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Spodoptera frugiperda is a migratory agricultural pest with fast-spreading speed, long migration distance, and wide host range, which seriously threatens the safety of economic crops. To predict the trends of S. frugiperda and its parasitoid wasp Trichogramma pretiosum in their habitats under current and future climatic conditions, based on MaxEnt model and geographic distribution data of their historical occurrence, we project the feasibility of introducing T. pretiosum to control S. frugiperda by evaluating on their potential global distribution. The results show that, under the current greenhouse gas concentration, the potential distribution area of S. frugiperda is concentrated in 50° N-30° S, with a total area of 1.74 × 106 km2 , and the potential distribution area of T. pretiosum in the whole world is 2.91 × 106 km2 . The suitable areas of T. pretiosum cover almost all the suitable areas of S. frugiperda, which indicates that T. pretiosum can be introduced to control S. frugiperda. The results of this study can provide a theoretical basis for the monitoring and early warning of S. frugiperda and the use of T. pretiosum to control S. frugiperda.
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Mariposas , Vespas , Animais , Spodoptera , Controle Biológico de Vetores/métodos , Mariposas/parasitologia , Produtos AgrícolasRESUMO
BACKGROUND: Understanding the burden of cervical cancer (CC) in young women aged 15-44 years old are essential for formulating effective preventive strategies. METHODS: Utilizing the Global Burden of Disease 2019 Study, we estimated incidence, disability-adjusted life-years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) due to CC among young women from 1990 to 2019. Additionally, we evaluated the temporal trends using estimated annual percentage changes (EAPCs) during this period. We conducted a decomposition analysis to assess the absolute contributions of three components: population growth, population age structure and epidemiologic changes. RESULTS: Globally, there were 187 609.22 incident cases of CC worldwide, resulting in 2621 917.39 DALYs in 2019. From1990 to 2019, the age-standardized rates were decline, only the age-standardized YLDs rate (EAPC = 0.02; 95% CI: -0.02 to 0.05) showed a stable trend. The largest increase in age-standardized incidence rate (ASIR) and age-standardized YLDs rate observed in the high-middle social demographic index (SDI) quintiles. Population growth and age structure changes were associated with substantial changes in cases of CC, especially in South Asia and East Asia. CONCLUSIONS: Globally, the burden of CC in young women continues to increase, as measured by the absolute number. As populations are growing and age structure changes were associated with substantial changes in cases of CC, governments will face increasing demand for treatment, and support services for CC, especially in South Asia and East Asia.
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Carga Global da Doença , Saúde Global , Neoplasias do Colo do Útero , Humanos , Feminino , Adolescente , Neoplasias do Colo do Útero/epidemiologia , Adulto Jovem , Adulto , Incidência , Saúde Global/estatística & dados numéricos , Anos de Vida Ajustados por Deficiência , Anos de Vida Ajustados por Qualidade de VidaRESUMO
Electrochemical synthesis of hydrogen peroxide (H2O2) via the two-electron oxygen reduction reaction (2e--ORR) provides an alternative method to the energy-intensive anthraquinone method. Metal macrocycles with precise coordination are widely used for 2e--ORR electrocatalysis, but they have to be commonly loaded on conductive substrates, thus exposing a large number of 2e--ORR-inactive sites that result in poor H2O2 production rate and efficiency. Herein, guided by first-principle predictions, a substrate-free and two-dimensional conductive metal-organic framework (Ni-TCPP(Co)), composed of Co-N4 sites in porphine(Co) centers and Ni2O8 nodes, is designed as a multi-site catalyst for H2O2 electrosynthesis. The approperiate distance between the CoN4 and Ni2O8 sites in Ni-TCPP(Co) weakens the electron transfer between them, thus ensuring their inherent activities and creating high-density active sites. Meanwhile, the intrinsic electronic conductivity and porosity of Ni-TCPP(Co) further facilitate rapid reaction kinetics. Therefore, outstanding 2e--ORR electrocatalytic performance has been achieved in both alkaline and neutral electrolytes (>90%/85% H2O2 selectivity within 0-0.8 V vs. RHE and >18.2/18.0 mol g-1 h-1 H2O2 yield under alkaline/neutral conditions), with confirmed feasibility for water purification and disinfection applications. This strategy thus provides a new avenue for designing catalysts with precise coordination and high-density active sites, promoting high-efficiency electrosynthesis of H2O2 and beyond.
