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1.
Environ Sci Technol ; 55(17): 11894-11905, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488355

RESUMO

Elevated concentrations of dietary selenium (Se) cause abnormalities and extirpation of fish inhabiting in Se-contaminated environments. However, its effect on fish behavior and the underlying mechanisms remain largely unknown. In this study, two-month-old zebrafish (Danio rerio) was fed seleno-l-methionine (Se-Met) at environmentally relevant concentrations (i.e., control (2.61), low (5.43), medium (12.16), and high (34.61) µg Se/g dry weight (dw), respectively, corresponding to the C, L, M, and H treatments) for 60 days. Targeted metabolomics, histopathological, and targeted transcriptional endpoints were compared to behavioral metrics to evaluate the effects of dietary exposure to Se-Met . The results showed that the levels of total Se and malondialdehyde in fish brains were increased in a dose-dependent pattern. Meanwhile, mitochondrial damages and decreased activities of the mitochondria respiratory chain complexes were observed in the neurons at the M and H treatments. In addition, dietary Se-Met affected neurotransmitters, metabolites, and transcripts of the genes associated with the dopamine, serotonin, gamma-aminobutyric acid, acetylcholine, and histamine signaling pathways in zebrafish brains at the H treatments. The total swimming distance and duration in the Novel Arm were lowered in fish from the H treatment. This study has demonstrated that dietary Se-Met affects the ultrastructure of the zebrafish brain, neurotransmitters, and associated fish behaviors and may help enhance adverse outcome pathways for neurotransmitter-behavior key events in zebrafish.


Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Antioxidantes , Encéfalo , Neurotransmissores , Selenometionina
2.
Biomed Pharmacother ; 143: 112101, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34474340

RESUMO

Chronic obstructive pulmonary disease (COPD) is among the leading causes of death worldwide, and is characterized by persistent respiratory symptoms and airflow limitation due to chronic airway inflammation. Cigarette smoking is a major risk factor for COPD. This study aims to determine the therapeutic effects of polysaccharides extracted from Dendrobium officinale (DOPs), a valuable traditional Chinese Medicinal herb, on cigarette smoke (CS)-induced airway inflammation in a rat passive smoking model. Male Sprague-Dawley rats were exposed to CS or sham air (SA) as control for a 56-day period. On Day 29, rats were subdivided and given water, DOPs or N-acetylcysteine (NAC) via oral gavage on a daily basis for the remaining duration. DOPs reduced CS-induced oxidative stress as evidenced by reducing malondialdehyde (MDA) levels in the lung. DOPs also exerted potent anti-inflammatory properties as evidenced by a reduction in the number of lymphocytes and monocytes in serum, significantly attenuating infiltration of inflammatory cells in lung tissue, as well as pro-inflammatory mediators in serum, bronchoalveolar lavage (BAL) and lung. Additionally, DOPs inhibited the CS-induced activation of ERK, p38 MAPK and NF-κB signaling pathways. These findings suggest that DOPs may have potentially beneficial effects in limiting smoking-related lung oxidative stress, and inflammation mediated via the inhibition of MAPK and NF-κB signaling pathways in smokers, without or with COPD.

3.
Glycoconj J ; 38(5): 573-583, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34515910

RESUMO

To explore effect of the structural properties of porphyra haitanensis polysaccharide on its biological activity, degraded porphyra polysaccharides were separated and purified by Cellulose DEAE-52 and Sephadex G-100 chromatography, obtaining three purified components (P1, P2 and P3). All the three components were sulfate polysaccharides containing the repeating units of → 3) ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →, and → 3) ß-D-galactose (1 → 4) α-L-galactose-6-S (1 →, and → 3) 6-O-methyl-ß-D-galactose (1 → 4) 3,6-anhydro-α-L-galactose (1 →. The molecular weight of the three fractions was measured to be 300.3, 130.4 and 115.1 kDa, respectively. Their antioxidant activity was investigated by the determination of the free radical scavenging effect and ferric reducing power. It was found that P1, P2 and P3 possessed marked antioxidant activity. It was also found that they appreciably enhanced the proliferation, phagocytic ability and nitric oxide secretion in RAW264.7 cells. Lower molecular weight and higher sulfate content were beneficial to bioactivities of P. haitanensis polysaccharides. Overall, P2 and P3 possess superior immuno-modulatory activity to that of P1 and PHP. Thus, the current work will provide the basis for the better utilization of P. haitanensis to develop the related functional foods.

