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1.
Genes Dev ; 38(7-8): 308-321, 2024 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-38719541

RESUMO

The transcription factor Oct4/Pou5f1 is a component of the regulatory circuitry governing pluripotency and is widely used to induce pluripotency from somatic cells. Here we used domain swapping and mutagenesis to study Oct4's reprogramming ability, identifying a redox-sensitive DNA binding domain, cysteine residue (Cys48), as a key determinant of reprogramming and differentiation. Oct4 Cys48 sensitizes the protein to oxidative inhibition of DNA binding activity and promotes oxidation-mediated protein ubiquitylation. Pou5f1 C48S point mutation has little effect on undifferentiated embryonic stem cells (ESCs) but upon retinoic acid (RA) treatment causes retention of Oct4 expression, deregulated gene expression, and aberrant differentiation. Pou5f1 C48S ESCs also form less differentiated teratomas and contribute poorly to adult somatic tissues. Finally, we describe Pou5f1 C48S (Janky) mice, which in the homozygous condition are severely developmentally restricted after E4.5. Rare animals bypassing this restriction appear normal at birth but are sterile. Collectively, these findings uncover a novel Oct4 redox mechanism involved in both entry into and exit from pluripotency.


Assuntos
Diferenciação Celular , Reprogramação Celular , Fator 3 de Transcrição de Octâmero , Oxirredução , Fator 3 de Transcrição de Octâmero/metabolismo , Fator 3 de Transcrição de Octâmero/genética , Animais , Camundongos , Diferenciação Celular/genética , Reprogramação Celular/genética , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/metabolismo , Tretinoína/farmacologia , Tretinoína/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos
2.
J Biol Chem ; 300(3): 105754, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38360270

RESUMO

KDELR (Erd2 [ER retention defective 2] in yeasts) is a receptor protein that retrieves endoplasmic reticulum (ER)-resident proteins from the Golgi apparatus. However, the role of the KDELR-mediated ER-retrieval system in regulating cellular homeostasis remains elusive. Here, we show that the absence of Erd2 triggers the unfolded protein response (UPR) and enhances mitochondrial respiration and reactive oxygen species in an UPR-dependent manner in the fission yeast Schizosaccharomyces pombe. Moreover, we perform transcriptomic analysis and find that the expression of genes related to mitochondrial respiration and the tricarboxylic acid cycle is upregulated in a UPR-dependent manner in cells lacking Erd2. The increased mitochondrial respiration and reactive oxygen species production is required for cell survival in the absence of Erd2. Therefore, our findings reveal a novel role of the KDELR-Erd2-mediated ER-retrieval system in modulating mitochondrial functions and highlight its importance for cellular homeostasis in the fission yeast.


Assuntos
Retículo Endoplasmático , Mitocôndrias , Schizosaccharomyces , Resposta a Proteínas não Dobradas , Retículo Endoplasmático/genética , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático , Mitocôndrias/genética , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo
3.
FASEB J ; 38(13): e23727, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38877845

RESUMO

Oxidative stress is proposed as a regulatory element in various neurological disorders, which is involved in the progress of several neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Antioxidant drugs are widely used to alleviate neurodegenerative disorders. Astragalus membranaceus (Huangqi, AM) is a commonly used medicinal herb with a wide range of pharmacological effects. Here, the protective effect and mechanism of AM extract (AME) and its bioactive compounds against neurodegenerative disorders via alleviating oxidative stress were detected using adult Drosophila melanogaster. The drug safety was measured by development analysis; oxidative stress resistance ability was detected by survival rate under H2O2 environment; ROS level was detected by DHE staining and gstD1-GFP fluoresence assay; antioxidative abilitiy was represent by measuring antioxidant enzyme activity, antioxidative-related gene expression, and ATP and MFN2 levels. The neuroprotective effect was evaluated by lifespan and locomotion analysis in Aß42 transgenic and Pink1B9 mutants. AME dramatically increased the survival rates, improved the CAT activity, restored the decreased mRNA expressions of Sod1, Cat, and CncC under H2O2 stimulation, and ameliorated the neurobehavioral defects of the AD and PD. Thirteen small molecules in AM had antioxidant function, in which vanillic acid and daidzein had the most potent antioxidant effect. Vanillic acid and daidzein could increase the activities of SOD and CAT, GSH level, and the expressions of antioxidant genes. Vanillic acid could improve the levels of ATP and MFN2, and mRNA expressions of ND42 and SDHC to rescue mitochondrial dysfunction. Furthermore, vanillic acid ameliorated neurobehavioral defects of PD. Daidzein ameliorated neurobehavioral defect of Aß-induced AD mode. Taken together, AM plays a protective role in oxidative damage, thereby as a potential natural drug to treat neurodegenerative disorders.


