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1.
Org Lett ; 26(9): 1959-1964, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38407134

RESUMO

Phenols are versatile synthetic intermediates and key structural motifs in many natural products and biologically active compounds. We herein report a visible-light-induced aerobic oxidative hydroxylation of arylboronic acids/pinacol esters using air as oxidant and without using any catalysts and base, etc., additives, providing a green entry to a variety of phenols in a highly efficient and concise fashion. This novel reaction is enabled by photoactivation of an electron donor-acceptor complex, in which THF serves as both the solvent and electron donor. DFT studies indicated that the oxidation process involves a concerted hydrogen abstraction transfer from THF and dehydroxylation of boronic acid undergoing spin crossover from triplet to singlet to produce an active peroxoboronic acid intermidiate. Salient merits of this chemistry include broad substrate scope and excellent functional group tolerance, gram-scale synthesis, and versatile late-stage functionalizations as well as the use of air, visible light, and catalyst- and additive-free conditions. This strategy introduces a novel photoreaction mode with the aid of a solvent, offering a succinct and environmentally sustainable route for synthesizing phenols. The strong practicability and highly efficient access to modifying complex biorelevant molecules bode well for the potential applications of this chemistry in pharmaceutical chemistry.

2.
J Immunother Cancer ; 12(1)2024 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267222

RESUMO

BACKGROUND: Targeted immunotherapy with monoclonal antibodies (mAbs) is an effective and safe method for the treatment of malignancies. Development of mAbs with improved cytotoxicity, targeting new and known tumor-associated antigens, therefore continues to be an active research area. We reported that Dickkopf-1 (DKK1) is a good target for immunotherapy of human cancers based on its wide expression in different cancers but not in normal tissues. As DKK1 is a secreted protein, mAbs binding directly to DKK1 have limited effects on cancer cells in vivo. METHODS: The specificity and antibody-binding capacity of DKK1-A2 mAbs were determined using indirect ELISA, confocal imaging, QIFIKIT antibody-binding capacity and cell surface binding assays. The affinity of mAbs was determined using a surface plasmon resonance biosensor. A flow cytometry-based cell death was performed to detect tumor cell apoptosis. Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) assays were used to evaluate the ability of DKK1-A2 mAbs to mediate ADCC and CDC activities against tumor cells in vitro. Flow cytometry data were collected with an FACSymphony A3 cell analyzer and analyzed with FlowJo V.10.1 software. Human cancer xenograft mouse models were used to determine the in vivo therapeutic efficacy and the potential safety and toxicity of DKK1-A2 mAbs. In situ TUNEL assay was performed to detect apoptosis in tumors and mouse organs. RESULTS: We generated novel DKK1-A2 mAbs that recognize the DKK1 P20 peptide presented by human HLA-A*0201 (HLA-A2) molecules (DKK1-A2 complexes) that are naturally expressed by HLA-A2+DKK1+ cancer cells. These mAbs directly induced apoptosis in HLA-A2+DKK1+ hematologic and solid cancer cells by activating the caspase-9 cascade, effectively lysed the cancer cells in vitro by mediating CDC and ADCC and were therapeutic against established cancers in their xenograft mouse models. As DKK1 is not detected in most human tissues, DKK1-A2 mAbs neither bound to or killed HLA-A2+ blood cells in vitro nor caused tissue damage in tumor-free or tumor-bearing HLA-A2-transgenic mice. CONCLUSION: Our study suggests that DKK1-A2 mAbs may be a promising therapeutic agent to treat human cancers.


Assuntos
Antígeno HLA-A2 , Neoplasias , Humanos , Animais , Camundongos , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Peptídeos , Imunoterapia , Neoplasias/tratamento farmacológico , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular
3.
Sheng Wu Gong Cheng Xue Bao ; 39(12): 4796-4808, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38147982

RESUMO

This study aimed to explore the mechanism of how African swine fever virus (ASFV) I226R protein inhibits the cGAS-STING signaling pathway. We observed that I226R protein (pI226R) significantly inhibited the cGAS-STING-mediated type Ⅰ interferons and the interferon-stimulated genes production by dual-luciferase reporter assay system and real-time quantitative PCR. The results of co-immunoprecipitation assay and confocal microscopy showed that pI226R interacted with cGAS. Furthermore, pI226R promoted cGAS degradation through autophagy-lysosome pathway. Moreover, we found that pI226R decreased the binding of cGAS to E3 ligase tripartite motif protein 56 (TRIM56), resulting in the weakened monoubiquitination of cGAS, thus inhibiting the activation of cGAS and cGAS-STING signaling. In conclusion, ASFV pI226R suppresses the antiviral innate immune response by antagonizing cGAS, which contributes to an in-depth understanding of the immune escape mechanism of ASFV and provides a theoretical basis for the development of vaccines.


Assuntos
Vírus da Febre Suína Africana , Animais , Suínos , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Imunidade Inata , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transdução de Sinais/genética
4.
Sheng Wu Gong Cheng Xue Bao ; 39(12): 4809-4823, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38147983

RESUMO

In order to understand the prevalence and evolution of porcine reproductive and respiratory syndrome virus (PRRSV) in China and to develop subunit vaccine against the epidemic lineage, the genetic evolution analysis of PRRSV strains isolated in China from 2001 to 2021 was performed. The representative strains of the dominant epidemic lineage were selected to optimize the membrane protein GP5 and M nucleotide sequences, which were used, with the interferon and the Fc region of immunoglobulin, to construct the eukaryotic expression plasmids pCDNA3.4-IFNα-GP5-Fc and pCDNA3.4-IFNα-M-Fc. Subsequently, the recombinant proteins IFNα-GP5-Fc and IFNα-M-Fc were expressed by HEK293T eukaryotic expression system. The two recombinant proteins were mixed with ISA206VG adjuvant to immunize weaned piglets. The humoral immunity level was evaluated by ELISA and neutralization test, and the cellular immunity level was detected by ELISPOT test. The results showed that the NADC30-like lineage was the main epidemic lineage in China in recent years, and the combination of IFNα-GP5-Fc and IFNα-M-Fc could induce high levels of antibody and cellular immunity in piglets. This study may facilitate the preparation of a safer and more effective new PRRSV subunit vaccine.


Assuntos
Síndrome Respiratória e Reprodutiva Suína , Vírus da Síndrome Respiratória e Reprodutiva Suína , Vacinas Virais , Humanos , Animais , Suínos , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Síndrome Respiratória e Reprodutiva Suína/prevenção & controle , Células HEK293 , Proteínas do Envelope Viral/genética , Anticorpos Antivirais , Vacinas Virais/genética , Proteínas Recombinantes , Vacinas de Subunidades
5.
Autophagy ; 19(12): 3113-3131, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37482689

RESUMO

ABBREVIATIONS: aa: amino acid; ATF6: activating transcription factor 6; ATG5: autophagy related 5; CCPG1: cell cycle progression 1; CFTR: CF transmembrane conductance regulator; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CHX: cycloheximide; Co-IP: co-immunoprecipitation; CQ: chloroquine; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE1: endoplasmic reticulum to nucleus signaling 1; GFP: green fluorescent protein; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; HSV-1: herpes simplex virus type 1; IFIT1: interferon induced protein with tetratricopeptide repeats 1; IFNB1/IFN-ß: interferon beta 1; IRF3: interferon regulatory factor 3; ISG15: ISG15 ubiquitin like modifier; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAP3K7/TAK1: mitogen-activated protein kinase kinase kinase 7; MAVS: mitochondrial antiviral signaling protein; MOI: multiplicity of infection; NFKB/NF-κB: nuclear factor kappa B; NSP6: non-structural protein 6; Δ106-108: deletion of amino acids 106-108 in NSP6 of SARS-CoV-2; Δ105-107: deletion of amino acids 105-107 in NSP6 of SARS-CoV-2; RETREG1/FAM134B: reticulophagy regulator 1; RIGI/DDX58: RNA sensor RIG-I; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Autofagia/fisiologia , Estresse do Retículo Endoplasmático/fisiologia , Chaperona BiP do Retículo Endoplasmático , Interferons , Aminoácidos
6.
Environ Sci Pollut Res Int ; 30(27): 71284-71295, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37162673