4.
Water Res ; 204: 117602, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481283

RESUMO

Selenate and sulfide are both contaminants which severely pollute water bodies. Respective bioremediation of selenate- and sulfide-contaminated wastewaters requires abundant electron donors and acceptors. Here, we present a novel concept coupling biological selenate to selenite (shortcut deselenization) and chemical sulfide-driven selenite reduction, to remove multiple pollutants simultaneously. Vial tests showed that shortcut deselenization could save at least two thirds of operation time and one third of carbon source, compared to the complete deselenization to elemental selenium. Subsequent co-removal of sulfide and selenite was optimized at reaction pH of ∼10 and reactant molar ratio of ∼4. Using a newly-designed continuous flow system, >95% removal of both selenate and sulfide was achieved by coupling shortcut deselenization to sulfide oxidation. A series of characterization tools revealed that the final collected precipitates were comprised of high-purity hexagonal selenium (97.4%, wt) and inconsiderable sulfur (2.6%, wt). Superior over selenate-reducing solutions generally producing selenium mixed with reagents or microorganisms, the selenium products generated here were highly purified thus very favorable for further recovery and reuse. Overall, this proof-of-concept study provided a promising technology not only for co-removal of multiple pollutants, but also for substantial costs saving, as well as for valuable products recovery.


Assuntos
Poluentes Ambientais , Compostos de Selênio , Selênio , Ácido Selênico , Ácido Selenioso , Sulfetos , Águas Residuárias
5.
J Inorg Biochem ; 224: 111591, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34450410

RESUMO

Alzheimer's disease (AD) is known as a complex multifactorial syndrome and both metal chelators and amyloid ß peptide (Aß) inhibitors show promise against AD. Herein, four small hybrid compounds have been designed and synthesized utilizing 8-hydroxyquinoline, pyridine or imidazole as chelators and benzimidazole as the recognition moiety for AD treatment. These conjugates can capture Cu2+ from Aß and become dimers upon Cu2+ coordination and show high efficiency for both Cu2+ elimination and Aß assembly inhibition. Besides, these designed complexes can inhibit the production of Aß-induced reactive oxygen species (ROS), protect mitochondria from damage, and improve the survival rate of neuron cells. Our work provides a new strategy to combine hydrophobic interaction and metal ion chelation to design amyloid inhibitors.

6.
Stem Cell Res Ther ; 12(1): 477, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446107

RESUMO

BACKGROUND: Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode. METHODS: Flow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients. RESULTS: The in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1ß-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events. CONCLUSION: In sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.

