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J Anal Toxicol ; 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31965188


Diazepam abuse is widespread all over the word, leading to an increasing number of forensic cases such as suicide, drug-driving and robbery, but relevant studies are limited regarding the extraction of diazepam and its metabolites in oral fluid. This study aimed to investigate the pharmacokinetics of diazepam and its metabolites in oral fluid after a single oral dose in healthy volunteers. There was a total of 28 volunteers, and each ingested 5 mg diazepam orally, then ~2 mL oral fluid were collected from each participant at post-consumption time-points of prior (zero), 1, 2, 4, 8, 12, 24 h and 2, 3, 6, 12 and 15 days, respectively. All samples were extracted with solid-phase extraction and analyzed with high-performance liquid chromatography-tandem mass spectrometry method, and diazepam and nordazepam were detected in the oral fluid of volunteers. Pharmacokinetics of diazepam in oral fluid conformed to a two-compartment model, and k01_HL, k12_HL, k10_HL were 0.7 ± 1.1, 31.4 ± 68.5, 12.1 ± 11.6 h, respectively, nordazepam conformed to an one-compartment model, and k01_HL, k10_HL were 41.5 ± 44.8, 282.3 ± 365.5 h, respectively. Both diazepam and nordazepam could be detected continuously for 15 days, although there were individual differences, and the results regarding diazepam detecting in oral fluid will be of much help in forensic science and drug screening filed.

PeerJ ; 7: e7561, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31565558


A new species of ichthyosauriform is recognized based on 20 specimens, including nearly complete skeletons, and named Chaohusaurus brevifemoralis. A part of the specimens was previously identified as Chaohusaurus chaoxianensis and is herein reassigned to the new species. The new species differs from existing species of Chaohusaurus in a suite of features, such as the bifurcation of the caudal peak neural spine and a short femur relative to trunk length. The specimens include both complete and partially disarticulated skulls, allowing rigorous scrutiny of cranial sutures. For example, the squamosal does not participate in the margin of the upper temporal fenestra despite previous interpretations. Also, the frontal unequivocally forms a part of the anterior margin of the upper temporal fenestra, forming the most medial part of the anterior terrace. The skull of the holotype largely retains three-dimensionality with the scleral rings approximately in situ, revealing that the eyeball was uncovered in two different directions, that is, laterally and slightly dorsally through the main part of the orbit, and dorsally through the medial extension of the orbit into the skull roof. This skull construction is likely a basal feature of Ichthyosauromorpha. Phylogenetic analyses place the new species as a sister taxon of Chaohusaurus chaoxianensis.

Front Oncol ; 9: 369, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31143705


Intrahepatic cholangiocarcinoma (ICC) ranks as the second most malignant type of primary liver cancer with a high degree of incidence and a very poor prognosis. Fat mass and obesity-associated protein (FTO) functions as an eraser of the RNA m6A modification, but its roles in ICC tumorigenesis and development remain unknown. We showed here that the protein level of FTO was downregulated in clinical ICC samples and cell lines and that FTO expression was inversely correlated with the expression of CA19-9 and micro-vessel density (MVD). A Kaplan-Meier survival analysis showed that a low expression of FTO predicted poor prognosis in ICC. in vitro, decreased endogenous expression of FTO obviously reduced apoptosis of ICC cells. Moreover, FTO suppressed the anchorage-independent growth and mobility of ICC cells. Through mining the database, FTO was found to regulate the integrin signaling pathway, inflammation signaling pathway, epidermal growth factor receptor (EGFR) signaling pathway, angiogenesis, and the pyrimidine metabolism pathway. RNA decay assay showed that oncogene TEAD2 mRNA stability was impaired by FTO. In addition, the overexpression of FTO suppressed tumor growth in vivo. In conclusion, our study demonstrated the critical roles of FTO in ICC.