RESUMO

It is crucial to switch from nonrenewable energy to renewable energy sources to improve environmental quality. For this reason, innovations play a crucial part, yet the use of renewable energy is insufficient. This work contributes to the literature by Using both aggregate and disaggregated data, this study investigates the relationship between energy consumption, trade openness, human capital (HCA), and innovations in G11 nations. This study analyzed yearly data from 1990 to 2020 using empirical methods of augmented mean group (AMG) and cross-sectional autoregressive distributed lag (CS-ARDL) techniques. The findings highlight the significance of human capital, energy pricing, and innovations in fostering the growth of renewable energy in G-11 nations. A 1% increase in GDP and trade openness will enhance total energy consumption by 0.47% and 0.07%. GDP and trade are also increasing non and renewable energy consumption. A 1% increase in human capital and eco-innovations are increasing renewable energy by reducing non-renewable energy consumption. In addition, the G-11's rising commerce and GDP have increased their reliance on energy sources that rely on fossil fuels. The authors of this study suggest raising HCA as a means of encouraging the G-11 to use cleaner forms of energy. The need to bolster renewable energy to achieve a cleaner environment in the G-11 countries.


Assuntos
Dióxido de Carbono , Desenvolvimento Econômico , Humanos , Estudos Transversais , Energia Renovável , Fontes Geradoras de Energia
7.
Comput Intell Neurosci ; 2022: 3132016, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990136

RESUMO

Objective: To analyze the intervention effect of group counseling based on positive psychology on psychological crisis of college student. Method: SCL-90 mental health screening was performed on second-year students in a college by cluster stratification. Among the detected students, 210 were included into the group after brief interview and randomly assigned to the experimental group and the control group. The control group was given conventional intervention measures, and the experimental group was given group counseling according to the interview results. One week before the start, on the day of the end of the intervention and 3 months after the end of the intervention, the mental health level of all subjects was evaluated by symptom self-rating scale, general well-being scale, and adolescent mental resilience scale. Results: The scores of two groups were different at different time points during the intervention. With the extension of time, the score of the self-rating symptom scale in the experimental group decreased significantly, while the total score of the self-rating symptom scale in the control group increased, with statistical significance (P < 0.05). Before the intervention, there was no significant difference in general well-being between the two groups (P > 0.05). At 3 months after the end of intervention, the total score of the general well-being scale in the experimental group increased, while that in the control group decreased, with statistical significance (P < 0.05). Three months after the end of the intervention, the total score of adolescent mental resilience scale in the experimental group increased. Conclusion: Group counseling from the perspective of positive psychology can effectively improve the mental health status of medical students with psychological crisis and improve their mental resilience.


Assuntos
Psicologia Positiva , Estudantes de Medicina , Adolescente , Aconselhamento/métodos , Humanos , Saúde Mental , Universidades
8.
Org Biomol Chem ; 20(32): 6459-6463, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35894817

RESUMO

A mild and efficient visible-light-induced radical method was developed to produce C3-malonated five-membered heterocycles using 2-substituted thiophenes/furans and diethyl bromomalonate as the starting materials. Various 2-substituted (benzo)thiophenes/furans were suitable for the C3-ethoxycarbonylmethylation. The free radical mechanism was proposed based on the results of control experiments, cyclic voltammetry experiments and luminescence quenching experiments. We suggested that the heteroleptic halogen-bridged iridium(III) dimers might play an important role in this system.