7.
J Infect Public Health ; 14(9): 1169-1173, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34391173

RESUMO

BACKGROUND: Tenofovir disoproxil fumarate has been recommended for pre-exposure prophylaxis (PrEP) to prevent HIV infection. Several studies have shown short but potent intermittent PrEP could provide comparable protection to daily PrEP in men, suggesting such dosing strategy might be useful in Chinese as well. The objective of this study was to evaluate the impact of different dosing strategies on plasma concentrations of tenofovir. METHODS: An open label study in 40 Chinese healthy volunteers, randomized to receive the WHO-recommended dose of tenofovir (300mg) at four different dosing intervals: twice weekly for 4 weeks; once daily for 4 weeks with one missing dose in weeks 2-4; once daily for 4 weeks with two missing doses in weeks 2-4; and once every other day for 12 days. Plasma samples were collected at pre-dose, weekly trough and 24h post last dose and assayed using HPLC-UV. RESULTS: The tenofovir trough concentrations were below the lower limit of quantification with the twice weekly regimen. The trough concentrations (24h dosing interval) at the steady state were 51.7±12.1ng/ml and 53.5±13.8ng/ml (mean±SD) in the once daily groups. Missing doses, once or twice weekly, had no significant impact on trough concentrations. Prolongation of dosing interval to 48h resulted with concentrations at 24h and 48h (trough) of ∼40 and 20ng/ml, respectively. CONCLUSIONS: Intermittent tenofovir regimens resulted with remarkably low plasma concentrations in Chinese participants. Missing doses did not affect trough concentrations significantly.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Fármacos Anti-HIV/uso terapêutico , China , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Humanos , Masculino , Tenofovir/uso terapêutico
8.
Scand J Gastroenterol ; : 1-11, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34392745

RESUMO

Inflammatory bowel disease (IBD) is a life-threatening and chronic inflammatory disease of gastrointestinal tissue, with complex pathogenesis. Current research on IBD has mainly focused on bacteria; however, the role of fungi in IBD is largely unknown due to the incomplete annotation of fungi in current genomic databases. With the development of molecular techniques, the gut mycobiome has been found to have great diversity. In addition, increasing evidence has shown intestinal mycobiome plays an important role in the physiological and pathological processes of IBD. In this review, we will systemically introduce the recent knowledge about multi-dimensional fungal dysbiosis associated with IBD, the interactions between fungus and bacteria, the role of fungi in inflammation in IBD, and highlight recent advances in the potential therapeutic role of fungus in IBD, which may hold the keys to develop new predictive, therapeutic or prognostic approaches in IBD.

9.
Ann Palliat Med ; 10(7): 7706-7720, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353059

RESUMO

BACKGROUND: Osteoarthritis (OA) is a chronic joint disease characterized by cartilage destruction and periarticular osteophyte formation. One therapeutic option for this condition, the Wutou Decoction (WTD) Chinese medicine formula, is satisfactory in its efficacy. Here, we used bioinformatic and molecular docking techniques to investigate the mechanism of action of WTD in the treatment of OA. METHODS: The active compounds (and their target proteins) of 5 Chinese herbs in WTD were obtained by searching the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The action targets of WTD for OA were obtained by searching the Therapeutic Target Database and by mining the microarray data in the Gene Expression Omnibus. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed to identify key targets for OA treatment with the help of Database for Annotation, Visualization, and Integrated Discovery. Based on the Cytoscape software version 3.6.1, the visual networks of the "TCM drugs-Active Compounds-Targets-Diseases" and protein-protein interaction of the key targets of WTD for the treatment of OA were constructed. The core active compounds and the key targets obtained were molecularly docked and validated. RESULTS: Analyses revealed 140 active compounds in WTD, 123 of which had a total of 163 corresponding targets. In addition, 331 differentially expressed genes and 227 OA-related targets were obtained. The interaction networks among 32 key targets were identified. The biological processes of WTD in treating OA mainly involved regulation of inflammatory factors, transcription of genetic materials, cell cycle, angiogenesis, and endocrine regulation. The signaling pathways involved mainly included TNF signaling pathway, rheumatoid arthritis signaling pathway, cancer-related signals, vascular endothelial growth factor signaling pathway, and osteoclast differentiation signaling pathways. Molecular docking showed that 7 core compounds including quercetin and kaempferol had strong affinities with key target proteins for the WTD treatment of OA. CONCLUSIONS: WTD with multi-component can treats OA through multi-pathway. Its active compounds, including quercetin and kaempferol, can exert their therapeutic effects on OA by acting on TNF, PTGS2, MMP2, IL-6, IL-1ß, and other key targets to regulate inflammation, immunity, autophagy, and endocrine-related signaling pathways.


