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Supplementary Table 1. List of ingredients found exclusively in ultra-processed products. Supplementary Table 2. Household characteristics of the NielsenIQ Homescan Consumer panel between 2015 and 2019.

Precise prediction of phase diagrams in molecular dynamics (MD) simulations is challenging due to the simultaneous need for long time scales, large length scales and accurate interatomic potentials. We show that thermodynamic integration (TI) from low-cost force fields to neural network potentials (NNPs) trained using density-functional theory (DFT) enables rapid first-principles prediction of the solid-liquid phase boundary in the model salt NaCl. We use this technique to compare the accuracy of several DFT exchange-correlation functionals for predicting the NaCl phase boundary, and find that the inclusion of dispersion interactions is critical to obtain good agreement with experiment. Importantly, our approach introduces a method to predict solid-liquid phase boundaries for any material at an ab-initio level of accuracy, with the majority of the computational cost at the level of classical potentials.

Even with the ubiquitous sensing data in intelligent transportation systems, such as the mobile sensing of vehicle trajectories, traffic estimation is still faced with the data missing problem due to the detector faults or limited number of probe vehicles as mobile sensors. Such data missing issue poses an obstacle for many further explorations, e.g., the link-based traffic status modeling. Although many studies have focused on tackling this kind of problem, existing studies mainly focus on the situation in which data are missing at random and ignore the distinction between links of missing data. In the practical scenario, traffic speed data are always missing not at random (MNAR). The distinction for recovering missing data on different links has not been studied yet. In this paper, we propose a general linear model based on probabilistic principal component analysis (PPCA) for solving MNAR traffic speed data imputation. Furthermore, we propose a metric, i.e., Pearson score (p-score), for distinguishing links and investigate how the model performs on links with different p-score values. Experimental results show that the new model outperforms the typically used PPCA model, and missing data on links with higher p-score values can be better recovered. Agency for Science, Technology and Research (A*STAR) Published version This study is supported under the RIE2020 Industry Alignment Fund—Industry Collaboration Projects (IAF-ICP) Funding Initiative, as well as cash and in-kind contribution from the industry partner(s), and A*STAR under its Industry Alignment Fund (LOA Award I1901E0046).

A tannin, EA (1), and other nine non-tannins compounds, gallic acid (2), quercetin (3), myricetin (4), 3-O-methylellagic acid-4′-O-α-L-rhamnopyranoside (5), quercetin-3-O-β-D-galactopyranoside (6), kaempferol-3-O-β-D-glucoside (7), quercetin-3-O-β-D-glucuronide (8), quercetin-3-O-rutinoside (9), 3,3′,4-tri-O-methylellagic acid-4′-O-β-D-glucopyranosyl (10) were isolated from a valuable medicinal plant, Eucalyptus citriodora. Structural identification of these compounds was conducted using 1H NMR and 13C NMR spectroscopy and comparing their spectral data with those previously reported in literatures. The anti-inflammatory effects of EA were evaluated in ethanol-induced acute gastric ulcer mice models in our study. The result demonstrated that the intragastric administration of EA significantly prevented the gastric ulceration caused by ethanol treatments. Especially, the gastric tissue in the middle-dose EA (100 mg/kg) showed few ulcerations with only slight focal congestion which indicated that it has a significant protective effect on gastric ulcer by increasing the IL-10 and PGE2 levels, and reducing the IL-6, TNF-α, GAS and COX-2 levels. In addition, the middle-dose EA has no adverse effect on liver and kidney. These findings imply that EA exerts gastroprotective effects by means of its anti-inflammatory effects and may be a potential drug for anti-ulcer treatment.

PurposeA reduction of 80% in new Hepatitis C virus (HCV) infection is expected by 2030. However, high HCV reinfection rates have been reported among the high-risk population. This meta-analysis aimed to assess the HCV reinfection rate after successful treatment of HIV-1 coinfected MSM populations.MethodsBibliographic databases were searched and a random-effect model was utilized to calculate the pooled HCV reinfection rate. Sub-group and meta-regression were used to explore heterogeneity among selected studies. A funnel plot and Egger's regression test were performed to estimate the publication bias.ResultsSixteen studies with 9,017.2 person-years (PY) follow-up were included. The overall HCV reinfection rate following successful treatment among HIV-1-infected MSM was 5.27/100 PY (95% CI, 3.98, 6.96). Lower reinfection rates were observed in developed parts of Europe (5.28/100 PY; 95% CI, 3.73, 6.84) and North America (3.92/100 PY; 95% CI, 1.67, 6.17). Reinfection rates among people with HCV test intervals of fewer than 6 months (7.59/100 PY; 95% CI: 5.15, 10.03) were significantly higher than those with more than 6 months test interval (2.88/100 PY; 95% CI: 2.26, 3.50), with an adjusted RR of 1.86 (95% CI, 1.06, 3.13). The adjusted study factors explained 91.03% the of studies' heterogeneity.ConclusionHCV reinfection rate was high in successfully treated MSM who were coinfected with HIV-1. A shorter HCV test interval may help to explore more HCV reinfections. HCV reinfection rate studies from HIV-1 coinfected MSM in underdeveloped countries are urgently needed.Meta registrationPROSPERO: CRD42021285206, URL: https://www.crd.york.ac.uk/prospero/.

