Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 658
Filtrar
1.
J Geriatr Cardiol ; 21(5): 523-533, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38948897

RESUMO

OBJECTIVES: To evaluate the predictive value of fasting plasma glucose (FPG) for in-hospital mortality in patients with acute myocardial infarction (AMI) with different glucose metabolism status. METHODS: We selected 5,308 participants with AMI from the prospective, nationwide, multicenter CAMI registry, of which 2,081 were diabetic and 3,227 were nondiabetic. Patients were divided into high FPG and low FPG groups according to the optimal cutoff values of FPG to predict in-hospital mortality for diabetic and nondiabetic cohorts, respectively. The primary endpoint was in-hospital mortality. RESULTS: Overall, 94 diabetic patients (4.5%) and 131 nondiabetic patients (4.1%) died during hospitalization, and the optimal FPG thresholds for predicting in-hospital death of the two cohorts were 13.2 mmol/L and 6.4 mmol/L, respectively. Compared with individuals who had low FPG, those with high FPG were significantly associated with higher in-hospital mortality in diabetic cohort (10.1% vs. 2.8%; odds ratio [OR] = 3.862, 95% confidence interval [CI]: 2.542-5.869) and nondiabetic cohort (7.4% vs. 1.7%; HR = 4.542, 95%CI: 3.041-6.782). After adjusting the potential confounders, this significant association was not changed. Furthermore, FPG as a continuous variable was positively associated with in-hospital mortality in single-variable and multivariable models regardless of diabetic status. Adding FPG to the original model showed a significant improvement in C-statistic and net reclassification in diabetic and nondiabetic cohorts. CONCLUSIONS: This large-scale registry indicated that there is a strong positive association between FPG and in-hospital mortality in AMI patients with and without diabetes. FPG might be useful to stratify patients with AMI.

2.
Sci Rep ; 14(1): 15043, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951582

RESUMO

Pile is a common foundation on the slope, which poses a serious threat to the construction and operation if the slope deformation and causes landslide. In this study, a model device of pile foundation on landslide was independently developed by relative displacement loading between pile and soil to explore the influence of landslide deformation on pile and analysis the soil failure rule and the deformation characteristics of pile in different stages of landslide deformation, a few model tests were completed including the relative displacement between soil and pile from 1 to 17 cm, and the pile diameter and the modulus of slide bed were also considered. The results indicated that: the evolution process of landslide deformation with pile foundation on could be divided into four stages including soil compaction, cracks growth, yield stage, and failure stage; ratios of the maximum soil pressure and bending moment growth from the soil compaction stage to the cracks growth stage to the total growth in these four stages are both exceeding 60%; the soil pressure increases with the increase of pile diameter and sliding bed modulus. Therefore, it is best to effectively monitor and control the landslide in the initial soil compression stage that in soil compaction stage and methods such as increasing pile foundations or reinforcing the sliding bed can be used for protection.

