Hollow cage-like PtCu nanozyme-regulated photo-activity of porous CdIn2S4/SnO2 heterojunctions for ultrasensitive PEC sensing of streptomycin.

Streptomycin (STR) is extensively employed for preventive and curative purposes in animals, which is accumulated in human body through food chain and induces serious health problems. Herein, highly photoactive type II heterojunctions of porous CdIn2S4/SnO2 microspheres were initially prepared, which can effectively inhibit the recombination of the charge-hole pairs. Besides, the peroxidase-mimicking catalytic property of the hollow PtCu nanocages (PtCu NCs) was carefully investigated by UV-vis spectroscopy, where catalytic oxidation of tetramethylbenzidine behaved as the benchmarked reaction. On such basis, a highly selective photoelectrochemical (PEC) aptasensor was established with the CdIn2S4/SnO2 heterojunctions for bioanalysis of streptomycin, coupled by the PtCu NCs nanozyme-catalyzed biocatalytic precipitation to achieve signal magnification. Specifically, the home-made nanozyme was applied for catalytic oxidation of 3,3'-diaminobenzidine to generate insulating precipitate in aqueous H2O2 system and thereby block the light harvesting on the photoanode, showing steeply declined PEC responses. The as-built aptasensor showed a broad linear range of 0.01-200 nM with a low limit of detection of 7.50 pM (S/N = 3) for such analysis, combined by exploring its practical detection in milk samples. This work shows excellent nanozyme-catalyzed signal amplification for fabrication of ultrasensitive PEC biosensors towards other antibiotics detection.

Ultrasensitive PEC cytosensor for breast cancer cells detection and inhibitor screening based on plum-branched CdS/Bi2S3 heterostructures.

Breast cancer is the most common malignant tumor in women, which seriously threatens the life and health of patients. Therefore, facile and sensitive detection of human breast cancer cells is crucial for cancer diagnosis. In this work, plum-branched CdS/Bi2S3 heterostructures (CdS/Bi2S3 HSs) were synthesized under hydrothermal condition, whose photoelectrochemical (PEC) property and biocompatibility were scrutinously investigated. In parallel, a signal amplification strategy was designed based on immune recognition between epidermal growth factor receptor (EGFR) overexpressed on membrane of breast cancer cells MDA-MB-231 and its aptamer. Integration of the above together, a highly sensitive PEC cytosensor was developed for analysis of target MDA-MB-231 cells, exhibiting a wider linear range of 1 × 102 âˆ¼ 3 × 105 cells mL-1 with a limit of detection (LOD) down to 6 cells mL-1 (S/N = 3). Further, the biosensor was explored for anticancer drug (e.g., dacomitinib) screening by monitoring the variations in the PEC signals of the expressed EGFR upon drug stimulation. The obtained CdS/Bi2S3 HSs are identified as promising and feasible photoactive material for determination of cancer cells and drug screening in clinic and related research.

Cu2+-regulated one-pot wet-chemical synthesis of uniform PdCu nanostars for electrocatalytic oxidation of ethylene glycol and glycerol.

The fabrication of effective and stable electrocatalysts is crucial for practical applications of direct alcohol fuel cells (DAFCs). In this study, bimetallic PdCu nanostars (PdCu NSs) were fabricated by a Cu2+-modulated one-pot wet-chemical method, where cetyltrimethyl ammonium bromide (CTAB) worked as a structure-regulating reagent. The morphology, compositions, crystal structures and formation mechanism of the as-prepared PdCu NSs were investigated by a series of techniques. The unique architectures created abundant active sites, which resulted in a large electrochemical active surface area (9.5 m2 g-1). The PdCu NSs showed negative shifts in the onset potentials and large forward peak current densities by contrast with those of commercial Pd black for the catalytic ethylene glycol oxidation reaction (EGOR) and glycerol oxidation reaction (GOR). It revealed that the PdCu NSs outperformed Pd black in the similar surroundings. This work provides a constructive strategy for fabrication of high-efficiency electrocatalysts for alcohol fuel cells.

Pharmacokinetics of Diazepam and Its Metabolites in Urine of Chinese Participants.

BACKGROUND: Urine is conventionally used as a specimen to document diazepam-related crimes; however, few reports have described the pharmacokinetics of diazepam and its metabolites in urine. OBJECTIVE: This study aimed to investigate the pharmacokinetics of diazepam and its metabolites, including glucuronide compounds, in the urine of Chinese participants. METHODS: A total of 28 volunteers were recruited and each participant ingested 5 mg of diazepam orally. Ten milliliters of urine were collected from each participant at post-consumption timepoints of prior (zero), 1, 2, 4, 8, 12, and 24 h and 2, 3, 6, 12, and 15 days. All samples were extracted by solid-phase extraction and analyzed using high-performance liquid chromatography-tandem mass spectrometry. Diazepam and its main metabolites, except for temazepam, were detected in the urine of volunteers. Pharmacokinetic parameters were analyzed using the pharmacokinetic software DAS according to the non-compartment model. RESULTS: Urinary diazepam peaked at 2.38 ng/mL (Cmax) and 1.93 h (Tmax). The urinary metabolite nordiazepam peaked at 1.17 ng/mL and 100.21 h; temazepam glucuronide (TG) peaked at 145.61 ng/mL and 41.14 h; and oxazepam glucuronide (OG) peaked at 101.57 ng/mL and 165.86 h. The elimination half-life (t½z) and clearance (CLz/F) for diazepam were 119.58 h and 65.77 L/h, respectively. The t½z of the metabolites nordiazepam, TG, and OG was 310.58 h, 200.17 h, and 536.44 h, respectively. Finally, this study found that both diazepam and its main metabolites in urine were detectable for at least 15 days, although there were individual differences. CONCLUSION: The results regarding diazepam pharmacokinetics in urine would be of great help in forensic science and drug screening.

