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Hyaluronic acid (HA) is the main component of the extracellular matrix (ECM) of joints, and it is important for a lubricating joint during body movement. Degradation is the main metabolic process of HA in vivo. Hyaluronidases (HAase) were known for HA degradation. The inflammation-induced HA rapid-metabolism can reduce HA viscosity and concentration in joints. Mast cells (MC) containing their specific proteases were found in synovium tissue. It is unclear if MC-proteases could be involved in HA degradation pathways. This study aims to explore the correlations between HA concentration vs mast cell proteases, or matrix metalloproteinase-2/9 (MMP-2/9) and to investigate the association of MC-specific proteases with disrupted synovial HA homeostasis in rheumatoid arthritis (RA) or collagen-induced arthritis rats. The synovial fluid samples from no-RA and RA patients were collected; the collagen-induced arthritis (CIA) rat model was established; HA concentration and the activities of MC-protease and MMP-2/9 in the samples were detected, and the correlations were analyzed. In vitro interaction experiment was carried out by mixing MC-proteases with HA to observe the degradation speed. The HA concentrations in synovial fluids were decreased in RA patients and CIA rats compared with those in no-RA subjects or normal rats respectively. The activities of mast cell proteases in synovial fluids were increased and positively correlated with MMP-9, but negatively correlated with HA concentrations. In vitro study, the addition of MC-chymase and tryptase promoted the speed in HA degradation. MC-proteases may influence HA degradation pathway.

Qualitative and quantitative analyses of quercetin (Qu) and isorhamnetin (Is) in Hippophae rhamnoides L. fruits hydrolysis products from 10 different origins were conducted by high-performance thin-layer chromatography (HPTLC), using 3% sodium acetate silica gel G plate (Anhui Liangchen), dichloromethane–ethyl acetate–formic acid (7:3:1, V/V) as the developing reagent, 1% ethanol solution of aluminum trichloride as the chromogenic agent, scanning at a wavelength of 390 nm. The content of Qu and Is in H. rhamnoides L. fruits hydrolysis products from 10 different producing areas was determined. The results showed that the RF value of Qu was 0.48 ± 0.05, the linear range was 0.06–0.42 μg/μL, and the correlation coefficient was 0.9990, indicating that the linear correlation of Qu was good. The RF value of Is was 0.64 ± 0.05, the linear range was 0.04–0.44 μg/μL, and the correlation coefficient was 0.9993, indicating that the linear correlation of Is was good. The precision analyses of Qu and Is showed that the RSD was

The combination processes of metal-assisted chemical etching (AgNO3 + HF + H2O2) and rounding etching (HNO3 + HF + H2O) were used for the texturization of diamond wire sawn (DWS) multi-crystalline silicon (mc-Si) wafers. The evolution of texture structure on the DWS mc-Si wafers was investigated in detail. The chemically microsurface-sphericizing (CMS) textures, which were nearly smooth spherical structure with a size of approximately 2–3 μm, were fabricated successfully on the DWS mc-Si wafers with the combination processes. Compared with the conventional metal-assisted chemical etching (MACE) textures, the CMS textures were improved on surface recombination and the filling of electrode, thereby boosting the electrical performance of the solar cells and the cell-to-module (CTM) loss at the module end. These CMS textures resulted in an increase in the output power of the photovoltaic module by 0.047 W per cell. The fabrication of these CMS textures may be easily scaled up in the photovoltaic production line.

ObjectiveTo determine the levels of gallic acid and ellagic acid by using high-performance liquid chromatography (HPLC) with R software hierarchical cluster analysisin Elaeagnus angustifolia L. gathered from different locations in Xinjiang.MethodsA chromatographic column Diamonsil C18 with a size of 4.6 × 250 mm and 5 μm was used with methanol as A and 0.1% phosphoric acid aqueous solution as B as the mobile phase. The flow rate was 1 mL/min for the gradient elution and the injection volume was 5 μL. HPLC was performed with a detection wavelength of 260 nm and chromatographic column of 35 °C. In addition, R software hierarchical clustering method was used for studying the levels of gallic acid and ellagic acid in E. angustifolia L. from 10 areas.ResultsGallic acid and ellagic acid showed a good linear relationship between 7.375 and 236 μg/mL with a correlation coefficient of 0.9999, and between 3.625 and 116 μg/mL with a correlation coefficient of 0.9999 respectively. The average recovery values were 103.98 and 101.57%, and the Relative Standard Deviation (RSD) values were 1.92 and 1.47%.ConclusionDifferences in the levels of gallic acid and ellagic acid in E. angustifolia L. leaves from different areas in Xinjiang showed that both were the highest in Kuitun.