3.
BMJ ; 386: e079143, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043397

RESUMO

OBJECTIVE: To evaluate the effectiveness of a clinical decision support system (CDSS) in improving the use of guideline accordant antihypertensive treatment in primary care settings in China. DESIGN: Pragmatic, open label, cluster randomised trial. SETTING: 94 primary care practices in four urban regions of China between August 2019 and July 2022: Luoyang (central China), Jining (east China), and Shenzhen (south China, including two regions). PARTICIPANTS: 94 practices were randomised (46 to CDSS, 48 to usual care). 12 137 participants with hypertension who used up to two classes of antihypertensives and had a systolic blood pressure <180 mm Hg and diastolic blood pressure <110 mm Hg were included. INTERVENTIONS: Primary care practices were randomised to use an electronic health record based CDSS, which recommended a specific guideline accordant regimen for initiation, titration, or switching of antihypertensive (the intervention), or to use the same electronic health record without CDSS and provide treatment as usual (control). MAIN OUTCOME MEASURES: The primary outcome was the proportion of hypertension related visits during which an appropriate (guideline accordant) treatment was provided. Secondary outcomes were the average reduction in systolic blood pressure and proportion of participants with controlled blood pressure (<140/90 mm Hg) at the last scheduled follow-up. Safety outcomes were patient reported antihypertensive treatment related events, including syncope, injurious fall, symptomatic hypotension or systolic blood pressure <90 mm Hg, and bradycardia. RESULTS: 5755 participants with 23 113 visits in the intervention group and 6382 participants with 27 868 visits in the control group were included. Mean age was 61 (standard deviation 13) years and 42.5% were women. During a median 11.6 months of follow-up, the proportion of visits at which appropriate treatment was given was higher in the intervention group than in the control group (77.8% (17 975/23 113) v 62.2% (17 328/27 868); absolute difference 15.2 percentage points (95% confidence interval (CI) 10.7 to 19.8); P<0.001; odds ratio 2.17 (95% CI 1.75 to 2.69); P<0.001). Compared with participants in the control group, those in the intervention group had a 1.6 mm Hg (95% CI -2.7 to -0.5) greater reduction in systolic blood pressure (-1.5 mm Hg v 0.3 mm Hg; P=0.006) and a 4.4 percentage point (95% CI -0.7 to 9.5) improvement in blood pressure control rate (69.0% (3415/4952) v 64.6% (3778/5845); P=0.07). Patient reported antihypertensive treatment related adverse effects were rare in both groups. CONCLUSIONS: Use of a CDSS in primary care in China improved the provision of guideline accordant antihypertensive treatment and led to a modest reduction in blood pressure. The CDSS offers a promising approach to delivering better care for hypertension, both safely and efficiently. TRIAL REGISTRATION: ClinicalTrials.gov NCT03636334.


Assuntos
Anti-Hipertensivos , Sistemas de Apoio a Decisões Clínicas , Hipertensão , Atenção Primária à Saúde , Humanos , Hipertensão/tratamento farmacológico , Feminino , Masculino , China , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Idoso , Guias de Prática Clínica como Assunto , Registros Eletrônicos de Saúde , Fidelidade a Diretrizes , Pressão Sanguínea/efeitos dos fármacos
4.
Plants (Basel) ; 13(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38999629

RESUMO

Leaf color mutants serve as ideal materials for studying photosynthesis, chlorophyll metabolism, and other physiological processes. Here, we identified a spontaneous yellow-leaf mutant (yl1) with chlorophyll-reduced leaves from G. hirsutum L. cv ZM24. Compare to wild type ZM24 with green leaves, yl1 exhibited patchy yellow leaves and reduced chlorophyll content. To further explore the mechanisms of the patchy yellow phenotype of the mutant plant, the transcriptomics and proteomics profiles were conducted for the mutant and wild types. A total of 9247 differentially expressed genes (DEGs) and 1368 differentially accumulated proteins (DAPs) were identified. Following gene ontology (GO) annotation and KEGG enrichment, the DEGs/DAPs were found to be significantly involved in multiple important pathways, including the obsolete oxidation-reduction process, photosynthesis, light-harvesting, the microtubule-based process, cell redox homeostasis, and the carbohydrate metabolic process. In photosynthesis and the light-harvesting pathway, a total of 39 DAPs/DEGs were identified, including 9 genes in the PSI, 7 genes in the PS II, 9 genes in the light-harvesting chlorophyll protein complex (LHC), 10 genes in the PsbP family, and 4 genes in the cytochrome b6/f complex. To validate the reliability of the omics data, GhPPD1, a DAPs in the PsbP family, was knocked down in cotton using the TRV-based VIGS system, and it was observed that the GhPPD1-silenced plants exhibited patchy yellow color, accompanied by a significant decrease in chlorophyll content. In conclusion, this study integrated transcriptomic and proteomic approaches to gain a deeper understanding of the mechanisms underlying the chlorophyll-reduced leaf phenotype.

