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1.
Artigo em Inglês | MEDLINE | ID: mdl-33530915

RESUMO

BACKGROUND: Autophagy plays a 'double-edged sword' in the process of tumorigenesis, development and metastasis. OBJECTIVE: In this study, we explored the effect of PI3K/AKT/mTOR autophagy related signaling pathway on regulating and controlling the invasion and metastasis of liver cancer cells by Bufalin. METHODS: The cell counting , migration , adhesion and invasion assay were used to evaluate the effect of Bufalin on the cell proliferation, invasion and metastasis. The protein expression of PI3K/AKT/mTOR signaling pathway were detected by Western Blotting technique. RESULTS: After inhibiting autophagy of HCC-LM3 cells, the inhibitory effect of Bufalin on adhesion, migration and invasion of HCC-LM3 cells was significantly enhanced. The synergistic inhibition was strongest when different autophagy inhibitors were combined with 3MA and CQ. After inhibiting autophagy, Bufalin significantly inhibited the protein expression of P-AKT, Cyclin D1, MMP-2, MMP-9 and VEGF in HCC-LM3 cells. The protein expression of PTEN and E-Cadherin in HCC-LM3 cells was significantly increased. CONCLUSION: The present study shows that the anti-tumor effect of Bufalin mainly inhibit the proliferation, extracellular matrix degradation and angiogenesis of HCC by influencing autophagy. These findings confirm the capability of Bufalin in inhibiting metastasis of HCC and in parallel to current patents could be applied as a novel therapeutic strategy in the prevention of metastasis of HCC.

2.
Nanoscale ; 13(5): 3275-3284, 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33533772

RESUMO

A novel enhanced chemiluminescent immunoassay (CLIA) for ultrasensitive and excellent precisive determination of cardiac troponin I (cTnI) was reported. The method made full use of poly[(N-isopropyl acrylamide)-co-(methacrylic acid)] (P(NIPAM-co-MAA)) microspheres as new potential signal enhancers and magnetic fluorescent nanoparticles as internal standards for better precision. This protocol involved a sandwich format, in which the antigen in the sample was captured by the immobilized antibodies on the surface of magnetic fluorescent beads and recognized by the other antibodies labeled with acridinium ester (AE)-loaded P(NIPAM-co-MAA) microspheres. The combination of the remarkable sensitivity of the enhanced CLIA method and the use of P(NIPAM-co-MAA) microspheres as anti-cTnI carriers for acridinium ester signal amplification provided an extremely sensitive limit of blank (LoB) at 0.097 pg mL-1, a limit of detection (LoD) at 0.116 pg mL-1, and a limit of quantitation (LoQ) at 0.606 pg mL-1, much greater than those achieved by the classical chemiluminescence immunoassay (CLIA, Getein). Moreover, the intra-day variable coefficient can be improved to 1.21-2.12%, and inter-day variability was 2.01-3.49% under the application of magnetic fluorescent beads as an internal standard. The sensitivity and precision have reached a high level, comparable with the current commercial detection kits. The results showed a good correlation with a commercial chemiluminescence assay (CLIA, Abbott), with a correlation coefficient of 0.9883. This proposed method has been successfully applied to the clinical determination of cTnI in the human serum.

3.
Cell Stem Cell ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33567267

RESUMO

The use of the dual recombinase-mediated intersectional genetic approach involving Cre-loxP and Dre-rox has significantly enhanced the precision of in vivo lineage tracing, as well as gene manipulation. However, this approach is limited by the small number of Dre recombinase driver constructs available. Here, we developed more than 70 new intersectional drivers to better target diverse cell lineages. To highlight their applicability, we used these new tools to study the in vivo adipogenic fate of perivascular progenitors, which revealed that PDGFRa+ but not PDGFRa-PDGFRb+ perivascular cells are the endogenous progenitors of adult adipocytes. In addition to lineage tracing, we used members of this new suite of drivers to more specifically knock out genes in complex tissues, such as white adipocytes and lymphatic vessels, that heretofore cannot be selectively targeted by conventional Cre drivers alone. In summary, these new transgenic tools expand the intersectional genetic approach while enhancing its precision.

