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1.
BMC Public Health ; 24(1): 2298, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39256716

RESUMO

BACKGROUND: Understanding the impact of environmental factors on physical activity (PA) and physical fitness (PF) is crucial for promoting a healthy lifestyle among children and adolescents. This study examines how awareness of sports policies, school, family, and community environments influence PA and PF in Chinese youth. METHODS: A cross-sectional study was conducted with 2747 children and adolescents (mean age 12.90 ± 2.49; 48.2% male) from 17 schools across five Chinese cities. Environmental factors were assessed via questionnaires, and PA levels were measured using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). PF metrics, including BMI, waist-to-height ratio, grip strength, vertical jump, and 20-m shuttle run test (20-mSRT), were measured onsite. Structural Equation Modeling (SEM) was used to explore relationships between environmental factors and PA/PF outcomes. RESULTS: The school environment scored highest (78.0 ± 9.5), while the community environment scored lowest (38.7 ± 18.0). Family environment positively influenced low-intensity PA (LPA) (ß = 0.102, P < 0.001) but negatively affected moderate-to-vigorous PA (MVPA) (ß = -0.055, P = 0.035). Community environment and awareness of sports policies positively impacted MVPA (ß = 0.216, P < 0.001; ß = 0.072, P = 0.009, respectively). Family environment positively influenced BMI reduction (ß = -0.103, P < 0.001) but negatively affected grip strength (ß = -0.063, P = 0.018). Community environment improved grip strength and 20-mSRT performance (ß = 0.088, P = 0.002; ß = 0.065, P = 0.027). CONCLUSIONS: School environments, despite high scores, do not significantly impact PA and PF. Community environments, though scoring lower, positively affect MVPA, grip strength, and 20-mSRT. Awareness of sports policies boosts MVPA, while family environments support LPA and BMI but are inversely related to MVPA and grip strength. Integrated strategies involving community infrastructure, family support, and policy awareness are essential for promoting active lifestyles among children and adolescents.


Assuntos
Exercício Físico , Aptidão Física , Instituições Acadêmicas , Esportes , Humanos , Masculino , Adolescente , Feminino , Estudos Transversais , Aptidão Física/fisiologia , Criança , China , Análise de Classes Latentes , Família , Inquéritos e Questionários , Características de Residência/estatística & dados numéricos , Política de Saúde
2.
Int J Mol Sci ; 25(17)2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39273659

RESUMO

GM1 gangliosidosis is a lysosomal storage disorder characterized by the accumulation of GM1 ganglioside, leading to severe neurodegeneration and early mortality. The disease primarily affects the central nervous system, causing progressive neurodegeneration, including widespread neuronal loss and gliosis. To gain a deeper understanding of the neuropathology associated with GM1 gangliosidosis, we employed single-nucleus RNA sequencing to analyze brain tissues from both GM1 gangliosidosis model mice and control mice. No significant changes in cell proportions were detected between the two groups of animals. Differential expression analysis revealed cell type-specific changes in gene expression in neuronal and glial cells. Functional analysis highlighted the neurodegenerative processes, oxidative phosphorylation, and neuroactive ligand-receptor interactions as the significantly affected pathways. The contribution of the impairment of neurotransmitter system disruption and neuronal circuitry disruption was more important than neuroinflammatory responses to GM1 pathology. In 16-week-old GM1 gangliosidosis mice, no microglial or astrocyte activation or increased expression of innate immunity genes was detected. This suggested that nerve degeneration did not induce the inflammatory response but rather promoted glial cell clearance. Our findings provide a crucial foundation for understanding the cellular and molecular mechanisms of GM1 gangliosidosis, potentially guiding future therapeutic strategies.


Assuntos
Modelos Animais de Doenças , Gangliosidose GM1 , Animais , Gangliosidose GM1/genética , Gangliosidose GM1/metabolismo , Gangliosidose GM1/patologia , Camundongos , Transcriptoma , Neuroglia/metabolismo , Neuroglia/patologia , Perfilação da Expressão Gênica , Neurônios/metabolismo , Neurônios/patologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Gangliosídeo G(M1)/metabolismo , Análise de Célula Única , Camundongos Endogâmicos C57BL
3.
iScience ; 27(9): 110757, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39280623

