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1.
Nat Immunol ; 20(1): 18-28, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30510222

RESUMO

Cyclic GMP-AMP synthase (cGAS) is a key sensor responsible for cytosolic DNA detection. Here we report that GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) is critical for DNA sensing and efficient activation of cGAS. G3BP1 enhanced DNA binding of cGAS by promoting the formation of large cGAS complexes. G3BP1 deficiency led to inefficient DNA binding by cGAS and inhibited cGAS-dependent interferon (IFN) production. The G3BP1 inhibitor epigallocatechin gallate (EGCG) disrupted existing G3BP1-cGAS complexes and inhibited DNA-triggered cGAS activation, thereby blocking DNA-induced IFN production both in vivo and in vitro. EGCG administration blunted self DNA-induced autoinflammatory responses in an Aicardi-Goutières syndrome (AGS) mouse model and reduced IFN-stimulated gene expression in cells from a patient with AGS. Thus, our study reveals that G3BP1 physically interacts with and primes cGAS for efficient activation. Furthermore, EGCG-mediated inhibition of G3BP1 provides a potential treatment for cGAS-related autoimmune diseases.


Assuntos
Doenças Autoimunes do Sistema Nervoso/metabolismo , DNA Helicases/metabolismo , Complexos Multiproteicos/metabolismo , Malformações do Sistema Nervoso/metabolismo , Nucleotidiltransferases/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Animais , Autoantígenos/imunologia , Autoantígenos/metabolismo , Doenças Autoimunes do Sistema Nervoso/tratamento farmacológico , Doenças Autoimunes do Sistema Nervoso/genética , Catequina/análogos & derivados , Catequina/uso terapêutico , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Citosol/imunologia , Citosol/metabolismo , DNA/imunologia , DNA/metabolismo , DNA Helicases/antagonistas & inibidores , DNA Helicases/genética , Modelos Animais de Doenças , Exodesoxirribonucleases/genética , Células HEK293 , Células HeLa , Humanos , Interferons/metabolismo , Camundongos , Camundongos Knockout , Malformações do Sistema Nervoso/tratamento farmacológico , Malformações do Sistema Nervoso/genética , Fármacos Neuroprotetores/uso terapêutico , Fosfoproteínas/genética , Proteínas de Ligação a Poli-ADP-Ribose/antagonistas & inibidores , Proteínas de Ligação a Poli-ADP-Ribose/genética , Ligação Proteica , RNA Helicases/antagonistas & inibidores , RNA Helicases/genética , Proteínas com Motivo de Reconhecimento de RNA/antagonistas & inibidores , Proteínas com Motivo de Reconhecimento de RNA/genética
2.
Cereb Cortex ; 34(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38863113

RESUMO

Neuropsychological and neuroimaging studies provide evidence for a degree of category-related organization of conceptual knowledge in the brain. Some of this evidence indicates that body part concepts are distinctly represented from other categories; yet, the neural correlates and mechanisms underlying these dissociations are unclear. We expand on the limited prior data by measuring functional magnetic resonance imaging responses induced by body part words and performing a series of analyses investigating the cortical representation of this semantic category. Across voxel-level contrasts, pattern classification, representational similarity analysis, and vertex-wise encoding analyses, we find converging evidence that the posterior middle temporal gyrus, the supramarginal gyrus, and the ventral premotor cortex in the left hemisphere play important roles in the preferential representation of this category compared to other concrete objects.


Assuntos
Mapeamento Encefálico , Imageamento por Ressonância Magnética , Humanos , Feminino , Masculino , Mapeamento Encefálico/métodos , Adulto , Adulto Jovem , Formação de Conceito/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Semântica
3.
Proc Natl Acad Sci U S A ; 119(6)2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35115397

RESUMO

The nature of the representational code underlying conceptual knowledge remains a major unsolved problem in cognitive neuroscience. We assessed the extent to which different representational systems contribute to the instantiation of lexical concepts in high-level, heteromodal cortical areas previously associated with semantic cognition. We found that lexical semantic information can be reliably decoded from a wide range of heteromodal cortical areas in the frontal, parietal, and temporal cortex. In most of these areas, we found a striking advantage for experience-based representational structures (i.e., encoding information about sensory-motor, affective, and other features of phenomenal experience), with little evidence for independent taxonomic or distributional organization. These results were found independently for object and event concepts. Our findings indicate that concept representations in the heteromodal cortex are based, at least in part, on experiential information. They also reveal that, in most heteromodal areas, event concepts have more heterogeneous representations (i.e., they are more easily decodable) than object concepts and that other areas beyond the traditional "semantic hubs" contribute to semantic cognition, particularly the posterior cingulate gyrus and the precuneus.


