Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 88
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Neuroimage ; 299: 120812, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39197559

RESUMO

Brain magnetic resonance imaging (MRI) is widely used in clinical practice for disease diagnosis. However, MRI scans acquired at different sites can have different appearances due to the difference in the hardware, pulse sequence, and imaging parameter. It is important to reduce or eliminate such cross-site variations with brain MRI harmonization so that downstream image processing and analysis is performed consistently. Previous works on the harmonization problem require the data acquired from the sites of interest for model training. But in real-world scenarios there can be test data from a new site of interest after the model is trained, and training data from the new site is unavailable when the model is trained. In this case, previous methods cannot optimally handle the test data from the new unseen site. To address the problem, in this work we explore domain generalization for brain MRI harmonization and propose Site Mix (SiMix). We assume that images of travelling subjects are acquired at a few existing sites for model training. To allow the training data to better represent the test data from unseen sites, we first propose to mix the training images belonging to different sites stochastically, which substantially increases the diversity of the training data while preserving the authenticity of the mixed training images. Second, at test time, when a test image from an unseen site is given, we propose a multiview strategy that perturbs the test image with preserved authenticity and ensembles the harmonization results of the perturbed images for improved harmonization quality. To validate SiMix, we performed experiments on the publicly available SRPBS dataset and MUSHAC dataset that comprised brain MRI acquired at nine and two different sites, respectively. The results indicate that SiMix improves brain MRI harmonization for unseen sites, and it is also beneficial to the harmonization of existing sites.


Assuntos
Encéfalo , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/normas , Algoritmos , Neuroimagem/métodos , Neuroimagem/normas
2.
Mol Biol Evol ; 40(10)2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37804524

RESUMO

Herbivorous insects such as whiteflies, planthoppers, and aphids secrete abundant orphan proteins to facilitate feeding. Yet, how these genes are recruited and evolve to mediate plant-insect interaction remains unknown. In this study, we report a horizontal gene transfer (HGT) event from fungi to an ancestor of Aleyrodidae insects approximately 42 to 190 million years ago. BtFTSP1 is a salivary protein that is secreted into host plants during Bemisia tabaci feeding. It targets a defensive ferredoxin 1 in Nicotiana tabacum (NtFD1) and disrupts the NtFD1-NtFD1 interaction in plant cytosol, leading to the degradation of NtFD1 in a ubiquitin-dependent manner. Silencing BtFTSP1 has negative effects on B. tabaci feeding while overexpressing BtFTSP1 in N. tabacum benefits insects and rescues the adverse effect caused by NtFD1 overexpression. The association between BtFTSP1 and NtFD1 is newly evolved after HGT, with the homologous FTSP in its fungal donor failing to interact and destabilize NtFD1. Our study illustrates the important roles of horizontally transferred genes in plant-insect interactions and suggests the potential origin of orphan salivary genes.


Assuntos
Afídeos , Hemípteros , Animais , Ferredoxinas/metabolismo , Plantas/metabolismo , Hemípteros/genética , Nicotiana/genética , Nicotiana/metabolismo , Afídeos/metabolismo , Proteínas e Peptídeos Salivares/genética
3.
New Phytol ; 243(4): 1506-1521, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38874414

RESUMO

Intercropping leads to different plant roots directly influencing belowground processes and has gained interest for its promotion of increased crop yields and resource utilization. However, the precise mechanisms through which the interactions between rhizosphere metabolites and the microbiome contribute to plant production remain ambiguous, thus impeding the understanding of the yield-enhancing advantages of intercropping. This study conducted field experiments (initiated in 2013) and pot experiments, coupled with multi-omics analysis, to investigate plant-metabolite-microbiome interactions in the rhizosphere of maize. Field-based data revealed significant differences in metabolite and microbiome profiles between the rhizosphere soils of maize monoculture and intercropping. In particular, intercropping soils exhibited higher microbial diversity and metabolite chemodiversity. The chemodiversity and composition of rhizosphere metabolites were significantly related to the diversity, community composition, and network complexity of soil microbiomes, and this relationship further impacted plant nutrient uptake. Pot-based findings demonstrated that the exogenous application of a metabolic mixture comprising key components enriched by intercropping (soyasapogenol B, 6-hydroxynicotinic acid, lycorine, shikimic acid, and phosphocreatine) significantly enhanced root activity, nutrient content, and biomass of maize in natural soil, but not in sterilized soil. Overall, this study emphasized the significance of rhizosphere metabolite-microbe interactions in enhancing yields in intercropping systems. It can provide new insights into rhizosphere controls within intensive agroecosystems, aiming to enhance crop production and ecosystem services.


Assuntos
Microbiota , Rizosfera , Microbiologia do Solo , Zea mays , Zea mays/microbiologia , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Nutrientes/metabolismo , Raízes de Plantas/microbiologia , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Agricultura/métodos , Solo/química , Biomassa
4.
Anaerobe ; 88: 102863, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38718918

RESUMO

This paper reports a case of Bacteroides fragilis induced spondylitis. Diagnosis was confirmed through blood culture and metagenomic sequencing of pus for pathogen detection. Due to persistent lumbar pain, surgical intervention became imperative, resulting in favorable postoperative outcomes. A detailed patient history revealed a severe episode of oral ulceration two weeks before symptom onset, although a direct link to the infection remained elusive. Leveraging insights from this case, we conducted a comprehensive literature review on B. fragilis spondylitis, elucidating clinical manifestations, diagnostic methodologies, and therapeutic strategies.


Assuntos
Infecções por Bacteroides , Bacteroides fragilis , Úlceras Orais , Espondilite , Humanos , Bacteroides fragilis/isolamento & purificação , Bacteroides fragilis/genética , Infecções por Bacteroides/diagnóstico , Infecções por Bacteroides/microbiologia , Infecções por Bacteroides/tratamento farmacológico , Espondilite/microbiologia , Espondilite/diagnóstico , Úlceras Orais/microbiologia , Úlceras Orais/diagnóstico , Masculino , Antibacterianos/uso terapêutico , Feminino , Pessoa de Meia-Idade
5.
J Environ Manage ; 358: 120886, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38648726

RESUMO

Intercropping-driven changes in nitrogen (N)-acquiring microbial genomes and functional expression regulate soil N availability and plant N uptake. However, present data seem to be limited to a specific community, obscuring the viewpoint of entire N-acquiring microbiomes and functions. Taking maize intercropped with legumes (peanut and soybean) and non-legumes (gingelly and sweet potato) as models, we studied the effects of intercropping on N transformations and N-acquiring microbiomes in rhizosphere soil across four maize growth stages. Meanwhile, we compiled promising strategies such as random forest analysis and structural equation model for the exploitation of the associations between microbe-driven N dynamics and soil-plant N trade-offs and maize productivity. Compared with monoculture, maize intercropping significantly increased the denitrification rate of rhizosphere soils across four maize growth stages, net N mineralization in the elongation and flowering stages, and the nitrification rate in the seedling and mature stages. The abundance of most N-acquiring microbial populations was influenced significantly by intercropping patterns and maize growth stages. Soil available N components (NH4+-N, NO3--N, and dissolved organic N content) showed a highly direct effect on plant N uptake, which mainly mediated by N transformations (denitrification rate) and N-acquiring populations (amoB, nirK3, and hzsB genes). Overall, the adaptation of N-acquiring microbiomes to changing rhizosphere micro-environments caused by intercropping patterns and maize development could promote soil N transformations and dynamics to meet demand of maize for N nutrient. This would offer another unique perspective to manage the benefits of the highly N-effective and production-effective intercropping ecosystems.


Assuntos
Nitrogênio , Rizosfera , Solo , Zea mays , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Nitrogênio/metabolismo , Solo/química , Microbiologia do Solo , Microbiota , Agricultura/métodos
6.
Small ; 19(40): e2302961, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37264718

RESUMO

Constructing the adjustable surface conductive networks is an innovation that can achieve a balance between enhanced attenuation and impedance mismatch according to the microwave absorption mechanism. However, the traditional design strategies remain significant challenges in terms of rational selection and controlled growth of conductive components. Herein, a hierarchical construction strategy and quantitative construction technique are employed to introduce conductive metal-organic frameworks (MOFs) derivatives in the classic yolk-shell structure composed of electromagnetic components and the cavity for remarkable optimized performance. Specifically, the surface conductive networks obtained by carbonized ZIF-67 quantitative construction, together with the Fe3 O4 magnetic core and dielectric carbon layer linked by the cavity, achieve the cooperative enhancement of impedance matching optimization and synergistic attenuation in the Fe3 O4 @C@Co/N-Doped C (FCCNC) absorber. This interesting design is further verified by experimental results and simulation calculations. The products FCCNC-2 yield a distinguished minimum reflection loss of -66.39 dB and an exceptional effective absorption bandwidth of 6.49 GHz, indicating that moderate conduction excited via hierarchical and quantitative design can maximize the absorption capability. Furthermore, the proposed versatile methodology of surface assembly paves a new avenue to maximize beneficial conduction effect and manipulate microwave attenuation in MOFs derivatives.

7.
Microb Pathog ; 169: 105652, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35753601

RESUMO

Psychrophilic bacteria are a type of microorganisms that normally grow in low-temperature environments. They are usually found in extremely cold environments. However, as people's demand for low-temperature storage of food becomes higher, psychrophilic bacteria have also begun to appear in cold storage and refrigerators, which has become a food safety hazard. In this paper, the optimal cooling strategies of psychrophilic bacteria are reviewed from the aspects of the cell membrane, psychrophilic enzymes, antifreeze proteins, cold shock proteins, gene regulation, metabolic levels and antifreeze agents, and the principle of psychrophilic mechanism is briefly described. The application of thermophilic bacteria and its products adapted to cold environments in food fields are analyzed. The purpose of this paper is to provide ideas for future research on psychrophilic bacteria based on the mechanism and application of psychrophilic bacteria.


Assuntos
Bactérias , Temperatura Baixa , Adaptação Fisiológica , Bactérias/metabolismo , Humanos
8.
Microb Pathog ; 162: 105306, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34822970

RESUMO

Foodborne diseases caused by foodborne pathogens are one of the main problems threatening human health and safety. The emergence of multi-drug resistant strains due to the abuse of antibiotics has increased the difficulty of clinical treatment. Research on the drug resistance mechanism of foodborne pathogens has become an effective method to solve multi-drug resistant strains. In this paper, the four main drug resistance mechanisms, including reduced cell membrane permeability, efflux pump mechanism, target site mutation mechanism, and enzymatic hydrolysis, were used to systematically analyze the drug resistance of Salmonella, Listeria monocytogenes, and Escherichia coli. And the new methods were discussed that may be used to solve the drug resistance of foodborne pathogens such as CRISPR and bacteriophages. This review provided a certain theoretical basis for the treatment of foodborne diseases.


Assuntos
Doenças Transmitidas por Alimentos , Listeria monocytogenes , Resistência a Medicamentos , Escherichia coli/genética , Microbiologia de Alimentos , Humanos , Listeria monocytogenes/genética , Salmonella/genética
9.
Arch Virol ; 167(10): 2079-2083, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35751691

RESUMO

The spotted lanternfly (Lycorma delicatula) is an invasive pest that causes serious economic losses in fruit and wood production. Here, we identified a novel iflavirus named "Lycorma delicatula iflavirus 1" (LDIV1), in a spotted lanternfly. The full genome sequence of LDIV1 is 10,222 nt in length and encodes a polyprotein containing a picornavirus capsid-protein-domain-like domain, a cricket paralysis virus capsid superfamily domain, an RNA helicase domain, a peptidase C3 superfamily domain, and an RNA-dependent RNA polymerase (RdRp) domain. LDIV1 replicates in the host insect and activates small interfering RNA (siRNA)-based host antiviral immunity. Phylogenetic analysis demonstrated that LDIV1 is most closely related to an unspecified member of the order Picornavirales, with 61.7% sequence identity in the RdRp region and 57.6% sequence identity in the coat protein region, and thus meets the demarcation criteria for new species in the genus Iflavirus. To the best of our knowledge, LDIV1 is the first virus discovered in L. delicatula.


Assuntos
Hemípteros , Vírus de RNA , Animais , Filogenia , RNA Polimerase Dependente de RNA , Análise de Sequência de DNA
10.
J Environ Manage ; 314: 115087, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35447443

RESUMO

Biochar is a promising novel material for mitigating phosphorus (P) loss and enhancing P retention in chemical-amended agricultural soils. However, the optimal application rate for aforesaid effectiveness and potential drivers of the process are not well understood. Herein, a column-based pot experiment was carried out to investigate how and to what extent reed-biochar is effective in positively triggering P loss and availability in paddy soils treated by chemical fertilizer. Compared with chemical-only treatment, the accumulated leakage of total P, dissoluble P, and particulate P in chemical fertilizer coupled with 1-4% reed-biochar treatment decreased by 5.3-13.3%, 8.3-10.4%, and 3.0-15.4%, respectively. The accumulated leakage of total P and dissoluble P in 6-8% rate treatments was increased by 5.6-7.5% and 18.3-32.9%, respectively. Increasing reed-biochar rate from 1% to 8% caused an enhancement in soil total P and available P content and P activation coefficient, and the 4% rate achieved a similar effectiveness to the higher rate. Reed-biochar application increased the abundance and diversty of soil phoD-harboring microbes (P < 0.05), while the increment had little to do with the application rate. Soil phoD-harboring community composition and total C content were the main predictors of the P leaching losses, and meanwhile, the total C content was the dominated predictor of soil P retention and availability. These results suggest that adding 1-4% reed-biochar was more beneficial to mitigate paddy P loss and to enhance soil P availability. This study highlights the importance of understanding how microbial populations mediate P transformation to decipher the biochar-driven improvement of soil P utilization.


Assuntos
Oryza , Solo , Carvão Vegetal , Fertilizantes/análise , Fósforo
11.
Small ; 17(26): e2100510, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34081390

RESUMO

The design and fabrication of transition metal dichalcogenides (TMDs) are of paramount significance for water-splitting process. However, the limited active sites and restricted conductivity prevent their further application. Herein, a polarization boosted strategy is put forward for the modification of TMDs to promote the absorption of the intermediates, leading to the improved catalytic performance. By the forced assembly of TMDs (WS2 as the example) and carbon nanotubes (CNTs) via spray-drying method, such frameworks can remarkably achieve low overpotentials and superior durability in alkaline media, which is superior to most of the TMDs-based catalysts. The two-electrode cell for water-splitting also exhibits perfect activity and stability. The enhanced catalytic performance of WS2 /CNTs composite is mainly owing to the strong polarized coupling between CNTs and WS2 nanosheets, which significantly promotes the charge redistribution on the interface of CNTs and WS2 . Density functional theory (DFT) calculations show that the CNTs enrich the electron content of WS2 , which favors electron transportation and accelerates the catalysis. Moreover, the size of WS2 is restricted caused by the confinement of CNTs, leading to the increased numbers of active sites, further improving the catalysis. This work opens a feasible route to achieve the optimized assembling of TMDs and CNTs for efficient water-splitting process.

12.
Small ; 17(30): e2100559, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34185440

RESUMO

While metal-based electrocatalysts have garnered extensive attention owing to the large variety of enzyme-mimic properties, the search for such highly-efficient catalysts still relies on empirical explorations, owing to the lack of predictive indicators as well as the ambiguity of structure-activity relationships. Notably, surface electronic structures play a crucial role in metal-based catalysts yet remain unexplored in enzyme-mimics. Herein, the authors investigate the electronic structure as a possible indicator of electrocatalytic activities of H2 O2 decomposition and glucose oxidation using Pd@Pt core-shell nanocrystals as a well-defined platform. The electron densities of the Pd@Pt are modulated with the correlation of strain through precise control of surface orientation and the number of atomic layers. The close relationships between the electrocatalytic activities and the surface charge accumulation are found, in which the increase of the electron accumulation can enhance both the enzyme-mimic activities. As a result, the Pd@Pt3L icosahedra with compressive strain in Pt shells exhibit the highest electrocatalytic activities for H2 O2 decomposition and glucose oxidation. Such systematic and comprehensive study provides the structure-activity relationships and paves a new way for the rational design of metal-based electrocatalysts. Especially, the charge accumulation degrees may serve as a general performance indicator for metal-based catalysts.


Assuntos
Nanopartículas , Platina , Catálise , Eletrônica , Paládio
13.
Exp Cell Res ; 397(1): 112335, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33132134

RESUMO

PURPOSE: Skp2, an oncoprotein, regulates tumor proliferation, invasion and metastasis. Ku70 is a critical component of the non-homologous end-joining (NHEJ) process. Both Skp2 and Ku70 are positively associated in multiple cancers. However, there is no report about the relationship between Skp2 and Ku70 proteins. METHODS: In this study, we carried out Bioinformatics and molecular biological methods to investigate the relationship between Skp2 and Ku70 proteins. RESULTS: We first observed Skp2 and Ku70 mRNAs were significantly increased in cervical cancer tissues. And we identified Ku70 as a Skp2-binding protein and the binding site located in the C-terminal of Ku70 protein. We further found that Skp2 knockdown decreased the Ku70 protein level in cells, and increase the cellular apoptosis and DNA damage, suggesting Skp2 mediates the Ku70 protein stability and function via post-translational modification. CONCLUSION: The direct interaction between Skp2 and Ku70 proteins mediates the DNA damage repair and cellular apoptosis by regulating Ku70 stability and function via post-translational modification. The molecular mechanisms how Skp2 stabilize Ku70 would be clarified in our following research work.


Assuntos
Apoptose , Dano ao DNA , Reparo do DNA , Autoantígeno Ku/metabolismo , Processamento de Proteína Pós-Traducional , Proteínas Quinases Associadas a Fase S/metabolismo , Neoplasias do Colo do Útero/patologia , Feminino , Humanos , Autoantígeno Ku/genética , Proteínas Quinases Associadas a Fase S/genética , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/metabolismo
14.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(4): 693-697, 2021 Jul.
Artigo em Zh | MEDLINE | ID: mdl-34323051

RESUMO

OBJECTIVE: To study the different methods of artificial intelligence (AI)-assisted Ki-67 scoring of clinical invasive ductal carcinoma (IDC) of the breast and to compare the results. METHODS: A total of 100 diagnosed IDC cases were collected, including slides of HE staining and immunohistochemical Ki-67 staining and diagnosis results. The slides were scanned and turned into whole slide image (WSI), which were then scored with AI. There were two AI scoring methods. One was fully automatic counting by AI, which used the scoring system of Ki-67 automatic diagnosis to do counting with the whole image of WSI. The second method was semi-automatic AI counting, which required manual selection of areas for counting, and then relied on an intelligent microscope to conduct automatic counting. The diagnostic results of pathologists were taken as the results of pure manual counting. Then the Ki-67 scores obtained by manual counting, semi-automatic AI counting and automatic AI counting were pairwise compared. The Ki-67 scores obtained from the manual counting (pathological diagnosis results), semi-automatic AI and automatic AI counts were pair-wise compared and classified according to three levels of difference: difference ≤10%, difference of >10%-<30% and difference ≥30%. Intra-class correlation coefficient ( ICC) was used to evaluate the correlation. RESULTS: The automatic AI counting of Ki-67 takes 5-8 minutes per case, the semi-automatic AI counting takes 2-3 minutes per case, and the manual counting takes 1-3 minutes per case. When results of the two AI counting methods were compared, the difference in Ki-67 scores was all within 10% (100% of the total), and the ICC index being 0.992. The difference between manual counting and semi-automatic AI was less than 10% in 60 cases (60% of the total), between 10% and 30% in 37 cases (37% of the total), and more than 30% in only 3 cases (3% of the total), ICC index being 0.724. When comparing automatic AI with manual counting, 78 cases (78% of the total) had a difference of ≤10%, 17 cases (17% of the total) had a difference of between 10% and 30%, and 5 cases (5%) had a difference of ≥30%, the ICC index being 0.720. The ICC values showed that there was little difference between the results of the two AI counting methods, indicating good repeatability, but the repeatability between AI counting and manual counting was not particularly ideal. CONCLUSION: AI automatic counting has the advantage of requiring less manpower, for the pathologist is involved only for the verification of the diagnosis results at the end. However, the semi-automatic method is better suited to the diagnostic habits of pathologists and has a shorter turn-over time compared with that of the fully automatic AI counting method. Furthermore, in spite of its higher repeatability, AI counting, cannot serve as a full substitute for pathologists, but should instead be viewed as a powerful auxiliary tool.


Assuntos
Neoplasias da Mama , Inteligência Artificial , Neoplasias da Mama/diagnóstico , Feminino , Humanos , Antígeno Ki-67 , Microscopia , Reprodutibilidade dos Testes
15.
Cancer Sci ; 111(9): 3210-3221, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32519357

RESUMO

Non-small-cell lung cancer (NSCLC) is the leading global cause of cancer-related death. Due to the lack of reliable diagnostic or prognostic biomarkers, the prognosis of NSCLC remains poor. Consequently, there is an urgent need to explore the mechanisms underlying this condition in order to identify effective biomarkers. G-protein-signaling modulator 2 (GPSM2) is widely recognized as a determinant of mitotic spindle orientation. However, its role in cancer, especially NSCLC, remains uncertain. In this study, we found that GPSM2 was downregulated in NSCLC tissues and was correlated with a poor prognosis. Furthermore, the knockdown of GPSM2 promoted NSCLC cell metastasis in vitro and in vivo and accelerated the process of epithelial-mesenchymal transition (EMT). Mechanistically, we showed that silencing GPSM2 induced cell metastasis and EMT through the ERK/glycogen synthase kinase-3ß/Snail pathway. These results confirm that GPSM2 plays an important role in NSCLC. Moreover, GPSM2, as an independent prognostic factor, could be a potential prognostic biomarker and drug target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Fatores de Transcrição da Família Snail/genética , Adulto , Idoso , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Bases de Dados Genéticas , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Técnicas de Silenciamento de Genes , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Camundongos , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Fatores de Transcrição da Família Snail/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Pharmacol Res ; 159: 105007, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32561477

RESUMO

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were first-line treatments for NSCLC patients with EGFR-mutations. However, about 30 % of responders relapsed within six months because of acquired resistance. In this study, we used Connectivity Map (CMap) to discover a drug capable of reversing acquired EGFR-TKIs resistance. To investigate Lymecycline's ability to reverse acquired EGFR-TKIs resistance, two Icotinib resistant cell lines were constructed. Lymecycline's ability to suppress the proliferation of Icotinib resistant cells in vitro and in vivo was then evaluated. Molecular targets were predicted using network pharmacology and used to identify the molecular mechanism. Growth factor receptor-bound protein 2 (GRB2) is an EGFR-binding adaptor protein essential for EGFR phosphorylation and regulation of AKT/ERK/STAT3 signaling pathways. Lymecycline targeted GRB2 and inhibited the resistance of the cell cycle to EGFR-TKI, arresting disease progression and inducing apoptosis in cancer cells. Combined Lymecycline and Icotinib treatment produced a synergistic effect and induced apoptosis in HCC827R5 and PC9R10 cells. Cell proliferation in resistant cancer cells was significantly inhibited by the combined Lymecycline and Icotinib treatment in mouse models. Lymecycline inhibited the resistance of the cell cycle to EGFR-TKI and induced apoptosis in NSCLC by inhibiting EGFR phosphorylation and GRB2-mediated AKT/ERK/STAT3 signaling pathways. This provided strong support that Lymecycline when combined with EGFR targeting drugs, enhanced the efficacy of treatments for drug-resistant NSCLC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Éteres de Coroa/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína Adaptadora GRB2/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Limeciclina/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/enzimologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Adaptadora GRB2/genética , Proteína Adaptadora GRB2/metabolismo , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Ecotoxicol Environ Saf ; 176: 119-124, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-30925327

RESUMO

Organochlorine pesticides (OCPs) and organophosphate pesticides (OPPs) posed severe threats to the aquatic environment in China. The toxicity data of 18 priority OCPs and OPPs for Chinese and American species were collected, and their species sensitivity distributions (SSDs) and ecotoxicity were compared. Physicochemical characteristics and chemical structures were used to analyze the difference in the pesticide toxicity. Results suggested that there is no significant difference between the HC5 values (hazardous concentration protecting 95% of species) of China and America as a whole. However, the HC5 values of nearly half of these pesticides (8/18) differ dramatically between Chinese and American due to the different resident species distribution. It indicated that it is necessary to develop local water quality criteria in China. The regression analysis of pesticides toxicity differences indicated a decrease in LC50/EC50 values (for Oncorhynchus mykiss and Carassius auratu) with the increase in molecular weights of pesticides. Pesticides with larger MWs might be more toxic to aquatic species. Similar trend was also observed in the regression analysis of a decrease in both American and Chinese HC5 values for with increase of the number of containing halogen atoms. It indicated the potency of these parameters to be used to predict the ecotoxicity of pesticide.


Assuntos
Ecotoxicologia/métodos , Água Doce/química , Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Qualidade da Água/normas , Animais , China , Ecotoxicologia/normas , Peixes/classificação , Peixes/crescimento & desenvolvimento , Hidrocarbonetos Clorados/química , Hidrocarbonetos Clorados/toxicidade , Peso Molecular , Praguicidas/química , Poluentes Químicos da Água/química
18.
Angew Chem Int Ed Engl ; 58(46): 16590-16600, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31535753

RESUMO

We report a new approach for nanosilicon-graphene hybrids with uniquely stable solid electrolyte interphase. Expanded graphite is gently exfoliated creating "defect-free" graphene that is non-catalytic towards electrolyte decomposition, simultaneously introducing high mass loading (48 wt. %) Si nanoparticles. Silane surface treatment creates epoxy chemical tethers, mechanically binding nano-Si to CMC binder through epoxy ring-opening reaction while stabilizing the Si surface chemistry. Epoxy-tethered silicon pristine-graphene hybrid "E-Si-pG" exhibits state-of-the-art performance in full battery opposing commercial mass loading (12 mg cm-2 ) LiCoO2 (LCO) cathode. At 0.4 C, with areal capacity of 1.62 mAh cm-2 and energy of 437 Wh kg-1 , achieving 1.32 mAh cm-2 , 340.4 Wh kg-1 at 1 C. After 150 cycles, it retains 1.25 mAh cm-2 , 306.5 Wh kg-1 . Sputter-down XPS demonstrates survival of surface C-Si-O-Si groups in E-Si-pG after repeated cycling. The discovered synergy between support defects, chemical-mechanical stabilization of Si surfaces, and SEI-related failure may become key LIB anode design rule.

19.
Cell Biol Int ; 42(10): 1292-1299, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29885023

RESUMO

Tyrosine kinase Inhibitors (TKIs) of epidermal growth factor receptor (EGFR) has considerably benefited for non-small cell lung carcinomas (NSCLC) harbor mutations in EGFR. However, the factors attenuating EGFR-TKI efficiency are obstacles to inhibit the proliferation of EGFR-mutant NSCLC cells successfully. Clarifying the insensitivity mechanisms of EGFR-TKI would help to develop new treatment strategy. In this study, the sensitivity of EGFR-mutant NSCLC cell lines, PC9 and HCC827, to icotinib was detected. Similar with other EGFR-TKIs such as gefitinib and erlortinib in previous research, the proliferation of two cell lines was apparently inhibited. However, we surprisingly found that contrast with the suppression of EGFR-AKT/ERK pathway, STAT3 was significantly activated in PC9 cells with the treatment of icotinib, but not in HCC827 cells. Further study confirmed that icotinib concomitantly induced IL-6 secretion and src activation in PC9 cells. Moreover, with the treatment of IL-6 neutralizing antibody or src inhibitor, dasatinib, icotinib-induced phosphorylation of STAT3 was reduced, as well as the sensitivity of PC9 to icotinib was also partially increased. Our results suggest that Src/IL-6/STAT3 bypass pathway is activated to maintain cell survival when the EGFR pathway was inhibited by TKIs, even in some EGFR-mutant NSCLC cells sensitive to TKIs. This finding provides a groundwork for potential combinatorial treatment with TKIs and Src or STAT3 inhibitor to improve icotinib sensitivity.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Éteres de Coroa/farmacologia , Receptores ErbB/metabolismo , Quinazolinas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Éteres de Coroa/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/genética , Humanos , Interleucina-6/metabolismo , Neoplasias Pulmonares/metabolismo , Mutação , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/metabolismo , Quinazolinas/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
20.
Sensors (Basel) ; 18(10)2018 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-30322173

RESUMO

A single piezoelectric patch can be used as both a sensor and an actuator by means of the self-sensing piezoelectric actuator, and the function of self-sensing shows several advantages in many application fields. However, some problems exist in practical application. First, a capacitance bridge circuit is set up to realize the function of self-sensing, but the precise matching of the capacitance of the bridge circuit is hard to obtain due to the standardization of electric components and variations of environmental conditions. Second, a local strain is induced by the self-sensing actuator that is not related to the global vibration of the structure, which would affect the performance of applications, especially in active vibration control. The above problems can be tackled by the feedforward compensation method that is proposed in this paper. A configured piezoelectric self-sensing circuit is improved by a feedforward compensation tunnel, and a gain of compensation voltage is adjusted by the time domain and frequency domain's steepest descent algorithms to alleviate the capacitance mismatching and local strain problems. The effectiveness of the method is verified in the experiment of the active vibration control in a wind tunnel, and the control performance of compensated self-sensing actuation is compared to the performance with capacitance mismatching and local strain. It is found that the above problems have negative effects on the stability and performance of the vibration control and can be significantly eliminated by the proposed method.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA