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1.
Int J Gen Med ; 17: 5015-5027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39494359

RESUMO

Objective: The study aimed to explore the clinical diagnostic significance of lipoprotein(a) [Lp(a)] and neck circumference (NC) in patients with coronary heart disease (CHD). Methods: This cross-sectional study was conducted at Chengde Central Hospital from September 2021 to June 2023, enrolling 791 patients with suspected CHD who underwent selective coronary angiography (CAG). Patients were categorized into CHD and non-CHD groups based on the severity of arterial narrowing. Subsequently, the diagnostic value of Lp(a) combined with NC in patients with CHD was assessed using receiver operating characteristic (ROC) curves. Based on the results of multivariate logistic regression, a nomogram was constructed, and its clinical applicability was validated using decision curve analysis (DCA) and clinical impact curve (CIC). Results: Multivariate logistic regression proved that high Lp(a) and high NC are risk factors for CHD, with OR of 1.836 (95% CI: 1.282-2.630) and 1.383 (1.0.978-1.955), respectively. Patients in the high NC or Lp(a) group exhibited a higher prevalence of multi-vessel disease. The area under the ROC curve (AUC) of the predictive model combining high Lp(a) and high NC was 0.710 (95% CI: 0.670-0.751) and also demonstrated good calibration (Hosmer-Lemeshow goodness-of-fit test P value=0.494). The DCA and CIC confirmed the clinical utility of the nomogram developed to predict CHD based on the combination of high Lp(a) and high NC. Conclusion: The levels of Lp(a) and NC exhibit a significant correlation with the presence of CHD, and their combined assessment holds specific clinical value in the diagnosis of CHD.

2.
Cell Rep ; 43(11): 114843, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39412988

RESUMO

Seed germination is the initial step of the whole life cycle for an individual plant, and thus it needs to be tightly controlled to avoid plant growth under unfavorable conditions. Here, we report that FERONIA (FER), a receptor-like kinase, controls early seed germination under ABA conditions. FER interacts with and phosphorylates cytosolic ABA receptor kinase 1 (CARK1) protein, a receptor-like cytoplasmic kinase (RLCK) that modulates ABA signaling. In both the fer-4 and cark1 mutants, ABA-triggered SNF1-related protein kinase 2 (SnRK2) activation and ABI5 protein accumulation are attenuated. FER phosphorylates the Ser233 and Thr234 residues of CARK1, and the CARK1 protein with the substitutions of these two residues with Ala exhibits a reduced kinase activity and fails to rescue the increased seed germination rate of the cark1 mutant under ABA conditions. Collectively, our study not only uncovers an RLCK protein that functions downstream of FER but also provides a mechanistic insight into ABA-mediated early seed germination regulation by the FER-CARK1 module.

3.
Front Immunol ; 15: 1449211, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39359732

RESUMO

Objective: This study aimed to investigate the efficacy, long-term prognosis and safety of combining chemotherapy with regorafenib and immune checkpoint inhibitors as first-line treatment for patients with advanced biliary tract carcinoma (BTC). Methods: In this single arm phase II trial, twenty-nine patients with advanced BTC were included, all of whom received gemcitabine-based chemotherapy combined with regorafenib and immune checkpoint inhibitors as the first-line treatment. And the study analyzed anti-tumor efficacy, long-term prognosis, and adverse reactions. Results: Among the patients, 0 patient achieved complete response, 18 patients (62.1%) achieved partial response, 8 patients (27.6%) had stable disease, and 3 patients (10.3%) experienced progressive disease. The corresponding objective response rate (ORR) was 18/29 (62.1%), and the disease control rate (DCR) was 26/29 (89.7%). The median overall survival (OS) was 16.9 months (95% confidence interval [CI]: 12.0 -21.8) and the median progress free survival (PFS) was 10.2 months (95% CI: 7.8- 12.6). The 1-year OS and PFS were 65% (95% CI: 0.479-0.864) and 41% (95% CI: 0.234-0.656), respectively. The incidence of adverse reactions was 27/29 (93.1%), and the incidence of grade III/IV adverse reactions was 5/29 (17.2%). Conclusion: The combination of chemotherapy, regorafenib, and immune checkpoint inhibitors as a first-line treatment for patients with advanced BTC may has good anti-tumor efficacy without causing serious adverse reactions, and can significantly improve the long-term prognosis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Biliar , Inibidores de Checkpoint Imunológico , Compostos de Fenilureia , Piridinas , Humanos , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/mortalidade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/administração & dosagem , Adulto , Resultado do Tratamento , Gencitabina , Prognóstico , Estadiamento de Neoplasias
4.
Nanomaterials (Basel) ; 14(19)2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39404321

