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1.
J Environ Sci (China) ; 148: 38-45, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39095173

RESUMO

Nitrate (NO3-) is a widespread pollutant in high-salt wastewater and causes serious harm to human health. Although electrochemical removal of nitrate has been demonstrated to be a promising treatment method, the development of low-cost electro-catalysts is still challenging. In this work, a phosphate modified iron (P-Fe) cathode was prepared for electrochemical removal of nitrate in high-salt wastewater. The phosphate modification greatly improved the activity of iron, and the removal rate of nitrate on P-Fe was three times higher than that on Fe electrode. Further experiments and density functional theory (DFT) calculations demonstrated that the modification of phosphoric acid improved the stability and the activity of the zero-valent iron electrode effectively for NO3- removal. The nitrate was firstly electrochemically reduced to ammonium, and then reacted with the anodic generated hypochlorite to N2. In this study, a strategy was developed to improve the activity and stability of metal electrode for NO3- removal, which opened up a new field for the efficient reduction of NO3- removal by metal electrode materials.


Assuntos
Eletrodos , Ferro , Nitratos , Fosfatos , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Águas Residuárias/química , Nitratos/química , Ferro/química , Fosfatos/química , Poluentes Químicos da Água/química , Eliminação de Resíduos Líquidos/métodos , Técnicas Eletroquímicas/métodos
3.
PLoS One ; 19(8): e0308090, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39106225

RESUMO

Evidence regarding the role of dietary patterns in metabolic syndrome (MetS) is limited. The mechanistic links between dietary patterns, insulin resistance, and MetS are not fully understood. This study aimed to evaluate the associations between dietary patterns and the risk of MetS in a Chinese population using a longitudinal design. Data from the China Health and Nutrition Survey, a nationally representative survey, were analyzed. MetS cases were identified based on biomarker data collected in 2009. Factor analysis was employed to identify dietary patterns, while logistic regression models were utilized to examine the association between dietary patterns and MetS. Mediation models were applied to assess multiple mediation effects. Two dietary patterns were revealed by factor analysis. Participants in the higher quartiles of the traditional Chinese dietary pattern had lower odds of MetS than those in the lowest quartile (Q1) (OR = 0.58, 95%CI: 0.48, 0.69 for Q4; OR = 0.75, 95%CI: 0.63, 0.89 for Q3). Conversely, participants in the higher quartiles of the modern Chinese dietary pattern had higher odds of MetS compared to those in the lowest quartile (Q1) (OR = 1.40, 95%CI: 1.17, 1.68 for Q4; OR = 1.27, 95%CI: 1.06, 1.52 for Q3). Significant associations between dietary patterns and MetS were mediated by insulin resistance. Therefore, dietary patterns in Chinese adults are associated with MetS, and these associations appear to be mediated through insulin resistance. These findings underscore the critical role of dietary patterns in the development of MetS and establish a foundation for culturally tailored dietary interventions aimed at reducing rates the prevalence of MetS among Chinese adults.


Assuntos
Dieta , Resistência à Insulina , Síndrome Metabólica , Humanos , Síndrome Metabólica/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Dieta/efeitos adversos , Fatores de Risco , Povo Asiático , Idoso , Inquéritos Nutricionais , Comportamento Alimentar , Padrões Dietéticos , População do Leste Asiático
4.
Artigo em Inglês | MEDLINE | ID: mdl-39120985

RESUMO

To accurately segment various clinical lesions from computed tomography(CT) images is a critical task for the diagnosis and treatment of many diseases. However, current segmentation frameworks are tailored to specific diseases, and limited frameworks can detect and segment different types of lesions. Besides, it is another challenging problem for current segmentation frameworks to segment visually inconspicuous and small-scale tumors (such as small intestinal stromal tumors and pancreatic tumors). Our proposed framework, CDI-NSTSEG, efficiently segments small non-salient tumors using multi-scale visual information and non-local target mining. CDI-NSTSEG follows the diagnostic process of clinicians, including preliminary screening, localization, refinement, and segmentation. Specifically, we first explore to extract the unique features at three different scales (1×, 0.5×, and 1.5×) based on the scale space theory. Our proposed scale fusion module (SFM) hierarchically fuses features to obtain a comprehensive representation, similar to preliminary screening in clinical diagnosis. The global localization module (GLM) is designed with a non-local attention mechanism. It captures the long-range semantic dependencies of channels and spatial locations from the fused features. GLM enables us to locate the tumor from a global perspective and output the initial prediction results. Finally, we design the layer focusing module (LFM) to gradually refine the initial results. LFM mainly conducts context exploration based on foreground and background features, focuses on suspicious areas layer-by-layer, and performs element-by-element addition and subtraction to eliminate errors. Our framework achieves state-of-the-art segmentation performance on small intestinal stromal tumor and pancreatic tumor datasets. CDI-NSTSEG outperforms the best comparison segmentation method by 7.38% Dice on small intestinal stromal tumors.