RESUMO

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is crucial in flavivirus infections, modulating the host immune response through interactions with viral proteins. Despite its importance, the relationship between TRAF6 and Zika virus (ZIKV) remains poorly understood. Our prior proteomics analysis revealed reduced TRAF6 protein levels in ZIKV-infected human trophoblast cells compared to non-infected controls. Subsequent studies in cell models and murine tissues confirmed a significant reduction in both TRAF6 mRNA and protein levels post-ZIKV infection. Further investigations unveiled that ZIKV induces P62-mediated degradation of TRAF6, with NS1 identified as the primary contributor. Co-localization and interaction studies demonstrated that NS1 promotes the association of P62, a key autophagy mediator, with TRAF6. Notably, our findings revealed TRAF6 enhances ZIKV infection, NS1 ubiquitination, NS1 expression, and the production of inflammatory cytokines and chemokines. These insights highlight the intricate TRAF6-ZIKV relationship, offering potential for drug targeting NS1-TRAF6 interactions to manage ZIKV infections effectively.

4.
Mol Med ; 30(1): 152, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289602

RESUMO

VEXAS syndrome, an uncommon yet severe autoimmune disorder stemming from a mutation in the UBA1 gene, is the focus of this paper. The overview encompasses its discovery, epidemiological traits, genetic underpinnings, and clinical presentations. Delving into whether distinct genotypes yield varied clinical phenotypes in VEXAS patients, and the consequent adjustment of treatment strategies based on genotypic and clinical profiles necessitates thorough exploration within the clinical realm. Additionally, the current therapeutic landscape and future outlook are examined, with particular attention to the potential therapeutic roles of IL-6 inhibitors and JAK inhibitors, alongside an elucidation of prevailing limitations and avenues for further research. This study contributes essential theoretical groundwork and clinical insights for both diagnosing and managing VEXAS syndrome.


Assuntos
Interleucina-6 , Inibidores de Janus Quinases , Enzimas Ativadoras de Ubiquitina , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Inibidores de Janus Quinases/uso terapêutico , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/antagonistas & inibidores , Mutação , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Doenças Autoimunes/diagnóstico
5.
Heliyon ; 10(18): e37696, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39323827

RESUMO

Hypoxic-ischemic (HI) can cause neonatal brain damage leading to disability. Patients with HI experience long-term neurological issues impacting quality of life. Limited clinical treatments are available despite extensive research on HI's molecular mechanisms. Genistein-3'-sodium sulfonate (GSS), a phytoestrogen, has been found to improve acute brain injury in neonatal rats caused by hypoxic-ischemia, but its potential for chronic stage neurological recovery in HI is unknown. HI neonatal rats were treated with 1 mg/kg GSS once a day for 21 days. Then, a series of behavioral experiments was performed to evaluate the learning, memory, cognition, anxiety level and depression-like behaviors of the rats. GSS treatment reduced neuronal loss, enhanced learning, memory and cognitive function while also alleviated anxiety and depression-like behaviors in HI rats during the recovery period. These findings indicated that GSS exerted enhance neurological function in HI rats during the chronic stage, prompting further research on how it works to potentially develop new therapies.

6.
Artigo em Inglês | MEDLINE | ID: mdl-39307968

RESUMO

Lead-free double perovskites (DPs) have superior phase stability and optical properties, which make them competitive for future applications in illumination and displays. However, the preparation of DPs was mainly based on high-temperature heating and hydrochloric acid as a solvent to form powders, which increased the risk and cost of the preparation process and limited its further application. In this study, the growth of Cs2NaInCl6: Sb3+ DPs in polyvinylidene difluoride (PVDF) films was achieved using an in situ fabrication strategy with DMSO as the solvent. The prepared Cs2NaInCl6: Sb3+@PVDF composite films (CFs) can achieve a bright blue emission under 302 nm irradiation. To achieve the optimal luminescent performance of CFs, the photoluminescence (PL) intensity of Cs2NaInCl6: Sb3+@PVDF CFs under various in situ preparation conditions was compared. In addition, the photoluminescence quantum yield (PLQY) of CFs was increased from 0.72% to 83.77% by adjusting the doping amount of Sb3+, and the fluorescence lifetimes t1 and t2 were 131.08 and 1048.52 ns, respectively. Temperature-dependent PL spectroscopy and density functional theory (DFT) calculations indicate that these excellent optical properties are derived from the self-trapped excitons (STEs) at the [SbCl6]3- octahedron and [InCl6]3- octahedron connected via Cl-Na-Cl. The CFs also demonstrated excellent environmental stability, maintaining a relatively stable PL intensity even under conditions of water immersion, high temperatures, and ultraviolet (UV) radiation. Finally, we used the CFs to assemble a blue light-emitting device (LED), which showed good and stable blue emission performance at different currents. This work can provide a new idea for preparing DPs, which is conducive to promoting their commercial application in high-performance optoelectronic devices.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39255186