Chronic kidney disease is a progressive disease that may lead to end-stage renal disease. Interstitial fibrosis develops as the disease progresses. Therapies that focus on fibrosis to delay or reverse progressive renal failure are limited. We and others showed that sphingosine kinase 2-deficient mice (Sphk2−/−) develop less fibrosis in mouse models of kidney fibrosis. Sphingosine kinase2 (SphK2), one of two sphingosine kinases that produce sphingosine 1- phosphate (S1P), is primarily located in the nucleus. S1P produced by SphK2 inhibits histone deacetylase (HDAC) and changes histone acetylation status, which can lead to altered target gene expression. We hypothesized that Sphk2 epigenetically regulates downstream genes to induce fibrosis, and we performed a comprehensive analysis using the combination of RNA-seq and ChIP-seq. Bst1/CD157 was identified as a gene that is regulated by SphK2 through a change in histone acetylation level, and Bst1−/− mice were found to develop less renal fibrosis after unilateral ischemia-reperfusion injury, a mouse model of kidney fibrosis. Although Bst1 is a cell-surface molecule that has a wide variety of functions through its varied enzymatic activities and downstream intracellular signaling pathways, no studies on the role of Bst1 in kidney diseases have been reported previously. In the current study, we demonstrated that Bst1 is a gene that is regulated by SphK2 through epigenetic change and is critical in kidney fibrosis., Frontiers in Medicine, 9, art. no. 993698; 2022

Perovskite single-crystal (SC) or quasi-single-crystal (QSC) films are promising candidates for excellent performance of photoelectric devices. However, it is still a great challenge to fabricate large-area continuous SC or QSC films with proper thickness. Herein, we propose a pressure-assisted high-temperature solvent-engineer (PTS) strategy to grow large-area continuous MAPbI3 QSC films with uniformly thin thickness and orientation. Dramatic grain growth (∼100 μm in the lateral dimension) and adequate boundary fusion are realized in them, vastly eliminating the grain boundaries. Thus, remarkable diminution of the trap density (ntrap: 7.43 × 1011 cm-3) determines a long carrier lifetime (τ2: 1.7 μs) and superior photoelectric performance of MAPbI3-based lateral photodetectors; for instance, an ultrahigh on/off ratio (>2.4 × 106, 2 V), great stability, fast response (283/306 μs), and high detectivity (1.41 × 1013) are achieved. The combination properties and performance of the QSC films surpass most of the reported MAPbI3. This effective approach in growing perovskite QSC films points out a novel way for perovskite-based optoelectronic devices with superior performance.

The binary-lipid system of soybean phosphatidylcholine (SPC) and glycerol dioleate (GDO) can hydrate to gels on contacting with aqueous mediums, which has emerged as a versatile and promising delivery matrix for extended drug release applications. In the present work, we have characterized the gelation process of this SPC/GDO lyotropic gel (SGLG) system by rheology and evaluated the drug release profiles from the SGLG formulations with different SPC/GDO mass ratios. Our study has demonstrated that simply adjusting the SPC/GDO mass ratio can tune the lipid gelation behavior and modulate the drug release profiles. More importantly, the drug release from the SGLG formulations follows a two-compartment (fast and slow release compartments) release kinetics that has not been reported before. We posit that the fast release compartment corresponds to the passive diffusion of the drug during the early stage of the gel formation. After the boundary gel phase generation, the drug release is then dominated by the slow diffusion process from SGLG. The pharmacokinetic studies in rats match well with the in vitro studies, suggesting that the binary-lipid formulation is an excellent candidate for on-demand sustained drug delivery system.

Accurate vehicle type classification serves a significant role in the intelligent transportation system. It is critical for ruler to understand the road conditions and usually contributive for the traffic light control system to response correspondingly to alleviate traffic congestion. New technologies and comprehensive data sources, such as aerial photos and remote sensing data, provide richer and high-dimensional information. Also, due to the rapid development of deep neural network technology, image based vehicle classification methods can better extract underlying objective features when processing data. Recently, several deep learning models have been proposed to solve the problem. However, traditional pure convolutional based approaches have constraints on global information extraction, and the complex environment, such as bad weather, seriously limits the recognition capability. To improve the vehicle type classification capability under complex environment, this study proposes a novel Densely Connected Convolutional Transformer in Transformer Neural Network (Dense-TNT) framework for the vehicle type classification by stacking Densely Connected Convolutional Network (DenseNet) and Transformer in Transformer (TNT) layers. Three-region vehicle data and four different weather conditions are deployed for recognition capability evaluation. Experimental findings validate the recognition ability of our proposed vehicle classification model with little decay, even under the heavy foggy weather condition., Comment: 10 pages, 8 figures, 5 tables

Additional file 4: Supplemental Fig. 1. Effects of SNPs in APOA5, APOC3, APOB, APOE, and LDLR on serum triglyceride levels after lipid challenge. Subjects were divided into two genotypic groups separated by sex. A. APOA5 (n=25 and =22 for the CC+CG genotype in men and women, respectively; n=142 and =160 for the GG genotype in men and women, respectively). B. APOC3 (n=108 and =122 for the CC+CT genotype in men and women, respectively; n=58 and =59 for the TT genotype in men and women, respectively). C. APOB (n=72 and =82 for the CC+CT genotype in men and women, respectively; n=93 and =90 for the TT genotype in men and women, respectively). D. APOE (n=40 and =56 for the CC+CT genotype in men and women, respectively; n=127 and =126 for the TT genotype in men and women, respectively). E. LDLR (n=31 for the CT+TT genotype in both men and women; n=135 and =151 for the CC genotype in men and women, respectively). All data were adjusted for age and BMI and are presented as mean±SE. *,P

Additional file 2: Supplemental Table 1. Comparison of the observed SNP frequencies between this study and the 1000 genome project.

