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OBJECTIVE: To investigate the effect of aerobic exercise intervention to inhibit cardiomyocyte apoptosis and thus improve cardiac function in myocardial infarction (MI) mice by regulating CTGF expression through miR-133a-3p. METHODS: Male C57/BL6 mice, 7-8 weeks old, were randomly divided into sham-operated group (S group), sham-operated +aerobic exercise group (SE group), myocardial infarction group (MI group) and MI + aerobic exercise group (ME group). The mice were anesthetized the day after training and cardiac function was assessed by cardiac echocardiography. Myocardial collagen volume fraction (CVF%) was analyzed by Masson staining. Myocardial CTGF, Bax and Bcl-2 were detected by Western blotting, and myocardial miR-133a-3p was measured by RT-qPCR. RESULTS: Compared with the S group, miR-133a-3p, Bcl-2 and EF were significantly decreased and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly increased in the MI group. Compared with the MI group, miR-133a-3p, Bcl-2 and EF were significantly increased, cardiac function was significantly improved, and CTGF, Bax, Bax/ Bcl-2, Caspase 3, Cleaved Caspase-3, LVIDd, LVIDs and CVF were significantly decreased in ME group. The miR-133a-3p was significantly lower and CTGF was significantly higher in the H2O2 intervention group compared with the control group of H9C2 rat cardiomyocytes. miR-133a-3p was significantly higher and CTGF was significantly lower in the AICAR intervention group compared to the H2O2 intervention group. Compared with the control group of H9C2 rat cardiomyocytes, CTGF, Bax and Bax/Bcl-2 were significantly increased and Bcl-2 was significantly decreased in the miR-133a-3p inhibitor intervention group; CTGF, Bax and Bax/Bcl-2 were significantly decreased and Bcl-2 was significantly upregulated in the miR-133a-3p mimics intervention group. CONCLUSION: Aerobic exercise down-regulated CTGF expression in MI mouse myocardium through miR-133a-3p, thereby inhibiting cardiomyocyte apoptosis and improving cardiac function.
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MicroRNAs , Infarto do Miocárdio , Ratos , Masculino , Camundongos , Animais , Caspase 3/metabolismo , Regulação para Baixo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Peróxido de Hidrogênio/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/terapia , Infarto do Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose/genéticaRESUMO
BACKGROUND: We aimed to unbiasedly map the genetic mutation profile of HNSC and CESC associated with HPV status in the Chinese population (SYSU-cohort) and compare them with Western population (TCGA-cohort). METHODS: Fifty-one HNSC patients (SYSU-HNSC) and 38 CESC patients (SYSU-CESC) were enrolled in this study. Genomic alterations were examined, and the profile was produced using the YuanSuTM450 gene panel (OrigiMed, Shanghai, China). The altered genes were inferred and compared to Western patients from TCGA cohorts. RESULTS: Compared to the TCGA-HNSC cohort, FGFR3 mutation was identified as a novel target in SYSU-HNSC with therapeutic potential. Compared to the TCGA-CESC cohort, some epigenetic regulation-associated genes were frequently mutated in SYSU-CESC cohort (KMT2C, KMT2D, KDM5C, KMT2A). CONCLUSION: In summary, our study provides unbiased insights into the genetic landscape of HNSC and CESC in the Chinese population and highlights potential novel therapeutic targets that may benefit Chinese patients.
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Neoplasias de Cabeça e Pescoço , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Epigênese Genética , China , Neoplasias de Cabeça e Pescoço/genética , MutaçãoRESUMO
BACKGROUND: Gastric cancer (GC) remains a global challenge due to its high morbidity and mortality rates especially in Asia as well as poor response to treatment. As a member of the adhesion protein family and transmembrane glycoprotein, EpCAM expressed excessively in cancer cells including GC cells. The database assay showed that EpCAM is excessively expressed and easily mutated in cancers, especially in early stage of GC. METHODS: To explore the roles EpCAM plays in oncogenesis and progression of GC, the expression of EpCAM was deleted in GC cells with CRISPR/Cas9 method, and then the changes of cell proliferation, apoptosis, motility and motility associated microstructures in EpCAM-deleted GC cells (EpCAM-/-SGC7901) were detected to evaluate the rules EpCAM played. RESULTS: The results showed that EpCAM deletion caused cell proliferation, motility and the development of motility-relevant microstructures inhibited significantly, apoptotic trend and contact inhibition enhanced in EpCAM-deleted GC cells. The results of western blot suggested that EpCAM modulates the expression of epithelial/endothelial mesenchymal transition (EMT) correlated genes. All results as above indicated that EpCAM plays important roles to enhance the oncogenesis, malignancy and progression as a GC enhancer. CONCLUSIONS: Combining our results and published data together, the interaction of EpCAM with other proteins was also discussed and concluded in the discussion. Our results support that EpCAM can be considered as a novel target for the diagnosis and therapy of GC in future.