4.
Arch Biochem Biophys ; 699: 108754, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33450239

RESUMO

Drug resistance is one of the major challenges for treatment of hepatocellular carcinoma (HCC) with sorafenib. Our present study found that sorafenib resistant (SR) HCC cells showed epithelial-mesenchymal transition (EMT) characteristics with the downregulation of epithelial marker and upregulation of mesenchymal makers. The expression of Snail, a core factor of EMT, was increased in HCC/SR cells, while knockdown of Snail can restore sorafenib sensitivity and EMT potential of HCC/SR cells. Further, the upregulation of protein stability was responsible for the upregulation of Snail in HCC/SR cells. ATM and CSN2, which can stabilize Snail protein, were increased in HCC/SR cells. Knockdown of ATM and CSN2 can suppress the expression of Snail and increase sorafenib sensitivity of HCC/SR cells. It indicated that targeted inhibition of Snail might be helpful to overcome sorafenib resistance of HCC patients.

5.
Environ Int ; 148: 106383, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33465664

RESUMO

BACKGROUND: The prevalence of metabolic syndrome (MetS) rapidly increased over the past decades. However, little evidence exists about the effects of long-term exposure to ambient air pollution on MetS in children and adolescents. OBJECTIVE: This study aims to assess the association between long-term ambient air pollution and the prevalence of MetS in a large population of Chinese children and adolescents. METHODS: In 2013, a total of 9,897 children and adolescents aged 10 to 18 years were recruited from seven provinces/municipalities in China. MetS was defined based on the recommendation by the International Diabetes Federation (IDF). Satellite based spatio-temporal models were used to estimate exposure to ambient air pollution (including particles with diameters ≤1.0 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10), and nitrogen dioxide (NO2)). Individual exposure was calculated according to 94 schools addresses. After adjustment for a range of covariates, generalized linear mixed-effects models were utilized to evaluate the associations between air pollutants and the prevalence of MetS and its components. In addition, several stratified analyses were examined according to sex, weight status, outdoor physical activity time, and sugar-sweetened beverages (SSBs) intake. RESULTS: The prevalence of MetS was 2.8%. The odds ratio of MetS associated with a 10 µg/m3 increase in PM1, PM2.5, PM10 and NO2 was 1.20 (95%CI: 0.99, 1.46), 1.31 (95%CI: 1.05, 1.64), 1.32 (95%CI: 1.08, 1.62), and 1.33 (95%CI: 1.03, 1.72), respectively. Regarding the MetS components, we observed associations between all pollutants and abdominal obesity. In addition, long-term PM1 and NO2 exposures were associated with the prevalence of elevated fasting blood glucose. Stratified analyses detected that the associations between air pollutants and the prevalence of MetS were stronger in boys (Pinteraction < 0.05). CONCLUSIONS: We found that long-term exposure to PM2.5, PM10, and NO2 were positively associated with the prevalence of MetS in children and adolescents. Our findings may have certain public health implications for some comprehensive strategy of environment improvement and lifestyles changes in order to reduce the burden of non-communicable disease.

6.
FEBS Open Bio ; 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33455085

RESUMO

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20-hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20-HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

7.
Neurosci Lett ; 746: 135585, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33352278

RESUMO

BACKGROUND: Fluoxetine hydrochloride is one of the familiar antidepressants of the second generation and has the effect of inhibiting the reuptake of 5-hydroxytryptamine by central nervous system. Both clinical trials and animal experiments show that it has good antidepressant effect, but there are few reports on its clinical efficacy in treating depression patients from the perspective of metabolomics. This study aimed at evaluating the antidepressant effect of fluoxetine hydrochloride by metabolomics, so that to find out its specific biomarkers and related metabolic characteristics of depression in the treatment of depression and analyze the intervention mechanism of fluoxetine hydrochloride in depression. METHOD: Twenty depression patients and twenty healthy volunteers were recruited in clinical. Using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) to analyze serum metabolites of depression patients pretherapy and post-treatment and compared with healthy people. RESULT: Finally, we have detected 16 specific biomarkers of depression. Compared with the healthy group, the level of 10 biomarkers in the depression group was significantly increased (P < 0.05) and 6 biomarkers were significantly decreased (P < 0.01). After 8 weeks of fluoxetine hydrochloride treatment, all the biomarkers have showed a tendency of callback. The metabolic pathways involved amino acid metabolism, energy metabolism and lipid metabolism. CONCLUSION: In our study, the antidepressant effect of fluoxetine hydrochloride in clinic was proved by metabolomics and provided basis for clinical use of fluoxetine hydrochloride. At the same time, the biomarkers that may be related to the occurrence of depression are determined to provide objective basis for the diagnosis of depression.

