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1.
Food Chem ; 338: 127794, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798827

RESUMO

In this research, a three-step strategy was utilized for discriminating turmeric samples from different provinces and regions in China. Firstly, MRM-based UPLC-MS/MS method for chemical profiling of curcuminoids in turmeric samples was established. Then, response surface methodology was applied for optimizing the extraction process of targeted curcuminoids. Finally, multivariate analysis was conducted for systematic characterization of 66 curcuminoids in turmeric. Principal component analysis (PCA) and orthogonal projection to latent structure-discriminant analysis (OPLS-DA) revealed that turmeric samples from Sichuan and other regions could be classified into two distinct groups. Turmeric samples from the same group had similar curcuminoids content distribution. 25 differential curcuminoids were discovered through OPLS-DA, among which most curcuminoids were more abundant in Sichuan. Furthermore, turmeric samples from different provinces could be clearly discriminated based on hierarchical cluster analysis (HCA) using the screened differential curcuminoids.

2.
Sci Total Environ ; 750: 141615, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32858294

RESUMO

Although polyhalogenated carbazoles (PHCZs) can be generated and detected in drinking water, their occurrence and potential health risks to humans via drinking water ingestion are not well known. In this study, 11 PHCZs were screened in drinking water samples from Wuhan, the most populous city in central China. The total concentration of PHCZs could be up to 53.48 ng/L with a median level of 8.19 ng/L, which was comparable to polychlorinated biphenyls and poly- and perfluoroalkyl substances reported in the literatures for drinking water. Composition profiles revealed that 3,6-dichlorocarbazole, 3-chlorocarbazole, 3-bromocarbazole and 3,6-dibromocarbazole were the predominant PHCZ congeners in the tested samples. Regional differences in the levels and patterns of PHCZs suggested that anthropogenic releases should be the dominant source compared to natural generation. Boiling of the water samples caused no significant change in PHCZs concentrations after correcting the volume change due to evaporation. Potential health risks associated to the levels of PHCZs in drinking water were assessed using the toxic equivalent (TEQs) method. The estimated daily intake of PHCZs via drinking water ingestion is up to 0.38 pg-TEQ/kg body weight/day for infants, nearly 4.5 times higher than that for adults, and appears to reach the maximum permissible concentration set by certain authority agencies. Overall, drinking water ingestion represents an important exposure pathway for PHCZs. This is the first comprehensive study on the abundance and health risks of PHCZs in drinking water.


Assuntos
Água Potável , Bifenilos Policlorados , Poluentes Químicos da Água , Carbazóis , China , Poluentes Químicos da Água/análise
3.
Plant Physiol Biochem ; 157: 339-347, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33186851

RESUMO

Celery (Apium graveolens L.) is a leafy vegetable of Apiaceae, which is greatly popular because of its rich nutrients. Lutein and ß-carotene are two important carotenoids. Lycopene epsilon cyclase (LCY-ε) is a key branch point enzyme in the carotenoid biosynthetic pathway. In this study, we cloned the AgLCY-ε gene from celery and overexpressed it in Arabidopsis. The results showed that both lutein and ß-carotene accumulation increased significantly in transgenic Arabidopsis hosting AgLCY-ε gene, compared with wild type (WT) plants. The transcription levels of AtPSY and AtCRTISO genes involved in carotenoids biosynthesis also increased in transgenic lines. One-month-old transgenic Arabidopsis seedlings were treated with 200 mM NaCl. The malondialdehyde (MDA) content in transgenic Arabidopsis plants after salt treatment was significantly lower, and the activities of the two antioxidant enzymes, superoxide dismutase (SOD) and peroxidase (POD), were significantly increased than that of WT plants. Overexpression of AgLCY-ε gene showed increased lutein and ß-carotene accumulations, and enhanced salt tolerance in transgenic plants.

