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1.
J Hepatol ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759889

RESUMO

BACKGROUND & AIMS: The liver is the main organ of ketogenesis, while ketones are mainly metabolized in peripheral tissues via the critical enzyme 3-oxoacid CoA-transferase 1 (OXCT1). We previously found that ketolysis is reactivated in hepatocellular carcinoma (HCC) cells through OXCT1 expression to promote tumor progression; however, whether OXCT1 regulates antitumor immunity remains unclear. METHODS: To investigate the expression pattern of OXCT1 in HCC in vivo, we conducted multiplex immunohistochemistry experiments on human HCC specimens. To explore the role of OXCT1 in mouse HCC tumor-associated macrophages (TAMs), we generated LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice. RESULTS: Here, we found that inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis. Initially, we found that OXCT1 was highly expressed in liver macrophages under steady state and that OXCT expression was further increased in TAMs. OXCT1 deficiency in macrophages suppressed tumor growth by reprogramming TAMs toward an antitumor phenotype, reducing CD8+ T-cell exhaustion and increasing CD8+ T-cell cytotoxicity. Mechanistically, high OXCT1 expression induced the accumulation of succinate, a byproduct of ketolysis, in TAMs, which promoted Arg1 transcription by increasing the H3K4me3 level in the Arg1 promoter. In addition, pimozide, an inhibitor of OXCT1, suppressed Arg1 expression as well as TAM polarization toward the protumor phenotype, leading to decreased CD8+ T-cell exhaustion and slower tumor growth. Finally, high expression of OXCT1 in macrophages was positively associated with poor survival in patients with HCC. CONCLUSIONS: In conclusion, our results demonstrate that OXCT1 epigenetically suppresses antitumor immunity, suggesting that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer. IMPACT AND IMPLICATIONS: The intricate metabolism of liver macrophages plays a critical role in shaping hepatocellular carcinoma progression and immune modulation. Targeting macrophage metabolism to counteract immune suppression presents a promising avenue for hepatocellular carcinoma treatment. Herein, we found that the ketogenesis gene OXCT1 was highly expressed in tumor-associated macrophages (TAMs) and promoted tumor growth by reprogramming TAMs toward a protumor phenotype. Pharmacological targeting or genetic downregulation of OXCT1 in TAMs enhances antitumor immunity and slows tumor growth. Our results suggest that suppressing OXCT1 activity in TAMs could be an effective approach for treating liver cancer.

2.
Pestic Biochem Physiol ; 188: 105228, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36464348

RESUMO

A new series of cyclopropane-1,1-dicarboxylic (CPD) acid analogues were designed and synthesized. CPD is an inhibitor of ketol-acid reductoisomerase (KARI), an enzyme of the branched chain amino acid pathway in plants. The structures of CPD analogues were characterized by 1H NMR and HRMS. The structure of N,N'-bis(4-(tert-butyl)phenyl)cyclopropane-1,1-dicarboxamide was further elucidated by X-ray diffraction. The herbicidal activities of these compounds were tested against lettuce (Lactuca sativa) and bentgrass (Agrostis stolonifera). Most of these compounds exhibited low herbicidal activity against both plant species. Among them, N,N'-bis(2-ethylphenyl)cyclopropane-1,1-dicarboxamide displayed moderate activity against bentgrass. Inhibition of KARI activity by the CPD analogues was also assessed experimentally and by molecular docking simulation with results supporting inhibition of KARI as their mode of action. These results provide the basis for design of more effective KARI inhibitors.


Assuntos
Herbicidas , Herbicidas/farmacologia , Simulação de Acoplamento Molecular , Ácidos Dicarboxílicos/farmacologia , Ciclopropanos/farmacologia
3.
Molecules ; 27(10)2022 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-35630795

RESUMO

Sulfonylurea herbicides can lead to serious weed resistance due to their long degradation times and large-scale applications. This is especially true for chlorsulfuron, a widely used acetolactate synthase inhibitor used around the world. Its persistence in soil often affects the growth of crop seedlings in the following crop rotation, and leads to serious environmental pollution all over the world. Our research goal is to obtain chlorsulfuron-derived herbicides with high herbicidal activities, fast degradation times, as well as good crop safety. On account of the slow natural degradation of chlorsulfuron in alkaline soil, based on the previously reported results in acidic soil, the degradation behaviours of 5-substituted chlorsulfuron analogues (L101-L107) were investigated in a soil with pH 8.39. The experimental data indicated that 5-substituted chlorsulfuron compounds could accelerate degradation rates in alkaline soil, and thus, highlighted the potential for rational controllable degradation in soil. The degradation rates of these chlorsulfuron derivatives were accelerated by 1.84-77.22-fold, compared to chlorsulfuron, and exhibited excellent crop safety in wheat and corn (through pre-emergence treatment). In combination with bioassay activities, acidic and alkaline soil degradation, and crop safety, it was concluded that compounds L104 and L107, with ethyl or methyl groups, are potential green sulfonylurea herbicides for pre-emergence treatment on wheat and corn. This paper provides a reference for the further design of new sulfonylurea herbicides with high herbicidal activity, fast, controllable degradation rates, and high crop safety.


Assuntos
Herbicidas , Solo , Herbicidas/química , Sulfonamidas/farmacologia , Compostos de Sulfonilureia/química , Compostos de Sulfonilureia/farmacologia , Triazinas/química
4.
Molecules ; 27(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35208944

RESUMO

In this study, a high-performance thin layer chromatography (HPTLC) method by two step gradient elution with two mobile phases was developed for the simultaneous analysis of seven constituents in Ophiopogonis Radix. The chromatography was performed on silica gel 60 F254 plate with dichloromethane-methanol-ethyl acetate-water (70:25:12:3, v/v/v/v) and dichloromethane-methanol (300:1, v/v) as the mobile phase for two step gradient elution. Then, the HPTLC profiles were observed after derivatization with 10% sulfuric acid in ethanol solution. The obtained HPTLC images were further analyzed by chemometric approaches and the samples could be clustered based on regions and/or growth years, which were two important factors affecting the constituents in Ophiopogonis Radix. Furthermore, five compounds including ophiopogonin D, ophiopojaponin C, ophiopogonin D', ophiopogonin C' and methylophiopogonanone B were screened as potential lipase inhibitors from Ophiopogonis Radix by the HPTLC-bioautographic method. The binding modes and interactions between the five compounds and lipase were further explored by molecular docking analysis. The developed HPTLC method could be used for quality control of Ophiopogonis Radix and screening of the potential lipase inhibitors.


Assuntos
Inibidores Enzimáticos , Lipase , Simulação de Acoplamento Molecular , Ophiopogon/química , Animais , Cromatografia em Camada Fina , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Lipase/antagonistas & inibidores , Lipase/química , Suínos
5.
J Cell Physiol ; 236(6): 4555-4564, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33241567

RESUMO

Selenium (Se) is an essential trace element in organism. Se deficiency can cause many diseases, including vascular disease. Studies have shown that inflammation is the main inducement of vascular disease, microRNA (miRNA) can influence inflammation in various ways, and Se deficiency can affect miRNAs expression. To study the mechanism of aorta damage caused by Se deficiency, we constructed a Se deficiency porcine aorta model and found that Se deficiency can significantly inhibit miR-223, which downregulates the expression of nucleotide-binding oligomerization domain-like receptor family 3 (NLRP3). Subsequently, we found that in Se deficiency group, NLRP3, and its downstream (caspase-1, apoptosis-related spot-like protein [ASC], IL-18, IL-1ß) expression was significantly increased. In vitro, we cultured pig iliac endothelium cell lines, and constructed miR-223 knockdown and overexpression models. NLRP3 messenger RNA and protein levels were significant increased in the knockdown group, and decreased in the overexpression group. The results of this study show that Se deficiency in porcine arteries can induce inflammation through miR-223/NLRP3.


Assuntos
Aorta/metabolismo , Aortite/metabolismo , Células Endoteliais/metabolismo , Inflamassomos/metabolismo , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Selênio/deficiência , Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Animais , Aorta/imunologia , Aorta/patologia , Aortite/genética , Aortite/imunologia , Aortite/patologia , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Caspase 1/genética , Caspase 1/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Células Endoteliais/imunologia , Células Endoteliais/patologia , Inflamassomos/genética , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transdução de Sinais , Sus scrofa
6.
Ecotoxicol Environ Saf ; 209: 111819, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33360786

RESUMO

Cadmium (Cd) is a toxic trace element that can enter the environment with industrial waste and accumulate in the body but the health effects of Cd on ternary pigs are still lacking in research. In order to explore the effect of Cd on the apoptosis of pig spleen and its mechanism, this study chose ternary pig as the research object to detect relevant indicators in pig spleen under Cd exposure. The results of this study showed that Cd exposure can induce apoptosis by promoting the absorption of various toxic trace elements in the spleen and inducing oxidative stress. We also found that the mechanism of Cd-induced apoptosis is closely related to the VDR/CREB1 pathway. On the one hand, Cd exposure can activate VDR, and indirectly regulate the CYP family, affecting the normal function of the spleen. On the other hand, VDR and its downstream genes antagonize the toxicity of Cd by maintaining the stability of the mitochondrial-related endoplasmic reticulum membrane structure. Our research will help researchers to further understand the physiological toxicity of Cd.