RESUMO

Perovskite oxide LaFeO3(LFO) emerges as a potential candidate for formaldehyde (HCHO) detection due to its exceptional electrical conductivity and abundant active metal sites. However, the sensitivity of the LFO sensor needs to be further enhanced. Herein, a series of LaxIn1-xFeO3 (x = 1.0, 0.9, 0.8, and 0.7) nanofibers (LxIn1-xFO NFs) with different ratios of La/In were obtained via the electrospinning method followed by a calcination process. Among all these LxIn1-xFO NFs sensors, the sensor based on the L0.8In0.2FO NFs possessed the maximum response value of 18.8 to 100 ppm HCHO at the operating temperature of 180 °C, which was 4.47 times higher than that based on pristine LFO NFs (4.2). Furthermore, the L0.8In0.2FO NFs sensor also exhibited a rapid response/recovery time (2 s/22 s), exceptional repeatability, and long-term stability. This excellent gas sensing performance of the L0.8In0.2FO NFs can be attributed to the large number of oxygen vacancies induced by the replacement of the A-site La3+ by In3+, the large specific surface area, and the porous structure. This research presents an approach to enhance the HCHO gas sensing capabilities by adjusting the introduced oxygen vacancies through the doping of A-sites in perovskite oxides.

5.
Nat Commun ; 15(1): 9285, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-39468146

RESUMO

The nucleus accumbens (NAc) regulates reward-motivated behavior, but the temporal dynamics of NAc neurons that enable "free-willed" animals to obtain rewards remain elusive. Here, we recorded Ca2+ activity from individual NAc neurons when mice performed self-paced lever-presses for sucrose. NAc neurons exhibited three temporally-sequenced clusters, defined by times at which they exhibited increased Ca2+ activity: approximately 0, -2.5 or -5 sec relative to the lever-pressing. Dopamine D1 receptor (D1)-expressing neurons and D2-neurons formed the majority of the -5-sec versus -2.5-sec clusters, respectively, while both neuronal subtypes were represented in the 0-sec cluster. We found that pre-press activity patterns of D1- or D2-neurons could predict subsequent lever-presses. Inhibiting D1-neurons at -5 sec or D2-neurons at -2.5 sec, but not at other timepoints, reduced sucrose-motivated lever-pressing. We propose that the time-specific activity of D1- and D2-neurons mediate key temporal features of the NAc through which reward motivation initiates reward-seeking behavior.


Assuntos
Neurônios , Núcleo Accumbens , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Recompensa , Animais , Núcleo Accumbens/metabolismo , Núcleo Accumbens/citologia , Núcleo Accumbens/fisiologia , Masculino , Receptores de Dopamina D1/metabolismo , Camundongos , Neurônios/metabolismo , Neurônios/fisiologia , Receptores de Dopamina D2/metabolismo , Motivação/fisiologia , Sacarose/metabolismo , Camundongos Endogâmicos C57BL , Cálcio/metabolismo , Comportamento Animal/fisiologia , Fatores de Tempo
6.
Adv Mater ; : e2410355, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350446

RESUMO

Balancing optical modulation and response time is crucial for achieving high coloration efficiency in electrochromic materials. Here, internal electric fields are introduced to titanium dioxide nanosheets by constructing abundant amorphous-crystalline interfaces, ensuring large optical modulation while reducing response time and therefore improving coloration efficiency. Aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) reveals the presence of numerous amorphous-crystalline phase boundaries in titanium dioxide nanosheets. Kelvin probe force microscopy (KPFM) exhibits an intense surface potential distribution, demonstrating the presence of internal electric fields. Density functional theory (DFT) calculations confirm that the amorphous-crystalline heterointerfaces can generate internal electric fields and reduce diffusion barriers of lithium ions. As a result, the amorphous-crystalline titanium dioxide nanosheets exhibit better coloration efficiency (35.1 cm2 C-1) than pure amorphous and crystalline titanium dioxide nanosheets.