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Fashioning microporous covalent organic frameworks (COFs) into single crystals with ordered macropores allows for an effective reduction of the mass transfer resistance and the maximum preservation of their intrinsic properties but remains unexplored. Here, we report the first synthesis of three-dimensional (3D) ordered macroporous single crystals of the imine-linked 3D microporous COFs (COF-300 and COF-303) via a template-assisted modulated strategy. In this strategy, COFs crystallized within the sacrificial colloidal crystal template, assembled from monodisperse polystyrene microspheres, and underwent an aniline-modulated amorphous-to-crystalline transformation to form large single crystals with 3D interconnected macropores. The effects of the introduced macroporous structure on the sorption performances of COF-300 single crystals were further probed by iodine. Our results indicate that iodine adsorption occurred in micropores of COF-300 but not in the introduced macropores. Accordingly, the iodine adsorption capacity of COF single crystals was governed by their micropore accessibility. The relatively long diffusion path in the non-macroporous COF-300 single crystals resulted in a limited micropore accessibility (48.4%) and thus a low capacity in iodine adsorption (1.48 g·g-1). The introduction of 3D ordered macropores can greatly shorten the microporous diffusion path in COF-300 single crystals and thus render all their micropores fully accessible in iodine adsorption with a capacity (3.15 g·g-1) that coincides well with the theoretical one.
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Effective control over the crystallization of metal-organic framework (MOF) films is of great importance not only for the performance study and optimization in related applications but also for the fundamental understanding of the involved reticular chemistry. Featuring many technological advantages, electrochemical synthesis has been extensively reported for many MOF materials but is still challenged by the production of dense oriented films with a large-range tuning of thickness. Here, we report a ligand-oxidation-based anodic strategy capable of synthesizing oriented films of two-dimensional (2D) and three-dimensional (3D) conductive M-catecholate MOFs (2D Cu3(HHTP)2, 2D Zn3(HHTP)2, 2D Co3(HHTP)2, 3D YbHHTP, and 2D Cu2TBA) with tunable thicknesses up to tens of micrometers on commonly used electrodes. This anodic strategy relies on the oxidation of redox-active catechol ligands and follows a stepwise electrochemical-chemical reaction mechanism to achieve effective control over crystallizing M-catecholate MOFs into films oriented in the [001] direction. Benefiting from the electrically conductive nature, Cu3(HHTP)2 films could be thickened at a steady rate (17.4 nm·min-1) from â¼90 nm to 10.7 µm via a growth mechanism differing from those adopted in previous electrochemical synthesis of dense MOF films with limited thickness due to the self-inhibition effect. This anodic synthesis could be further combined with a templating strategy to fabricate not only films with well-defined 2D features in sizes from micrometers to millimeters but also high aspect ratio mesostructures, such as nanorods, of Cu3(HHTP)2.
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BACKGROUND: To investigate the relationship between polymorphisms of P2X3, P2X7 genes and environment interaction with susceptibility of childhood asthma. METHODS: We conducted a matched case-control study with 170 cases and 175 healthy controls. The rs10896611, rs2276038, rs3781899 in P2X3 and rs1718119, rs3751143 in P2X7 polymorphisms were genotyped using the technique of an improved multiplex ligation detection reaction. Gene-gene, gene-environment and haplotype-environment interactions were tested using the generalized multi-factor dimensionality reduction method. RESULTS: There were no differences between cases and controls in allele or genotype frequencies of P2X3 and P2X7. The C/C, G/C genotypes of rs10896611, and C/C, C/T genotypes of rs2276038 and G/G, G/A genotypes of rs3781899 were associated with asthmatic cough (p > 0.05). The haplotype GCT of P2X3 reduced the risk of asthma (OR = 0.48, p = 0.048), and the haplotypes AGT (OR = 0.45, p = 0.001) and GCC (OR = 2.16, p = 0.002) were associated with asthmatic cough. The haplotype AA of P2X7 increased risk of asthma severity (p < 0.05). The three-locus model indicated a potential haplotype-environment interaction in GCT, ETS, and pet (p = 0.001). CONCLUSIONS: The rs10896611, rs2276038 and rs3781899 of P2X3 minor alleles increased the risk of asthmatic cough. Haplotype GCT of P2X3 was a protective factor for asthma, the haplotype AGT was a protective factor and GCC was a risk factor for asthma with cough. In addition, the interactions of haplotype GCT of P2X3, ETS and pet may increase an individual's susceptibility to asthma.
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Asma , Polimorfismo de Nucleotídeo Único , Criança , Humanos , Interação Gene-Ambiente , Frequência do Gene , Predisposição Genética para Doença , Estudos de Casos e Controles , Tosse , Asma/genética , Genótipo , Haplótipos , AlelosRESUMO
OBJECTIVE: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF). METHODS: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. RESULTS: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up. CONCLUSION: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population.
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Fibrilação Atrial , Cardiomiopatias , Humanos , Fibrilação Atrial/terapia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Doença do Sistema de Condução Cardíaco/terapia , Estimulação Cardíaca Artificial/métodosRESUMO
Modal-free optimization algorithms do not require specific mathematical models, and they, along with their other benefits, have great application potential in adaptive optics. In this study, two different algorithms, the single-dimensional perturbation descent algorithm (SDPD) and the second-order stochastic parallel gradient descent algorithm (2SPGD), are proposed for wavefront sensorless adaptive optics, and a theoretical analysis of the algorithms' convergence rates is presented. The results demonstrate that the single-dimensional perturbation descent algorithm outperforms the stochastic parallel gradient descent (SPGD) and 2SPGD algorithms in terms of convergence speed. Then, a 32-unit deformable mirror is constructed as the wavefront corrector, and the SPGD, single-dimensional perturbation descent, and 2SPSA algorithms are used in an adaptive optics numerical simulation model of the wavefront controller. Similarly, a 39-unit deformable mirror is constructed as the wavefront controller, and the SPGD and single-dimensional perturbation descent algorithms are used in an adaptive optics experimental verification device of the wavefront controller. The outcomes demonstrate that the convergence speed of the algorithm developed in this paper is more than twice as fast as that of the SPGD and 2SPGD algorithms, and the convergence accuracy of the algorithm is 4% better than that of the SPGD algorithm.
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In healthcare, wireless body area networks (WBANs) can be used to constantly collect patient body data and assist in real-time medical services for patients from physicians. In such security- and privacy-critical systems, the user authentication mechanism can be fundamentally expected to prevent illegal access and privacy leakage occurrences issued by hacker intrusion. Currently, a significant quantity of new WBAN-oriented authentication protocols have been designed to verify user identity and ensure that body data are accessed only with a session key. However, those newly published protocols still unavoidably affect session key security and user privacy due to the lack of forward secrecy, mutual authentication, user anonymity, etc. To solve this problem, this paper designs a robust user authentication protocol. By checking the integrity of the message sent by the other party, the communication entity verifies the other party's identity validity. Compared with existing protocols, the presented protocol enhances security and privacy while maintaining the efficiency of computation.
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Segurança Computacional , Privacidade , Humanos , Confidencialidade , Atenção à Saúde , ComunicaçãoRESUMO
Saline-alkali stress is a universal abiotic stress factor limiting fruit tree cultivation worldwide. Apple (Malus×domestica Borkh.) is one of the fruits with the largest yields worldwide. Tea crabapple (Malus hupehensis Rehd. var. pingyiensis Jiang) is a type of common apple rootstock in China. Because facultative apomixis occurs in this species, it is often used in molecular research. The present study investigated the molecular mechanism of the response of indoleacetic acid (IAA) and cytokinins [zeatin, trans-zeatin riboside (tZR), isopentenyladenine (iP), and isopentenyladenosine (iPA)] to mixed saline-alkali stress (MSAS) in tea crabapple leaves. The endogenous hormone content of tea crabapple leaves under MSAS was measured, and the expression of stress response-related genes was analyzed by RNA sequencing. The results showed that the concentration of IAA was initially higher and then lower than that in the control, whereas the concentration of zeatin, tZR, iP, and iPA was higher than that in the control. A total of 1262 differentially expressed genes were identified in the three comparison groups. Further analyses suggested that IAA and cytokinin biosynthetic genes were mostly upregulated in tea crabapple leaves, indicating that auxin and cytokinin signaling pathway regulation occurred in response to MSAS. These findings suggest that IAA and cytokinins play an important role in the response of tea crabapple to MSAS. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01275-4.