Assuntos
Apoptose/fisiologia , Cádmio/toxicidade , Substâncias Perigosas/toxicidade , Baço/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Suínos
7.
Plant Biotechnol J ; 17(7): 1446-1457, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30623555

RESUMO

In Arabidopsis, the initiation and proliferation of stomatal lineage cells is controlled by SPEECHLESS (SPCH). Phosphorylation of SPCH at the post-translational level has been reported to regulate stomatal development. Here we report that IDD16 acts as a negative regulator for stomatal initiation by directly regulating SPCH transcription. In Arabidopsis, IDD16 overexpression decreased abaxial stomatal density in a dose-dependent manner. Time course analysis revealed that the initiation of stomatal precursor cells in the IDD16-OE plants was severely inhibited. Consistent with these findings, the transcription of SPCH was greatly repressed in the IDD16-OE plants. In contrast, IDD16-RNAi transgenic line resulted in enhanced stomatal density, suggesting that IDD16 is an intrinsic regulator of stomatal development. ChIP analysis indicated that IDD16 could directly bind to the SPCH promoter. Furthermore, Arabidopsis plants overexpressing IDD16 exhibited significantly increased drought tolerance and higher integrated water use efficiency (WUE) due to reduction in leaf transpiration. Collectively, our results established that IDD16 negatively regulates stomatal initiation via trans-repression of SPCH, and thus provide a practical tool for increasing plant WUE through the manipulation of IDD16 expression.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Regulação da Expressão Gênica de Plantas , Estômatos de Plantas/fisiologia , Arabidopsis/fisiologia , Secas
8.
J Neurovirol ; 25(3): 342-353, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30767174

RESUMO

Growing evidence points to persistent neurological injury in chronic HIV infection. It remains unclear whether chronically HIV-infected individuals on combined antiretroviral therapy (cART) develop progressive brain injury and impaired neurocognitive function despite successful viral suppression and immunological restoration. In a longitudinal neuroimaging study for the HIV Neuroimaging Consortium (HIVNC), we used tensor-based morphometry to map the annual rate of change of regional brain volumes (mean time interval 1.0 ± 0.5 yrs), in 155 chronically infected and treated HIV+ participants (mean age 48.0 ± 8.9 years; 83.9% male) . We tested for associations between rates of brain tissue loss and clinical measures of infection severity (nadir or baseline CD4+ cell count and baseline HIV plasma RNA concentration), HIV duration, cART CNS penetration-effectiveness scores, age, as well as change in AIDS Dementia Complex stage. We found significant brain tissue loss across HIV+ participants, including those neuro-asymptomatic with undetectable viral loads, largely localized to subcortical regions. Measures of disease severity, age, and neurocognitive decline were associated with greater atrophy. Chronically HIV-infected and treated individuals may undergo progressive brain tissue loss despite stable and effective cART, which may contribute to neurocognitive decline. Understanding neurological complications of chronic infection and identifying factors associated with atrophy may help inform strategies to maintain brain health in people living with HIV.


Assuntos
Encéfalo/patologia , Infecções por HIV/patologia , Adulto , Antirretrovirais/uso terapêutico , Atrofia/patologia , Atrofia/virologia , Imagem de Tensor de Difusão , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
9.
Proc Natl Acad Sci U S A ; 113(51): E8335-E8343, 2016 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-27930298