RESUMO

The goal of few-shot segmentation (FSS) is to segment unlabeled images belonging to previously unseen classes using only a limited number of labeled images. The main objective is to transfer label information effectively from support images to query images. In this study, we introduce a novel meta-learning framework called layer-wise mutual information (LayerMI), which enhances the propagation of label information by maximizing the mutual information (MI) between support and query features at each layer. Our approach involves the utilization of a LayerMI Block based on information-theoretic co-clustering. This block performs online co-clustering on the joint probability distribution obtained from each layer, generating a target-specific attention map. The LayerMI Block can be seamlessly integrated into the meta-learning framework and applied to all convolutional neural network (CNN) layers without altering the training objectives. Notably, the LayerMI Block not only maximizes MI between support and query features but also facilitates internal clustering within the image. Extensive experiments demonstrate that LayerMI significantly enhances the performance of baseline and achieves competitive performance compared to state-of-the-art methods on three challenging benchmarks: PASCAL-5 i , COCO-20 i , and FSS-1000.

8.
Sci Total Environ ; 952: 175899, 2024 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-39222813

RESUMO

Ongoing warming will influence plant photosynthesis via thermal effects and by enhancing water deficit. As the primary limiting factor for the growth and development of plants in arid deserts, water may alter the potential warming effects on plant photosynthesis and lead to increased uncertainty in plant dynamics. Here, we used open-top chambers (OTCs) to evaluate the impacts of in situ warming (+0.5 and +1.5 °C) on the photosynthesis and growth of two representative desert plants, Artemisia ordosica and Grubovia dasyphylla, from wet to dry spells. The plant traits associated with photosynthetic diffusive and biochemical processes were also measured to explore the underlying mechanisms involved. We found that warming significantly increased the net photosynthetic rate (Anet) during wet spells under 1.5 °C warming in both plants, while only increased that of A. ordosica under 0.5 °C warming. During dry spells, Anet decreased both in A. ordosica and G. dasyphylla, with the rates of declining being 48 % and 41 %, respectively, higher than control under warming. Consequently, warming significantly amplified photosynthetic responses to drought events, which offset the positive warming effects during wet spells and led to unchanged plant biomass in both species. Besides, alterations in plant traits tended to be associated with positive warming effects during wet spells, and the negative effects of drought were mainly due to stomatal limitation. Our results emphasised that the potential benefits of warming during wet spells may be reversed during drought events. Thus, the adverse effects of ongoing warming on desert productivity may increase during dry spells in growing seasons and during dry years.


Assuntos
Artemisia , Clima Desértico , Secas , Fotossíntese , Artemisia/fisiologia , Aquecimento Global , Mudança Climática , China
9.
Int J Mol Sci ; 25(17)2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39273429

RESUMO

Breast cancer is the most prevalent malignant tumor among women with high heterogeneity. Traditional techniques frequently struggle to comprehensively capture the intricacy and variety of cellular states and interactions within breast cancer. As global precision medicine rapidly advances, single-cell RNA sequencing (scRNA-seq) has become a highly effective technique, revolutionizing breast cancer research by offering unprecedented insights into the cellular heterogeneity and complexity of breast cancer. This cutting-edge technology facilitates the analysis of gene expression profiles at the single-cell level, uncovering diverse cell types and states within the tumor microenvironment. By dissecting the cellular composition and transcriptional signatures of breast cancer cells, scRNA-seq provides new perspectives for understanding the mechanisms behind tumor therapy, drug resistance and metastasis in breast cancer. In this review, we summarized the working principle and workflow of scRNA-seq and emphasized the major applications and discoveries of scRNA-seq in breast cancer research, highlighting its impact on our comprehension of breast cancer biology and its potential for guiding personalized treatment strategies.