Assuntos
Medicamentos de Ervas Chinesas , Osteoartrite , Biologia Computacional , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Fator A de Crescimento do Endotélio Vascular
10.
Ann Palliat Med ; 10(7): 8024-8033, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34353087

RESUMO

BACKGROUND: Health-related quality of life (HRQOL) has become an important part of the evaluation of clinical efficacy and prognosis in gastric cancer. This study aimed to assess the HRQOL of patients with gastric cancer using the a five-level EuroQol five-dimensional questionnaire (EQ-5D-5L) and explore the factors influencing patients' perceived quality of life. For those significant factors, we can take appropriate measures to intervene to extend patient survival and improve the quality of life. METHODS: A cross-sectional questionnaire survey was administered to 243 patients with gastric cancer in the First Affiliated Hospital of Suzhou University from December 2018 to December 2020. HRQOL was measured by the Chinese version of the EQ-5D-5L. Nonparametric test analyses and a Tobit regression model were used to identify the independent variables associated with the EQ-5D-5L utility scores. RESULTS: In this research, the mean score was 0.810, and the median was 0.893. Approximately 25% of patients reported no problems at all in any of the five dimensions. Problems in pain and discomfort were the most frequently reported (64.2%). Nonparametric test analyses showed that patients who did not have health insurance, or who had a history of alcohol use, a family history of cancer, had received surgery only, or had an interval of less than 1 week between taking this survey and their last treatment, demonstrated lower EQ-5D-5L scores. The Tobit regression model confirmed that health insurance, family history, and treatment were significantly associated with EQ-5D-5L scores. CONCLUSIONS: The HRQOL of gastric cancer patients can be measured by EQ-5D-5L, and the results may provide a guide for choosing an appropriate individualized treatment plan.


Assuntos
Qualidade de Vida , Neoplasias Gástricas , China , Estudos Transversais , Nível de Saúde , Humanos , Inquéritos e Questionários
11.
Nucleic Acids Res ; 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34417598

RESUMO

DNA methylation is widespread amongst eukaryotes and prokaryotes to modulate gene expression and confer viral resistance. 5-Methylcytosine (m5C) methylation has been described in genomes of a large fraction of bacterial species as part of restriction-modification systems, each composed of a methyltransferase and cognate restriction enzyme. Methylases are site-specific and target sequences vary across organisms. High-throughput methods, such as bisulfite-sequencing can identify m5C at base resolution but require specialized library preparations and single molecule, real-time (SMRT) sequencing usually misses m5C. Here, we present a new method called RIMS-seq (rapid identification of methylase specificity) to simultaneously sequence bacterial genomes and determine m5C methylase specificities using a simple experimental protocol that closely resembles the DNA-seq protocol for Illumina. Importantly, the resulting sequencing quality is identical to DNA-seq, enabling RIMS-seq to substitute standard sequencing of bacterial genomes. Applied to bacteria and synthetic mixed communities, RIMS-seq reveals new methylase specificities, supporting routine study of m5C methylation while sequencing new genomes.

12.
Environ Pollut ; 289: 117944, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34391046

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) can affect the male reproductive system in vertebrates, but the underlying molecular mechanism is still elusive. Therefore, in this study, we aimed to dig the in-depth mechanism of DEHP-induced reproductive toxicity on male zebrafish via testicular transcriptome using embryo exposed at the environmentally relevant concentration (ERC) of 100 µg/L for 111 days. Moreover, our results were further confirmed via in silico technique and bioassay experimental in vitro (cell lines) and in vivo (zebrafish). The results showed DEHP exposure could affect male spermatogenesis, altered gonad histology, and reduced egg fertilization rate. Transcriptome analysis identified 1879 significant differentially expressed genes enriched in the exposure group. Twenty-seven genes related to three pathways of reproduction behavior were further validated by qPCR. In silico molecular docking revealed that DEHP and its metabolism bind to the zebrafish progesterone receptor (Pgr), suggesting the potential disruption of DEHP to the normal Pgr signaling. To further validate it, a wild-type Pgr plasmid and its mutants on specific binding sites were constructed. The transfection and microinjection experiment demonstrated that these binding sites mutations of Pgr affected the expression levels of male reproductive toxicity. Taken together, our study provided new insight into the molecular mechanisms of male reproductive toxicity induced by DEHP, and Pgr may serve as an important target binding by DEHP pollution, which needs further study in the future.