Assuntos
Antioxidantes , Astragalus propinquus , Drosophila melanogaster , Doenças Neurodegenerativas , Estresse Oxidativo , Animais , Estresse Oxidativo/efeitos dos fármacos , Astragalus propinquus/química , Drosophila melanogaster/efeitos dos fármacos , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Extratos Vegetais/farmacologia , Animais Geneticamente Modificados , Medicamentos de Ervas Chinesas/farmacologia , Peróxido de Hidrogênio , Peptídeos beta-Amiloides/metabolismo
4.
Nano Lett ; 24(1): 61-66, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38113396

RESUMO

The decay of excited states via radiative and nonradiative paths is well understood in molecules and bulk semiconductors but less so in nanocrystals. Here, we perform time-resolved photoluminescence (t-PL) experiments on CsPbBr3 metal-halide perovskite nanocrystals, with a time resolution of 3 ps, sufficient to observe the decay of both excitons and biexcitons as a function of temperature. The striking result is that the radiative rate constant of the single exciton increases at low temperatures with an exponential functional form, suggesting quantum coherent effects with dephasing at high temperatures. The opposing directions of the radiative and nonradiative decay rate constants enable enhanced brightening of PL from excitons to biexcitons due to quantum effects, promoting a faster approach to the quantum theoretical limits of light emission. Ab initio quantum dynamics simulations reproduce the experimental observations of radiation controlled by quantum spatial coherence enhanced at low temperatures.

5.
J Am Chem Soc ; 146(17): 12215-12224, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629769

RESUMO

We report the construction of frustrated Lewis pairs (FLPs) in a metal-organic framework (MOF), where both Lewis acid (LA) and Lewis base (LB) are fixed to the backbone. The anchoring of a tritopic organoboron linker as LA and a monotopic linker as LB to separate metal oxide clusters in a tetrahedron geometry allows for the precise control of distance between them. As the type of monotopic LB linker varies, pyridine, phenol, aniline, and benzyl alcohol, a series of 11 FLPs were constructed to give fixed distances of 7.1, 5.5, 5.4, and 4.8 Å, respectively, revealed by 11B-1H solid-state nuclear magnetic resonance spectroscopy. Keeping LA and LB apart by a fixed distance makes it possible to investigate the electrostatic effect by changing the functional groups in the monotopic LB linker, while the LA counterpart remains unaffected. This approach offers new chemical environments of the active site for FLP-induced catalysis.

6.
Eur Respir J ; 63(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38514095

RESUMO

INTRODUCTION: Patients with allergic bronchopulmonary aspergillosis (ABPA) suffer from repeated exacerbations. The involvement of T-cell subsets remains unclear. METHODS: We enrolled ABPA patients, asthma patients and healthy controls. T-helper type 1 (Th1), 2 (Th2) and 17 (Th17) cells, regulatory T-cells (Treg) and interleukin (IL)-21+CD4+T-cells in total or sorted subsets of peripheral blood mononuclear cells and ABPA bronchoalveolar lavage fluid (BALF) were analysed using flow cytometry. RNA sequencing of subsets of CD4+T-cells was done in exacerbated ABPA patients and healthy controls. Antibodies of T-/B-cell co-cultures in vitro were measured. RESULTS: ABPA patients had increased Th2 cells, similar numbers of Treg cells and decreased circulating Th1 and Th17 cells. IL-5+IL-13+IL-21+CD4+T-cells were rarely detected in healthy controls, but significantly elevated in the blood of ABPA patients, especially the exacerbated ones. We found that IL-5+IL-13+IL-21+CD4+T-cells were mainly peripheral T-helper (Tph) cells (PD-1+CXCR5-), which also presented in the BALF of ABPA patients. The proportions of circulating Tph cells were similar among ABPA patients, asthma patients and healthy controls, while IL-5+IL-13+IL-21+ Tph cells significantly increased in ABPA patients. Transcriptome data showed that Tph cells of ABPA patients were Th2-skewed and exhibited signatures of follicular T-helper cells. When co-cultured in vitro, Tph cells of ABPA patients induced the differentiation of autologous B-cells into plasmablasts and significantly enhanced the production of IgE. CONCLUSION: We identified a distinctly elevated population of circulating Th2-skewed Tph cells that induced the production of IgE in ABPA patients. It may be a biomarker and therapeutic target for ABPA.