5.
J Colloid Interface Sci ; 672: 642-653, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38865878

RESUMO

Photo-thermal co-catalytic reduction of CO2 to synthesize value-added chemicals presents a promising approach to addressing environmental issues. Nevertheless, traditional catalysts exhibit low light utilization efficiency, leading to the generation of a reduced number of electron-hole pairs and rapid recombination, thereby limiting catalytic performance enhancement. Herein, a Mott-Schottky heterojunction catalyst was developed by incorporating nitrogen-doped carbon coated TiO2 supported nickel (Ni) nanometallic particles (Ni/x-TiO2@NC). The optimal Ni/0.5-TiO2@NC sample displayed a conversion rate of 71.6 % and a methane (CH4) production rate of 65.3 mmol/(gcat·h) during photo-thermal co-catalytic CO2 methanation under full-spectrum illumination, with a CH4 selectivity exceeding 99.6 %. The catalyst demonstrates good stability as it shows no decay after two reaction cycles. The Mott-Schottky heterojunction catalysts display excellent efficiency in separating photo-generated electron-hole pairs and elevate the catalysts' temperature, thus accelerating the reaction rate. The in-situ experiments revealed that light-induced electron transfer effectively facilitates H2 dissociation and enhances surface defects, thereby promoting CO2 adsorption. This study introduces a novel approach for developing photo-thermal catalysts for CO2 reduction, aiming to enhance solar energy utilization and facilitate interface electron transfer.

6.
J Thorac Dis ; 16(5): 3338-3349, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38883659

RESUMO

Background: The significant progress has been made in targeted therapy for lung adenocarcinoma (LUAD) in the past decade. Only few targeted therapeutics have yet been approved for the treatment of lung squamous cell carcinoma (LUSC). Several higher frequency of gene alterations are identified as potentially actionable in LUSC. Our work aimed to explore the complex interplay of multiple genetic alterations and pathways contributing to the pathogenesis of LUSC, with a very low frequency of a single driver molecular alterations to develop more effective therapeutic strategies in the future. Methods: We retrospectively analyzed the targeted next-generation sequencing (NGS) data (approximately 600 genes) of 335 patients initially diagnosed with non-small cell lung cancer (NSCLC) at our institution between January 2019 and March 2023 and explored the somatic genome alteration difference between LUSC and LUAD. Results: We analyzed that the presence of loss-of-function (LoF) mutations (nonsense, frameshift, and splice-site variants) in histone-lysine N-methyltransferase 2D (KMT2D) was much more prevalent in LUSC (11/53, 20.8%) than in LUAD (6/282, 2.1%). Moreover, our data indicated TP53 co-mutated with KMT2D LoF in 90.9% (10/11) LUSC and 33.3% (2/6) LUAD. Notably, the mutation allele fraction (MAF) of KMT2D was very similar to that of TP53 in the co-mutated cases. Genomic profiling of driver gene mutations of NSCLC showed that 81.8% (9/11) of the patients with LUSC with KMT2D LoF mutations had PIK3CA amplification and/or FGFR1 amplification. Conclusions: Our results prompted that somatic LoF mutations of KMT2D occur frequently in LUSC, but are less frequent in LUAD and therefore may potentially contribute to the pathogenesis of LUSC. Concurrent TP53 mutations, FGFR1 amplification, and PIK3CA amplification are very common in LUSC cases with KMT2D LoF mutations. It needs more deeper investigation on the interplay of the genes and pathways and uses larger cohorts in the future.

