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Additional file 1: Experiment methods. Synthesis of NI derivative (NI-BOC, NI-NH2), CYS-ALG and NI-CYS-ALG polymers; degree detection of NI and CYS; content detection of insulin; muco-adhesion studies of NI-CYS-ALG and GR-NPs; hypoglycemic effect of GR-NPs on mice. Figure S1. The synthetic flow chart of NI-CYS-ALG conjugate. Figure S2.1H NMR spectrum of 2-nitroimidazole, 6-(boc-amino)hexyl bromide, NI derivative (NI-BOC, NI-NH2), CYS, ALG and CYS-ALG. Figure S3. Zeta potential changes of NI-CYS-ALG conjugate under mucin particle adhesion method with different contents of cysteine (1:2-2:1, weight ratios). Figure S4. Zeta potential changes of GR-NPs under mucin particle adhesion method with different contents of cysteine (1:2, 1:1, 2:1, weight ratios). Figure S5. TEM images and size distribution of GR-NPs. Figure S6. Drug loading and encapsulation efficiency of GR-NPs with different content of cysteine (1:2, 1:1, 2:1, weight ratios). Figure S7. Particle size of GR-NPs in different days (1d, 3d, 5d). Figure S8. H&E staining observation of SD rat intestine after oral administration of GR-NPs and saline for 3 h. Figure S9. CLSM observation of cell adhesion with FITC-INS (control) and FITC-INS/GOx loaded GR-NPs after 30 min incubation. Figure S10. CLSM images of FITC-INS/GOx GR-NPs and FITC-INS in intestinal tissue (duodenum, ileum, jejunum and colon) of rats after 2 h oral administration. Figure S11. Plasma glucose levels in diabetic mice following oral administration of INS-loaded NPs, INS/GOx GR-NPs, saline or insulin solution, and following subcutaneous injection of insulin solution, and in normal rats following oral administration of INS/GOx GR-NPs. Table S1. Concentration of CYS and NI in NI-CYS-ALG polymer with different weight ratios of CYS/ALG. Table S2. Particle size and Zeta potential of GR-NPs.

Recent years, textual semantic similarity measurements play an important role in Natural Language Processing. The semantic similarity between concepts or terms can be measured by various resources like corpora, ontologies, taxonomies, etc. With the development of deep learning, distributed vector models are constructed for extracting the latent semantic information from corpora. Most of existing models create a single prototype vector to represent the meaning of a word such as CBOW. However, due to lexical ambiguity, encoding word meaning with a single vector is problematic. In this work, the authors propose a knowledge-augmented multiple-prototype model by using corpora and ontologies. Based on the distributed word vector learned by the CBOW model, the authors append the concept definition and the relational knowledge vector into the target word vector to enrich the semantic information of the word. Finally, the authors perform the experiments on well-known datasets to verify the efficiency of the authors' approach.

The assessment of semantic similarity between lexical terms plays a critical part in semantic-oriented applications for natural language processing and cognitive science. The optimization of calculation models is still a challenging issue for improving the performance of similarity measurement. In this paper, we investigate WordNet-based measures including distance-based, information-based, feature-based and hybrid. Among them, the distance-based measures are considered to have the lowest computational complexity due to simple distance calculation. However, most of existing works ignore the meronymy relation between concepts and the non-uniformity of path distances caused by various semantic relations, in which path distances are simply determined by conceptual hyponymy relation. To solve this problem, we propose a novel model to calculate the path distance between concepts, and also propose a similarity measure which nonlinearly transforms the distance to semantic similarity. In the proposed model, we assign different weights in accordance with various relations to edges that link different concepts. On basis of the distance model, we use five structure properties of WordNet for similarity measurement, which consist of multiple meanings, multiple inheritance, link type, depth and local density. Our similarity measure is compared against state-of-the-art WordNet-based measures on M&C dataset, R&G dataset and WS-353 dataset. According to experiment results, the proposed measure in this work outperforms others in terms of both Pearson and Spearman correlation coefficients, which indicates the effectiveness of our distance model. Besides, we construct six additional benchmarks to prove that the proposed measure maintains stable performance.

Silver nanoclusters (AgNCs) were first coated with bovine serum albumin (BSA) and then encapsulated into porous metal–organic frameworks of ZIF-8 by the protein-mediated biomineralization process. Unexpectedly, the fluorescence intensities of the yielded AgNCs-BSA@ZIF-8 nanocomposites were discovered to be continuously enhanced during each of the BSA coating and ZIF-8 encapsulation steps. Compared to common AgNCs, greatly improved photostability and storage stability of AgNCs could also be expected. More importantly, having benefited from the ZIF-8 shells, the prepared nanocomposites could possess the specific accumulation and sensitive response to Cu2+ ions, resulting in the rational quenching of their fluorescence intensities. Moreover, AgNCs-BSA@ZIF-8 nanocomposites were coated onto the hydrophobic arraying slides toward a microdots array-based fluorimetric method for the fast and sensitive evaluation of Cu2+ ions. It was discovered that the developed fluorimetric strategy could ensure the high-through...

The severe air pollution across China in the past several years has made the Chinese government recognize its significant impacts on public health and society, and take enormous efforts to improve the air quality all over the country, especially during the Twelfth Five-Year Plan (12th FYP). However, the overall effectiveness of these air pollution control policies remains unclear. In this study, we selected the 31 municipalities and provincial capital cities in mainland China as study settings. We collected the annual average population size, mortality rates (total mortality and mortality due to cardiovascular diseases, respiratory diseases, total cancer, lung cancer and breast cancer) and concentrations of air pollutants (PM10, PM2.5, SO2 and NO2) in each capital city from 2010 to 2015 from national or local Statistical Yearbooks. The effect sizes of air pollutants on mortality were obtained from previously published meta analyses or cohort studies. We first estimated the annual mortality rates attributed to the changes in air pollutant concentrations for every city in each year. Then, we further estimated the mortality benefits in the scenarios where the air quality had reached the grade II levels of Chinese Ambient Air Quality Standards (CAAQS) and World Health Organization (WHO) guidelines. In most capital cities, we observed dominant decreases in air pollutant concentrations during the 12th FYP, particularly from 2013 to 2015, which has led to significant mortality benefits for the public. A total of 121,658 deaths (0.441‰) have been prevented due to the decrease of PM2.5concentrations from 2013 to 2015 in all included cities. The morality benefits were larger in capital cities located in the key regions (the three main regions and ten city groups) than the other cities. In addition, more mortality benefits could be obtained in the future if the air quality reaches the grade II levels of Chinese Ambient Air Quality Standards (CAAQS) or WHO guidelines. We concluded that substantial mortality benefits achieved during the 12th FYP may be attributed to the improvements in China's air quality, which indicated the significant effectiveness of air pollution control policies.