5.
Nat Commun ; 15(1): 6626, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103353

RESUMO

N-Myc is a key driver of neuroblastoma and neuroendocrine prostate cancer (NEPC). One potential way to circumvent the challenge of undruggable N-Myc is to target the protein homeostasis (proteostasis) system that maintains N-Myc levels. Here, we identify heat shock protein 70 (HSP70) as a top partner of N-Myc, which binds a conserved "SELILKR" motif and prevents the access of E3 ubiquitin ligase, STIP1 homology and U-box containing protein 1 (STUB1), possibly through steric hindrance. When HSP70's dwell time on N-Myc is increased by treatment with the HSP70 allosteric inhibitor, STUB1 is in close proximity with N-Myc and becomes functional to promote N-Myc ubiquitination on the K416 and K419 sites and forms polyubiquitination chains linked by the K11 and K63 sites. Notably, HSP70 inhibition significantly suppressed NEPC tumor growth, increased the efficacy of aurora kinase A (AURKA) inhibitors, and limited the expression of neuroendocrine-related pathways.


Assuntos
Proteínas de Choque Térmico HSP70 , Neoplasias da Próstata , Proteostase , Ubiquitina-Proteína Ligases , Ubiquitinação , Masculino , Humanos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/genética , Proteínas de Choque Térmico HSP70/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitinação/efeitos dos fármacos , Linhagem Celular Tumoral , Animais , Aurora Quinase A/metabolismo , Aurora Quinase A/genética , Aurora Quinase A/antagonistas & inibidores , Proteína Proto-Oncogênica N-Myc/metabolismo , Proteína Proto-Oncogênica N-Myc/genética , Camundongos , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Tumores Neuroendócrinos/metabolismo , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia
6.
Neuroimage ; 298: 120773, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39122058

RESUMO

Non-invasive neuroimaging has revealed specific network-based resting-state dynamics in the human brain, yet the underlying neurophysiological mechanism remains unclear. We employed intracranial electroencephalography to characterize local field potentials within the default mode network (DMN), frontoparietal network (FPN), and salience network (SN) in 42 participants. We identified stronger within-network phase coherence at low frequencies (θ and α band) within the DMN, and at high frequencies (γ band) within the FPN. Hidden Markov modeling indicated that the DMN exhibited preferential low frequency phase coupling. Phase-amplitude coupling (PAC) analysis revealed that the low-frequency phase in the DMN modulated the high-frequency amplitude envelopes of the FPN, suggesting frequency-dependent characterizations of intrinsic brain networks at rest. These findings provide intracranial electrophysiological evidence in support of the network model for intrinsic organization of human brain and shed light on the way brain networks communicate at rest.

7.
Nat Commun ; 15(1): 6948, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138165

RESUMO

Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion. In particular, we identify a subpopulation of mesenchyme cells in the mid-suture region that upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. Moreover, combinatorial mutation of BMP antagonists enriched in this mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data reveal establishment of a non-osteogenic mesenchyme population in the mid-suture region that restricts bone formation through local BMP antagonism, thus ensuring proper suture morphology.


Assuntos
Proteínas Morfogenéticas Ósseas , Suturas Cranianas , Mesoderma , Osteogênese , Proteínas de Peixe-Zebra , Peixe-Zebra , Animais , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Suturas Cranianas/metabolismo , Suturas Cranianas/embriologia , Suturas Cranianas/crescimento & desenvolvimento , Proteínas de Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Proteínas Morfogenéticas Ósseas/genética , Mesoderma/metabolismo , Mesoderma/embriologia , Mesoderma/citologia , Regulação da Expressão Gênica no Desenvolvimento , Transdução de Sinais , Crânio/embriologia , Análise de Célula Única , Mutação
8.
Am J Primatol ; : e23676, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148233