7.
Front Plant Sci ; 15: 1355090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828217

RESUMO

Clubroot disease poses a significant threat to Brassica crops, necessitating ongoing updates on resistance gene sources. In F2 segregants of the clubroot-resistant inbred line BrT18-6-4-3 and susceptible DH line Y510, the genetic analysis identified a single dominant gene responsible for clubroot resistance. Through bulk segregant sequencing analysis and kompetitive allele-specific polymerase chain reaction assays, CRA8.1.6 was mapped within 110 kb (12,255-12,365 Mb) between markers L-CR11 and L-CR12 on chromosome A08. We identified B raA08g015220.3.5C as the candidate gene of CRA8.1.6. Upon comparison with the sequence of disease-resistant material BrT18-6-4-3, we found 249 single-nucleotide polymorphisms, seven insertions, six deletions, and a long terminal repeat (LTR) retrotransposon (5,310 bp) at 909 bp of the first intron. However, the LTR retrotransposon was absent in the coding sequence of the susceptible DH line Y510. Given the presence of a non-functional LTR insertion in other materials, it showed that the LTR insertion might not be associated with susceptibility. Sequence alignment analysis revealed that the fourth exon of the susceptible line harbored two deletions and an insertion, resulting in a frameshift mutation at 8,551 bp, leading to translation termination at the leucine-rich repeat domain's C-terminal in susceptible material. Sequence alignment of the CDS revealed a 99.4% similarity to Crr1a, which indicate that CRA8.1.6 is likely an allele of the Crr1a gene. Two functional markers, CRA08-InDel and CRA08-KASP1, have been developed for marker-assisted selection in CR turnip cultivars. Our findings could facilitate the development of clubroot-resistance turnip cultivars through marker-assisted selection.

8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(6): 651-660, 2024 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-38818548

RESUMO

Dystrophinopathies caused by variants of DMD gene are a group of muscular diseases including Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy. With the advancement of genetic testing techniques and wider implementation of genetic screening, especially the expanded carrier screening, more and more individuals carrying DMD gene variants have been identified, whereas the genetic counseling capacity is relatively insufficient. Currently there is still a lack of professional norms for genetic counseling on dystrophinopathies. In this consensus, the main points to be covered in the pre- and post-test consultation have been discussed, with an aim to provide genetic counseling guidance for the disease diagnosis, treatment, and family reproduction.


Assuntos
Distrofina , Aconselhamento Genético , Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/genética , Distrofina/genética , Testes Genéticos/métodos , Consenso
9.
Int J Pharm ; 660: 124262, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-38815637

RESUMO

Monoclonal antibodies (mAbs) have become the predominant treatment modality for various diseases due to their high affinity and specificity. Although antibodies also have great potential for neurological diseases, they couldn't fully meet the therapeutic requirements due to their high molecular weight and limitations in crossing the blood-brain barrier (BBB). Herein, an innovative strategy based on exosomes (Exos) platform was developed to enhance the delivery of cetuximab (CTX) into the brain, and in combination with doxorubicin (DOX) for the synergistic targeted therapy of glioblastoma (GBM). The in vitro/vivo experiments have shown that exosomes could effectively promote BBB penetration and increase the content of CTX in glioma cells and brain lesions. Cytotoxicity and wound healing experiments have shown that CTX-Exo-DOX could significantly inhibit the proliferation of tumor cells. Finally, in vivo results showed that CTX-Exo-DOX significantly prolonged the survival time of tumor-bearing rats to 28 days, which was 1.47 times that of the DOX group. In summary, exosomes could deliver more antibodies into the brain, and CTX-Exo-DOX is a promising co-delivery system for the treatment of GBM. The results of this study will also provide a prospective strategy for antibody drugs in the treatment of neurological diseases.


Assuntos
Barreira Hematoencefálica , Neoplasias Encefálicas , Cetuximab , Doxorrubicina , Exossomos , Glioblastoma , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Doxorrubicina/farmacocinética , Exossomos/metabolismo , Animais , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Cetuximab/administração & dosagem , Cetuximab/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Humanos , Linhagem Celular Tumoral , Barreira Hematoencefálica/metabolismo , Ratos , Sistemas de Liberação de Medicamentos/métodos , Masculino , Encéfalo/metabolismo , Ratos Sprague-Dawley , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Ratos Nus
10.
Food Chem ; 455: 139902, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38820644

RESUMO

High-pressure homogenization modified quinoa protein (HQP) was added to porcine myofibrillar proteins (MP) to study its the influence on protein conformation, water distribution and dynamical rheological characteristics of low-salt porcine MP (0.3 M NaCl). Based on these results, the WHC, gel strength, and G' value of the low-salt MP gel were significantly improved with an increase in the added amount of HQP. A moderate amount of HQP (6%) increased the surface hydrophobicity and active sulfhydryl content of MP (P < 0.05). Moreover, the addition of HQP decreased particle size and endogenous fluorescence intensity. FT-IR results indicated that the conformation of α-helix gradually converted to ß-sheet by HQP addition. The incorporation of HQP also shortened the T2 relaxation time and enhanced the proportion of immobile water, contributing to the formation of a compact and homogeneous gel structure. In conclusion, the moderate addition of HQP can effectively enhance the structural stability and functionality of low-salt MP.