A solid-state fluorimetric strategy has been developed using test strips coated with Q-graphene-loaded metal-organic framework nanocomposites featuring water-triggered fluorescence turn-on. It can facilitate the real-time evaluation of trace water in organic solvents, with the level down to about 0.015% in alcohol.

An ultrasensitive and high-throughput visualized colorimetric method has been initially developed with a wettable microwells array for probing guanine base-containing anthrax DNAs in blood based on silver deposition amplified by the synergic TiO2 photocatalysis and guanine photoreduction under visible light. Hydrophilic microwells were first created on the hydrophobic slides to yield the wettable microwells array, on which photocatalytic titanium dioxide (TiO2) nanoparticles were deposited with dopamine (DA) to yield TiO2@DA for anchoring single strand DNA (ssDNA) capture probes without guanine bases. After the hybridization of the targeted anthrax DNAs, exonuclease I (Exo I) was introduced into the microwells to selectively digest the unhybridized ssDNA probes. The silver deposition was further conducted by the synergic photocatalysis of TiO2@DA and photoreduction of guanine bases of anthrax DNAs, thus achieving the amplified silver signals for the visualized colorimetric assays. Moreover, benefitting from the wettability feature of the hydrophilic–hydrophobic interfaces of the microwells array so fabricated, DNA analytes could be accumulated from the sample droplets through the condensing enrichment process to realize the ultrasensitive detection, in addition to circumventing any crossover contaminants between the sample droplets. The developed visualized colorimetric method with the microwells array was subsequently applied for probing anthrax DNAs in blood with levels down to 1.0 fM. DNAs with single-base and double-base mutations could also be identified accurately. Importantly, such a biosensing design route of a wettable microwells array, in combination with the photocatalytic silver deposition and specific Exo I-catalytic probe digestion, may promise extensive applications for the high-throughput, ultrasensitive, and selective detection of guanine-containing DNA targets with ultra-trace levels in complicated samples like blood.

Idiopathic pulmonary fibrosis (IPF) induces significant morbidity and mortality, for which there are limited therapeutic options available. Here, we found that tetraethylthiuram disulphide (disulfiram, DSF), a derivative of thiuram, used in the treatment of alcohol abuse, has an inhibitory effect on bleomycin (BLM)-induced pulmonary fibrosis via the attenuation of the fibroblast-to-myofibroblast transition, migration, and proliferation of fibroblasts. Furthermore, DSF inhibited the activation of primary pulmonary fibroblasts and fibroblast cell line under transforming growth factor-β 1 (TGF-β1) challenge. Mechanistically, the anti-fibrotic effect of DSF on fibroblasts depends on the inhibition of TGF-β signalling. We further determined that DSF interrupts the interaction between SMAD3 and TGF-β receptor Ι (TBR Ι), and identified that DSF directly binds with SMAD3, in which Trp326, Thr330, and Cys332 of SMAD3 are critical binding sites for DSF. Collectively, our results reveal a powerful anti-fibrotic function of DSF in pulmonary fibrosis through the inhibition of TGF-β/SMAD signalling in pulmonary fibroblasts, indicating that DSF is a promising therapeutic candidate for IPF.

Nanozymes are artificial enzymes, which can substitute natural enzymes for wide range of catalysis-based applications. However, it is challenging to explore novel mimic enzymes or multi-enzyme mimics. Herein we report the facile preparation of uniform CuS nanoclusters (NCs), which possessed outstanding tetra-enzyme mimetic catalytic activities, including peroxidase (POD)-mimics, catalase (CAT)-mimics, ascorbic acid oxidase (AAO)-mimics and superoxide dismutase (SOD)-mimics. The catalytic mechanism of POD-like was coming from the oxygen vacancies of CuS. Furthermore, the steady-state kinetics of POD-, CAT- and AAO mimics of CuS NCs were systematically explored. On basis of the enzymatic cascade reaction that acid phosphatase (ACP) involved in a weak acidic environment, in the presence of O-phenylenediamine, quinoxaline fluorescent substance will be generated. Thus, a fluorescent biosensor platform was proposed for detection of ACP with the linear range of 0.05–25 U L−1 and limit of detection of 0.01 U L−1. The as-proposed method was applicable to real serum sample detection accurately and reproducibly. Considering the simple preparation, good stability, excellent multi-enzyme activities and controllable experimental operation, CuS NCs would provide a basis for expanding to other biocatalytic and biomedical applications.

As a valuable tool for text understanding, semantic similarity measurement enables discriminative semantic-based applications in the fields of natural language processing, information retrieval, computational linguistics and artificial intelligence. Most of the existing studies have used structured taxonomies such as WordNet to explore the lexical semantic relationship, however, the improvement of computation accuracy is still a challenge for them. To address this problem, in this paper, we propose a hybrid WordNet-based approach CSSM-ICSP to measuring concept semantic similarity, which leverage the information content(IC) of concepts to weight the shortest path distance between concepts. To improve the performance of IC computation, we also develop a novel model of the intrinsic IC of concepts, where a variety of semantic properties involved in the structure of WordNet are taken into consideration. In addition, we summarize and classify the technical characteristics of previous WordNet-based approaches, as well as evaluate our approach against these approaches on various benchmarks. The experimental results of the proposed approaches are more correlated with human judgment of similarity in term of the correlation coefficient, which indicates that our IC model and similarity detection approach are comparable or even better for semantic similarity measurement as compared to others.

Gamma ray can promote cancer cell apoptosis and cell cycle arrest. It is often used in the clinical treatment of tumors, including lung cancer. In this study, we aimed to explore the role of gamma ray treatment and its correlation with BTG2 in cell proliferation, apoptosis, and cell cycle arrest regulation in a lung cancer cell line. A549 cell viability, apoptosis rate, and cell cycle were investigated after gamma ray treatment. We then used siRNA for BTG2 to detect the effect of BTG2 knockdown on the progress of gamma ray-treated lung cancer cells. Finally, we investigated the signaling pathway by which gamma ray might regulate BTG2. We found that gamma ray inhibited A549 cell viability and promoted apoptosis and cell cycle arrest, while BTG2 knockdown could relieve the effect caused by gamma ray on A549 cells. Moreover, we confirmed that the effect of BTG2 partly depends on p53 expression and gamma ray-promoting BTG2 expression through the JNK/NF-B signaling pathway. Our study assessed the possible mechanism of gamma ray in tumor treatment and also investigated the role of BTG2 in gamma ray therapy. All these findings might give a deep understanding of the effect of gamma ray on the progression of lung cancer involving BTG2.

Most existing research examines the spatial patterns of manufacturing and producer services via separate investigations and from provincial and municipal perspectives. This paper, however, analyzes the co-location of manufacturing and producer services and their influencing factors from an intra-urban perspective. This empirical study is based in Nanjing and uses a 2001 basic unit census dataset and a 2008 economic census dataset at the firm level. The results show that the suburbanization process of manufacturing was much faster than that of producer services and indicate the establishment of producer services in the urban core and manufacturing in the periphery. The employment of producer services was highly concentrated in urban centers in the two interval years, but gradually expanded to surrounding new towns such as Jiangning, Pukou, and Luhe. In contrast, the employment in manufacturing was dispersed with substantial distribution in the old city and in suburban development zones. Manufacturing and producer services were largely co-located in the new towns of Jiangning and Pukou and national development zones. The spatial autoregression model indicates that the spatial distribution of manufacturing and producer services was subject to the joint effects of agglomeration economics and urban land price, which led the two sectors to retain a degree of spatial separability, even though their co-location was preferable. The distribution of manufacturing was significantly affected by land prices and constantly re-concentrated from urban centers to development zones and township industrial parks in suburban areas. Comparatively, the distribution of producer services was not significantly affected by land price and gradually occupied city centers with high land prices because the sector had a stronger capacity for bid rent.

Micelles with phosphatidylcholine surfaces have numerous advantages, such as good biocompatibility and high enrichment of drug in tumor tissue. In this study, we developed hyaluronic acid-coated phosphatidylcholine micelles, prepared via electrostatic attraction, for targeting the delivery of doxorubicin (DOX) to tumors. An amphiphilic copolymer poly(caprolactone)-poly(N,N-diethylaminoethyl methacrylate)-r-poly(2-(methacryloyloxy) ethyl phosphoryl choline) (PCL-PDEAMPC) was designed and synthesized successfully. PCL-PDEAMPC micelles and their DOX-loaded micelles were prepared by the dialysis method and were coated with hyaluronic acid (HA). The results showed that the micelle diameters increased a little and the zeta potential changed from positive to negative after coating with HA. The in vitro DOX release from phosphatidylcholine micelles could be triggered by pH, and the release from HA-coated PCL-PDEAMPC micelles was slower than that from PCL-PDEAMPC micelles. The in vitro cytotoxicity of the micelles was investigated using the MTT method in 4T1 cells. The results showed that the half maximal inhibitory concentration (IC50) of PCL-PDEAMPC-HA/DOX micelles was lower than that of PCL-PDEAMPC/DOX micelles. The CLSM images of cellular uptake indicated the ability of these micelles to enter into 4T1 cells. The experiments of in vivo antitumor effect and safety evaluation of DOX-loaded micelles demonstrated that the HA-coated DOX micelles had a better treatment effect and lower toxicity to 4T1-bearing Kunming mice. HA-decorated PCL-PDEAMPC micelles are therefore potential carriers for 4T1 tumor treatment.

Phosphorylcholine micelles based on pH/reduction responsive copolymers, poly(e-caprolactone)-ss-b-poly((N,N-diethylaminoethyl methacrylate)-r-poly(2-methacryloyloxyethyl phosphorylcholine)) (PCL-ss-PDEAPMPC) were developed for the intracellular delivery of doxorubicin. The micelles were spherical (less than 90 nm in diameter) and demonstrated pH/reduction sensitivity. The DOX loaded micelles presented the fastest drug release under simultaneously acidic and reductive conditions. Although PCL20-ss-PDEA5PMPC10 had lower pH sensitivity than PCL20-ss-PDEA15PMPC10, the DOX loaded micelles of the former released the drug faster than the latter at pH 5.0 and in the presence of a reductant. The cytotoxicities of the blank micelles and the drug-loaded micelles were investigated using the human cervical cancer cell line (HeLa). The IC50 (half maximal inhibitory concentration) of PCL20-ss-PDEA5PMPC10 micelles was the lowest among PCL-ss-PDEAPMPC micelles. The results of CLSM and flow cytometry showed that the micelles effectively delivered the drug cargo into cancer cells. The cellular uptake pathways of PCL-ss-PDEAPMPC micelles were mainly clathrin-mediated endocytosis, and accompanied by a certain degree of giant pinocytosis.

An optically pumped two-dimensional organic quasi-crystal microcavity laser is demonstrated based on conjugated polymer poly(2-methoxy, 5-(2′-3ethylhexyloxy)-1,4-phenylene vinylene) (MEH-PPV). The optical resonator consists of the octagonal quasi-crystal for light localization in-plane by the bandgap effect and the distributed Bragg reflector introduced between the slab-substrate interface by inhibiting the scattering and absorption of light in the substrate to achieve vertical confinement of the light. A modified point-defect traps and localizes photons into the microcavity, forcing the wave oscillation along the vertical waveguide. The experimental results show that the single-mode lasing action by optical pumping is observed at 602.2 nm with an FWHM of 0.7 nm. The threshold of lasing is lowered to 6.9 μJ/pulse.

Background The traditional treatment for diabetes usually requires frequent insulin injections to maintain normoglycemia, which is painful and difficult to achieve blood glucose control. Results To solve these problems, a non-invasive and painless oral delivery nanoparticle system with bioadhesive ability was developed by amphipathic 2-nitroimidazole–l-cysteine–alginate (NI–CYS–ALG) conjugates. Moreover, in order to enhance blood glucose regulation, an intelligent glucose-responsive switch in this nanoparticle system was achieved by loading with insulin and glucose oxidase (GOx) which could supply a stimulus-sensitive turnover strategy. In vitro tests illustrated that the insulin release behavior was switched “ON” in response to hyperglycemic state by GOx catalysis and “OFF” by normal glucose levels. Moreover, in vivo tests on type I diabetic rats, this system displayed a significant hypoglycemic effect, avoiding hyperglycemia and maintaining a normal range for up to 14 h after oral administration. Conclusion The stimulus-sensitive turnover strategy with bioadhesive oral delivery mode indicates a potential for the development of synthetic GR-NPs for diabetes therapy, which may provide a rational design of proteins, low molecular drugs, as well as nucleic acids, for intelligent releasing via the oral route.

A nanocomposite nanozyme has been fabricated through mineralizing gold-silver bimetals into Hemin (Hem)-coupled melamine (MA) polymer matrix for visual colorimetric analysis of H

Mesoporous silver-melamine (Ag-MA) nanocomposites were synthesized by controlled supramolecular self-assembly with various structural morphologies. It was discovered that the rod-like Ag-MA nanocomposites could present the larger Hg2+-enhanced catalysis by forming Ag-Hg alloys. Also, they could display large surface-to-volume area and high aqueous stability for the selective Hg2+ enrichment and absorption of Hg2+ ions by yielding the stable coordination complexes. A catalysis-based colorimetric method was thus developed using 96-wells plates to probe Hg2+ ions in blood and wastewater with the linear Hg2+ concentrations ranging from 1.0 nM to 600 nM and 0.50 nM to 700 nM, respectively. Besides, mesoporous Ag-MA absorbents could facilitate the removal of Hg2+ ions in wastewater with the removal efficiency up to 99.76 % and the absorption capacity of 598.99 mg g−1.