Additional file 1: Figure S1. A, Heatmap of RMWs in OS tissue from the Target dataset and GSE21257 dataset. B, GO and KEGG analyses of DEGs. Figure S2. Survival analysis of OS patients with differential expression of CSTF2, ADAR and WTAP in both TCGA and GEO datasets. Figure S3. The correlation between risk RMW expression and clinical characteristics. Figure S4. The relationship between the risk score and immune infiltration was analysed using Pearson’s correlation analysis. Table S1. Univariate Cox analysis revealed prognosis-related DEGs in the high- and low-risk groups. Table S2. The relationship between TF and prognosis-related DEGs. Table S3. Drug prediction using the CMap database.

Additional file 1

Additional file 3: Supplemental Table 2. Distribution of the observed SNP genotype in sex/age/BMI groups.

Electric Vehicle (EV) charging demand and charging station availability forecasting is one of the challenges in the intelligent transportation system. With the accurate EV station situation prediction, suitable charging behaviors could be scheduled in advance to relieve range anxiety. Many existing deep learning methods are proposed to address this issue, however, due to the complex road network structure and comprehensive external factors, such as point of interests (POIs) and weather effects, many commonly used algorithms could just extract the historical usage information without considering comprehensive influence of external factors. To enhance the prediction accuracy and interpretability, the Attribute-Augmented Spatial-Temporal Graph Informer (AST-GIN) structure is proposed in this study by combining the Graph Convolutional Network (GCN) layer and the Informer layer to extract both external and internal spatial-temporal dependence of relevant transportation data. And the external factors are modeled as dynamic attributes by the attribute-augmented encoder for training. AST-GIN model is tested on the data collected in Dundee City and experimental results show the effectiveness of our model considering external factors influence over various horizon settings compared with other baselines., Comment: 10 pages; 17 figures; Under review for IEEE Transaction on Vehicular Technology

As extreme weather events have become more frequent in recent years, improving the resilience and reliability of power systems has become an important area of concern. In this paper, a robust preventive-corrective security-constrained optimal power flow (RO-PCSCOPF) model is proposed to improve power system reliability under N−k outages. Both the short-term emergency limit (STL) and the long-term operating limit (LTL) of the post-contingency power flow on the branch are considered. Compared with the existing robust corrective SCOPF model that only considers STL or LTL, the proposed RO-PCSCOPF model can achieve a more reliable generation dispatch solution. In addition, this paper also summarizes and compares the solution methods for solving the N−k SCOPF problem. The computational efficiency of the classical Benders decomposition (BD) method, robust optimization (RO) method, and line outage distribution factor (LODF) method are investigated on the IEEE 24-bus Reliability Test System and 118-bus system. Simulation results show that the BD method has the worst computation performance. The RO method and the LODF method have comparable performance. However, the LODF method can only be used for the preventive SCOPF and not for the corrective SCOPF. The RO method can be used for both. Education Department of Guangdong Province: New and Integrated Energy System Theory and Technology Research Group [Project Number 2016KCXTD022]; National Natural Science Foundation of China (51907031); The National Natural Science Foundation of China 51907031; Guangdong Basic and Applied Basic Research Foundation (Guangdong-Guangxi Joint Foundation) 2021A1515410009; China Scholarship Council; Brunel University London BRIEF Funding.

A facile and versatile synthesis strategy for the bis(1,2,3-triazole) formation reaction was developed from tosylhydrazones and N-amino (N-NH2) azole instead of C-amino amine derivatives. The novel...

Chitosan is a considerably versatile and promising biomaterial and can easily form a 3D hierarchical porous scaffold. In this work, a novel boronate-affinity monolithic column modified with a boronic acid-chitosan complex was prepared and characterized by different methods such as Fourier transform infrared spectroscopy, scanning electron microscopy, thermal gravimetric analysis, specific surface area analysis and pore size distribution analysis. The synthesized monolithic column was used for polymer monolithic microextraction combined with high performance liquid chromatography for the simultaneous determination of cytidine, uridine, inosine, and guanosine in milk powder samples. Several parameters affecting extraction efficiency, including the eluent proportion, eluent flow rate, sample flow rate, sample volume, and sample pH were investigated. The boronate-affinity monolithic column showed high enrichment ability due to the selective formation of cyclic borate esters between nucleosides and boronic acid groups at high pH and the release of cyclic borates at low pH values. Under the optimum operating conditions, the linear range was 0.1-50 μg mL-1, and the correlation coefficients were in the range of 0.9993-0.9994. The LOD and LOQ were in the range of 0.0027-0.0034 and 0.0090-0.011 μg mL-1, respectively. In addition, the results of recovery and relative standard deviation were satisfactory.

All-inorganic mixed-halide perovskite thin films exhibit intriguing one- and two-photon absorption properties and optical stabilities. However, perovskite polycrystalline thin films prepared via conventional methods generally possess high trap densities, which reduces the efficiency of carrier transport. Thus, highly sensitive dual-mode photodetection in both the visible and near-infrared (NIR) regions is seemingly difficult to achieve. To overcome these issues, we utilized a spin-coating thermal-pressed (SCTP) strategy to grow CsPbI1.5Br1.5 QSC films with high crystallinity and a uniform orientation. The SCTP-grown films were found to be densely stacked with large single-crystal grains that vertically spanned the entire film thickness. The crystals were determined to be approximately 40 µm in diameter, which resulted from the removal of a significant number of grain boundaries and surface defects. The trap density of the SCTP-grown film was markedly decreased (ntrap: (8.55 ± 0.96) × 1011 cm–3), and it demonstrated a long carrier lifetime (τ2: 132.53 ± 9.45 ns) and a large two-photon absorption coefficient (β: 0.94 ± 0.04 cm·GW–1), all of which made the SCTP-grown CsPbI1.5Br1.5 QSC film superior to other reported CsPbI3−xBrx quantum dots and films. The visible and NIR dual-mode photodetection of the film at 532 and 1030 nm, respectively, was demonstrated with giant single-/two-photon responses. In addition, the surface nonlinear optics of the SCTP-grown QSC films were innovatively studied. This endowed the high-quality all-inorganic perovskite QSC films with optical properties beneficial for high-contrast photodetection necessary in application such as encryption imaging and high-efficiency solar cells.