4.
J Genet Genomics ; 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-33184002

RESUMO

One of the main causes of pregnancy failure and fetus abortion is oocyte aneuploidy. Oocyte aneuploidy has a dramatic high prevalence in older women. Decades of research has uncovered many possible causes of aneuploidy in aged oocytes, such as unsatisfactory crossover formation, cohesin loss, spindle assembly defects, spindle assembly checkpoint malfunction, microtubule-kinetochore attachment failure, kinetochore misorientation, mitochondria dysfunction-induced increases in reactive oxygen species, protein acetylation, DNA damage, and others. However, questions still need to be answered if these aneuploidization factors have inherent relations and how to prevent oocyte aneuploidization in aged oocytes. Epidemiologically, oocyte aneuploidy has been found to be weakly associated with higher homocysteine concentration, obesity, ionizing radiation, and even seasonality. What can these statistical epidemiology data tell us? In this review, we summarize the research progress and epidemiologic data about oocyte aneuploidy and present an integrated view of oocyte aneuploidization.

5.
Nat Commun ; 11(1): 4917, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004802

RESUMO

Maternal mRNA clearance is an essential process that occurs during maternal-to-zygotic transition (MZT). However, the dynamics, functional importance, and pathological relevance of maternal mRNA decay in human preimplantation embryos have not yet been analyzed. Here we report the zygotic genome activation (ZGA)-dependent and -independent maternal mRNA clearance processes during human MZT and demonstrate that subgroups of human maternal transcripts are sequentially removed by maternal (M)- and zygotic (Z)-decay pathways before and after ZGA. Key factors regulating M-decay and Z-decay pathways in mouse have similar expression pattern during human MZT, suggesting that YAP1-TEAD4 transcription activators, TUT4/7-mediated mRNA 3'-oligouridylation, and BTG4/CCR4-NOT-induced mRNA deadenylation may also be involved in the regulation of human maternal mRNA stability. Decreased expression of these factors and abnormal accumulation of maternal transcripts are observed in the development-arrested embryos of patients who seek assisted reproduction. Defects of M-decay and Z-decay are detected with high incidence in embryos that are arrested at the zygote and 8-cell stages, respectively. In addition, M-decay is not found to be affected by maternal TUBB8 mutations, although these mutations cause meiotic cell division defects and zygotic arrest, which indicates that mRNA decay is regulated independent of meiotic spindle assembly. Considering the correlations between maternal mRNA decay defects and early developmental arrest of in vitro fertilized human embryos, M-decay and Z-decay pathway activities may contribute to the developmental potential of human preimplantation embryos.


Assuntos
Blastocisto/metabolismo , Desenvolvimento Embrionário/fisiologia , Estabilidade de RNA/fisiologia , RNA Mensageiro Estocado/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Animais , Técnicas de Cultura Embrionária , Feminino , Fertilização In Vitro/métodos , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Masculino , Meiose/genética , Camundongos , Mutação , Oócitos/metabolismo , Cultura Primária de Células , RNA-Seq , Tubulina (Proteína)/genética , Zigoto/metabolismo
6.
Pharmacol Ther ; : 107698, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33039419

RESUMO

The contribution of natural products (NPs) to cardiovascular medicine has been extensively documented, and many have been used for centuries. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 40 years, approximately 50% of newly developed cardiovascular drugs were based on NPs, suggesting that NPs provide essential skeletal structures for the discovery of novel medicines. After a period of lower productivity since the 1990s, NPs have recently regained scientific and commercial attention, leveraging the wealth of knowledge provided by multi-omics, combinatorial biosynthesis, synthetic biology, integrative pharmacology, analytical and computational technologies. In addition, as a crucial part of complementary and alternative medicine, Traditional Chinese Medicine has increasingly drawn attention as an important source of NPs for cardiovascular drug discovery. Given their structural diversity and biological activity NPs are one of the most valuable sources of drugs and drug leads. In this review, we briefly described the characteristics and classification of NPs in CVDs. Then, we provide an up to date summary on the therapeutic potential and the underlying mechanisms of action of NPs in CVDs, and the current view and future prospect of developing safer and more effective cardiovascular drugs based on NPs.