The present study aimed to investigate the effect of 7, 8-diacetoxy-4-methylcoumarin (DAMTC) on lung adenocarcinoma cells (A549) and analyze the molecular mechanism underlying DAMTC-treated lung adenocarcinoma. Gene expression profile GSE29698 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in 3 DAMTC-treated A549 samples were analyzed and compared with 3 DAMTC-untreated samples using the limma package. Gene Ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by the functional annotation and protein-protein interaction (PPI) network construction. Finally, pathway crosstalk analysis was conducted. A total of 500 upregulated and 389 downregulated DEGs were identified. The upregulated and downregulated DEGs were enriched in different GO terms and pathways, including metabolic process, p53 signaling pathway and metabolic pathways. A total of 9 DEGs were determined to have node degrees >16 in the PPI network, including interleukin 6 (IL6), MDM2 oncogene, E3 ubiquitin protein ligase (MDM2), cell division cycle 42 (CDC42) and MYC associated factor X (MAX). Furthermore, numerous DEGs were identified to function as transcription factors and tumor suppressor genes, including histone deacetylase 3 and MAX. Additionally, apoptosis, tight junction, and endocytosis pathway were determined to cross-talk with small cell and non-small cell lung cancer. The DEGs (IL6, MDM2, CDC42 and MAX) involved in different pathways, including the p53 signaling pathway and endocytosis, may be the potential targets for DAMTC in lung adenocarcinoma. The elucidation of the underlying mechanism of the DAMTC effect may make it a potential drug.

As metabolomics is widely used in the study of disease mechanisms, an increasing number of studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with an HFD for 30 and 50 days. The results indicated quercetin exhibited hepatoprotective activity in 30-day HFD-induced NAFLD rats by regulating fatty acid related metabolites (adrenic acid, etc.), inflammation-related metabolites (arachidonic acid, etc.), oxidative stress-related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin did not improve NAFLD in the 50-day HFD, perhaps quercetin was unable to reverse the inflammation induced by a long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD in early stages. Furthermore, combining metabolomics and experimental approaches opens avenues to study the effects and mechanisms of drugs for complex diseases.

As an information carrier with rich semantics, images contain more sentiment than texts and audios. So, images are increasingly used by people to express their opinions and sentiments in social network. The sentiments of the images are overall and should come from different regions. So, the recognition of the sentiment regions will help to concentrate on important factors the affect the sentiments. Meanwhile, deep learning method for image sentiment classification needs simple and efficient approach for simultaneously carrying out pruning and feature selection whilst optimizing the weights. Motivated by these observations, we design a region-based convolutional neural network using group sparse regularization for image sentiment classification: R-CNNGSR. The method obtains the initial sentiment prediction model through CNN using group sparse regularization to get compact neural network, and then automatically detect the sentiment regions by combining the underlying features and sentimental features. Finally, the whole image and the sentiment region are fused to predict the overall sentiment of the images. Experiment results demonstrate that our proposed R-CNNGSR significantly outperforms the state-of-the-art methods in image sentiment classification.

Background Bile salt hydrolase plays an important role in bile acid-mediated signaling pathways, which regulate lipid absorption, glucose metabolism, and energy homeostasis. Several reports suggest that changes in the composition of bile acids are found in many diseases caused by dysbacteriosis. Results Here, we present the taxonomic identification of bile salt hydrolase (BSH) in human microbiota and elucidate the abundance and activity differences of various bacterial BSH among 11 different populations from six continents. For the first time, we revealed that bile salt hydrolase protein sequences (BSHs) are distributed in 591 intestinal bacterial strains within 117 genera in human microbiota, and 27.52% of these bacterial strains containing BSH paralogs. Significant variations are observed in BSH distribution patterns among different populations. Based on phylogenetic analysis, we reclassified these BSHs into eight phylotypes and investigated the abundance patterns of these phylotypes among different populations. From the inspection of enzyme activity among different BSH phylotypes, BSH-T3 showed the highest enzyme activity and is only found in Lactobaclillus. The phylotypes of BSH-T5 and BSH-T6 mainly from Bacteroides with high percentage of paralogs exhibit different enzyme activity and deconjugation activity. Furthermore, we found that there were significant differences between healthy individuals and patients with atherosclerosis and diabetes in some phylotypes of BSHs though the correlations were pleiotropic. Conclusion This study revealed the taxonomic and abundance profiling of BSH in human gut microbiome and provided a phylogenetic-based system to assess BSHs activity by classifying the target sequence into specific phylotype. Furthermore, the present work disclosed the variation patterns of BSHs among different populations of geographical regions and health/disease cohorts, which is essential to understand the role of BSH in the development and progression of related diseases. Electronic supplementary material The online version of this article (10.1186/s40168-019-0628-3) contains supplementary material, which is available to authorized users.

A wettable well was fabricated on an electrode, which was further modified with carbon quantum dot-scaffolded nanocomposites of melamine and copper for probing histidine through a unique displacement reaction route. The developed electrode with wettable well enables the condensing enrichment of analytes from the sample droplets, improving the electroanalytical sensitivity.

A highly selective and reproducible electroanalysis strategy was developed for probing histidine using tetrahedral copper metal organic frameworks. It can facilitate His detection through the stable “turn-on” signal output of solid-state CuCl electrochemistry at a potential approaching zero, with the level down to about 25 nM in blood.

As metabolomics is widely used in the study of disease mechanisms, more and more studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with a HFD for 30 and 50 days. Results indicated quercetin exhibited hepatoprotective activity in HFD-induced NAFLD rats in 30 days by regulating fatty acids related metabolites (adrenic acid, etc.), inflammation related metabolites (arachidonic acid, etc.), oxidative stress related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin couldn’t improve NAFLD in 50 days maybe it couldn’t reverse the inflammation condition induced by long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD at early stages. Furthermore, combining metabolomics and experimental approaches opens up avenues of effects and mechanisms of drugs for complex diseases.

