Efficient Holes Abstraction by Precisely Decorating Ruthenium Single Atoms and RuOx Clusters on ZnIn2S4 for Photocatalytic Pure Water Splitting.

Developing efficient photocatalysts for two-electron water splitting with simultaneous H2O2 and H2 generation shows great promise for practical application. Currently, the efficiency of two-electron water splitting is still restricted by the low utilization of photogenerated charges, especially holes, of which the transfer rate is much slower than that of electrons. Herein, Ru single atoms and RuOx clusters are co-decorated on ZnIn2S4 (RuOx/Ru-ZIS) to employ as multifunctional sites for efficient photocatalytic pure water splitting. Doping of Ru single atoms in the ZIS basal plane enhances holes abstraction from bulk ZIS by regulating the electronic structure, and RuOx clusters offer a strong interfacial electric field to remarkably promote the out-of-plane migration of holes from ZIS. Moreover, Ru single atoms and RuOx clusters also serve as active sites for boosting surface water oxidation. As a result, an excellent H2 and H2O2 evolution rates of 581.9 µmol g-1 h-1 and 464.4 µmol g-1 h-1 is achieved over RuOx/Ru-ZIS under visible light irradiation, respectively, with an apparent quantum efficiency (AQE) of 4.36% at 400 nm. This work paves a new way to increase charge utilization by manipulating photocatalyst using single atom and clusters.

Synergistic effect of Na doping and CoSe2 cocatalyst for enhanced photocatalytic hydrogen evolution performance of ZnIn2S4.

Element doping has been demonstrated as a useful strategy to regulate the band gap and electronic structure of photocatalyst for improving photocatalytic activity. Herein, ZnIn2S4 (ZIS) nanosheets were doped with alkali metal ions (Li+, Na+ or K+) by a simple solution method. Experimental characterizations reveal that alkali metal ions doping reduce the band gap, raise the conduction band position, and improve surface hydrophilicity of ZIS. In addition, theoretical calculations show that Na doping increases the electron density at valence band maximum and surrounding S atom, which is conducive to produce more electrons and effective utilization of electrons, respectively. Benefited from above factors, Na-doped ZIS (Na-ZIS) shows the highest photocatalytic hydrogen evolution performance. Furthermore, CoSe2 cocatalyst is loaded on the surface of Na-ZIS (CS/Na-ZIS), which further improve the charge separation and prolong the lifetime of charges. As a result, the optimized CS/Na-ZIS shows a H2 evolution rate of 4525 µmol·g-1·h-1 with an apparent quantum efficiency of 27.5 % at 420 nm, which are much higher than that of pure ZIS. This study provides an in-depth understanding of the synergistic effect of Na doping and CoSe2 cocatalyst in ameliorating photocatalytic activity.

Rapid Detection of Estrogens in Cosmetics by Chemical Derivatization and Paper-Spray Ionization Mass-Spectrometry.

Estrogens in personal care products are harmful to customers. Conventional methods such as HPLC and LC-MS require tedious sample pretreatment and long analytical time. Paper-spray ionization mass spectrometry (PSI-MS) is a powerful tool for the determination of compounds with little time and minimal pretreatment procedures. Since most estrogens show poor responses in PSI-MS, we developed a chemical derivatization and PSI-MS method to determinate three estrogens: estradiol, estriol and ethinyloestradiol with estradiol valerate as the internal standard (I.S.). After derivatization with 2-fluoro-1-methyl-pyridinium-p-toluene-sulfonate, the three estrogens could be quantified in seconds. This method showed good linearity in the range of 0.1~30 µg·mL-1, with R2 > 0.999. Their recovery results were all between 85%~115%. The limits of detection (LOD) were 0.04 µg·mL-1, 0.02 µg·mL-1 and 0.02 µg·mL-1 for estradiol, estriol and ethinyloestradiol respectively, which improved around 200, 2000, and 900 times compared to non-derivative PSI-MS. The method could quantitatively determine estrogens in cosmetics.

Self-assembly fabrication of chitosan-tannic acid/MXene composite film with excellent antibacterial and antioxidant properties for fruit preservation.

It is highly urgent to develop a simple and effective strategy to extend the shelf life of time-sensitive fruits, which are very susceptible to spoilage over time, resulting in considerable food waste. Herein, a biopolymer-based composite film with superior antibacterial and antioxidant properties was developed by introducing MXene and tannic acid into a chitosan network via hydrogen bonding and an electrostatic self-assembly method. The results show that the mechanical properties, water and heat resistance, antibacterial and antioxidant capabilities of the obtained Chitosan-Tannic acid/MXene film are significantly increased to meet the use of packaging film scenarios. The fruit preservation experiments also confirmed that the composite film can effectively extend the shelf life of bananas and grapes through its excellent water vapor and oxygen barrier. These desirable performances enable our newly designed composite film to be an effective and competitive packaging material to solve the fresh fruit preservation dilemma.