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BACKGROUND: It is critical to understand the sensitivity, response direction and magnitude of carbohydrates and secondary compounds to warming for predicting the structure and function of the tundra ecosystem towards future climate change. RESULTS: Open-top chambers (OTCs) were used to passively increase air and soil temperatures on Changbai Mountain alpine tundra. After seven years' continuous warming (+ 1.5 °C), the vegetation coverage, nonstructural carbohydrates (soluble sugars and starch) and secondary compounds (total phenols, flavonoids and triterpenes) of leaves and roots in three dominant dwarf shrubs, Dryas octopetala var. asiatica, Rhododendron confertissimum and Vaccinium uliginosum, were investigated during the growing season. Warming did not significantly affect the concentrations of carbohydrates but decreased total phenols for the three species. Carbohydrates and secondary compounds showed significantly seasonal pattern and species-specific variation. No significant trade-off or negative relationship between carbohydrates and secondary compounds was observed. Compared to Dr. octopetala var. asiatica, V. uliginosum allocated more carbon on secondary compounds. Warming significantly increased the coverage of Dr. octopetala var. asiatica, did not change it for V. uliginosum and decreased it for Rh. confertissimum. Rh. confertissimum had significantly lower carbohydrates and invested more carbon on secondary compounds than the other two species. CONCLUSIONS: Enhanced dominance and competitiveness of Dr. octopetala var. asiatica was companied by increased trend in carbohydrate concentrations and decreased ratio of secondary compounds to total carbon in the warming OTCs. We, therefore, predict that Dr. octopetala var. asiatica will continue to maintain dominant status, but the competition ability of V. uliginosum could gradually decrease with warming, leading to changes in species composition and community structure of the Changbai tundra ecosystem under future climate warming.
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Ecossistema , Triterpenos , Carboidratos , Carbono , Flavonoides , Fenóis , Solo , Amido , Açúcares , TundraRESUMO
OBJECTIVES: To systematically evaluate the efficacy and safety of bosentan in the treatment of persistent pulmonary hypertension of the newborn (PPHN). METHODS: Chinese Journal Full-text Database, Weipu Database, Wanfang Data, China Biology Medicine disc, PubMed, Web of Science, Embase, and Cochrane Library were searched for literature on bosentan in the treatment of PPHN published up to August 31, 2021. RESULTS: A total of 8 randomized controlled trials were included for Meta analysis. The results of the Meta analysis showed that compared with the control group, the bosentan treatment group had a significantly lower treatment failure rate (RR=0.23, P<0.001), a significantly greater reduction in pulmonary artery pressure [mean difference (MD)=-11.79, P<0.001)], significantly greater increases in oxygen partial pressure (MD=10.21, P=0.006) and blood oxygen saturation (MD=8.30, P<0.001), and a significantly shorter length of hospital stay (MD=-1.35, P<0.001). The descriptive analysis showed that the bosentan treatment group had a lower degree of tricuspid regurgitation than the control group after treatment. The main adverse reactions of bosentan treatment included abnormal liver function, anemia and edema. The results of subgroup analysis based on treatment regimen, research area, and drug dose were consistent with those before stratification. CONCLUSIONS: Bosentan is effective in the treatment of PPHN. However, when using bosentan, attention should be paid to adverse reactions such as abnormal liver function.
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Hipertensão Pulmonar , Bosentana/uso terapêutico , China , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Recém-Nascido , Falha de TratamentoRESUMO
OBJECTIVES: To study the association of the single nucleotide polymorphisms (SNPs) of the adenylyl cyclase IX (ADCY9) gene at rs1967309, rs2230739, rs2601814, rs2601825, rs2601796, and rs2283497 loci and gene-environment interaction with childhood bronchial asthma (asthma for short). METHODS: A total of 123 children with asthma who attended the hospital from March 2019 to September 2021 were enrolled as the asthma group, among whom 84 (68.3%) had mild-to-moderate attacks and 39 (31.7%) had severe attacks. A total of 124 healthy children were enrolled as the control group. The association of the SNPs and haplotypes of the ADCY9 gene at the above 6 loci with the susceptibility to childhood asthma was evaluated. The method of generalized multifactor dimensionality reduction was used to analyze gene-environment interaction. RESULTS: Polymorphisms were observed for the ADCY9 gene at the above six loci in both the asthma and control groups, and there were significant differences in genotype and allele frequencies at the rs1967309 locus between the two groups (P<0.05). There was no significant difference in the distribution frequency of haplotypes TA and GG between the asthma and control groups (P>0.05). The generalized multifactor dimensionality reduction analysis showed interaction between rs1967309 locus and allergen contact (P<0.05), which increased the risk of asthma (OR=1.585, P<0.05). CONCLUSIONS: The rs1967309 locus of the ADCY9 gene is associated with the susceptibility to childhood asthma, and the locus and allergen contact have a synergistic effect on the development of asthma.