Figure S1. The enterohepatic circulation of bile acids. Figure S2. The analysis flowcharts. Figure S3. Genera characterization of BSHs obtained from NCBI database. Figure S4. The sequence identity of reported BSH sequences. Figure S5. Reported conserved residues of BSH in PDB database. Figure S6. Taxonomic identification of BSHs in HMP database. Figure S7. The Taxonomic identification and paralogs distribution of BSHs in HMP. Figure S8. Phylogenetic tree of BSHs in the gut microbiome of 11 populations. Figure S9. SDS-PAGE of BSH and Standard curve used in ninhydrin assay. Figure S10. Molecular docking results between BSH-T0 and bile acids. Figure S11. Molecular docking studies between BSH-T1 and bile acids. Figure S12. Molecular docking studies between BSH-T2 and bile acids. Figure S13. Molecular docking studies between BSH-T3 and bile acids. Figure S14. Molecular docking studies between BSH-T4 and bile acids. Figure S15. Molecular docking studies between BSH-T5 and bile acids. Figure S16. Molecular docking studies between BSH-T6 and bile acids. Figure S17. Molecular docking studies between BSH-T7 and bile acids. Figure S18. Enzyme activity comparisons between substrates in each BSH phylotype. Figure S19. Relationship between average RA of BSHs with WHO released phenotypes in 11 populations. Figure S20. The relative abundance of BSHs among case-control cohorts. Figure S21. Standard curve of bile acids used in LC-MS/MS. Figure S22. Typical LC spectrum of different bile acids. (PDF 4413 kb)

It is challenging to explore specific, stable and cost-effective biorecognizing elements for a wide range of applications including biosensing and nanomedicine. As the primary pro-angiogenic factor, vascular endothelial growth factor (VEGF) plays crucial roles in tumor metastasis. It holds great significance to detect VEGF in clinical diagnostics. Especially, the level of the isoform VEGF165 is usually called as the key index of many malignant tumors. Herein, phage monoclones bound to VEGF165 were selected from the pIII phage display library. Based on the phage capture assay, the phage monoclone expressing peptide LSTSPHT exhibited the best affinity and specificity against VEGF165. Then, peptide V (with the peptide sequence of LSTSPHTGGGSC) was synthesized as VEGF165 capturer to develop an enzyme-linked chemiluminescence immunoassay (ELCLIA). Under the optimal conditions, the proposed ELCLIA method showed wide linear range (10–1000 pg mL−1) and lower limit of detection (5.7 pg mL−1). Moreover, the as-developed ELCLIA was capable of detecting VEGF165 in human serum samples accurately and reproducibly. Due to its good selectivity, stability and cost-effectiveness, the VEGF165-specific peptide is prospected as a novel biointerface in sensing and tumor metastasis related diagnosis and therapy.

Background Diabetic nephropathy is a frequent microvascular complication of diabetes mellitus that causes end-stage renal disease most of the time. In China, Shenkang injection is one of widely used traditional Chinese medicine for treating chronic kidney disease, but its efficacy and safety have not yet been clarified. We will systematically review the current randomized controlled trial (RCT) evidence to summarize the efficacy and safety of Shenkang injection in treating diabetic nephropathy. Methods We will search 7 literature databases including PubMed, EMBASE, Cochrane Library, Sinomed, Chinese National Knowledge Infrastructure, Wanfang, and VIP. Two trial registry platforms will also be searched. The time frame of the search will be from the inceptions of the databases to December 31, 2020. RCTs assessing Shenkang injection combined with basic treatments versus basic treatments alone for treating diabetic nephropathy will be included. The risk of bias within the individual RCTs will be evaluated using criteria proposed by the Cochrane Handbook 5.1.0. The primary outcomes to be investigated are glomerular filtration rate and serum creatinine; the secondary outcome will include 24-hour urine albumin excretion rate, blood urea nitrogen, fasting blood glucose, postprandial blood glucose, hemoglobin A1c, total cholesterol, triglyceride, response to treatment, and incidence of adverse events. The effect data of individual RCTs by performing random-effects model meta-analysis. Statistical heterogeneity will be measured by the Cochran Q test and I-squared statistics. Three subgroup analyses, set based on clinical experience, will be performed to explore the sources of heterogeneity. Sensitivity analyses excluding RCTs with high risk of bias and using fixed effect model will be done to test the robustness of the meta-analytic results. Publication bias across included RCTs will be evaluated by funnel plots and Egger test. Results This study will provide systematic review on the efficacy and safety of Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy by rigorous quality assessment and reasonable data synthesis. The results will be submitted to a peer-reviewed journal for publication. Conclusion This systematic review will provide the best evidence currently on Shenkang Injection as adjuvant therapy in patients with diabetic nephropathy. Inplasy registration number INPLASY2020110014.

In this paper, the separation of tungsten and molybdenum by selective precipitation is evaluated, and the addition of cetyltrimethyl ammonium bromide (CTAB), as complex agent, is developed to reduce Mo loss. Thermodynamic equilibrium calculations show that manganese salt has selectivity to precipitate tungsten from molybdenum. Through single factor experiments, the influence of precipitation factors is studied systematically. The results show that CTAB can enhance the separation of molybdenum and tungsten by manganese salts. Under optimal conditions (temperature 50 °C, n(Mo)/n(CTAB) = 2, n(Mo)/n(W) = 10, time 1 h), the loss rate of Mo is 0.73%, the precipitation rate of W is 89.57%, and the separation factor is 2411.67, which is much higher than the separation factor of molybdenum and tungsten without CTAB. The results of XRD and SEM show that the precipitates mainly consist of MnWO4 and a small amount of MnMoO4 with the shape of the flower cluster composed of flakes. The complex effect of CTAB is verified by the simulation of Cambridge sequential total energy package (CASTEP). The results of geometric optimization, total energy and density of states together with FTIR spectra reveal the complex mechanism of CTAB with MoO42−. As an inexpensive and green sorbent, CTAB can be used to enhance the effect of manganese salt precipitation method for selective separation of W and Mo ions.

Semantic-oriented service matching is one of the challenges in automatic Web service discovery. Service users may search for Web services using keywords and receive the matching services in terms of their functional profiles. A number of approaches to computing the semantic similarity between words have been developed to enhance the precision of matchmaking, which can be classified into ontology-based and corpus-based approaches. The ontology-based approaches commonly use the differentiated concept information provided by a large ontology for measuring lexical similarity with word sense disambiguation. Nevertheless, most of the ontologies are domain-special and limited to lexical coverage, which have a limited applicability. On the other hand, corpus-based approaches rely on the distributional statistics of context to represent per word as a vector and measure the distance of word vectors. However, the polysemous problem may lead to a low computational accuracy. In this paper, in order to augment the semantic information content in word vectors, we propose a multiple semantic fusion (MSF) model to generate sense-specific vector per word. In this model, various semantic properties of the general-purpose ontology WordNet are integrated to fine-tune the distributed word representations learned from corpus, in terms of vector combination strategies. The retrofitted word vectors are modeled as semantic vectors for estimating semantic similarity. The MSF model-based similarity measure is validated against other similarity measures on multiple benchmark datasets. Experimental results of word similarity evaluation indicate that our computational method can obtain higher correlation coefficient with human judgment in most cases. Moreover, the proposed similarity measure is demonstrated to improve the performance of Web service matchmaking based on a single semantic resource. Accordingly, our findings provide a new method and perspective to understand and represent lexical semantics.

