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PTFE/GF(glass fiber) composites are widely applied in high-frequency printed circuit board (PCB) substrate materials due to the excellent dielectric properties of PTFE and the low thermal expansion coefficient of GF. However, the poor interface compatibility between PTFE and GF affects the performance of the composite substrates. In this study, tetraethyl orthosilicate (TEOS) was used as the silicon source, and polydimethylsiloxane (PDMS) was the organic precursor to modify the surface of GF through the sol–gel method to promote the interface compatibility of GF and PTFE. The modified GF noted T-GF was filled in PTFE to prepare PTFE/T-GF composites. SEM, FTIR, XPS, and contact angle confirmed that organic–inorganic hybrids were successfully loaded on GF's surface. Moreover, compared with PTFE/GF and the conventional coupling agent modified GF filled PTFE composites, the PTFE/T-GF exhibited improved dielectric constant (2.305), decreased dielectric loss (9.08E−4), higher bending strength (21.45 MPa) and bending modulus (522 MPa), better thermal conductivity (0.268 W/m*K) and lower CTE (70 ppm/°C), making it has promising application as the substrate materials for high frequency PCB.

Pseudomonas fluorescens is a specific spoilage microorganism of refrigerated marine fish, which possesses strong adaptability to low temperature. Cold shock proteins (CSPs) play an important role in bacterial cold adaptation. In this study, the CSP genes were obtained from the genome of P. fluorescens PF08 by search the conserved domain of CSPs through HMMER software, and their physicochemical property, structure and function were analyzed by bioinformatics. A total of five typical CSPs are identified in P. fluorescens PF08 genome (PfCSPs). The results showed that the five PfCSPs are all small hydrophilic acidic proteins with molecular weight around 7.4 kDa. They are located in the cytoplasm and are non-secretory and non-transmembrane proteins. Multiple sequence alignment analysis indicated the CSPs were highly conserved between different species, especially in DNA-binding sites and RNA-binding motifs that can bind to single-stranded DNA and RNA. The five PfCSPs were clustered together with CspD from Escherichia coli and Salmonella typhimurium , which suggested that a close homology and high functional similarity among the five PfCSPs and CspD. The secondary and tertiary structures of the PfCSPs are accordance with the characteristics of the CSPs family and ligand binding sites with higher likelihood were found in PfCSPs. The five PfCSPs were predicted to interact with some of the same proteins that involved in virulence, stress responses (including low temperature), cell growth, ribosome assembly and RNA degradation. The results provides references for further elucidation of the function of CSPs in the process of low temperature adaptation of P. fluorescens .

Purely organic materials with dual room temperature phosphorescence (RTP) phenomenon were reported recently, but the underlying mechanism was still ambiguous. Herein, we revealed the source of dual RTP emission, taking CzDPS crystal as prototype, by using hybrid quantum mechanics and molecular mechanics (QM/MM) coupled with the thermal vibration correlation function rate theory. Theoretical calculations verified that the emission lifetimes are prolonged from 70 ms in the higher triplet state T

We develop a mathematical model of the wild mosquito dispersal with impulsive releases of the sterile mosquitoes and obtain a threshold condition that determines the eradication and uniform persistence of the wild mosquitoes using Floquet theory and impulsive comparison theorem. The effect of the dispersal rate on dynamics is investigated by means of numerical simulation. Additionally, we investigate a three-dimensional dispersal model of mosquitoes with impulsive state feedback control to effectively control the abundance of the wild mosquitoes below the acceptable level when the density of the wild mosquitoes reaches a certain threshold. Dynamics of such state-dependent control is also presented by applying numerical simulations since it is difficult to implement theoretical analysis. Finally, a brief discussion is given.

In this paper, a delayed mosquito population suppression model, where the number of sexually active sterile mosquitoes released is regarded as a given nonnegative function, and the birth process is density dependent by considering larvae progression and the intra-specific competition within the larvae, is developed and studied. A threshold value [Formula: see text] for the releases of sterile mosquitoes is determined, and it is proved that the origin is globally asymptotically stable if the number of sterile mosquitoes released is above the threshold value [Formula: see text]. Besides, the case when the number of sterile mosquitoes released stays at a constant level [Formula: see text] is also considered. In the special case, it is also proved that the origin is globally asymptotically stable if and only if [Formula: see text] and that the model exhibits other complicated dynamics such as bi-stability and semi-stability when [Formula: see text]. Numerical examples are also provided to illustrate our main theoretical results.

Background Owing to high genetic diversities of tumor cells and low response rate of standard chemotherapy, patients with triple negative breast cancer (TNBC) have short progression-free survivals and poor outcomes, which need to explore an effective approach to improve therapeutic efficacy. Methods Novel gadolinium doped carbon dots (Gd@CDs) have been designed and prepared through hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2′-(ethylenedioxy)bis(ethylamine) and gadolinium chloride. The synthesized nanostructures were characterized. Taking advantage of good biocompatibility of Gd@CDs, a nanoplatform based on Gd@CDs has been developed to co-deliver chemotherapy drug doxorubicin hydrochloride (Dox) and a near-infrared (NIR) photothermal agent, IR825 for magnetic resonance imaging (MRI) guided photothermal chemotherapy for TNBC. Results The as-synthesized Dox@IR825@Gd@CDs displayed favorable MRI ability in vivo. Upon NIR laser irradiation, Dox@IR825@Gd@CDs could convert the NIR light to heat and efficiently inhibit tumor growth through photothermal chemotherapy in vitro and in vivo. Additionally, the impact of photothermal chemotherapy on the murine motor coordination was assessed by rotarod test. Dox@IR825@Gd@CDs presented low toxicity and high photothermal chemotherapy efficiency. Conclusion A noble theranostic nanoplatform (Dox@IR825@Gd@CDs) was developed that could be tailored to achieve loading of Dox and IR825, intracellular delivery, favorable MRI, excellent combination therapy with photothermal therapy and chemotherapy to enhance therapeutic effect against TNBC cells. This study will provide a promising strategy for the development of Gd-based nanomaterials for MRI and combinational therapy for TNBC. Graphic abstract

Background Laryngeal cancer has the highest mortality rate among head and neck tumours. RNA N6-methyladenosine (m6A) is the most plentiful and variable in mammalian mRNA. Yet, the m6A regulatory mechanism underlying the carcinogenesis or progression of LSCC remains poorly understood. Methods The m6A RNA methylation quantification kit was used to detect tissue methylation levels. m6A microarray analysis, mRNA transcriptomic sequencing (mRNA-seq), and proteomics were used to determine RBM15, TMBIM6, and IGF2BP3. Immunohistochemical (IHC), quantitative real-time PCR (qRT-PCR) and Western blot were used to investigate RBM15, TMBIM6, and IGF2BP3 expression in tissue samples and cell lines. The biological effects of RBM15 were detected both in vitro and in vivo. The combination relationship between RBM15/IGF2BP3 and TMBIM6 was verified by RNA immunoprecipitation (RIP) assay, Methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNase Mazf, and luciferase report assay. RNase Mazf was used to determine the methylation site on TMBIM6 mRNA. Hoechst staining assay was used to confirm the apoptotic changes. The actinomycin D verified TMBIM6 stability. Results The global mRNA m6A methylation level significantly increased in LSCC patients. RBM15, as a “writer” of methyltransferase, was significantly increased in LSCC and was associated with unfavorable prognosis. The knockdown of RBM15 reduced the proliferation, invasion, migration, and apoptosis of LSCC both in vitro and in vivo. The results were reversed after overexpressing RBM15. Mechanically, TMBIM6 acted as a downstream target of RBM15-mediated m6A modification. Furthermore, RBM15-mediated m6A modification of TMBIM6 mRNA enhanced TMBIM6 stability through IGF2BP3-dependent. Conclusion Our results revealed the essential roles of RBM15 and IGF2BP3 in m6A methylation modification in LSCC, thus identifying a novel RNA regulatory mechanism.

A metal–ligand complex is a useful noncovalent bond to build up a cross-link network. Unfortunately, it is a challenge to construct the coordination cross-link networks in commercial elastomers wit...

The effects of edbile coatings, based on pullulan and sodium carboxymethylcellulose (PUL–CMC) with gallic acid (GA) and/or e-polylysine hydrochloride (PL), on the quality of sea bass (Lateolabrax maculatus) fillets during storage at 4 °C for 20 days were assessed in this study. Total viable counts (TVC), thiobarbituric acid (TBA), pH value, total volatile basic nitrogen (TVB-N), water holding capacity (WHC), water migration, texture profiles, and electronic nose results were measured at five day intervals. The results showed that treatments with PUL–CMC–GA, PUL–CMC–PL, and PUL–CMC–GA–PL coatings retarded the increase of the TVC, TBA, pH, and TVB-N value when compared with the results of the control group. These coatings significantly maintained the content of immobile water, WHC, texture and flavor properties of the fish. In addition, use of PUL–CMC–GA–PL was more effective than use of PUL–CMC–GA and PUL–CMC–PL. The TVC, TVB-N, and pH in the PUL–CMC–GA–PL group were all lower than those in the other groups during the whole storage time. The TBA value in the PUL–CMC–GA–PL group remained below 0.7 mg malonaldehyde (MDA) per kg at 20 d, which was extended by 10 d when compared with the values for the other groups. The WHC in PUL–CMC–GA–PL only decreased by 6.53% during 20 d of storage. The results indicated that GA combined with PL had a synergistic effect on improving the preservation properties of PUL–CMC, which could inhibit lipid oxidation, protein degradation and microbial growth, and maintain better texture characteristics during the storage of sea bass fillets.

Introduction: Laryngeal squamous cell carcinoma (LSCC) is diverse in its natural history and responsiveness to treatments. There is an urgent need to generate candidate biomarkers for the stratification and individualization of treatment to avoid overtreatment or inadequate treatment. Long noncoding RNA nuclear paraspeckle assembly transcript 1 (NEAT1) has been identified as an oncogenic gene in multiple human tumors entitles, and dysregulation of NEAT1 was tightly linked to carcinogenesis and cancer progression. Methods: One hundred two paraffin samples of LSCC patients were collected. Furthermore, in situ hybridization (ISH), Kaplan-Meier, and MTT were used to analyze the relationship between NEAT1 and the progress of LSCC. Results: In this study, ISH revealed that NEAT1 was strongly expressed in the nucleus. The increased expression of NEAT1 was correlated with T grade, neck nodal metastasis, clinical stage, drinking history, or smoking history of LSCC. The Kaplan-Meier analysis indicated that patients with higher NEAT1 expression had a worse overall survival in LSCC patients. In addition, NEAT1 knockdown significantly inhibited the growth of LSCC cells. Conclusion: Together, these results suggested that NEAT1 involved in the progress of LSCC and might act as a tumor oncogenic gene. This study provides a potential new marker and target for gene therapy in the treatment of LSCC.