Assuntos
Formação de Conceito/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico/métodos , Cognição/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Lobo Parietal/fisiologia , Semântica , Adulto Jovem
4.
Development ; 148(14)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34152408

RESUMO

The development of ovarian follicles constitutes the foundation of female reproduction. The proliferation of granulosa cells (GCs) is a basic process required to ensure normal follicular development. However, the mechanisms involved in controlling GC cell cycle are not fully understood. Here, by performing gene expression profiling in the domestic pig (Sus scrofa), we showed that cell cycle arrest at G0/G1 phase is highly correlated with pathways associated with hypoxic stress and FOXO signalling. Specifically, the elevated proportion of GCs at the arrested G0/G1 phase was accompanied by increased nuclear translocation of FOXO1 under conditions of hypoxia both in vivo and in vitro. Furthermore, phosphorylation of 14-3-3 by the JNK kinase is required for hypoxia-mediated FOXO1 activation and the resultant G0/G1 arrest. Notably, a FOXO1 mutant without DNA-binding activity failed to induce G0/G1 arrest of GCs during hypoxia. Importantly, we identified a new target gene of FOXO1, namely TP53INP1, which contributes to suppression of the G1-S cell cycle transition in response to hypoxia. Furthermore, we demonstrated that the inhibitory effect of the FOXO1-TP53INP1 axis on the GC cell cycle is mediated through a p53-CDKN1A-dependent mechanism. These findings could provide avenues for the clinical treatment of human infertility caused by impaired follicular development.


Assuntos
Proteínas de Transporte/metabolismo , Pontos de Checagem do Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Proteína Forkhead Box O1/metabolismo , Proteínas de Choque Térmico/metabolismo , Hipóxia/metabolismo , Folículo Ovariano/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Proteínas de Transporte/genética , Ciclo Celular , Divisão Celular , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Feminino , Proteína Forkhead Box O1/genética , Fase G1 , Células da Granulosa/metabolismo , Proteínas de Choque Térmico/genética , Humanos , Hipóxia/genética , Fosforilação , Fase de Repouso do Ciclo Celular , Transdução de Sinais , Proteína Supressora de Tumor p53/genética
5.
BMC Cancer ; 24(1): 95, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233827

RESUMO

BACKGROUND: Sarcopenia has received increasing attention in non-small cell lung cancer (NSCLC). Red blood cell distribution width (RDW) is a significant component of the complete blood count and indicates the heterogeneity of erythrocyte volume. Little information is known about RDW in relation to sarcopenia in early-stage (IA-IIIA) NSCLC. The purpose of the present study was to investigate the association between RDW and sarcopenia risk in early-stage NSCLC patients. METHODS: This study included 378 patients with pathologically confirmed stage IA-IIIA NSCLC. Sarcopenia was defined by measuring the skeletal muscle index (SMI) at the eleventh thoracic vertebra level. The maximum Youden index on the receiver operating characteristic (ROC) curve was used to estimate the cutoff value for RDW to predict sarcopenia. Logistic regression analyses were carried out to assess the independent risk factors for sarcopenia in NSCLC. RESULTS: The ROC curve indicated that the best cutoff point for RDW to predict sarcopenia was 12.9 (sensitivity of 43.80% and specificity of 76.76%, respectively). Moreover, there were significant differences in hemoglobin (p < 0.001), comorbidities (p = 0.001), histological type (p = 0.002), and cancer stage (p = 0.032) between the high RDW and low RDW groups. Logistic regression analyses revealed that high RDW is an independent risk factor for sarcopenia in early-stage NSCLC. CONCLUSION: RDW is associated with sarcopenia risk in early-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcopenia , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Sarcopenia/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia , Eritrócitos/patologia , Curva ROC , Prognóstico
6.
Langmuir ; 40(31): 16511-16520, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39072506