8.
Mol Med Rep ; 23(2): 1, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33313950

RESUMO

Gli proteins are key transcription factors of the Hedgehog (HH) signaling pathway, which is associated with tumorigenesis and drug resistance. However, the role of the HH signaling pathway in epithelial ovarian cancer (EOC) remains unclear. Studies have demonstrated that in some tumors, homeobox protein NANOG (NANOG), a known stem cell marker, is a downstream effector of Gli. However, limited research has been conducted on the association between Gli and NANOG in EOC, particularly regarding their roles in the tumor stemness, such as tumor development, drug resistance and patient prognosis. Thus, the aim of the present study was to explore the aforementioned issues. In this study, Gli1, Gli2 and NANOG expression in EOC tissues was assessed using immunohistochemistry. Gene expression was also assessed using western blotting and reverse transcription­quantitative PCR in SKOV3 cells treated with a Gli inhibitor and an HH agonist. Furthermore, cell proliferation, colony­forming ability and cisplatin sensitivity were assessed using Cell Counting Kit­8 and colony formation assays. The results showed that both Gli1 and NANOG were associated with cisplatin resistance and EOC disease stage, while the nuclear expression of Gli2 was significantly associated with cisplatin resistance. Together, the expression of Gli and NANOG predicted poor patient prognosis. Targeting Gli with GANT61 impeded tumor proliferation, reversed cisplatin resistance and colony formation, and reduced NANOG expression. To conclude, Gli and NANOG may be effective indicators of platinum resistance and prognosis in EOC. Targeting Gli may reduce the stemness of ovarian cancer cell, which may be achieved via indirect targeting of NANOG.

9.
Environ Res ; 192: 110289, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33027626

RESUMO

BACKGROUND: Previous studies have indicated that exposure to green space may benefit human health. However, the available evidence concerning the effects of greenness, especially school-based greenness, on pediatric obesity is scarce. OBJECTIVE: To explore the association between school-based greenness and adiposity in children and adolescents in China. METHOD: We conducted a nationwide cross-sectional study of 56,620 children and adolescents (aged 6-18 years) in seven provinces/municipalities across China. School-based greenness was assessed using satellite-derived Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) within 100-, 500-, and 1000-m circular buffers around each school's address. Generalized linear mixed regression models were used to estimate associations of greenness with BMI z-scores (zBMI), waist circumference, and prevalent overweight/obesity. We also explored the potential mediating role of ambient air pollution and physical activity in the greenness-adiposity associations. RESULT: In the adjusted model, an IQR increase in NDVI-1000m was associated with lower zBMI (ß: -0.11, 95% confidence interval[CI]: -0.13,-0.09) and waist circumference (ß: -0.64, 95%CI: -0.78,-0.50). Consistently, an IQR increase in NDVI-100m, NDVI-500m, NDVI-1000m was associated with 7-20% lower odds of overweight/obesity in the adjusted models. Air pollutants mediated 6.5-29.1% of the association between greenness and zBMI. No significant mediation effect was observed for physical activity. CONCLUSION: Higher school-based greenness levels were associated with lower zBMI, waist circumference, and lower odds of overweight and obesity in children and adolescents. Ambient air pollutants may partially mediate the greenness-adiposity associations.

10.
Biosens Bioelectron ; 175: 112883, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33341318

RESUMO

The content of cardiac troponin I (CTnI) in human blood is the key factor in judging acute myocardial infarction (AMI). In order to detect the content of CTnI, we constructed a sandwich-type electrochemical immunosensor based on hydrogen peroxide (H2O2) as a signal source. Dendritic platinum-copper alloy nanoparticles (DPCN) loaded on molybdenum disulfide (MoS2) nanosheets (DPCN/MoS2) as secondary antibodies (Ab2) label provided signal amplification. The hollow three-dimensional (3D) pyramid-shaped structure of DPCN exposed abundant active sites and exhibited excellent catalytic properties. MoS2 nanosheets with flower-like structure and a larger specific surface area can effectively load more DPCN. The combination of MoS2 and DPCN enhanced the catalytic performance of DPCN/MoS2 towards H2O2 reduction and realized signal amplification. For the substrate material, the two-dimensional (2D) metal-organic framework (Co-BDC, 1,4-benzenedicarboxylate is abbreviated as BDC) was hybridized with MoS2 nanosheets to load gold nanoparticles (Au NPs). The obtained Au/Co-BDC/MoS2 had low catalytic activity and excellent electrical conductivity, which was used to load primary antibodies (Ab1) to effectively enhance the sensitivity. Under the best conditions, we constructed the immunosensor with the detection range of 10 fg/mL to 100 ng/mL and the limit of detection (LOD) of 3.02 fg/mL. At the same time, the content of CTnI in human serum was tested with satisfactory results. Therefore, the constructed immunosensor has important significance in the sensitive and accurate detection of CTnI and early diagnosis of AMI.