NMR Assignments of Six Asymmetrical N-Nitrosamine Isomers Determined in an Active Pharmaceutical Ingredient by DFT Calculations.

N-nitrosamines, which are well-known pro-mutagens, are found in drugs, pickled food and tobacco. Therefore, controlling their concentrations is very important. When an HPLC, GC or NMR analysis is conducted to investigate certain asymmetrical N-nitrosamines, two sets of signals attributed to the asymmetric N-nitrosamine isomers are usually observed. However, few reports on the NMR assignment of asymmetrical N-nitrosamine isomers have been published. In this study, we investigated the NMR assignments of the Z/E isomers of six asymmetrical N-nitrosamines by means of density functional theory (DFT) calculations. The configuration of the major isomer of asymmetrical N-nitrosamine 3 was the Z-configuration. The configuration of the major isomers of asymmetrical N-nitrosamines 4-7 was the E-configuration. Then, we determined the Z/E ratios of these asymmetrical N-nitrosamines by means of variable temperature (VT) and room temperature (RT) 1H-NMR experiments. The ratios of the Z/E isomer 3 quickly increased beyond 100% in the VT 1H NMR experiments. The ratios of Z/E isomers 4-7 were increased in the range of 10-60% in the VT 1H NMR experiments. The results of this study indicate that identifying the isomers of asymmetrical N-nitrosamine is necessary to control the quality of N-nitrosamines for active pharmaceutical ingredients (APIs).

Quantification of Alfacalcidol Tablets Dissolution Content by Chemical Derivatization and LC-MS.

Application of liquid chromatography-mass spectrometry (LC-MS) in analyzing the content of alfacalcidol tablets dissolution faces big challenges due to the low amount of alfacalcidol in each tablet and the low ionization efficacy of the compound with electrospray ionization (ESI) or atmospheric-pressure chemical ionization (APCI). Here, extraction, derivatization, and LC-MS quantitation method have been developed and validated for measuring alfacalcidol tablets dissolution content. After alfacalcidol dissolution solution was extracted with dichloromethane to remove surfactant and inorganic salts, alfacalcidol was then derivatized via a Cookson reagent, 4-phenyl-1, 2, 4-triazoline-3, 5-dione (PTAD), under ambient conditions. Alfacalcidol derivative was successfully analyzed by LC-MS. Limit of detection (LOD) of the derivatized alfacalcidol was improved 100 times (0.01 µg/mL) compared with the nontreated compound (1 µg/mL). The new method was then validated following International Conference on Harmonization (ICH) guidance. The method shows a good linearity with r 2 > 0.99. Interday and intraday reproducibility was 3.3% and 7.9%, respectively. This procedure can be used in quantification of alfacalcidol tablets dissolution content and corresponding pharmaceutical quality control.

Quantitative analysis of finasteride tablets dissolution content with non-isotopically labeled internal standard by paper spray ionization mass spectrometry.

Paper spray ionization, one of the ambient mass spectrometry technologies, has been developed to characterize the content of drugs in various complex matrixes including urine, whole blood, dissolution solutions, and so on. An isotopically labeled compound as internal standard is often used in quantitative paper spray ionization experiments. But high cost and difficult to access impede the application of this type of internal standards. Application of non-isotopically labeled compounds as internal standards will make this technology more prevalent. In this paper, we explored the application of finasteride impurity as the internal standard in paper spray ionization-mass spectrometry to measure the dissolution content of finasteride tablets. The new method was optimized and the results were compared to those from high-performance liquid chromatography. The whole analysis time was several minutes and limit of detection for finasteride was around 4.8 ng/mL. The results from paper spray ionization-mass spectrometry were similar to those from high-performance liquid chromatography. Combination of paper spray ionization-mass spectrometry and non-isotopically labeled internal standard renders a new method to analyze drug dissolution content with high specificity, low limit of detection, and simple sample preparation within short time period.

Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: a meta-analysis.