Assuntos
Chenopodium quinoa , Géis , Proteínas de Plantas , Reologia , Água , Animais , Chenopodium quinoa/química , Suínos , Água/química , Proteínas de Plantas/química , Géis/química , Interações Hidrofóbicas e Hidrofílicas , Miofibrilas/química , Proteínas Musculares/química , Conformação Proteica
11.
Clin Transl Oncol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776034

RESUMO

BACKGROUND: The aim of this study is to explore the prognostic value and immune signature of ITGB4 expression in lung adenocarcinoma (LUAD) brain metastasis. METHODS: We comprehensively screened genes associated with LUAD brain metastasis by integrating datasets from the GEO database and TMT-based quantitative proteomics profiles. Univariable survival and Multivariate Cox analysis was used to compare several clinical characteristics with survival, and a risk model was constructed. The biological functions were explored via GO and KEGG analysis. Gene set enrichment analysis (GSEA) was performed using the TCGA dataset. In addition, we use TIMER to explore the collection of ITGB4 Expression and Immune Infiltration Level in LUAD. The ability of ITGB4 to regulate tumor metastasis was further assessed by migration, invasion assay and Western-blot in H1975-BrM4 cells. RESULTS: We found that ITGB4 was the only gene with high clinical diagnostic and prognostic value in LUAD. Enrichment analysis indicated that ITGB4 is associated with brain metastasis, infiltration of immune cells, and the response to immunotherapy. ITGB4 expression can effectively predict the outcomes of patients with LUAD who are receiving anti-PD-1 therapy. ITGB4 knockdown inhibited the invasion, migration of H1975-BrM4 brain metastasis cells, as well as epithelial-mesenchymal transition (EMT) abilities. The heightened expression of ITGB4 protein was shown to promote EMT and enhance the metastatic potential. ITGB4 promotes the progression in H1975-BrM4 cells via MEK/ERK signaling pathway. CONCLUSIONS: Our findings indicate that the expression of ITGB4 is linked to the occurrence of brain metastasis and infiltration of immune cells, suggesting that ITGB4 might be a clinical treatment target for LUAD.

12.
Mol Med ; 30(1): 71, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38797859

RESUMO

Diabetes mellitus, a chronic metabolic disease, often leads to numerous chronic complications, significantly contributing to global morbidity and mortality rates. High glucose levels trigger epigenetic modifications linked to pathophysiological processes like inflammation, immunity, oxidative stress, mitochondrial dysfunction, senescence and various kinds of cell death. Despite glycemic control, transient hyperglycemia can persistently harm organs, tissues, and cells, a latent effect termed "metabolic memory" that contributes to chronic diabetic complications. Understanding metabolic memory's mechanisms could offer a new approach to mitigating these complications. However, key molecules and networks underlying metabolic memory remain incompletely understood. This review traces the history of metabolic memory research, highlights its key features, discusses recent molecules involved in its mechanisms, and summarizes confirmed and potential therapeutic compounds. Additionally, we outline in vitro and in vivo models of metabolic memory. We hope this work will inform future research on metabolic memory's regulatory mechanisms and facilitate the development of effective therapeutic compounds to prevent diabetic complications.


