 476, 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38764010

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is the leading cause of blinding eye disease among working adults and is primarily attributed to the excessive proliferation of microvessels, which leads to vitreous hemorrhage and retinal traction, thereby significantly impairing patient vision. NSUN2-mediated RNA m5C methylation is implicated in various diseases, and in this investigation, we focused on elucidating the impact of NSUN2 on the regulation of the expression of the downstream gene MUC1, specifically through RNA m5C methylation, on the progression of DR. METHOD: Utilizing Microarray analysis, we examined patient vitreous fluid to pinpoint potential therapeutic targets for DR. Differential expression of NSUN2 was validated through qRT-PCR, Western blot, and immunofluorescence in human tissue, animal tissue, and cell model of DR. The relationship between NSUN2 and DR was explored in vitro and in vivo through gene knockdown and overexpression. Various techniques, such as MeRIP-qPCR and dot blot, were applied to reveal the downstream targets and mechanism of action of NSUN2. RESULTS: The levels of both NSUN2 and RNA m5C methylation were significantly elevated in the DR model. Knockdown of NSUN2 mitigated DR lesion formation both in vitro and in vivo. Mechanistically, NSUN2 promoted MUC1 expression by binding to the RNA m5C reader ALYREF. Knockdown of ALYREF resulted in DR lesion alterations similar to those observed with NSUN2 knockdown. Moreover, MUC1 overexpression successfully reversed a series of DR alterations induced by NSUN2 silencing. CONCLUSIONS: NSUN2 regulates the expression of MUC1 through ALYREF-mediated RNA m5C methylation, thereby regulating the progression of DR and providing a new option for the treatment of DR in the future.


Assuntos
Retinopatia Diabética , Progressão da Doença , Metiltransferases , Mucina-1 , Metilação de RNA , Animais , Humanos , Masculino , Retinopatia Diabética/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Metilação , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos Endogâmicos C57BL , Mucina-1/metabolismo , Mucina-1/genética
6.
J Transl Med ; 22(1): 562, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867291

RESUMO

BACKGROUND: Intravitreal injections of angiogenesis inhibitors have proved efficacious in the majority of patients with ocular angiogenesis. However, one-fourth of all treated patients fail to derive benefits from intravitreal injections. tRNA-derived small RNA (tsRNA) emerges as a crucial class of non-coding RNA molecules, orchestrating key roles in the progression of human diseases by modulating multiple targets. Through our prior sequencing analyses and bioinformatics predictions, tRNA-Cys-5-0007 has shown as a potential regulator of ocular angiogenesis. This study endeavors to elucidate the precise role of tRNA-Cys-5-0007 in the context of ocular angiogenesis. METHODS: Quantitative reverse transcription PCR (qRT-PCR) assays were employed to detect tRNA-Cys-5-0007expression. EdU assays, sprouting assays, transwell assays, and Matrigel assays were conducted to elucidate the involvement of tRNA-Cys-5-0007 in endothelial angiogenic effects. STZ-induced diabetic model, OIR model, and laser-induced CNV model were utilized to replicate the pivotal features of ocular vascular diseases and evaluate the influence of tRNA-Cys-5-0007 on ocular angiogenesis and inflammatory responses. Bioinformatics analysis, luciferase activity assays, RNA pull-down assays, and in vitro studies were employed to elucidate the anti-angiogenic mechanism of tRNA-Cys-5-0007. Exosomal formulation was employed to enhance the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. RESULTS: tRNA-Cys-5-0007 expression was down-regulated under angiogenic conditions. Conversely, tRNA-Cys-5-0007 overexpression exhibited anti-angiogenic effects in retinal endothelial cells, as evidenced by reduced proliferation, sprouting, migration, and tube formation abilities. In diabetic, laser-induced CNV, and OIR models, tRNA-Cys-5-0007 overexpression led to decreased ocular vessel leakage, inhibited angiogenesis, and reduced ocular inflammation. Mechanistically, these effects were attributed to the targeting of vascular endothelial growth factor A (VEGFA) and TGF-ß1 by tRNA-Cys-5-0007. The utilization of an exosomal formulation further potentiated the synergistic anti-angiogenic and anti-inflammatory efficacy of tRNA-Cys-5-0007. CONCLUSIONS: Concurrent targeting of tRNA-Cys-5-0007 for anti-angiogenic and anti-inflammatory therapy holds promise for enhancing the effectiveness of current anti-angiogenic therapy.