BACKGROUND: The standard treatment for osteoporosis was controversial. Denosumab and bisphosphonates were two most common drugs. The purpose of this study was to compare the efficacy and safety of denosumab with bisphosphonates to treat osteoporosis. METHODS: Published literatures, only including randomized controlled trials (RCTs), were searched in the following electronic databases: PubMed, Embase, Web of Science, Cochrane Library, and Google database from inception to April 20 2018. Studies that compared denosumab with bisphosphonates to treat osteoporosis were included. Random-effect model was used for meta-analysis due to the unavoidable clinical heterogeneity. We used the risk of fracture as the primary outcome. Stata 12.0 was used for meta-analysis. RESULTS: Eleven studies involving 5446 patients (denosumab = 2873, bisphosphonates = 2573) were included in the present meta-analysis. There was no significant difference between the risk of fracture (risk ratio (RR), 1.13; 95% confidence interval (CI), 0.82-1.55; P = 0.466), adverse events (AEs) (RR 1.00; 95% CI 0.96-1.04; P = 0.957) and withdrawn due to AEs (RR 0.68; 95% CI 0.34-137; P = 0.280). Denosumab compared with bisphosphonates significantly increased change in total hip, femoral neck, lumbar spine, and one-third radius bone mineral density (BMD) for postmenopausal osteoporosis patients (P < 0.05). CONCLUSIONS: Our meta-analysis suggested that denosumab but not bisphosphonates significantly increased change in total hip, femoral neck, lumbar spine, and one-third radius BMD for postmenopausal osteoporosis patients. Current evidence suggested no benefit of denosumab for reducing risk of fracture than bisphosphonates. More long-term follow-up RCTs are needed to identify the potential complications of denosumab.

Electrical Stimulation with a Conductive Polymer Promotes Neurite Outgrowth and Synaptogenesis in Primary Cortical Neurons in 3D.

Deficits in neurite outgrowth and synaptogenesis have been recognized as an underlying developmental aetiology of psychosis. Electrical stimulation promotes neuronal induction including neurite outgrowth and branching. However, the effect of electrical stimulation using 3D electrodes on neurite outgrowth and synaptogenesis has not been explored. This study examined the effect of 3D electrical stimulation on 3D primary cortical neuronal cultures. 3D electrical stimulation improved neurite outgrowth in 3D neuronal cultures from both wild-type and NRG1-knockout (NRG1-KO) mice. The expression of synaptophysin and PSD95 were elevated under 3D electrical stimulation. Interestingly, 3D electrical stimulation also improved neural cell aggregation as well as the expression of PSA-NCAM. Our findings suggest that the 3D electrical stimulation system can rescue neurite outgrowth deficits in a 3D culturing environment, one that more closely resembles the in vivo biological system compared to more traditionally used 2D cell culture, including the observation of cell aggregates as well as the upregulated PSA-NCAM protein and transcript expression. This study provides a new concept for a possible diagnostic platform for neurite deficits in neurodevelopmental diseases, as well as a viable platform to test treatment options (such as drug delivery) in combination with electrical stimulation.

[Analysis of Changing the Original Test Result after Retesting in National Medical Device Sampling and Testing from 2013 to 2016].

The types and the reasons of changing the original test result after retesting in national medical device sampling and testing from 2013 to 2016, are summarized and analyzed. Firstly, collecting data of "standards not complied" and retesting. Then, giving specific examples when summarizing five types of changing the original test result after retesting. Meanwhile, analyzing the relevant reasons, discovering the deep problems. Finally, giving suggestions for the above problems.

Time-dependent effects of olanzapine treatment on the expression of histidine decarboxylase, H1 and H3 receptor in the rat brain: The roles in olanzapine-induced obesity.

Antipsychotic treatment, particularly olanzapine and clozapine, induces severe obesity. The Histamine H1 receptor is considered to be an important contributor to olanzapine-induced obesity, however how olanzapine modulates the histaminergic system is not sufficiently understood. This study examined the effect of olanzapine on key molecules of the histaminergic system, including histidine decarboxylase (HDC), H1 receptor (H1R) and H3 receptor (H3R), in the brain at different stages of olanzapine-induced obesity. During short-term treatment (8-day), olanzapine increased hypothalamic HDC mRNA expression and H1R binding in the arcuate nucleus (Arc) and ventromedial hypothalamus (VMH), without changing H3R binding density. HDC mRNA and Arc H1R binding were positively correlated with increased food intake, feeding efficiency and weight gain. When the treatment was extended to 16 and 36 days, H1R binding was increased not only in the hypothalamic Arc and VMH but also in the brainstem dorsal vagal complex (DVC). The H1R bindings in the Arc, VMH and DVC were positively correlated with weight gain induced by olanzapine treatment. However, the expression of HDC and H3R mRNA was not increased. These results suggest that olanzapine time-dependently modulates histamine neurotransmission, which suggested the different neuronal mechanisms underlying different stages of weight gain development. Treatment targeting the H1R may be effective for both short- and long-term olanzapine-induced weight gain.