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Adenilil Ciclases , Asma , Interação Gene-Ambiente , Predisposição Genética para Doença , Adenilil Ciclases/genética , Alérgenos , Asma/genética , Criança , Genótipo , Humanos , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Stroke is the leading cause of adult disability and death worldwide. Mitochondrial dysfunction has been recognized as a marker of neuronal death during ischemic stroke. Maintaining the function of mitochondria is important for improving the survival of neurons and maintaining neuronal function. Damaged mitochondria induce neuronal cell apoptosis by releasing reactive oxygen species (ROS) and pro-apoptotic factors. Mitochondrial fission and fusion processes and mitophagy are of great importance to mitochondrial quality control. This paper reviews the dynamic changes in mitochondria, the roles of mitochondria in different cell types, and related signaling pathways in ischemic stroke. This review describes in detail the role of mitochondria in the process of neuronal injury and protection in cerebral ischemia, and integrates neuroprotective drugs targeting mitochondria in recent years, which may provide a theoretical basis for the progress of treatment of ischemic stroke. The potential of mitochondrial-targeted therapy is also emphasized, which provides valuable insights for clinical research.
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Isquemia Encefálica , Mitocôndrias , Animais , Apoptose , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Sistemas de Liberação de Medicamentos , Humanos , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Dinâmica Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/fisiologia , Mitofagia/efeitos dos fármacos , Mitofagia/fisiologia , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Acidente Vascular Cerebral/metabolismoRESUMO
This study analyzed the roles of puerarin and LncRNA ANRIL in myocardial ischemia-reperfusion injury. Hypoxia/reperfusion (H/R) model was established with H9C2 cells. Effects of puerarin of gradient concentrations on cardiomyocytes at different time points of hypoxia and reoxygenation were detected by quantitative real-time polymerase chain reaction (qRT-PCR), cell counting kit-8 (CCK-8), and microscope observation. Effects of puerarin on cardiomyocyte viability, ANRIL expression, contents of lactate dehydrogenase (LDH) and malondialdehyde (MDA), apoptosis, and expressions of autophagy-related genes after H/R injury were determined by CCK-8, quantitative real-time polymerase chain reaction (qRT-PCR), ELISA, flow cytometry, and Western blot, respectively. After cell transfection, the effects of overexpressed and knockdown of ANRIL on cardiomyocytes and H/R-injured cardiomyocytes were examined by rescue experiments. The ischemia-reperfusion (I/R)-injured rat model was established to examine the protective effect of puerarin in vivo. Prolonged hypoxia downregulated ANRIL expression in cardiomyocytes and reduced cardiomyocyte viability. Prolonged reoxygenation increased apoptosis. Both cardiomyocyte viability and ANRIL expression showed a dose-dependent relationship with puerarin. Puerarin reversed the effects of H/R injury on cardiomyocyte viability, ANRIL expression, contents of LDH and MDA, apoptosis, and expressions of autophagy-related genes. Overexpression and knockdown of ANRIL regulated the functions of cardiomyocytes and the expressions of autophagy-related genes. Puerarin reversed the effects of knockdown of ANRIL on H/R-injured cells. The results of In vivo experiments confirmed that puerarin protected myocardial tissues by up-regulating ANRIL and inhibiting autophagy.