Assuntos
Aspergilose Broncopulmonar Alérgica , Linfócitos B , Líquido da Lavagem Broncoalveolar , Células Th2 , Humanos , Masculino , Feminino , Aspergilose Broncopulmonar Alérgica/imunologia , Adulto , Células Th2/imunologia , Pessoa de Meia-Idade , Estudos de Casos e Controles , Linfócitos B/imunologia , Líquido da Lavagem Broncoalveolar/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Linfócitos T Reguladores/imunologia , Asma/imunologia , Células Th17/imunologia , Linfócitos T Auxiliares-Indutores/imunologia
7.
Small ; : e2401437, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38932671

RESUMO

Fluorophores with color-shifting characteristics have attracted enormous research interest in the quantitative application of RNA sensors. It reports here a simple synthesis, luminescent properties, and co-transcription ability of de-conjugated triphenylmethane leucomalachite green (LMG). This novel clusteroluminescence fluorophore is rapidly synthesized from malachite green (MG) in reductive transcription system containing dithiothreitol, emitting fluorescence in the UV region through space conjugation. The co-transcribed MG RNA aptamer (MGA) bound to the ligand, resulting in red fluorescence from the through-bond conjugation. Given the equilibrated color-shifting fluorophores, they are rationally employed in a 3WJ-based rolling circle transcription switch, with the target-aptamer acting as an activator to achieve steric allosterism. This one-pot system allows the target to compete continuously for allosteric sites, and the activated transcription switches continue to amplify MGA forward, achieving accurate Aflatoxin 1 quantification at the picomolar level in 1 h. Due to the programmability of this RNA sensor, the design method of target-competitive aptamers is standardized, making it universally applicable.

8.
Bioinformatics ; 39(12)2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-38109668

RESUMO

MOTIVATION: There is mounting evidence that the subcellular localization of lncRNAs can provide valuable insights into their biological functions. In the real world of transcriptomes, lncRNAs are usually localized in multiple subcellular localizations. Furthermore, lncRNAs have specific localization patterns for different subcellular localizations. Although several computational methods have been developed to predict the subcellular localization of lncRNAs, few of them are designed for lncRNAs that have multiple subcellular localizations, and none of them take motif specificity into consideration. RESULTS: In this study, we proposed a novel deep learning model, called LncLocFormer, which uses only lncRNA sequences to predict multi-label lncRNA subcellular localization. LncLocFormer utilizes eight Transformer blocks to model long-range dependencies within the lncRNA sequence and shares information across the lncRNA sequence. To exploit the relationship between different subcellular localizations and find distinct localization patterns for different subcellular localizations, LncLocFormer employs a localization-specific attention mechanism. The results demonstrate that LncLocFormer outperforms existing state-of-the-art predictors on the hold-out test set. Furthermore, we conducted a motif analysis and found LncLocFormer can capture known motifs. Ablation studies confirmed the contribution of the localization-specific attention mechanism in improving the prediction performance. AVAILABILITY AND IMPLEMENTATION: The LncLocFormer web server is available at http://csuligroup.com:9000/LncLocFormer. The source code can be obtained from https://github.com/CSUBioGroup/LncLocFormer.


Assuntos
Aprendizado Profundo , RNA Longo não Codificante , RNA Longo não Codificante/genética , Software , Biologia Computacional/métodos
9.
Cell Commun Signal ; 22(1): 401, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148095