RESUMO

An intelligent delivery nanoformulation could enhance the utilization efficacy, uptake, and translocation of pesticides in plants. Herein, a redox/pH-triggered and fluorescent smart delivery nanoformulation was designed and constructed by using hollow mesoporous organosilica nanoparticles (HMONs) and ZnO quantum dots as the nanocarrier and capping agent, respectively. Boscalid was further loaded to generate Boscalid@HMONs@ZnO with a loading rate of 9.8% for controlling Botrytis cinerea (B. cinerea). The quantity of boscalid released by Boscalid@HMONs@ZnO in a glutathione environment or at pH 3.0 was 1.3-fold and 1.9-fold higher than that in a neutral condition. Boscalid@HMONs@ZnO has 1.7-fold the toxicity index of boscalid technical against B. cinerea in antifungal experiments. Pot experiments revealed that the efficacy of Boscalid@HMONs@ZnO was significantly enhanced more than 1.27-fold compared to commercially available water-dispersible granules of boscalid. Due to the fluorescence properties of Boscalid@HMONs@ZnO, pesticide transport's real-time monitoring of pesticide translocation in tomato plants could be observed by confocal laser scanning microscopy. Fluorescence images revealed that HMONs@ZnO had been effectively transported via treated leaves or roots in tomato plants. This research showed the successful application of HMONs@ZnO as a nanocarrier for controlling disease and offered an effective avenue to explore the real-time tracking of pesticide translocation in plants.


Assuntos
Botrytis , Nanopartículas , Oxirredução , Óxido de Zinco , Botrytis/efeitos dos fármacos , Nanopartículas/química , Óxido de Zinco/química , Óxido de Zinco/farmacologia , Concentração de Íons de Hidrogênio , Corantes Fluorescentes/química , Compostos de Bifenilo/química , Pontos Quânticos/química , Pontos Quânticos/toxicidade , Solanum lycopersicum/química , Praguicidas/química , Praguicidas/toxicidade , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Liberação Controlada de Fármacos , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Niacinamida/análogos & derivados
7.
EMBO Rep ; 23(1): e53166, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34779554

RESUMO

Cyclic GMP-AMP synthase (cGAS) functions as a key sensor for microbial invasion and cellular damage by detecting emerging cytosolic DNA. Here, we report that GTPase-activating protein-(SH3 domain)-binding protein 1 (G3BP1) primes cGAS for its prompt activation by engaging cGAS in a primary liquid-phase condensation state. Using high-resolution microscopy, we show that in resting cells, cGAS exhibits particle-like morphological characteristics, which are markedly weakened when G3BP1 is deleted. Upon DNA challenge, the pre-condensed cGAS undergoes liquid-liquid phase separation (LLPS) more efficiently. Importantly, G3BP1 deficiency or its inhibition dramatically diminishes DNA-induced LLPS and the subsequent activation of cGAS. Interestingly, RNA, previously reported to form condensates with cGAS, does not activate cGAS. Accordingly, we find that DNA - but not RNA - treatment leads to the dissociation of G3BP1 from cGAS. Taken together, our study shows that the primary condensation state of cGAS is critical for its rapid response to DNA.


Assuntos
DNA Helicases , Nucleotidiltransferases , Proteínas de Ligação a Poli-ADP-Ribose , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , DNA/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , Nucleotidiltransferases/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/genética , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/genética , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Grânulos de Estresse
8.
Mol Biol Rep ; 51(1): 386, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441676