Assuntos
Complicações do Diabetes , Humanos , Animais , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/etiologia , Epigênese Genética , Estresse Oxidativo , Hiperglicemia/metabolismo
13.
PLoS One ; 19(5): e0295105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38820459

RESUMO

INTRODUCTION AND AIMS: In the specialized nursing setting, nurses are susceptible to developing negative mental health issues. Such conditions among nurses can potentially result in unfavorable medical outcomes. Consequently, this study aims to explore the role of social support in regulating between sleep and mental health in nurses. METHODS: A cross-sectional study was carried out in September 2022 on 1219 nurses in Quanzhou. The study comprised general demographic information and utilized various questionnaires, namely the Social Support Rate Scale (SSRS), Pittsburgh Sleep Quality Index Questionnaire (PSQI), Generalized Anxiety Disorder Questionnaire (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). The data analysis was performed using t-tests, ANOVAs, Pearsons correlations and hierarchical regression analyses in SPSS software. RESULTS: Results show that significant associations of sleep quality and social support with anxiety and depression. Simple slope analysis shows that under low levels of social support, sleep quality has a positive impact on anxiety(ß = 0.598) and depression(ß = 0.851), and the impact is significant. Under high levels of social support, sleep quality also has a positive impact on anxiety(ß = 0.462) and depression(ß = 0.578), but the impact is smaller. This indicates that as the level of social support increases, the positive predictive effect of sleep quality on anxiety and depression gradually diminishes. CONCLUSIONS: Social support has the potential to alter the impact of sleep quality on anxiety and depression. Therefore, healthcare policymakers need to focus on enhancing the level of social support and mitigating the impact of poor sleep on anxiety and depression.


Assuntos
Ansiedade , COVID-19 , Depressão , Saúde Mental , Enfermeiras e Enfermeiros , Qualidade do Sono , Apoio Social , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Feminino , Adulto , Estudos Transversais , Masculino , China/epidemiologia , Enfermeiras e Enfermeiros/psicologia , Ansiedade/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Inquéritos e Questionários , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/isolamento & purificação , Adulto Jovem , População do Leste Asiático
14.
Molecules ; 29(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38792234

RESUMO

The tumor microenvironment (TME) can aid tumor cells in evading surveillance and clearance by immune cells, creating an internal environment conducive to tumor cell growth. Consequently, there is a growing focus on researching anti-tumor immunity through the regulation of immune cells within the TME. Various bioactive compounds in traditional Chinese medicine (TCM) are known to alter the immune balance by modulating the activity of immune cells in the TME. In turn, this enhances the body's immune response, thus promoting the effective elimination of tumor cells. This study aims to consolidate recent findings on the regulatory effects of bioactive compounds from TCM on immune cells within the TME. The bioactive compounds of TCM regulate the TME by modulating macrophages, dendritic cells, natural killer cells and T lymphocytes and their immune checkpoints. TCM has a long history of having been used in clinical practice in China. Chinese medicine contains various chemical constituents, including alkaloids, polysaccharides, saponins and flavonoids. These components activate various immune cells, thereby improving systemic functions and maintaining overall health. In this review, recent progress in relation to bioactive compounds derived from TCM will be covered, including TCM alkaloids, polysaccharides, saponins and flavonoids. This study provides a basis for further in-depth research and development in the field of anti-tumor immunomodulation using bioactive compounds from TCM.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Neoplasias , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Animais , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo
15.
Ecotoxicol Environ Saf ; 279: 116480, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38772146

RESUMO

Microcystins (MCs) are toxic to the central nervous system of mammals. However, the direct toxicity of MCs on mammalian brain cells and the involved molecular mechanisms are not fully elucidated. Here, we incubated primary astrocytes, the major glial cell-type in the brain, with 0-12.5 µM concentrations of MC-LR for 48 h, and the impairment was evaluated. We found that MC-LR caused significant increases in the cell viability at the range of 0.05-1 µM concentrations with the highest density at 0.1 µM concentration. Treatment with 0.1 µM MC-LR induced YAP nuclear translocation and decreased the ratio of p-YAP to YAP. It also decreased mRNA levels of the upstream regulator (AMOT), and enhanced expressions of YAP interacted genes (Egfr, Tead1, and Ctgf) in primary astrocytes. Overexpression of AMOT significantly attenuated the increase of MC-LR-induced astrocyte proliferation and the expression of YAP downstream genes. These results indicate that Hippo signaling contributed to MC-LR-caused astrocyte proliferation. Further, reactive astrogliosis was observed in the mice brain after MC-LR exposure to environmentally relevant concentrations (20 or 100 µg/L) through drinking water for 16 weeks. Pathological observations revealed that 100 µg/L MC-LR exposure caused neuronal damages with characteristics of shrunken or vacuolation in the region of the cerebral cortex, striatum and cerebellum. These results were accompanied with increased oxidative stress and inflammatory response. Our data reveal the potential astrocytic mechanisms in MC-induced neurotoxicity and raise an alarm for neurodegenerative disease risk following daily exposure to MC-LR.