RESUMO

TP53 mutation (TP53-mut) correlates with inferior survival in many cancers, whereas its prognostic role in diffuse large B-cell lymphoma (DLBCL) is still in controversy. Therefore, more precise risk stratification needs to be further explored for TP53-mut DLBCL patients. A set of 2637 DLBCL cases from multiple cohorts, was enrolled in our analysis. Among the 2637 DLBCL patients, 14.0% patients (370/2637) had TP53-mut. Since missense mutations account for the vast majority of TP53-mut DLBCL patients, and most non-missense mutations affect the function of the P53 protein, leading to worse survival rates, we distinguished patients with missense mutations. A TP53 missense mutation risk model was constructed based on a 150-combination machine learning computational framework, demonstrating excellent performance in predicting prognosis. Further analysis revealed that patients with high-risk missense mutations are significantly associated with early progression and exhibit dysregulation of multiple immune and metabolic pathways at the transcriptional level. Additionally, the high-risk group showed an absolutely suppressed immune microenvironment. To stratify the entire cohort of TP53-mut DLBCL, we combined clinical characteristics and ultimately constructed the TP53 Prognostic Index (TP53PI) model. In summary, we identified the truly high-risk TP53-mut DLBCL patients and explained this difference at the mutation and transcriptional levels.


Assuntos
Linfoma Difuso de Grandes Células B , Proteína Supressora de Tumor p53 , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Humanos , Proteína Supressora de Tumor p53/genética , Prognóstico , Mutação de Sentido Incorreto/genética , Mutação/genética , Microambiente Tumoral/genética , Masculino , Feminino , Fatores de Risco , Pessoa de Meia-Idade
10.
Ann Allergy Asthma Immunol ; 133(2): 168-176.e1, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38777120

RESUMO

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) is characterized by enhanced TH2 inflammatory response. Fractional exhaled nitric oxide (FeNO) measurement has been used as a valuable tool in predicting the development and management of asthma, another typical TH2 inflammation. However, the clinical significance of FeNO in ABPA remains unclear. OBJECTIVE: To investigate the association between FeNO and the prognosis of patients with ABPA to provide a basis for the use of FeNO in evaluating the efficacy of glucocorticoids in ABPA treatment. METHODS: This study comprised 2 parts; 58 patients were enrolled in the retrospective study. Clinical indexes in patients with different prognoses were compared, and receiver operating characteristic curve analysis was used to determine the threshold value. The prospective observational study involved 61 patients who were regularly followed up at 4 to 6 weeks and 6 months since the initial treatment. Patients were grouped on the basis of baseline FeNO values; correlation analysis was performed in the clinical data. RESULTS: Different prognoses were observed between patients with high and low baseline FeNO values, with a threshold value of 57 parts per billion. The percentage of Aspergillus fumigatus-specific IgE, percentage of positive A fumigatus-specific IgG, and relapse/exacerbation rate differed significantly between the high and low FeNO groups. Patients with higher FeNO needed longer treatment duration and showed shorter interval between glucocorticoid withdrawal and the next relapse/exacerbation. CONCLUSION: Our findings indicate that the level of FeNO is associated with the prognosis of ABPA. It can serve as an independent and valuable biomarker for evaluating the effectiveness of glucocorticoid treatment.


Assuntos
Aspergilose Broncopulmonar Alérgica , Aspergillus fumigatus , Biomarcadores , Glucocorticoides , Óxido Nítrico , Humanos , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergilose Broncopulmonar Alérgica/diagnóstico , Feminino , Masculino , Glucocorticoides/uso terapêutico , Adulto , Prognóstico , Biomarcadores/análise , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Aspergillus fumigatus/imunologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Imunoglobulina E/sangue , Estudos Prospectivos , Teste da Fração de Óxido Nítrico Exalado , Imunoglobulina G
11.
BMC Neurol ; 24(1): 45, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273251

RESUMO

PURPOSE: To explore the predictive value of radiomics in predicting stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients and construct a prediction model based on clinical features and DWI-MRI radiomics features. METHODS: Univariate and multivariate logistic regression analyses were used to identify the independent clinical predictors for SAP. Pearson correlation analysis and the least absolute shrinkage and selection operator with ten-fold cross-validation were used to calculate the radiomics score for each feature and identify the predictive radiomics features for SAP. Multivariate logistic regression was used to combine the predictive radiomics features with the independent clinical predictors. The prediction performance of the SAP models was evaluated using receiver operating characteristics (ROC), calibration curves, decision curve analysis, and subgroup analyses. RESULTS: Triglycerides, the neutrophil-to-lymphocyte ratio, dysphagia, the National Institutes of Health Stroke Scale (NIHSS) score, and internal carotid artery stenosis were identified as clinically independent risk factors for SAP. The radiomics scores in patients with SAP were generally higher than in patients without SAP (P < 0. 05). There was a linear positive correlation between radiomics scores and NIHSS scores, as well as between radiomics scores and infarct volume. Infarct volume showed moderate performance in predicting the occurrence of SAP, with an AUC of 0.635. When compared with the other models, the combined prediction model achieved the best area under the ROC (AUC) in both training (AUC = 0.859, 95% CI 0.759-0.936) and validation (AUC = 0.830, 95% CI 0.758-0.896) cohorts (P < 0.05). The calibration curves and decision curve analysis further confirmed the clinical value of the nomogram. Subgroup analysis showed that this nomogram had potential generalization ability. CONCLUSION: The addition of the radiomics features to the clinical model improved the prediction of SAP in AIS patients, which verified its feasibility.


Assuntos
AVC Isquêmico , Pneumonia , Acidente Vascular Cerebral , Estados Unidos , Humanos , Estudos de Viabilidade , Radiômica , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Infarto
12.
Bioorg Chem ; 150: 107590, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38955003

RESUMO

The c-ros oncogene 1 (ROS1), an oncogenic driver, is known to induce non-small cell lung cancer (NSCLC) when overactivated, particularly through the formation of fusion proteins. Traditional targeted therapies focus on inhibiting ROS1 activity with ROS 1 inhibitors to manage cancer progression. However, a new strategy involving the design of protein degraders offers a more potent approach by completely degrading ROS1 fusion oncoproteins, thereby effectively blocking their kinase activity and enhancing anti-tumour potential. Utilizing PROteolysis-TArgeting Chimera (PROTAC) technology and informed by molecular docking and rational design, we report the first ROS1-specific PROTAC, SIAIS039. This degrader effectively targets multiple ROS1 fusion oncoproteins (CD74-ROS1, SDC4-ROS1 and SLC34A2-ROS1) in engineered Ba/F3 cells and HCC78 cells, demonstrating anti-tumour effects against ROS1 fusion-driven cancer cells. It suppresses cell proliferation, induces cell cycle arrest, and apoptosis, and inhibits clonogenicity. The anti-tumour efficacy of SIAIS039 surpasses two approved drugs, crizotinib and entrectinib, and matches that of the top inhibitors, including lorlatinib and taletrectinib. Mechanistic studies confirm that the degradation induced by 039 requires the participation of ROS1 ligands and E3 ubiquitin ligases, and involves the proteasome and ubiquitination. In addition, 039 exhibited excellent oral bioavailability in a mouse xenograft model, highlighting its potential for clinical application. In conclusion, our study presents a promising and novel therapeutic strategy for ROS1 fusion-positive NSCLC by targeting ROS1 fusion oncoproteins for degradation, laying the foundation for the development of further PROTAC and offering hope for patients with ROS1 fusion-positive NSCLC.


Assuntos
Antineoplásicos , Proliferação de Células , Descoberta de Drogas , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Humanos , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/metabolismo , Animais , Estrutura Molecular , Camundongos , Relação Estrutura-Atividade , Apoptose/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Relação Dose-Resposta a Droga , Proteólise/efeitos dos fármacos , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/síntese química , Camundongos Nus
13.
BMC Psychiatry ; 24(1): 387, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783266

RESUMO

BACKGROUND: Low concentrations of S100B have neurotrophic effects and can promote nerve growth and repair, which plays an essential role in the pathophysiological and histopathological alterations of major depressive disorder (MDD) during disease development. Studies have shown that plasma S100B levels are altered in patients with MDD. In this study, we investigated whether the plasma S100B levels in MDD differ between genders. METHODS: We studied 235 healthy controls (HCs) (90 males and 145 females) and 185 MDD patients (65 males and 120 females). Plasma S100B levels were detected via multifactor assay. The Mahalanobis distance method was used to detect the outliers of plasma S100B levels in the HC and MDD groups. The Kolmogorov-Smirnov test was used to test the normality of six groups of S100B samples. The Mann-Whitney test and Scheirer-Ray-Hare test were used for the comparison of S100B between diagnoses and genders, and the presence of a relationship between plasma S100B levels and demographic details or clinical traits was assessed using Spearman correlation analysis. RESULTS: All individuals in the HC group had plasma S100B levels that were significantly greater than those in the MDD group. In the MDD group, males presented significantly higher plasma S100B levels than females. In the male group, the plasma S100B levels in the HC group were significantly higher than those in the MDD group, while in the female group, no significant difference was found between the HC and MDD groups. In the male MDD subgroup, there was a positive correlation between plasma S100B levels and years of education. In the female MDD subgroup, there were negative correlations between plasma S100B levels and age and suicidal ideation. CONCLUSIONS: In summary, plasma S100B levels vary with gender and are decreased in MDD patients, which may be related to pathological alterations in glial cells.


Assuntos
Transtorno Depressivo Maior , Subunidade beta da Proteína Ligante de Cálcio S100 , Humanos , Transtorno Depressivo Maior/sangue , Masculino , Feminino , Subunidade beta da Proteína Ligante de Cálcio S100/sangue , Adulto , Fatores Sexuais , Pessoa de Meia-Idade , Caracteres Sexuais , Biomarcadores/sangue , Estudos de Casos e Controles
14.
Artigo em Inglês | MEDLINE | ID: mdl-38804531

RESUMO

OBJECTIVES: The glow discharge plasma (GDP) procedure has proven efficacy in grafting allylamine onto zirconia dental implant surfaces to enhance osseointegration. This study explored the enhancement of zirconia dental implant properties using GDP at different energy settings (25, 50, 75, 100, and 200 W) both in vitro and in vivo. MATERIALS AND METHODS: In vitro analyses included scanning electron microscopy, wettability assessment, energy-dispersive X-ray spectroscopy, and more. In vivo experiments involved implanting zirconia dental implants into rabbit femurs and later evaluation through impact stability test, micro-CT, and histomorphometric measurements. RESULTS: The results demonstrated that 25 and 50 W GDP allylamine grafting positively impacted MG-63 cell proliferation and increased alkaline phosphatase activity. Gene expression analysis revealed upregulation of OCN, OPG, and COL-I. Both 25 and 50 W GDP allylamine grafting significantly improved zirconia's surface properties (p < .05, p < .01, p < .001). However, only 25 W allylamine grafting with optimal energy settings promoted in vivo osseointegration and new bone formation while preventing bone level loss around the dental implant (p < .05, p < .01, p < .001). CONCLUSIONS: This study presents a promising method for enhancing Zr dental implant surface's bioactivity.

15.
Lipids Health Dis ; 23(1): 5, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38185630

RESUMO

BACKGROUND: Lipid management in clinic is critical to the prevention and treatment of Chronic kidney disease (CKD), while the manifestations of lipid indicators vary in types and have flexible association with CKD prognosis. PURPOSE: Explore the associations between the widely used indicators of lipid metabolism and their distribution in clinic and CKD prognosis; provide a reference for lipid management and inform treatment decisions for patients with non-dialysis CKD stage 3-5. METHODS: This is a retrospective cohort study utilizing the Self-Management Program for Patients with Chronic Kidney Disease Cohort (SMP-CKD) database of 794 individuals with CKD stages 3-5. It covers demographic data, clinical diagnosis and medical history collection, laboratory results, circulating lipid profiles and lipid distribution assessments. Primary endpoint was defined as a composite outcome(the initiation of chronic dialysis or renal transplantation, sustained decline of 40% or more in estimated glomerular filtration rate (eGFR), doubled of serum creatinine (SCr) from the baseline, eGFR less than 5 mL/min/1.73m2, or all-cause mortality). Exposure variables were circulating lipid profiles and lipid distribution measurements. Association were assessed using Relative risks (RRs) (95% confidence intervals (CIs)) computed by multivariate Poisson models combined with least absolute shrinkage and selection operator (LASSO) regression according to categories of lipid manifestations. The best model was selected via akaike information criterion (AIC), area under curve (AUC), receiver operating characteristic curve (ROC) and net reclassification index (NRI). Subgroup analysis and sensitivity analysis were performed to assess the interaction effects and robustness.. RESULTS: 255 individuals reached the composite outcome. Median follow-up duration was 2.03 [1.06, 3.19] years. Median age was 58.8 [48.7, 67.2] years with a median eGFR of 33.7 [17.6, 47.8] ml/min/1.73 m2. Five dataset were built after multiple imputation and five category-based Possion models were constructed for each dataset. Model 5 across five datasets had the best fitness with smallest AIC and largest AUC. The pooled results of Model 5 showed that total cholesterol (TC) (RR (95%CI) (per mmol/L) :1.143[1.023,1.278], P = 0.018) and percentage of body fat (PBF) (RR (95%CI) (per percentage):0.976[0.961,0.992], P = 0.003) were significant factors of composite outcome. The results indicated that comprehensive consideration of lipid metabolism and fat distribution is more critical in the prediction of CKD prognosis.. CONCLUSION: Comprehensive consideration of lipid manifestations is optimal in predicting the prognosis of individuals with non-dialysis CKD stages 3-5.