An Experimental Pharmacokinetics Study of Diazepam and Its Metabolites in Oral Fluid of Chinese Population.

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.

Repeated evolution of durophagy during ichthyosaur radiation after mass extinction indicated by hidden dentition.

Marine tetrapods quickly diversified and were established as marine top predators after the end-Permian Mass extinction (EPME). Ichthyosaurs were the forerunner of this rapid radiation but the main drivers of the diversification are poorly understood. Cartorhynchus lenticarpus is a basal ichthyosauriform with the least degree of aquatic adaptation, holding a key to identifying such a driver. The unique specimen appeared edentulous based on what was exposed but a CT scanning revealed that the species indeed had rounded teeth that are nearly perpendicular to the jaw rami, and thus completely concealed in lateral view. There are three dental rows per jaw ramus, and the root lacks infoldings of the dentine typical of ichthyopterygians. The well-developed and worn molariform dentition with three tooth rows supports the previous inference that the specimen is not of a juvenile. The premaxilla and the corresponding part of the dentary are edentulous. Molariform dentition evolved three to five times independently within Ichthyosauriformes in the Early and Middle Triassic. Convergent exploitation of hard-shelled invertebrates by different subclades of ichthyosauriforms likely fueled the rapid taxonomic diversification of the group after EPME.

Study on the Pharmacokinetics of Diazepam and Its Metabolites in Blood of Chinese People.

BACKGROUND AND OBJECTIVES: Driving under the influence of diazepam is increasing in China. The pharmacokinetics of diazepam and its metabolites, especially the glucuronide metabolites, are helpful in the identification of diazepam use by drivers. This study aimed to investigate the pharmacokinetics of diazepam and its metabolites (nordazepam, oxazepam, oxazepam glucuronide and temazepam glucuronide) in the blood of Chinese people, and to provide basic data for identifying diazepam use and estimating the time of last diazepam ingestion. METHODS: A total of 28 participants (14 men, 14 women) were recruited and each person received 5 mg diazepam orally. Whole blood was collected at 0 h (pre-dose), and 1 h, 2 h, 4 h, 8 h, 12 h, and 24 h, and at 2 days, 3 days, 6 days, 12 days, and 15 days post-dose. Analytes of interest were extracted via solid-phase extraction and analyzed by a liquid chromatography tandem mass spectrometry method operated in a positive multiple response monitoring mode. Pharmacokinetic parameters were analyzed by a pharmacokinetic software DAS according to the non-compartment model. The time of last diazepam use was estimated using the concentration ratios of diazepam to metabolites and metabolites to metabolites from controlled drug administration studies. RESULTS: The respective time of maximum concentration, the maximum concentration and the elimination half-life of diazepam were 1.04 ± 1.00 h, 87.37 ± 31.92 ng/mL and 129.07 ± 75.00 h; of nordazepam were 133.14 ± 109.63 h, 3.80 ± 1.75 ng/mL, and 229.73 ± 236.83 h; of oxazepam were 100.29 ± 87.16 h, 1.62 ± 2.64 ng/mL, and 382.86 ± 324.58 h; of temazepam glucuronide were 44.43 ± 55.41 h, 2.08 ± 0.88 ng/mL, and 130.53 ± 72.11 h; and of oxazepam glucuronide were 66.86 ± 56.33 h, 1.10 ± 0.41 ng/mL, and 240.66 ± 170.12 h. A good correlation model was obtained from the concentration ratio of diazepam to nordazepam and the time of diazepam use, and the prediction errors were less than 20%. CONCLUSIONS: This study provides a sensitive method to identify diazepam ingestion by monitoring diazepam and its metabolites including glucuronides, as well as to infer the time following oral consumption.

m6A Reader YTHDC2 Promotes Radiotherapy Resistance of Nasopharyngeal Carcinoma via Activating IGF1R/AKT/S6 Signaling Axis.

N6-methyladenosine (m6A) modification has been reported as a critical regulator of gene transcript expression. Although m6A modification plays important roles in tumor development, its role in therapeutic resistance remains unknown. In this study, we aimed to examine the expression level of m6A-modification related proteins and elucidate the effect of m6A-related proteins on radiation response in nasopharyngeal carcinoma (NPC). Among the genes that participated in m6A modification, YTHDC2, a m6A reader, was found to be consistently highly expressed in radioresistant NPC cells. Knocking down of YTHDC2 expression in radioresistant NPC cells improved the therapeutic effect of radiotherapy in vitro and in vivo, whereas overexpression of YTHDC2 in radiosensitive NPC cells exerted an opposite effect. Bioinformatics and mechanistic studies revealed that YTHDC2 could physically bound to insulin-like growth factor 1 receptor (IGF1R) messenger RNA and promoted translation initiation of IGF1R mRNA, which in turn activated the IGF1R-AKT/S6 signaling pathway. Thus, the present study suggests that YTHDC2 promotes radiotherapy resistance of NPC cells by activating the IGF1R/ATK/S6 signaling axis and may serve as a potential therapeutic target in radiosensitization of NPC cells.

The new ichthyosauriform Chaohusaurus brevifemoralis (Reptilia, Ichthyosauromorpha) from Majiashan, Chaohu, Anhui Province, China.

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.

Downregulation of Fat Mass and Obesity Associated (FTO) Promotes the Progression of Intrahepatic Cholangiocarcinoma.

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.

[Evaluation of Effect of Urban Non-point Source Pollution Control on Porous Asphalt-Bio-retention Combined Roads].

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.

hPCL3s Promotes Hepatocellular Carcinoma Metastasis by Activating ß-Catenin Signaling.

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.

Insulin-producing acinar cells in adult human pancreas.

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.