Assuntos
Astrócitos , Proliferação de Células , Via de Sinalização Hippo , Toxinas Marinhas , Microcistinas , Transdução de Sinais , Microcistinas/toxicidade , Animais , Astrócitos/efeitos dos fármacos , Via de Sinalização Hippo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas de Sinalização YAP , Sobrevivência Celular/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Receptores ErbB/metabolismo , Fatores de Transcrição de Domínio TEA , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética
16.
Int J Cardiol Cardiovasc Risk Prev ; 21: 200265, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577011

RESUMO

Background: The present study aimed to develop and validate a prediction nomogram model for 5-year all-cause mortality in diabetic patients with hypertension. Methods: Data were extracted from the National Health and Nutrition Examination Survey (NHANES). A total of 3291 diabetic patients with hypertension in the NHANES cycles for 1999-2014 were selected and randomly assigned at a ratio of 8:2 to the training cohort (n = 2633) and validation cohort (n = 658). Multivariable Cox regression was conducted to establish a visual nomogram model for predicting the risk of 5-year all-cause mortality. Receiver operating characteristic curves and C-indexes were used to evaluate the discriminant ability of the prediction nomogram model for all-cause mortality. Survival curves were created using the Kaplan-Meier method and compared by the log-rank test. Results: The nomogram model included eight independent predictors: age, sex, education status, marital status, smoking, serum albumin, blood urea nitrogen, and previous cardiovascular disease. The C-indexes for the model in the training and validation cohorts were 0.76 (95% confidence interval: 0.73-0.79, p < 0.001) and 0.75 (95% confidence interval: 0.69-0.81, p < 0.001), respectively. The calibration curves indicated that the model had satisfactory consistency in the two cohorts. The risk of all-cause mortality gradually increased as the tertiles of the nomogram model score increased (log-rank test, p < 0.001). Conclusion: The newly developed nomogram model, a readily useable and efficient tool to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension, provides a novel risk stratification method for individualized intervention.

17.
Acta Diabetol ; 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583120

RESUMO

BACKGROUND: Metabolic unhealth (MUH) is closely associated with cardiovascular disease (CVD). Life's Essential 8 (LE8), a recently updated cardiovascular health (CVH) assessment, has some overlapping indicators with MUH but is more comprehensive and complicated than MUH. Given the close relationship between them, it is important to compare these two measurements. METHODS: This population-based cross-sectional survey included 20- to 80-year-old individuals from 7 National Health and Nutrition Examination Survey (NHANES) cycles between 2005 and 2018. Based on the parameters provided by the American Heart Association, the LE8 score (which ranges from 0 to 100) was used to classify CVH into three categories: low (0-49), moderate (50-79), and high (80-100). The MUH status was evaluated by blood glucose, blood pressure, and blood lipids. The associations were assessed by multivariable regression analysis, subgroup analysis, restricted cubic spline models, and sensitivity analysis. RESULTS: A total of 22,582 participants were enrolled (median of age was 45 years old), among them, 11,127 were female (weighted percentage, 49%) and 16,595 were classified as MUH (weighted percentage, 73.5%). The weighted median LE8 scores of metabolic health (MH) and MUH individuals are 73.75 and 59.38, respectively. Higher LE8 scores were linked to lower risks of MUH (odds ratio [OR] for every 10 scores increase, 0.53; 95% CI 0.51-0.55), and a nonlinear dose-response relationship was seen after the adjustment of potential confounders. This negative correlation between LE8 scores, and MUH was strengthened among elderly population. CONCLUSIONS: Higher LE8 and its subscales scores were inversely and nonlinearly linked with the lower presence of MUH. MUH is consistent with LE8 scores, which can be considered as an alternative indicator when it is difficult to collect the information of health behaviors.