RESUMO

BACKGROUND: There was significant difference in muscle development between fat-type and lean-type pig breeds. METHODS AND RESULTS: In current study, transcriptome analysis and bioinformatics analysis were used to compare the difference in longissimus dorsi (LD) muscle at three time-points (38 days post coitus (dpc), 58 dpc, and 78 dpc ) between Huainan (HN) and Large white (LW) pig breeds. A total of 24500 transcripts were obtained in 18 samples, and 2319, 2799, and 3713 differently expressed genes (DEGs) were identified between these two breeds at 38 dpc, 58 dpc, and 78 dpc, respectively. And the number and foldchange of DEGs were increased, the alternative splice also increased. The cluster analysis of DEGs indicated the embryonic development progress of LD muscle between these two breeds was different. There were 539 shared DEGs between HN and LW at three stages, and the top-shared DEGs were associated with muscle development and lipid deposition, such as KLF4, NR4A1, HSP70, ZBTB16 and so on. CONCLUSIONS: The results showed DEGs between Huainan (HN) and Large white (LW) pig breeds, and contributed to the understanding the muscle development difference between HN and LW, and provided basic materials for improvement of meat quality.


Assuntos
Biologia Computacional , Perfilação da Expressão Gênica , Feminino , Gravidez , Suínos/genética , Animais , Análise por Conglomerados , Desenvolvimento Embrionário , Obesidade , Vitaminas
9.
J Sci Food Agric ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38804719

RESUMO

BACKGROUND: To mitigate post-harvest losses and inform harvesting decisions at the same time as ensuring fruit quality, precise ripeness determination is essential. The complexity arises in assessing guava ripeness as a result of subtle alterations in some varieties during the ripening process, making visual assessment less reliable. The present study proposes a non-destructive method employing thermal imaging for guava ripeness assessment, involving obtaining thermal images of guava samples at different ripeness stages, followed by data pre-processing. Five deep learning models (AlexNet, Inception-v3, GoogLeNet, ResNet-50 and VGGNet-16) were applied, and their performances were systematically evaluated and compared. RESULTS: VGGNet-16 demonstrated outstanding performance, achieving average precision of 0.92, average sensitivity of 0.93, average specificity of 0.96, average F1-score of 0.92 and accuracy of 0.92 within a training duration of 484 s. CONCLUSION: The present study presents a scalable and non-destructive approach for guava ripeness determination, contributing to waste reduction and enhancing efficiency in supply chains and fruit production. These initiatives align with environmentally friendly practices in agriculture. © 2024 Society of Chemical Industry.

10.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1172-1185, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621964

RESUMO

Cyclopeptides isolated from a variety of plants are a class of cyclic nitrogen-containing compounds, and they are primarily formed by peptide bonds between amino acids, generally containing 2 to 37 L-configuration encoded or non-encoded amino acid residues. Cyclopeptides have significant values in scientific research as natural small-molecule metabolites produced by plants. The available studies have revealed that such natural products are ubiquitous in plants, which mainly include cyclic dipeptides, cyclic tetrapeptides, cyclic pentapeptides, cyclic hexapeptides, cyclic heptapeptides, cyclic octapeptides, cyclic nonapeptides, and cyclic decapeptides. Among them, cyclic dipeptides, cyclic hexapeptides, and cyclic octapeptides are the major active compounds. It has been reported that plant cyclopeptides have novel and unique chemical structures. They possess diverse pharmacological activities, such as antineoplastic, antimicrobial, antimalarial, anti-inflammatory, and antiviral activities. This paper summarizes the research achievements of plant cyclopeptides since 2006, aiming to provide theoretical reference for the research and application of plant cyclopeptides in medicine, health, and agriculture fields.


Assuntos
Anti-Infecciosos , Antineoplásicos , Peptídeos Cíclicos/química , Antineoplásicos/farmacologia , Anti-Infecciosos/farmacologia , Dipeptídeos
11.
Zhongguo Zhong Yao Za Zhi ; 49(8): 2158-2168, 2024 Apr.
Artigo em Zh | MEDLINE | ID: mdl-38812231