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Neoplasias Gástricas , Humanos , Molécula de Adesão da Célula Epitelial/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Neoplasias Gástricas/patologia , Proteínas/genética , Carcinogênese/genética , Ásia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Proliferação de Células , Movimento Celular/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Cardiolipin (CL) plays a pivotal role in mitochondria-mediated apoptosis. Acyl-CoA: lysocardiolipin acyltransferase 1 (ALCAT1) can accelerate CL reactive oxygen production and cause mitochondrial damage. Although we have demonstrated that aerobic exercise significantly reduced ALCAT1 levels in MI mice, what is the temporal characteristic of ALCAT1 after MI? Little is known. Based on this, the effect of exercise on ALCAT1 in MI rats needs to be further verified. Therefore, this paper aimed to characterize ALCAT1 expression, and investigate the possible impact of exercise on ALCAT1 and its role in fibrosis, antioxidant capacity, and apoptosis in MI rats. Our results indicated that the potential utility of MI increased ALCAT1 expression within 1-6 h of MI, and serum CK and CKMB had significant effects in MI at 24 h, while LDH exerted an effect five days after MI. Furthermore, ALCAT1 expression was upregulated, oxidative capacity and excessive apoptosis were enhanced, and cardiac function was decreased after MI, and aerobic exercise can reverse these changes. These findings revealed a previously unknown endogenous cardiac injury factor, ALCAT1, and demonstrated that ALCAT1 damaged the heart of MI rats, and aerobic exercise reduced ALCAT1 expression, oxidative stress, and apoptosis after MI-induced cardiac injury in rats.
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Superhydrophobic/electromagnetic interference (EMI) shielding materials have received a great deal of attention, attributing to their excellent water repellence characteristic. However, it is really challenging to simultaneously achieve materials with superhydrophobicity, high EMI shielding performance, and long-term stability of these materials that can operate around the clock in harsh service conditions. Herein, a novel strategy to create an integrated microskeleton magnetic nanofiller composite (IMMNC) with exceptional liquid repellency, enhanced EMI shielding effectiveness, and extreme environment reliability is reported. The superhydrophobicity of the IMMNC was maintained after extreme mechanical and chemical damage due to the synergistic enhancement between epoxy-silicone oligomers/polymerized rosin and microskeleton. Consecutively hierarchical micro/nanoarchitectures and conductive pathways endow the IMMNC with a high EMI shielding effectiveness up to 80.7 dB and a satisfactory antifouling capacity for solid and water-based contaminants. More interestingly, this composite still maintains a superior EMI shielding performance after being subjected to ultrasonic vibration, low (-20 °C) or high temperature (300 °C), and even strong acid (1 M), demonstrating its great potential and reliability as a high-performance EMI shielding material resistant to harsh operating conditions. This work provides an efficient and practical solution for developing next-generation EMI shielding materials with high reliability in an all-weather complex and changeable environment.
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OBJECTIVE: Tai Chi is an ancient philosophy used to explain the universe. The Tai Chi symbol is represented by Yin/Yang fishes. The authors describe a novel radial forearm flap (RFF) design for the reconstruction of circular defects based on the Tai Chi symbol. METHODS: Eleven consecutive patients with craniofacial skin or mucus defects underwent reconstruction with a Tai Chi RFF. Patient perioperative and follow-up information was collected. RESULTS: The diameter of the Tai Chi RFF was 5 to 6 cm. All flaps healed uneventfully without ischemic problems, and all donor site defects were closed primarily without skin grafts. Remarkably, 2 patients received a tattoo to mark the Tai Chi symbol and greatly appreciate the shape of the flap. CONCLUSIONS: The Tai Chi flap is an economically friendly flap design that can be used to prevent skin grafts while providing psychological comfort to patients.