Graphene has presented promising features for application in lithium ion batteries(LIBs) due to its superior electronic conductivity and high surface area. It has been successfully used for modifying cathode materials to meet the increasing demand for LIBs with longer cycle life. However, the improving effect of graphene on cycling stability is still unclear, which restricts its further application in LIBs. Herein, graphene coated hollow sphere-like structure LiNi0.5Mn1.5O4(LNMO) was designed and the improvement mechanism of graphene coating on LNMO's cycling stability was investigated. The results show that graphene coating not only contributes to suppress structural deformation from mechanistic reaction and extend solid-solution reaction, but also helps protect electrode from corrosion by the products from electrolyte decomposition and suppress the generation of surface defects, especially at high temperature. Owing to graphene coating, graphene coated LNMO can deliver a discharge capacity of 91 mAh g−1 with high capacity retention of 82.5% after 1000 cycles under 20C and 83.8 mAh g−1 with 94.5% capacity retention after 100 cycles under 2C at 55 °C. This work deeply explores the effect of graphene coating on cycling stability from crystal stability and surface stability, which will help a wider application of graphene in energy storage field.

Qiuying Li, Hua Huo, Wenli Hu, Yin Sui, Yunbiao Tang Department of Drug Clinical Trial Management Agency, General Hospital of Northern Theater Command, Shenyang 110840, People’s Republic of ChinaCorrespondence: Yunbiao Tang; Hua HuoDepartment of Drug Clinical Trial Management Agency, General Hospital of Northern Theater Command, Shenyang, People’s Republic of ChinaTel/Fax +86-24-28897206Email tangyb99@163.com; SZYQBGS@163.comPurpose: This study compared the bioequivalence of two formulations of escitalopram oxalate 20 mg tablets in terms of bioavailability and tolerability in healthy Chinese male and female subjects.Patients and Methods: A randomized, single-blind, two-period, two-sequence crossover study was performed under fasting and fed conditions, with a 21-day washout period. In total, 24 healthy subjects (18 males and 6 females) were enrolled in the fasting test and the fed test, respectively. Blood samples were collected over 168 h post-dose in each period. The concentrations of escitalopram in plasma were determined by high-performance liquid chromatography coupled with a tandem mass spectrometry. Pharmacokinetic parameters used for bioequivalence assessment were determined from the drug concentration data using noncompartmental analysis.Results: All subjects showed good medication compliance. The 90% confidence intervals (CIs) for the geometric mean ratios of AUC0-t, AUC0-∞, and Cmax were within the bioequivalence acceptance criteria (80.00% to 125.00%). Adverse events were recorded and no deaths or serious adverse events (SAEs) occurred.Conclusion: Escitalopram oxalate 20 mg tablets produced in China were bioequivalent to the reference formulation (Lexapro®) in healthy Chinese male and female subjects under fasting and fed conditions.Keywords: escitalopram, escitalopram oxalate tablets, clinical trials, LC-MS/MS, pharmacokinetics, bioequivalence

The Fenton reaction has attracted extensive attention due to its potential to be a highly efficient and environmentally friendly wastewater treatment technology. Noble copper-doped carbon dots (CuCDs) are prepared through a simple one-step hydrothermal method with 3,4-dihydroxyhydrocinnamic acid, 2,2'-(ethylenedioxy)bis(ethylamine) and copper chloride, endowing the Fenton reaction with enhanced catalytic activity for rhodamine B (RhB) degradation. The effects of the concentration of CuCDs, temperature, pH, oxygen (O

The hollow microspherical structure cathode materials of bimetallic disulfide CoxNi1-xS2 (x varied from 0.1 to 0.5) for lithium thermal battery were synthesized by hydrothermal method. The structure, morphology, and composition of the hollow CoxNi1-xS2 were evaluated by field emission scanning electron microscope (FESEM), energy-dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD). The thermal stability was assessed by differential thermal analyzer (DTA). The thermal battery fabricated with CoxNi1-xS2 as cathode active material and LiB as anode exhibits the good electrochemical performance at 450 °C. Especially when x = 0.1, the initial discharge voltage reached 2.037 V, and specific capacity was 297.4 mA h g−1 at cut-off voltage of 1.5 V during constant current discharge. The bimetal disulfide material also presented advantages of reducing the internal resistance of the single cell.

Background: Dysregulated expression of miR-532-3p has been observed in several types of cancer and plays a key role in tumor progression and metastasis. In this study, we analyzed the role and molecular mechanism of miR-532-3p in lymphoma progression. Methods: The expression of miR-532-3p in lymphoma sample tissues was analyzed using the GEO database and in cell lines by quantitative reverse transcription (qRT)-PCR. The functions of miR-532-3p in lymphoma cell proliferation and apoptosis were analyzed by CCK-8 assay and Annexin V-FITC/propidium iodide staining, respectively. In vivo, the tumor weight and volume were measured. The target gene of miR-532-3p was predicted using miRanda software, and then luciferase, qRT-PCR, and western blot assays were performed to verify that β-catenin was the downstream target gene of miR-532-3p. Results: miR-532-3p was decreased in lymphoma tissues and cell lines. In vitro and in vivo experiments showed that overexpression of miR-532-3p inhibited lymphoma cell proliferation and promoted apoptosis. Mechanistic studies demonstrated that β-catenin was a functional target gene of miR-532-3p. Furthermore, we found that overexpression of β-catenin reversed the tumor-suppression activities caused by overexpression of miR-532-3p in lymphoma proliferation and apoptosis. Conclusion: This study demonstrates that miR-532-3p functions as a tumor inhibitor in lymphoma progression by targeting β-catenin, suggesting miR-532-3p/β-catenin as a new diagnosis marker or potential therapeutic target in lymphoma.

Li7La3Zr2O12 (LLZO) has been considered as one of the most promising electrolytes for lithium batteries due to its high safety and wide electrochemical window. However, few reports were observed for the application of LLZO on lithium thermal batteries. In this paper, LLZO was studied as the electrolyte of lithium thermal battery. To further improve the performance of LLZO, LLZO-LiCl-LiBr-LiF composite electrolyte was designed by mechanical mixing LiCl-LiBr-LiF eutectic salt with LLZO. The doping content of LiCl-LiBr-LiF was also investigated, and the results showed that the optimize content was 15% (in weight) LiCl-LiBr-LiF. For instance, the specific capacity of the battery using LLZO-(LiCl-LiBr-LiF)x (x = 15%) as electrolyte was 224.6 mAh g−1, the active material utilization rate was 85.08%, and the service life of lithium thermal battery can be extended to 25 min under 80 mA cm−2 at 550 °C. The superior electrochemical properties of LLZO-(LiCl-LiBr-LiF)x (x = 15%) were ascribed to the larger ionic conductivity (2.802 × 10−2 S cm−1 at 550 °C). Our study not only successfully improves the electrochemical properties of LLZO by compositing with LiCl-LiBr-LiF electrolyte but also paves the way for the practical application of LLZO-LiCl-LiBr-LiF composite in the lithium thermal batteries.

ACT001, which is derived from an ancient anti-inflammatory drug, has been shown to cross the blood-brain barrier in preclinical studies and has demonstrated anti-glioblastoma (GBM) activity in clinical trials. However, its pharmacological potential for anti-GBM immune response modulation remains unclear. The chemical structure of ACT001 indicates that it may bind to STAT3 and thus modulate antitumor immune response. Methods: Bioinformatics and immunohistochemistry (IHC) were used to assess STAT3 and PD-L1 expression in gliomas. Western blotting, RT-PCR and immunofluorescence were used to detect PD-L1 and p-STAT3 expression in glioma cells exposed to ACT001. Chromatin immunoprecipitation, an ACT001-Biotin probe, and a dual-luciferase reporter assay were used to detect direct modulation. The in vivo efficacy of ACT001 was evaluated in GL261 murine glioma model. Survival analyses were conducted using the log-rank (Mantel-Cox) test. Results: Bioinformatic analysis of 1,837 samples from 4 public glioma datasets showed that STAT3 mRNA expression was correlated with the degree of malignancy and therapeutic resistance and that STAT3 mRNA expression was related to immunosuppression, leukocyte infiltration, and PD-L1 expression. IHC staining of 53 tissue samples confirmed that relatively high phosphorylated STAT3 and PD-L1 protein expression was associated with a relatively advanced World Health Organization (WHO) glioma grade. Next, we confirmed that ACT001 treatment reduced PD-L1 expression and STAT3 phosphorylation. An ACT001-biotin probe was used to verify that ACT001 bound to STAT3. We also demonstrated that STAT3 bound to the PD-L1 promoter. The inhibition of PD-L1 expression and STAT3 phosphorylation by ACT001 could be rescued by STAT3 overexpression. Additionally, ACT001 inhibited GBM growth and decreased PD-L1 expression in vivo. The expression of the M2 markers CD206 and CD163 was decreased, while that of the antitumor immune markers iNOS and IFNγ was increased by ACT001 in vivo. Conclusion: Our results demonstrate that STAT3 plays a key role in immunosuppression of glioma and is inhibited by ACT001. ACT001 inhibits PD-L1 transcription and modulates anti-tumor immune response in glioma bearing mice. These findings will help us to understand the mechanism of ACT001 in GBM therapy.

Considering the rhizosphere microbes easily affected by the environmental factors, we formulate a three-dimensional diffusion model of the rhizosphere microbes with the impulsive feedback control to describe the complex degradation and movement by introducing beneficial microbes into the plant rhizosphere. The sufficient conditions for existence of the order-1 periodic solution are obtained by using the geometrical theory of the impulsive semi-dynamical system. We show the impulsive control system tends to an order-1 periodic solution if the control measures are achieved. Furthermore, we investigate the stability of the order-1 periodic solution by means of a novel method introduced in the literature [Y. Ye, The Theory of the Limit Cycle, Shanghai Science and Technology Press, 1984.]. Finally, mathematical results are justified by some numerical simulations.

Stepwise modification of ovatodiolide revealed a prodrug, NMP-diepoxyovatodiolide, which can provide sustained release of an active compound, substantial metabolic stability and a unique accumulation profile in the liver. Besides, NMP-diepoxyovatodiolide demonstrated therapeutic benefits in an acute autoimmune hepatitis mouse model and a broad safety window. Therefore, NMP-diepoxyovatodiolide is a very promising candidate for further development of liver-related drugs.

The combined effects of cinnamaldehyde (CA) and ultrahigh pressure (UP) treatment on the flavor of olive flounder (Paralichthys olivaceus) fillets during storage at 4 °C for 20 days were investigated. Changes in total viable count, trimethylamine, ATP-related compounds, free amino acids, TCA-soluble peptides, electronic nose (E-nose) analysis and sensory quality were measured. The results indicated that CA and UP treatment, especially CA combined with UP, significantly reduced undesirable flavor compounds including inosine, hypoxanthine, TMA, and bitter amino acids, and accumulated pleasant flavor compounds such as inosine monophosphate and umami-related amino acids. In addition, the combination of CA and UP was shown to be more effective for retarding protein degradation and microbial growth than CA or UP treatment alone. In accordance with the results of E-nose analysis and sensory evaluation, CA combined with UP treatment had great potential for improving the flavor quality of refrigerated flounder fillets and extending their storage life.

Background. To explore the curative effect of Shuangshen Decoction combined with immunological preparations in the treatment of pediatric nephrotic syndrome and its influence on concurrent infection and recurrence rate. Methods. Ninety children with nephrotic syndrome were divided into the routine group and the combined group. The routine group received conventional treatment and immune agents, and the combined group was treated with Shuangshen Decoction on the basis of the routine group. The clinical indexes of the two groups were analyzed and followed up. The infection rate and recurrence rate were calculated. Results. The TCM syndrome scores in the combined group were significantly lower than those in the routine group. The total effective rate of the combined group was significantly higher than that of the routine group. The recurrence rate and infection rate of the combined group were significantly lower than those of the routine group. The incidence of adverse reactions in the combined group was significantly lower than that in the routine group. Conclusion. Shuangshen Decoction combined with immune preparations is effective in treating pediatric nephrotic syndrome and can reduce the incidence of adverse reactions, infection rate, and recurrence rate.

Fabrication of anti-wetting coatings with anti-biofouling and anti-biofilm properties has become a hot spot of attention in recent years. However, the anti-biofilm mechanism of anti-bacterial adhesion coatings with different wet resistance properties has not been explored in detail. In this work, SiO

Cerebral ischaemia-reperfusion injury (CIRI) is a common disease characterized by severe attacks and a high disabling rate worldwide. Oxidative stress injury has been proposed as a major risk factor for CIRI. Ginkgo biloba extract (GBE) has been shown to elicit vascular protective effects, the main components of which are Ginkgo flavonoids (GF) and ginkgolides (GL). Our previous study showed that GF and GL played a central role in protecting CIRI, but the mechanism remains unclear. This study aimed to further reveal the protective effect mechanism of GF and GL in rats with CIRI.The antioxidant activity in vitro was assessed by the DPPH method. The model used in this study was established by middle cerebral artery occlusion (MCAO) and reperfusion; the level of CIRI was assessed by nerve function score and TTC staining; we measured the oxidative stress indices in the brain cortex, including LDH, GSH-Px, and the protein contents of Akt, p-Akt, Nrf2, and HO-1; HPLC-MS was used to detect drug concentrations in rat plasma at different times after administration of GF and GL; and the pharmacokinetic parameters of each component were calculated by Drug and Statistic Version 3.2.6 (DAS 3.2.6) software and SPSS 17.0.Regarding the DPPH free radical scavenging ability, GF performed better free radical scavenging ability than GL. In terms of the nerve function score and TTC staining, there were no statistically significant differences among the GF, GL and combined groups; however, there were significant differences in reducing the activity of LDH and increasing the activity of GSH-Px in the three administration groups. For the expression of Akt, p-Akt, Nrf2, and HO-1, the combined group had a significant effect compared with that in the GF or GL group. In addition, there was a significant multicomponent interaction in vivo in the combined group compared with the GF or GL group.After GF and GL were used in combination, the effect of anti-CIRI was more pronounced. This result indicated that GF and GL might improve CIRI by activating the PI3K/Akt/Nrf2 signalling pathway and promoting multicomponent interactions in vivo.

Plant essential oils lose their activity due to unstable chemical properties and volatility, and the coating can improve their stability by encapsulating. The three-layer coatings were prepared by tape casting method with flaxseed gum (FG) and chitosan (CS) as film-forming materials, eugenol (EG) and laurel essential oil (LEO) as preservatives. The composite coatings were characterized, and their physicochemical properties, release properties, antibacterial and antioxidant properties were determined. Meanwhile, the protective effect of the composite coatings on rainbow trout fillets myofibril protein was studied. The mechanical properties of the FG/CS/FG coatings are better than FG coating. The release of EG and LEO from the coatings are followed simple diffusion mechanism. After added essential oils, the antibacterial and antioxidant properties of the composite coatings are significantly enhanced. In the preservation process of the rainbow trout fillets, the composite coatings can reduce the carbonyl content, increase the sulfhydryl content and Ca2+-ATPase activity. The β-sheet content is 6.09%–15.63% higher than that of control, indicating the coatings are helpful to maintain the order of myofibril protein. The composite coatings slowed down the decrease of antioxidant enzyme activity, thus delay the protein oxidation. Because of long-term antibacterial and antioxidant properties, the composite coatings have potential value in food preservation or food packaging materials.

BackgroundPrunella vulgaris L. has been a traditional Chinese anti-inflammatory medicine for hundreds of years. However, clinic evidence indicates that it also causes a cluster of metabolic syndromes such as reduced appetite, diabetes, diarrhea etc. To date, the mechanisms of the anti-inflammation and associated symptoms by P. vulgaris treatment remain unclear. MethodsNetwork pharmacology studies using TCMSP and Genecards database, Cytoscape, GO and KEGG were applied to reveal the ingredients, hub molecules and their interactions, and enriched biologic processes associated with analgesic and glucose intolerance. Some active gradients and target genes were obtained from the comparisons of relevant databases in TCMSP and Genecards. Connections of validated and predicted gradients, target genes and diseases were visualized through Cytoscape. GO and KEGG were applied to identify the significantly engaged hub genes, biological processes and signaling pathways. To further validate GC and BDNF effects, C57BL/6J male mice were randomly divided into 5 groups, control (C), dexamethasone (Dex, 1 mg/kg/day), PE-treated (35mg, 70mg), and PE (70mg) + mifepristone (2.5 mg/kg/day) (PEM group). Mice were pretreated by water extract of P. vulgaris spica (PE) for 3-4 weeks followed by one of the following tests: acetic acid-induced writhing, hot plate test, rotaroad test, food intake, glucose tolerance test (GTT). Quantitative PCR was applied to detect hepatic and hypothalamic gene expression. Plasma brain-derived neurotrophic factor (BDNF), glucocorticoids, IL1β, IL6 and IL10 were measured by ELISA. ResultsNetwork pharmacology studies revealed that BDNF, GCs and GC-responsive or down-stream genes such as GC-induced leucine zipper protein (GILZ), glucose-6-phosphatase catalytic subunit 1, protein kinase B (PKB), etc. were intensively involved into anti-inflammation and glucose intolerance. Acetic acid-induced writhing and hot plate tests confirmed the peripheral and central analgesic effects of PE treatment. Based on the results of feeding behavior tests, 4-week PE treatment impeded food intake but increased the ratio of bodyweight gain to food intake. GTT revealed PE treatment impaired glucose disposal in mice. Finally, real time PCR confirmed that hepatic GC-target genes, such as G6Pase, GILZ, SGK1, PKB were up-regulated, and hypothalamic neuropeptide Y (NPY) and agouti-related protein (AGRP) expression were decreased by PE administration. Glycogen synthase kinase 3 beta (Gsk3 β) was mildly increased. Hypothalamic BDNF was up-regulated, whereas hepatic BDNF was down-regulated. Plasma BDNF and GCs were increased, and IL1β, IL6 and IL10 were decreased by PE treatments (pConclusionsGCs, BDNF, SGK1, insulin and PKB are most relevant molecules to analgesic and glucose intolerance when P. vulgaris is applied. PE treatment plays the analgesic role through the GC, GILZ and PKB regulatory pathways, and regulates the levels of some pro-inflammatory cytokines. Meanwhile, it upregulates G6PC1and GSK3β expression to increase plasma glucose level leading glucose intolerance. Although PE treatment decreases food intake, it makes mice to be prone to obesity. The corresponding increase of plasma BDNF may act as a counterpart to GC effects leading animals to adapt environments more easily.

Many NHPP software reliability growth models (SRGMs) have been proposed to assess software reliability during the past 40 years, but most of them have focused on modeling the fault detection process (FDP) in two ways: one is to ignore the fault correction process (FCP), i.e., faults are assumed to be instantaneously removed after the failure caused by the faults is detected. However, in real software development, it is not always reliable as fault removal usually needs time, i.e., the faults causing failures cannot always be removed at once and the detected failures will become more and more difficult to correct as testing progresses. Another way to model the fault correction process is to consider the time delay between the fault detection and fault correction. The time delay has been assumed to be constant and function dependent on time or random variables following some kind of distribution. In this paper, some useful approaches to the modeling of dual fault detection and correction processes are discussed. The dependencies between fault amounts of dual processes are considered instead of fault correction time-delay. A model aiming to integrate fault-detection processes and fault-correction processes, along with the incorporation of a fault introduction rate and testing coverage rate into the software reliability evaluation is proposed. The model parameters are estimated using the Least Squares Estimation (LSE) method. The descriptive and predictive performance of this proposed model and other existing NHPP SRGMs are investigated by using three real data-sets based on four criteria, respectively. The results show that the new model can be significantly effective in yielding better reliability estimation and prediction.

Background：The HOX family transcription factor HOXB9 is a crucial element in the progression of various cancers. In the previous study conducted by the investigators, a drastically higher HOXB9 expression was reported in laryngeal squamous cell cancer (LSCC), when compared to adjacent normal laryngeal squamous tissues. Furthermore, a high level of HOXB9 was closely correlated with histological grade and overall survival in LSCC patients. However, the underlying molecular mechanisms have not been fully elucidated.Results: The present study explored the molecular mechanisms of HOXB9 in LSCC progression. Furthermore, the in vitro and in vivo studies revealed that the gene knockout of HOXB9 using the CRISPR/CAS9 system inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. Mechanistic studies in LSCC cell lines and human LSCC specimens demonstrated that HOXB9 promotes LSCC progression by directly upregulating the MMP12 expression at the level of its transcription.Conclusions: Collectively, the present study is the first to demonstrate the role of HOXB9 in the regulation of LSCC progression by enhancing the upregulation of MMP12.

Polylactic acid (PLA) is a promising food packaging material with biocompatible, nontoxic and biodegradable. In order to reduce the deterioration of aquatic products caused by microorganisms, PLA coaxial nanofiber films with cinnamaldehyde (CMA), tea polyphenol (TP) and its composite as core materials were prepared by using coaxial electrospinning technology. Its microscopic morphology and structure were characterized separately, and its thermal stability, wettability and mechanical properties were determined. The antibacterial activity and antibacterial mechanism of nanofiber films were studied with Shewanella putrefaciens (S. putrefaciens) which is the dominant spoilage of aquatic products as the target of action. The results show that the CMA/TP (m/m = 2:5)-PLA coaxial nanofibers have small diameter, uniform distribution, smooth surface, no pores and fracture. At the same time, the film has strong hydrophobicity, good thermal stability and mechanical properties. Its antibacterial performance is better than that of single-core nanofiber films, which effectively destroys the cell membrane of S. putrefaciens, increases the permeability of cell membrane, and interferes with the synthesis and expression of its protein. The coaxial nanofiber films with CMA, TP and its composite as core material can be used as a fresh-keeping material with antibacterial properties, and has potential application value in the field of food preservation.

Increasing experimental evidences suggest that cell phenotypic variation often depends on the accumulation of some special proteins. Recently, a lot of studies have shown that the complexity of promoter architecture plays a major role in regulating transcription and controlling expression dynamics and further phenotype. One unanswered question is why the organism chooses such a complex promoter architecture and how the promoter architecture affects the timing of proteins amount up to a given threshold. To address this issue, we study the effect of promoter architecture on the first-passage time (FPT) by formulating a multi-state gene model, that may reflect the complexity of promoter architecture. We derive analytical formulae for FPT moments in each case of irreversible promoter and reversible promoter regulation, which is the first time to give these analytical results in the existing literature. We show that the mean and noise of FPT increase with the state number of promoter architecture if the mean residence time at \begin{document}$ off$\end{document} states is not fixed. Inversely, if the mean residence time at \begin{document}$ off$\end{document} states is fixed, then complex promoter architecture will not vary the mean of FPT but will tend to decrease the noise of FPT. Our results show that, in the same inactive promoter states, the noise of FPT with promoters in irreversible case is always less than that in reversible case. In conclusion, our results reveal the effect of the promoter architecture on FPT and enhance understanding of the regulation mechanism of gene expression.

The aim of this study was to confirm the anti-inflammatory effect and explore the adverse effects and underlying mechanisms of Prunella vulgaris L., which has been extensively used for hundreds of years in East Asia. Network pharmacology studies predicted that glucocorticoids (GCs), GC-targeting molecules, and brain-derived neurotrophic factor (BDNF) were intensively involved in the anti-inflammation and glucose intolerance. To attest the effects and underlying mechanisms, C57 male mice were randomly divided into 5 groups, control (C), dexamethasone (Dex), water extract of P. vulgaris (PE 35 or 70 mg), and PE (70 mg) + mifepristone (PEM). After a 3-week treatment, acetic acid-induced writhing and hot plate tests confirmed the peripheral and central analgesic effects, respectively. Plasma GCs and BDNF were significantly increased. Coincidently, plasma pro-inflammatory cytokines, including IL1β, IL6, and IL10, were decreased by PE treatment, which were blocked by the application of mifepristone ( P < 0.5). Western blots confirmed GC receptor (GR) translocation, and decreased cyclooxygenase 2 in the lumber spine by PE treatment. Food intake was impeded after a 4-week PE treatment, but the ratio of bodyweight gain to food intake was increased in a time-dependent manner. An intraperitoneal glucose tolerance test disclosed that PE treatment impaired glucose disposal in mice. Quantitative polymerase chain reaction (PCR) showed that hepatic GC-responsive genes such as GC-induced leucine zipper protein and glucose-6-phosphatase catalytic subunit 1 were up-regulated, and hypothalamic neuropeptide Y and agouti-related protein expressions were decreased by PE treatment. Hypothalamic BDNF was up-regulated, whereas hepatic BDNF was down-regulated. The regulation of these genes by PE was reversed by mifepristone administration. In conclusion, PE treatment plays analgesic and glucose regulation roles simultaneously through GC-induced signaling pathways, and P. vulgaris may provide a natural ligand of GR for the treatment of inflammation with glucose dysregulation.

Toll-like receptors (TLRs), which are essential components of the innate immune response, play an important role in acute kidney injury (AKI). Toll-like receptor 2 (TLR2) is constitutively expressed in tubular epithelial cells of the kidney and participates in cisplatin-induced AKI. The autophagy is a dynamic catabolic process that maintains intracellular homeostasis, which is involved in the pathogenesis of AKI. Recent studies demonstrate that PI3K/Akt signaling pathway regulates autophagy in response to various stimuli. Therefore, we propose that cisplatin might activate TLR2, which subsequently phosphorylates PI3K/Akt, leading to enhanced autophagy of renal tubular epithelial cells and protecting cisplatin-induced AKI. We found that TLR2 expression was significantly increased in the kidney after the cisplatin treatment. TLR2-deficient mice exacerbated renal injury in cisplatin-induced AKI, with higher serum creatinine and blood urea nitrogen, more severe morphological injury compared with that of wild-type mice. In vitro, we found that inhibition of TLR2 reduced tubular epithelial cell autophagy after the cisplatin treatment. Mechanistically, TLR2 inhibited autophagy via activating PI3K/Akt signaling pathway in renal tubular epithelial cells after the cisplatin treatment. Take together, these results suggest that TLR2 may protect cisplatin-induced AKI by activating autophagy via PI3K/Akt signaling pathway.

Tetraethyl orthosilicate (TEOS) was used as the silicon source, and polydimethylsiloxane (PDMS) was the organic precursor to modify the surface of glass fiber (GF) through the sol-gel method. The modified GF noted T-GF was filled in PTFE to prepare PTFE/T-GF composites. SEM, FTIR, XPS, and contact angle confirmed that organic-inorganic hybrids were successfully loaded on GF's surface. Compared with PTFE/GF and the conventional coupling agent modified GF filled PTFE composites, the properties of PTFE/T-GF composites, including dielectric properties, mechanical properties, moisture absorption, thermal conductivity, and coefficient of thermal expansion (CTE), enhanced significantly for the improvement of compatibility of PTFE and GF. Moreover, the PTFE/T-GF exhibited improved dielectric constant (2.305), decreased dielectric loss (9.08E-4), higher bending strength (21.45 MPa) and bending modulus (522 MPa), better thermal conductivity (0.268 W/m*K) and lower CTE (70 ppm/℃), making it has promising application as the substrate materials for printed circuit board.

Qiuying Li,1 Lihui Jia,1 Wenli Hu,1 Shu Dong,2 Chaohong Cai1 1Department of Drug Clinical Trial Management Agency, General Hospital of Northern Theater Command, Shenyang, People’s Republic of China; 2Clinical Trial Operations and Management Unit, Jilin Sihuan Pharmaceutical Co. Ltd, Meihekou, People’s Republic of ChinaCorrespondence: Chaohong Cai; Lihui JiaDepartment of Drug Clinical Trail Management Agency, General Hospital of Northern Theater Command, Shenyang, People’s Republic of ChinaTel +86-24-28897206Fax +86-24-23890028Email sycch@sina.com; jlhui20@163.comPurpose: To evaluate the bioequivalence and safety of two formulations of 25 mg tenofovir alafenamide tablets in Chinese healthy male and female subjects under fed and fasting conditions.Patients and Methods: This was a randomized, open-label, single-center, crossover study consisting of a fasting trial with two periods and a fed trial with four periods. In total, 42 healthy subjects were enrolled in the fasting trial and 32 healthy subjects were enrolled in the fed trial. In each period, blood samples for pharmacokinetic analysis were collected until 72 hours post-dose. The plasma concentrations of tenofovir alafenamide and tenofovir were measured and noncompartmental analysis was used to determine pharmacokinetic parameters. Throughout the entire study, subjects’ safety was monitored by assessment of physical examinations, vital signs, 12-lead electrocardiography, clinical laboratory parameters, and treatment emergent adverse events (TEAEs).Results: Forty subjects completed the fasting trial and 32 subjects completed the fed trial. The 90% confidence intervals (CIs) of the geometric mean ratios for AUC0-t, AUC0-∞, and Cmax for the two formulations were within 80.00% to 125.00%, which met the bioequivalence acceptance criteria. The study drugs were well tolerated by all subjects.Conclusion: This study demonstrated that the test formulation of 25 mg tenofovir alafenamide tablets was bioequivalent to the formulation marketed under the brand name VEMLIDY® in healthy Chinese male and female subjects under fasting and fed conditions.Keywords: tenofovir alafenamide, safety, pharmacokinetics, bioequivalence

Rhubarb anthraquinone glycosides (RAGs) have been proven to have significant therapeutic effects on ischemic stroke, and this effect may be related to the microbiome-gut-brain axis. In this study, an HPLC-FLD method was established to measure brain-gut neurotransmitters of rats with cerebral ischemia-reperfusion injury (CIRI), to explore whether the mechanism of RAGs against CIRI is related to the microbiome-gut-brain axis. A Shimadzu ODS-3 C18 column was used for chromatographic separation, and 5-hydroxytryptamine (5-HT), 5-hydroxy indole acetic acid (5-HIAA), glutamic acid (Glu), aspartic acid (Asp), and γ-aminobutyric acid (GABA) were determined simultaneously. The results showed that there is an excellent linear relationship (R2 ≥ 0.9990) and a high separation degree in the HPLC-FLD method. Whereas the contents of Asp and Glu in the brain and colon increased (p < 0.05), the contents of 5-HT, 5-HIAA, and GABA in the brain and colon decreased (p < 0.05) after CIRI. RAGs could effectively reduce the contents of Asp and Glu (p < 0.05), and increase the contents of 5-HT, 5-HIAA, and GABA in the brain and colon (p < 0.05). Combined with the previous experimental results, we can speculate that RAGs can regulate intestinal flora disorder caused by CIRI, and then regulate the imbalance between the release and decomposition of neurotransmitters caused by intestinal flora disorder.

Additional file 1: Table S1. The primers used in this study.