RESUMO

Using unmanned aerial vehicles (UAVs) for surveys on thermostatic animals has gained prominence due to their ability to provide practical and precise dynamic censuses, contributing to developing and refining conservation strategies. However, the practical application of UAVs for animal monitoring necessitates the automation of image interpretation to enhance their effectiveness. Based on our past experiences, we present the Sichuan snub-nosed monkey (Rhinopithecus roxellana) as a case study to illustrate the effective use of thermal cameras mounted on UAVs for monitoring monkey populations in Qinling, a region characterized by magnificent biodiversity. We used the local contrast method for a small infrared target detection algorithm to collect the total population size. Through the experimental group, we determined the average optimal grayscale threshold, while the validation group confirmed that this threshold enables automatic detection and counting of target animals in similar datasets. The precision rate obtained from the experiments ranged from 85.14% to 97.60%. Our findings reveal a negative correlation between the minimum average distance between thermal spots and the count of detected individuals, indicating higher interference in images with closer thermal spots. We propose a formula for adjusting primate population estimates based on detection rates obtained from UAV surveys. Our results demonstrate the practical application of UAV-based thermal imagery and automated detection algorithms for primate monitoring, albeit with consideration of environmental factors and the need for data preprocessing. This study contributes to advancing the application of UAV technology in wildlife monitoring, with implications for conservation management and research.

9.
Commun Biol ; 7(1): 1054, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191965

RESUMO

The kidney is vulnerable to ischemia and reperfusion (I/R) injury that can be fatal after major surgery. Currently, there are no effective treatments for I/R-induced kidney injury. Trimethylamine N-oxide (TMAO) is a gut-derived metabolite linked to many diseases, but its role in I/R-induced kidney injury remains unclear. Here, our clinical data reveals an association between preoperative systemic TMAO levels and postoperative kidney injury in patients after post-cardiopulmonary bypass surgery. By genetic deletion of TMAO-producing enzyme flavin-containing monooxygenase 3 (FMO3) and dietary supplementation of choline to modulate TMAO levels, we found that TMAO aggravated acute kidney injury through the triggering of endoplasmic reticulum (ER) stress and worsened subsequent renal fibrosis through TGFß/Smad signaling activation. Together, our study underscores the negative role of TMAO in I/R-induced kidney injury and highlights the therapeutic potential through the modulation of TMAO levels by targeting FMO3, thereby mitigating acute kidney injury and preventing subsequent renal fibrosis.


Assuntos
Injúria Renal Aguda , Rim , Metilaminas , Oxigenases , Traumatismo por Reperfusão , Animais , Traumatismo por Reperfusão/metabolismo , Oxigenases/metabolismo , Oxigenases/genética , Camundongos , Masculino , Metilaminas/metabolismo , Rim/metabolismo , Rim/patologia , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/prevenção & controle , Camundongos Knockout , Camundongos Endogâmicos C57BL , Humanos , Fibrose , Transdução de Sinais , Estresse do Retículo Endoplasmático , Fator de Crescimento Transformador beta/metabolismo
10.
Exp Gerontol ; 195: 112538, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39116956

RESUMO

Amyotrophic lateral sclerosis as a fatal neurodegenerative disease currently lacks effective therapeutic agents. Thus, finding new therapeutic targets to drive disease treatment is necessary. In this study, we utilized brain and plasma proteins as genetic instruments obtained from genome-wide association studies to conduct a Mendelian randomization analysis to identify potential drug targets for amyotrophic lateral sclerosis. Additionally, we validated our results externally using other datasets. We also used Bayesian co-localization analysis and phenotype scanning. Furthermore, we constructed a protein-protein interaction network to elucidate potential correlations between the identified proteins and existing targets. Mendelian randomization analysis indicated that elevated levels of ANO5 (OR = 1.30; 95 % CI, 1.14-1.49; P = 1.52E-04), SCFD1 (OR = 3.82; 95 % CI, 2.39-6.10; P = 2.19E-08), and SIGLEC9 (OR = 1.05; 95% CI, 1.03-1.07; P = 4.71E-05) are associated with an increased risk of amyotrophic lateral sclerosis, with external validation supporting these findings. Co-localization analysis confirmed that ANO5, SCFD1, and SIGLEC9 (coloc.abf-PPH4 = 0.848, 0.984, and 0.945, respectively) shared the same variant with amyotrophic lateral sclerosis, further substantiating potential role of these proteins as a therapeutic target. There are interactive relationships between the potential proteins and existing targets of amyotrophic lateral sclerosis. Our findings suggested that elevated levels of ANO5, SCFD1, and SIGLEC9 are connected with an increased risk of amyotrophic lateral sclerosis and might be promising therapeutic targets. However, further exploration is necessary to fully understand the underlying mechanisms involved.