RESUMO

This study systematically explored the transdermal diffusion law of functional substances of Jingu Zhitong Gel(JGZTG). The transdermal diffusion research methods of JGZTG were investigated by single factor trial with the automated transdermal(dry-heat) sampling system. High performance liquid chromatography(HPLC) content determination method was established to determine the contents of ferulic acid, senkyunolide I, cinnamic acid, hydroxy-ε-xanthoxylin, hydroxy-α-xanthoxylin, and hydroxy-ß-xanthoxylin in the transdermal diffusion solution of JGZTG. The transdermal diffusion law of the components within 16 h was investigated. The results showed that the optimal transdermal diffusion method of JGZTG was as follows: Rat skin was used as the transdermal barrier; normal saline was used as the receiving medium; the dosage of JGZTG was 0.3 g, and the receiving solution was extracted by ethyl acetate. The results of transdermal diffusion showed that the release of ferulic acid, cinnamic acid, and senkyunolide I increased significantly at 0-8 h and slowed down at 8-16 h. The drug release was a synergic process of diffusion and dissolution, in which ferulic acid and cinnamic acid followed Higuchi and Ritger-Peppas equations, and liguolactone I followed Higuchi equation. The transdermal diffusion curves of hydroxy-ε-zanthoxylin, hydroxy-α-zanthoxylin, and hydroxy-ß-zanthoxylin showed continuous release within 16 h, and the drug release was skeleton dissolution. The diffusion law followed zero-order equation, first-order equation, and Ritger-Peppas equation. In clonclusion, it is a controlled release of ferulic acid, ligustrone I, cinnamic acid, hydroxy-ε-pyrroxylin, hydroxy-α-pyrroxylin, and hydroxy-ß-pyrroxylin in JGZTG, which can maintain stable blood drug concentration with 16 h, and the cumulative transmittance of each component with 12 h can reach 80% of cumulative transmittance with 24 h, which is in line with the clinical drug use law of bis in die.


Assuntos
Medicamentos de Ervas Chinesas , Absorção Cutânea , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/administração & dosagem , Ratos , Animais , Difusão , Administração Cutânea , Pele/metabolismo , Pele/química , Géis/química , Masculino , Ratos Sprague-Dawley , Cromatografia Líquida de Alta Pressão , Cinamatos/farmacocinética , Cinamatos/análise , Cinamatos/química , Ácidos Cumáricos/farmacocinética , Ácidos Cumáricos/análise
12.
J Biol Chem ; 298(5): 101830, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35300979

RESUMO

Owing to the avascular environment within ovarian follicles, granulosa cells (GCs) are believed to live in a hypoxic niche. Follicle-stimulating hormone (FSH)-mediated steroidogenesis is crucial for normal growth and maturation of ovarian follicles, but it remains unclear how FSH stimulates estradiol (E2) synthesis under hypoxic conditions. Here, we aimed to explore whether FSH affects the ATP production required for estrogen synthesis from the perspective of glucose metabolism. It was observed that the levels of both E2 and HIF-1α were markedly increased in a dose-dependent manner in mouse ovarian GCs after the injection of FSH in vivo, indicating that hypoxia/HIF-1α may be relevant to FSH-induced E2 synthesis. By treating hypoxic GCs with FSH in vitro, we further revealed that the activation of the AMP-activated protein kinase (AMPK)-GLUT1 pathway, which in turn stimulates ATP generation, may be essential for FSH-mediated E2 production during hypoxia. In contrast, inhibition of AMPK or GLUT1 with siRNAs/antagonist both repressed glycolysis, ATP production, and E2 synthesis despite FSH treatment. Moreover, blocking HIF-1α activity using siRNAs/PX-478 suppressed AMPK activation, GLUT1 expression, and E2 levels in FSH-treated GCs. Finally, the in vitro findings were verified in vivo, which showed markedly increased AMPK activity, GLUT1 expression, glycolytic flux, ATP levels, and E2 concentrations in ovarian GCs following FSH injection. Taken together, these findings uncovered a novel mechanism for FSH-regulating E2 synthesis in hypoxic GCs by activating glycolytic metabolism through the HIF-1α-AMPK-GLUT1 pathway.