Recent years, textual semantic similarity measurements play an important role in Natural Language Processing. The semantic similarity between concepts or terms can be measured by various resources like corpora, ontologies, taxonomies, etc. With the development of deep learning, distributed vector models are constructed for extracting the latent semantic information from corpora. Most of existing models create a single prototype vector to represent the meaning of a word such as CBOW. However, due to lexical ambiguity, encoding word meaning with a single vector is problematic. In this work, the authors propose a knowledge-augmented multiple-prototype model by using corpora and ontologies. Based on the distributed word vector learned by the CBOW model, the authors append the concept definition and the relational knowledge vector into the target word vector to enrich the semantic information of the word. Finally, the authors perform the experiments on well-known datasets to verify the efficiency of the authors' approach.

A comparison of electrochemical performance between LiFe0.4Mn0.595Cr0.005PO4/C and LiMnPO4/C cathode materials was conducted in this paper. The cathode samples were synthesized by a nano-milling-assisted solid-state process using caramel as carbon sources. The prepared samples were investigated by XRD, SEM, TEM, energy-dispersive X-ray spectroscopy (EDAX), powder conductivity test (PCT), carbon-sulfur analysis, electrochemical impedance spectroscopy (EIS), and galvanostatic charge-discharge cycling. The results showed that LiFe0.4Mn0.595Cr0.005PO4/C exhibited high specific capacity and high energy density. The initial discharge capacity of LiFe0.4Mn0.595Cr0.005PO4/C was 163.6 mAh g−1 at 0.1C (1C = 160 mA g−1), compared to 112.3 mAh g−1 for LiMnPO4/C. Moreover, the Fe/Cr-substituted sample showed good cycle stability and rate performance. The capacity retention of LiFe0.4Mn0.595Cr0.005PO4/C was 98.84 % over 100 charge-discharge cycles, while it was only 86.64 % for the pristine LiMnPO4/C. These results indicated that Fe/Cr substitution enhanced the electronic conductivity for the prepared sample and facilitated the Li+ diffusion in the structure. Furthermore, LiFe0.4Mn0.595Cr0.005PO4/C composite presented high energy density (606 Wh kg−1) and high power density (574 W kg−1), thus suggested great potential application in lithium ion batteries (LIBs).

The assessment of semantic similarity between terms is one of the challenging tasks in knowledge-based applications, such as multimedia retrieval, automatic service discovery and emotion mining. By means of similarity estimation, the comprehension of textual resources can become more feasible and accurate. Some studies have proposed the integration of various assessment methods for taking advantage of different semantic resources, but most of them simply employ average operation or regression training. In this paper, we address this problem by combining the corpus-based similarity methods with the WordNet-based methods based on a differential evolution (DE) algorithm. Specifically, this DE-based approach conducts similarity assessment in a continuous vector space. It is validated against a variety of similarity approaches on multiple benchmark datasets. Empirical results demonstrate that our approach outperforms existing works and more conforms to the human judgement of similarity. The results also prove the expressiveness of continuous vectors learned from neural network on latent lexical semantics. HighlightsWe combine corpus-based and WordNet-based similarity methods based on differential evolution (DE) algorithm.We assess semantic similarity between terms in a continuous vector space to improve similarity computation in terms of accuracy.Empirical results demonstrate that our approach outperforms related works and conforms more to the human judgement of similarity.The robustness of our approach is presented by the steady results.Our findings provide a new perspective to estimate lexical semantics.

Magnetic hierarchical flower-like Co3O4 spheres (Co3O4 nanoflowers) were facilely prepared via one-step surfactant-free and template-free wet chemical route at room temperature. The formation mechanism of Co3O4 nanoflowers was explored. The as-prepared Co3O4 nanoflowers exhibited excellent tetra-enzyme mimetic activities, including oxidase-like, peroxidase-like, catalase-like and superoxide dismutase (SOD)-like activity. The catalytic mechanism of the Co3O4 nanoflowers was studied in detail. The oxidase-like catalytic activity of Co3O4 nanoflowers was derived from the inherent oxygen vacancies of Co3O4, while the peroxidase-like catalytic activity originated from the •OH radical generated by hydrogen peroxide (H2O2). Only one specific enzyme mimics reaction with Co3O4 nanoflowers can be obtained by inhibiting specifically other nanozymes via varying pH, adding appropriate scavengers or selecting its specific substrate. Further, the steady-state kinetic and catalytic performance of the oxidase-, peroxidase- and catalase mimics of Co3O4 nanoflowers were studied. Based on the oxidase-like and peroxidase-like activities of Co3O4 nanoflowers, bifunctional colorimetric sensing platforms were constructed for the sensitive detection of acid phosphatase (ACP) with the linear range of 0.1–25 U L-1 and H2O2 with the linear range of 4–400 μM. Further, it is capable of detecting ACP in serum samples and H2O2 in water samples, respectively. Thus, the tetra-enzyme mimetic Co3O4 nanoflowers show broad prospects in the fields of biosensors, tumor therapy, environmental monitoring and biocatalysis.

The hierarchical porous carbon with high specific surface area was facilely synthesized by calcination of Enteromorpha prolifera (EP), a renewable ocean waste biomass. The resultant carbon exhibited bienzyme mimetic properties including oxidase-like and peroxidase-like activities, which can be regulated by varying carbonized temperature. The reaction mechanism of the oxidase-like activity of EP-based hierarchical porous carbon (EPC) contributes to singlet oxygen and superoxide anions generated during the reaction, while the peroxidase-like activity arises from hydroxyl radicals. Finally, a sensitive colorimetric biosensor for acid phosphatase was explored based on the oxidase-like activity, demonstrating a linear range of 0.5–15 U/L and the limit of detection (LOD) of 0.1 U/L (S/N = 3). A fluorescent biosensor for H2O2 was also developed with the linear range of 0.05–80 μM and a LOD of 0.017 μM (S/N = 3), based on OH produced with the peroxidase-like activity, which react with terephthalic acid to form 2-hydroxyterephthalic acid. Further, incorporated with glucose oxidase, fluorometric sensing of glucose was realized with the linear range of 0.05–10 mM and a LOD of 30 μM. The bi-enzyme mimics also exhibited high reproducibility and stability. Thus, this EPC can be promising candidates for broad applications in sensing, nanomedicine, industrial catalysis and environmental engineering.

