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1.
Cancer Med ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31912664

RESUMO

PURPOSE: Previous studies provide inconsistent interpretations of the effect of inherited genetic factors on the survival and prognosis of patients with breast cancer. The aim of this study was to examine the effect of germline BRCA1 and BRCA2 mutation on survival and subsequent breast events in Chinese women who underwent breast-conserving surgery. METHODS: A retrospective review of the clinical and pathological records was performed in patients diagnosed with primary invasive breast cancer between 2005 and 2018 in the cancer registry database. Clinicopathological data and data regarding treatment and outcomes, including date and site of disease progression, were collected. The survival outcomes and independent risk factors were conducted using SPSS. RESULTS: Overall, a total of 501 patients who underwent breast-conserving surgery were identified and subjected to analyses, of which 63 cases with BRCA1 or BRCA2 mutation. The median age at diagnosis was 41 (range, 24-74) for carriers and 37 (range, 17-84) for noncarriers. After a median follow-up time of 61 months (range, 8-161) and 70 months (range, 0-153), respectively, in carriers and noncarriers, the overall survival (P = .173) and disease-free survival (P = .424) were not significantly different. Analogously, there was no significant difference between the two groups about the outcomes of ipsilateral breast tumor recurrence (P = .348), yet the contralateral breast cancer (CBC) was overt worse than noncarriers (P < .001). When adjusted to confounding factors, BRCA mutation was the only independent risk factors to CBC (HR = 7.89, P = .01). CONCLUSION: In this study, BRCA mutation carriers have higher risk of CBC. And, BRCA mutation is the only independent risk factor to CBC. Therefore, intensive surveillance and follow-up as well as more effective individual prevention are urgent. Decisions on alternatively effective prevention, especially the prevention of CBC, are urgent and should take into account patient prognosis and preferences.

2.
Reprod Toxicol ; 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923462

RESUMO

High-resolution metabolomics (HRM) profiling of metabolic fingerprints can improve understanding of how poly and perfluoroalkyl substances (PFASs) induce metabolic alterations of in utero environment and impact fetal health. HRM profiling and quantification of PFASs were performed for 397 maternal perinatal serum samples collected from 1959-1967 in the Child Health and Development Studies (CHDS). We used Metabolome-Wide Association Studies (MWAS) and pathway enrichment analysis for metabolic associations with PFOS, its precursor EtFOSAA, and EtFOSAA-to-PFOS ratio. Distinct metabolic profiles were found with EtFOSAA and PFOS. Urea cycle metabolites such as arginine, lysine and creatine had opposite associations with EtFOSAA (negative) and PFOS (positive); whereas, carnitine shuttle metabolites were found to be exclusively and positively associated with PFOS indicating perturbation in fatty acid metabolism. These differential metabolic associations for precursor and end-product represent an important first step in identifying how PFASs alter the in utero environment and potentially leads to disease risk.

3.
Hum Cell ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31894477

RESUMO

This study was performed to investigate the role of PTK7 in esophageal squamous cell carcinoma (ESCC) stem-like cells (CSCs). PTK7 expression in ESCCs identified by RT-qPCR, and CSC-like cells were isolated from populations of NEC and TE-1 cells. The CSC-like cells were verified by flow cytometric analyses performed using CD34 and CD133 antibodies, and RT-qPCR and western blot assays were used to examine the self-renewal capability of CSC-like cells. CSC-like cells treated with PTK7 siRNA or a P53-specific inhibitor (PFTα) were analyzed for their sphere formation capacity and their apoptosis and migration/invasion capabilities by sphere formation, flow cytometry, and transwell assay, respectively. Their levels of P53, MKK3, and cleaved caspase 3 expression were examined by western blot analysis. Our results revealed that a majority of the isolated CSC-like cells were CD34+/CD133+ double positive cells. Nango, Sox2, and OCT4 were dramatically increased in the separated CSC-like cells, which had the pluripotency and self-renewal properties of stem cells. Additional, PTK7 was dramatically upregulated in the ESCC tissues and CSC-like cells. An investigation of the function of CSC-like cells revealed that knockdown of PTK7 reduced their sphere formation, promoted apoptosis, and suppressed their migration and invasion abilities, all of which could be significantly reversed by PFTα. Mechanistic studies showed that PFTα could attenuate the upregulation of P53, MKK3, and cleaved caspase 3 expression that was induced by PTK7 knockdown in CSC-like cells. PTK7 increased the malignant behaviors of CSC-like cells derived from ESCC cells by regulating p53. Therefore, this study suggests PTK7 as an underlying target for therapy against ESCC.