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Procedimentos de Cirurgia Plástica , Tai Chi Chuan , Antebraço/cirurgia , Humanos , Transplante de Pele , Retalhos Cirúrgicos/cirurgiaRESUMO
Transition metal single-atom catalysts (SACs) have emerged as a research hotspot in CO2RRs. However, tuning the electronic configuration of a metal single-atom by employing new heteroatoms still remains a challenge. Herein, a carbon matrix loaded with a N and P co-coordinated Ni single-atom (denoted as Ni-NPC) was prepared for an efficient CO2RR. XANES and EXAFS were conducted to explore the coordination environment and charge distribution of the Ni-NPC catalyst. DFT calculations indicated that the Ni atom gained electrons from the P atom, and the Ni-NPC sample had a decreased energy barrier of +0.97 eV after doping with P atoms, which was favorable to overcome the limiting-step bottleneck for promoting CO2RR. Due to the rich Ni atomic active sites and superior P-doping effect, Ni-NPC exhibited a maximum FECO of 92% with a high current density of 22.6 mA cm-2 at -0.8V vs. RHE, which was far superior to those of NC, NPC and Ni-NC catalysts. Moreover, both the FECO and current density of the Ni-NPC catalyst remained stable for more than 16 h at -0.8 V vs. RHE, indicating a high stability for long-term CO2RR experiments.
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BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is threatening the world with the symptoms of seasonal influenza. This study was conducted to investigate the patient characteristics and clinical value of blood markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 187 patients, diagnosed with COVID-19 (non-severe and severe cases) and admitted to hospital between January 27th and March 8th of 2020, were enrolled in the present study. RESULTS: A higher proportion of clinical symptoms, including cough, expectoration, myalgia, and fatigue were observed in the non-severe group. The level of white blood cell count, neutrophils, CRP, IL-6 and IL-8 were significantly increased, while the platelet count was remarkedly decreased in the severe group. The risk model based on lymphocyte, IL-6, IL-8, CRP and platelet counts had the highest area under the receiver operator characteristic curve (AUROC). The baseline of IL-6, IL-8 and CRP was positively correlated with other parameters except in the cases of lymphocyte, hemoglobin and platelet counts. The baseline of the platelet count was negatively correlated with other parameters except in the lymphocyte and hemoglobin counts. Additionally, there was no connection between the severity of COVID-19 and cultures of blood, sputum or catheter secretion. CONCLUSIONS: The present study suggested that high leucocyte and low platelets counts were independent predictive markers of the severity of COVID-19.
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COVID-19 , Área Sob a Curva , Biomarcadores , Humanos , Contagem de Linfócitos , Contagem de Plaquetas , Estudos Retrospectivos , SARS-CoV-2RESUMO
OBJECTIVES: Despite substantial advances in treatment, clinical outcomes for oral squamous cell carcinoma (OSCC) remain unsatisfactory. Tumor-infiltrating lymphocytes (TILs) are an important prognostic factor for patients and are heterogeneous. Some studies have suggested that TCF1/TCF7+ T cells and tertiary lymphatic structure/organ (TLS) play an important role in tumor immunity. However, how they affect tumor immunity and whether they are related to prognosis in OSCC have not been reported in detail. MATERIALS AND METHODS: We isolated OSCC cells and performed single-cell RNA sequencing (scRNA-seq). We used immunohistochemistry (IHC) to analyze the relationship between TLSs and prognosis. Multiplex immunohistochemistry (MIHC), flow cytometry (FCM) and spatial analysis were performed to verify the characteristics of TCF1/TCF7+ T cells. The prognostic significance and upstream regulatory network of the TCF1/TCF7+ T cell subpopulation were determined by multivariate analysis and Scenic software. RESULTS: We found a strong association between TCF1/TCF7+ T cell subsets, TLSs and prognosis. The results suggested that TCF1/TCF7+ T cells express high levels of TLS-related genes and low levels of immune checkpoint molecules. Finally, we found that TCF1/TCF7+ T cells were significantly associated with favorable outcomes. We also describe the upstream drivers that these cells rely on. CONCLUSIONS: TCF1/TCF7+ T cells could be used as a new therapeutic target to regulate the immune response of OSCC and are expected to be a new prognostic marker.