7.
Chem Commun (Camb) ; 56(89): 13820-13823, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33079084

RESUMO

Herein, copper-catalyzed direct C-C bond cleavage of amides fused to 8-aminoquinoline as a directing group to form urea in the presence of amines and dioxygen is reported. Compared to the previous C-H aminations of amides via C-H activation, this reaction presents a catalyst and oxidant controlled C-C bond cleavage strategy that enables amidation through a radical process. CuBr/Ag2CO3/O2 shows the best catalytic result at 150 °C. A series of aryl and alkyl amides were compatible with this transformation. Notably, this method provided access to cyclohexanone, one of the most important industrial materials. The pathway of this reaction was investigated.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32866103

RESUMO

Time series clustering is usually an essential unsupervised task in cases when category information is not available and has a wide range of applications. However, existing time series clustering methods usually either ignore temporal dynamics of time series or isolate the feature extraction from clustering tasks without considering the interaction between them. In this article, a time series clustering framework named self-supervised time series clustering network (STCN) is proposed to optimize the feature extraction and clustering simultaneously. In the feature extraction module, a recurrent neural network (RNN) conducts a one-step time series prediction that acts as the reconstruction of the input data, capturing the temporal dynamics and maintaining the local structures of the time series. The parameters of the output layer of the RNN are regarded as model-based dynamic features and then fed into a self-supervised clustering module to obtain the predicted labels. To bridge the gap between these two modules, we employ spectral analysis to constrain the similar features to have the same pseudoclass labels and align the predicted labels with pseudolabels as well. STCN is trained by iteratively updating the model parameters and the pseudoclass labels. Experiments conducted on extensive time series data sets show that STCN has state-of-the-art performance, and the visualization analysis also demonstrates the effectiveness of the proposed model.

9.
Bioorg Chem ; 103: 104200, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32890998

RESUMO

Tumor-specific prodrug treatment renders the exclusive delivery of antitumor agents with the lowest untoward effects. In this work, we reported the synthesis and biological assessment of four NQO1-activatable combretastatin A-4 prodrugs constituted by active drug CA-4, different self-immolating linkers, and NQO1-responsive trigger groups. The in vitro antiproliferative activities showed that prodrug 4 displayed greater selective toxicity toward the tumor cells that overexpressed NQO1, taxol-resistant A549 cells, hypoxia-exposed A549 and HepG2 cells, and incurred lower damage to normal cells in comparison with combretastatin A-4, prodrugs 1, 2, and 3. Moreover, based on a mechanistic study, NQO1 triggered prodrug 4 to effectively liberate the parent drug combretastatin A-4 and kill tumor cells. Furthermore, we also demonstrated that prodrug 4 exerted a stronger anticancer effect and greater safety than combretastatin A-4 under in vivo conditions. Hence, from the above results, NQO1 can be used as a specific delivery system for releasing anticancer agents; besides, prodrug 4 can serve as a candidate lead for developing specific anticancer agents.