Assuntos
Neoplasias da Mama , Análise de Sequência de RNA , Análise de Célula Única , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Análise de Célula Única/métodos , Feminino , Análise de Sequência de RNA/métodos , Microambiente Tumoral/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Medicina de Precisão/métodos , Transcriptoma
10.
Medicine (Baltimore) ; 103(36): e39489, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39252273

RESUMO

BACKGROUND: In patients with schizophrenia, Diankuang Mengxing Decoction with antipsychotics is one of the treatments for it. However, little information is available regarding the difference between the therapeutic effect of Diankuang Mengxing Decoction with antipsychotics and other treatments. Systematic evaluation is conducted to assess the efficacy and safety of Diankuang Mengxing Decoction and other antipsychotics, which are used to treat schizophrenia. METHODS: We performed a systematic review (PROSPERO ID: CRD42023414603). This entailed a computerized search of several research databases from their respective dates of establishment until April 11, 2023, which collected clinical randomized controlled trials of Diankuang Mengxing Decoction combined with antipsychotics. The databases that contributed to this study were PubMed, Web of Science, Embase, EBSCOhost, Cochrane, Scopus, and Google Scholar. Each publication was screened according to defined inclusion and exclusion criteria, and appropriate literature was extracted and evaluated for quality, for which meta-analysis was performed using RevMan 5.4. RESULTS: A literature review of 456 publications resulted in the inclusion of 18 randomized controlled trials with data collected from a total of 1636 patients. Meta-analytical results showed combination with risperidone, olanzapine, chlorpromazine, clozapine, ziprasidone, or aripiprazole increased the overall effectiveness of Diankuang Mengxing Decoction when treating schizophrenia (P < . 00001), among whom olanzapine demonstrated the greatest enhancement (Z = 3.65, odds ratio = 4.26, 95% CI: 1.96-9.28, P = .0003). The 4-week/30-day treatment (P = .0003) and a dosage of 400 mL/d of Diankuang Mengxing Decoction (P = .0004) were more effective. Also, there were widespread reductions to the Positive And Negative Syndrome Scale (PANSS) total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, general psychopathology scores (P < .05 for all), as well as the incidence of adverse effects (Z = 2.79, odds ratio = 0.34, 95% CI: 0.16-0.73, P = .005) in patients with schizophrenia. CONCLUSION: The combination of Diankuang Mengxing Decoction with different antipsychotics can improve the overall prognosis of patients with schizophrenia; Diankuang Mengxing Decoction combined olanzapine, a dosage of 400 mL/d and a duration of 4 weeks/30 days being the best in this regard, by alleviating the symptoms and diminishing the disorder's adverse effects. To build on this work, more large-sample, multi-center, and high-quality clinical studies in the future would help to further validate our findings.


Assuntos
Antipsicóticos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas , Ensaios Clínicos Controlados Aleatórios como Assunto , Esquizofrenia , Esquizofrenia/tratamento farmacológico , Humanos , Antipsicóticos/uso terapêutico , Antipsicóticos/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Resultado do Tratamento
11.
Angew Chem Int Ed Engl ; : e202410347, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39091135

RESUMO

Polyethylene oxide (PEO)-based all solid-state lithium metal batteries (ASSLMBs) are strongly hindered by the fast dendrite growth at the Li metal/electrolyte interface, especially under large rates. The above issue stems from the suboptimal interfacial chemistry and poor Li+ transport kinetics during cycling. Herein, a SnF2-catalyzed lithiophilic-lithiophobic gradient solid electrolyte interphase (SCG-SEI) of LixSny/LiF-Li2O is in-situ formed. The superior ionic LiF-Li2O rich upper layer (17.1 nm) possesses high interfacial energy and fast Li+ diffusion channels, wherein lithiophilic LixSny alloy layer (8.4 nm) could highly reduce the nucleation overpotential with lower diffusion barrier and promote rapid electron transportation for reversible Li+ plating/stripping. Simultaneously, the insoluble SnF2-coordinated PEO promotes the rapid Li+ ion transport in the bulk phase. As a result, an over 46.7 and 3.5 times improvements for lifespan and critical current density of symmetrical cells are achieved, respectively. Furthermore, LiFePO4-based ASSLMBs deliver a recorded cycling performance at 5 C (over 1000 cycles with a capacity retention of 80.0%). More importantly, impressive electrochemical performances and safety tests with LiNi0.8Mn0.1Co0.1O2 and pouch cell with LiFePO4, even under extreme conditions (i.e., 100 ℃), are also demonstrated, reconfirmed the importance of lithiophilic-lithiophobic gradient interfacial chemistry in the design of high-rate ASSLMBs for safety applications.