According to the content and characteristics of ideological and political education website, a network education platform with functions of teacher-student interaction, psychological counseling and students' self-display is designed. This system mainly uses Microsoft VS 2015 and MSSQL2016 as the processing tool and DB system, and ASP.NET 2.0 as development software based on WEB2.0. The content of the system design mainly includes four core functional modules: teaching, propaganda, consultation and communication, supervision and system management module. Finally, the implementation and testing of the relevant modules of the ideological and political education information platform are completed, which proves that the scheme in this paper has a certain degree of reliability, maintainability, scalability and good adaptability.

A thin-layer of Ni(OH)2 was in situ formed on the surface of Ni2P nanopillars (Ni(OH)2@Ni2P/E-NF) via a facile hydrothermal treatment in H2O. Ni(OH)2@Ni2P/E-NF exhibits superior activity for the hydrogen evolution reaction with an overpotential of only 43 mV to achieve 10 mA cm−2 and a good durability during the long-term operation in an alkaline medium. The excellent performance of Ni(OH)2@Ni2P/E-NF is likely ascribed to the strong interfacial coupling of Ni(OH)2 and Ni2P, which promotes the dissociation of water and concomitantly converts hydrogen intermediates (Had) to H2. Keywords: Nickel hydroxide, Nickel phosphide, Etching, Hydrogen evolution reaction

A series of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene)pyrrolidin-2-one derivatives were designed, synthesized, and evaluated for their anticonvulsant activities. In the preliminary screening, compounds 5, 6a–6f and 6h–6i showed promising anticonvulsant activities in MES model, while 6f and 6g represented protection against seizures at doses of 100 mg/kg and 0.5 h in scPTZ model. The most active compound 6d had a high-degree protection against the MES-induced seizures with ED50 value of 4.3 mg/kg and TD50 value of 160.9 mg/kg after intraperitoneal (i.p.) injection in mice, which provided 6d in a high protective index (TD50/ED50) of 37.4 comparable to the reference drugs. Beyond that, 6d has been selected and evaluated in vitro experiment to estimate the activation impact. Apparently, 6d clearly inhibits the Nav1.1 channel. Our preliminary results provide new insights for the development of small-molecule activators targeting specifically Nav1.1 channels to design potential drugs for treating epilepsy. The computational parameters, such as homology modeling, docking study, and ADME prediction, were made to exploit the results.

In this study, we prepared paclitaxel (PTX) loaded bovine serum albumin (BSA) microparticles (MPs) of different sizes (0.5, 1.0, and 3.0 µm) and converted them into dry powders (DPs) of a uniform size (∼5.0 µm) through spray-drying techniques. The aim of preparing different sized PTX-MPs is to investigate the size-based in vivo biodistribution and retention of PTX in the lungs after intratracheal administration. Following the in vitro characterizations, the anti-tumor efficacy of the DPs containing differently sized PTX-BSA-MPs administered through intratracheal insufflation was compared with intravenously administered PTX solution (Taxol). While the fastest drug release was found for the 0.5 µm group, the 1.0 and 3.0 μm groups showed the highest anti-tumor efficiency in vivo. Taken together, our results demonstrate that the initial particle size of the incorporated particles, i.e., MPs, is crucial for the anti-tumor efficacy of DPs administered by inhalation, and the initial particle size should be regarded as one of the key factors in the development and quality control of such preparations.

A reversibly disulfide-crosslinked pullulan nanoparticle with folic acid (FA) decoration (FA-Pull-LA CLNPs) was fabricated for dual-targeted and reduction-responsive anti-tumoral liver drug delivery based on the specific affinity of pullulan and FA to overexpress asialoglycoprtein receptors (ASGPR) and folate receptors (FR), respectively. Paclitaxel (PTX)-loaded FA-Pull-LA nanoparticles (NPs) with satisfactory size, polydispersity index (PDI), and zeta potential exhibited much faster PTX release in the presence of 10mM glutathione (GSH) rather than physiological conditions. In vitro cellular assays confirmed the dual targetability and endosomal accumulation of FA-Pull-LA NPs. In SMMC-7721 tumor-bearing mice, FA-Pull-LA-PTX CLNPs showed the strongest anti-tumor efficiency as well as the lowest toxicity among all three groups. Conclusively, the present study implied that reversibly crosslinked FA-Pull-LA NPs with dual-targeting capacity provided a stable and intelligent platform for efficient liver cancer therapy, which should be further studied for a wide range of anti-cancer applications.

An exoskeleton robot is a kind of wearable mechanical instrument designed according to the shape and function of the human body. The main purpose of its design and manufacture is to enhance human strength, assist human walking and to help patients recover. The walking state of the exoskeleton robot should be highly consistent with the state of the human, so the accurate locomotion pattern recognition is the premise of the flexible control of the exoskeleton robot. In this paper, a simulated annealing (SA) algorithm-based support vector machine model is proposed for the recognition of different locomotion patterns. In order to improve the overall performance of the support vector machine (SVM), the simulated annealing algorithm is adopted to obtain the optimal parameters of support vector machine. The pressure signal measured by the force sensing resistors integrated on the sole of the shoe is fused with the position and pose information measured by the inertial measurement units attached to the thigh, shank and foot, which are used as the input information of the support vector machine. The max-relevance and min-redundancy algorithm was selected for feature extraction based on the window size of 300 ms and the sampling frequency of 100 Hz. Since the signals come from different types of sensors, normalization is required to scale the input signals to the interval (0,1). In order to prevent the classifier from overfitting, five layers of cross validation are used to train the support vector machine classifier. The support vector machine model was obtained offline in MATLAB. The finite state machine is used to limit the state transition and improve the recognition accuracy. Experiments on different locomotion patterns show that the accuracy of the algorithm is 97.47% ± 1.16%. The SA-SVM method can be extended to industrial robots and rehabilitation robots.

One of the main challenges for immune checkpoint blockade antibodies lies in malignancies with limited T-cell responses or immunologically “cold” tumors. Inspired by the capability of fever-like heat in inducing an immune-favorable tumor microenvironment, mild photothermal therapy (PTT) is proposed to sensitize tumors to immune checkpoint inhibition and turn “cold” tumors “hot.” Here we present a combined all-in-one and all-in-control strategy to realize a local symbiotic mild photothermal-assisted immunotherapy (SMPAI). We load both a near-infrared (NIR) photothermal agent IR820 and a programmed death-ligand 1 antibody (aPD-L1) into a lipid gel depot with a favorable property of thermally reversible gel-to-sol phase transition. Manually controlled NIR irradiation regulates the release of aPD-L1 and, more importantly, increases the recruitment of tumor-infiltrating lymphocytes and boosts T-cell activity against tumors. In vivo antitumor studies on 4T1 and B16F10 models demonstrate that SMPAI is an effective and promising strategy for treating “cold” tumors., Mild photothermal therapy can be used to induce a favourable immunological response. In this study, the authors combine a photothermal therapy sensitizer and anti-PD-L1 into a lipid gel and find that, on controlled delivery to tumours, it potentiates anti-PD therapy and boosts anticancer efficacy.

Despite the critical importance of the elastic properties of modern materials, there is not a singular model that can predict the modulus to an accuracy needed for industrial glass design. To address this problem, we propose an approach to calculate the elastic modulus based on the free energy density of topological constraints in the glass-forming network. Our approach shows quantitatively accurate agreement with glasses across a variety of compositional families. Moreover, using temperature-dependent constraint theory, the temperature dependence of the modulus can also be predicted. Our approach is general and theoretically can be applied to any network glass.

Self-matt coating of waterborne polyurethane (WBPU) was synthesized by combining prepolymer and self-emulsification methods. The emulsion was fabricated from both hydroxy carboxylic acid and aminosulfonic acid types of hydrophilic chain-extending agents, in which the 2-[(2-aminoethyl) amino] ethane sulphonate sodium (AAS salt) was produced in laboratory. This emulsion demonstrated an excellent matt performance without the addition of extra matting agents after filming. Four different kinds of surface properties were measured on the film: the specular gloss (60° gloss meter), the contact angle (CA), the surface roughness degree (3D Surface Profilometer), and the topography of the coatings surface (SEM). The results showed that tons of spherical particles with diameter in a few micrometers were aggregated on the film surface. The effect of the roughness parameters (R a and R q ) and the average particle size of the emulsions on the specular gloss degree were probed. The research indicated that the emulsion with average particle size in the range of 2.5–3.0 µm and, meanwhile, the film with roughness parameters R a and R q both greater than 1 µm could attain the best matt effect. The WBPU emulsions showed good physical and mechanical properties, and were introduced into wood varnish for matting purpose.

Clinical application of exenatide, a peptide drug widely used for the treatment of type 2 diabetes mellitus, is greatly limited due to its short plasma half-life of 2.4 hours. To prolong the half-life of exenatide, a water in oil in oil (W/O/O) method was employed to prepare exenatide-loaded PLGA microspheres with a satisfactory particle size of 75.22 μm and a span value of 1.13. Optimized exenatide-loaded microspheres were endowed with high entrapment efficiency (83.8 ± 1.3%) and low initial burst release (1.31 ± 0.13%). Degradation pattern of the peptide-loaded microspheres was investigated by monitoring the changes in molecular weight, appearance, and release profile. Histological study proved the safety of the microspheres. In the pharmacokinetics and pharmacodynamics study, the long acting formulation had relative bioavailability of 70.31% and it achieved a hypoglycemic activity for up to 3 weeks in diabetic mice. A single subcutaneous injection of exenatide-loaded microspheres exhibited a comparable effect on controlling blood glucose to exenatide solution, which was injected twice per day at the same dose of exenatide. In conclusion, the exenatide-loaded microspheres might be a promising long acting formulation for glycemic control with low initial burst release and reduced risk of gastrointestinal intolerance and hypoglycemia.

Iron-mediated oxidative stress is implicated in the pathogenesis of renal ischemia-reperfusion injury. Hepcidin is an endogenous acute phase hepatic hormone that prevents iron export from cells by inducing degradation of the only known iron export protein, ferroportin. In this study, we used a mouse model to investigate the effect of renal ischemia-reperfusion injury on systemic iron homeostasis and determine if dynamic modulation of iron homeostasis with hepcidin has therapeutic benefit in the treatment of AKI. Renal ischemia-reperfusion injury induced hepatosplenic iron export through increased ferroportin expression, which resulted in hepatosplenic iron depletion and an increase in serum and kidney nonheme iron levels. Exogenous hepcidin treatment prevented renal ischemia-reperfusion-induced changes in iron homeostasis. Hepcidin also decreased kidney ferroportin expression and increased the expression of cytoprotective H-ferritin. Hepcidin-induced restoration of iron homeostasis was accompanied by a significant reduction in ischemia-reperfusion-induced tubular injury, apoptosis, renal oxidative stress, and inflammatory cell infiltration. Hepcidin -: deficient mice demonstrated increased susceptibility to ischemia-reperfusion injury compared with wild-type mice. Reconstituting hepcidin-deficient mice with exogenous hepcidin induced hepatic iron sequestration, attenuated the reduction in renal H-ferritin and reduced renal oxidative stress, apoptosis, inflammation, and tubular injury. Hepcidin-mediated protection was associated with reduced serum IL-6 levels. In summary, renal ischemia-reperfusion injury results in profound alterations in systemic iron homeostasis. Hepcidin treatment restores iron homeostasis and reduces inflammation to mediate protection in renal ischemia-reperfusion injury, suggesting that hepcidin-ferroportin pathway holds promise as a novel therapeutic target in the treatment of AKI.

The outliers in geomagnetic measured data can seriously impact the geomagnetic matching results and greatly affect the geomagnetic matching efficiency. A geomagnetic matching algorithm which has anti-outlier ability and can adjust the displacement, heading and zoom errors is investigated in this paper. Firstly, L1 norm is introduced for robust estimation. Secondly, by combining the affine transformation, the correlate criterion and the Taylor series expansion for geomagnetic information, a mathematical expression of the displacement, heading and zoom errors is obtained. Thirdly, according to L1 norm weight function and the mathematical expression, the robust target function is acquired. Then the geomagnetic matching problem is converted to the solutions of nonlinear equations to minimize the function. Finally, Broyden iteration is applied to implement the novel algorithm. Simulation results show that the matching error of the novel algorithm is decreased to 31.08% to the conventional iterative contour matching algorithm when the outlier is 31nT. Meanwhile, the position error of the novel algorithm is 0.0195° while the conventional iterative contour matching algorithm fails to match when the outlier is 310nT.

ZnT7 (Slc30a7) is a widely expressed zinc transporter involved in sequestration of zinc into the Golgi apparatus and vesicular compartments. znt7-knockout (KO) mice are mildly zinc-deficient and lean. Despite their lean phenotype, adult male znt7-KO mice are prone to insulin resistance. We hypothesized that fat partitioning from adipose to nonadipose tissues causes insulin resistance in znt7-KO mice. Here, we used biological and biochemical methods, including fatty acid and oxylipin profiling, EM, immunohistochemistry, quantitative RT-PCR, and Western blot analysis, to identify the underlying mechanism of insulin resistance in znt7-KO mice. We found that insulin resistance in this model was primarily associated with increased intracellular fatty acid levels in the skeletal muscle, which promoted intracellular lipid accumulation and production of bioactive lipid mediators, such as 12,13-dihydroxyoctadecanoic acid (12,13-DiHOME) and 12-hydroxyeicosatetraenoic acid (12-HETE). The expression of fatty acid-binding protein 3 (Fabp3) was dramatically up-regulated in the znt7-KO muscle cells accompanied by increased expression of Cd36, Slc27a1, and Slc27a4, the three major fatty acid transporters in the skeletal muscle. We also demonstrated that znt7-KO muscle cells had increased fatty acid oxidative capacity, indicated by enlarged mitochondria and increased mRNA or protein expression of key enzymes involved in the fatty acid mitochondrial shuttle and β-oxidation. We conclude that increased fatty acid uptake in the znt7-KO skeletal muscle is a key factor that contributes to the excessive intracellular lipid deposit and elevated production of bioactive lipid mediators. These mediators may play pivotal roles in oxidative stress and inflammation, leading to insulin resistance.

Yutong Wang,1–3,* Liping Huang,1,2,* Yan Shen,1,2,* Lidan Tang,1,2,4 Runing Sun,1,5 Di Shi,6 Thomas J Webster,6 Jiasheng Tu,1,2 Chunmeng Sun1,2 1Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, China Pharmaceutical University, 2State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 3Department of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 4Changzhou Second People’s Hospital, Changzhou, 5School of Engineering, China Pharmaceutical University, Nanjing, People’s Republic of China; 6Department of Chemical Engineering, Northeastern University, Boston, MA, USA *These authors contributed equally to this work Abstract: To achieve enhanced physical stability of poly(ethylene glycol)-poly(D,L-lactide) polymeric micelles (PEG-PDLLA PMs), a mixture of methoxy PEG-PDLLA-polyglutamate (mPEG-PDLLA-PLG) and mPEG-PDLLA-poly(L-lysine) (mPEG-PDLLA-PLL) copolymers was applied to self-assembled stable micelles with polyion-stabilized cores. Prior to micelle preparation, the synthetic copolymers were characterized by 1H-nuclear magnetic resonance (NMR) and infrared spectroscopy (IR), and their molecular weights were calculated by 1H-NMR and gel permeation chromatography (GPC). Dialysis was used to prepare PMs with deoxypodophyllotoxin (DPT). Transmission electron microscopy (TEM) images showed that DPT polyion complex micelles (DPT-PCMs) were spherical, with uniform distribution and particle sizes of 36.3±0.8nm. In addition, compared with nonpeptide-modified DPT-PMs, the stability of DPT-PCMs was significantly improved under various temperatures. In the meantime, the pH sensitivity induced by charged peptides allowed them to have a stronger antitumor effect and a pH-triggered release profile. As a result, the dynamic characteristic of DPT-PCM was retained, and high biocompatibility of DPT-PCM was observed in an in vivo study. These results indicated that the interaction of anionic and cationic charged polyionic segments could be an effective strategy to control drug release and to improve the stability of polymer-based nanocarriers. Keywords: polyion complex micelles, electrostatic interaction, oligopeptide, stability, pharmacokinetics

Simultaneously using sulfonic and carboxylic acid as hydrophilic chain-extending agents, a new type of solvent-free and chemical matt waterborne polyurethane resin was prepared and investigated. The chemical structure containing urethane and urea groups in this novel carboxylate/sulfonate type of waterborne polyurethane (CSWPU) resin was confirmed by FTIR, 1H and 13C NMR spectra. An obvious advantage for the environment is that, unlike the traditional synthetic method for waterborne polyurethane, the reactive system doesn't need any organic solvent to reduce the viscosity of the prepolymer in the process of prepolymerization. In addition, the gloss extinction was generated by the drying process of the resin itself, without the requirement of any matting agents. 3D-AFM images indicate that the surface of the matt CSWPU films was extremely rough and was comprised of many spherical particles with diameters in the range of 0.8–3.0 μm arranged on the films' surface. The matt CSWPU resin tended to have a relatively higher molecular weight and lower swelling ratio. Moreover, an increase of sulfonic hydrophilic chain-extending agent content or the initial molecular weight of the soft segment facilitated the improvement of thermal stability.

A hyaluronic acid–platinum(IV) nanoconjugate with a high drug loading capacity was developed to mitigate the side effects of platinum(II). Pt(IV), HA–EDA, and HA–EDA–Pt(IV) nanoconjugates were investigated by 1H NMR, 13C NMR, FT-NIR, and DSC. Negatively charged polymer–drug conjugates were of a uniform size around 186.4 nm and spherical in shape. In vitro antiproliferation and in vivo apoptosis assays proved that the nanomedicine possessed high cytotoxicity towards cancer cells. The enhanced antitumor effect was attributed to HA receptor-mediated endocytosis. Nanoscale conjugates exhibited desirable blood compatibility and negligible stimulation to blood vessels. The systemic toxicity study showed that polymer–drug conjugates were much safer than the parent drug evidenced by biochemical and histological analyses. The concise design of the nanoconjugate offers a simple way to overcome the toxicity and non-selectivity of cisplatin, which could improve therapeutical outcomes of platinum drugs in cancer therapy.

Nanotechnology-based chemotherapy is efficient in cancer treatment due to the targeted delivery of small molecules via nano-carriers, which are usually regarded as "inert". However, nano-materials are more preferred as carriers since many cause synergistic anti-tumor effects along with the drug cargo. In this study, a "bioactive" tocopherol succinate (TOS) was grafted to hyaluronic acid (HA) via of disulfide bonds to obtain HA-ss-TOS conjugates which can assemble into nano-micelles but dissociate when exposed to reducing environments in vitro and in vivo. Moreover, paclitaxel-loaded HA-ss-TOS micelles (HA-ss-TOS-PTX) can be efficiently taken up by B16F10 cells overexpressing CD 44, thereafter exhibiting enhanced cytotoxicity. The in vivo imaging study here revealed much greater tumor accumulation of Dir-labeled HA-ss-TOS compared to the free Dir group. In vivo antitumor activities further ensured that the PTX-loaded HA-ss-TOS micelles provided superior antineoplastic responses versus PTX-loaded HA-TOS micelles and Taxol. Moreover, the subcellular dissociated TOS from HA-ss-TOS showed synergistic effects with PTX. These experimental results revealed that reduction-responsive PTX-loaded polymeric nano-micelles with multi-functional properties hold great potential for anti-tumor treatment and, thus, should be further studied.

Zinc deficiency impairs the immune system leading to frequent infections. Although zinc is known to play critical roles in maintaining healthy immune function, the underlying molecular targets are largely unknown. In this study, we demonstrate that zinc is important for the CD154-CD40-mediated activation of downstream signaling pathways in human B lymphocytes. CD40 is a receptor localized on the cell surface of many immune cells, including B lymphocytes. It binds to CD154, a membrane protein expressed on antigen-activated T helper (Th) lymphocytes. This CD154-CD40 interaction leads to B-cell activation. We showed that cellular zinc deficiency impaired the CD154-CD40-mediated p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. We also showed that zinc supplemental treatment of B lymphocytes had limited effect on this CD40-mediated p38 MAPK signaling. Most importantly, we demonstrated that the zinc transporter protein zinc transporter 7 (ZNT7) interacted with CD40 using immunoprecipitation analyses. ZNT7 knockdown in B lymphocytes had a negative effect on the cell surface expression of CD40. Consequently, the CD40-mediated p38 MAPK signaling transduction was down-regulated in ZNT7 KD B lymphocytes. Conversely, this p38 MAPK signaling activity was up-regulated by overexpression (OE) of ZNT7 in B lymphocytes. Moreover, we found that ZNT7 knockdown in B lymphocytes constitutively up- and down-regulated the inhibitor of i kappa B kinase and AKT serine/threonine kinase phosphorylation, respectively, which implies the activation of survival signaling in ZNT7 KD B cells. We conclude that CD40 is the target molecule for ZNT7 in regulation of immune function of B lymphocytes.

Rendering high-quality perovskite films is integral for excellent performance of optoelectronic devices and highly challenging as well. Here, we establish a two-round pressure-assisted solvent-engineering (TPS) strategy to achieve remarkable enhancement in grain size (~400 μm2), crystallinity, orientation and, especially, boundary fusion. Crystal growth and boundary welding of MAPbI3 grains are mainly attributed to pressure-enhanced ion diffusion and defect elimination, which facilitates lateral enlargement of grains and formation of ultra-smooth film. Dramatic diminution of trap density determines long carrier lifetime and improved lateral charge transport, as demonstrated by the superior performance of MAPbI3-based photodetectors, e.g. ultrahigh on/off ratio (~106), good stability, fast response, high responsivity and high detectivity (1.3 × 1014 Jones). When upconversion nanoparticles are uniformly assembled on the high-quality MAPbI3 films, interestingly, the hybrid device exhibits dominantly elevated photoelectric capability in near infrared range (NIR, 980 nm) with long-term stability in ambient air. The results and method pave a novel way for ongoing fabrication of efficient and stable optoelectronic devices based on high-quality perovskite films.

Core-crosslinked pullulan nanoparticles (Pull-LA-CLNPs) were synthesized by the reduction-sensitive strategy for paclitaxel (PTX) delivery. Pull-LA-CLNPs showed high stability against extensive dilution, high salt concentration and organic solvent. In vitro drug release study showed that PTX release from Pull-LA-NPs at pH 7.4 and 5.4 was significantly influenced by addition of DTT. In cytotoxicity assay, PTX loaded Pull-LA-CLNPs showed a low IC50 at 0.51μg/mL. Asialoglycoprotein receptor (ASGPR) competitive inhibition and intracellular distribution studies performed by flow cytometer, fluorescence microscope and confocal laser scanning microscopy (CLSM) showed that Pull-LA-NPs could be efficiently taken up by the cells via ASGPR-mediated endocytosis and mainly distributed in cytoplasm. From in vivo pharmacokinetics study, Pull-LA-CLNPs displayed the longest systemic retention time and slowest plasma elimination rate in comparison with Taxol and Pull-LA-NCLNPs. In conclusion, Pull-LA-CLNPs is a promisingly safe, biodegradable and cell-specific nano-carrier to deliver lipophilic anticancer drugs.

Let ${\mathbb{D}}^{m\times~n}$ be the set of $m\times~n$ matrices over a division ring $\mathbb{D}$.Two matrices $A,B\in~{\mathbb{D}}^{m\times~n}$ are adjacent if ${\rm~rank}(A-B)=1$. By the adjacency, ${\mathbb{D}}^{m\times~n}$ is a connected graph.Suppose that $\mathbb{D},~\mathbb{D}'$ are division rings with $|\mathbb{D}|\geq~4$ and $m,n,m',n'\geq2$ are integers.Using the geometric method, we characterize every non-degenerate graph homomorphism$\varphi$ from ${\mathbb{D}}^{m\times~n}$ to ${\mathbb{D}'}^{m'\times~n'}$ if $\varphi(0)=0$ and $\varphi$ preserves the dimensions of two standard maximal adjacent setsof different types in ${\mathbb{D}}^{m\times~n}$. As a 推论, when $\mathbb{D}$ is an EAS (every endomorphism to be automatically surjective) division ring, we get algebraic formulas of every non-degenerate graph homomorphismfrom ${\mathbb{D}}^{m\times~n}$ to $\mathbb{D}^{m'\times~n'}$.

Background The last decade has seen rapid changes to Chinese packaged foods which are causing serious adverse health outcomes. There is an urgent need for data to inform policy responses and monitor their implementation if diet-related diseases are to be prevented. Method A systematic review of existing studies was done and new data were collected from the labels of pre-packaged foods for sale in Beijing in 2013. The prevalence of nutrition labelling and the completeness of nutrient declarations was determined before and after the introduction of mandatory nutrition labelling in January 2013. Results There were data describing 22,636 foods prior to 2013 and 11,489 foods after 2013. The prevalence of nutrition labelling was much higher (87% vs. 44%) after the mandatory regulation was implemented in 2013. Reporting of energy, protein, fat, carbohydrate and sodium which are required by the regulation all improved. Nutrients not required by the regulation like saturated fat, trans fat and sugar were infrequently reported. Conclusion Mandatory nutrition labelling proved highly effective in China and is recommended to other countries. Ongoing collection of data will allow monitoring of changes in the packaged food supply. The FoodSwitch smartphone application will shortly be launched in China to facilitate this.

By using the Smith normal form of polynomial matrix and algebraic methods, this paper discusses the solvability for the linear matrix equation ΣAiXBi=C over a field, and obtains the explicit formulas of general solution or unique solution.

The outliers in the geomagnetic survey data seriously affect the precision of the geomagnetic matching navigation and badly disrupt its reliability. A novel algorithm which can eliminate the outliers influence is investigated in this paper. First, the weight function is designed and its principle of the robust estimation is introduced. By combining the relation equation between the matching trajectory and the reference trajectory with the Taylor series expansion for geomagnetic information, a mathematical expression of the longitude, latitude and heading errors is acquired. The robust target function is obtained by the weight function and the mathematical expression. Then the geomagnetic matching problem is converted to the solutions of nonlinear equations. Finally, Newton iteration is applied to implement the novel algorithm. Simulation results show that the matching error of the novel algorithm is decreased to 7.75% compared to the conventional mean square difference (MSD) algorithm, and is decreased to 18.39% to the conventional iterative contour matching algorithm when the outlier is 40nT. Meanwhile, the position error of the novel algorithm is 0.017° while the other two algorithms fail to match when the outlier is 400nT.

The effect of surface modification of Si3N4 particle on the colloidal behavior and the rheological properties of aqueous Si3N4 suspensions under steady and oscillatory conditions are investigated in detail. Due to the decrease of the oxidizing level, the isoelectric point (IEP) of the modified particle shifts to basic region gently. Attempts have been made to apply rheological models to the suspensions with various solid volume fraction (φ). For the as-received suspensions, the Sisco model provides the best fit in the range of φ ≤ 0.30 while the Casson model in 0.35 ≤ φ ≤ 0.45. The shear behavior of modified suspensions fits to Sisco model in the range of φ ≤ 0.40 and Casson model in 0.45 ≤ φ ≤ 0.54. The rheological behavior of modified suspensions is improved efficiently. The critical strain decreases and the linear viscoelastic regime narrows continuously with increasing solid concentration. For the modified suspensions, the linear viscoelastic regime broadens and the corresponding elastic modulus decreases sharply. With increasing solid concentration, the characteristic frequency shifts toward lower frequencies and the suspension transforms from more viscous to more elastic.