Assuntos
Dietilexilftalato , Animais , Dietilexilftalato/toxicidade , Masculino , Simulação de Acoplamento Molecular , Reprodução , Transcriptoma , Peixe-Zebra/genética
13.
J Chromatogr A ; 1654: 462474, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34438300

RESUMO

The current study presents a convenient, rapid and effective simultaneous extraction/derivatization (SEDP) strategy for effective pretreatment of catecholamines (CAs). Commercial zirconium oxide (ZrO2) nanoparticles were employed for the selective capturing of cis-diol containing CAs to remove the biological interferences and phenyl isothiocyanate (PITC) was used for derivatization to improve the ionization and to improve the chromatographic separation. The extraction and derivatization procedures were integrated into one step to simplify the sample pretreatment. Excessive derivatization reagents were removed as well, reducing the degree of contaminations in mass spectrometry. The factors affecting the SEDP process were optimized and the results showed that the detection sensitivity and chromatographic separation of CAs greatly improved compared with underivatized CAs, during LC-MS/MS analysis. Combined with ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), quantifying the concentration of norepinephrine (NE), epinephrine (E) and dopamine (DA) in biological fluids was validated in ranges of 1-200.0 ng/mL with a satisfactory correlation coefficient (R2 > 0.997). The obtained recoveries were in the range of 91.0-109.5% with RSDs less than 9.4%. Finally, significant changes in CAs levels in urine samples of healthy people and pheochromocytoma patients were detected. The developed method offers comparative advantages in terms of sensitivity, specificity and selectivity.


Assuntos
Neoplasias das Glândulas Suprarrenais , Catecolaminas , Cromatografia Líquida , Feocromocitoma , Espectrometria de Massas em Tandem , Urinálise , Catecolaminas/análise , Catecolaminas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Humanos , Feocromocitoma/urina , Sensibilidade e Especificidade , Extração em Fase Sólida , Urinálise/métodos
14.
Mol Biotechnol ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34435325

RESUMO

The prognosis of metastasis gastric cancer patients remains poor and the identification of novel molecular markers will improve the management of gastric cancer patients. The present study aimed to investigate the clinical significance and functional role of miR-466 in gastric cancer peritoneal metastasis. miR-466 expression was confirmed by RT-qPCR. The biological functions were examined by MTT assay, Transwell migration, and invasion assays. The Kaplan-Meier survival curve and multivariate Cox regression analysis were used to investigate the clinical role of miR-466. The logistic regression analysis was performed to reveal the risk factors associated with peritoneal metastasis. miR-466 expression was downregulated in gastric cancer cell lines, tumor tissues, and peritoneal metastasis tissues compared with respective controls. Increased miR-466 expression inhibited proliferation, migration, and invasion of gastric cancer cells. Besides, the lower expression of miR-466 in gastric cancer patients was associated with peritoneal dissemination. Furthermore, multivariate Cox proportional hazard regression analyses demonstrated miR-466 expression level as an independent predictor of prognosis of gastric cancer. The present study provides novel evidence for the clinical and biological significance of miR-466 expression as a possible biomarker for the prognosis and identifying patients with peritoneal metastasis, as well as a potential therapeutic target in patients with gastric cancer.