Huan Jing Ke Xue ; 39(9): 4096-4104, 2018 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-30188050


Different combinations of low impact development (LID) technologies can be applied for control of urban non-point source pollution. There are currently few evaluations of urban non-point source pollution and pollution load reduction based on a combination of porous asphalt and bio-retention. Taking Shenzhen International Low Carbon City as an example, road-deposited sediments were collected prior to and after rainfall events. Runoff was monitored under six typical rainfall events, from porous asphalt and the inlet/outlet of bio-retention. Through analysis of changes in the process of "build-up-wash-off-transport" of pollutant loads, the average build-up of road-deposited sediments in the study area was found to be (15.80±3.79) g·m-2; the mass percentage of road-deposited sediments (size>250 µm) was approximately 65.14%. The average wash-off percentage of six different intensity rainfall events was 17.15%, and road-deposited sediments (size<105 µm) were carried by 62.71%-74.94%. The average pollution loads of surface runoff pollutants SS, TN, and TP were 2.02, 0.025, and 0.0013 g·m-2, respectively. The removal rates of SS, TN, and TP through porous asphalt under infiltration and filtration were 70.26%, 46.29%, and 19.27%, respectively. The secondary purification removal rates of runoff water in bio-retention were 85.25%, 20.22%, and 70.27%, respectively. Pollutant loads into Dingshan River totaled 0.08, 0.011, and 0.0003 g·m-2, representing 4.05%, 43.47%, and 24.39% of runoff. The combination thus had a significant effect on runoff purification. Through quantitative research on the formation of non-point source pollution, this paper provides a scientific basis for estimating pollution loads of urban non-point source pollution and evaluating the performance of LID projects. It makes suggestions for the popularization and application of LID and sponge city design in China.

Cancer Res ; 78(10): 2536-2549, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29483096


Two isoforms of human Polycomb-like protein 3 (hPCL3) have been reported as components of the nuclear Polycomb repressive complex 2 (PRC2), with the short isoform (hPCL3s) showing a dominant cytoplasmic localization. The function of cytoplasmic hPCL3s has, however, not been addressed. In this study, we report that hPCL3s is upregulated in clinical hepatocellular carcinoma (HCC) samples and its expression correlated with HCC clinical features. hPCL3s positively regulated the migration, invasion, and metastasis of HCC cells. hPCL3s interacted with components of the cytoplasmic ß-catenin destruction complex, inhibited ß-catenin degradation, and activated ß-catenin/T-cell factor signaling. Downstream of the ß-catenin cascade, IL6 mediated the motility-promoting functions of hPCL3s. Forced expression of hPCL3s in the liver of a HCC mouse model promoted tumorigenesis and metastasis. Taken together, these data show that hPCL3s promotes the metastasis of HCC by activating the ß-catenin/IL6 pathway.Significance: hPCL3s has an oncogenic role in hepatocellular carcinoma by activating the ß-catenin/IL6 signaling axis to promote metastasis. Cancer Res; 78(10); 2536-49. ©2018 AACR.

Carcinoma Hepatocelular/patologia , Interleucina-6/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Nucleares/metabolismo , beta Catenina/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas de Ligação a DNA , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Invasividade Neoplásica/genética , Proteínas Nucleares/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Fatores de Transcrição , Via de Sinalização Wnt/genética , Ensaios Antitumorais Modelo de Xenoenxerto
Pancreas ; 43(4): 592-6, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24713842


OBJECTIVE: The aim of this study was to characterize cells expressing insulin and amylase in adult human pancreas. METHODS: We applied serial section and immunohistochemistry to pancreas samples from 5 adult nondiabetic subjects (2 men and 3 women;mean age, 65.8 years; random plasma glucose level, 5.1 mM). Cells expressing insulin and amylase were captured by immunofluorescence and confocal miscroscopy. RESULTS: We found a widespread occurrence of insulin-producing cells in exocrine acini and amylase-reactive acinar cells in well-formed islets. The insulin-producing cells in exocrine acini predominantly formed single and double cell units though cell clusters, and islands occurred. Acini containing insulin-producing cells outnumbered the islets with a factor of approximately 5. Confocal microscopy and double immunostaining identified acinar A-cells coexpressing both amylase and insulin. CONCLUSIONS: The acinar A-cells represent a distinct category of pancreatic cell populations and might be possible endogenous progenitors of insulin-producing cells in normal and abnormal metabolic homeostasis.

Células Secretoras de Insulina/química , Insulina/análise , Pâncreas Exócrino/química , Idoso , Amilases/análise , Autopsia , Feminino , Imunofluorescência , Humanos , Masculino , Microscopia Confocal , Pessoa de Meia-Idade , Pâncreas Exócrino/citologia