Assuntos
Esclerose Lateral Amiotrófica , Encéfalo , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Mapas de Interação de Proteínas , Proteômica , Humanos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/tratamento farmacológico , Proteômica/métodos , Encéfalo/metabolismo , Anoctaminas/genética , Teorema de Bayes , Proteínas Sanguíneas/análise , Proteínas Sanguíneas/metabolismo , Predisposição Genética para Doença
11.
Jt Dis Relat Surg ; 35(3): 513-520, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39189559

RESUMO

OBJECTIVES: This study aims to explore the mechanisms of dual regulation of osteoarthritis (OA) progression by the involvement of estrogen receptor (ER) in autophagy and inflammation. MATERIALS AND METHODS: Bioinformatics methods were used to explore the relationship among associated genes. Western blot assays were used to detect related protein expression of OA in C28I2 and induced OA cellular model. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis were used to detect OA related gene expression in C28I2 and induced OA cellular model. Co-immunoprecipitation (CO-IP) analysis were used to verify the direct interaction between ER and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). RESULTS: The C28I2 cellular model of OA was induced by interleukin-1ß (IL-1ß). The small interfering ribonucleic acid (SiRNA)-mediated knockdown of autophagy-related 16 like 1 (ATG16L1) in C28I2 decreased the expression of MAP1LC3B (LC3B) and NLRP3. Besides, ER-beta (ERß) agonist changed the gene expression of NLRP3 and ATG16L1. Moreover, CO-IP analysis indicated the direct interaction between ER and NLRP3. CONCLUSION: Our study results revealed that ATG16L1, NLRP3, and IL-1ß interacted closely and ERß was involved in OA process by affecting autophagy and inflammatory activation.


Assuntos
Proteínas Relacionadas à Autofagia , Receptor beta de Estrogênio , Proteína 3 que Contém Domínio de Pirina da Família NLR , Osteoartrite , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteoartrite/genética , Humanos , Receptor beta de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/genética , Autofagia , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Linhagem Celular
12.
JAMA Neurol ; 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39186280

RESUMO

Importance: In several randomized clinical trials, endovascular thrombectomy led to better functional outcomes than conventional treatment at 90 days poststroke in patients with acute basilar artery occlusion. However, the long-term clinical outcomes of these patients have not been well delineated. Objective: To evaluate 1-year clinical outcomes in patients with acute basilar artery occlusion following endovascular thrombectomy vs control. Design, Setting, and Participants: This study is an extension of the ATTENTION trial, a multicenter, randomized clinical trial. Patients were included between February 2021 and January 2022, with 1-year follow-up through April 2023. This multicenter, population-based study was conducted at 36 comprehensive stroke sites. Patients with acute basilar artery occlusion within 12 hours of estimated symptom onset were included. Of the 342 patients randomized in the ATTENTION trial, 330 (96.5%) had 1-year follow-up information available. Exposures: Endovascular thrombectomy (thrombectomy group) vs best medical treatment (control group). Main Outcomes and Measures: The primary outcome was defined as a score of 0 to 3 on the modified Rankin Scale (mRS) at 1 year. Secondary outcomes were functional independence (mRS score 0-2), excellent outcome (mRS score 0-1), level of disability (distribution of all 7 mRS scores), mortality, and health-related quality of life at 1 year. Results: Among 330 patients who had 1-year follow-up data, 227 (68.8%) were male, and the mean (SD) age was 67.0 (10.7) years. An mRS score 0 to 3 at 1 year was achieved by 99 of 222 patients (44.6%) in the thrombectomy group and 21 of 108 (19.4%) in the control group (adjusted rate ratio, 2.23; 95% CI, 1.51-3.29). Mortality at 1 year compared with 90 days was more frequent in both the thrombectomy group (101 of 222 [45.5%] vs 83 of 226 [36.7%]) and the control group (69 of 108 [63.9%] vs 63 of 114 [55.3%]). Excellent outcome (mRS score 0-1) at 1 year compared with 90 days increased in the thrombectomy group (62 of 222 [27.9%] vs 45 of 226 [19.9%]) but not in the control group (9 of 108 [8.3%] vs 9 of 114 [7.9%]) resulting in a magnified treatment benefit. Conclusions and Relevance: Among patients with basilar artery occlusion within 12 hours of onset, the benefits of endovascular thrombectomy at 1 year compared with 90 days were sustained for favorable (mRS score 0-3) outcome and enhanced for excellent (mRS score 0-1) outcome.