Assuntos
Insuficiência Renal Crônica , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Distribuição Tecidual , Prognóstico , Insuficiência Renal Crônica/terapia , Lipídeos
16.
BMC Public Health ; 24(1): 538, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38383355

RESUMO

BACKGROUND: Large-scale outbreaks of scrub typhus combined with its emergence in new areas as a vector-borne rickettsiosis highlight the ongoing neglect of this disease. This study aims to explore the long-term changes and regional leading factors of scrub typhus in China, with the goal of providing valuable insights for disease prevention and control. METHODS: This study utilized a Bayesian space-time hierarchical model (BSTHM) to examine the spatiotemporal heterogeneity of scrub typhus and analyze the relationship between environmental factors and scrub typhus in southern and northern China from 2006 to 2018. Additionally, a GeoDetector model was employed to assess the predominant influences of geographical and socioeconomic factors in both regions. RESULTS: Scrub typhus exhibits a seasonal pattern, typically occurring during the summer and autumn months (June to November), with a peak in October. Geographically, the high-risk regions, or hot spots, are concentrated in the south, while the low-risk regions, or cold spots, are located in the north. Moreover, the distribution of scrub typhus is influenced by environment and socio-economic factors. In the north and south, the dominant factors are the monthly normalized vegetation index (NDVI) and temperature. An increase in NDVI per interquartile range (IQR) leads to a 7.580% decrease in scrub typhus risk in northern China, and a 19.180% increase in the southern. Similarly, of 1 IQR increase in temperature reduces the risk of scrub typhus by 10.720% in the north but increases it by 15.800% in the south. In terms of geographical and socio-economic factors, illiteracy rate and altitude are the key determinants in the respective areas, with q-values of 0.844 and 0.882. CONCLUSIONS: These results indicated that appropriate climate, environment, and social conditions would increase the risk of scrub typhus. This study provided helpful suggestions and a basis for reasonably allocating resources and controlling the occurrence of scrub typhus.


Assuntos
Tifo por Ácaros , Humanos , Tifo por Ácaros/epidemiologia , Teorema de Bayes , China/epidemiologia , Estações do Ano , Fatores Econômicos , Incidência
17.
Ren Fail ; 46(1): 2306224, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38345016

RESUMO

BACKGROUND: Recent individual studies have indicated that ultra-processed food (UPF) consumption may be associated with the incidence of chronic kidney disease (CKD). We conducted a systematic review and meta-analysis based on those longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD, and synthesizing the results. METHOD: PubMed, Embase, The Cochrane Library, Web of Science, and Scopus were searched from inception through 22 March 2023. Any longitudinal studies evaluating the relationship between UPF consumption and the risk of incident CKD were included. Two researchers independently conducted the literature screening and data extraction. RR and its 95% CI were regarded as the effect size. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of the studies included, and the effect of UPF consumption on the risk of incident CKD was analyzed with STATA version 15.1. This study's protocol was registered in PROSPERO (CRD42023411951). RESULTS: Four cohort studies with a total of 219,132 participants were included after screening. The results of the meta-analysis suggested that the highest UPF intake was associated with an increased risk of incident CKD (RR = 1.25; 95% CI: 1.18-1.33). CONCLUSIONS: High-dose UPF intake was associated with an increased risk of incident CKD. However, the underlying mechanisms remain unknown. Thus, more standardized clinical studies and further exploration of the mechanisms are needed in the future.