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Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Subpopulações de Linfócitos T , Estruturas Linfoides Terciárias , Fator 1-alfa Nuclear de Hepatócito , Humanos , Linfócitos do Interstício Tumoral , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/imunologia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Fator 1 de Transcrição de Linfócitos TRESUMO
PURPOSE: The limited efficacy of chimeric antigen receptor (CAR) T-cell therapies with solid malignancies prompted us to test whether epigenetic therapy could enhance the antitumor activity of B7-H3.CAR T cells with several solid cancer types. EXPERIMENTAL DESIGN: We evaluated B7-H3 expression in many human solid cancer and normal tissue samples. The efficacy of the combinatorial therapy with B7-H3.CAR T cells and the deacetylase inhibitor SAHA with several solid cancer types and the potential underlying mechanisms were characterized with in vitro and ex vivo experiments. RESULTS: B7-H3 is expressed in most of the human solid tumor samples tested, but exhibits a restricted expression in normal tissues. B7-H3.CAR T cells selectively killed B7-H3 expressing human cancer cell lines in vitro. A low dose of SAHA upregulated B7-H3 expression in several types of solid cancer cells at the transcriptional level and B7-H3.CAR expression on human transgenic T-cell membrane. In contrast, the expression of immunosuppressive molecules, such as CTLA-4 and TET2, by T cells was downregulated upon SAHA treatment. A low dose of SAHA significantly enhanced the antitumor activity of B7-H3.CAR T cells with solid cancers in vitro and ex vivo, including orthotopic patient-derived xenograft and metastatic models treated with autologous CAR T-cell infusions. CONCLUSIONS: Our results show that our novel strategy which combines SAHA and B7-H3.CAR T cells enhances their therapeutic efficacy with solid cancers and justify its translation to a clinical setting.
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Antígenos B7 , Inibidores de Histona Desacetilases/uso terapêutico , Imunoterapia Adotiva , Neoplasias/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Animais , Terapia Combinada , Humanos , Camundongos , Células Tumorais CultivadasRESUMO
Dermestidae generally appears on dry corpses and carcasses, especially if mummified or skeletonized. They are forensically important insect species for estimating longer postmortem intervals (PMI). As they develop, Dermestidae larvae undergo multiple larval ecdyses; however, a lack of guidelines for determining the larval instar limits their forensic application. Herein, we explored how temperature impacts the development of Dermestes tessellatocollis Motschulsky, 1860 (Coleoptera: Dermestidae). At seven constant temperatures (16, 19, 22, 25, 28, 31, and 34 °C), the developmental time from egg to adult was 163.87 ± 9.19, 103.56 ± 3.02, 63.59 ± 2.88, 51.49 ± 2.74, 47.86 ± 3.01, 44.62 ± 4.65, and 41.80 ± 4.87 days respectively. Four morphological indexes, including head capsule width, pronotum width, mesonotum width, and body length, were taken in vivo at regular intervals to identify methods for larval instar determination in D. tessellatocollis. The acquired morphological data were used to simulate fitted curves and equations depicting the relationship between the four morphological indexes and instars. From the validation experiment, we could hardly determine a specific instar based on the morphological indexes. The combination of morphometric data (head capsule, pronotum, and mesonotum width) generated the classification accuracy at 100%, 87.5%, 85%, and 93% for the 1st, 2nd/3rd, 4th/5th, and 6th/7th instars, respectively. Nevertheless, the accuracy was unsatisfactory for application in forensic casework. This study provides fundamental development data for adopting D. tessellatocollis in minimum postmortem interval (PMImin) estimations; however, further studies are needed to improve the classification accuracy for the larval instar determination.