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Autofagia/efeitos dos fármacos , Isoflavonas/uso terapêutico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miócitos Cardíacos/efeitos dos fármacos , RNA Longo não Codificante/genética , Vasodilatadores/uso terapêutico , Animais , Isoflavonas/farmacologia , Ratos , Regulação para Cima , Vasodilatadores/farmacologiaRESUMO
Microglia are the inherent immune effector cells in the central nervous system (CNS), are activated rapidly when the CNS is stimulated by ischaemia, infection, injury, etc. and participate in and aggravate the development of inflammatory reactions in the CNS. During the process of microglial activation, inflammatory factors such as TNF-α and IL-1ß and an abundance of reactive oxygen species (ROS)/reactive nitrogen species (RNS), are released by damaged nerve cells. LXW7 is a small molecule peptide and specifically binds with integrin αvß3. Cerium oxide nanoparticles (nanoceria) are strong free radical scavengers and are widely used in many studies. In this research, a model of inflammation was established using lipopolysaccharide (LPS) to induce BV2 microglia activation, and the effects of CeO2@PAA (synthetic nanoscale cerium oxide particles), LXW7 and CeO2@PAA-LXW7 were evaluated. We detected the expression level of inflammatory factors, the release of NO in BV2 cells and the generation of intracellular ROS. The expression levels of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3) and their phosphorylated proteins were detected in BV2 microglia. We found that CeO2@PAA, LXW7 and CeO2@PAA-LXW7 all effectively inhibited the activation of BV2 microglia, reduced the production of cytokines and the release of NO and reduced the production of intracellular ROS. The three treatments all inhibited the phosphorylation of FAK and STAT3 in BV2 microglia. Regarding these effects, CeO2@PAA-LXW7 was more effective than the other two monotherapies. Our data indicate that CeO2@PAA, LXW7 and CeO2@PAA-LXW7 can exert a neuroprotective function by inhibiting the inflammatory response of LPS-induced BV2 microglia. LXW7 may inhibit the activation of FAK and STAT3 signals in combination with integrin αvß3 to restrain neuroinflammation and the antioxidative stress effect of cerium oxide; hence, CeO2@PAA-LXW7 can exert a more robust anti-inflammatory and neuroprotective effect via synergistically suppressing the ability of LXW7 to influence the integrin pathway and the free radical-scavenging ability of CeO2@PAA.
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Resinas Acrílicas/química , Cério/química , Inflamação/patologia , Microglia/patologia , Nanopartículas/química , Peptídeos/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Integrina alfaVbeta3/metabolismo , Interleucina-1beta/metabolismo , Lipopolissacarídeos , Camundongos , Microglia/efeitos dos fármacos , Modelos Biológicos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
CeO2 nanoparticles (nanoceria) have been used in many studies as a powerful free radical scavenger, and LXW7, a small-molecule peptide, can specifically target the integrin αvß3, whose neuroprotective effects have also been demonstrated. The objective of this study is to observe the neuroprotective effect and potential mechanism of CeO2@PAA-LXW7, a new compound that couples CeO2@PAA (nanoceria modified with the functional group of polyacrylic acid) with LXW7 via a series of chemical reactions, in H2O2-induced NGF-differentiated PC12 cells. We examined the effects of LXW7, CeO2@PAA, and CeO2@PAA-LXW7 on the viability of primary hippocampal neurons and found that there was no significant difference under control conditions, but increased cellular viability was observed in the case of H2O2-induced injury. We used H2O2-induced NGF-differentiated PC12 cells as the classical injury model to investigate the neuroprotective effect of CeO2@PAA-LXW7. In this study, LXW7, CeO2@PAA, and CeO2@PAA-LXW7 inhibit H2O2-induced oxidative stress by reducing the production of reactive oxygen species (ROS) and regulating Bax/Bcl-2, cleaved caspase-3 and mitochondrial cytochrome C (cyto C) in the apoptotic signaling pathways. We found that the levels of phosphorylation of focal adhesion kinase (FAK) and of signal transducer and activator of transcription 3 (STAT3) increased significantly in H2O2-induced NGF-differentiated PC12 cells, whereas LXW7, CeO2@PAA, and CeO2@PAA-LXW7 suppressed the increase to different degrees. Among the abovementioned changes, the inhibitory effect of CeO2@PAA-LXW7 on H2O2-induced changes, including the increases in the levels of p-FAK and p-STAT3, is more obvious than that of LXW7 or CeO2@PAA alone. In summary, these results suggest that integrin signaling participates in the regulation of apoptosis via the regulation of ROS and of the apoptosis pathway in H2O2-induced NGF-differentiated PC12 cells. LXW7, CeO2@PAA, and CeO2@PAA-LXW7 can play neuroprotective roles by counteracting the oxidative stress and apoptosis induced by H2O2 in NGF-differentiated PC12 cells. CeO2@PAA-LXW7 exerting a more powerful synergistic effect via the conjunction of LXW7 and CeO2@PAA.