11.
Mol Cancer Ther ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298587

RESUMO

Glioblastoma multiforme (GBM; grade IV glioma) is the most malignant type of primary brain tumor and is characterized by rapid proliferation and invasive growth. Intermedin (IMD) is an endogenous peptide belonging to the calcitonin gene-related peptide family and has been reported to play important roles in cell survival and invasiveness in several types of cancers. In this study, we found that the expression level of IMD was positively related to the malignancy grade of gliomas. The highest expression of IMD was found in GBM, indicating that IMD may play important roles in glioma malignancy. IMD increased the invasive ability of glioma cells by promoting filopodia formation, which is dependent on ERK1/2 activation. IMD-induced ERK1/2 phosphorylation also promoted GBM cell proliferation. In addition, IMD enhanced mitochondrial function and hypoxia-induced responses in GBM cells. Treatment with anti-IMD monoclonal antibodies not only inhibited tumor growth in both ectopic and orthotopic models of GBM but also significantly enhanced the antitumor activity of temozolomide (TMZ). Our study may provide novel insights into the mechanism of GBM cell invasion and proliferation and provide an effective strategy to improve the therapeutic effect of GBM treatments.

12.
Biomed Chromatogr ; : e5046, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33283319

RESUMO

Radix Gentianae Macrophyllae (RGM) is a traditional Chinese medicine belonging to Gentiana genus including four species of original herbs. For the lack of characteristic constituents, it is difficult to discriminate different original RGMs or even differentiate with other herbs in the same genus. The current research was aimed to explore the characteristic aromatic compounds, verify their significance in distinguishing different origin of RGM herbs and provide a simple and effective quality evaluation method. In which, a selective extraction method was developed for non-iridoid compounds and the extract was then subjected to UPLC-QTOF-MS analysis to obtain the RGM-MS ion pair database for non-iridoid components. HPLC-DAD quantitative analysis method was further developed based on characteristic aromatic compounds (2-phenylethyl ß-D-glucopyranoside, 2-methoxyanofinic acid and gentioxepine) after the ion screening among MS database. By means of PCA and HCA analysis, the significant relationship between aromatic compounds contents and different species of RGM has been revealed. As the result, the significance of 2-phenylethyl ß-D-glucopyranoside, 2-methoxyanofinic acid and gentioxepine in distinguishing four species of RGM herbs was verified and a sensitive and reproducible HPLC-DAD method was established using these markers, which can be used for the classification and quantitative analysis of RGMs.

13.
Entropy (Basel) ; 22(9)2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-33286824

RESUMO

Generative adversarial networks (GANs), which are a promising type of deep generative network, have recently drawn considerable attention and made impressive progress. However, GAN models suffer from the well-known problem of mode collapse. This study focuses on this challenge and introduces a new model design, called the encoded multi-agent generative adversarial network (E-MGAN), which tackles the mode collapse problem by introducing the variational latent representations learned from a variable auto-encoder (VAE) to a multi-agent GAN. The variational latent representations are extracted from training data to replace the random noise input of the general multi-agent GANs. The generator in E-MGAN employs multiple generators and is penalized by a classifier. This integration guarantees that the proposed model not only enhances the quality of generated samples but also improves the diversity of generated samples to avoid the mode collapse problem. Moreover, extensive experiments are conducted on both a synthetic dataset and two large-scale real-world datasets. The generated samples are visualized for qualitative evaluation. The inception score (IS) and Fréchet inception distance (FID) are adopted to measure the performance of the model for quantitative assessment. The results confirmed that the proposed model achieves outstanding performances compared to other state-of-the-art GAN variants.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33374532

RESUMO

The expansion of agriculture and intensive mechanized production have resulted in the loss of habitats and biodiversity, which has led to the loss of ecological services such as the biological control of pests and diseases, and insect-borne pollination. Current studies mainly focus on the impact of small-scale crop diversity (such as intercropping) on ecological service but lack research on the effects of crop diversity at the landscape scale. In this study, vegetation-dwelling arthropods in naked oat (Avena chinensis) fields under different planting patterns were collected at different growth stages by standardized sweep netting sampling, and the differences in arthropod communities and temporal dynamics were analyzed. Taking this information as an example, the effects of crop diversity at the landscape scale caused by different planting patterns on arthropod communities were studied. It was found that herbivores were the most abundant functional group in the arthropod community in naked oat fields, accounting for 70.13% of the total abundance, followed by natural enemies, accounting for 23.45%, and, finally, other insects. The abundance and species richness of natural enemies in naked oat fields under diversified planting pattern were significantly higher than those under intensive planting pattern, while the abundance and species richness of herbivorous pests showed no significant difference between the two planting patterns. Planting patterns significantly affected the composition and structure of arthropod communities in naked oat fields. Significantly higher ratio of natural enemy to pest and more diverse natural enemies under the diversified planting pattern have shown better biological control potential and the significance of biodiversity protection.