Electrical Stimulation Using Conductive Polymer Polypyrrole Counters Reduced Neurite Outgrowth of Primary Prefrontal Cortical Neurons from NRG1-KO and DISC1-LI Mice.

Deficits in neurite outgrowth, possibly involving dysregulation of risk genes neuregulin-1 (NRG1) and disrupted in schizophrenia 1 (DISC1) have been implicated in psychiatric disorders including schizophrenia. Electrical stimulation using conductive polymers has been shown to stimulate neurite outgrowth of differentiating human neural stem cells. This study investigated the use of the electroactive conductive polymer polypyrrole (Ppy) to counter impaired neurite outgrowth of primary pre-frontal cortical (PFC) neurons from NRG1-knock out (NRG1-KO) and DISC1-locus impairment (DISC1-LI) mice. Whereas NRG1-KO and DISC1-LI exhibited reduced neurite length and number of neurite branches compared to wild-type controls, this was not apparent for cultures on electroactive Ppy. Additionally, the use of the Ppy substrate normalised the synaptophysin and PSD95 protein and mRNA expression whereas both are usually reduced by NRG1-KO or DISC1-LI. Our findings support the utility of Ppy mediated electrical stimulation to prevent the reduction of neurite outgrowth and related synaptic protein expression in the primary PFC neurons from NRG1-KO and DISC1-LI mice, providing proof-of-concept for treating neurodevelopmental diseases including schizophrenia.

[Analysis of Quality Status of National Medical Device Supervision and Inspection from 2013 to 2016].

In this paper, we analyze the status of the medical device testing and the situation of the unqualifie varieties by sorting out the situation of the national medical device supervision and inspection from 2013 to 2016. We analyze the results of the inspection deeply, and find that the safety risk points exists in the quality of the medical device testing products and management system, product technology requirements, the national standards, industry standards or other aspects, then explain one by one with typical examples. At the same time the corresponding suggestions are put forward to production companies and regulators respectively on the existing problems.

Chronic rhein treatment improves recognition memory in high-fat diet-induced obese male mice.

High-fat (HF) diet modulates gut microbiota and increases plasma concentration of lipopolysaccharide (LPS) which is associated with obesity and its related low-grade inflammation and cognitive decline. Rhein is the main ingredient of the rhubarb plant which has been used as an anti-inflammatory agent for several millennia. However, the potential effects of rhein against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, C57BL/6J male mice were fed an HF diet for 8 weeks to induce obesity, and then treated with oral rhein (120 mg/kg body weight/day in HF diet) for a further 6 weeks. Chronic rhein treatment prevented the HF diet-induced recognition memory impairment assessed by the novel object recognition test, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits in the perirhinal cortex. Furthermore, rhein inhibited the HF diet-induced increased plasma LPS level and the proinflammatory macrophage accumulation in the colon and alteration of microbiota, including decreasing Bacteroides-Prevotella spp. and Desulfovibrios spp. DNA and increasing Bifidobacterium spp. and Lactobacillus spp. DNA. Moreover, rhein also reduced body weight and improved glucose tolerance in HF diet-induced obese mice. In conclusion, rhein improved recognition memory and prevented obesity in mice on a chronic HF diet. These beneficial effects occur via the modulation of microbiota, hypoendotoxinemia, inhibition of macrophage accumulation, anti-neuroinflammation and the improvement of BDNF expression. Therefore, supplementation with rhein-enriched food or herbal medicine could be beneficial as a preventive strategy for chronic HF diet-induced cognitive decline, microbiota alteration and neuroinflammation.

Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice.

Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora.

Olanzapine Prevents the PCP-induced Reduction in the Neurite Outgrowth of Prefrontal Cortical Neurons via NRG1.

Accumulating evidence suggests that reducing neurite outgrowth and synaptic plasticity plays a critical role in the pathology of cognitive deficits in schizophrenia. The N-methyl-D-aspartate receptor antagonist phencyclidine (PCP) can induce symptoms of schizophrenia as well as reduce dendritic spine density and neurite growth. The antipsychotic drug olanzapine may improve these deficits. This study aimed to investigate: (1) if olanzapine prevents PCP-induced suppression of neurite outgrowth and synaptic protein expression; (2) if olanzapine affects the Akt-GSK3 signaling pathway; and (3) the role of neuregulin 1 (NRG1) in this process. Immunofluorescence revealed that PCP treatment for 24 hours reduces both neurite length (28.5%) and the number of neurite branches (35.6%) in primary prefrontal cortical neuron cultures. PCP reduced protein and mRNA expressions of synaptophysin (24.9% and 23.2%, respectively) and PSD95 (31.5% and 21.4%, respectively), and the protein expression of p-Akt (26.7%) and p-GSK3ß (35.2%). Olanzapine co-treatment prevented these PCP-induced effects in normal neurons but not in neurons from NRG1-knockout mice. These results indicate that NRG1 mediates the preventive effects of olanzapine on the PCP-induced impairment of neurite outgrowth and synaptic protein expression. This study provides potential targets for interventions on improving the efficacy of olanzapine on preventing cognitive deficits in schizophrenia.