Assuntos
Proteínas Quinases Ativadas por AMP , Estradiol , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Estradiol/metabolismo , Estradiol/farmacologia , Feminino , Hormônio Foliculoestimulante/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glicólise , Células da Granulosa/metabolismo , Hipóxia/metabolismo , Camundongos , Transdução de Sinais
13.
Biochem Biophys Res Commun ; 663: 192-201, 2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37141668

RESUMO

The neuroprotective effects of hydrogen have been demonstrated, but the mechanism is still poorly understood. In a clinical trial of inhaled hydrogen in patients with subarachnoid hemorrhage (SAH), we found that hydrogen reduced the accumulation of lactic acid in the nervous system. There are no studies demonstrating the regulatory effect of hydrogen on lactate and in this study we hope to further clarify the mechanism by which hydrogen regulates lactate metabolism. In cell experiments, PCR and Western Blot showed that HIF-1α was the target related to lactic acid metabolism that changed the most before and after hydrogen intervention. HIF-1α levels were suppressed by hydrogen intervention treatment. Activation of HIF-1α inhibited the lactic acid-lowering effect of hydrogen. We have also demonstrated the lactic acid-lowering effect of hydrogen in animal studies. Our work clarifies that hydrogen can regulate lactate metabolism via the HIF-1αpathway, providing new insights into the neuroprotective mechanisms of hydrogen.


Assuntos
Ácido Láctico , Hemorragia Subaracnóidea , Animais , Ácido Láctico/metabolismo , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/metabolismo , Western Blotting , Terapia Respiratória , Subunidade alfa do Fator 1 Induzível por Hipóxia
14.
Langmuir ; 39(50): 18466-18475, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38054693

RESUMO

Extremely inefficient utilization of pesticides has prompted a study of low-cost, sustainable, and smart application systems. Herein, as a promising pesticide nanocarrier, hollow mesoporous organosilica nanoparticles (HMONs) were first synthesized by using inexpensive CaCO3 nanoparticles as the hollow templates. A redox/near-infrared light dual-triggered pesticide release system was further achieved via loading avermectin (AVM) into the HMONs and coating a layer of polydopamine (PDA). The as-prepared AVM@HMONs@PDA displays a favorable pesticide load capability (24.8 wt %), outstanding photothermal performance, and high adhesion to leaves. In addition, with glutathione (GSH), the AVM cumulative release from AVM@HMONs@PDA was 3.5 times higher than that without GSH. Under ultraviolet light irradiation, the half-life of AVM@HMONs@PDA was prolonged by 17.0-fold compared to that of the AVM technical. At day 21 after treatment in the insecticidal activity, the median lethal concentrations (LC50) values displayed that the toxicity of AVM@HMONs@PDA for Panonychus citri (McGregor) was enhanced 4.0-fold compared with the commercial emulsifiable concentrate. In the field trial, at day 28 after spraying, AVM@HMONs@PDA was significantly more control effective than AVM-EC in controlling the P. citri (McGregor), even at a 50% reduced dosage. Moreover, HMONs@PDA was safe for crops. This research presents a novel preparation approach for HMONs, and it also offers a promising nanoplatform for the precise release of pesticides.


Assuntos
Nanopartículas , Praguicidas , Praguicidas/toxicidade , Nanopartículas/toxicidade , Ivermectina/toxicidade , Raios Ultravioleta
15.
J Org Chem ; 88(15): 10753-10760, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37467194

RESUMO

A tetramethylammonium iodide (TBAI)-mediated cyclization and methylsulfonylation of propargylic amides enabled by dimethyl sulfite as a SO2 surrogate and methyl source have been developed. The transition metal-free and oxidant-free reaction provides a practical and efficient approach for the selective synthesis of methylsulfonyl oxazoles in moderate to excellent yields with good functional group compatibility.