Assuntos
Artrópodes/classificação , Avena , Biodiversidade , Animais , Ecossistema , Herbivoria
15.
Ying Yong Sheng Tai Xue Bao ; 31(10): 3267-3272, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33314814

RESUMO

To elucidate the composition of semiochemicals of Apriona germari and its function in sexual communication, GC-MS was used to detect the composition of semiochemicals of the overall body and the end abdominal tissue extracts in A. germari. Y-tube olfactometer was used to determine the olfactory response of adult female and male to the standard compounds of the five main extracts. The contact reaction test with male and female adults was performed to the eluted adults that smeared tandard compounds. The results showed that the main ingredients of semiochemicals were alkanes and alkenes with more than 10 carbons. Concentration of (Z)-9-Tricosene was the highest, followed by heptacosane, nonacosane, nonadecene, octacosane, 9-Hexylheptadecane, aldehyde, and ester. Results of the olfactory reaction showed that nonacosane had a significant attractivity to both male and female adults, and that heptacosane had a significant attractivity only to female adults. Nonadecene had a extremely significant repellent activity to female adults. 1-docosene and (Z)-9-Tricosene had no evident role to the male and female adults. Results of the contact test showed that male adults had the strongest courtship responses to the eluted adults with 1-docosene, heptacosane and nonacosane. Female adults had the strongest courtship responses to the eluted adults with nonacosane. Our results indicated that 1-docosene, heptacosane, and nonacosane were important component of the sex pheromone of A. germari, which played an important role in the sexual communication.


Assuntos
Besouros , Atrativos Sexuais , Animais , Comunicação , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino
16.
Ying Yong Sheng Tai Xue Bao ; 31(9): 2977-2984, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-33345498

RESUMO

Stellera chamaejasme is one of most common poisonous plant species in degraded grasslands of China. S. chamaejasme could dominate the community in some severely degraded grasslands, which is a serious threat to the sustainable development of animal husbandry in natural grasslands. In this study, S. chamaejasme population was divided into 10 age classes according to the number of branches. We investigated the age structure of S. chamaejasme population and population dynamic indices, and quantified the survival status of S. chamaejasme population by compiling a static life table, drawing a survival curve, conducting survival analysis. The age structure of S. chamaejasme population in the study area was growth type. The number of individuals in Ⅰ age class was sufficient but with relatively low survival rate. The population structure of S. chamaejasme was fitted the growing type. The development process of population was fluctuating. The number of individuals would drop sharply in Ⅱ and Ⅷ, indicating that these two age classes were the bottleneck period in the development of S. chamaejasme population. The survival curves of S. chamaejasme population was the Deevey-Ⅱ type. The results of survival analysis showed that the population had a sharp decrease in the early stage and was stable in the later stage, which was because the value of fx and λx of S. chamaejasme in Ⅰ or Ⅱ age class were the highest. In conclusion, sufficient young individuals (Ⅰ) was the basis for the expansion of S. chamaejasme population in the degraded typical steppe. The low transformation rate of young individuals to adults might be one of the reasons explaining why S. chamaejasme population could not expand rapidly in the early stage of grassland degradation. Therefore, it was suggested to intervene early when the number of S. chamaejasme was limited.


Assuntos
Thymelaeaceae , Animais , China , Humanos
17.
Sci Adv ; 6(46)2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33188015

RESUMO

High-performance lightweight materials are urgently needed, given the pressing quest for weight reduction and the associated energy savings and emission reduction. Here, by incorporating the multi-principal element feature of compositionally complex alloys, we develop the concept of lightweight steels further and propose a new class of compositionally complex steels (CCSs). This approach allows us to use the high solid solution strengthening and shift the alloys' compositions into previously unattainable phase regions where both nanosized shearable κ-carbides and non-shearable B2 particles are simultaneously formed. The achievement of dual-nanoprecipitation in our CCSs leads to materials with ultrahigh specific tensile strength (up to 260 MPa·cm3 g-1) and excellent tensile elongation (13 to 38%), a combination outperforming all other high-strength high-entropy alloys and advanced lightweight steels. Our concept of CCSs is thus useful for guiding the design of ultrastrong lightweight metallic materials.

18.
Phytochemistry ; 181: 112572, 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33166750

RESUMO

Five undescribed compounds were separated from Abrus mollis leaves, including two truxillate forms (abrusamide D, H) and three truxinate forms (abrusamide E, F, G). The absolute configuration of abrusamide D was determined by X-ray crystallography. Abrusamide A was reassessed and corrected to be ß-truxinate configuration rather than α-form. LC-MS/MS and CD spectroscopy were applied to determine and analyze ten compounds, including four truxillate forms (abrusamide B ~ D and H), four truxinate forms (abrusamide E ~ G and A), and two precursors [(E)-N-(4-hydroxycinnamoyl) tyrosine, (Z)-N-(4-hydroxycinnamoyl) tyrosine]. It showed that the fragmentation pattern of truxillate was symmetric, while that of truxinate was asymmetric and irregular. The CD Cotton effect was related to cyclobutane configuration. These findings provided strong evidence for the cyclobutane dimers to discriminate their configuration. In addition, the bioactivity assay showed that the compounds had low toxicity and anti-inflammatory effect.

19.
J Phys Chem Lett ; 11(22): 9952-9956, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33170715

RESUMO

Reversible chemistries have been extensively explored to construct highly crystalline covalent organic frameworks (COFs) via defect correction. However, the mechanisms of defect correction that can explain the formation of products as single crystals, polycrystal/crystallites, or amorphous solids remain unknown. Herein, we employed molecular dynamics simulations combined with a polymerization model to investigate the growth kinetics of two-dimensional COFs. By virtue of the Arrhenius two-state model describing reversible reactions, we figured out the conditions in terms of active energy and binding energy for different products. Specifically, the ultraslow growth of COFs under high reversibility of reactions corresponding to low binding energies resulted in a single crystal by inhibiting the emergence of nuclei as well as correcting defects through continually dropping small defective fragments off at crystal boundaries. High bonding energies responsible for the high nucleation rate and rapid growth that incorporated defects in crystals and caused the division of crystals through defect correcting processes led to small crystallites or polycrystals. The insights into the mechanisms help us to understand and further control the growth kinetics by exploiting reversible conditions to synthesize COFs of higher quality.

20.
J Cancer ; 11(24): 7276-7282, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193891

RESUMO

Objective: The management of indeterminate thyroid nodules is challenging. Molecular testing has emerged as a promising method for stratifying this gray area of fine-needle aspiration (FNA) cytology. Next-generation sequencing (NGS) can be used to test a large variety of genetic changes with very small amounts of nucleic acids obtained from FNA samples. Methods: Thyroid FNA assays were classified according to the Bethesda System for Reporting Thyroid Cytopathology after routine ThinPrep® slide preparation. Indeterminate nodules with surgical outcomes were assayed with an 18-gene NGS panel with the residual ThinPrep® material, including nodules categorized as atypia of undetermined significance (AUS)/follicular lesions of undetermined significance (FLUS) or follicular neoplasm (FN)/suspicious for a follicular neoplasm (SFN). We evaluated the diagnostic efficacy of the 18-gene panel for thyroid malignancies and potential malignancies and compared it with a well-accepted examination, ThyroSeq v2 testing. Results: A total of 36 indeterminate nodules were assayed, seven were categorized as AUS/FLUS and 29 as FN/SFN. All of them had adequate DNA for the NGS procedure. When noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was considered malignant, the risk of malignancy was 71.4% for AUS/FLUS nodules, and 69.0%for FN/SFN nodules. The 18-gene panel showed 72.0% sensitivity, 72.7% specificity, 85.7% positive predictive value (PPV), and 53.3% negative predictive value (NPV) in identifying malignancies and potential malignancies in the indeterminate nodules. Compared with a multicenter report from ThyroSeq v2 testing, 18-gene panel showed a lower NPV (p=0.005), but a higher PPV (p=0.02). Conclusions: NGS assays are feasible on residual ThinPrep® material, with the advantage of not requiring additional FNA procedure. The 18-gene panel testing can be used as a 'rule in' test for surgical management based on indeterminate nodules and showed a lower NPV but a higher PPV compared to ThyroSeq v2 testing.

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