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Besouros/crescimento & desenvolvimento , Temperatura , Animais , Entomologia Forense , Larva/crescimento & desenvolvimento , Pupa/crescimento & desenvolvimentoRESUMO
To promote the faradaic efficiency of the electrocatalytic CO2 reduction reaction (CO2RR) with low-cost catalysts, single Ni atoms with higher positive charges induced by hydroxyls were proposed to form an atomically dispersed Ni-N4 structure in a cheap honeycomb-like carbon matrix for electrocatalytic CO2 reduction. Extended X-ray absorption fine structure spectroscopy, aberration-corrected High-angle annular dark-field scanning transmission electron microscopy and X-ray photoelectron spectroscopy measurements confirmed that the active-center structure consists of single Ni atoms and the adjacent hydroxyl via hydrothermal treatment (H-Ni/NC). Density functional theory calculations indicated that the isolated Ni atoms with higher positive charges induced by the hydroxyl decreased the free energy of the rate-limiting step to 1.05 eV for the CO2RR. The faradaic efficiency (FE) of CO2 reduction into CO was ≥88.0% over the H-Ni/NC catalyst in the potential range of -0.5 to -0.9 V (vs. RHE). The peak CO FE reached 97% at -0.7 V due to the synergistic effect between the unsaturated Ni-N4 active sites and the hydroxyl species.
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PURPOSE: Carotid atherosclerotic plaque is closely associated with cerebral white matter lesions (WMLs), while intraplaque neovascularization (IPN) contributes significantly to arterial remodeling and plaque vulnerability. In this study, we aim to evaluate the correlation of carotid IPN with cerebral WMLs. METHODS: The presence of IPN and WMLs were assessed by contrast-enhanced ultrasound (CEUS) and MRI respectively. IPN was evaluated utilizing semi-quantification visual grading scale and WMLs was divided according to Fazekas grading scale. We investigated the baseline data, Fazekas grades, and IPN grades among 269 participants. We explored the influences of each variable on Fazekas grades using ordinal logistic regression and evaluated the relationship between IPN grades and WMLs Fazekas grades. RESULTS: Increased age (OR: 1.06, P<0.001), hypertension (OR: 2.17, P=0.002), cerebral infarction (OR: 1.74, P=0.046), and elevated carotid IPN grading were significantly associated with aggravated Fazekas grades (grade 2 or 3). To be specific, people having grade 3, 2, and 1 carotid IPN were 25.84 (P<0.001), 10.64 (P<0.001), and 5.96 (P=0.010) times as likely to have elevated Fazekas grades compared with those who having grade 0 carotid IPN. CONCLUSION: Increased carotid IPN is independently correlated with aggravated cerebral WMLs.
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Doenças das Artérias Carótidas/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Leucoencefalopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neovascularização Patológica , Fosfolipídeos/administração & dosagem , Placa Aterosclerótica , Hexafluoreto de Enxofre/administração & dosagem , Ultrassonografia Doppler em Cores , Idoso , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/patologia , Feminino , Humanos , Leucoencefalopatias/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de RiscoRESUMO
To efficiently and selectively produce liquid hydrocarbon fuels, e.g., methanol, by CO2 photoelectrochemical reduction, CdS nanoparticles (NPs) anchored on the nitrogen-doped carbon particles (NCP) with core-shell dodecahedral porous structure were used as cathode catalysts. Electron paramagnetic resonance (EPR) spectra indicated that CdS/NCP treated at 500⯰C had the maximum S-vacancies. The heterojunction generated between CdS with abundant S-vacancies and NCP with a high content of pyridinic N acted as synergistic catalyst for CO2 reduction. CdS/NCP-500 catalyst exhibited a selectivity of 77.3% towards methanol with a total carbon atom conversion rate of 3052â¯nmol·h-1·cm-2. Density functional theory (DFT) calculations revealed that the S-vacancies decreased the energy barrier for CO2 conversion into methanol product. NCP, exhibiting a high adsorption capacity for CO2, allowed the conversion of COOH* into CO* (ΔEâ¯=â¯-3.6â¯eV), which was then transferred to the CdS surface displaying abundant S-vacancies for the reduction into the methanol product.