12.
J Med Virol ; 96(8): e29842, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39115036

RESUMO

To explore the impacts of cytomegalovirus (CMV) infection and antiviral treatment (AVT) on native liver survival (NLS) in biliary atresia (BA) infants. This retrospective cohort study included infants diagnosed as BA between January 2015 and December 2021 at Hunan Children's Hospital. CMV infection was defined by DNA polymerase chain reaction alone (DNA data set) and combination of DNA and immunoglobulin M (CMV data set). In the DNA data set of 330 patients, 234 patients (70.9%) survived with their native liver in 2 years, with 113 (73.9%) in the DNA- cohort, 70 (65.4%) in the DNA+ and AVT- cohort and 51 (72.9%) in the DNA+ and AVT+ cohort, without significant differences by log-rank tests. In patients administrated between 2015 and March 2019, there were 206 evaluable patients in the DNA data set, with rates of 5-year NLS of 68.3% in the DNA- cohort, similar to that in the DNA+ and AVT+ cohort (62.2%, p = 0.546), but significantly higher than that in the DNA+ and AVT- cohort (51.4%, p = 0.031). Similar trends were also observed in the CMV data set, although statistically insignificant. CMV infection before or on the day of HPE can reduce the rate of 5-year NLS and AVT was recommended for CMV-infected BA infants.


Assuntos
Antivirais , Atresia Biliar , Infecções por Citomegalovirus , Citomegalovirus , Humanos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Estudos Retrospectivos , Atresia Biliar/tratamento farmacológico , Antivirais/uso terapêutico , Feminino , Masculino , Lactente , Citomegalovirus/genética , Citomegalovirus/efeitos dos fármacos , Prognóstico , DNA Viral , Recém-Nascido
13.
Sci Rep ; 14(1): 18537, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39122797

RESUMO

Sandification can degrade the strength and quality of dolomite, and to a certain extent, compromise the stability of a tunnel's surrounding rock as an unfavorable geological boundary. Sandification degree classification of sandy dolomite is one of the non-trivial challenges faced by geotechnical engineering projects such as tunneling in complex geographical environments. The traditional methods quantitatively measuring the physical parameters or analyzing some visual features are either time-consuming or inaccurate in practical use. To address these issues, we, for the first time, introduce the convolutional neural network (CNN)-based image classification methods into dolomite sandification degree classification task. In this study, we have made a significant contribution by establishing a large-scale dataset comprising 5729 images, classified into four distinct sandification degrees of sandy dolomite. These images were collected from the vicinity of a tunnel located in the Yuxi section of the CYWD Project in China. We conducted comprehensive classification experiments using this dataset. The results of these experiments demonstrate the groundbreaking achievement of CNN-based models, which achieved an impressive accuracy rate of up to 91.4%. This accomplishment underscores the pioneering role of our work in creating this dataset and its potential for applications in complex geographical analyses.

15.
EBioMedicine ; 106: 105269, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39111250

RESUMO

BACKGROUND: Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines. METHODS: This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4+ T cells, and 11 CD8+ T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice. FINDINGS: Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups. INTERPRETATION: Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine. FUNDING: Funding bodies are described in the Acknowledgments section.


Assuntos
Epitopos de Linfócito B , Vírus da Influenza B , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Camundongos , Vírus da Influenza B/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Feminino , Epitopos de Linfócito B/imunologia , Vírus da Influenza A/imunologia , Anticorpos Antivirais/imunologia , Epitopos de Linfócito T/imunologia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Vacinas de DNA/imunologia , Vacinas de DNA/administração & dosagem , Estações do Ano , Vírus da Influenza A Subtipo H3N2/imunologia , Humanos
16.
Nat Commun ; 15(1): 6624, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103352

RESUMO

Electrocatalytic H2 production from seawater, recognized as a promising technology utilizing offshore renewables, faces challenges from chloride-induced reactions and corrosion. Here, We introduce a catalytic surface where OH- dominates over Cl- in adsorption and activation, which is crucial for O2 production. Our NiFe-based anode, enhanced by nearby Cr sites, achieves low overpotentials and selective alkaline seawater oxidation. It outperforms the RuO2 counterpart in terms of lifespan in scaled-up stacks, maintaining stability for over 2500 h in three-electrode tests. Ex situ/in situ analyses reveal that Cr(III) sites enrich OH-, while Cl- is repelled by Cr(VI) sites, both of which are well-dispersed and close to NiFe, enhancing charge transfer and overall electrode performance. Such multiple effects fundamentally boost the activity, selectively, and chemical stability of the NiFe-based electrode. This development marks a significant advance in creating durable, noble-metal-free electrodes for alkaline seawater electrolysis, highlighting the importance of well-distributed catalytic sites.