16.
BMC Genomics ; 22(1): 571, 2021 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-34303345

RESUMO

BACKGROUND: Impatiens L. is a genus of complex taxonomy that belongs to the family Balsaminaceae (Ericales) and contains approximately 1000 species. The genus is well known for its economic, medicinal, ornamental, and horticultural value. However, knowledge about its germplasm identification, molecular phylogeny, and chloroplast genomics is limited, and taxonomic uncertainties still exist due to overlapping morphological features and insufficient genomic resources. RESULTS: We sequenced the chloroplast genomes of six different species (Impatiens chlorosepala, Impatiens fanjingshanica, Impatiens guizhouensis, Impatiens linearisepala, Impatiens loulanensis, and Impatiens stenosepala) in the karst area of China and compared them with those of six previously published Balsaminaceae species. We contrasted genomic features and repeat sequences, assessed sequence divergence and constructed phylogenetic relationships. Except for those of I. alpicola, I. pritzelii and I. glandulifera, the complete chloroplast genomes ranging in size from 151,366 bp (I. alpicola) to 154,189 bp (Hydrocera triflora) encoded 115 distinct genes [81 protein-coding, 30 transfer RNA (tRNA), and 4 ribosomal RNA (rRNA) genes]. Moreover, the characteristics of the long repeat sequences and simple sequence repeats (SSRs) were determined. psbK-psbI, trnT-GGU-psbD, rpl36-rps8, rpoB-trnC-GCA, trnK-UUU-rps16, trnQ-UUG, trnP-UGG-psaJ, trnT-UGU-trnL-UAA, and ycf4-cemA were identified as divergence hotspot regions and thus might be suitable for species identification and phylogenetic studies. Additionally, the phylogenetic relationships based on Maximum likelihood (ML) and Bayesian inference (BI) of the whole chloroplast genomes showed that the chloroplast genome structure of I. guizhouensis represents the ancestral state of the Balsaminaceae family. CONCLUSION: Our study provided detailed information about nucleotide diversity hotspots and the types of repeats, which can be used to develop molecular markers applicable to Balsaminaceae species. We also reconstructed and analyzed the relationships of some Impatiens species and assessed their taxonomic statuses based on the complete chloroplast genomes. Together, the findings of the current study might provide valuable genomic resources for systematic evolution of the Balsaminaceae species.


Assuntos
Balsaminaceae , Genoma de Cloroplastos , Impatiens , Balsaminaceae/genética , Teorema de Bayes , China , Cloroplastos/genética , Evolução Molecular , Genômica , Impatiens/genética , Filogenia
17.
Org Lett ; 23(15): 5611-5615, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34240601

RESUMO

An efficient cascade reaction of 1-indanylidenemalononitrile with 3-benzylidenebenzofuran-2(3H)-one divergently promoted by DABCO or chiral organocatalyst was developed under mild reaction conditions, and various spiro-dihydrofluorene-benzofuranones were produced in gratifying results, respectively. It is worth noting that both the spiro and axially chiral products can be obtained by tuning the reaction conditions. The mechanism of the transformation was also studied by quantum chemical calculations.

18.
BMC Cardiovasc Disord ; 21(1): 321, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34193080

RESUMO

BACKGROUND: Congenital heart disease (CHD) is the leading cause of mortality from birth defects. In adult CHD patients with successful surgical repair, cardiac complications including heart failure develop at late stage, likely due to genetic causes. To date, many mutations in cardiac developmental genes have been associated with CHD. Recently, regulatory variants in genes have been linked to many human diseases. Although mutations and splicing variants in GATA4 gene have been reported in CHD patients, few regulatory variants of GATA4 gene are identified in CHD patients. METHODS: GATA4 gene regulatory region was investigated in the patients with atrial septal defects (ASD) (n = 332) and ethnic-matched controls (n = 336). RESULTS: Five heterozygous regulatory variants including four SNPs [g.31360 T>C (rs372004083), g.31436G>A, g.31437C>A (rs769262495), g.31487C>G (rs1053351749) and g.31856C>T (rs1385460518)] were only identified in ASD patients. Functional analysis indicated that the regulatory variants significantly affected the transcriptional activity of GATA4 gene promoter. Furthermore, two of the five regulatory variants have evidently effected on transcription factor binding sites. CONCLUSIONS: Our data suggested that GATA4 gene regulatory variants may confer ASD susceptibility by decreasing GATA4 levels.