Wide-Scope Screening of Illegal Adulterants in Dietary and Herbal Supplements via Rapid Polarity-Switching and Multistage Accurate Mass Confirmation Using an LC-IT/TOF Hybrid Instrument.

A new analytical strategy was developed that integrates a generic sample preparation into a liquid chromatography-multistage ion trap/time-of-flight mass spectrometry (LC-IT(MS(n))/TOF), allowing for large-scale screening and qualitative confirmation of wide-scope illegal adulterants in different food matrices. Samples were pretreated by a fast single-tube multifunction extraction for accurate multistage mass measurement on the hybrid LC-IT/TOF system. A qualitative validation performed for over 500 analyte-matrix pairs showed the method can reduce most of the matrix effects and achieve a lower limit of confirmation at 0.1 mg/kg for 73% of the target compounds. A unique combination of dual-polarity detection, retention time, isotopic profile, and accurate MS(n) spectra enables more comprehensive and precise confirmation, based on the multiparameter matching by automated library searching against the user-created database. Finally, the applicability of this LC-IT(MS(n))/TOF-based screening procedure for discriminating coeluting isobars, identifying nontarget adulterants, and even tentatively elucidating unexpected species in real samples is demonstrated.

Bardoxolone Methyl Prevents Fat Deposition and Inflammation in Brown Adipose Tissue and Enhances Sympathetic Activity in Mice Fed a High-Fat Diet.

Obesity results in changes in brown adipose tissue (BAT) morphology, leading to fat deposition, inflammation, and alterations in sympathetic nerve activity. Bardoxolone methyl (BARD) has been extensively studied for the treatment of chronic diseases. We present for the first time the effects of oral BARD treatment on BAT morphology and associated changes in the brainstem. Three groups (n = 7) of C57BL/6J mice were fed either a high-fat diet (HFD), a high-fat diet supplemented with BARD (HFD/BARD), or a low-fat diet (LFD) for 21 weeks. BARD was administered daily in drinking water. Interscapular BAT, and ventrolateral medulla (VLM) and dorsal vagal complex (DVC) in the brainstem, were collected for analysis by histology, immunohistochemistry and Western blot. BARD prevented fat deposition in BAT, demonstrated by the decreased accumulation of lipid droplets. When administered BARD, HFD mice had lower numbers of F4/80 and CD11c macrophages in the BAT with an increased proportion of CD206 macrophages, suggesting an anti-inflammatory effect. BARD increased phosphorylation of tyrosine hydroxylase in BAT and VLM. In the VLM, BARD increased energy expenditure proteins, including beta 3-adrenergic receptor (ß3-AR) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Overall, oral BARD prevented fat deposition and inflammation in BAT, and stimulated sympathetic nerve activity.

Arachidonic acid impairs hypothalamic leptin signaling and hepatic energy homeostasis in mice.

Epidemiological evidence suggests that the consumption of a diet high in n-6 polyunsaturated fatty acids (PUFA) is associated with the development of leptin resistance and obesity. We aim to examine the central effect of n-6 PUFA, arachidonic acid (ARA) on leptin sensitivity and leptin-regulated hepatic glucose and lipid metabolism. We found that intracerebroventricular injection of ARA (25 nmol/day) for 2.5 days reversed the effect of central leptin on hypothalamic JAK2, pSTAT3, pAkt, and pFOXO1 protein levels, which was concomitant with a pro-inflammatory response in the hypothalamus. ARA also attenuated the effect of central leptin on hepatic glucose and lipid metabolism by reversing the mRNA expression of the genes involved in gluconeogenesis (G6Pase, PEPCK), glucose transportation (GLUT2), lipogenesis (FAS, SCD1), and cholesterol synthesis (HMG-CoA reductase). These results indicate that an increased exposure to central n-6 PUFA induces central cellular leptin resistance with concomitant defective JAK2-STAT3 and PI3K-Akt signaling.