Assuntos
Furanos , Tiofenos , Luz , Estrutura Molecular
9.
Talanta ; 246: 123494, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35523020

RESUMO

The rigorous and reasonable evaluation of uncertainty is crucial for the reliability of the results of a reference measurement procedure. A new uncertainty budget is proposed for uncertainty evaluation of a reference measurement procedure for total thyroxine in human serum based on isotope dilution liquid chromatography-mass spectrometry. In this work, a measurement model for uncertainty evaluation of triple isotope dilution-mass spectrometry was established. The propagation of uncertainties assigned to various input quantities was expressed in strict accordance with the measurement model. A detailed description of the uncertainty evaluation process for the measurement result of a specific serum is given, including the estimate of the input quantities and the determination of the combined standard uncertainty. The expanded uncertainty of the specific human serum (at coverage probability of 95%) was 4.8 nmol/L at the concentration level of 113.6 nmol/L.


Assuntos
Isótopos , Tiroxina , Humanos , Espectrometria de Massas/métodos , Reprodutibilidade dos Testes , Incerteza
10.
J Hepatocell Carcinoma ; 9: 171-188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35308603

RESUMO

Background and Aims: Hepatocellular carcinoma (HCC) is a common malignant disease with high morbidity and mortality throughout the world. While Borealin is a putative oncogene that is dysregulated in multiple tumors, its exact role in HCC remains less investigated. Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) assays were employed to examine the relative amount of Borealin. Gene set enrichment analysis (GSEA) and other bioinformatic analyses were implemented to probe into the potential functions of Borealin. The biological roles and mechanisms of Borealin in the tumorigenesis and development of HCC were further evaluated using a battery of functional assays in vivo and in vitro. Results: Borealin was enhanced in the HCC tissue samples and hepatoma cells when compared with the nontumor tissues and normal liver cells. Higher Borealin expression was positively linked with advanced pathological phenotypes and inferior overall survival. The overexpression of Borealin promoted the cells' abilities on proliferation, invasion and epithelial-mesenchymal transition (EMT) in vitro, facilitated tumor growth and lung metastasis in vivo, whereas the silencing of Borealin inhibited these capabilities in vitro. Furthermore, Borealin interacted with ß-catenin and further activated the Wnt/ß-catenin signaling pathway, which endowed HCC cells with highly aggressive and metastatic capabilities. Conclusion: Borealin was identified as an oncogene that could promote HCC growth and metastasis by activating the WNT/ß-catenin signaling pathway. These findings extended the understanding of Borealin in HCC tumorigenesis and development and highlighted the significance of Borealin in HCC diagnosis and treatment.

11.
Biomed Res Int ; 2021: 9963700, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604389

RESUMO

The study is aimed at observing the influence of microribonucleic acid- (miRNA-) 30a-50p on the pulmonary fibrosis in mice with Streptococcus pneumoniae infection through the regulation of autophagy by Beclin-1. Specific pathogen-free mice were instilled with Streptococcus pneumoniae through the trachea to establish the pulmonary fibrosis model. Then, they were divided into the miRNA-30a-50p mimics group (mimics group, n = 10) and miRNA-30a-5p inhibitors group (inhibitors group, n = 10), with the control group (n = 10) also set. Pulmonary tissue wet weight/dry weight (W/D) was detected. The content of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and myeloperoxidase (MPO) was determined using enzyme-linked immunosorbent assay (ELISA). Besides, the changes in the pulmonary function index dynamic lung compliance (Cdyn), plateau pressure (Pplat), and peak airway pressure (Ppeak) were monitored, and the gene and protein expression levels were measured via quantitative PCR (qPCR) and Western blotting. The expression level of miRNA-30a-5p was substantially raised in the mimics group (p < 0.05), but extremely low in the inhibitors group (p < 0.05). The mimics group had obviously raised levels of serum aminotransferase (AST), glutamic-pyruvic transaminase (GPT), alkaline phosphatase (ALP), and pulmonary tissue W/D (p < 0.05). Additionally, the expression levels of TNF-α, IL-6, and MPO were notably elevated in the mimics group, while their expression levels showed the opposite conditions in the inhibitors group (p < 0.05). According to the HE staining results, the inhibitors group had arranged orderly cells, while the mimics group exhibited lung injury, pulmonary edema, severe inflammatory response, and alveolar congestion. In the inhibitors group, Cdyn was remarkably elevated, but Pplat and Ppeak declined considerably (p < 0.05). Besides, the inhibitors group exhibited elevated messenger RNA (mRNA) levels of Beclin-1 and LC3, lowered mRNA levels of α-SMA and p62, a raised protein level of Beclin-1, and a markedly decreased protein level of p62 (p < 0.05). Silencing miRNA-30a-5p expression can promote the expression of Beclin-1 to accelerate the occurrence of autophagy, thereby treating pulmonary fibrosis in mice with Streptococcus pneumoniae infection.


Assuntos
Autofagia/genética , Proteína Beclina-1/metabolismo , MicroRNAs/metabolismo , Infecções Pneumocócicas/genética , Fibrose Pulmonar/genética , Fibrose Pulmonar/microbiologia , Actinas/metabolismo , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Regulação da Expressão Gênica , Mediadores da Inflamação/metabolismo , Pulmão/patologia , Pulmão/fisiopatologia , Camundongos , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Tamanho do Órgão , Testes de Função Respiratória , Proteína Sequestossoma-1/metabolismo , Transaminases/sangue
12.
Chem Commun (Camb) ; 57(59): 7308-7311, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34223574

RESUMO

A mild and efficient visible-light-induced synthesis of C-3 dicarbonyl coumarins from 3-arylacetylene coumarins without a photocatalyst was reported. This iodide-mediated method exhibited broad substrate scope and good functional group tolerance, and a series of C-3 dicarbonyl coumarins were obtained in moderate to excellent yields. Based on the control experimental results, it was found that the visible-light-induced oxidation might be via both radical and ionic processes. Moreover, some synthesized compounds displayed high sensitivity to hydrogen peroxide (H2O2) with a low detection limit (DL, down to 0.149 µM).

13.
J Org Chem ; 85(23): 15051-15061, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33147963

RESUMO

Despite the various attractive properties of γ-pyrones, there are still some deficiencies in their synthetic approaches such as lower atom economy, multistep processes, and prefunctionalization of the reagents. In this work, an efficient and simple (CF3CO)2O/CF3SO3H-mediated "one-pot" approach was realized to produce γ-pyrones by applying aromatic ketones/heteroarenes and carboxylic acids as the starting materials. The target products were isolated in moderate to excellent yields. The reaction mechanism was studied by density functional theory calculational methods. The results of experimental and theoretical investigations not only helped us explain the reason of high selectivity formation of ß-diketones but also proved that 1,3,5-ketones might be important intermediates for the cyclization to afford γ-pyrones.

14.
RNA Biol ; 17(10): 1391-1401, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32602777

RESUMO

Each gene typically has multiple alternatively spliced transcripts. Different transcripts are assumed to play a similar biological role; however, some transcripts may simply lose their function due to loss of important functional domains. Here, we show that two different transcripts of lncRNA gene ANRIL associated with coronary artery disease (CAD) play antagonizing roles against each other. We previously reported that DQ485454, the short transcript, is downregulated in coronary arteries from CAD patients, and reduces monocyte adhesion to endothelial cells (ECs) and transendothelial monocyte migration (TEM). Interestingly, the longest transcript NR_003529 is significantly upregulated in coronary arteries from CAD patients. Overexpression of ANRIL transcript NR_003529 increases monocyte adhesion to ECs and TEM, whereas knockdown of NR_003529 expression reduces monocyte adhesion to ECs and TEM. Much more dramatic effects were observed for the combination of overexpression of NR_003529 and knockdown of DQ485454 or the combination of knockdown of NR_003529 and overexpression of DQ485454. The antagonizing effects of ANRIL transcripts NR_003529 and DQ485454 were associated with their opposite effects on expression of downstream target genes EZR, CXCL11 or TMEM106B. Our results demonstrate that different transcripts of lncRNA can exert antagonizing effects on biological functions, thereby providing important insights into the biology of lncRNA. The data further support the hypothesis that ANRIL is the causative gene at the 9p21 CAD susceptibility locus.


Assuntos
Processamento Alternativo , Doença da Artéria Coronariana/genética , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , RNA Longo não Codificante/genética , Biomarcadores , Adesão Celular/genética , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/metabolismo , Vasos Coronários/metabolismo , Vasos Coronários/patologia , Suscetibilidade a Doenças , Técnicas de Silenciamento de Genes , Humanos , Monócitos/metabolismo , Monócitos/patologia , Isoformas de RNA , Migração Transendotelial e Transepitelial/genética
15.
Org Biomol Chem ; 18(17): 3346-3353, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32301954

RESUMO

A mild and simple one-pot stepwise method to synthesize 3-arylacetylene coumarins from alkynoates was demonstrated. This catalytic system involves photosensitizer-free photocatalysis and thermocatalysis processes. A series of alkynoates and phenylacetylenes were well tolerated in the optimized multi-catalytic system. The corresponding 3-arylacetylene coumarins were obtained in moderate to excellent yields. The results of the studies of their optical properties showed that the aromatic ring at the C4-position of coumarins is unfavorable for improving the molecular fluorescence quantum yield in solution. Based on the spectral studies and X-ray single crystal diffraction analysis, it was found that AIE activities may exist in some of the 3-arylvinyl-4-aryl-coumarins in their solid state. We expect that these molecules may have potential optical applications.

16.
Int J Biol Macromol ; 157: 434-443, 2020 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-32315678

RESUMO

The fractional polysaccharide SMWP-U&E was isolated from Salvia miltiorrhiza residue. SMWP-U&E consists of 91.40% carbohydrates and has an average molecular weight of 5.07 × 105 Da. The polysaccharides are mainly composed of arabinose (Ara), fructose (Fru), mannose (Man), glucose (Glc), and galactose (Gal), and their mole percentages are 3.72%, 4.11%, 6.18%, 32.08% and 53.91%, respectively. When effected on weaned piglets, 1.5 g/kg SMWP-U&E supplementation significantly increased the villus height to crypt depth ratio in ileum. PCR-denaturing gradient gel electrophoresis and qRT-PCR results indicated that SMWP-U&E supplementation could change the density of intestinal microbiota and the populations of Lactobacillus and Escherichia coli in jejunum, ileum, caecum, and colon. The supplementation also increased contents of IgA, IgG, IgM, IL-2, IFN-γ, and IL-10; promoted T-AOC and SOD activities; and reduced MDA level in the serum. These findings suggest that SMWP-U&E improves digestion and nutrient absorption in weaned piglets, exerts beneficial effects on intestinal morphology and microflora, and enhances the immune and antioxidant capabilities in mode of weaned piglets. Thus, SMWP-U&E exhibits potential as a new type of plant-derived additive and novel prebiotics.


Assuntos
Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Salvia miltiorrhiza/química , Animais , Biomarcadores , Microbioma Gastrointestinal/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Monossacarídeos/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-Atividade , Suínos
17.
J Am Heart Assoc ; 9(7): e014146, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32237974

RESUMO

Background Epistasis describes how gene-gene interactions affect phenotypes, and could have a profound impact on human diseases such as coronary artery disease (CAD). The goal of this study was to identify gene-gene interactions in CAD using an easily generalizable multi-stage approach. Methods and Results Our forward genetic approach consists of multiple steps that combine statistical and functional approaches, and analyze information from global gene expression profiling, functional interactions, and genetic interactions to robustly identify gene-gene interactions. Global gene expression profiling shows that knockdown of ANRIL (DQ485454) at 9p21.3 GWAS (genome-wide association studies) CAD locus upregulates TMEM100 and TMEM106B. Functional studies indicate that the increased monocyte adhesion to endothelial cells and transendothelial migration of monocytes, 2 critical processes in the initiation of CAD, by ANRIL knockdown are reversed by knockdown of TMEM106B, but not of TMEM100. Furthermore, the decreased monocyte adhesion to endothelial cells and transendothelial migration of monocytes induced by ANRIL overexpression was reversed by overexpressing TMEM106B. TMEM106B expression was upregulated by >2-fold in CAD coronary arteries. A significant association was found between variants in TMEM106B (but not in TMEM100) and CAD (P=1.9×10-8). Significant gene-gene interaction was detected between ANRIL variant rs2383207 and TMEM106B variant rs3807865 (P=0.009). A similar approach also identifies significant interaction between rs6903956 in ADTRP and rs17465637 in MIA3 (P=0.005). Conclusions We demonstrate 2 pairs of epistatic interactions between GWAS loci for CAD and offer important insights into the genetic architecture and molecular mechanisms for the pathogenesis of CAD. Our strategy has broad applicability to the identification of epistasis in other human diseases.


Assuntos
Doenças Cardiovasculares/genética , Células Endoteliais/metabolismo , Epistasia Genética , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Interpretação Estatística de Dados , Redes Reguladoras de Genes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Modelos Estatísticos , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fenótipo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Medição de Risco , Transcriptoma
18.
Plant Physiol Biochem ; 151: 157-165, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32222679

RESUMO

Brassinazole-resistant (BZR) transcription factors have important roles in the brassinosteroid (BR) signalling pathway and are widely involved in plant growth and abiotic stress processes. However, there are few studies on the functions and regulatory mechanisms of BZR TFs in birch. In this study, 5 BZR genes were identified from birch. The qRT-PCR results showed that the expression levels of most BpBZRs were significantly downregulated and/or upregulated in at least one organ following NaCl and PEG stress or ABA, GA3 and JA treatments. In particular, BpBZR1 expression was changed in all three organs after exposure to NaCl stress at all time points, indicating that this gene may be involved in salt stress. The BpBZR1 transcription factor was shown to have transcriptional activation activity in a yeast two-hybrid assay. Through a transient transformation system, we found that overexpression of BpBZR1 in birch resulted in lower H2O2 and MDA accumulation, higher SOD and POD activities and maintained a higher photosynthetic intensity and a lower chlorophyll degradation rate than those of the control plants under salt stress. These results preliminarily showed that overexpression of the BpBZR1 gene increased the tolerance of birch to salt stress.


Assuntos
Betula/fisiologia , Proteínas de Ligação a DNA/fisiologia , Proteínas de Plantas/fisiologia , Estresse Fisiológico , Fatores de Transcrição/fisiologia , Betula/genética , Regulação da Expressão Gênica de Plantas
19.
J Colloid Interface Sci ; 559: 244-253, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31630017

RESUMO

Lithium-sulfur batteries hold broad prospects as the low-cost and high-energy storage system. However, the practical application is limited by the intrinsic insulating nature of sulfur and severe shuttle effect of soluble polysulfide intermediates. Herein, we demonstrate a convenient self-assembly strategy for encapsulating carbon nanotubes in nitrogen-doped hollow carbon shells, to construct a nitrogen-doped tube-in-tube carbon nanostructure (NTTC) as a host material of sulfur. In this peculiar structure, the highly conductive carbon nanotube cores facilitate the electron transfer while the hollow porous structure is capable of accommodating high sulfur content of 70 wt% in the composites. Moreover, the nitrogen doping helps to alleviate the shuttle effect owing to enhanced chemisorption towards polysulfides. Benefiting from these merits, the NTTC/S composite with the high areal mass loading of ~2.5 mg cm-2 presents a high reversible capacity (1346.9 mAh g-1 at 0.05 C) and excellent rate capability (533.5 mAh g-1 at 3C). More impressively, NTTC/S electrode exhibits good cycling stability at a high rate of 2 C corresponding to slight capacity decay of 0.055% per cycle over 500 discharge/charge cycles.

20.
Opt Express ; 27(16): 22923-22929, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31510576

RESUMO

The dark current of a photodetector is a key parameter for high-sensitivity optical receivers. We report low-dark-current, triple-mesa avalanche photodiodes that have ~50 times lower dark current than conventional single-mesa devices, and suppress surface leakage. The tolerances of triple-mesa avalanche photodiode parameters are presented.

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