Assuntos
Inibidores da Angiogênese , Anti-Inflamatórios , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Humanos , RNA de Transferência/metabolismo , RNA de Transferência/genética , Camundongos Endogâmicos C57BL , Proliferação de Células/efeitos dos fármacos , Neovascularização de Coroide/patologia , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismo , Masculino , Oftalmopatias/tratamento farmacológico , Oftalmopatias/patologia , Oftalmopatias/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Neovascularização Patológica , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/patologia , Retinopatia Diabética/metabolismo , Camundongos , Células Endoteliais da Veia Umbilical Humana/metabolismo
7.
BMC Cancer ; 24(1): 139, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287300

RESUMO

BACKGROUND: Identifying lymph node metastasis areas during surgery for early invasive lung adenocarcinoma remains challenging. The aim of this study was to develop a nomogram mathematical model before the end of surgery for predicting lymph node metastasis in patients with early invasive lung adenocarcinoma. METHODS: In this study, we included patients with invasive lung adenocarcinoma measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to January 2022. Preoperative biomarker results, clinical features, and computed tomography characteristics were collected. The enrolled patients were randomized into a training cohort and a validation cohort in a 7:3 ratio. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. Recipient operating characteristic (ROC) curves were used to assess the discrimination ability of the model. Calibration capability was assessed using the Hosmer-Lemeshow test and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). RESULTS: The overall incidence of lymph node metastasis was 13.23% (61/461). Six indicators were finally determined to be independently associated with lymph node metastasis. These six indicators were: age (P < 0.001), serum amyloid (SA) (P = 0.008); carcinoma antigen 125 (CA125) (P = 0. 042); mucus composition (P = 0.003); novel aspartic proteinase of the pepsin family A (Napsin A) (P = 0.007); and cytokeratin 5/6 (CK5/6) (P = 0.042). The area under the ROC curve (AUC) was 0.843 (95% CI: 0.779-0.908) in the training cohort and 0.838 (95% CI: 0.748-0.927) in the validation cohort. the P-value of the Hosmer-Lemeshow test was 0.0613 in the training cohort and 0.8628 in the validation cohort. the bias of the training cohort corrected C-index was 0.8444 and the bias-corrected C-index for the validation cohort was 0.8375. demonstrating that the prediction model has good discriminative power and good calibration. CONCLUSIONS: The column line graphs created showed excellent discrimination and calibration to predict lymph node status in patients with ≤ 2 cm invasive lung adenocarcinoma. In addition, the predictive model has predictive potential before the end of surgery and can inform clinical decision making.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Adenocarcinoma/cirurgia , Imuno-Histoquímica , Metástase Linfática , Nomogramas , Estudos Retrospectivos
8.
Int J Gynecol Pathol ; 43(3): 233-241, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-37733028