17.
Cell Death Discov ; 10(1): 367, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39152126

RESUMO

Chordin-like 1 (CHRDL1) is a secreted protein that serves as an endogenous antagonist of bone morphogenetic proteins (BMPs). In the developing retina, Bmp4 has been demonstrated to be essential for sustaining the proliferation of progenitor cells and facilitating the differentiation of glial cells. Despite these efforts, the precise effects of Bmp4 inhibition on the developing retina are yet to be fully understood. We sought to address this question by overexpressing Chrdl1 in the developing retina. In this study, we explored the impact of Bmp4 inhibition on the developing mouse retina by conditionally overexpressing the Bmp4 inhibitor Chrdl1. Initially, we characterized the expression patterns of Bmp4 and Chrdl1 in the developing mouse retina from E10.5 to P12.5. Additionally, we utilized various molecular markers to demonstrate that Bmp4 inhibition disrupts both neuronal and Müller glial differentiation in the developing mouse retina. Moreover, through the application of RNA-seq analysis, distinctively expressed retinal genes under the modulation of Bmp4 signaling were discerned, encompassing the upregulation of Id1/2/3/4 and Hes1/5, as well as the downregulation of Neurod1/2/4 and Bhlhe22/23. Lastly, electroretinogram (ERG) and optomotor response (OMR) assays were conducted to illustrate that Bmp4 inhibition impairs the functional connectivity of various cells in the retina and consequently affects visual function. Collectively, this study demonstrates that inhibiting Bmp4 promotes the differentiation of retinal neurons over Müller glia by activating the expression of genes associated with neuron specification. These findings offer molecular insights into the role of Bmp4 signaling in mammalian retinal development.

18.
Acta Pharmacol Sin ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39187678

RESUMO

Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

19.
J Transl Med ; 22(1): 799, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39210368

RESUMO

Artificial intelligence (AI) can acquire characteristics that are not yet known to humans through extensive learning, enabling to handle large amounts of pathology image data. Divided into machine learning and deep learning, AI has the advantage of handling large amounts of data and processing image analysis, consequently it also has a great potential in accurately assessing tumour microenvironment (TME) models. With the complex composition of the TME, in-depth study of TME contributes to new ideas for treatment, assessment of patient response to postoperative therapy and prognostic prediction. This leads to a review of the development of AI's application in TME assessment in this study, provides an overview of AI techniques applied to medicine, delves into the application of AI in analysing the quantitative and spatial location characteristics of various cells (tumour cells, immune and non-immune cells) in the TME, reveals the predictive prognostic value of TME and provides new ideas for tumour therapy, highlights the great potential for clinical applications. In addition, a discussion of its limitations and encouraging future directions for its practical clinical application is presented.


Assuntos
Inteligência Artificial , Microambiente Tumoral , Humanos , Neoplasias/patologia , Prognóstico
20.
Front Biosci (Landmark Ed) ; 29(8): 286, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39206891

RESUMO

Being one of the pivotal adipocytokines, adiponectin binds to various receptors and exerts diverse biological functions, encompassing anti-fibrosis, anti-atherosclerosis, anti-ischemia-reperfusion, regulation of inflammation, and modulation of glucose and lipid metabolism. Alterations in adiponectin levels are observed in patients afflicted with diverse cardiovascular diseases. This paper comprehensively reviews the impact of adiponectin on the pathogenesis and progression of cardiovascular diseases, elucidating the underlying cellular and molecular mechanisms along with the associated cell signaling pathways. Furthermore, it deliberates on the diagnostic and predictive efficacy of adiponectin as a protein marker for cardiovascular diseases. Additionally, it outlines methods for manipulating adiponectin levels in vivo. A thorough understanding of these interconnections can potentially inform clinical strategies for the prevention and management of cardiovascular diseases.


Assuntos
Adiponectina , Doenças Cardiovasculares , Humanos , Adiponectina/metabolismo , Adiponectina/sangue , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/sangue , Biomarcadores/sangue , Biomarcadores/metabolismo , Transdução de Sinais , Animais , Receptores de Adiponectina/metabolismo
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