4.
Bioorg Med Chem ; 28(2): 115258, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31864776

RESUMO

Proguanil, a member of biguanide family, has excellent anti-proliferative activities. Fluorine-containing compounds have been demonstrated to have super biological activities including enhanced binding interactions, metabolic stability, and reduced toxicity. In this study, based on the intermediate derivatization methods, we synthesized 13 new fluorine-containing proguanil derivatives, and found that 7a,7d and 8e had much lower IC50 than proguanil in 5 human cancerous cell lines. The results of clonogenic and scratch wound healing assays revealed that the inhibitory effects of derivatives 7a,7d and 8e on proliferation and migration of human cancer cell lines were much better than proguanil as well. Mechanistic study based on representative derivative 7a indicated that this compound up-regulates AMPK signal pathway and downregulates mTOR/4EBP1/p70S6K. In conclusion, these new fluorine-containing derivatives show potential for the development of cancer chemotherapeutic drugs.

5.
Bioorg Chem ; : 103487, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31831161

RESUMO

Based on the structural characteristics of aztreonam (AZN) and its target PBP3, a series of new monobactam derivatives bearing various substituents on oxime residue were prepared and evaluated for their antibacterial activities against susceptible and resistant Gram-negative bacteria. Among them, compounds 8p and 8r displayed moderate potency with MIC values of 0.125-32 µg/mL against most tested Gram-negative strains, comparable to AZN. Meanwhile, the combination of 8p and 8r with avibactam as a ß-lactamases inhibitor, in a ratio of 1:16, showed a promising synergistic effect against both ESBLs- and NDM-1-producing K. pneumoniae, with significantly reduced MIC values up to 8-fold and >256-fold respectively. Furthermore, both of them demonstrated excellent safety profiles both in vitro and in vivo. The results provided powerful information for further structural optimization of monobactam antibiotics to fight ß-lactamase-producing resistant Gram-negative bacteria.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31820254

RESUMO

Transport and retention of nano PbO (nPbO) in quartz sand-alluvial soil mixture column and alluvial soil column were investigated. The dissolution kinetics of nano size lead chemicals in alluvial soil and nPbO in different soils were investigated through aging experiment and batch extraction experiment. nPbO was trapped mainly near the inlet of both quartz sand-alluvial soil mixture column and alluvial soil column. pH value (6, 7, and 8) and ion strength (1 and 10 mM CaCl2) did not have obvious effect on the retention of nPbO. nPbO, nPbSO4, and nPbCO3 experienced distinguishable dissolution in alluvial soil, but had similar dissolution trend. The dissolution kinetics of nPbO in alluvial soil and black soil were similar, increasing fast at 0-60 days and then slowing down. The dissolution of nPbO in red soil extracted by using HCl solution, CaCl2 solution and deionized water increased obviously from 90 to 180 days, differed from that by using EDTA extraction. The dissolution kinetics from three contaminated soils assessed by EDTA was similar. Overall, although nPbO had much weaker transport than Pb (II), dissolution would improve its mobility greatly.

7.
ISA Trans ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31784046

RESUMO

This paper addresses the problem of adaptive disturbance rejection for the course tracking of marine vessels with unknown motion model parameters including the control coefficient and marine environmental disturbances under actuator constraint. An adaptive disturbance estimator is constructed to obtain disturbance estimations, without the priori information of vessel motion model dynamic parameters. The Nussbaum-gain function is inserted to alleviate the requirement on the control coefficient. A saturation dynamic filter is adopted to address the actuator constraint effect. By the fusion of the command filtered backstepping method, the adaptive disturbance rejection tracking controller is designed. The computational burden is reduced due to command filters to avoid the virtual stabilizing function differentiation. Stability analysis proves the vessel course trajectory tracking and the closed-loop steering stability. Numerical simulations on an unmanned surface vessel validate the adaptive course tracking approach.

8.
PeerJ ; 7: e7929, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31788352

RESUMO

The C2H2 zinc finger protein (C2H2-ZFP) transcription factor family regulates the expression of a wide variety of genes in response to various developmental processes or abiotic stresses; however, these proteins have not yet been comprehensively analyzed in tomato (Solanum lycopersicum). In this study, a total of 104 C2H2-ZFs were identified in an uneven distribution across the entire tomato genome, and include seven segmental duplication events. Based on their phylogenetic relationships, these genes were clustered into nine distinct categories analogous to those in Arabidopsis thaliana. High similarities were found between the exon-intron structures and conserved motifs of the genes within each group. Correspondingly, the expression patterns of the C2H2-ZF genes indicated that they function in different tissues and at different developmental stages. Additionally, quantitative real-time PCR (qRT-PCR) results demonstrated that the expression levels of 34 selected C2H2-ZFs are changed dramatically among the roots, stems, and leaves at different time points of a heat stress treatment, suggesting that the C2H2-ZFPs are extensively involved in the heat stress response but have potentially varying roles. These results form the basis for the further molecular and functional analysis of the C2H2-ZFPs, especially for those members that significantly varied under heat treatment, which may be targeted to improve the heat tolerance of tomato and other Solanaceae species.

9.
Org Lett ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31802677

RESUMO

A highly diastereo- and enantioselective Ir-catalyzed hydrogenation of unfunctionalized 2,3-disubstituted quinolines, especially 3-alkyl-2-arylquinolines, has been realized. The success of this hydrogenation is ascribed to the use of a structurally fine-tuned chiral phosphine-phosphoramidite ligand with a (Sa)-3,3'-dimethyl H8-naphthyl moiety and (Rc)-1-phenylethylamine backbone. The hydrogenation displayed broad functional group tolerance, thus furnishing a wide range of optically active 2,3-disubstituted tetrahydroquinolines in up to 96% ee and with perfect cis-diastereoselectivity.

10.
J Biophotonics ; : e2389, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804752

RESUMO

Development of label-free methods for accurate classification of cells with high throughput can yield powerful tools for biological research and clinical applications. We have developed a deep neural network of DINet for extracting features from cross-polarized diffraction image (p-DI) pairs on multiple scales of pixel to accurately classify cells in 5 types. A total of 6185 cells were measured by a polarization diffraction imaging flow cytometry (p-DIFC) method followed by cell classification with DINet on p-DI data. The averaged value and standard deviation of classification accuracy were found to be 98.9% ±1.00% on test datasets for 5-fold training and test. The invariance of DINet to image translation, rotation and blurring has been verified with an expanded p-DI dataset. To study the feature based classification by DINet, two sets of correctly and incorrectly classified cells were selected and compared for each of two prostate cell types. It has been found that the signature features of large dissimilarities between p-DI data of the two cell sets of the same type increase markedly from convolutional layers 1 and 2 to layers 3 and 4. These results clearly demonstrate the importance of high-order correlations extracted at the deep layers for accurate and robust cell classification. This article is protected by copyright. All rights reserved.

11.
Beilstein J Nanotechnol ; 10: 2229-2237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807408

RESUMO

Electrodes with high conductivity and flexibility are crucial to the development of flexible lithium-ion batteries. In this study, three-dimensional (3D) LiFePO4 and Li4Ti5O12 fiber membrane materials were prepared through electrospinning and directly used as self-standing electrodes for lithium-ion batteries. The structure and morphology of the fibers, and the electrochemical performance of the electrodes and the full battery were characterized. The results show that the LiFePO4 and Li4Ti5O12 fiber membrane electrodes exhibit good rate and cycle performance. In particular, the all-fiber-based gel-state battery composed of LiFePO4 and Li4Ti5O12 fiber membrane electrodes can be charged/discharged for 800 cycles at 1C with a retention capacity of more than 100 mAh·g-1 and a coulombic efficiency close to 100%. The good electrochemical performance is attributed to the high electronic and ionic conductivity provided by the 3D network structure of the self-standing electrodes. This design and preparation method for all-fiber-based lithium-ion batteries provides a novel strategy for the development of high-performance flexible batteries.

12.
Neurosci Bull ; 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823302

RESUMO

Characterizing the three-dimensional (3D) morphological alterations of microvessels under both normal and seizure conditions is crucial for a better understanding of epilepsy. However, conventional imaging techniques cannot detect microvessels on micron/sub-micron scales without angiography. In this study, synchrotron radiation (SR)-based X-ray in-line phase-contrast imaging (ILPCI) and quantitative 3D characterization were used to acquire high-resolution, high-contrast images of rat brain tissue under both normal and seizure conditions. The number of blood microvessels was markedly increased on days 1 and 14, but decreased on day 60 after seizures. The surface area, diameter distribution, mean tortuosity, and number of bifurcations and network segments also showed similar trends. These pathological changes were confirmed by histological tests. Thus, SR-based ILPCI provides systematic and detailed views of cerebrovascular anatomy at the micron level without using contrast-enhancing agents. This holds considerable promise for better diagnosis and understanding of the pathogenesis and development of epilepsy.

13.
Elife ; 82019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825310

RESUMO

Mammalian two-pore-channels (TPC1, 2; TPCN1, TPCN2) are ubiquitously- expressed, PI(3,5)P2-activated, Na+-selective channels in the endosomes and lysosomes that regulate luminal pH homeostasis, membrane trafficking, and Ebola viral infection. Whereas the channel activity of TPC1 is strongly dependent on membrane voltage, TPC2 lacks such voltage dependence despite the presence of the presumed 'S4 voltage-sensing' domains. By performing high-throughput screening followed by lysosomal electrophysiology, here we identified a class of tricyclic anti-depressants (TCAs) as small-molecule agonists of TPC channels. TCAs activate both TPC1 and TPC2 in a voltage-dependent manner, referred to as Lysosomal Na+ channel Voltage-dependent Activators (LyNa-VAs). We also identified another compound which, like PI(3,5)P2, activates TPC2 independent of voltage, suggesting the existence of agonist-specific gating mechanisms. Our identification of small-molecule TPC agonists should facilitate the studies of the cell biological roles of TPCs and can also readily explain the reported effects of TCAs in the modulation of autophagy and lysosomal functions.

14.
Leuk Lymphoma ; : 1-10, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878809

RESUMO

Hypomethylating agents (HMA) showed overall survival (OS) benefits in patients with higher-risk myelodysplastic syndromes (HR-MDS) in clinical trials. We conducted a retrospective cohort study of Surveillance, Epidemiology, and End Results (SEER)-Medicare data of patients ≥66 years diagnosed with refractory anemia with excess blasts (RAEB), a proxy for HR-MDS, in 01/2001-04/2004 (pre-period) or 01/2006-12/2011 (post-period). Association between post-period diagnosis and OS was examined using propensity scores (PS)-matched samples. Among 1876 RAEB patients, median OS was 9 months and 30.8% received HMAs (3.6% in pre-period; 43.0% in post-period) with no association between post-period diagnosis and OS. In the top PS quartile, post-period diagnosis was associated with a 74% lower risk of death (Hazard ratio [HR] = 0.26, 95%-CI: 0.10-0.69, p = 0.007), while outcomes were worse in the lowest PS quartile (HR = 2.80, 95%-CI: 1.06-7.36, p = 0.037). HMA lead to a 3-month OS benefit for patients most likely to receive HMA but not for unselected RAEB cohort.

15.
ISA Trans ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31882177

RESUMO

This paper develop a novel composite anti-disturbance control (CADC) method for a class of stochastic nonlinear systems in which input saturation and multiple heterogeneous disturbances occur. The disturbances include additive white noise, multiplicative white noise and modeled disturbances with coupling of energy-limited white noise and state signals. The input saturation item of system is approximated by the polytopic bounding method. In order to estimate the modeled disturbances, a novel stochastic saturating disturbance observer (SSDO) is designed. The CADC scheme is presented by integrating SSDO with convex hull expression of saturated linear feedback law, such that the superior anti-disturbance performance to be achieved while overcoming the effects of input saturation. Finally, the validity and usability of the developed scheme are testified by the numerical simulation and practical application example.

16.
Cell Death Differ ; 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31853006

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

17.
Tree Physiol ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31860727

RESUMO

Most bamboo species including Moso bamboo (Phyllostachys edulis) are tropical or subtropical plants that greatly contribute to human wellbeing. Low temperature is one of the main environmental factors restricting bamboo growth and geographic distribution. Our knowledge of the molecular changes during bamboo adaption to cold stress remains limited. Here, we provided a general overview of the cold-responsive transcriptional profiles in Moso bamboo by systematically analyzing its transcriptomic response under cold stress. Our results showed that low temperature induced strong morphological and biochemical alternations in Moso bamboo. To examine the global gene expression changes in response to cold, 12 libraries (non-treated, cold-treated 0.5 h, 1 h and 24 h at -2°C) were sequenced using an Illumina sequencing platform. Only a few differentially expressed genes (DEGs) at early stage while a large number of DEGs at late stage were identified in this study, suggesting that the majority of cold response genes in bamboo are late-responsive genes. A total of 222 transcription factors from 24 different families were differentially expressed during 24h cold treatment, and the expressions of several well-known C-repeat/dehydration responsive element-binding factor (CBF) negative regulators were significantly up-regulated in response to cold, indicating the existence of special cold response networks. Our data also revealed that the expression of genes related to cell wall and the biosynthesis of fatty acids were altered in response to cold stress, indicating their potential roles in the acquisition of bamboo cold tolerance. In summary, our studies showed that both plant-kingdom conserved and species-specific cold response pathways exist in Moso bamboo, which lays the foundation for studying the regulatory mechanisms underlying bamboo cold stress response and provides useful gene resources for the construction of cold-tolerant bamboo through genetic engineering in the future.

18.
Nanotechnology ; 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31860898

RESUMO

In this paper, wafer-scale dense and meosoporous TiO2 films are fabricated via spin-coating and thermal treatment. A photo-curable resin, acrylated polytitanoxane tetramer (Ti-resin), is synthesized as the precursor of TiO2 to deposit dense films. Refractive index of TiO2 films at 500nm is tuned from 2.17 (dense) to 1.49 (porous) by changing film porosity via adding different amount of polystyrene (PS) to the precursor solvent. A reactive compatibilizer containing one mercapto group and three benzyl rings is synthesized to reduce phase separation and prevent film crack of porous films during the calcinations. The deposition protocol is optimized to prevent infiltration of dense TiO2 layers into porous TiO2 layers. Film thicknesses of both dense and porous TiO2 films can be linearly tuned by changing deposition number. All-TiO2 1D photonic crystals with different structural colors are successfully fabricated on quartz and silicon wafers with reflectivity of at least 90%, covering the spectrum from 400 to 800nm.

19.
Int J Biol Macromol ; 145: 646-654, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31887383

RESUMO

In the present study, an exopolysaccharide (EPS) producer Rhodococcus erythropolis HX-2 was isolated from Xinjiang oil field, China. The HX-2 EPS (name HPS) production reached 8.957 g/L by RSM in MSM medium. The HPS was purified by ethanol precipitation and fractionation by DEAE-Cellulose and Sepharose column, the yield of HPS was 3.736 g/L. HPS composed by glucose, galactose, fucose, mannose and glucuronic acid. FT-IR spectroscopy indicated the presence of a large amount of hydroxyl groups. NMR spectroscopy indicated the existence of both α and ß-configuration for sugar moieties present in HPS. The degradation temperature (255.4 °C) of the HPS was determined by thermogravimetric analysis (TGA). A reticular structure of HPS was observed by SEM and the AFM analysis of the HPS revealed straight chains line. Meanwhile, the WSI and WHC of HPS were 92.15 ± 3.05% and 189.45 ± 5.65%, respectively. Finally, In vitro anticancer activity purified EPS was evaluated on L929 normal cells, A549 cancer cells, SMMC-7721 liver cancer cells and Hela cervical cancer cell. HPS inhibited the growth of cancer cells in a certain concentration without damage to normal cells. These characteristics indicate that its potential application value in food, industry and pharmaceutical application.

20.
Huan Jing Ke Xue ; 40(8): 3501-3508, 2019 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854755

RESUMO

The external pollution of Dianchi Lake has been effectively controlled with the implementation of the integrated water environment control project. However, further attention should be paid to endogenous pollutants, such as surface sediments. To investigate the distribution of 16 polycyclic aromatic hydrocarbons (PAHs) in surface sediments of Dianchi Lake, PAH concentrations in 19 surface sediment samples (collected in December 2016) were quantitatively measured by gas chromatography-mass spectrometry (GC-MS). The spatial and temporal distribution, sources, and ecological risks were also analyzed. The concentration of total PAHs (TPAHs) in the Dianchi Lake surface sediments varied in the range of 92.31-1546.78 ng·g-1 with an average of 496.30 ng·g-1. The average concentration of TPAHs in the surface sediments from Caohai (932.37 ng·g-1) was much greater than that from Waihai (380.02 ng·g-1). With the implement of the integrated water environment control project, the concentration of TPAHs in the surface sediments from Dianchi Lake was significantly lower than those detected in 2012, and was already relatively low level among other key waterbodies in China. The PAH with the highest concentration was fluoranthene (80.65 ng·g-1) and the substance with the highest toxic equivalent quantity (TEQ) was dibenz[a, h] anthracene (42.97 ng·g-1). The PAHs were mainly composed of 4 ring and 5-6 ring compounds (with the concentration ratio of 40.38% and 40.22%, respectively), which indicated that the proportions of middle-ring and high-ring compounds were generally consistent. The results of the molecular diagnostic ratio analysis showed that the primary source of PAHs in Dianchi Lake surface sediments are biomass and coal combustion. Based on the potential ecological risk marker comparison method, the entire lake was classified as having a low ecological risk, while the ecological risk of Caohai was relatively higher, which should be concerned further. The results provide initial data and act as an important reference for the conservation and improvement of water quality in Dianchi Lake.

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