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BACKGROUND: Plant immune responses can be induced by plant growth-promoting rhizobacteria (PGPRs), but the exact compounds that induce resistance are poorly understood. Here, we identified the novel natural elicitor 3,4-dihydroxy-3-methyl-2-pentanone from the PGPR Bacillus subtilis HN09, which dominates HN09-induced systemic resistance (ISR). RESULTS: The HN09 strain, as a rhizobacterium that promotes plant growth, can induce systemic resistance of Arabidopsis thaliana plants against Pseudomonas syringae pv. tomato DC3000, and the underlying role of its metabolite 3,4-dihydroxy-3-methyl-2-pentanone in this induced resistance mechanism was explored in this study. The stereoisomers of 3,4-dihydroxy-3-methyl-2-pentanone exhibited differential bioactivity of resistance induction in A. thaliana. B16, a 1:1 mixture of the threo-isomers (3R,4S) and (3S,4R), was significantly superior to B17, a similar mixture of the erythro-isomers (3R,4R) and (3S,4S). Moreover, B16 induced more expeditious and stronger callose deposition than B17 when challenged with the pathogen DC3000. RT-qPCR and RNA-seq results showed that B16 and B17 induced systemic resistance via JA/ET and SA signalling pathways. B16 and B17 activated different but overlapping signalling pathways, and these compounds have the same chemical structure but subtle differences in stereo configuration. CONCLUSIONS: Our results indicate that 3,4-dihydroxy-3-methyl-2-pentanone is an excellent immune elicitor in plants. This compound is of great importance to the systemic resistance induced by HN09. Its threo-isomers (3R,4S) and (3S,4R) are much better than erythro-isomers (3R,4R) and (3S,4S). This process involves SA and JA/ET signalling pathways.
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Arabidopsis/imunologia , Bacillus subtilis/química , Pentanonas/farmacologia , Doenças das Plantas/imunologia , Imunidade Vegetal , Transdução de Sinais/imunologia , Arabidopsis/microbiologia , Resistência à Doença , Pentanonas/química , Doenças das Plantas/microbiologia , EstereoisomerismoRESUMO
OBJECTIVES: To evaluate the value of ultrafast pulse wave velocity (ufPWV) for the quantitative assessment of carotid stiffness and its associated with atherosclerosis (AS) risk. METHODS: The present study included 233 patients with hyperlipoidaemia (AS risk group) and 114 healthy adults as the control group. The carotid (n = 694) intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS) and pulse wave velocity-end of systole (PWV-ES) were measured on sample images. Differences, distributive characteristics and correlation evaluation were assessed in patients (ages 18-29, 30-39, 40-49, 50-59, 60-69 and ≥70) and carotids (control group vs AS risk group). RESULTS: The cIMT, PWV-BS and PWV-ES increased with age; PWV-ES and cIMT showed an early significant increase in the 30-39 years group, whereas PWV-BS displayed a significant increase at 40-49 years compared with the 18- to 29-years group. Besides, PWV-ES correlated well with age compared with PWV-BS and cIMT. For carotid level, cIMT, PWV-BS and PWV-ES measurements were higher in the AS risk group compared with control. To compare the value of ufPWV and cIMT in early AS assessment, we subdivided groups into cIMT subgroups using a cut-off thickness of 0.050 cm. PWV-ES measurements were higher in the AS risk group compared with the control in the 0.040-0.050 cm (not thickened) and 0.051-0.060 cm (thickened) cIMT subgroups. CONCLUSIONS: Carotid ufPWV measurement at PWV-ES is a novel modality for the early diagnosis and quantitative assessment of arterial stiffness associated with atherosclerotic risk. KEY POINTS: ⢠ufPWV technique is real-time and well repeatable for assessing carotid stiffness ⢠ufPWV measurements increase and correlate well with age ⢠PWV-ES is a quantitative predictor for the early assessment of AS.
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Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/fisiopatologia , Análise de Onda de Pulso , Rigidez Vascular , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Espessura Intima-Media Carotídea , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Sístole , Ultrassonografia , Adulto JovemRESUMO
α-Aminophosphonates compounds containing 3,5-diphenyl-2-isoxazoline were synthesized and evaluated for their bioactivity. Seventeen of them showed good bioactivity (protection effect > 50%) in vivo against papaya ringspot virus, while two of them (V29 and V45) exhibited excellent antiviral activity (both 77.8%). In the latter case, the antiviral activity was close to that of antiphytovirucides ningnanmycin and dufulin (both 83.3%) at 500 mg/L. The preliminary structure-activity relationships indicated that the bioactivity was strongly influenced by the substituents.
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Antivirais , Isoxazóis , Organofosfonatos , Potyvirus/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Isoxazóis/química , Isoxazóis/farmacologia , Organofosfonatos/química , Organofosfonatos/farmacologiaAssuntos
Acantoma/patologia , Dermoscopia/métodos , Porocarcinoma Écrino/patologia , Neoplasias Primárias Múltiplas/patologia , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Acantoma/diagnóstico , Biópsia por Agulha , Diagnóstico Diferencial , Porocarcinoma Écrino/diagnóstico , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias das Glândulas Sudoríparas/diagnósticoRESUMO
Organophosphorus (OP) insecticides play an important role in pest control. Many OP insecticides have been removed from the market because of their high toxicity to humans. We designed and synthesized a new OP insecticide with the goal of providing a low cost, and less toxic insecticide. The mode of action of O, O-diethyl O-(4-(5-phenyl-4, 5-dihydroisoxazol-3-yl) phenyl) phosphorothioate (XP-1408) was studied in Drosophila melanogaster. Bioassays showed that XP-1408 at a concentration of 50 mg/L delayed larval development. Molecular docking into Drosophila acetylcholinesterase (AChE) and voltage-gated sodium channels suggested that XP-1408 fitted into their active sites and could be inhibitory. Whole-cell patch clamp recordings indicated that XP-1408 exhibited synergistic effects involving the inhibition of cholinergic synaptic transmission and blockage of voltage-gated potassium (Kv) channels and sodium (Nav) channels. In conclusion, the multiple actions of XP-1408 rendered it as a lead compound for formulating OP insecticides with a novel mode of action.
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Inseticidas/química , Inseticidas/farmacologia , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Fosfatos/química , Fosfatos/farmacologia , Animais , Relação Dose-Resposta a Droga , Drosophila/efeitos dos fármacos , Inseticidas/síntese química , Modelos Moleculares , Conformação Molecular , Compostos Organofosforados/síntese química , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Relação Estrutura-Atividade , Transmissão Sináptica/efeitos dos fármacosRESUMO
Phloem-mobile insecticides are efficient for piercing and sucking insect control. Introduction of sugar or amino acid groups to the parent compound can improve the phloem mobility of insecticides, so a glycinergic-fipronil conjugate (GlyF), 2-(3-(3-cyano-1-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-((trifluoromethyl)sulfinyl)-1H-pyrazole-5-yl)ureido) acetic acid, was designed and synthesized. Although the "Kleier model" predicted that this conjugate is not phloem mobile, GlyF can be continually detected during a 5 h collection of Ricinus communis phloem sap. Furthermore, an R. communis seedling cotyledon disk uptake experiment demonstrates that the uptake of GlyF is sensitive to pH, carbonyl cyanide m-chlorophenylhydrazone (CCCP), temperature, and p-chloromercuribenzenesulfonic acid (pCMBS) and is likely mediated by amino acid carrier system. To explore the roles of amino acid transporters (AATs) in GlyF uptake, a total of 62 AAT genes were identified from the R. communis genome in silico. Phylogenetic analysis revealed that AATs in R. communis were organized into the ATF (amino acid transporter) and APC (amino acid, polyaminem and choline transporter) superfamilies, with five subfamilies in ATF and two in APC. Furthermore, the expression profiles of 20 abundantly expressed AATs (cycle threshold (Ct) values <27) were analyzed at 1, 3, and 6 h after GlyF treatment by RT-qPCR. The results demonstrated that expression levels of four AAT genes, RcLHT6, RcANT15, RcProT2, and RcCAT2, were induced by the GlyF treatment in R. communis seedlings. On the basis of the observation that the expression profile of the four candidate genes is similar to the time course observation for GlyF foliar disk uptake, it is suggested that those four genes are possible candidates involved in the uptake of GlyF. These results contribute to a better understanding of the mechanism of GlyF uptake as well as phloem loading from a molecular biology perspective and facilitate functional characterization of candidate AAT genes in future studies.