16.
Cell Mol Biol (Noisy-le-grand) ; 69(7): 181-186, 2023 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-37715388

RESUMO

Growing evidence suggested that long non-coding RNA (lncRNA) played a crucial role in the progression of ulcerative colitis (UC). Therefore, the purpose of this study is to understand how the lncRNA CBR3-AS1, which has been found to be up-regulated in UC, contributes to the bio-progression of the disease. To determine the concentration and relationship of the lncRNA CBR3-AS1, miRNA-145-5p, and FN1 in the LPS-induced Caco-2 model cells, qRT-PCR was employed in this study.  Starbase was used to predict the target sites of the lncRNA CBR3-AS1 and the miRNA-145-5p, and Targetscan was used to predict the probable linking points of the FN1 and the miRNA-145-5p, which was confirmed by a twofold luciferase reporter test. The vitality of Caco-2 cells was determined using the CCK-8 and FCM tests. Using the ELISA kit, TNF, IFN, IL-6, and IL-17 were identified. The results of the experiment show that in Caco-2 cells treated with 10 ng/mL LPS, LncRNA CBR3-AS1 was up-regulated. Additionally, Caco-2 cells' LPS-induced apoptosis and inflammatory response were inhibited by lncRNA CBR3-AS1 inhibition. Dual-luciferase reporter experiments demonstrated that miRNA-145-5p and lncRNA CBR3-AS1 might connect. Moreover, miRNA-145-5p, which was shown to be poorly expressed in UC, was found to suppress inflammatory and apoptotic responses in Caco-2 cells activated by LPS. It's significant that FN1 was confirmed to be miRNA-145-5p's downstream target. Sh-CBR3-AS1's inhibitory effects were reversed by miRNA-145-5p knockdown, and the effects of the miRNA-145-5p inhibitor were reversed by sh-FN1. In conclusion, LncRNA CBR3-AS1 may offer a unique method for treating UC by suppressing the function of miRNA-145-5p, which is implicated in the development of UC.


Assuntos
Colite Ulcerativa , MicroRNAs , RNA Longo não Codificante , Humanos , Células CACO-2 , Colite Ulcerativa/genética , Lipopolissacarídeos , MicroRNAs/genética , RNA Longo não Codificante/genética
17.
Int J Hyperthermia ; 40(1): 2226847, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37394476

RESUMO

OBJECTIVE: To predict the risk of postoperative reintervention for uterine fibroids using clinical-imaging features and T2WI radiomics before high-intensity focused ultrasound (HIFU) ablation. METHODS: Among patients with uterine fibroids treated with HIFU from 2019 to 2021, 180 were selected per the inclusion and exclusion criteria (42 reintervention and 138 non-reintervention). All patients were randomly assigned to either the training (n = 125) or validation (n = 55) cohorts. Multivariate analysis was used to determine independent clinical-imaging features of reintervention risk. The Relief and LASSO algorithm were used to select optimal radiomics features. Random forest was used to construct the clinical-imaging model based on independent clinical-imaging features, the radiomics model based on optimal radiomics features, and the combined model incorporating the above features. An independent test cohort of 45 patients with uterine fibroids tested these models. The integrated discrimination index (IDI) was used to compare the discrimination performance of these models. RESULTS: Age (p < .001), fibroid volume (p = .001) and fibroid enhancement degree (p = .001) were identified as independent clinical-imaging features. The combined model had AUCs of 0.821 (95% CI: 0.712-0.931) and 0.818 (95% CI: 0.694-0.943) in the validation and independent test cohorts, respectively. The predictive performance of the combined model was 27.8% (independent test cohort, p < .001) and 29.5% (independent test cohort, p = .001) better than the clinical-imaging and radiomics models, respectively. CONCLUSION: The combined model can effectively predict the risk of postoperative reintervention for uterine fibroids before HIFU ablation. It is expected to help clinicians to develop accurate, personalized treatment and management plans. Future studies will need to be prospectively validated.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade , Leiomioma , Neoplasias Uterinas , Feminino , Humanos , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/cirurgia , Leiomioma/diagnóstico por imagem , Leiomioma/cirurgia , Diagnóstico por Imagem , Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Resultado do Tratamento , Imageamento por Ressonância Magnética , Estudos Retrospectivos
18.
BMC Vet Res ; 19(1): 46, 2023 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-36765329

RESUMO

BACKGROUND: Porcine epidemic diarrhea (PED), caused by PED virus (PEDV), is a severe enteric disease burdening the global swine industry in recent years. Especially, the mortality of PED in neonatal piglets approaches 100%. Maternal antibodies in milk, particularly immunoglobulin A (IgA) antibodies, are of great importance for protection neonatal suckling piglets against PEDV infection as passive lactogenic immunity. Therefore, appropriate detection methods are required for detecting PEDV IgA antibodies in milk. In the current study, we prepared monoclonal antibodies (mAbs) against PEDV spike (S) glycoprotein. An enzyme-linked immunosorbent assay (ELISA) was subsequently developed based on PEDV antigen capture by a specific anti-S mAb. RESULTS: The developed ELISA showed high sensitivity (the maximum dilution of milk samples up to 1:1280) and repeatability (coefficient of variation values < 10%) in detecting PEDV IgA antibody positive and negative milk samples. More importantly, the developed ELISA showed a high coincidence rate with a commercial ELISA kit for PEDV IgA antibody detection in clinical milk samples. CONCLUSIONS: The developed ELISA in the current study is applicable for PEDV IgA antibody detection in milk samples, which is beneficial for evaluating vaccination efficacies and neonate immune status against the virus.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Doenças dos Suínos , Animais , Suínos , Leite , Anticorpos Antivirais , Antígenos Virais , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/prevenção & controle , Ensaio de Imunoadsorção Enzimática/veterinária , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Monoclonais , Imunoglobulina A
19.
Cell Mol Life Sci ; 79(3): 137, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35182235

RESUMO

Renal interstitial fibrosis is the pathological basis of end-stage renal disease, in which the heterogeneity of macrophages in renal microenvironment plays an important role. However, the molecular mechanisms of macrophage plasticity during renal fibrosis progression remain unclear. In this study, we found for the first time that increased expression of Twist1 in macrophages was significantly associated with the severity of renal fibrosis in IgA nephropathy patients and mice with unilateral ureteral obstruction (UUO). Ablation of Twist1 in macrophages markedly alleviated renal tubular injury and renal fibrosis in UUO mice, accompanied by a lower extent of macrophage infiltration and M2 polarization in the kidney. The knockdown of Twist1 inhibited the chemotaxis and migration of macrophages, at least partially, through the CCL2/CCR2 axis. Twist1 downregulation inhibited M2 macrophage polarization and reduced the secretion of the profibrotic factors Arg-1, MR (CD206), IL-10, and TGF-ß. Galectin-3 was decreased in the macrophages of the conditional Twist1-deficient mice, and Twist1 was shown to directly activate galectin-3 transcription. Up-regulation of galectin-3 recovered Twist1-mediated M2 macrophage polarization. In conclusion, Twist1/galectin-3 signaling regulates macrophage plasticity (M2 phenotype) and promotes renal fibrosis. This study could suggest new strategies for delaying kidney fibrosis in patients with chronic kidney disease.


Assuntos
Fibrose/patologia , Galectina 3/metabolismo , Nefropatias/patologia , Ativação de Macrófagos , Proteína 1 Relacionada a Twist/metabolismo , Obstrução Ureteral/complicações , Animais , Fibrose/etiologia , Fibrose/metabolismo , Galectina 3/genética , Humanos , Nefropatias/etiologia , Nefropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais , Proteína 1 Relacionada a Twist/genética
20.
Skin Pharmacol Physiol ; 36(3): 160-164, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36917958

RESUMO

Autism is a neurodevelopmental disorder. Individuals with autism can exhibit multiple neurological symptoms such as deficit in social communication, restricted interests, and repetitive behaviors. Recent study showed that murine model of autism displays an increased transepidermal water loss (TEWL) and dry skin. But whether epidermal functions are also altered in children with autism is unknown. In the present study, TEWL, stratum corneum hydration, and skin surface pH were compared between children with autism (N = 56) and normal controls (N = 48). Our results showed that children with autism exhibited lower stratum corneum hydration levels, higher TEWL, and elevated skin surface pH in comparison to normal controls (p < 0.0001 for all). These results demonstrate that children with autism exhibit epidermal dysfunction.


Assuntos
Transtorno Autístico , Humanos , Criança , Animais , Camundongos , Transtorno Autístico/metabolismo , Epiderme/metabolismo , Água/metabolismo , Perda Insensível de Água , Pele
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