10.
Zhongguo Zhong Yao Za Zhi ; 45(16): 3945-3951, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893593

RESUMO

In order to observe the anti-tumor effect of cinobufotalin on H22 liver cancer mice and to explore its regulatory mechanism, 50 Kunming mice were subcutaneously inoculated with H22 intraperitoneal passage cells under the armpit to establish H22 hepatocellular carcinoma model. They were then randomly divided into model group, cinobufotalin low dose group, cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, which received 0.01% ethanol solution, 1 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cinobufotalin, 5 mg·kg~(-1) cisplatin, 5 mg·kg~(-1)cisplatin + 5 mg·kg~(-1) cinobufotalin respectively for 10 days. The general condition of mice during the intervention was observed, and the inhibition rate, tumor mass, thymus index, histopathological changes of the tumors, apoptotic rate of the tumors, the expressions of phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), apoptosis related gene(Fas), Fas ligand(FasL) mRNA and protein phosphorylated Akt(pAkt) protein in the tumors of each group were compared. The results showed that during the modeling period, the mice showed a decline in food intake, dark fur, poor mental status, and gradually worsened over time. The mental status of mice in each intervention group was improved gradually, especially in the cisplatin+cinobufotalin group. As compared with the model group, the tumor mass of each intervention group was lower(P<0.05). As compared with the cinobufotalin low dose group, the tumor mass was lower and inhibition rate was higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, the tumor mass was lower and the inhibition rate was higher in cisplatin+cinobufotalin group(P<0.05). As compared with the model group, the thymus index was higher in cinobufotalin high dose group and cisplatin + cinobufotalin group, while was lower in cisplatin group(P<0.05). As compared with the cinobufotalin low dose group, the thymus index was higher in the cinobufotalin high dose group and lower in the cisplatin group(P<0.05). As compared with the cinobufotalin high dose group, the thymus index was lower in cisplatin group(P<0.05). As compared with cisplatin group, the thymus index was higher in cisplatin+cinobufotalin group(P<0.05). Pathological staining showed that a large number of heterogeneous cells and mitotic phenomena were observed in the model group. Cell fragments and neutrophils were observed in the tumor tissues of the intervention groups, showing diffuse necrosis, and the diffuse necrosis was more obvious in the cisplatin+cinobufotalin group. As compared with the model group, the apoptotic rate of the tumors and the relative expressions of Fas mRNA and protein were higher in the intervention groups, while the relative expressions of PI3 K, FasL mRNA and protein and the relative expression of pAkt protein were lower in the intervention groups(P<0.05). As compared with the cinobufotalin low dose group, the apoptotic rate of the tumors and relative expression of Fas and protein were higher in the cinobufotalin high dose group, cisplatin group and cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower(P<0.05). As compared with the cinobufotalin high dose group and the cisplatin group, apoptotic rate of the tumors and the relative expression of Fas mRNA and protein were higher in the cisplatin+cinobufotalin group, while the relative expressions of PI3 K, FasL mRNA and protein and pAkt protein were lower in the cisplatin+cinobufotalin group(P<0.05). In summary, cinobufotalin has significant anti-tumor effect on H22 liver cancer mice, and can enhance the immune function of mice and synergistically enhance the effect of chemotherapy. Its mechanism may be associated with regulating PI3 K/Akt/Fas/FasL signaling pathway related genes and protein expression.


Assuntos
Bufanolídeos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Apoptose , Cisplatino , Proteína Ligante Fas , Camundongos
11.
Curr Pharm Des ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938344

RESUMO

Neurological diseases bring great mental and physical torture to the patients, and have long-term and sustained negative effects on families and society. The attention to neurological diseases is increasing, and the improvement of the material level is accompanied by an increase in the demand for mental level. The p75 neurotrophin receptor (p75NTR) is a low-affinity neurotrophin receptor and involved in diverse and pleiotropic effects in the developmental and adult central nervous system (CNS). Since neurological diseases are usually accompanied by the regression of memory, the pathogenesis of p75NTR also activates and inhibits other signaling pathways, which has a serious impact on the learning and memory of patients. The results of studies shown that p75NTR is associated with LTP/LTD-induced synaptic enhancement and inhibition, suggest that p75NTR may be involved in the progression of synaptic plasticity. And its pro-apoptotic effect is associated with activation of proBDNF and inhibition of proNGF, and TrkA/p75NTR imbalance leads to pro-survival or pro-apoptotic phenomena. It can be inferred that p75NTR mediates apoptosis in the hippocampus and amygdale, which may affect learning and memory behavior. This article mainly discusses the relationship between p75NTR and learning memory and associated mechanisms, which may provide some new ideas for the treatment of neurological diseases.