13.
Nat Commun ; 15(1): 5919, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39004626

RESUMO

Pregnane X receptor (PXR) has been reported to regulate glycolipid metabolism. The dysfunction of intestinal barrier contributes to metabolic disorders. However, the role of intestinal PXR in metabolic diseases remains largely unknown. Here, we show that activation of PXR by tributyl citrate (TBC), an intestinal-selective PXR agonist, improves high fat diet (HFD)-induced obesity. The metabolic benefit of intestinal PXR activation is associated with upregulation of ß-1,3 galactosyltransferase 5 (B3galt5). Our results reveal that B3galt5 mainly expresses in the intestine and is a direct PXR transcriptional target. B3galt5 knockout exacerbates HFD-induced obesity, insulin resistance and inflammation. Mechanistically, B3galt5 is essential to maintain the integrity of intestinal mucus barrier. B3galt5 ablation impairs the O-glycosylation of mucin2, destabilizes the mucus layer, and increases intestinal permeability. Furthermore, B3galt5 deficiency abolishes the beneficial effect of intestinal PXR activation on metabolic disorders. Our results suggest the intestinal-selective PXR activation regulates B3galt5 expression and maintains metabolic homeostasis, making it a potential therapeutic strategy in obesity.


Assuntos
Dieta Hiperlipídica , Galactosiltransferases , Resistência à Insulina , Mucosa Intestinal , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade , Receptor de Pregnano X , Animais , Obesidade/metabolismo , Obesidade/genética , Receptor de Pregnano X/metabolismo , Receptor de Pregnano X/genética , Galactosiltransferases/metabolismo , Galactosiltransferases/genética , Camundongos , Dieta Hiperlipídica/efeitos adversos , Mucosa Intestinal/metabolismo , Masculino , Intestinos , Humanos
14.
Sci Rep ; 14(1): 15361, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965388

RESUMO

T-cell receptor (TCR) detection can examine the extent of T-cell immune responses. Therefore, the article analyzed characteristic data of glioma obtained by DNA-based TCR high-throughput sequencing, to predict the disease with fewer biomarkers and higher accuracy. We downloaded data online and obtained six TCR-related diversity indices to establish a multidimensional classification system. By comparing actual presence of the 602 correlated sequences, we obtained two-dimensional and multidimensional datasets. Multiple classification methods were utilized for both datasets with the classification accuracy of multidimensional data slightly less to two-dimensional datasets. This study reduced the TCR ß sequences through feature selection methods like RFECV (Recursive Feature Elimination with Cross-Validation). Consequently, using only the presence of these three sequences, the classification AUC value of 96.67% can be achieved. The combination of the three correlated TCR clones obtained at a source data threshold of 0.1 is: CASSLGGNTEAFF_TRBV12_TRBJ1-1, CASSYSDTGELFF_TRBV6_TRBJ2-2, and CASSLTGNTEAFF_TRBV12_TRBJ1-1. At 0.001, the combination is: CASSLGETQYF_TRBV12_TRBJ2-5, CASSLGGNQPQHF_TRBV12_TRBJ1-5, and CASSLSGNTIYF_TRBV12_TRBJ1-3. This method can serve as a potential diagnostic and therapeutic tool, facilitating diagnosis and treatment of glioma and other cancers.


Assuntos
Algoritmos , Glioma , Sequenciamento de Nucleotídeos em Larga Escala , Receptores de Antígenos de Linfócitos T , Glioma/genética , Glioma/diagnóstico , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Receptores de Antígenos de Linfócitos T/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/diagnóstico
15.
Soft Matter ; 20(30): 6002-6015, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39027971

RESUMO

Cancer metastasis starts from early local invasion, during which tumor cells detach from the primary tumor, penetrate the extracellular matrix (ECM), and then invade neighboring tissues. However, the cellular mechanics in the detaching and penetrating processes have not been fully understood, and the underlying mechanisms that influence cell polarization and migration in the 3D matrix during tumor invasion remain largely unknown. In this study, we employed a dual tumor-spheroid model to investigate the cellular mechanisms of the tumor invasion. Our results revealed that the tensional force field developed by the active contraction of cells and tissues played a pivotal role in tumor invasion, acting as the driving force for remodeling the collagen fibers during the invasion process. The remodeled collagen fibers promoted cell polarization and migration because of the stiffening of the fiber matrix. The aligned fibers facilitated tumor cell invasion and directed migration from one spheroid to the other. Inhibiting/shielding the cellular contractility abolished matrix remodeling and re-alignment and significantly decreased tumor cell invasion. By developing a coarse-grained cell model that considers the mutual interaction between cells and fibers, we predicted the tensional force field in the fiber network and the associated cell polarization and cell-matrix interaction during cell invasion, which revealed a mechano-chemical coupling mechanism at the cellular level of the tumor invasion process. Our study highlights the roles of cellular mechanics at the early stage of tumor metastasis and may provide new therapeutic strategies for cancer therapy.


Assuntos
Movimento Celular , Invasividade Neoplásica , Humanos , Matriz Extracelular/metabolismo , Modelos Biológicos , Fenômenos Biomecânicos , Resistência à Tração , Linhagem Celular Tumoral , Esferoides Celulares/patologia , Colágeno/metabolismo , Colágeno/química , Neoplasias/patologia , Neoplasias/metabolismo
16.
Eur J Pharm Sci ; : 106865, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39067534

RESUMO

OBJECTIVE: To prepare chitosan-loaded nanoparticles (NPs) that enhance the oral bioavailability of puerarin (Pur) and render it responsive to reactive oxygen species (ROS). SIGNIFICANCE: This research makes substantial progress towards the theory of intelligent drug delivery, offering a new reference for combining Pur with other natural medicinal active ingredients. METHODS: The acylation reaction between chitosan and ROS-sensitive 3-carboxyphenylboronic acid (PBA) was used to synthesise ROS-sensitive phenylboronylated chitosan (PBACS). Subsequently, PBACS-PBA-Pur-NPs and PBACS-TPP-Pur-NPs were prepared via ion gelation after the addition of PBA and sodium tripolyphosphate(TPP), respectively. The physicochemical and functional properties of both NPs were compared, and their differences were preliminarily studied through molecular docking. RESULTS: Reactive oxygen species-sensitive PBACS was successfully synthesised. Of the two NPs prepared, PBACS-TPP-Pur-NPs had a size of 127.2 ± 0.80 nm, polydispersity index (PDI) of 0.129 ± 0.0008, and an encapsulation rate of 95.75 ± 0.387%, whereas PBACS-PBA-Pur-NPs had a size of 149.8 ± 0.1414 nm, PDI of 0.389 ± 0.0012, and an encapsulation rate of 91.77 ± 0.279%. The micromorphology of the PBACS-TPP-Pur-NPs exhibited better physical properties. However, PBACS-PBA-Pur-NPs demonstrated a faster in vitro release and more significant in vitro anti-inflammatory effects. Pharmacokinetically, the AUC0-24, Tmax, and Cmax of PBACS-PBA-Pur-NPs were 3.485, 2.117, and 3.339 times higher, respectively, than those of Pur. The AUC0-24, Tmax, and Cmax of PBACS-TPP-Pur-NPs were 2.41, 1.33, and 2.03 times higher, respectively, than those of Pur. Molecular simulation revealed that the binding energy of PBACS-PBA-Pur -NPs was approximately -4.34 kcal/mol and that of PBACS-TPP-Pur-NPs was even lower, approximately -5.93 kcal/mol, suggesting that the NPs prepared with TPP are more densely packed than those designed with PBA, resulting in slower and reduced drug release. CONCLUSION: The NPs constructed in this study effectively reduced inflammatory factors at the disease site, providing a theoretical and experimental basis for the application of nano drugs in inflammatory disease models. In addition, the molecular docking study of the two NPs offered insights into the relationship between the release and structure of subsequent nano drugs.

17.
Acta Trop ; 257: 107310, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38955319

RESUMO

PURPOSE: To investigate the clinical features of hand, foot, and mouth disease (HFMD) caused by coxsackievirus A6 (CVA6) and this work may help early diagnose of atypical HFMD. METHODS: From January 2013 to December 2019, a total of 7,208 patients with a clinical diagnosis of HFMD in Xi'an Children's Hospital, Xi'an Central Hospital, and Xi'an Jiaotong University Second Affiliated Hospital, were included in this observational study. The clinical data, specimens and follow-up results were collected. Real-time RT‒PCR was performed for the detection and typing of enterovirus nucleic acids. RESULTS: Of the 7,208 clinically diagnosed HFMD patients, 5,622 were positive for enterovirus nucleic acids, and the positive proportions of CVA6, enterovirus 71 (EV-A71), coxsackievirus A16 (CVA16), and other enteroviruses were 31.0% (1,742/5,622), 27.0% (1,518/5,622), 35.0% (1,968/5,622), and 7.0% (394/5,622), respectively. Based on the etiology, patients were divided into CVA6 group, EV-A71group, and CVA16 group. The mean age at onset was significantly higher in the CVA6 group (4.62±2.13 years) than in the EV-A71 group and CVA16 group (3.45±2.25 years and 3.35±2.13 years, respectively; both P < 0.05). The male/female ratio was 1.45 (1,031/711) in the CVA6 group and was not significantly different from the other two groups. The incidence of fever was significantly higher in the CVA6 group [82.5% (1,437/1,742)] than in the EV-A71 group [51.3% (779/1,518)] and the CVA16 group [45.9% (903/1,968)] (P < 0.05). In the CVA6 group, the rashes were more frequently on the trunk and elbows/knees and were significantly different from the other two groups (P < 0.05). The number of patients with two or more rash morphologies was significantly higher in the CVA6 group than in the other two groups (P < 0.05). The incidence of bullous rash in the CVA6 group [20.2%; n = 352] was higher than in the EV-A71 group [0.33%; n = 5] and CVA16 group [0.66%; n = 13] (P < 0.05). The incidence of neurological complications was significantly higher in the EV-A71 group [52.1% (791/1,518)] than in the CVA16 group [5.1% (100/1,968)] and the CVA6 group [0.8% (14/1,742)] (P < 0.05). In the follow-up period, 160 patients (9.2%) with CVA6 HFMD experienced onychomadesis, but no onychomadesis was observed in the EV-A71 and CVA16 groups. The average WBC count was significantly higher in the CVA6 group than in the CVA16 group (P < 0.05). The number of patients with increased CRP was significantly larger in the CVA6 group than in the CVA16 group but was significantly smaller than that in the EV-A71 group (P < 0.05). CONCLUSIONS: CVA6 has become one of the main pathogens of HFMD in the Xi'an area during 2013-2019. The main clinical manifestations were slightly different from those of HFMD caused by EV-A71 or CVA16, with a higher frequency of fever, diverse morphologies and diffuse distribution of rashes, fewer neurological complications and some onychomadesis.


Assuntos
Enterovirus , Doença de Mão, Pé e Boca , Humanos , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/virologia , Masculino , Feminino , China/epidemiologia , Pré-Escolar , Lactente , Enterovirus/genética , Enterovirus/isolamento & purificação , Enterovirus/classificação , Criança , Adolescente
18.
Comput Biol Med ; 178: 108759, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38917530

RESUMO

BACKGROUND: The retinal vasculature, a crucial component of the human body, mirrors various illnesses such as cardiovascular disease, glaucoma, and retinopathy. Accurate segmentation of retinal vessels in funduscopic images is essential for diagnosing and understanding these conditions. However, existing segmentation models often struggle with images from different sources, making accurate segmentation in crossing-source fundus images challenging. METHODS: To address the crossing-source segmentation issues, this paper proposes a novel Multi-level Adversarial Learning and Pseudo-label Denoising-based Self-training Framework (MLAL&PDSF). Expanding on our previously proposed Multiscale Context Gating with Breakpoint and Spatial Dual Attention Network (MCG&BSA-Net), MLAL&PDSF introduces a multi-level adversarial network that operates at both the feature and image layers to align distributions between the target and source domains. Additionally, it employs a distance comparison technique to refine pseudo-labels generated during the self-training process. By comparing the distance between the pseudo-labels and the network predictions, the framework identifies and corrects inaccuracies, thus enhancing the accuracy of the fine vessel segmentation. RESULTS: We have conducted extensive validation and comparative experiments on the CHASEDB1, STARE, and HRF datasets to evaluate the efficacy of the MLAL&PDSF. The evaluation metrics included the area under the operating characteristic curve (AUC), sensitivity (SE), specificity (SP), accuracy (ACC), and balanced F-score (F1). The performance results from unsupervised domain adaptive segmentation are remarkable: for DRIVE to CHASEDB1, results are AUC: 0.9806, SE: 0.7400, SP: 0.9737, ACC: 0.9874, and F1: 0.8851; for DRIVE to STARE, results are AUC: 0.9827, SE: 0.7944, SP: 0.9651, ACC: 0.9826, and F1: 0.8326. CONCLUSION: These results demonstrate the effectiveness and robustness of MLAL&PDSF in achieving accurate segmentation results from crossing-domain retinal vessel datasets. The framework lays a solid foundation for further advancements in cross-domain segmentation and enhances the diagnosis and understanding of related diseases.


Assuntos
Vasos Retinianos , Humanos , Vasos Retinianos/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
19.
Virulence ; 15(1): 2367671, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38910312

RESUMO

Viral diseases are among the main threats to public health. Understanding the factors affecting viral invasion is important for antiviral research. Until now, it was known that most viruses have very low plaque-forming unit (PFU)-to-particle ratios. However, further investigation is required to determine the underlying factors. Here, using quantitative single-particle analysis methods, the invasion of Semliki Forest virus (SFV), Japanese encephalitis virus (JEV), and influenza A virus (IAV) containing attachment to the cell surface, entry into the cell, transport towards the cell interior, and fusion with endosomes to release nucleocapsids were quantitatively analysed in parallel. It was found that for SFV with an PFU-to-particle ratio of approximately 1:2, an entry efficiency of approximately 31% limited infection. For JEV, whose PFU-to-particle ratio was approximately 1:310, an attachment efficiency of approximately 27% and an entry efficiency of 10% were the main factors limiting its infection. Meanwhile, for IAV with PFU-to-particle ratios of 1:8100, 5% attachment efficiency, 9% entry efficiency, and 53% fusion efficiency significantly limited its infection. These results suggest that viruses with different infectivities have different limited steps in the invasion process. Moreover, there are significant differences in attachment efficiencies among viruses, emphasizing the pivotal role of attachment in viral invasion. The influence of the virus purification method on virus invasion was also investigated. This study, for the first time, reports the efficiencies of different stages of virus invasion, leading to a better understanding of virus invasion and providing a protocol to quantitatively analyse the virus invasion efficiency.


Assuntos
Vírus da Influenza A , Vírus da Floresta de Semliki , Internalização do Vírus , Vírus da Influenza A/fisiologia , Animais , Vírus da Floresta de Semliki/fisiologia , Humanos , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Linhagem Celular , Ligação Viral , Endossomos/virologia
20.
J Colloid Interface Sci ; 673: 321-332, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38878367

RESUMO

Binder-free self-supported carbon cloth electrode provides novel strategies for the preparation of MOFs, effectively improving the conductivity and promoting charge transfer. Combining MOFs with vanadate to form a unique heterogeneous structure provides a large specific surface area and more active sites, further enhancing the kinetics of MOFs. Herein, a self-supported carbon cloth electrode is prepared by in-situ growth of CoNi-MOFs on activated carbon cloth (AC) and coating with NiVO3. The heterostructure increases the specific surface area and exposes more active sites to promote the adsorption and diffusion of ions, thus enhancing the kinetic activity and optimizing charge storage behavior. As expected, the NiVO3@CoNi-MOF/AC exhibits a specific capacitance of up to 19.20 F/cm2 at 1 mA/cm2. The asymmetric supercapacitors (ASCs) assembled by NiVO3@CoNi-MOF/AC and annealed activated carbon cloth achieve an energy density of 1.27 mWh/cm2 at a power density of 4 mW/cm2 and have a capacitance retention of 96.43 % after 10,000 cycles. In addition, the NiVO3@CoNi-MOF/AC as electrocatalyst has an overpotential of 370 mV at 10 mA/cm2 and a Tafel slope of 208 mV dec-1, demonstrating remarkable electrocatalytic oxygen evolution reaction performance. These unique heterostructures endow the electrode with more electrochemical selectivity and provide new key insights for designing multifunctional materials.

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