RESUMO

The studies on the molecular classification of endometrioid carcinoma (EC) with microcystic, elongated, and fragmented (MELF) pattern invasion are limited. In this study, 77 cases of ECs with MELF patterns in Chinese women were collected. The molecular classification of the fifth edition of the World Health Organization was used to classify the molecular subtypes using immunohistochemistry staining (mismatch repair [MMR]-immunohistochemistry: MSH2, MSH6, MLH1, and PMS2; p53) and Sanger sequencing targeted POLE . The results showed that the prevalence of the 4 molecular subtypes in EC with MELF pattern was 6.5% (5/77) for POLE mutation, 20.8% (16/77) for MMR deficient, 11.7% (9/77) for p53-mutant, and 61.0% (47/77) for no specific molecular profile. The clinicopathological characteristics of each subtype were compared. The p53-mutant and no specific molecular profile subgroups were associated with higher International Federation of Gynecology and Obstetrics stage and International Federation of Gynecology and Obstetrics grade, deeper myometrial invasion, lymphovascular space invasion, lymph node metastasis, and absence of tumor-infiltrating lymphocytes, whereas the POLE mutation and MMR deficient subgroups were associated with lower aggressive features and prominent tumor-infiltrating lymphocytes. Progression-free survival showed that the p53-mutant and no specific molecular profile subgroups had a poorer prognosis than the POLE mutation and MMR deficient subgroups. However, lymph node metastasis was an independent factor associated with a higher risk of disease recurrence in multivariate analysis. In conclusion, ECs with MELF patterns can be divided into 4 molecular subtypes with discrepancies in aggressive clinicopathological characteristics and tumor-infiltrating lymphocytes. Molecular classification has clinical significance in a morpho-molecular approach for ECs with MELF patterns.

9.
Cell Biol Toxicol ; 40(1): 7, 2024 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-38267743

RESUMO

Air pollution has greatly increased the risk of idiopathic pulmonary fibrosis (IPF). Circular RNAs (circRNAs) have been found to play a significant role in the advancement of IPF, but there is limited evidence of correlation between circRNAs and lung epithelial cells (LECs) in IPF. This research aimed to explore the influence of circRNAs on the regulation of EMT progression in LECs, with the objective of elucidating its mechanism and establishing its association with IPF. Our results suggested that the downregulation of circGRHPR in peripheral blood of clinical cases was associated with the diagnosis of IPF. Meanwhile, we found that circGRHPR was downregulated in transforming growth factor-beta1 (TGF-ß1)-induced A549 and Beas-2b cells. It is a valid model to study the abnormal EMT progression of IPF-associated LECs in vitro. The overexpression of circGRHPR inhibited the abnormal EMT progression of TGF-ß1-induced LECs. Furthermore, as the sponge of miR-665, circGRHPR released the expression of E3 ubiquitin-protein ligase NEDD4-like (NEDD4L), thus promoting its downstream transforming growth factor beta receptor 2 (TGFBR2) ubiquitination. It is helpful to reduce the response of LECs to TGF-ß1 signaling. In summary, circGRHPR/miR-665/NEDD4L axis inhibited the abnormal EMT progression of TGF-ß1-induced LECs by promoting TGFBR2 ubiquitination, which provides new ideas and potential targets for the treatment of IPF.


Assuntos
Fibrose Pulmonar Idiopática , MicroRNAs , Humanos , Receptor do Fator de Crescimento Transformador beta Tipo II , RNA Circular/genética , Fator de Crescimento Transformador beta1/genética , Fibrose Pulmonar Idiopática/genética , Células Epiteliais , Transição Epitelial-Mesenquimal/genética , Pulmão , MicroRNAs/genética
10.
Nanotechnology ; 35(14)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38134436

RESUMO

Due to the misuse and overuse of the antibiotic tetracycline (TC), as well as its refractory degradability, it has become a stubborn environmental contaminant. In this study, a self-standing polyacrylonitrile-based ZIF-67@CNT/ACF aligned anodic membrane was fabricated by innovatively incorporating ZIF-67@CNT nanoparticles into an aligned carbon nanofiber (ACF) membrane to treat the TC. The flow-through nanoporous construction of the ZIF-67@CNT/ACF membrane reactor can compress the diffusion boundary layer on the electrode surface to enhance mass transfer under microscopic laminar flow, which can further enhance the degradation rate. In addition, the enhanced degradation performance also benefited from the significant electrooxidation capacity of the ZIF-67@CNT/ACF membrane. At the optimal electrocatalytic condition of 3.0 V applied potential and pH 6, the degradation rate reached 81% in 1 h for an initial TC concentration of 10 mg l-1. The refractory and highly toxic TC was electrochemically degraded into small non-toxic molecules. Our results indicate that electrocatalytic TC degradation can be enhanced by ZIF-67@CNT/ACF membrane.

11.
BMC Gastroenterol ; 24(1): 176, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773485

RESUMO

BACKGROUND: Angiogenesis is a critical step in colorectal cancer growth, progression and metastasization. CT are routine imaging examinations for preoperative clinical evaluation in colorectal cancer patients. This study aimed to investigate the predictive value of preoperative CT enhancement rate (CER) and CT perfusion parameters on angiogenesis in colorectal cancer, as well as the association of preoperative CER and CT perfusion parameters with serum markers. METHODS: This retrospective analysis included 42 patients with colorectal adenocarcinoma. Median of microvessel density (MVD) as the cut-off value, it divided 42 patients into high-density group (MVD ≥ 35/field, n = 24) and low-density group (MVD < 35/field, n = 18), and 25 patients with benign colorectal lesions were collected as the control group. Statistical analysis of CER, CT perfusion parameters, serum markers were performed in all groups. Receiver operating curves (ROC) were plotted to evaluate the diagnostic efficacy of relevant CT perfusion parameters for tumor angiogenesis; Pearson correlation analysis explored potential association between CER, CT perfusion parameters and serum markers. RESULTS: CER, blood volume (BV), blood flow (BF), permeability surface (PS) and carbohydrate antigen 19 - 9 (CA19-9), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), trefoil factor 3 (TFF3), vascular endothelial growth factor (VEGF) in colorectal adenocarcinoma were significantly higher than those in the control group, the parameters in high-density group were significantly higher than those in the low-density group (P < 0.05); however, the time to peak (TTP) of patients in colorectal adenocarcinoma were significantly lower than those in the control group, and the high-density group showed a significantly lower level compared to the low-density group (P < 0.05). The combined parameters BF + TTP + PS and BV + BF + TTP + PS demonstrated the highest area under the curve (AUC), both at 0.991. Pearson correlation analysis showed that the serum levels of CA19-9, CA125, CEA, TFF3, and VEGF in patients showed positive correlations with CER, BV, BF, and PS (P < 0.05), while these indicators exhibited negative correlations with TTP (P < 0.05). CONCLUSIONS: Some single and joint preoperative CT perfusion parameters can accurately predict tumor angiogenesis in colorectal adenocarcinoma. Preoperative CER and CT perfusion parameters have certain association with serum markers.


Assuntos
Adenocarcinoma , Antígeno Carcinoembrionário , Neoplasias Colorretais , Neovascularização Patológica , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Colorretais/sangue , Neoplasias Colorretais/patologia , Neoplasias Colorretais/irrigação sanguínea , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adenocarcinoma/irrigação sanguínea , Idoso , Neovascularização Patológica/diagnóstico por imagem , Neovascularização Patológica/sangue , Tomografia Computadorizada por Raios X/métodos , Antígeno Carcinoembrionário/sangue , Biomarcadores Tumorais/sangue , Adulto , Densidade Microvascular , Antígeno CA-19-9/sangue , Curva ROC , Fator A de Crescimento do Endotélio Vascular/sangue , Volume Sanguíneo , Cuidados Pré-Operatórios/métodos
12.
BMC Geriatr ; 24(1): 110, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287262

RESUMO

BACKGROUND: Frailty contributes to adverse outcomes in older adults and places a heavy burden on healthcare resources. Dysphagia is associated with frailty, but the mechanisms by which dysphagia affects frailty in older adults are unclear. This study aimed to investigate a serial mediating effect of self-perceived oral health and self-reported nutritional status in the relationship between dysphagia and frailty among hospitalized older patients in China. METHODS: This cross-sectional study included 1200 patients aged ≥ 65 years in the Department of Geriatrics, Shaanxi Provincial People's Hospital. A structured face-to-face interview was used to survey the following questionnaires: General Information Questionnaire, Tilburg Frailty Indicators (TFI), Eating Assessment Tool-10 (EAT-10), 30mL Water Swallow Test (WST), Geriatric Oral Health Assessment Index (GOHAI), and Short-Form Mini-Nutritional Assessment (MNA-SF). A total of 980 participants with complete data were included in the analysis. Statistical analysis was performed using SPSS 26.0 and Amos 28.0 software. Spearman's correlation analysis was used for correlation analysis of study variables. The results of the multivariate linear regression analysis for frailty were used as covariates in the mediation analysis, and the structural equation model (SEM) was used to analyze the mediating effects among the study variables. RESULTS: Dysphagia, self-perceived oral health, self-reported nutritional status, and frailty were significantly correlated (P<0.001). Dysphagia was found to directly affect frailty (ß = 0.161, 95%CI = 0.089 to 0.235) and through three significant mediation pathways: (1) the path through self-perceived oral health (ß = 0.169, 95%CI = 0.120 to 0.221), accounting for 36.98% of the total effect; (2) the path through self-reported nutritional status (ß = 0.050, 95%CI = 0.023 to 0.082), accounting for 10.94% of the total effect; (3) the path through self-perceived oral health and self-reported nutritional status (ß = 0.077, 95%CI = 0.058 to 0.102), accounting for 16.85% of the total effect. The total mediation effect was 64.77%. CONCLUSIONS: This study indicated that dysphagia was significantly associated with frailty. Self-perceived oral health and self-reported nutritional status were serial mediators of this relationship. Improving the oral health and nutritional status of hospitalized older patients may prevent or delay the frailty caused by dysphagia.


Assuntos
Transtornos de Deglutição , Fragilidade , Idoso , Humanos , Estado Nutricional , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Fragilidade/complicações , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Autorrelato , Estudos Transversais , Saúde Bucal , Avaliação Geriátrica/métodos
13.
Biomed Chromatogr ; 38(7): e5907, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38783548

RESUMO

VX-548 is an orally active and highly selective NaV 1.8 inhibitor that is undergoing development for the treatment of acute pain. The aim of this study was to develop a liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the measurement of VX-548 in monkey plasma. VX-548 was extracted from the plasma using acetonitrile-mediated protein precipitation. The quantitative analysis was performed on a Thermo Vantage TSQ mass spectrometer with ibrutinib as an internal standard. Chromatography was performed on a Waters ACQUITY UPLC BEH C18 column with 0.1% aqueous formic acid and acetonitrile as mobile phase. The precursor-to-product ion transitions were m/z 474.2 > 165.0 and m/z 441.2 > 138.1 for VX-548 and internal standard, respectively. This developed method was successfully validated in the concentration range of 1-1000 ng/mL. The calibration curve showed excellent linearity with a correlation coefficient of >0.999. The precision expressed as relative standard deviation (RSD) was <8.4%, whereas the accuracy denoted as relative error (RE) ranged from -5.0% to 9.1%. The mean recovery was >84%. VX-548 was stable in monkey plasma after storage under certain conditions. The validated method was successfully applied to the pharmacokinetic study of VX-548 in monkey plasma after single oral (2 mg/kg) and intravenous (1 mg/kg) administrations.


Assuntos
Espectrometria de Massas em Tandem , Animais , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Modelos Lineares , Masculino , Sensibilidade e Especificidade , Limite de Detecção , Estabilidade de Medicamentos
14.
BMC Surg ; 24(1): 56, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355554

RESUMO

OBJECTIVES: In this study, we aimed to develop a multiparameter prediction model to improve the diagnostic accuracy of invasive adenocarcinoma in pulmonary pure glass nodules. METHOD: We included patients with pulmonary pure glass nodules who underwent lung resection and had a clear pathology between January 2020 and January 2022 at the Qilu Hospital of Shandong University. We collected data on the clinical characteristics of the patients as well as their preoperative biomarker results and computed tomography features. Thereafter, we performed univariate and multivariate logistic regression analyses to identify independent risk factors, which were then used to develop a prediction model and nomogram. We then evaluated the recognition ability of the model via receiver operating characteristic (ROC) curve analysis and assessed its calibration ability using the Hosmer-Lemeshow test and calibration curves. Further, to assess the clinical utility of the nomogram, we performed decision curve analysis. RESULT: We included 563 patients, comprising 174 and 389 cases of invasive and non-invasive adenocarcinoma, respectively, and identified seven independent risk factors, namely, maximum tumor diameter, age, serum amyloid level, pleural effusion sign, bronchial sign, tumor location, and lobulation. The area under the ROC curve was 0.839 (95% CI: 0.798-0.879) for the training cohort and 0.782 (95% CI: 0.706-0.858) for the validation cohort, indicating a relatively high predictive accuracy for the nomogram. Calibration curves for the prediction model also showed good calibration for both cohorts, and decision curve analysis showed that the clinical prediction model has clinical utility. CONCLUSION: The novel nomogram thus constructed for identifying invasive adenocarcinoma in patients with isolated pulmonary pure glass nodules exhibited excellent discriminatory power, calibration capacity, and clinical utility.


Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Modelos Estatísticos , Prognóstico , Estudos Retrospectivos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Nomogramas
15.
J Sci Food Agric ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38716684

RESUMO

BACKGROUND: Yangjiang douchi (YD) is a traditional fermented soybean product, which is popular in Chinese cuisine for its unique flavor. However, due to its high salt content and unstable flavor, its competitiveness in the international market is gradually weakening. Microorganisms have a key role in the production process of YD because it is a fermented food but the effect of microorganisms on the volatile compounds of YD is also not currently clear. RESULTS: In this paper, aroma compounds and microbial diversity in different fermentation stages of YD were analyzed using gas chromatography-mass spectrometry/olfactometry (GC-MS/O) and IlluminaMiseq system sequencing. A total of 78 aroma-active compounds were detected throughout the fermentation process and they influenced the formation of flavor in YD. Fungi flora were relatively single in YD, and bacteria were rich and varied. A total of 418 species of bacteria were present during fermentation, with unclassified_Staphylococcus, Staphylococcus_kloosii, and Bacillus_velezensis_Bacillus predominating. There were 25 species of fungi at the species level, and Aspergillus minisclerotigenes (OTU 4) played a dominant role in the whole fermentation process. CONCLUSION: Staphylococcus and Bacillus in the bacterial genus were strongly correlated with most flavor compounds detected, and A. minisclerotigenes in the fungi were more relevant to flavor compounds. This research provides a theoretical basis for the enhancement of the flavor of traditional fermented douchi in China. © 2024 Society of Chemical Industry.

16.
Development ; 147(6)2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32094118

RESUMO

The most significant feature of meiosis is the recombination process during prophase I. CXXC finger protein 1 (CXXC1) binds to CpG islands and mediates the deposition of H3K4me3 by the SETD1 complex. CXXC1 is also predicted to recruit H3K4me3-marked regions to the chromosome axis for the generation of double-strand breaks (DSBs) in the prophase of meiosis. Therefore, we deleted Cxxc1 before the onset of meiosis with Stra8-Cre The conditional knockout mice were completely sterile with spermatogenesis arrested at MII. Knockout of Cxxc1 led to a decrease in the H3K4me3 level from the pachytene to the MII stage and caused transcriptional disorder. Many spermatogenesis pathway genes were expressed early leading to abnormal acrosome formation in arrested MII cells. In meiotic prophase, deletion of Cxxc1 caused delayed DSB repair and improper crossover formation in cells at the pachytene stage, and more than half of the diplotene cells exhibited precocious homologous chromosome segregation in both male and female meiosis. Cxxc1 deletion also led to a significant decrease of H3K4me3 enrichment at DMC1-binding sites, which might compromise DSB generation. Taken together, our results show that CXXC1 is essential for proper meiotic crossover formation in mice and suggest that CXXC1-mediated H3K4me3 plays an essential role in meiotic prophase of spermatogenesis and oogenesis.


Assuntos
Troca Genética/fisiologia , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Meiose/fisiologia , Transativadores/fisiologia , Animais , Células Cultivadas , Embrião de Mamíferos , Feminino , Masculino , Meiose/genética , Metilação , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Oogênese/genética , Processamento de Proteína Pós-Traducional/genética , Espermatogênese/genética , Transativadores/genética
17.
J Virol ; 96(17): e0077422, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-35972291

RESUMO

XIAP-associated factor 1 (XAF1) is an interferon (IFN)-stimulated gene (ISG) that enhances IFN-induced apoptosis. However, it is unexplored whether XAF1 is essential for the host fighting against invaded viruses. Here, we find that XAF1 is significantly upregulated in the host cells infected with emerging RNA viruses, including influenza, Zika virus (ZIKV), and SARS-CoV-2. IFN regulatory factor 1 (IRF1), a key transcription factor in immune cells, determines the induction of XAF1 during antiviral immunity. Ectopic expression of XAF1 protects host cells against various RNA viruses independent of apoptosis. Knockout of XAF1 attenuates host antiviral innate immunity in vitro and in vivo, which leads to more severe lung injuries and higher mortality in the influenza infection mouse model. XAF1 stabilizes IRF1 protein by antagonizing the CHIP-mediated degradation of IRF1, thus inducing more antiviral IRF1 target genes, including DDX58, DDX60, MX1, and OAS2. Our study has described a protective role of XAF1 in the host antiviral innate immunity against RNA viruses. We have also elucidated the molecular mechanism that IRF1 and XAF1 form a positive feedback loop to induce rapid and robust antiviral immunity. IMPORTANCE Rapid and robust induction of antiviral genes is essential for the host to clear the invaded viruses. In addition to the IRF3/7-IFN-I-STAT1 signaling axis, the XAF1-IRF1 positive feedback loop synergistically or independently drives the transcription of antiviral genes. Moreover, XAF1 is a sensitive and reliable gene that positively correlates with the viral infection, suggesting that XAF1 is a potential diagnostic marker for viral infectious diseases. In addition to the antitumor role, our study has shown that XAF1 is essential for antiviral immunity. XAF1 is not only a proapoptotic ISG, but it also stabilizes the master transcription factor IRF1 to induce antiviral genes. IRF1 directly binds to the IRF-Es of its target gene promoters and drives their transcriptions, which suggests a unique role of the XAF1-IRF1 loop in antiviral innate immunity, particularly in the host defect of IFN-I signaling such as invertebrates.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Fator Regulador 1 de Interferon , Infecções por Vírus de RNA , Vírus de RNA , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Animais , Proteínas Reguladoras de Apoptose/imunologia , Humanos , Imunidade Inata , Fator Regulador 1 de Interferon/imunologia , Camundongos , Camundongos Knockout , Infecções por Vírus de RNA/imunologia , Replicação Viral
18.
Microb Pathog ; 183: 106320, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37625663

RESUMO

BACKGROUND: Transmissible gastroenteritis virus (TGEV), which belongs to the coronaviruses (CoVs), causes diarrhea and high mortality rates in piglets and poses a huge threat and loss to the pig industry in China. METHOD: We estimated the prevalence of TGEV in Chinese pig animals from 1983 to 2022 by screening 36 papers on TGEV investigations in China from databases such as China Knowledge Network (CNKI), Wanfang Database, Science and Technology Journal Repository (VIP), PubMed, and ScienceDirect, excluding duplicate literature and other host studies according to the exclusion criteria we developed, and excluding literature with incomplete data to extract information from studies that could estimate the prevalence of TGEV infection in pigs in mainland China. RESULTS: A total of 36 studies (including data from 50,403 pigs) met our evaluation criteria. The overall estimated prevalence of TGEV infection in pigs in China is 10% (3887/50403), and the prevalence of TGEV in northeast China is 38% (2582/3078700) is significantly higher than the rest of China. The prevalence of TGEV infection was related to the sampling season and region. CONCLUSION: The results of the study show that the prevalence of TGEV is clearly seasonal and regional. Therefore, further research and monitoring of the prevalence of TGEV infection and the development of control programs based on different conditions are essential. In addition, effective and robust regulatory measures should be taken in colder regions to prevent the spread and transmission of TGEV in pigs.


Assuntos
Gastroenterite Suína Transmissível , Vírus da Gastroenterite Transmissível , Animais , China/epidemiologia , Diarreia , Gastroenterite/epidemiologia , Gastroenterite/veterinária , Prevalência , Suínos , Gastroenterite Suína Transmissível/epidemiologia , Gastroenterite Suína Transmissível/virologia
19.
J Sleep Res ; 32(3): e13781, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36372957

RESUMO

Despite the high sensitivity of the STOP-Bang questionnaire [snoring, tiredness, observed apneas, high blood pressure, body mass index, age, neck size, gender] questionnaire (SBQ), which is widely used to screen individuals at high risk of obstructive sleep apnea (OSA), few studies have evaluated the discrimination related to sex in the SBQ. Therefore, our study aimed to assess whether SBQ performance is gender-related and modified by changing body mass index (BMI) and neck circumference (NC) cut-off values. A total of 470 patients attended the sleep centres. They were divided into moderate-to-severe OSA and non-moderate-to-severe OSA groups based on the apnea-hypopnea index (AHI) and the results of the SBQ screening. The predictive performance of the SBQ screening instrument was evaluated by 2 × 2 contingency tables and discriminatory ability, which was estimated from the area under the curve (AUC) obtained from receiver operating characteristic curve. Our results suggest that when screening for moderate-to-severe OSA, the original SBQ has higher sensitivity and lower specificity for men; however, women have higher specificity and lower sensitivity. The SBQ achieved the maximum AUC of 0.783 for men and 0.634 for women when the BMI cut-off value was established at 30 kg/m2 and the NC cut-off value was established at 38 cm in men, and the BMI cut-off value was established at 25 kg/m2 and the NC cut-off value at 36 cm in women. Balancing the optimal sensitivity and specificity, the cut-off value of the optimal modified SBQ total scores for men was determined to be ≥4 and ≥3 for women.


Assuntos
Programas de Rastreamento , Apneia Obstrutiva do Sono , Masculino , Humanos , Feminino , Programas de Rastreamento/métodos , Polissonografia , Inquéritos e Questionários , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , China/epidemiologia
20.
Psychol Health Med ; 28(5): 1358-1367, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35016579

RESUMO

Previous studies have reported high rates of poor mental health among nursing students, but few studies focused on the internal pathway of mental health. This cross-sectional study was conducted at a vocational medical school and investigated 384 nursing students. Symptom Check List-90, Index of Well-Being Scale and Cynical Attitudes Toward College Scale were used to test mental health, subjective well-being (SWB) and cynicism of nursing students, respectively. Academic cynicism, social cynicism and institutional cynicism were negatively related to mental health. SWB not only directly had positive effect on mental health, but had an indirect effect on mental health through academic cynicism, social cynicism and institutional cynicism.


Assuntos
Saúde Mental , Estudantes de Enfermagem , Humanos , Estudantes de Enfermagem/psicologia , Estudos Transversais , Inquéritos e Questionários
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