Assuntos
Fator de Transcrição GATA4/genética , Comunicação Interatrial/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Animais , Sítios de Ligação , Estudos de Casos e Controles , Linhagem Celular , Criança , Pré-Escolar , Regulação para Baixo , Feminino , Fator de Transcrição GATA4/metabolismo , Predisposição Genética para Doença , Comunicação Interatrial/diagnóstico por imagem , Comunicação Interatrial/metabolismo , Heterozigoto , Humanos , Lactente , Masculino , Miócitos Cardíacos/metabolismo , Fenótipo , Regiões Promotoras Genéticas , Ratos , Transcrição Genética , Adulto Jovem
19.
J Am Chem Soc ; 143(26): 9912-9921, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34160199

RESUMO

A copper(I)-catalyzed asymmetric alkylation of HPAr1Ar2 with alkyl halides is uncovered, which provides an array of P-stereogenic phosphines in generally high yield and enantioselectivity. The electrophilic alkyl halides enjoy a broad substrate scope, including allyl bromides, propargyl bromide, benzyl bromides, and alkyl iodides. Moreover, 11 unsymmetrical diarylphosphines (HPAr1Ar2) serve as competent pronucleophiles. The present methodology is also successfully applied to catalytic asymmetric double and triple alkylation, and the corresponding products were obtained in moderate diastereo- and excellent enantioselectivities. Some 31P NMR experiments indicate that bulky HPPhMes exhibits weak competitively coordinating ability to the Cu(I)-bisphosphine complex, and thus the presence of stoichiometric HPAr1Ar2 does not affect the enantioselectivity significantly. Therefore, the high enantioselectivity in this reaction is attributed to the high performance of the unique Cu(I)-(R,RP)-TANIAPHOS complex in asymmetric induction. Finally, one monophosphine and two bisphosphines prepared by the present reaction are employed as efficient chiral ligands to afford three structurally diversified Cu(I) complexes, which demonstrates the synthetic utility of the present methodology.

20.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 37(7): 590-595, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34140069

RESUMO

Objective To prepare universal secondary antibodies those can bind to the IgG from mice and rabbits, and use the antibodies in a variety of immunoassays. Methods The fusion genes of staphylococcal protein A (SPA), streptococcal protein G (SPG), and horseradish peroxidase (HRP) were synthesized, and cloned into the vector pcDNATM3.1 to generate the eukaryotic expression plasmids. The plasmids were transiently transfected into HEK293F cells for expression. The fusion protein expressed in the plasmid was detected by SDS-PAGE and Western blotting, and its immunoactivity was measured by Western blotting, ELISA, and immunohistochemical staining. Results Restriction enzyme digestion and gene sequencing showed the pPA-HRP, pPG-HRP, and pPA/G-HRP plasmids were successfully created. Coomassie brilliant blue staining and Western blotting indicated that the fusion proteins PA-HRP, PG-HRP, and PA/G-HRP successfully expressed in HEK293F cells. Western blotting, ELISA, and immunohistochemical staining showed that IgGs derived from mice and rabbits could be recognized and bound by the three kinds of fusion protein, of which the fusion protein PA/G-HRP exhibited the highest affinity. Conclusion The fusion protein PA/G-HRP with high and universal IgG affinity is successfully prepared. The PA/G-HRP can replace traditional secondary antibodies against mouse and rabbit IgG in a variety of immunological assays.


Assuntos
Eucariotos , Proteína Estafilocócica A , Animais , Ensaio de Imunoadsorção Enzimática , Peroxidase do Rábano Silvestre , Imunoglobulina G , Camundongos , Coelhos
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