7.
Front Public Health ; 12: 1379094, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39351031

RESUMO

Introduction: Online health communities have become the main source for people to obtain health information. However, the existence of poor-quality health information, misinformation, and rumors in online health communities increases the challenges in governing information quality. It not only affects users' health decisions but also undermines social stability. It is of great significance to explore the factors that affect users' ability to discern information in online health communities. Methods: This study integrated the Stimulus-Organism-Response Theory, Information Ecology Theory and the Mindsponge Theory to constructed a model of factors influencing users' health information discernment abilities in online health communities. A questionnaire was designed based on the variables in the model, and data was collected. Utilizing Structural Equation Modeling (SEM) in conjunction with fuzzy-set Qualitative Comparative Analysis (fsQCA), the study analyzed the complex causal relationships among stimulus factors, user perception, and the health information discernment abilities. Results: The results revealed that the dimensions of information, information environment, information technology, and information people all positively influenced health information discernment abilities. Four distinct configurations were identified as triggers for users' health information discernment abilities. The core conditions included information source, informational support, technological security, technological facilitation, and perceived risk. It was also observed that information quality and emotional support can act as substitutes for one another, as can informational support and emotional support. Discussion: This study provides a new perspective to study the influencing factors of health information discernment abilities of online health community users. It can provide experiences and references for online health community information services, information resource construction and the development of users' health information discernment abilities.


Assuntos
Internet , Humanos , Inquéritos e Questionários , Feminino , Masculino , Adulto , Informação de Saúde ao Consumidor , Análise de Classes Latentes , Comportamento de Busca de Informação , Lógica Fuzzy , Adulto Jovem , Pessoa de Meia-Idade
8.
Comput Methods Programs Biomed ; 256: 108403, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39236563

RESUMO

BACKGROUND: Acute heart failure (AHF) in the intensive care unit (ICU) is characterized by its criticality, rapid progression, complex and changeable condition, and its pathophysiological process involves the interaction of multiple organs and systems. This makes it difficult to predict in-hospital mortality events comprehensively and accurately. Traditional analysis methods based on statistics and machine learning suffer from insufficient model performance, poor accuracy caused by prior dependence, and difficulty in adequately considering the complex relationships between multiple risk factors. Therefore, the application of deep neural network (DNN) techniques to the specific scenario, predicting mortality events of patients with AHF under intensive care, has become a research frontier. METHODS: This research utilized the MIMIC-IV critical care database as the primary data source and employed the synthetic minority over-sampling technique (SMOTE) to balance the dataset. Deep neural network models-backpropagation neural network (BPNN) and recurrent neural network (RNN), which are based on electronic medical record data mining, were employed to investigate the in-hospital death event judgment task of patients with AHF under intensive care. Additionally, multiple single machine learning models and ensemble learning models were constructed for comparative experiments. Moreover, we achieved various optimal performance combinations by modifying the classification threshold of deep neural network models to address the diverse real-world requirements in the ICU. Finally, we conducted an interpretable deep model using SHapley Additive exPlanations (SHAP) to uncover the most influential medical record features for each patient from the aspects of global and local interpretation. RESULTS: In terms of model performance in this scenario, deep neural network models outperform both single machine learning models and ensemble learning models, achieving the highest Accuracy, Precision, Recall, F1 value, and Area under the ROC curve, which can reach 0.949, 0.925, 0.983, 0.953, and 0.987 respectively. SHAP value analysis revealed that the ICU scores (APSIII, OASIS, SOFA) are significantly correlated with the occurrence of in-hospital fatal events. CONCLUSIONS: Our study underscores that DNN-based mortality event classifier offers a novel intelligent approach for forecasting and assessing the prognosis of AHF patients in the ICU. Additionally, the ICU scores stand out as the most predictive features, which implies that in the decision-making process of the models, ICU scores can provide the most crucial information, making the greatest positive or negative contribution to influence the incidence of in-hospital mortality among patients with acute heart failure.


Assuntos
Insuficiência Cardíaca , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Redes Neurais de Computação , Humanos , Insuficiência Cardíaca/mortalidade , Doença Aguda , Masculino , Aprendizado de Máquina , Idoso , Feminino , Aprendizado Profundo , Bases de Dados Factuais , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Algoritmos , Mineração de Dados/métodos , Registros Eletrônicos de Saúde
9.
Plant Physiol ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39288195

RESUMO

Brassinosteroids (BRs) are well known for their important role in the regulation of plant growth and development. Plants with deficiency in BR signaling show delayed plant development and exhibit late flowering phenotypes. However, the precise mechanisms involved in this process require investigation. In this study, we cloned homologs of BRASSINOSTEROID INSENSITIVE 2 (SlBIN2), the GSK3-like protein kinase in tomato (Solanum lycopersicum). We characterized growth-related processes and phenotypic changes in the transgenic lines and found that SlBIN2s transgenic lines have delayed development and slow growing phenotypes. SlBIN2s work redundantly to negatively regulate BR signaling in tomato. Furthermore, the transcription factor SlBIN2.1-INTERACTING MYB-LIKE 1 (SlBIML1) was identified as a downstream substrate of SlBIN2s that SlBIN2s interact with and phosphorylate to synergistically regulate tomato developmental processes. Specifically, SlBIN2s modulated protein stability of SlBIML1 by phosphorylating multiple amino acid residues, including the sites Thr266 and Thr280. This study reveals a branch of the BR signaling pathway that regulates the vegetative growth phase and delays floral transition in tomato without the feedback affecting BR signaling. This information enriches our understanding of the downstream transduction pathway of BR signaling and provides potential targets for adjusting tomato flowering time.

10.
Front Biosci (Landmark Ed) ; 29(8): 291, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39206899

RESUMO

Neurodegenerative disorders are typified by the progressive degeneration and subsequent apoptosis of neuronal cells. They encompass a spectrum of conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), epilepsy, brian ischemia, brian injury, and neurodegeneration with brain iron accumulation (NBIA). Despite the considerable heterogeneity in their clinical presentation, pathophysiological underpinning and disease trajectory, a universal feature of these disorders is the functional deterioration of the nervous system concomitant with neuronal apoptosis. Ferroptosis is an iron (Fe)-dependent form of programmed cell death that has been implicated in the pathogenesis of these conditions. It is intricately associated with intracellular Fe metabolism and lipid homeostasis. The accumulation of Fe is observed in a variety of neurodegenerative diseases and has been linked to their etiology and progression, although its precise role in these pathologies has yet to be elucidated. This review aims to elucidate the characteristics and regulatory mechanisms of ferroptosis, its association with neurodegenerative diseases, and recent advances in ferroptosis-targeted therapeutic strategies. Ferroptosis may therefore be a critical area for future research into neurodegenerative diseases.


Assuntos
Ferroptose , Ferro , Doenças Neurodegenerativas , Ferroptose/fisiologia , Humanos , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/fisiopatologia , Ferro/metabolismo , Animais , Neurônios/metabolismo , Neurônios/patologia
11.
Front Immunol ; 15: 1444958, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39211045

RESUMO

As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated.


Assuntos
Anti-Inflamatórios , Antioxidantes , Hidrogênio , Pneumopatias , Estresse Oxidativo , Animais , Humanos , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Citocinas/metabolismo , Hidrogênio/análise , Mediadores da Inflamação/metabolismo , Pneumopatias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
12.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39105602

RESUMO

In this paper, an improved CKF (Cubature Kalman Filter) target tracking method is adopted to solve the tracking and pointing problem in the field of the Active Denial System. The math model of the system is built and the precision requirement is analyzed. The improved CKF method is input as the feedforward compensation for system control to improve the system tracking performance. In the process of the iterative CKF algorithm, nonlinear means are used. The method makes full use of measurement information and estimates the target velocity acceleration model parameters through the neural network, which is used as the input of the CKF to modify the process parameters of CKF and improve the state estimation accuracy. At the same time, the limited lower bound method is used to ensure that the gain reaches the lower bound bottom line of the precision demand, so that it does not tend to zero with time, so as to avoid affecting its rapid response ability during maneuvering and so that the prediction error is also controlled within the range of the precision demand. The simulation and experimental results show the superiority of the method and make the system fully meet the design requirements.