Assuntos
Alimento Processado , Insuficiência Renal Crônica , Humanos , Estudos de Coortes , Fast Foods/efeitos adversos , Fast Foods/estatística & dados numéricos , Alimento Processado/estatística & dados numéricos , Incidência , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Fatores de Risco
18.
J Environ Manage ; 365: 121601, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38959771

RESUMO

Tetracycline (TC) is widely present in the environment, and adsorption technology is a potential remediation method. S/N co-doped tea residue biochar (SNBC) was successfully prepared by hydrothermal carbonization method using tea residue as raw material. S was doped by Na2S2O3·5H2O, and N was doped by N in tea residue. The adsorption efficiency of SNBC could reach 94.16% when the concentration of TC was 100 mg L-1. The adsorption effect of SNBC on TC was 9.38 times more than that of unmodified biochar. Tea biochar had good adsorption effect at pH 4-9. The maximum adsorption capacity of 271 mg g-1 was calculated by the Langmuir isotherm model. The adsorption mechanism involved many mechanisms such as pore filling, π-π interaction and hydrogen bonding. The adsorbent prepared in this study could be used as an effective adsorbent in the treatment of TC wastewater.


Assuntos
Carvão Vegetal , Chá , Tetraciclina , Poluentes Químicos da Água , Carvão Vegetal/química , Tetraciclina/química , Adsorção , Chá/química , Poluentes Químicos da Água/química , Nitrogênio/química , Purificação da Água/métodos , Concentração de Íons de Hidrogênio , Águas Residuárias/química
19.
J Environ Manage ; 359: 121061, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38728983

RESUMO

China's commitment to attaining carbon neutrality by 2060 has galvanized research into carbon sequestration, a critical approach for mitigating climate change. Despite the rapid urbanization observed since the turn of the millennium, a comprehensive analysis of how urbanization influences urban carbon storage throughout China remains elusive. Our investigation delves into the nuanced effects of urbanization on carbon storage, dissecting both the direct and indirect influences by considering urban-suburban gradients and varying degrees of urban intensity. We particularly scrutinize the roles of climatic and anthropogenic factors in mediating the indirect effects of urbanization on carbon storage. Our findings reveal that urbanization in China has precipitated a direct reduction in carbon storage by approximately 13.89 Tg of carbon (Tg C). Remarkably, urban sprawl has led to a diminution of vegetation carbon storage by 8.65 Tg C and a decrease in soil carbon storage by 5.24 Tg C, the latter resulting from the sequestration of impervious surfaces and the elimination of organic matter inputs following vegetation removal. Meanwhile, carbon storage in urban greenspaces has exhibited an increase of 6.90 Tg C and offsetting 49.70% of the carbon loss induced by direct urbanization effects. However, the indirect effects of urbanization predominantly diminish carbon storage in urban greenspaces by an average of 5.40%. The degree of urban vegetation management emerges as a pivotal factor influencing the indirect effects of urbanization on carbon storage. To bolster urban carbon storage, curbing urban sprawl and augmenting urban green spaces are imperative strategies. Insights from this study are instrumental in steering sustainable urban planning and advancing towards the goal of carbon neutrality.


Assuntos
Sequestro de Carbono , Carbono , Mudança Climática , Urbanização , China , Carbono/análise , Solo/química
20.
Geriatr Nurs ; 58: 225-231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38838404

RESUMO

OBJECTIVE: To cross-culturally adapt the Australian National University Alzheimer Disease Risk Index (ANU-ADRI) and verify the reliability and validity of its cognitive activity domain. METHODS: According to Beaton's guidelines, the ANU-ADRI was were translated into Chinese. The psychometric properties of ANU-ADRI its cognitive activity was conducted among community-dwelling residents (n = 442) in Changchun, Harbin and Hegang from December 2021 to July 2023. RESULTS: The Chinese version of the ANU-ADRI had good content validity and face validity. Exploratory factor analysis of cognitive activity revealed a 3-factor structure, with a cumulative variance contribution rate of 64.124 %. Confirmatory factor analysis revealed a good model fit (x2/df = 1.664, RMSEA = 0.055, RMR = 0.090, GFI = 0.942, CFI = 0.919, IFI = 0.921, TLI = 0.902, and NFI = 0.824). The internal consistency (Cronbach's α = 0.807) and test-retest reliability (ICC = 0.787) were considered satisfactory. CONCLUSION: The ANU-ADRI showed acceptable reliability and validity for assessing risk factors for Alzheimer's disease among middle-aged and elderly community-dwelling residents.


Assuntos
Doença de Alzheimer , Vida Independente , Psicometria , Humanos , Masculino , Estudos Transversais , Feminino , Reprodutibilidade dos Testes , Idoso , China , Inquéritos e Questionários , Medição de Risco/métodos , Austrália , Comparação Transcultural , Fatores de Risco , Tradução , Pessoa de Meia-Idade
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