There are opportunities for improvements to the efficiency and toxicity of widely used cancer chemotherapy agents such as doxorubicin (DOX·HCl) and 7-Ethyl-10-hydroxycamptothecin (SN38). We developed a safe and effective combination therapy by encapsulating DOX into micelles of a zwitterionic polymer prodrug, SN38 conjugate of poly (α-azide caprolactone-co-caprolactone)-b-poly (2-methacryloyloxyethyl phosphorylcholine [P(CL/CL-g-SN38)-b-PMPC)] which was described in our previous work. The polymer prodrug micelles displayed a higher loading capacity of DOX due to the π-π stacking effect between DOX and SN38 in comparison with the micelles self-assembled by prodrug's precursor, poly(α-azide caprolactone-co-caprolactone)-b-poly(2-methacryloyloxyethyl phosphorylcholine (P(ACL/CL)-b-PMPC). The DOX loaded prodrug micelles decelerated the release of DOX, and also prolonged its circulation. The micelles showed favorable cellular internalization by 4T1 cells. DOX loaded SN38 prodrug micelles displayed good in vitro anticancer effects owing to the synergistic action of doxorubicin and SN38 and were as effective as DOX·HCl, but with lower toxicity than DOX·HCl. Given the synergetic effects of free drug and polymer prodrug, this nanomedicine may offer a safe and effective drug delivery methodology for conventional drug formations.

A fluorimetric test strips-based strategy has been initially developed for probing trace cysteine (Cys) in hela cells using gold-silver (Au-Ag) nanospheres and metal-organic frameworks of ZIF-8. Bimetallic Au-Ag nanoclusters were first synthesized by the protein-templated biominerization and then harvested by a desolvation route to form Au-Ag nanospheres showing strong fluorescence that could be specifically quenched by Cys. The as-prepared nanospheres were coated onto test strips to be further shelled with ZIF-8 by using a vacuum-aided fast drying route with super-hydrophobic patterns. It was discovered that the so fabricated test strips could not only achieve uniform coatings of fluorescent nano-probes, but also the ZIF-8 shell-enabled improvement of fluorescence, environmental and storage stabilities. In addition to the evaluation of Cys in serum samples, the developed fluorimetric test strips can facilitate the direct detection of Cys in hela cells with the linear concentrations ranging from 0.0032 to 32.0 μM, thus promising for the point-of-care monitoring of low-level Cys for the clinical early diagnosis of some diseases like cancers. Besides, such a proposed protocol forthe fabrication of stable and uniform test strips using MOFs coatings and super-hydrophobic patterns may be tailored for designing various solid-state testing platforms for the extensive analysis applications.

Metal-free fluorescent covalent organic frameworks (COFs) were synthesized initially with Q-Graphene (QG) scaffolds by the one-step covalent reactions of melamine-aldehyde and phenol-aldehyde poly-condensations using paraformaldehyde. It was discovered that onion-like hollow QG, which consists of multi-layer graphene and different carbon allotropes having a high proportion of folded edges and surface defects, could endow the scaffolded COFs with enhanced green fluorescence and environmental stability. Unexpectedly, they could exhibit the powerful absorption for Cu2+ ions resulting in the specific quenching of fluorescence. A fluorimetric strategy with QG-scaffolded COFs was thereby developed to probe Cu2+ ions separately in blood and wastewater with the linear concentration ranges of 0.0010–10.0 μM (limit of detection of 0.50 nM) and 0.0032–32.0 μM (limit of detection of 2.4 nM), respectively, promising the potential applications for the field-applicable monitoring of Cu2+ ions in the clinical and environmental analysis fields. In addition, the prepared COFs sorbents were employed to absorb Cu2+ ions in wastewater showing high removal efficiency. More importantly, such an one-pot fabrication route with hollow QG scaffolds may be tailorable extensively for the preparation of a variety of metal-free multifunctional COFs with enhanced fluorescence, water solubility, environmental stability, and metal removal capability.

A high-throughput and sensitive fluorimetric analysis method has been developed with wettable microwells array for probing short-chain microRNAs (miRNAs) in blood using silver nanoclusters (AgNCs) with red fluorescence amplified and stabilized by metal organic frameworks (MOFs). Glass slides were first spotted with polyacrylic acid to form hydrophilic microdots and then patterned with hydrophobic hexadecyltrimethoxysilane, followed by etching the microdots to yield the microwells array. Furthermore, the DNA capture probes with silver-binding G sequences were covalently bound onto the functionalized microwells to hybridize with targeting miRNAs. Exonuclease I catalytic digestion was then conducted to remove any single-strand DNA probes unhybridized. Eventually, AgNCs were applied to specifically recognize the G sequences of DNA probes survived to be further coated with MOFs of zeolitic imidazolate framework (ZIF-8). Unexpectedly, the red fluorescence of AgNCs probes could be dramatically enhanced due to the "electron-donor effect" of nitrogen-containing ligands of ZIF-8 coatings, together with improved sensing stability. High detection sensitivity and reproducibility could thereby be expected for detecting miRNAs in the blood with the concentrations linearly ranging from 0.175 to 500 pM. Markedly different from the common sandwiched DNA detection methods, the developed fluorimetric strategy using AgNCs coated with MOFs and DNA probes designed with silver-recognizing sequences would be tailored for quantifying various kinds of short-chain miRNAs with low levels in the complicated blood media.

SummaryBile salt hydrolase (BSH) in gut bacteria can hydrolyze conjugated bile salts to unconjugated bile acids and amino acids. Thereby play a crucially important role in host health by reducing serum cholesterol levels, preserving bile acids balance and regulating various metabolism as signaling molecules. Here we present the taxonomic identification of BSHs in human microbiota and elucidate the abundance and activity differences of various bacterial BSHs among 11 different populations. For the first time, we have revealed BSH are distributed in 154 intestinal bacterial strains within 33 genera in human microbiota. However, these BSHs present obviously differentiation for the sequence identity being from 28.6% to 100%, and the 32.7% bacteria strains having more than one paralogs of BSHs with dissimilarity. Therefore, we reclassified the BSHs from the different genera into 6 phylotypes basing on their phylogenetic tree, and demonstrate the significant abundance patterns of BSH phylotypes among different populations. From the enzyme activity comparison, the representative sequence of BSH-T3 was shown highest enzyme activity in 6 phylotypes. Meanwhile, BSH-T3 sequences which all distributed inLactobacillusshow highest abundance in Chinese and Austrian. The information illustrated by this study is useful for investigating the population differences of bile acid metabolism related diseases, and further giving a new suggestion on selection of probiotics or development of pharmaceutical proteins based upon the activity of BSH phylotypes to regulate host metabolism and maintain fitness.

Within the field of conflict between the conservation of natural resources and the production of food, the use of genetically modified organisms (GMO) remains subject of highly controversial discussions. On the one hand, genetic engineering allows the creation of high-yield or pest and pesticide-resistant plants and thus enables better production, even in areas with difficult agricultural conditions. On the other hand, the use of GMO in agriculture carries the risk of out crossing with natural sorts which could endanger biodiversity. Therefore, the attitude of consumers towards GMO is quiet critical—in China as well as in the European Union. This article deals with the legal system that Germany, the European Union, and China established to master this balance between the use of GMO and environmental and consumer protection within the margin set by international law.