RESUMO

To cope with environmental stresses, plants often adopt a memory response upon primary stress exposure to facilitate a quicker and stronger reaction to recurring stresses. However, it remains unknown whether light is involved in the manifestation of stress memory. Proline accumulation is a striking metabolic adaptation of higher plants during various environmental stresses. Here we show that salinity-induced proline accumulation is memorable and HY5-dependent light signaling is required for such a memory response. Primary salt stress induced the expression of Δ1-pyrroline-5-carboxylate synthetase 1 (P5CS1), encoding a proline biosynthetic enzyme and proline accumulation, which were reduced to basal level during the recovery stage. Reoccurring salt stress-induced stronger P5CS1 expression and proline accumulation were dependent upon light exposure during the recovery stage. Further studies demonstrated that salt-induced transcriptional memory of P5CS1 is associated with the retention of increased H3K4me3 level at P5CS1 during the recovery stage. HY5 binds directly to light-responsive element, C/A-box, in the P5CS1 promoter. Deletion of the C/A-box or hy5 hyh mutations caused rapid reduction of H3K4me3 level at P5CS1 during the recovery stage, resulting in impairment of the stress memory response. These results unveil a previously unrecognized mechanism whereby light regulates salt-induced transcriptional memory via the function of HY5 in maintaining H3K4me3 level at the memory gene.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/efeitos da radiação , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Glutamato-5-Semialdeído Desidrogenase/metabolismo , Luz , Complexos Multienzimáticos/metabolismo , Proteínas Nucleares/metabolismo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Sais/química , Estresse Fisiológico , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas , Glutamato-5-Semialdeído Desidrogenase/genética , Histonas/metabolismo , Complexos Multienzimáticos/genética , Mutação , Proteínas Nucleares/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Plantas Geneticamente Modificadas/efeitos dos fármacos , Plantas Geneticamente Modificadas/efeitos da radiação , Pirróis , Sementes/metabolismo , Transdução de Sinais , Transcrição Gênica , Técnicas do Sistema de Duplo-Híbrido
10.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(7): 690-695, 2019 Jul.
Artigo em Zh | MEDLINE | ID: mdl-31315770

RESUMO

OBJECTIVE: To study the clinical features of acute lymphoblastic leukemia (ALL) in children with IKAROS family zinc finger 1 (IKZF1) deletion, and to observe the effect of increasing the intensity of chemotherapy on the prognosis of this disease. METHODS: A total of 278 children diagnosed with ALL between December 2015 and February 2018 were systematically treated according to the Chinese Children's Leukemia Group-ALL 2008 protocol (CCLG-ALL 2008). The patients were divided into an IKZF1-deleted group and a control group according to the presence or absence of IKZF1. The IKZF1-deleted group was treated with the regimen for high-risk group (HR) in the CCLG-ALL 2008 protocol, while the control group received different intensities of chemotherapy according to clinical risk classification. The clinical features and event-free survival rate (EFS) were compared between the two groups. RESULTS: A total of 24 (8.6%) cases of 278 children were found to have large deletions of exons of the IKZF1 gene. The IKZF1-deleted group had significantly higher proportions of cases with white blood cell count ≥50×109/L at initial diagnosis, BCR-ABL1 fusion gene positive, minimal residual disease ≥10% on the 15th day of induction remission treatment, minimal residual disease-high risk and clinical risk classification-high risk compared with the control group (P<0.05). The 3-year EFS rate (76%±10%) in the IKZF1-deleted group was lower than that in the control group (84%±4%), but with no significant difference between the two groups (P=0.282). The estimated 3-year EFS rate in the IKZF1-deleted-non-HR group (actually treated with the chemotherapy regimen for HR in the CCLG-ALL 2008 protocol) was 82%±12%, which was lower than that in the control-non-HR group (86%±5%), but there was no significant difference (P=0.436). CONCLUSIONS: ALL children with IKZF1 deletion have worse early treatment response, and increasing the intensity of chemotherapy might improve the prognosis.


Assuntos
Fator de Transcrição Ikaros/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Intervalo Livre de Doença , Deleção de Genes , Humanos , Neoplasia Residual , Prognóstico
11.
Zhonghua Nan Ke Xue ; 24(4): 349-354, 2018 Apr.
Artigo em Zh | MEDLINE | ID: mdl-30168957

RESUMO

OBJECTIVE: To investigate the clinical effects of the combined therapy of Compound Xuanju Capsules (CXJC) and traditional Chinese medicinal formula on infertility in male smokers. METHODS: A total of 176 male infertility patients were divided into a smoking and a non-smoking group and the former further divided into mild, moderate and heavy smokers according to the daily consumption of cigarettes and the length of smoking history. The patients were treated with CXJC combined with traditional Chinese medicinal formula for 3 four-week courses and the therapeutic results were evaluated by comparing the indicators of the traditional Chinese medicine (TCM) syndrome, routine semen parameters, sperm morphology, and sperm DNA fragmentation index (DFI) among different groups before and after treatment. RESULTS: The baseline TCM syndrome scores were remarkably higher in the heavy smokers than in the non-smoking group (P < 0.05) but showed no statistically significant differences between the mild and moderate smokers (P > 0.05). The baseline percentage of sperm head defects and DFI were also markedly higher in the heavy and moderate smokers than in the non-smoking group (P < 0.05). Compared with the baseline, significant improvement was achieved after treatment in the TCM syndrome, routine semen parameters, sperm morphology and sperm DFI, especially in the heavy smokers in the percentages of grade a+b sperm (ï¼»17.12 ± 2.54ï¼½ vs ï¼»30.15 ± 3.10ï¼½%, P < 0.05), morphologically normal sperm (ï¼»15.54 ± 1.98ï¼½ vs ï¼»26.82 ± 3.52ï¼½%, P < 0.05), and head-defective sperm (ï¼»27.02 ± 2.14ï¼½ vs ï¼»22.07 ± 1.52ï¼½%, P < 0.05). CONCLUSIONS: Sperm quality is significantly decreased while the risk of infertility remarkably increased in moderate and heavy smokers. The combined therapy of CXJC and traditional Chinese medicinal formula can effectively improve semen quality, sperm morphology and sperm DFI in male smokers with infertility, though more evidence is to be collected from further studies.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Infertilidade Masculina/tratamento farmacológico , Fumantes , Povo Asiático , Cápsulas , Fragmentação do DNA , Quimioterapia Combinada , Humanos , Masculino , Medicina Tradicional Chinesa , não Fumantes , Sêmen , Análise do Sêmen , Cabeça do Espermatozoide , Espermatozoides
12.
Neuroimage ; 144(Pt A): 35-57, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27666385

RESUMO

We propose a generalized reduced rank latent factor regression model (GRRLF) for the analysis of tensor field responses and high dimensional covariates. The model is motivated by the need from imaging-genetic studies to identify genetic variants that are associated with brain imaging phenotypes, often in the form of high dimensional tensor fields. GRRLF identifies from the structure in the data the effective dimensionality of the data, and then jointly performs dimension reduction of the covariates, dynamic identification of latent factors, and nonparametric estimation of both covariate and latent response fields. After accounting for the latent and covariate effects, GRLLF performs a nonparametric test on the remaining factor of interest. GRRLF provides a better factorization of the signals compared with common solutions, and is less susceptible to overfitting because it exploits the effective dimensionality. The generality and the flexibility of GRRLF also allow various statistical models to be handled in a unified framework and solutions can be efficiently computed. Within the field of neuroimaging, it improves the sensitivity for weak signals and is a promising alternative to existing approaches. The operation of the framework is demonstrated with both synthetic datasets and a real-world neuroimaging example in which the effects of a set of genes on the structure of the brain at the voxel level were measured, and the results compared favorably with those from existing approaches.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/genética , Modelos Teóricos , Neuroimagem/métodos , Humanos
13.
Hum Brain Mapp ; 38(9): 4444-4458, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28580697

RESUMO

Structural brain changes that occur during development and ageing are related to mental health and general cognitive functioning. Individuals differ in the extent to which their brain volumes change over time, but whether these differences can be attributed to differences in their genotypes has not been widely studied. Here we estimate heritability (h2 ) of changes in global and subcortical brain volumes in five longitudinal twin cohorts from across the world and in different stages of the lifespan (N = 861). Heritability estimates of brain changes were significant and ranged from 16% (caudate) to 42% (cerebellar gray matter) for all global and most subcortical volumes (with the exception of thalamus and pallidum). Heritability estimates of change rates were generally higher in adults than in children suggesting an increasing influence of genetic factors explaining individual differences in brain structural changes with age. In children, environmental influences in part explained individual differences in developmental changes in brain structure. Multivariate genetic modeling showed that genetic influences of change rates and baseline volume significantly overlapped for many structures. The genetic influences explaining individual differences in the change rate for cerebellum, cerebellar gray matter and lateral ventricles were independent of the genetic influences explaining differences in their baseline volumes. These results imply the existence of genetic variants that are specific for brain plasticity, rather than brain volume itself. Identifying these genes may increase our understanding of brain development and ageing and possibly have implications for diseases that are characterized by deviant developmental trajectories of brain structure. Hum Brain Mapp 38:4444-4458, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Variação Biológica Individual , Encéfalo/diagnóstico por imagem , Modelos Genéticos , Característica Quantitativa Herdável , Encéfalo/anatomia & histologia , Encéfalo/crescimento & desenvolvimento , Interação Gene-Ambiente , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Modelos Neurológicos , Tamanho do Órgão/genética , Estudos em Gêmeos como Assunto
14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 37(2): 527-31, 2017 Feb.
Artigo em Zh | MEDLINE | ID: mdl-30291772

RESUMO

In case of GMAW-P application, the product quality is strongly dependent on the arc plasma performances. Therefore, in order to improve the application, it is important to understand and characterize the fundamental plasma properties. In this paper, different techniques (high speed camera ,optical emission spectroscopy system, electrical data acquisition system, synchronous triggering device) were used to characterize the arc characteristic. The metal diffusion process from the peak time to the base time is discussed, as well as its physical characteristics. The results show that, in the peak time phase, a high concentration of metal vapor arc is concentrated in the plasma center of the range of about 1 mm, during the transition from the peak to the base pulse periods, the diffusion leads to an iron vapor flux from regions in the arc core to the arc fringes. The iron mol fraction of the peak time was up to 75%, only taking up 35% of the base time.

15.
J Org Chem ; 81(13): 5495-503, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27243934

RESUMO

An efficient synthesis of dihydrobenzo[c]phenanthridinones was achieved by utilizing an indium(0)-mediated intramolecular cyclization reaction under ligand- and base-free conditions. A variety of functional groups were tolerated in the present protocol.

16.
Bioorg Med Chem ; 24(2): 92-103, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26682702

RESUMO

A series of (2-benzoylethen-1-ol)-containing benzothiazine derivatives was synthesized, and their herbicidal activities were first evaluated. The bioassay results indicated that some of 3-benzoyl-4-hydroxy-2-methyl-2H-1,2-benzothiazine-1,1-dioxide derivatives displayed good herbicidal activity in greenhouse testing, especially, compound 4w had good pre-emergent herbicidal activities against Brassica campestris, Amaranthus retroflexus and Echinochloa crusgalli even at a dosage of 187.5 g ha(-1). More importantly, compound 4w displayed significant inhibitory activity against Arabidopsis thaliana HPPD and was identified as the most potent candidate with IC50 value of 0.48 µM, which is better than the commercial herbicide sulctrione (IC50=0.53 µM) and comparable with the commercial herbicide mesotrione (IC50=0.25 µM). The structure-activity relationships was studied and provided some useful information for improving herbicidal activity. The present work indicated that (2-benzoylethen-1-ol)-containing 1,2-benzothiazine motif could be a potential lead structure for further development of novel HPPD inhibiting-based herbicides.


Assuntos
4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , Arabidopsis/enzimologia , Óxidos S-Cíclicos/farmacologia , Descoberta de Drogas , Herbicidas/farmacologia , Tiazinas/farmacologia , 4-Hidroxifenilpiruvato Dioxigenase/metabolismo , Amaranthus/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Brassica/efeitos dos fármacos , Óxidos S-Cíclicos/química , Relação Dose-Resposta a Droga , Echinochloa/efeitos dos fármacos , Herbicidas/síntese química , Herbicidas/química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Tiazinas/síntese química , Tiazinas/química
17.
Proc Natl Acad Sci U S A ; 110(12): 4768-73, 2013 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-23471985

RESUMO

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer's disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain's connectivity pattern, allowing us to discover genetic variants that affect the human brain's wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer's disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism (MACROD2), development (NEDD4), and mental retardation (UBE2A) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.


Assuntos
Doença de Alzheimer/genética , Encéfalo/fisiopatologia , Cromossomos Humanos Par 11/genética , Proteínas da Matriz Extracelular/genética , Variação Genética , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto , Transtorno Autístico/diagnóstico por imagem , Transtorno Autístico/genética , Transtorno Autístico/fisiopatologia , Encéfalo/diagnóstico por imagem , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Feminino , Estudo de Associação Genômica Ampla , Humanos , Imageamento por Ressonância Magnética , Masculino , Ubiquitina-Proteína Ligases Nedd4 , Radiografia , Índice de Gravidade de Doença , Enzimas de Conjugação de Ubiquitina/genética , Ubiquitina-Proteína Ligases/genética
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(4): 913-8, 2016 Apr.
Artigo em Zh | MEDLINE | ID: mdl-30048079

RESUMO

During the process of laser are hybrid welding, the metal vapor from the wire end has great influence on the electron number and the particles in the plasma, which changes the absorption of the laser irradiation and the energy input to workpiece. In this paper, an optical emission spectroscopy system was employed to estimate plasma temperature and the electron number densities distribution. A high speed camera was used to analyze the plasma shape behavior. By using the Beer-Lambert law, the laser absorption rate under different welding mode was calculated. The result show that the metal vapor from the wire tip lead the electron density increase, and it make the laser energy absorption rates decreased.

19.
Ecotoxicology ; 24(7-8): 1419-29, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25967937

RESUMO

Planktonic community structure was investigated during outbreak of harmful Phaeocystis globosa bloom in a subtropical bay, the Maowei Sea, South China Sea. The phytoplankton assemblage was numerically dominated by colonial P. globosa, with its abundance ranging from 1.23 × 10(8) to 11.12 × 10(8) cells m(-3) and contributing nearly 90 % to the total abundance. Totally 66 mesozooplankton (>169 µm) and 19 ciliates species were recorded, with the densities ranged from 169 to 1633 ind m(-3) and 74 to 1118 cells L(-1), respectively. The dominant species for mesozooplankton were Copepoda (larvae), Bestiola sinicus, B. amoyensis, Macrura (larvae) and Acartia spinicauda, respectively. The ciliate assemblage was numerically dominated by Codonella rapa, Strombidium globosaneum and Mesodinium rubrum. During the bloom, P. globosa seemed to be negatively affected by the nutrient phosphate significantly (p < 0.05). However, no correlation between P. globosa and ciliate assemblage was detected, but P. globosa was negatively correlated with total biomass of mesozooplankton and abundance of B. sinicus (p < 0.05), suggesting that P. globosa was uncoupled from the grazing by both ciliates and mesozooplankton when appearing as colonies form. On the other hand, both positive and negative correlations among the dominant groups of mesozooplankton and ciliates were observed (p < 0.05) which possibly indicated that the predation of mesozooplankton upon ciliates might be strengthened during the Phaeocystis bloom and the complex effect also varied from species to species.


Assuntos
Baías/análise , Eutrofização , Cadeia Alimentar , Haptófitas/fisiologia , Plâncton/fisiologia , China
20.
Ecotoxicology ; 24(7-8): 1529-39, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26024618

RESUMO

Bacterial metabolism plays a dual role [bacterial production (BP) and bacterial respiration (BR)] in the aquatic ecosystem and potentially leads to hypoxia in the coastal eutrophic area. Bacterial growth efficiency (BGE) is an important index showing the contribution of bacterial metabolism to marine biological production and carbon budget in the pelagic ecosystem. In this study, the spatial and seasonal variety as well as diurnal variation dynamics of BGE and associated ecological characteristics were investigated in a partly eutrophicated subtropical bay (the Daya Bay) located in the northern South China Sea. Furthermore, the relationship between bacterial metabolism and potential hypoxia event was analyzed. The average BGE was 0.14 and 0.22 in summer and winter, respectively, which was lower than the mean value ever reported in other coastal and estuarine waters. The diurnal variations of BGE and BP were widely fluctuated in the Daya Bay, with approximately 3-8 fold variation of BP and 2-3 fold variation of BR in different seasons, suggesting the importance of short-term ecological dynamics on evaluating the long-term ecological processes in the coastal waters. BR was the predominant contributor to the bacterial carbon demand; however, the variation of BGE was controlled by BP in both seasons. BGE was always high in the near-shore waters with higher eutrophic level and more active BP and BR. The bacterial metabolism could deplete dissolved oxygen (DO) in the Daya bay within about 9 days when the water body was enclosed and photosynthesis was prohibited. Therefore, low DO concentration and potential hypoxia was more likely to be found in the near-shore waters of the Daya Bay in summer, since the water was stratified and enclosed with poor water exchange capacity in this area. While in winter, hypoxia seldom occurred due to vertical mixing throughout the water column. Further biological-physical coupling research is recommended to find out the detailed formation mechanism of hypoxia in the bay, and to predict the potential hypoxia events and their environmental impacts in the future.


Assuntos
Bactérias/crescimento & desenvolvimento , Baías/microbiologia , Eutrofização , Anaerobiose , Bactérias/efeitos dos fármacos , China , Ecossistema , Estações do Ano
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