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Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Resinas Acrílicas , Animais , Cério , Peróxido de Hidrogênio/farmacologia , Neurônios/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Peptídeos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Two-dimensional (2D) layered graphitic carbon nitride (gCN) nanosheets offer intriguing electronic and chemical properties. However, the exfoliation and functionalisation of gCN for specific applications remain challenging. We report a scalable one-pot reductive method to produce solutions of single- and few-layer 2D gCN nanosheets with excellent stability in a high mass yield (35 %) from polytriazine imide. High-resolution imaging confirmed the intact crystalline structure and identified an AB stacking for gCN layers. The charge allows deliberate organic functionalisation of dissolved gCN, providing a general route to adjust their properties.
RESUMO
Reproductive function is controlled by the pulsatile release of hypothalamic gonadotropin-releasing hormone (GnRH), which regulates the expression of the gonadotropins luteinizing hormone and FSH in pituitary gonadotropes. Paradoxically, Fshb gene expression is maximally induced at lower frequency GnRH pulses, which provide a very low average concentration of GnRH stimulation. We studied the role of secreted factors in modulating gonadotropin gene expression. Inhibition of secretion specifically disrupted gonadotropin subunit gene regulation but left early gene induction intact. We characterized the gonadotrope secretoproteome and global mRNA expression at baseline and after Gαs knockdown, which has been found to increase Fshb gene expression (1). We identified 1077 secreted proteins or peptides, 19 of which showed mRNA regulation by GnRH or/and Gαs knockdown. Among several novel secreted factors implicated in Fshb gene regulation, we focused on the neurosecretory protein VGF. Vgf mRNA, whose gene has been implicated in fertility (2), exhibited high induction by GnRH and depended on Gαs In contrast with Fshb induction, Vgf induction occurred preferentially at high GnRH pulse frequency. We hypothesized that a VGF-derived peptide might regulate Fshb gene induction. siRNA knockdown or extracellular immunoneutralization of VGF augmented Fshb mRNA induction by GnRH. GnRH stimulated the secretion of the VGF-derived peptide NERP1. NERP1 caused a concentration-dependent decrease in Fshb gene induction. These findings implicate a VGF-derived peptide in selective regulation of the Fshb gene. Our results support the concept that signaling specificity from the cell membrane GnRH receptor to the nuclear Fshb gene involves integration of intracellular signaling and exosignaling regulatory motifs.
Assuntos
Hormônio Foliculoestimulante/biossíntese , Regulação da Expressão Gênica/fisiologia , Gonadotrofos/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Neuropeptídeos/metabolismo , Peptídeos/metabolismo , Transdução de Sinais/fisiologia , Animais , Linhagem Celular , Gonadotrofos/citologia , Camundongos , Fatores de Crescimento Neural , RNA Mensageiro/biossínteseRESUMO
The drug-serum albumin interaction plays a dominant role in drug efficacy and disposition. The glycation of serum albumin that occurs during diabetes may affect its drug-binding properties in vivo. In order to evaluate the interactivity characteristics of cyanidin-3-O-glucoside (C3G) with human serum albumin (HSA) and glycated human serum albumin (gHSA), this study was undertaken using multiple spectroscopic techniques and molecular modeling analysis. Time-resolved fluorescence and the thermodynamic parameters indicated that the quenching mechanism was static quenching, and hydrogen bonding and Van der Waals force were the main forces. The protein fluorescence could be quenched by C3G, whereas the polarity of the fluorophore was not obviously changed. C3G significantly altered the secondary structure of the proteins. Furthermore, the interaction force that existed in the HSA-C3G system was greater than that in the gHSA-C3G system. Fluorescence excitation emission matrix spectra, red edge excitation shift, Fourier transform infrared spectroscopy and circular dichroism spectra provided further evidence that glycation could inhibit the binding between C3G and proteins. In addition, molecular modeling analysis supported the experimental results. The results provided more details for the application of C3G in the treatment of diabetes.