The power lithium ion battery has been widely used for its excellent performance, with the waste batteries increased yearly and causing environmental pollution and resource waste. The problem must be solved immediately. In this paper, through the “alkaline separation-roasting-acid leaching” process, spent lithium ion battery anode is handled so that to achieve the extraction of valuable metals in the anode. The results show positive active material can separate from the aluminum foil by means of the using of NaOH solution. Under the process of 700 ℃ high-temperature roasting for 2 h, active substances Li (NixCo1-x) O2 transform into NiO, CoO, etc., and it is conducive to subsequent acid leaching. After roasting, the acid leaching of active substance is conducted through respectively using hydrochloric acid and sulfuric acid. The leaching rate of Li, Ni, Co are 99.9, 99.5, 99.2% under the optimum conditions in hydrochloric acid system respectively: the concentration of the acid 2 mol/L, the ratio of solid-liquid 60 mg/ml, leaching temperature 90 ℃ and leaching time 50 min. In sulfuric acid system, the leaching rate of Li, Ni, Co are all closer to 100% under the optimum conditions: the concentration of the acid 2 mol/L, the S/L 75 mg/ml, leaching temperature 85 ℃ leaching time 50 min and volume ratio of hydrogen peroxide is 5%. Through the fitting calculation, acid leaching is applied to the nuclear reaction model and leaching of lithium nickel and cobalt are controlled by chemical reaction. Two kinds of acid system all have good results for metal extraction from waste lithium ion battery cathode material. Considering recycling cost and environmental impact, sulfuric acid system is better.

Stress has been demonstrated to play an important role in hair follicle function and the pathogenesis of some hair disorders. The central hypothalamic-pituitary-adrenal (HPA) axis is activated by stress stimuli, synthesizes and releases various components and eventually induces the pathogenesis and recurrence of peripheral diseases. Our aim is to compare the different responses under exposure of stress in hair follicle function among different mouse strains, and to detect the involvement of the central HPA axis after stress in hair follicle growth and melanogenesis. In this study, we exposed different mouse strains (C57BL/6, CBA/J, C3H/HeN, BALB/c and ICR) to a 21-day chronic restraint stress protocol and selected C57BL/6, CBA/J and BALB/c mice for further study because of their significant behavioral alterations. Then, we evaluated and compared the different responses and sensitivity to chronic restraint stress in hair follicle function and central HPA axis among the selected strains. The results showed that expression of POMC, CRF and GR mRNA and protein and serum levels of corticosterone were inhibited in response to stress. These findings suggested that chronic restraint stress may inhibit hair follicle growth and melanogenesis via regulating the key elements of the central HPA axis. In addition, the results revealed different mouse strains exhibit different responses in the central HPA axis and hair follicle after stress exposure. C57BL/6 might be the most sensitive strain among the three strains tested as well as an appropriate strain to study possible pathophysiological mechanisms by which the nervous system influences skin function and screen dermatological drugs suitable for psychotherapy. We believe the current study will provide some useful information for researchers who are interested in the bidirectional communication between the nervous and skin systems and the management of stress-induced cutaneous diseases.

Membrane technology has become a low-cost and high-efficiency separation technology for industrial processes over the past decennia. The colloidal route is an environmentally benign process for the preparation of ceramic membranes by using water as solvent. A stable, colloidal boehmite sol with an average particle size of 16 nm was prepared from aluminum tri-sec-butoxide using water as a solvent in the pH range of 3–4. Acetic acid was used as the peptizing agent instead of nitric acid. The stable sol was used to fabricate γ-alumina nanofiltration membranes on α-alumina microfiltration substrates by a dip-coating approach. The effects of the peptizing agents on the properties of the sols and the membranes were investigated. γ-alumina nanofiltration membranes with an average membrane thickness of 1.8 μm were obtained after sintered at 600 °C for 2 h. The molecular weight cut-off of the γ-alumina nanofiltration membranes, as obtained by filtration of an aqueous PEG solution, was approximately 1 kDa. This membrane also showed a typical retention for monovalent ions and divalent ions. Additionally, the nanofiltration membranes exhibited a relatively high pure-water flux (>20 L/(m 2 h bar)), which is four times higher than that of the γ-alumina nanofiltration membranes reported in the literature. The contribution ratios of different microstructure factors on pure-water flux were calculated. The change in tortuosity with a contribution ratio of 75.6% was the main factor for the improvement of pure-water flux.

A new aqueous sol was synthesized to prepare Ag-doped TiO2/Ti composite tight ultrafiltration (UF) membranes. This sol was prepared based on water (>95 wt%), for which the hydrodynamic size of 8 nm could be obtained by tuning the electrostatic and steric repulsive forces, breaking the limit of the polymeric sol–gel method to prepare tight UF membranes. For the preparation of the sol, high water content can significantly reduce the use of organic solvents and is more environment-benign. Moreover, Ag doping can considerably improve the toughness of the supported membranes to efficiently prevent the TiO2/Ti composite membranes from cracking and overcome the thermal expansion mismatch of ceramic membranes and their metallic supports. The prepared Ag-doped TiO2/Ti composite membranes presented a molecular weight cut-off of 3 kDa with a pure water flux of 24 L m−2 h−1 bar−1 and exhibited good dye removal capabilities. The proposed Ag doping method has considerable potential for the fabrication of integrated hybrid ceramic–metallic composite membranes.

The hybrid ceramic–metallic composite membranes combine the advantages of ceramic layers and metallic supports, but the composite membranes tend to crack during sintering process. The metal has superior ductility that could release the shrinkage stress, so that doping the metal into the ceramic membranes can resolve the problem of membrane cracking during sintering process. A new TiO 2 /Ti ceramic–metallic composite membrane was prepared by Ag doping method, from which the properties and performances were systematically investigated. It was found that the appropriate amount of 6 dwb% (on a dry weight of TiO 2 basis, dwb) Ag doping can obtain the uniform Ag nanoparticles with about 5 nm, that can efficiently enhance the mechanical properties of strength and toughness of the supported TiO 2 membranes due to the ductility of Ag nanoparticles, overcoming the thermal expansion mismatch between ceramic membranes and metallic supports. The novel as-prepared TiO 2 /Ti composite membranes presented a molecular weight cut-off (MWCO) of 180 kDa and a pure water flux of 178 L/(m 2 h bar). Moreover, the Ag doping method showed a superior photocatalytic performances on dye decomposition, so that a kind of photocatalytic membrane can be prepared for ultrafiltration (UF) process.