13.
Br J Haematol ; 205(4): 1361-1373, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38960449

RESUMO

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable efficacy in treating advanced B-cell malignancies by targeting CD19, but antigen-negative relapses and immune responses triggered by murine-derived antibodies remain significant challenges, necessitating the development of novel humanized multitarget CAR-T therapies. Here, we engineered a second-generation 4-1BB-CD3ζ-based CAR construct incorporating humanized CD19 single-chain variable fragments (scFvs) and BAFFR single-variable domains on heavy chains (VHHs), also known as nanobodies. The resultant CAR-T cells, with different constructs, were functionally compared both in vitro and in vivo. We found that the optimal tandem and bicistronic (BI) structures retained respective antigen-binding abilities, and both demonstrated specific activation when stimulated with target cells. At the same time, BI CAR-T cells (BI CARs) exhibited stronger tumour-killing ability and better secretion of interleukin-2 and tumour necrosis factor-alpha than single-target CAR-T cells. Additionally, BI CARs showed less exhaustion phenotype upon repeated antigen stimulation and demonstrated more potent and persistent antitumor effects in mouse xenograft models. Overall, we developed a novel humanized CD19/BAFFR bicistronic CAR (BI CAR) based on a combination of scFv and VHH, which showed potent and sustained antitumor ability both in vitro and in vivo, including against tumours with CD19 or BAFFR deficiencies.


Assuntos
Antígenos CD19 , Receptor do Fator Ativador de Células B , Imunoterapia Adotiva , Receptores de Antígenos Quiméricos , Humanos , Animais , Antígenos CD19/imunologia , Camundongos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva/métodos , Receptor do Fator Ativador de Células B/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Linfócitos T/imunologia , Linfoma de Células B/terapia , Linfoma de Células B/imunologia , Linhagem Celular Tumoral , Anticorpos de Cadeia Única/genética , Anticorpos de Cadeia Única/imunologia
14.
Theranostics ; 14(9): 3526-3547, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948071

RESUMO

Background: Immunotherapy has demonstrated its potential to improve the prognosis of patients with hepatocellular carcinoma (HCC); however, patients' responses to immunotherapy vary a lot. A comparative analysis of the tumor microenvironment (TME) in responders and non-responders is expected to unveil the mechanisms responsible for the immunotherapy resistance and provide potential treatment targets. Methods: We performed sequencing analyses using 10x Genomics technology on six HCC patients who responded to anti-PD-1 therapy and one HCC patient who did not respond. Additionally, we obtained single cell data from untreated, responsive, and nonresponsive HCC patients from public databases, and used part of the datasets as a validation cohort. These data were integrated using algorithms such as Harmony. An independent validation cohort was established. Furthermore, we performed spatial transcriptomic sequencing on the tumor adjacent tissues of three HCC responsive patients using 10x Genomics spatial transcriptomic technology. Additionally, we analyzed data about three HCC patients obtained from public databases. Finally, we validated our conclusions using immunofluorescence, flow cytometry, and in vivo experiments. Results: Our findings confirmed the presence of "immune barrier" partially accounting for the limited efficacy of immunotherapy. Our analysis revealed a significant increase in TREM2+ Macrophages among non-responsive patients expressing multiple immunosuppressive signals. anti-Csf1r monoclonal antibodies effectively eliminated these macrophages and augmented the therapeutic effects of anti-PD-1 therapy. TCR+ Macrophages possessed direct tumor-killing capabilities. IL1B+ cDC2 was the primary functional subtype of cDC2 cells. Absence of THEMIShi CD8+ T subtypes might diminish immunotherapeutic effects. Furthermore, CD8+ T cells entered a state of stress after anti-PD-1 treatment, which might be associated with CD8+ T cell exhaustion and senescence. Conclusions: The profiles of immune TMEs showed differences in HCC patients responsive, non-responsive and untreated. These differences might explain the discounted efficacy of immunotherapy in some HCC patients. The cells and molecules, which we found to carry unique capabilities, may be targeted to enhance immunotherapeutic outcomes in patients with HCC.


Assuntos
Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Neoplasias Hepáticas , Receptor de Morte Celular Programada 1 , Análise de Célula Única , Microambiente Tumoral , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Microambiente Tumoral/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Imunoterapia/métodos , Animais , Masculino , Camundongos , Feminino , Pessoa de Meia-Idade
15.
Nanomaterials (Basel) ; 14(14)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39057863

RESUMO

NaNbO3(NN)-based lead-free materials are attracting widespread attention due to their environment-friendly and complex phase transitions, which can satisfy the miniaturization and integration for future electronic components. However, NN materials usually have large remanent polarization and obvious hysteresis, which are not conducive to energy storage. In this work, we investigated the effect of introducing CaTiO3((1-x)NaNbO3-xCaTiO3) on the physical properties of NN. The results indicated that as x increased, the surface topography, oxygen vacancy and dielectric loss of the thin films were significantly improved when optimal value was achieved at x = 0.1. Moreover, the 0.9NN-0.1CT thin film shows reversible polarization domain structures and well-established piezoresponse hysteresis loops. These results indicate that our thin films have potential application in future advanced pulsed power electronics.

16.
Acta Biochim Biophys Sin (Shanghai) ; 56(8): 1199-1207, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38915288

RESUMO

FMS-like tyrosine kinase 3 (FLT3) is a receptor tyrosine kinase expressed in hematopoietic cells. Internal-tandem duplication domain (ITD) mutation and tyrosine kinase domain (TKD) mutation are the two most common mutations in acute myeloid leukemia (AML). Post-translational modifications (PTMs) of FLT3, such as glycosylation and ubiquitination, have been shown to impact various aspects of the protein in both wild-type (WT) and mutant forms of FLT3. In this review, we describe how the glycosylation status of FLT3 affects its subcellular localization, which significantly impacts the activation of downstream signaling, and the impact of specific ubiquitination on FLT3 function and stability, which may be associated with disease progression. Moreover, potential novel therapeutic strategies involving a combination of FLT3 tyrosine kinase inhibitors and drugs targeting glycosylation or ubiquitination are discussed.


Assuntos
Leucemia Mieloide Aguda , Processamento de Proteína Pós-Traducional , Ubiquitinação , Tirosina Quinase 3 Semelhante a fms , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Glicosilação , Mutação , Transdução de Sinais , Animais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
17.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 192-198, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836662

RESUMO

Intervertebral disc degeneration (IDD) is characterized by the decreased function and number of nucleus pulposus cells (NPCs) caused by excessive intervertebral disc (IVD) pressure. This research aims to provide novel insights into IDD prevention and treatment by clarifying the effect of andrographolide (ANDR) on IDD cell autophagy and oxidative stress under mechanical stress. Human primary NPCs were extracted from the nucleus pulposus tissue of non-IDD trauma patients. An IDD cell model was established by posing mechanical traction on NPCs. Through the construction of an IDD rat model, the influence of ANDR on IDD pathological changes was explored in vivo. The proliferation and autophagy of NPCs were decreased while the apoptosis rate and oxidative stress reaction were increased by mechanical traction. ANDR intervention obviously alleviated this situation. MiR-9 showed upregulated expression in IDD cell model, while FoxO3 and PINK1/Parkin were downregulated. Decreased proliferation and autophagy as well as enhanced apoptosis and oxidative stress response of NPCs were observed following miR-9 mimics and H89 intervention, while the opposite trend was observed after FoxO3 overexpression. FoxO3 is a direct target downstream miR-9. The in vivo experiments revealed that after ANDR intervention, the number of apoptotic cells in rat IVD tissue decreased and the autophagy increased. In conclusion, ANDR improves NPC proliferation, and autophagy, inhibits apoptosis and oxidative stress, and alleviates the pathological changes of IDD via the miR-9/FoxO3/PINK1/Parkin axis, which may be a new and effective treatment for IDD in the future.


Assuntos
Autofagia , Diterpenos , Proteína Forkhead Box O3 , Degeneração do Disco Intervertebral , MicroRNAs , Núcleo Pulposo , Estresse Oxidativo , Proteínas Quinases , Ratos Sprague-Dawley , Estresse Mecânico , Ubiquitina-Proteína Ligases , Adulto , Animais , Feminino , Humanos , Masculino , Ratos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Diterpenos/farmacologia , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , MicroRNAs/metabolismo , MicroRNAs/genética , Núcleo Pulposo/metabolismo , Núcleo Pulposo/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Transdução de Sinais/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética
18.
Mitochondrial DNA B Resour ; 9(6): 716-719, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38868489

RESUMO

The complete mitochondrial genome of Squamanita imbachii I. Saar, is unveiled in this research for the first time. It covers 76,643 base pairs (bp) and exhibits a guanine-cytosine (GC) content of 23%. The genome includes 14 conserved protein-coding genes, 1 DNA polymerase gene, 2 ribosomal RNA gene (RNS and RNL), 25 transfer RNA (tRNA) genes and 18 open reading frames (ORFs). Phylogenetic analysis, utilizing a mitochondrial gene dataset from 15 taxa across seven families within the Agaricales order, was conducted employing the maximum-likelihood (ML) approach. This analysis identified a close phylogenetic relationship between S. imbachii and Floccularia luteovirens (Alb. & Schwein.) Pouzar 1957, positioning both within the Squamanitaceae family.

19.
J Am Chem Soc ; 146(29): 19998-20008, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38865282

RESUMO

As the dimensionality of materials generally affects their characteristics, thin films composed of low-dimensional nanomaterials, such as nanowires (NWs) or nanoplates, are of great importance in modern engineering. Among various bottom-up film fabrication strategies, interfacial assembly of nanoscale building blocks holds great promise in constructing large-scale aligned thin films, leading to emergent or enhanced collective properties compared to individual building blocks. As for 1D nanostructures, the interfacial self-assembly causes the morphology orientation, effectively achieving anisotropic electrical, thermal, and optical conduction. However, issues such as defects between each nanoscale building block, crystal orientation, and homogeneity constrain the application of ordered films. The precise control of transdimensional synthesis and the formation mechanism from 1D to 2D are rarely reported. To meet this gap, we introduce an interfacial-assembly-induced interfacial synthesis strategy and successfully synthesize quasi-2D nanofilms via the oriented attachment of 1D NWs on the liquid interface. Theoretical sampling and simulation show that NWs on the liquid interface maintain their lowest interaction energy for the ordered crystal plane (110) orientation and then rearrange and attach to the quasi-2D nanofilm. This quasi-2D nanofilm shows enhanced electric conductivity and unique optical properties compared with its corresponding 1D geometry materials. Uncovering these growth pathways of the 1D-to-2D transition provides opportunities for future material design and synthesis at the interface.

20.
Polymers (Basel) ; 16(11)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38891547

RESUMO

High-temperature vapour-phase acetylation (HTVPA) is a simultaneous acetylation and heat treatment process for wood modification. This study was the first investigation into the impact of HTVPA treatment on the resistance of wood to biological degradation. In the termite resistance test, untreated wood exhibited a mass loss (MLt) of 20.3%, while HTVPA-modified wood showed a reduced MLt of 6.6-3.2%, which decreased with an increase in weight percent gain (WPG), and the termite mortality reached 95-100%. Furthermore, after a 12-week decay resistance test against brown-rot fungi (Laetiporus sulfureus and Fomitopsis pinicola), untreated wood exhibited mass loss (MLd) values of 39.6% and 54.5%, respectively, while HTVPA-modified wood exhibited MLd values of 0.2-0.9% and -0.2-0.3%, respectively, with no significant influence from WPG. Similar results were observed in decay resistance tests against white-rot fungi (Lenzites betulina and Trametes versicolor). The results of this study demonstrated that HTVPA treatment not only effectively enhanced the decay resistance of wood but also offered superior enhancement relative to separate heat treatment or acetylation processes. In addition, all the HTVPA-modified wood specimens prepared in this study met the requirements of the CNS 6717 wood preservative standard, with an MLd of less than 3% for decay-resistant materials.

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