12.
BMC Endocr Disord ; 20(1): 135, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873266

RESUMO

BACKGROUND: Euthyroid sick syndrome (ESS) frequently arises in children admitted with diabetic ketoacidosis/diabetic ketosis (DKA/DK). This study evaluates the interplay of various metabolic factors with occurrence of deranged thyroid function tests in children suffering from DKA/DK. METHODS: 98 DKA and 96 DK pediatric patients were selected from hospital records. Those on thyroxine replacement, with overt hypothyroidism, or with positive anti-thyroperoxidase (TPO) antibody were excluded. Tests for liver function, renal function, lipid profile, serum osmolarity, thyroid function, c-peptide levels, and glycosylated hemoglobin were done on all patients. Children were divided into euthyroid (n = 88) and ESS groups (n = 106). RESULTS: The ESS group had a higher level of white blood cell count (WBC), plasma glucose (PG), beta-hydroxybutyric acid (ß-HB), triglyceride (TG), anion gap (AG), glycosylated hemoglobin (HbA1c) and a lower level of HCO3-, prealbumin (PA), and albumin (ALB) compared with the euthyroid group (P < 0.05). Free T3 (FT3) levels were significantly correlated to ß-HB, HCO3-, AG, PA, and HbA1c (r = - 0.642, 0.681, - 0.377, 0.581, - 0.309, respectively; P < 0.01). Free T4 (FT4) levels were significantly correlated to ß-HB, HCO3-, and ALB levels (r = - 0.489, 0.338, 0.529, respectively; P < 0.01). TSH levels were significantly affected by HCO3- only (r = - 0.28; P < 0.01). HCO3- level was the most important factor deciding euthyroid or ESS on logistic regression analysis (OR = 0.844, P = 0.004, 95%CI = 0.751-0.948). CONCLUSIONS: Lower levels of free thyroid hormones and occurrence of ESS were associated with a higher degree of acidosis in children with DKA/DK.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32960033

RESUMO

Recently, white light-emitting devices (WLEDs) based on halide perovskites has been extensively studied. However, the lead toxicity and poor stability of conventional lead halide perovskites severely hinder their commercial applications. In this study, lead-free double perovskite Cs2AgInCl6 with a broadband emission was fabricated by a heat-assisted solution evaporation method, in which a compositional engineering by sodium (Na+) alloying and bismuth (Bi3+) doping was performed. The photoluminescence quantum yield was promoted from ∼1.1 to 46.4% and then to 87.2% by Na+ alloying and subsequent Bi3+ doping. In addition, the theory calculation reveals that the diffusion barrier of Cl- vacancy in Cs2AgInCl6 can be increased by Na+ alloying, which would contribute to the stability of the material. Experimentally, the resulting Cs2Ag0.7Na0.3InCl6:Bi products demonstrate a remarkable stability under heat, ultraviolet light, and moisture conditions. The above advantages make it possible for this material to be used as solid-state phosphors for WLED applications, and the Commission International de I'Eclairage color coordinates at (0.38, 0.44), correlated color temperature of 4347 K, and high color rendering index of 87.8 were achieved. More importantly, the WLED demonstrates a remarkable operation stability in air ambient, and only 4.5% emission decay occurs after a long working time for 1000 h, the longest lifetime for perovskite-based WLEDs as far as we know.

14.
New Phytol ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32996127

RESUMO

2,4-Dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA) and DIMBOA-glucoside (DIMBOA-Glc) are anti-insect benzoxazinoids in maize, yet very little information is known about how they are regulated. Reverse genetics, kinase activity analysis, phytohormone and DIMBOA/DIMBOA-Glc quantification, bioassays and transcriptome analysis were employed to study the function of ZmMPK6, a mitogen-activated protein kinase, in maize response to herbivory. ZmMPK6 was rapidly activated by wounding and simulated herbivory. Silencing ZmMPK6 in maize A188 compromised simulated herbivory-induced ethylene levels but not those of jasmonic acid or salicylic acid, and the ZmMPK6-silenced plants exhibited elevated DIMBOA/DIMBOA-Glc and insect resistance. An ethylene complementation experiment revealed that ZmMPK6 repressed the accumulation of DIMBOA/DIMBOA-Glc in an ethylene-dependent manner. Transcriptome analysis revealed that ZmMPK6 might meditate the transcription of BX1 by controlling a MYB transcription factor that is likely to be located in the ethylene signalling pathway and, furthermore, ZmMPK6 and ethylene signalling also specifically and commonly regulate the transcription of other benzoxazinoid biosynthetic genes. We also show that different maize lines have very different responses to simulated herbivory in terms of ZmMPK6 activation, ethylene emission and benzoxazinoid levels. These results uncover that ZmMPK6 and ethylene pathway are novel repressors of DIMBOA/DIMBOA-Glc and provide new insight into the regulatory mechanisms underlying these two pathways.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32997624

RESUMO

Incomplete time series classification (ITSC) is an important issue in time series analysis since temporal data often has missing values in practical applications. However, integrating imputation (replacing missing data) and classification within a model often rapidly amplifies the error from imputed values. Reducing this error propagation from imputation to classification remains a challenge. To this end, we propose an Adversarial Joint-learning Recurrent Neural Network (AJ-RNN) for ITSC, an end-to-end model trained in an adversarial and joint learning manner. We train the system to categorize the time series as well as impute missing values. To alleviate the error introduced by each imputation value, we use an adversarial network to encourage the network to impute realistic missing values by distinguishing real and imputed values. Hence, AJ-RNN can directly perform classification with missing values and greatly reduce the error propagation from imputation to classification, boosting the accuracy. Extensive experiments on 68 synthetic datasets and 4 real-world datasets from the expanded UCR time series archive demonstrate that AJ-RNN achieves state-of-the-art performance. Furthermore, we show that our model can effectively alleviate the accumulating error problem through qualitative and quantitative analysis based on the trajectory of the dynamical system learned by the RNN.

16.
Nat Prod Res ; : 1-6, 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32746709

RESUMO

Eight compounds were obtained from the dry fruits of Piper longum L., and their potential vascular relaxant activities were explored. The present study first revealed the access of Rosin (7) and Piperchabaoside (8) in the medicinal plant Piper longum L. The vessel tension studies showed that Piperine (2), (2E,4E,14Z)-N-isobutyleicosa-2,4,14-trienamide (3), and Piperlonguminine (6) exerted significant inhibitory effects on PE-induced mesenteric artery vasoconstriction. Furthermore, Calcium Imaging studies were applied to observe the effect of Piperine on the intracellular calcium in mesenteric artery smooth muscle cells (MASMCs). Piperine (2) was observed to promote the influx of extracellular calcium in MASMCs, and via an endothelium-independent mechanism involving Ca2+ entry. Piper longum L. might have a great potential to be further studied as a vascular relaxant, even to be a drug candidate of anti-hypertension.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32771970

RESUMO

PCs and SMs are the major types of glycerophospholipids and sphingophospholipids, the two main categories of phospholipids (PLs). To study the qualitative distribution of serum phosphatidylcholine (PC) and sphingomyelin (SM) in human and three rodent species, liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap-MS/MS) was used to identify them comprehensively through the accurate mass measurement of both precursor ions and their corresponding product ions. Based on the fragmentation rules of standards, the product ions at m/z 184.0733 were filtered to maximally screen possible PC and SM molecules. For PC, the fatty acid at sn-1 and sn-2 of the glycerol backbone was identified based on the product ions in negative mode. A total of 91 PCs and 31 SMs molecular species, consisting of 166 PCs and 39 SMs regioisomers, were detected in human serum, which is the most comprehensive identification of PC and SM species in serum. The qualitative distributions of PC in rat and SM in golden hamster, respectively, were more similar with that of human from an overall perspective. Those results provided guidance regarding to the animal model selection for mimicking lipid related-syndromes or diseases in human.

18.
Can J Gastroenterol Hepatol ; 2020: 8888405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32832491

RESUMO

Objective: There is a limited diagnosis of nonalcoholic fatty liver disease (NAFLD). Thus, the noninvasive assessments are worth exploring. We determined the associations of phase angles (PhAs) obtained from bioelectric impedance analysis (BIA) with the risk of NAFLD in an overweight population. Methods: A study involving 953 overweight participants was conducted in Wuhan city, China. The associations between PhAs (right arm, left arm, body trunk, right leg, left leg, and whole body) and the risk of NAFLD were conducted using multivariate logistic regression analyses. The associations of PhAs with the controlled attenuation parameter (CAP), a noninvasive assessment of liver steatosis and fibrosis, were also evaluated by both linear and logistic regression analyses. Results: The PhA values of the whole body, trunk, and legs were significantly lower (P < 0.05) in the NAFLD group than the non-NAFLD group. After adjustment for BMI, gender, education, income/year, hyperlipidemia, hypertension, diabetes, smoking, passive smoking, and drinking, significant associations of PhA values of the right leg, left leg, and whole body with the risk of NAFLD were observed. In addition, the PhA of the right leg, left leg, and whole body were significantly related to the CAP values. Further stratified analyses indicated that these associations were significant in the participants with BMI <30, but not in the participants with BMI ≥30. Conclusions: PhAs might be effective indicators in the management of NAFLD among overweight people.

19.
Oncogene ; 39(38): 6113-6128, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32814829

RESUMO

VHL mutations are the most common tumorigenic lesions in clear cell renal cell carcinoma (ccRCC) and result in continued activation of the HIF/VEGF pathway and uncontrolled cancer progression. Receptor tyrosine kinase (RTK) inhibitors such as sunitinib have been demonstrated to target tumorigenic signaling pathways, delay tumor progression, and improve patient prognosis in metastatic renal cell carcinoma (mRCC). Although several mechanisms of sunitinib resistance have been reported, the solutions to overcome this resistance remain unclear. In our study, we found that increased expression of Y-box binding protein 1 (YB1, a multidrug resistance associated protein) and EphA2 (a member of the erythropoietin-producing hepatocellular (Eph) receptor family, belonging to the RTK family) mediated sunitinib resistance and mRCC exhibited a large phenotypic dependence on YB1 and EphA2. In addition, our findings confirm that YB1 promotes the invasion, metastasis and sunitinib resistance of ccRCC by regulating the EphA2 signaling pathway. Furthermore, pharmacological inhibition of EphA2 through the small molecule inhibitor ALW-II-41-27 reduced the proliferation of sunitinib-resistant tumor cells, suppressed tumor growth in vivo, and restored the sensitivity of sunitinib-resistant tumor cells to sunitinib in vitro and in vivo. Mechanistically, YB1 increases the protein levels of EphA2 by maintaining the protein stability of EphA2 through inhibition of the proteasomal degradation pathway. Collectively, our findings provide the theoretical rationale that ccRCC metastasis and RTK-directed therapeutic resistance could be prospectively and purposefully targeted.

20.
Opt Express ; 28(12): 17307-17319, 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32679941

RESUMO

Polymer-templated nematic liquid crystal (LC) holographic gratings via visible-light recording are presented in the presence of reactive mesogens (RMs) and rose bengal (RB)/N-phenylglycine (NPG) photoinitiation systems. By optimizing the concentration of RMs in the polymer-templated LC gratings, the template after being washed out can be refilled with suitable fluidic components. And the dependence of the first-order diffraction efficiency (DE) on the concentration of RB and NPG molecules was discussed in detail. The polarization-dependency of diffraction properties was also investigated. It is revealed that the diffractive behaviors of polymer-templated LC gratings can be dynamically reconfigured by varying temperature or refilling organic solutions with different refractive index (RI). Furthermore, the potential for recording holograms using green light is explored. We expect that the reconfigurable polymer-templated LC gratings fabricated via visible-light interference would provide a facile approach to regulate the diffraction properties of holographic gratings apart from electric field, thus paving a way towards a class of novel anti-counterfeiting devices.

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