18.
J Chem Phys ; 160(15)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38629603

RESUMO

The extreme ultraviolet (EUV) nanolithography technology is the keystone for developing the next-generation chips. As conventional chemically amplified resists are approaching the resolution limit, metal-containing photoresists, especially tin-oxo clusters, seize the opportunity to embrace this challenge owing to their small sizes, precise atomic structures, and strong EUV absorption. However, atomistic insights into the mechanism for regulating their photolithographic behavior are lacking. Herein, we systematically explored the effects of ligands, counterions, and endohedral doping on the photophysical properties of tin-oxo cage clusters by first-principles calculations combined with molecular dynamics simulations. Photoresists assembled by allyl-protected clusters with small-size OH- or Cl- counterions have a high absorption coefficient at the EUV wavelength of 13.5 nm and a low energy cost for ligand detachment and superior stability to ensure high sensitivity and strong etch resistance, respectively. The photoresist performance can further be improved by endohedral doping of the metal-oxo nanocage with Ag+ and Cd2+ ions, which exhibit superatomic characteristics and are likely to be synthesized in laboratory. These theoretical results provide useful guidance for modification of metal-oxo clusters for high-resolution EUV photolithography.

19.
Nano Lett ; 24(14): 4256-4264, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38557048

RESUMO

Biological materials exhibit fascinating mechanical properties for intricate interactions at multiple interfaces to combine superb toughness with wondrous strength and stiffness. Recently, strong interlayer entanglement has emerged to replicate the powerful dissipation of natural proteins and alleviate the conflict between strength and toughness. However, designing intricate interactions in a strong entanglement network needs to be further explored. Here, we modulate interlayer entanglement by introducing multiple interactions, including hydrogen and ionic bonding, and achieve ultrahigh mechanical performance of graphene-based nacre fibers. Two essential modulating trends are directed. One is modulating dynamic hydrogen bonding to improve the strength and toughness up to 1.58 GPa and 52 MJ/m3, simultaneously. The other is tailoring ionic coordinating bonding to raise the strength and stiffness, reaching 2.3 and 253 GPa. Modulating various interactions within robust entanglement provides an effective approach to extend performance limits of bioinspired nacre and optimize multiscale interfaces in diverse composites.

20.
Int J Biol Macromol ; 267(Pt 1): 131418, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38582465

RESUMO

In this work, the effects of low-frequency alternating magnetic fields (LF-AMF) on the physicochemical, conformational, and functional characteristics of myofibrillar protein (MP) after iterative freeze-thaw (FT) cycles were explored. With the increasing LF-AMF treatment time, the solubility, active sulfhydryl groups, surface hydrophobicity, emulsifiability, and emulsion stability of MP after five FT cycles evidently elevated and then declined, and the peak value was obtained at 3 h. Conversely, the moderate LF-AMF treatment time can significantly reduce the average particle size, carbonyl content, and endogenous fluorescence intensity of MP. The rheology results showed that various LF-AMF treatment times would elevate the G' value of MP after iterative FT cycles. The FTIR spectroscopy results suggested that LF-AMF influenced the secondary structure of MP after multiple FT cycles, resulting in a depression in α-helix content and an increment in ß-folding proportion. Moreover, LF-AMF treatment induced the gradually lighter and wider myosin heavy chain bands of MP, implying that LF-AMF accelerated the degradation of macromolecular aggregates. Therefore, the LF-AMF treatment efficaciously ameliorates the structural and functional deterioration of MP after iterative FT cycles and could be used as a potential quality-improving technology in the frozen meat industry.


Assuntos
Congelamento , Campos Magnéticos , Proteínas Musculares , Reologia , Proteínas Musculares/química , Miofibrilas/química , Solubilidade , Animais , Fenômenos Químicos , Conformação Proteica , Interações Hidrofóbicas e Hidrofílicas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA