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Aberrant phosphorylation of receptor tyrosine kinases (RTKs) is usually involved in tumor initiation, progression, and metastasis. However, developing specific and efficient molecular tools to regulate RTK phosphorylation remains a considerable challenge. In this study, we reported novel aptamer-based chimeras to inhibit the phosphorylation of RTKs, such as c-Met and EGFR, by enforced recruitment of a protein tyrosine phosphatase receptor type F (PTPRF). Our studies revealed that aptamer-based chimeras displayed a generic and potent inhibitory effect on RTK phosphorylation induced by growth factor or auto-dimerization in different cell lines and modulated cell biological behaviors by recruiting PTPRF. Furthermore, based on angstrom accuracy of the DNA duplex, the maximum catalytic radius of PTPRF was determined as â¼25.84 nm, providing a basis for the development of phosphatase-recruiting strategies. Taken together, our study provides a generic methodology not only for selectively mediating RTK phosphorylation and cellular biological processes but also for developing novel therapeutic drugs.
Assuntos
Aptâmeros de Nucleotídeos , Transdução de Sinais , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Fosforilação , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Linhagem Celular Tumoral , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/químicaRESUMO
BACKGROUND: Statins are widely used for treating patients with ischemic stroke at risk of secondary cerebrovascular events. It is unknown whether Asian populations benefit from more intensive statin-based therapy for stroke recurrence. Therefore, in the present study we evaluated the effectiveness and safety of high-dose and moderate-dose statins for patients who had experienced mild ischemic stroke during the acute period. METHODS AND RESULTS: This multicenter prospective study included patients with mild ischemic stroke who presented within 72 hours of symptom onset. The outcomes of patients in the high-intensity and moderate-intensity statin treatment groups were compared, with the main efficacy outcome being stroke recurrence and the primary safety end point being intracranial hemorrhage. The propensity score matching method was employed to control for imbalances in baseline variables. Subgroup analyses were conducted to evaluate group differences. In total, the data of 2950 patients were analyzed at 3 months, and the data of 2764 patients were analyzed at 12 months due to loss to follow-up. According to the multivariable Cox analyses adjusted for potential confounders, stroke recurrence occurred similarly in the high-intensity statin and moderate-intensity statin groups (3 months: adjusted hazard ratio [HR], 1.12 [95% CI, 0.85-1.49]; P=0.424; 12 months: adjusted HR, 1.08 [95% CI, 0.86-1.34]; P=0.519). High-intensity statin therapy was associated with an increased risk of intracranial hemorrhage (3 months: adjusted HR, 1.81 [95% CI, 1.00-3.25]; P=0.048; 12 months: adjusted HR, 1.86 [95% CI, 1.10-3.16]; P=0.021). The results from the propensity score-matched analyses were consistent with those from the Cox proportional hazards analysis. CONCLUSIONS: Compared with moderate-intensity statin therapy, high-dose statin therapy may not decrease the risk of mild, noncardiogenic ischemic stroke recurrence but may increase the risk of intracranial hemorrhage. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR1900025214.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , AVC Isquêmico , Recidiva , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Feminino , Masculino , Estudos Prospectivos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Fatores de Tempo , Fatores de Risco , Pontuação de Propensão , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Índice de Gravidade de Doença , Prevenção Secundária/métodosRESUMO
Ziziphi Spinosae Semen (ZSS) is the first choice for the treatment of insomnia. This research aimed to reveal the spatial distribution of identifying quality markers of ZSS and to illustrate the metabolite quality characteristics of this herbal medicine. Here, we performed a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) in situ to detect and image 33 metabolites in ZSS, including three saponins, six flavonoids, four alkaloids, eight fatty acids, and 12 amino acids. The MALDI images of the metabolites clearly showed the heterogeneous spatial distribution in different regions of ZSS tissues, such as the cotyledon, endosperm, and radicle. The distribution area of two saponins, six flavonoids, and three alkaloids increased significantly after the fried processing of ZSS. Based on the ion images, samples with different processing technologies were distinguished unambiguously by the pattern recognition method of orthogonal partial least squares discrimination analysis (OPLS-DA). Simultaneously, 23 major influencing components exerting higher ion intensities were identified as the potential quality markers of ZSS. Results obtained in the current research demonstrate that the processing of ZSS changes its content and distribution of the medicinal components. The analysis of MALDI-MSI provides a novel MS-based molecular imaging approach to investigate and monitor traditional medicinal plants.
Assuntos
Flavonoides , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Ziziphus , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Ziziphus/química , Ziziphus/metabolismo , Flavonoides/análise , Flavonoides/metabolismo , Saponinas/análise , Saponinas/metabolismo , Alcaloides/análise , Alcaloides/metabolismo , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismoRESUMO
OBJECTIVE: The aim of this study was to explore the effects of Ninjurin 2 (NINJ2) polymorphisms on susceptibility to coronary heart disease (CHD). METHODS: We conducted a case-control study with 499 CHD cases and 505 age and gender-matched controls. Five single nucleotide polymorphisms (SNPs) in NINJ2 (rs118050317, rs75750647, rs7307242, rs10849390, and rs11610368) were genotyped by the Agena MassARRAY platform. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis to assess the association of NINJ2 polymorphisms and CHD risk-adjusted for age and gender. What's more, risk genes and molecular functions were screened via protein-protein interaction (PPI) network and functional enrichment analysis. RESULTS: Rs118050317 in NINJ2 significantly increased CHD risk in people aged more than 60 years and women. Rs118050317 and rs7307242 had strong relationships with hypertension risk in CHD patients. Additionally, rs75750647 exceedingly raised diabetes risk in cases under multiple models, whereas rs10849390 could protect CHD patients from diabetes in allele, homozygote, and additive models. We also observed two blocks in NINJ2. Further interaction network and enrichment analysis showed that NINJ2 played a greater role in the pathogenesis and progression of CHD. CONCLUSION: Our results suggest that NINJ2 polymorphisms are associated with CHD risk.
Assuntos
Moléculas de Adesão Celular Neuronais , Doença das Coronárias , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Humanos , Feminino , Masculino , Polimorfismo de Nucleotídeo Único/genética , Moléculas de Adesão Celular Neuronais/genética , Predisposição Genética para Doença/genética , Pessoa de Meia-Idade , Doença das Coronárias/genética , Estudos de Casos e Controles , Idoso , Fatores de Risco , GenótipoRESUMO
Carotenoid isomerase activity and carotenoid content maintain the appropriate tiller number, photosynthesis, and grain yield. Interactions between the strigolactone and abscisic acid pathways regulates tiller formation.
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Oryza , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Carotenoides/metabolismo , Grão Comestível/metabolismo , Isomerases/metabolismoRESUMO
Not only systolic blood pressure (SBP) but also diastolic blood pressure (DBP) increases the risk of recurrence in the short- or long-term outcomes of stroke. The interaction between DBP and antiplatelet treatment for China stroke patients is unclear. This multicenter, observational cohort study included 2976 minor ischemic stroke patients. Patients accepted single antiplatelet therapy (SAPT) or dual antiplatelet therapy (DAPT) after arrival, and baseline DBP levels were trichotomized into <90 mmHg, 90-110 mmHg and ≥110 mmHg. We explore the interaction effect between antiplatelet therapy and DBP on 90-days composite vascular events. A total of 257 (8.6%) patients reached a composite vascular event during follow-up. The interaction term between DBP levels and treatment group (SAPT vs. DAPT) was significant (P for interaction = 0.013). DAPT's adjusted HR for composite events in patients with DBP between 90 and 110 mmHg was 0.56 (95% confidence interval, 0.36 0.88; P = 0.011) and DBP ≥ 110 mmHg was 4.35 (95% confidence interval, 1.11-19.94; P = 0.046). The association between treatment and DBP was still consistent after propensity score matching of the baseline characteristics. The interaction term of DBP × treatment was not significant for the safety outcomes of severe bleeding (P for interaction = 0.301) or hemorrhage stroke (P for interaction = 0.831). In this cohort study based on the real world, patients with a DBP between 90 and 110 mmHg received a greater benefit from 90 days of DAPT than those with lower and higher baseline DBP. REGISTRATION: ( https://www.chictr.org.cn ; Unique identifier: ChiCTR1900025214).
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Inibidores da Agregação Plaquetária , Acidente Vascular Cerebral , Humanos , Pressão Sanguínea , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/farmacologia , Estudos de Coortes , Acidente Vascular Cerebral/tratamento farmacológico , China , Resultado do TratamentoRESUMO
Semen Ziziphi Spinosae (SZS) is the dried and ripe seeds of Ziziphus jujuba var. spinosa. Currently, the yield of naturally grown SZS is unstable owing to environmental factors. Grafting high-quality sour jujube scions onto sour jujube or jujube tree stocks can result in a greater yield. However, the effects of grafting on the quality and gene expression of SZS have rarely been reported. This study used a DNA barcoding technique, high-performance liquid phase-evaporative luminescence detector (HPLC-ELSD), and transcriptomics to investigate the origin and genetic differences between grafted and wild jujube seeds. DNA barcoding identified all samples as Ziziphus jujuba var. spinosa. HPLC-ELSD analysis revealed a higher content of grafted SZS compared to that of the wild SZS. Transcriptome analysis of the metabolic pathways in SZS showed that 22 and 19 differentially expressed gene sequences encoded enzymes related to flavonoids and saponin synthesis, respectively. Weighted correlation network analysis (WGCNA) identified 15 core genes governing the differences in medicinal components between grafted and wild SZS. This study demonstrated the use of DNA barcoding and fingerprint methods to identify jujube seed species and effectively capture ingredient information of medicinal materials. Additionally, transcriptome technology provided data for identifying core differential genes, facilitating studies on quality differences between grafted and wild SZS.
Assuntos
Transcriptoma , Ziziphus , Código de Barras de DNA Taxonômico , Sementes/genética , Extratos Vegetais , Ziziphus/genética , Cromatografia Líquida de Alta Pressão/métodosRESUMO
Conventional oral therapy for ulcerative colitis (UC) is associated with premature release or degradation of drugs in the harsh gastrointestinal environment, resulting in reduced therapeutic effectiveness. Consequently, the present study aims to develop a dual-targeted delivery system with a nanoparticle-in-microparticle (nano-in-micro) structure. The prepared Asiatic Acid-loaded delivery system (AA/CDM-BT-ALG) has pH-sensitive properties. Cellular uptake evaluation confirms that nanoparticles exhibit targeted absorption by macrophages and Caco-2 cells through mannose (Man) receptor and biotin-mediated endocytosis, respectively. Therefore, this mechanism effectively enhances intracellular drug concentration. Additionally, the biodistribution study conducted on the gastrointestinal tract of mice indicates that the colon of the microspheres group shows higher fluorescence intensity with longer duration than the other groups. This finding indicates that the microspheres exhibit selective accumulation in areas of colon inflammation. In vivo experiments in colitis mice showed that AA/CDM-BT-ALG significantly alleviates the histopathological characteristics of the colon, reduced neutrophil, and macrophage infiltration, and decreases pro-inflammatory cytokine expression. Furthermore, the effect of AA/CDM-BT-ALG on colitis is validated to be closely related to the TLR4/MyD88/NF-κB signaling pathway. The present findings suggest that the development of a dual-targeted delivery system is accomplished effectively, with the potential to serve as a drug-controlled release system for treating UC.
Assuntos
Colite Ulcerativa , Colite , Nanopartículas , Camundongos , Humanos , Animais , Colite Ulcerativa/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Células CACO-2 , Distribuição Tecidual , Colite/tratamento farmacológico , Colo/metabolismo , Colo/patologia , Nanopartículas/química , Modelos Animais de DoençasRESUMO
BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the association between different antiplatelet therapy regimens and the functional outcomes and bleeding complications among mild-to-moderate ischaemic stroke patients based on real-world data. METHODS: We used data from the SEACOAST trial (Safety and efficacy of aspirin-clopidogrel in acute noncardiogenic minor ischaemic stroke) to analyse the data of patients with mild-to-moderate stroke within 72 h after onset who were treated with aspirin or clopidogrel alone or a combination of clopidogrel and aspirin from September 2019 to November 2021. Propensity score matching (PSM) was used to balance the differences between groups. We performed an analysis to evaluate the association of different antiplatelet regimens and 90-day disability, which was defined as a modified Rankin Scale score ≥2, as well as disability ascribed to index or recurrent stroke by the local investigator. In terms of safety, we then compared the bleeding events between the two groups. RESULTS: A total of 2822 mild-to-moderate ischaemic stroke patients were treated with either clopidogrel plus aspirin (n = 1726, 61.2%) or aspirin/clopidogrel (n = 1096, 38.8%). Of 1726 patients in the dual antiplatelet group, 1350 (78.5%) received less than or equal to 30 days of combined therapy. At 90 days, 433 (15.3%) patients were disabled. Patients who received combined therapy had a lower overall disability rate (13.7% versus 17.9%; OR 0.78 (0.6-1.01); P = 0.064). However, investigators found that index stroke was the reason for significantly fewer patients in the dual antiplatelet group having disability (8.4% versus 12%; OR, 0.72 (0.52-0.98); P = 0.038). There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the dual and mono antiplatelet drug regimens (0.4% versus 0.2%; HR 1.5 (0.25, 8.98); P = 0.657). CONCLUSION: Aspirin plus clopidogrel was associated with a reduction in the incidence of disability attributed to index stroke. There was no statistically significant difference in the incidence of moderate to severe bleeding complications between the two antiplatelet drug regimens. TRIAL REGISTRATION NUMBER: ChiCTR1900025214.
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Bombyx batryticatus is derived from the dried larva of Bombyx mori Linnaeus infected by Beauveria bassiana (Bals.) Vuillant. Raw Bombyx batryticatus should be stir-fried before oral administration due to its irritation to the gastrointestinal tract. Nevertheless, it is still an arduous task to uncover the intrinsic mechanism of Bombyx batryticatus processing. In this study, we collected two types of Bombyx batryticatus, one being stir-fried and the other serving as a control. Then, an informative approach, which integrated matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) with chemometrics analysis, was established to screen processing-associated markers and reveal in situ spatial distribution patterns of protein-related metabolites. After optimization of experimental conditions, 21 ions were initially detected from Bombyx batryticatus, including amino acids and peptides. In addition, 15 differential markers were screened by orthogonal projection to potential structure discriminant analysis (OPLS-DA), which were localized and visualized in the transverse section of Bombyx batryticatus by MSI. Eventually, it can be demonstrated that the stir-frying process reduces toxicity while potentially boosting specific biological activities of Bombyx batryticatus. In summary, the established strategy could not only clarify the chemical transformation of protein-related metabolites from Bombyx batryticatus before and after frying with wheat bran, but also reveal the significance of Chinese medicine processing technology.
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BACKGROUND: The triglyceride-glucose (TyG) index, a simple measure of insulin resistance, is associated with intracranial atherosclerosis (ICAS) and stroke. In hypertensive populations, this association may be pronounced. The aim was to investigate the relationship between TyG and symptomatic intracranial atherosclerosis (sICAS) and recurrence risk in ischemic stroke patients with hypertension. METHODS: This prospective, multicenter cohort study included patients with acute minor ischemic stroke with a preadmission diagnosis of hypertension from September 2019 to November 2021 with a 3-month follow-up. The presence of sICAS was determined by a combination of clinical manifestations, the location of the infarction, and the corresponding artery with moderate-to-severe stenosis. ICAS burden was determined by the degree and number of ICAS occurrences. Fasting blood glucose (FBG) and triglyceride (TG) were measured to calculate TyG. The main outcome was ischemic stroke recurrence during the 90-day follow-up. Multivariate regression models were used to explore the association of TyG, sICAS, and ICAS burden with stroke recurrence. RESULTS: There were 1281 patients with a mean age of 61.6 ± 11.6 years; 70.1% were male, and 26.4% were diagnosed with sICAS. There were 117 patients who experienced stroke recurrence during follow-up. Patients were categorized according to quartiles of TyG. After adjusting for confounders, the risk of sICAS was greater (OR 1.59, 95% CI 1.04-2.43, p = 0.033) and the risk of stroke recurrence was significantly higher (HR 2.02, 95% CI 1.07-3.84, p = 0.025) in the fourth TyG quartile than in the first quartile. The restricted cubic spline (RCS) plot revealed a linear relationship between TyG and sICAS, and the threshold value for TyG was 8.4. Patients were then dichotomized into low and high TyG groups by the threshold. Patients with high TyG combined with sICAS had a higher risk of recurrence (HR 2.54, 95% CI 1.39-4.65) than patients with low TyG without sICAS. An interaction effect on stroke recurrence between TyG and sICAS was found (p = 0.043). CONCLUSION: TyG is a significant risk factor for sICAS in hypertensive patients, and there is a synergistic effect of sICAS and higher TyG on ischemic stroke recurrence. TRIAL REGISTRATION NUMBER: The study was registered on 16 August 2019 at https://www.chictr.org.cn/showprojen.aspx?proj=41160 (No. ChiCTR1900025214).
Assuntos
Hipertensão , Arteriosclerose Intracraniana , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Estudos de Coortes , Constrição Patológica , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Artérias , Hipertensão/diagnóstico , Hipertensão/epidemiologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Fatores de Risco , Glucose , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Triglicerídeos , Glicemia , BiomarcadoresRESUMO
As genetic inheritance is an inevitable risk factor in the development of coronary heart disease (CHD), it is critical to identify the polymorphisms of CHD risk. This study explored whether the NPAS4 polymorphisms are related to the CHD risk in the Chinese Han population. Five SNPs in NPAS4 were genotyped using Agena Mass ARRAY from 499 CHD and 500 controls. RT-PCR detected the NPAS4 expression levels in peripheral blood mononuclear cells from 50 CHD and 50 controls. χ2 test compared the distributions of gender, allele and genotypes frequencies between cases and controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). MDR analyzed the SNP-SNP interactions on risk of CHD. U test compared the differences in gene expression between different groups. The results showed that rs4466842 was correlated with an increased CHD risk in overall, males and age ≤ 60; rs117186164 and rs12785321 were significantly related to an increased CHD risk in male and age ≤ 60, respectively; haplotype Ars117186164Crs4466842 was significantly correlated with an increased CHD risk. SNP-SNP interactions results showed that the best model was the four-locus model was the combination of rs117770654, rs117957381, rs12785321, and rs4466842 (CVC = 10/10, Testing Sensitivity = 0.647). The expression levels of NPAS4 in the case group (0.365 ± 0.139) were significantly lower than that in the control group (0.782 ± 0.224) (P < 0.001). The results revealed that SNPs in NPAS4 may play an important role in the occurrence and development of CHD.
Assuntos
Doença das Coronárias , Predisposição Genética para Doença , Estudos de Casos e Controles , Doença das Coronárias/diagnóstico , Doença das Coronárias/genética , Humanos , Leucócitos Mononucleares , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Combination chemotherapy, which involves the simultaneous use of multiple anticancer drugs in adequate combinations to disrupt multiple mechanisms associated with tumor growth, has shown advantages in enhanced therapeutic efficacy and lower systemic toxicity relative to monotherapy. Herein, we employed coordination-driven self-assembly to construct discrete Pt(II) metallacycles as monodisperse, modular platforms for combining camptothecin and combretastatin A4, two chemotherapy agents with a disparate mechanism of action, in precise arrangements for combination chemotherapy. Formulation of the drug-loaded metallacycles with folic acidfunctionalized amphiphilic diblock copolymers furnished nanoparticles with good solubility and stability in physiological conditions. Folic acids on the surface of the nanoparticles promote their internalization into cancer cells. The intracellular reductive environment of cancer cells induces the release of the drug molecules at an exact 1:1 ratio, leading to a synergistic anticancer efficacy. In vivo studies on tumor-bearing mice demonstrated the favorable therapeutic outcome and minimal side effects of the combination chemotherapy approach based on a self-assembled metallacycle.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Camptotecina , Neoplasias , Platina , Estilbenos , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/química , Camptotecina/administração & dosagem , Camptotecina/farmacologia , Liberação Controlada de Fármacos , Sinergismo Farmacológico , Ácido Fólico/química , Humanos , Camundongos , Nanopartículas , Neoplasias/tratamento farmacológico , Platina/química , Polímeros/uso terapêutico , Estilbenos/administração & dosagem , Estilbenos/farmacologia , Microambiente TumoralRESUMO
High-temperature stress inhibits normal cellular processes and results in abnormal growth and development in plants. However, the mechanisms by which rice (Oryza sativa) copes with high temperature are not yet fully understood. In this study, we identified a rice high temperature enhanced lesion spots 1 (hes1) mutant, which displayed larger and more dense necrotic spots under high temperature conditions. HES1 encoded a UDP-N-acetylglucosamine pyrophosphorylase, which had UGPase enzymatic activity. RNA sequencing analysis showed that photosystem-related genes were differentially expressed in the hes1 mutant at different temperatures, indicating that HES1 plays essential roles in maintaining chloroplast function. HES1 expression was induced under high temperature conditions. Furthermore, loss-of-function of HES1 affected heat shock factor expression and its mutation exhibited greater vulnerability to high temperature. Several experiments revealed that higher accumulation of reactive oxygen species occurred in the hes1 mutant at high temperature. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and comet experiments indicated that the hes1 underwent more severe DNA damage at high temperature. The determination of chlorophyll content and chloroplast ultrastructure showed that more severe photosystem defects occurred in the hes1 mutant under high temperature conditions. This study reveals that HES1 plays a key role in adaptation to high-temperature stress in rice.
Assuntos
Oryza , Regulação da Expressão Gênica de Plantas , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , TemperaturaRESUMO
While the number of devices connected together as the Internet of Things (IoT) is growing, the demand for an efficient and secure model of resource discovery in IoT is increasing. An efficient resource discovery model distributes the registration and discovery workload among many nodes and allow the resources to be discovered based on their attributes. In most cases this discovery ability should be restricted to a number of clients based on their attributes, otherwise, any client in the system can discover any registered resource. In a binary discovery policy, any client with the shared secret key can discover and decrypt the address data of a registered resource regardless of the attributes of the client. In this paper we propose Attred, a decentralized resource discovery model using the Region-based Distributed Hash Table (RDHT) that allows secure and location-aware discovery of the resources in IoT network. Using Attribute Based Encryption (ABE) and based on predefined discovery policies by the resources, Attred allows clients only by their inherent attributes, to discover the resources in the network. Attred distributes the workload of key generations and resource registration and reduces the risk of central authority management. In addition, some of the heavy computations in our proposed model can be securely distributed using secret sharing that allows a more efficient resource registration, without affecting the required security properties. The performance analysis results showed that the distributed computation can significantly reduce the computation cost while maintaining the functionality. The performance and security analysis results also showed that our model can efficiently provide the required security properties of discovery correctness, soundness, resource privacy and client privacy.
Assuntos
Internet das Coisas , Segurança Computacional , Humanos , PrivacidadeRESUMO
Food spoilage is one of the biggest concerns for food safety worldwide. Here, we describe the construction of a carrier for biological agents by chemical combination of porous nanoMOFs and carboxymethylated filter paper (CMFP). When curcumin was encapsulated in nanoMOFs@CMFP, they showed the ability to act as super-long-acting food preserving agents with controllable release of curcumin. Although only 22.3% of curcumin was released into water in 600 h, 65.8% was released into PBS in the same time, and the release into PBS could be tuned by adding citric acid at the time of greatest requirement. Furthermore, the chemical stability of curcumin in nanoMOFs@CMFP was >4.9 times greater than for free curcumin. The outstanding antioxidant and antimicrobial activity of curcumin-loaded nanoMOFs@CMFP paste was demonstrated by prolonging the shelf life of pitayas, which illustrates its potential for development as long-acting and stable preserving paste for use in food preservation.
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Antibacterianos/farmacologia , Curcumina/farmacologia , Conservantes de Alimentos/química , Armazenamento de Alimentos , Nanoestruturas/química , Antibacterianos/química , Antibacterianos/farmacocinética , Antioxidantes/química , Antioxidantes/farmacologia , Cactaceae/química , Curcumina/química , Curcumina/farmacocinética , Conservantes de Alimentos/farmacologia , Estruturas Metalorgânicas/química , Testes de Sensibilidade Microbiana , PorosidadeRESUMO
The abscisic acid (ABA) receptor binds to ABA in plants and can activate the ABA signaling pathway to initiate stress resistance. Sour jujube (Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. Chou) is an economic tree crop in North China, which is strongly adapted to drought and salt stress. Here, we cloned and overexpressed the ZjPYR1 gene in Arabidopsis thaliana. After ABA treatment, the accumulation of ZjPYR1 increased significantly, suggesting that ABA may stabilize ZjPYR1 in the plants. Compared with the wild-type, the heterologous transgenic lines showed smaller stomatal openings under ABA treatment and a shorter root length and lower germination rate under ABA and salt treatment. Based on these results, we speculate that the overexpression of ZjPYR1 in A. thaliana effectively enhanced the stress resistance of the plants, and furthermore, that ZjPYR1 is a putative ABA receptor in sour jujube that increases plant adaptability to drought and salt stress. We report that ZjPYR1, like most ABA receptors in A. thaliana, is involved in mediating plant responses to ABA, such as stomatal closure and root length.
Assuntos
Ácido Abscísico/metabolismo , Arabidopsis/metabolismo , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Ziziphus/genética , Secas , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Germinação/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/fisiologia , Estômatos de Plantas/fisiologia , Plantas Geneticamente Modificadas/metabolismo , Estresse Salino , Transdução de Sinais , Estresse FisiológicoRESUMO
We have investigated the nano-indentation responses of graphene/aluminum systems via computational nano-indentation processes by using molecular dynamics simulations. The effects of system temperature, grain-orientation and bilayer graphene are also investigated. We demonstrate that, the graphene coating enlarges the load-carrying area by about 5.36 times and changes the deformation behaviors of aluminum substrate during nano-indentation processes. The load bearing capacity of graphene/Al system is significantly improved by about 4.7 times compared with that of bare Al system. It is revealed that higher system temperature weakens the ultimate indentation depth and corresponding load. The grain orientation of aluminum substrate hardly affect the indentation mechanical properties of graphene/Al system. The strengthening effect of bilayer graphene is about 1.5 times that of monolayer graphene.
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BACKGROUND: Hfq is a widely conserved bacterial RNA-binding protein which generally mediates the global regulatory activities involv ed in physiological process and virulence. The goal of this study was to characterize the biological function of hfq gene in Xanthomonas axonpodis pv. citri (Xac), the causal agent of citrus canker disease. RESULTS: An hfq mutant in Xac was generated by plasmid integration. The loss of hfq resulted in attenuation of bacterial growth, motility and biofilm formation. In addition, the hfq mutation impaired Xac resistance to H2O2 and both high and low pH environments, but did not affect the virulence to citrus. RNA-Seq analyses indicated that Hfq played roles in regulating the expression of 746 genes. In hfq mutant, gene expression related to chemotaxis, secretion system, two-component system, quorum sensing and flagellar assembly were repressed, whereas expression of ribosomal genes were significantly up-regulated. The down-regulated expression of three bacterial chemotaxis related genes and seven flagella genes, which involved in cell growth and biofilm formation, were further validated by RT-qPCR. CONCLUSIONS: The study demonstrated that hfq was involved in multiple biological processes in Xac. The results could serve as initiate points for identifying regulatory sRNAs and genes controlled by Hfq-sRNA interactions in Xac.
Assuntos
Perfilação da Expressão Gênica/métodos , Fator Proteico 1 do Hospedeiro/genética , Mutação , Xanthomonas axonopodis/fisiologia , Proteínas de Bactérias/genética , Biofilmes/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Doenças das Plantas/microbiologia , Percepção de Quorum , Análise de Sequência de RNA , Xanthomonas axonopodis/crescimento & desenvolvimentoRESUMO
Graphene is an ideal material in the reinforcement of metal-matrix composites owing to its outstanding mechanical and physical properties. Herein, we have investigated the surface enhancement of iron via a computational nanoindentation process using molecular dynamics simulations. The findings of our study show that graphene can enhance the critical yield strength, hardness and elastic modulus of the composite to different degrees with the change of the number of graphene layers. In the six tested models, the composite with trilayer graphene on the surface produces the strongest reinforcement, with an increased magnitude of 432.1% and 169.5% in the hardness and elastic modulus, respectively, compared with pure iron. Furthermore, it is revealed that high temperature could weaken the elastic bearing capacity of the graphene, resulting in a decrease on the elastic mechanical properties of the graphene/Fe composite.