Background Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates and has very limited therapeutic options. Sialylated human milk oligosaccharides (SHMOs) improve pathological changes in experimental NEC models. The objectives of this study were to investigate the involvement of NLRP3 inflammasome in NEC pathology and to explore the effects of SHMOs on toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/NLRP3 inflammatory pathway in experimental NEC. Methods The intestinal-tissue segments were collected from NEC infants, NLRP3 and caspase-1 positive cell were examined by immunohistochemistry. Newborn rats were hand-fed with formula containing or non-containing SHMOs (1500 mg/L) and exposed to hypoxia/cold stress to induce experimental NEC. The NEC pathological scores were evaluated; ileum protein expression of membrane TLR4 (mTLR4), inhibitor κB-α (IκB-α), NF-κB p65 subunit and phospho-NF-κB p65, as well as NLRP3 and caspase-1 were analyzed; ileum concentrations of interleukin-1β, interleukin-6, tumor necrosis factor-α (TNF-α) were also measured. Human colon epithelial Caco-2 cells were pre-treated with or without SHMOs and stimulated with TLR4 activator, lipopolysaccharide. Cell viabilities, mitochondrial membrane potential and supernatant matrix metalloprotease 2 (MMP-2) activities were analyzed. Results Increased frequencies of NLRP3 and caspase-1 positive cells were found in the lamina propria of damaged intestinal area of NEC neonates. SHMOs supplementation reduced NEC incidence and pathological damage scores of rats challenged with hypoxia/cold stress. Accumulation of interleukin-1β, interleukin-6 and TNF-α in NEC group were attenuated in SHMOs + NEC group. Protein expression of mTLR4, NLRP3 and caspase-1 were elevated, cytoplasmic IκB-α were reduced, nuclear phospho-NF-κB p65 were increased in the ileum of NEC rats. SHMOs supplementation ameliorated the elevation of mTLR4, NLRP3 and caspase-1, restored IκB-α in the cytoplasmic fraction and reduced phospho-NF-κB p65 in the nuclear fraction in the ileum of NEC rats. SHMOs pre-treatment improved Caco-2 cell viability, mitigated loss of mitochondrial membrane potential and modulated MMP-2 activities in the presence of lipopolysaccharide in-vitro. Conclusions This study provided clinical evidence of involvement of NLRP3 inflammasome in NEC pathology, and demonstrated the protective actions of SHMOs might be owing to the suppression of TLR4/NF-κB/NLRP3-mediated inflammation in NEC.

Epstein–Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) cells display conspicuous lipid accumulation. Here, we show that EBV‐encoded membrane protein 2A (LMP2A) induces lipid accumulation in NPC cells by inhibition of lipolytic gene, adipocyte triacylglycerol lipase (ATGL). Inhibition of ATGL results in enhanced lipid accumulation and migratory capacity in NPC cells. Loss of ATGL in NPC cells correlates with poor overall survival., Epstein–Barr virus (EBV)‐associated nasopharyngeal carcinoma (NPC) is one of the most common human cancers in South‐East Asia exhibiting typical features of lipid accumulation. EBV‐encoded latent membrane protein 2A (LMP2A) is expressed in most NPCs enhancing migration and invasion. We recently showed an increased accumulation of lipid droplets in NPC, compared with normal nasopharyngeal epithelium. It is important to uncover the mechanism behind this lipid metabolic shift to better understand the pathogenesis of NPC and provide potential therapeutic targets. We show that LMP2A increased lipid accumulation in NPC cells. LMP2A could block lipid degradation by downregulating the lipolytic gene adipose triglycerol lipase (ATGL). This is in contrast to lipid accumulation due to enhanced lipid biosynthesis seen in many cancers. Suppression of ATGL resulted in enhanced migration in vitro, and ATGL was found downregulated in NPC biopsies. The reduced expression level of ATGL correlated with poor overall survival in NPC patients. Our findings reveal a new role of LMP2A in lipid metabolism, correlating with NPC patient survival depending on ATGL downregulation.

The ring-opening polymerization (ROP) of cyclic esters/carbonates is a crucial approach for the synthesis of biocompatible and biodegradable polyesters. Even though numerous efficient ROP catalysts have been well established, their toxicity heavily limits the biomedical applications of polyester products. To solve the toxicity issues relating to ROP catalysts, we report herein a biocompatible coordination network, CZU-1, consisting of Zn4(μ4-O)(COO)6 secondary building units (SBUs), biomedicine-relevant organic linkers and guest water, which demonstrates high potential for use in the catalytic ROP synthesis of biomedicine-applicable polyesters. Both experimental and computational results reveal that the guest water in CZU-1 plays crucial roles in the activation of the Zn4(μ4-O)(COO)6 SBUs by generating μ4-OH Brønsted acid centers and Zn–OH Lewis acid centers, having a synergistic effect on the catalytic ROP of cyclic esters. Different to the mechanism reported in the literature, we propose a new reaction pathway for the catalytic ROP reaction, which has been confirmed using density functional theory (DFT) calculations, in situ diffuse reflectance IR Fourier transform spectroscopy (DRIFTS), and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS). Additionally, the hydroxyl end groups allow the polyester products to be easily post-modified with different functional moieties to tune their properties for practical applications. We particularly expect that the proposed catalytic ROP mechanism and the developed catalyst design principle will be generally applicable for the controlled synthesis of biomedicine-applicable polymeric materials., A new ring-opening polymerization mechanism is unveiled based on synergistic catalysis involving Brønsted and Lewis acid centers in a coordination framework.

A sensitive, reliable and rapid high-performance thin-layer chromatography (HPTLC) method for the determination of arctiin and arctigenin in Arctium tomentosum Mill. was established. A. tomentosum Mill. extract was used for chromatographic analysis. The ratio of chloroform and methanol was 48:5 as mobile phase. Temperature is 20–23 °C and humidity is less than 30%. The scanning wavelength is 280 nm. The results showed that arctiin had a good linear relationship in the range of 0.5315–5.8465 μg, r = 0.9982; arctigenin had a good linear relationship in the range of 0.5654–6.2194 μg, r = 0.9951. Precision analysis showed that the RSD

Monolithic MnOx/La–Al2O3 catalysts were prepared using manganese nitrate, manganese acetate and their mixed precursor for the catalytic oxidation of toluene. The activity results indicated that the MNMA catalyst prepared with the mixed precursor exhibited the best catalytic activity and that complete conversion of toluene was achieved at 270 °C under a GHSV of 12 000 h−1, which was 35 °C lower than the conversion of the MN catalyst prepared by manganese nitrate. N2 adsorption–desorption, X-ray diffraction (XRD), Raman spectroscopy, high resolution trans-mission electron microscopy (HRTEM), H2 temperature-programmed reduction (H2-TPR), O2 temperature-programmed desorption (O2-TPD), X-ray photoelectron spectroscopy (XPS) and in situ infrared diffuse reflectance spectroscopy (in situ DRIFTS) techniques were employed for the characterization of the catalysts’ properties. It was shown that the MNMA catalyst has better MnOx dispersion and more active α-MnO2 species as well as higher concentrations of Mn4+, surface adsorbed oxygen species and active Mn–O bonds. Therefore, this catalyst possessed better reducibility and the best oxygen mobility, which were conducive to the catalytic oxidation of toluene. In addition, the DRIFT spectra results showed that more benzoic acid intermediate was deeply oxidized to carbonate species at a lower temperature on the surface of MNMA catalyst, which improved the low temperature activity for toluene oxidation.

Background Synergistic chemoradiotherapy (CRT) has become a primary effective curative approach for many solid cancers. However, CRT is still associated with several obstacles, including the increases in side effects and systemic toxicity. Incorporating nanocarriers into CRT is a new and exciting approach to solve these obstacles. The purpose of the present study was to design a unique pH- and ultrasound-responsive perfluoropentane-encapsulated, paclitaxel (PTX)-loaded carboxymethyl chitosan nanodroplets (NDs) for combined imaging and synergistic CRT. Materials and Methods The NDs were prepared by a homogenization/emulsion method. Their physicochemical properties, echogenicity and biocompatibility were evaluated. PTX-loaded NDs with a high loading efficiency and encapsulation efficiency were prepared and their pH-responsive drug release profile was determined by dialysis sack method. Then, PC3 cells were exposed to (1) PTX (4 μg/mL), (2) NDs (30 μg/mL), (3) PTX-loaded NDs (34 μg/mL), (4) RT (6 Gy), (5) RT (10 Gy), (6) combination of PTX (4 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy), (7) combination of NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6Gy), (8) combination of PTX-loaded NDs (30 μg/mL), ultrasound (0.5 W/cm2, 30 s) and RT (6 Gy). 24 hrs later, CCK-8 assay, flow cytometry and migration assay were carried out to evaluate their therapeutic effects in CRT. Results The desired NDs were successfully prepared, which were with round, spherical shapes, relatively smooth surfaces, core-shell structures and uniform in sizes (

Ellipticine, a natural product from Ochrosia elliptica, has been broadly investigated for its anticancer effects. Although inflammation has been clearly identified as a key factor in the onset and progression of cancer, the relationship between ellipticine and inflammation remains unknown. Hence, the aims of the present study were to assess the effects of ellipticine on the inflammatory responses to lipopolysaccharide (LPS)-induced macrophages and to potentially identify the underlying mechanisms involved. Viability testing showed that ellipticine was not significantly toxic to Raw264.7 cells and actually conveyed protective effects to LPS-stimulated Raw264.7 cells and human peripheral blood monocytes by decreasing the secretion of inflammatory factors (TNF-α and IL-6). The results of western blot analysis and electrophoretic mobility shift assays showed that ellipticine markedly suppressed LPS-induced activation of the JNK/AP-1 (c-Fos and c-Jun) signaling pathway, but not ERK/p38/NF-κB pathway (p65 and p50) activation. Furthermore, ellipticine reduced the inflammatory response and mortality in a mouse model of LPS-induced endotoxic shock. Collectively, these data indicate that ellipticine may be a potential therapeutic agent for the treatment of inflammation-associated diseases.

Aim: To synthesize and evaluate a novel FH peptide-modified ultrasonic nanobubble-loading doxorubicin (FH-NB-DOX) for specially cancer-associated fibroblasts (CAFs) targeting and eradication. Materials & methods: The characteristics, cytotoxicity, contrast-enhanced ultrasound imaging (CEUI), targeting ability and specially eradicating CAFs of these NBs were investigated. Results: FH-NB-DOX (about 208 nm) showed a good CEUI, and achieved higher targeting ability due to the conjunction ability of FH peptide to tenascin C protein high-level expressed in CAFs. Under ultrasound irradiation, FH-NB-DOX could delivery more DOX into CAFs, thus exhibited stronger eradication role compared with NB-DOX and free DOX. Conclusion: These new NBs, which combines the advantages of targeted theranostic agent and CEUI, is expected to be a potential approach for tumor therapy based on CAF targeting.

The dysregulation of epigenetic modification and energy metabolism cooperatively contribute to the tumorigenesis of nasopharyngeal carcinoma (NPC). However, the detailed mechanisms underlying their joint contribution to NPC development and progression remain unclear. Here, we investigate the role of Acy1 Coenzyme A Acyltransferases1 (ACAT1), a key enzyme in the metabolic pathway of ketone bodies, in the proliferation and metastasis of NPC and to elucidate the underlying molecular mechanisms. Ketogenesis, plays a critical role in tumorigenesis. Previously, we reported two enzymes involved in ketone body metabolism mediate epigenetic silencing and act as tumor suppressor genes in NPC. Here, we identify another key enzyme, Acetyl-CoA acetyltransferase 1 (ACAT1), and show that its transcriptional inactivation in NPC is due to promoter hypermethylation. Ectopic overexpression of ACAT1 significantly suppressed the proliferation and colony formation of NPC cells in vitro. The migratory and invasive capacity of NPC cells was inhibited by ACAT1. The tumorigenesis of NPC cells overexpressing ACAT1 was decreased in vivo. Elevated ACAT1 in NPC cells was accompanied by an elevated expression of CDH1 and a reduced expression of vimentin and SPARC, strongly indicating that ACAT1 is involved in regulating epithelial-mesenchymal transition (EMT). We also found that ACAT1 contributes to increased intracellular levels of β-hydroxybutyrate (β-HB). Exogenously supplied β-HB significantly inhibits the growth of NPC cells in a dose-dependent manner. In summary, ACAT1 may function as a tumor suppressor via modulation of ketogenesis and could thus serve as a potential therapeutic target in NPC. In summary, our data suggest that regulation of ketogenesis may serve as adjuvant therapy in NPC.

Objective The aim of this study is to evaluate the cost-effectiveness of teriflunomide and fingolimod in relapsing-remitting patients in the first-line treatment from the perspective of the Chinese health system perspective.Methods A Markov model was developed to evaluate the cost effectiveness of disease-modifying drugs (DMDs) from the Chinese health system perspective.Cost input includes medication, follow-up, nursing, recurrence treatment and adverse reaction management.Treatment effects, including monthly confrmed disability worsening and annualized relapse rate.The output result was ICER and the threshold of willingness to pay(WTP) was three times per capita GDP.One-way sensitivity analysis and probability sensitivity analysis are carried out to test the stability of the model results.Results In the context of medical insurance with Chinese characteristics.The total cost of treatment with teriflunomide was ¥423,816.61, and the total cost of treatment with fingolimod was ¥656,055.95.The cumulative QALYs of teriflunomide was 5.14, and the cumulative QALYs of fingolimod was 5.25.The ICER value of Fingolimod and Liflunomide is ¥2139444.61/QALY, which is higher than WTP , so teriflunomide has a dominant advantage.Sensitivity analysis proves that the model was stable.Conclusion From the perspective of Chinese health system perspective, teriflunomide is the more cost-effective of the two interventions.

Activated-mast cells (MCs) within gingival-tissue of chronic-periodontitis (CP) patients, release various inflammatory-factors. Bradykinin is a nine-amino-acid peptide and pro-inflammatory mediator, produced through factor-XII-cascade or tryptase-cascade. The ability of MC-chymase in bradykinin generation has not been discussed yet. This study investigated the salivary levels of MC-chymase, high molecular weight kininogen (HMWK) and bradykinin of CP patients; examined the potential of MC-proteases in bradykinin production using biochemistry-models; and explored the effects of bradykinin on gingival fibroblasts (GFs). Saliva-samples were collected; MC-protease activities were detected; HMWK cleavage was assessed by western-blot and SDS-PAGE; bradykinin levels were measured using immunoassay. Primary GFs were extracted and cultured with or without bradykinin; cell-viability, gelatine-zymography and flow-cytometry were applied. Immunocytochemistry and western-blot were used to detect intracellular protein expressions of bradykinin-stimulated GFs. The data showed that the salivary-levels of MC-proteases, bradykinin, HMWK, and lactoferrin of CP-patients were increased. HMWK was cleaved by MC-chymase in-vitro, resulting in bradykinin generation. Bradykinin promoted cell proliferation, cell cycle and matrix-metalloproteinase-2(MMP-2) activity, and increased intracellular expressions of nuclear-factor-kappa-B(NF-κB), focal-adhesion-kinase(FAK), transforming-growth-factor-β(TGF-β), P38, P53 of GFs. MC-chymase promotes bradykinin production to stimulate GFs and to continue inflammation during CP development. A new BK-generation cascade found in this study provides a new basis for the pathogenesis of CP and the mechanism of continuous inflammation. The activation of MC-chymase/bradykinin-generation cascade depends on HMWK level and MC-chymase activity under inflammatory condition. MC-chymase contributes to bradykinin production, mediating the cross-talks between MCs and GFs. MC-chymase can be used as a therapeutic target and a salivary biomarker in this case.

Intracellular calcium signaling has been implicated in control of a variety of circadian processes in animals and plants but its role in microbial clocks has remained largely cryptic. To examine the role of intracellular Ca2+ in the Neurospora clock we screened knockouts of calcium transporter genes and identified a gene encoding a calcium exporter, nca-2, uniquely as having significant period effects. Loss of NCA-2 results in an increase in cytosolic calcium level, and this leads to hyper-phosphorylation of core clock components, FRQ and WC-1, and a short period as measured by both the core oscillator and overt clock. Genetic analyses showed that mutations in certain frq phospho-sites, and in Ca2+-calmodulin-dependent kinase (camk-2), are epistatic to nca-2 in controlling the pace of the oscillator. These data are consistent with a model in which elevated intracellular Ca+2 leads to increased activity of CAMK-2 leading to enhanced FRQ phosphorylation, accelerated closure of the circadian feedback loop, and a shortened circadian period length. At a mechanistic level some CAMKs undergo more auto-phosphorylations in Δnca-2, consistent with high calcium in the Δnca-2 mutant influencing the enzymatic activity of CAMKs. NCA-2 interacts with multiple proteins including CSP-6, a protein known to be required for circadian output. Most importantly, expression of nca-2 is circadian clock-controlled at both the transcriptional and translational levels, and this in combination with the period effects seen in strains lacking NCA-2, firmly places calcium signaling within the larger circadian system where it acts as both an input to and output from the core clock.ImportanceCircadian rhythms are based on cell-autonomous, auto-regulatory, feedback loops formed by interlocked positive and negative arms, and they regulate myriad molecular and cellular processes in most eukaryotes including fungi. Intracellular calcium signaling is also a process that impacts a broad range of biological events in most eukaryotes. Clues have suggested that calcium signaling can influence circadian oscillators through multiple pathways; however, mechanistic details have been lacking in microorganisms. Building on prior work describing calcium transporters in the fungus Neurospora, one such transporter, NCA-2, was identified as a regulator of circadian period length. Increased intracellular calcium levels caused by loss of NCA-2 results in over-activation of calcium-responsive protein kinases, in turn leading to a shortened circadian period length. Importantly, expression of NCA-2 is itself controlled by the molecular clock. In this way calcium signaling can be seen as providing both input to and output from the circadian system.

Mast cells (MCs) were accumulated in synovial tissue of rheumatoid arthritis (RA) patients. MC activation releases numerous mediators including MC-chymase. Synovial fibroblast shows a dramatic hyperplasia in RA articular cavity, but the effects of MC-chymase on synovial fibroblast are unknown. In this study, the collagen-induced-arthritis (CIA) rat model was employed to evaluate the dynamic changes of MC-chymase activity and other inflammatory factors during CIA development in-vivo. The fresh primary synovial fibroblasts from normal or CIA rats were extracted to compare the differences of these two cell-types, and to investigate the effects of MC-chymase on both-types of synovial fibroblast. The data showed that the dynamic changes in chymase activity in synovial fluids of CIA rats before and after immunizations were companied with the changes of tryptase, MMP-2/-9, TNF-α, IL-6, Co-II IgG, total protein, paw-thickness and body weight in-vivo. The baseline differences in cell grow rates, expression levels of p21, FAK, MMP-9 between normal and CIA-SFB have been seen. Compared to the normal synovial fibroblasts, CIA-SFB increased the percentage of the cells transferred to S or G2/M phases in cell cycle in-vivo; CIA-SFB become more proliferative with high-expression MMP-2/9 during CIA development. MC-chymase in-vitro promoted both types of synovial fibroblast proliferation and induced cell cycle changes, but CIA-synovial fibroblasts exhibited much stronger responses to MC-chymase stimulation by increased expression levels of p21, FAK, MMP-9 which associated with cell adhesion and migration. This study might give a new insight that the activated mast cell can be an important target cell for RA treatment and suggest that MC-chymase needs well attention for therapeutic aims.

Purpose: Caffeic acid phenethyl ester (CAPE) is the main polyphenol extracted from honeybee propolis, which inhibits the growth of several kinds of tumor. This study aimed to assess the inhibitory effect of CAPE in nasopharyngeal carcinoma (NPC), evaluate the synergistic action of CAPE in radiotherapy sensitivity of NPC cell lines and further elucidate the possible molecular mechanism involved. Materials and methods: CCK-8 assay was used to analyze cell proliferation ability. Colony formation assay was used to evaluate the clonogenic ability and radio-sensitiveness of NPC cells by CAPE treatment. Wound-healing and transwell assay were used to assess the motility of cells. The expression of key molecules of the epithelial-mesenchymal transition (EMT) was determined by western blot analysis and changes in radiation sensitivity were measured by colony-formation assay. cDNA microarray analysis was used to determine differentially expressed genes with and without CAPE treatment, with Gene Ontology enrichment of gene function and KEGG pathways determined. Cell cycle and apoptosis were detected by flow cytometry and western blot analysis. Results: CAPE suppressed the viability of NPC cell lines time- and dose-dependently. It induced apoptosis in NPC cells along with decreased expression of Bcl-XL and increased cleavage of PARP and expression of Bax. G1 phase arrest was induced by CAPE with ower expression of CDK4, CDK6, Rb and p-Rb. The migratory and invasive ability of NPC cells was decreased by the EMT pathway. The irradiation sensitivity of NPC cells was enhanced with CAPE treatment. CAPE specifically inhibited nuclear factor κB (NF-κB) signaling pathway by suppressing p65 subunit translocation from cytoplasm to nucleus. CAPE treatment was synergistic with chemotherapy and radiotherapy. Conclusion: CAPE may inhibit the proliferation and metastasis of NPC cells but enhance radiosensitivity in NPC therapy by inhibiting the NF-κB pathway. CAPE could be a potential therapeutic compound for NPC therapy.

High-performance thin-layer chromatography, which is a quick qualitative and quantitative method, was used to determine 3 kinds of organic acids, namely, ellagic acid, gallic acid, and ferulic acid, in Elaeagnus angustifolia L. leaves originating from 10 regions in Xinjiang Uygur Autonomous Region and 7 different growth stages in Urumqi, China. The developing solvent was toluene-ethyl formate-formic acid (5:6.55:1.49), the temperature was 25 ± 1°C, the humidity was 10%, and the detection wavelength was 290 nm. The linear ranges of ellagic acid, gallic acid, and ferulic acid were 0.0564–0.6768, 0.1006–1.2072, and 0.1004–1.2048 μg, respectively , and the linear correlation coefficients were 0.9953, 0.9993, and 0.9970, respectively. The results showed good linear relationships. Precision analyses revealed a relative standard deviation (RSD) of

Two-dimensional (2D) polyaniline with C3N stoichiometry, is a newly fabricated layered material that has been expected to possess fascinating electronic, thermal, mechanical and chemical properties. The nature of its counterpart nanoribbons offering even more tunability in properties because of the unique quantum confinement and edge effect, however, has not been revealed yet. Here we systemically study the mechanical, electronic and magnetic properties for various nanoribbons cutting from a monolayer C3N sheet along the typical crystallographic orientations. By the first-principles calculations we find that C3N nanoribbons exhibit sensitive responses to the externally applied electric field and strain. Specifically, the spin-selective half-metallicity depends on the external electric field or strain, as well as the ribbon width. For the asymmetric zigzag-edged ribbon, the spin-polarization rate approaches −100% at electric field strength −0.2 V/A. Interestingly, an applied strain can transform a symmetric zigzag-carbon-edge ribbon from a magnetic semiconductor to a half-metal. And the half-metal property remains unchanged when the strain increases from 8 to 15%, while the spin-up subband gap further increases to 0.46 eV. These numerical results may be useful to engineer and design magnetic-field-free spintronic devices based on the 2D C3N.

Halohydrin dehalogenases are usually recognized as strict β-position regioselective enzymes in the nucleophile-mediated ring-opening of epoxides. Here we found the HheG from Ilumatobacter coccineus exhibited excellent α-position regioselectivity in the azide-mediated ring-opening of styrene oxide derivatives 1a–1k, producing the corresponding 2-azido-2-aryl-1-ols 2a–2k with the yields up to 96%.

A mesoporous Ce0.65Zr0.35O2 support was synthesized via co-precipitation, and Pt/Ce0.65Zr0.35O2 and Pt-WO3/Ce0.65Zr0.35O2 catalysts were prepared through the incipient-wetness impregnation method for the catalytic oxidation of toluene. As evidenced by the catalytic activity results, the temperature for the complete conversion of toluene using the monolith Pt-WO3/Ce0.65Zr0.35O2 catalyst decreased by about 30 °C compared to that using Pt/Ce0.65Zr0.35O2. In addition, the physicochemical properties of the catalysts were characterized via N2 adsorption–desorption, XRD, H2-TPR, XPS and NH3-TPD experiments. The in situ DRIFTs technique was used to study the toluene catalytic oxidation process. The results showed that the excellent catalytic activity of Pt-WO3/Ce0.65Zr0.35O2 is ascribed to its good low-temperature reducibility, higher surface-adsorbed oxygen concentration, and greater medium strength acidity.

Ultrasound-targeted delivery of nanobubbles (NBs) has become a promising strategy for noninvasive drug delivery. The biosafety and drug-transporting ability of NBs have been a research hotspot, especially regarding chitosan NBs due to their biocompatibility and high biosafety. Since the drug-carrying capacity of chitosan NBs and the performance of ultrasound-assisted drug delivery remain unclear, the aim of this study was to synthesize doxorubicin hydrochloride (DOX)-loaded biocompatible chitosan NBs and assess their drug delivery capacity. In this study, the size distribution of chitosan NBs was measured by dynamic light scattering, while their drug-loading capacity and ultrasound-mediated DOX release were determined by a UV spectrophotometer. In addition, a clinical ultrasound imaging system was used to evaluate the ability of chitosan NBs to achieve imaging enhancement, while the biosafety profile of free chitosan NBs was evaluated by a cytotoxicity assay in MCF-7 cells. Furthermore, NB-mediated DOX uptake and the apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells were measured by flow cytometry. The results showed that the DOX-loaded NBs (DOX-NBs) exhibited excellent drug-loading ability as well as the ability to achieve ultrasound enhancement. Ultrasound (US) irradiation promoted the release of DOX from DOX-NBs in vitro. Furthermore, DOX-NBs effectively delivered DOX into mammalian cancer cells. In conclusion, biocompatible chitosan NBs are suitable for ultrasound-targeted DOX delivery and are thus a promising strategy for noninvasive and targeted drug delivery worthy of further investigation.

Rheumatoid arthritis (RA) is an autoimmune disease and characterized by the excessive cell proliferation, abnormal cell cycle of lymphocytes and synovial cells. The therapeutic effects of curcumin in active RA patients were reported, but limited by its insolubility and rapid systemic elimination. Dimethyl curcumin (DiMC) is a metabolically stable analogue of curcum with anti-inflammatory property. In this study, liposomes encapsulated dimethyl curcumin (Lipo-DiMC) was prepared to improve the bioavailability and metabolic-stability; collagen induced arthritis (CIA) rat model was employed to investigate the effects of Lipo-DiMC treatments during CIA progress. Physical assessments and routine-blood-test were performed. Fresh spleen lymphocytes were isolated from normal, CIA and Lipo-DiMC-treated CIA rats; flow-cytometry for cell-cycle analysis, western-blotting for intracellular signal pathway protein expressions, gelatin-zymography for matrix-metalloproteases 2/9 (MMP-2/9) and GF-AFC for dipeptidyl-peptidase I (DPPI) activity assay. Compared with untreated CIA rats, Lipo-DiMC treatments relieved paw-swellings, suppressed the increments of immunocytes numbers and inhibited DPPI and MMP-2/9 over-activity in blood. Lipo-DiMC adjusted CIA-induced cell cycle dysfunction at G0/G1-phase and S-phase of spleen lymphocytes for CIA rats. The intracellular expression-trends of P38, P21, Bcl-2, JNK-1 and DPPI of spleen lymphocytes were observed during CIA progress with and without Lipo-DiMC administrations. Lipo-DiMC exhibited its therapeutic functions by attenuating CIA development in rats, associated with down-regulating CIA-induced lymphocytes numbers, inhibiting over-expressed of DPPI and MMP-2/9, and adjusting cell cycles. These findings provide a new insight into the mechanism of Lipo-DiMC treatment in CIA rat model and suggest that Lipo-DiMC could be considered as a potential drug for RA treatment.

In this paper, we designed and synthesized two series of matrine analogues with ring-opening in the lactam portion of the molecule. Our in vitro cytotoxicity study showed that analogue N-(3-bromophenyl)-4-((1R,3aS,3a1S,10aR)-decahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridin-1-yl)butanamide (B11) with a meta -bromide on the phenyl ring displayed the best antiproliferative activity. Moreover, B11 induced cell cycle arrest in G1 phase and cell apoptosis in a dose-dependent manner in A549 cells. Molecular modeling revealed that B11 achieved a higher docking score compared to its precursor tert-butyl (1R,3aS,3a1S,10aR)-1-(4-((3-bromophenyl)amino)-4-oxobutyl)octahydro-1H,4H-pyrido[3,2,1-ij][1,6]naphthyridine-2(3H)-carboxylate (A11, an analogue of B11 with a Boc group) and parent compound matrine, possibly because B11 formed a hydrogen bond with SER91 and a halogen bond with GLN320 on the binding site of annexin A2. Overall, we discovered the potentital anti-cancer lead compound B11 , which can be used for further study both in vitro and in vivo .

Necrotizing enterocolitis (NEC) remains a fatal gastrointestinal disorder in neonates. Disialyllacto-N-tetraose (DSLNT), a function-unclear human milk-derived hexasaccharide, shows anti-NEC potential in previous animal studies. This study is aimed to explore the role of mast cell (MC), a fundamental cell type of mucosal immune system and protective DSLNT in regulating pathological process of NEC. For this purpose, infantile intestinal-tissues were collected from NEC neonates for examination of MCs and its proteases-positive cells. MC accumulation and MC-specific proteases (chymase, tryptase and dipeptidyl peptidase I) were firstly found in lesioned area of NEC infants in-vivo. Subsequent in-situ experiments on neonatal ileum segments showed that purified MC-chymase induced a destructive epithelial layer shedding from basement and microvascular endothelium damage in infantile intestinal segments. Human foreskin MC-activation model was established and DSLNT were applied; MC products (histamine and MC-proteases) were used as MC activation/degranulation indicators. In this in-vitro model, DSLNT pretreatment suppressed release of histamine, chymase and tryptase by MC to the tissue supernatants during lipopolysaccharide or complement C5a stimulation. Newborn rats were formula-hand-fed with or without DSLNT supplement and exposed to hypoxia/cold-stress to induce experimental-NEC-model. In NEC rats, DSLNT supplementation reduced the incidence and pathological scores of NEC, inhibited local accumulation of MC and reduced cytokines (IL-1β, IL-6 and TNF-α) levels in the ileum of rats. In conclusion, MC was causally implicated in epithelium barrier failure in pathogenesis of NEC. DSLNT favorably modulated MC homeostasis by regulating MC degranulation/accumulation, contributing to attenuated NEC. This indicated novel pathomechanisms and potential targets of NEC.

For the pristine phosphorene nanoribbons (PNRs) with edge states, there exist two categories of edge bands near the Fermi energy (${E}_{F}$), i.e., the shuttle-shaped twofold-degenerate and the near-flat simple degenerate edge bands. However, the usual experimental measurement may not distinguish the difference between the two categories of edge bands. Here we study the varying rule for the edge bands of PNRs under an external electrostatic field. By using the KWANT code based on the tight-binding approach, we find that the twofold-degenerate edge bands can be divided into two separated shuttles until the degeneracy is completely removed and a gap near ${E}_{F}$ is opened under a sufficiently strong in-plane electric field. Importantly, each shuttle from the ribbon upper or lower edge outmost atoms is identified according to the local density of states. However, under a small off-plane field the shuttle-shaped bands are easily induced into two near-flat bands contributed from the edge atoms of the top and bottom sublayers, respectively. The evidence provides the edge and sublayer degrees of freedom (DOF) for the PNRs with shuttle-shaped edge bands, which is obviously different from another category of PNRs intrinsically with near-flat edge bands. This is because the former category of ribbons solely have four zigzaglike atomic configurations at the edges in each unit cell, which also results in that the property is robust against the point defect in the ribbon center area. As an application, furthermore, based on this issue we propose a homogenous junction of a shuttle-edge-band PNR attached by two electric gates. Interestingly, the transport property of the junction with field manipulation well reflects the characteristics of the two DOFs. These findings may provide a further understanding on PNRs and initiate new developments in PNR-based electronics.

Background: Inflammation and apoptosis play a crucial role in the progression of nonalcoholic steatohepatitis (NASH). Suppressor of cytokine signaling 2 (SOCS2) is one of classic negative regulators of cytokine signaling, which has recently been described as anti-inflammatory mediators. However, the role of SOCS2 in macrophages during NASH progression and the relationship among SOCS2, inflammation, apoptosis and NASH is largely unknown. Herein, we aimed to study the function of SOCS2 in NASH progression. Methods: We detected SOCS2 expression in macrophages in human subjects without steatosis, with simple steatosis and with NASH to confirm the relationship between SOCS2 and NASH. Free fatty acids was used to establish stress environment in RAW cell lines stably overexpressing or knockdown SOCS2. In vitro and vivo assays also performed to study the molecular function of SOCS2 in NASH progression. Findings: Our human samples and NASH model in vitro illustrated that SOCS2 is decreased in macrophages during NASH progression and is negatively correlated to NASH level. Meanwhile, In vitro assays show SOCS2 overexpression in macrophages suppresses inflammation and apoptosis via inhibiting NF-κB signaling pathway, while SOCS2 knock-down in macrophages caused an increased activation of NF-κB, which can be blocked by ammonium 1-pyrrolidinedithiocarbamate (PDTC). In addition SOCS2 in macrophages also suppresses inflammation via limiting the activation of inflammasomes. Consist with these, our BMT model also confirm the SOCS2 function in macrophages during NASH. Interpretation: Our data strongly indicate that SOCS2 plays a inhibitor of inflammation and apoptosis via NF-κB signal pathway and inflammasome signal pathway in macrophages during NASH. Further studies are required to explore the potential prevention and therapeutic strategies of SOCS2 for this common liver disease. Funding Statement: This work was supported by the National Natural Science Foundation of China (Nos. 81970499 and 81770561), Jiangsu Medical Leading Talent, Innovation Team (No. CXTDA2017033), and Jiangsu Province “333” project (No. BRA2014332) and National Natural Science Foundation of China (Nos. 81972675). Declaration of Interests: The authors declare no conflict of interest relevant to the present manuscript. Ethics Approval Statement: All procedures that involved human sample collection were approved by the tissue bank of The Affiliated Drum Tower Hospital, Nanjing University (Nanjing, China). Informed consent for gene expression analysis of tissue was obtained from each patient before surgery, and the study was approved by our institutional ethics committee. The ethics committe of the Institutional Animal Care and Use Committee (IACUC). First Affiliated Hospital of Nanjing Medical University approved this study, (Ethics Number: 2018-SRFA-034).

Objectives: This investigation aimed to study the effect of rosemary essential oil on the transdermal absorption of crosslinked hyaluronic acid in vitro. Material and methods: The most suitable concentration of crosslinked hyaluronic acid was chosen and enhancing effects of rosemary essential oil on the permeation of crosslinked hyaluronic acid were evaluated. Results: The optimization of carbazole sulfate method by the 96-well plate was used to establish the standard curve of hyaluronic acid successfully. Crosslinked hyaluronic acid containing 5% (v/v) rosemary essential oil showed better skin penetration than blank control group in transdermal experiments. The combination of 5% (v/v) rosemary essential oil and 2%(v/v) azone as a permeability aid can achieve more effect than 5%(v/v) rosemary essential oil as a permeability aid. Conclusion: This study showed the enhancing effect of rosemary essential oil on crosslinked hyaluronic acid percutaneous absorption.

Gene vectors are nucleic acids that carry genetic materials or gene editing devices into cells to exert the sustained production of therapeutic proteins or to correct erroneous genes of the cells. However, the cell membrane sets a barrier for the entry of nucleic acid molecules, and nucleic acids are easily degraded or neutralized when they are externally administered into the body. Carriers to encapsulate, protect and deliver nucleic acid molecules therefore are essential for clinical applications of gene therapy. The secreted organelles, exosomes, which naturally mediate the communications between cells, have been engineered to encapsulate and deliver nucleic acids to the desired tissues and cells. The fusion of exosomes with liposomes can increase the loading capacity and also retain the targeting capability of exosomes. Altogether, this review summarizes the most recent designs of exosome-based applications for gene delivery and their future perspectives in gene therapy.

We analytically study the electronic structure and optical properties of zigzag-edged phosphorene nanoribbons (ZPNRs) using the tight-binding Hamiltonian and Kubo formula. By directly solving the discrete Schrodinger equation, we obtain the energy spectra and wavefunctions for N-ZPNR (where TV is the number of transverse zigzag atomic chains) and classify the eigenstates according to the lattice symmetry. Then, we obtain the optical transition selection rule of ZPNRs on the basis of symmetry analysis and analytical expressions of optical transition matrix elements. Under incident light that is linearly polarized along the ribbon, we determine that the optical transition selection rule for N-ZPNR with even- or odd-N is qualitatively different. Specifically, for even-N ZPNRs, the inter- (intra-) band selection rule is An =odd (even) because the parity of the wavefunction corresponding to the n-th subband in the conduction (valence) band is (-1)n[(-1)(n+1)] owing to the presence of C2x symmetry. However, the optical transitions between any subbands are possible owing to the absence of C2x symmetry. Our results provide a further understanding on the electronic states and optical properties of ZPNRs, which are useful for explaining the optical experiment data on ZPNR samples.

Xinxin Liu, Dandan Shi, Lu Guo, Xiaoying Zhou, Mengmeng Shang, Xiao Sun, Dong Meng, Yading Zhao, Jie Li Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Jie LiDepartment of Ultrasound, Qilu Hospital of Shandong University, Wenhua Western Road, Jinan 107#, People’s Republic of ChinaTel/Fax +86-531-82166101Email jieli301@163.comPurpose: To synthesize echogenic chitosan/perfluorohexane nanodroplets (CNDs) for DKK-2 gene delivering in a spatiotemporally controlled manner in vitro.Methods: The characteristics, contrast-enhanced ultrasound imaging, DNA binding and DNase protection capacity, DKK-2 gene transfection and effects on LNCaP cells of these CNDs were investigated.Results: The obtained CNDs showed positive surface charges and could attract the genetic cargo with negative surface charges to form nanocomplexes. Agarose gel electrophoresis confirmed binding of the CNDs and pDNA. DKK-2 pDNA-loaded CNDs, in combination with ultrasound, ruptured and released DKK-2 pDNA, entering LNCaP cells through nano-scale pores in the cell membrane, which further reduced the proliferation of LNCaP cells.Conclusion: These stable and safe CNDs may be a promising choice to achieve efficient ultrasound-mediated gene delivery to specific tissues in a spatiotemporally controlled manner.Keywords: nanodroplets, chitosan, DKK-2, ultrasonic gene transfer, prostate cancer

The study on the electronic especially optical properties of zigzag-edged phosphorene nanoribbons (ZPNRs) in an antiferromagnetic state has been rarely involved. Here we theoretically study the electronic and optical properties of a ZPNR with N chains ( N -ZPNR) modulated by a vertical electric field (VEF). Within the Hubbard model Hamiltonian combined with the self-consistent calculation, and by adopting the Green’s function method, we obtain the band structure and corresponding conductance for the system. The corresponding optical absorption spectrum is further obtained based on the Kubo formula. It is interesting to find that there is an even–odd effect on the electronic and optical properties of N -ZPNR induced by the VEF, which may fundamentally originate from the parity of the wavefunctions. The VEF lifts the degeneracy of the two edge bands for 12-ZPNR, but it only bends and shifts the two edge bands without lifting the spin degeneracy for 13-ZPNR. We further present the spatial distribution of the corresponding wavefunction to understand this even–odd effect more intuitively. As expected, the VEF can separate the spin-up and -down optical absorption for 12-ZPNR, but it does not break the spin degeneracy of the optical absorption for 13-ZPNR. Our results may provide a further understanding on the electronic and optical properties of N -ZPNR with an antiferromagnetic state, and may be useful to identify the even–odd property of ZPNR samples by detecting the optical absorption in experiment.

The central question in the field of 2D materials is how a material behaves when it is patterned at nanometer scale with different edge geometries. Due to the anisotropy inherent in the puckered structure, black phosphorene nanostructures may have more varieties of edge geometries. Here, we present a comprehensive 2D planar crystallographic characterization of phosphorene uniformly by a chiral vector (angle), from which a new type of edge atomic configuration, the slope edge geometry is discovered. The phosphorene nanoribbons (PNRs) with slope edges, like previously noticed zigzag and skewed-armchair PNRs, also own interesting twofold-degenerate edge states. These three marginal directions, together with the skewed-zigzag and armchair directions without edge states, divide a phosphorene into four regions among which the electronic property is different from each other. Further, for a PNR cutting along any possible direction, by taking into account the z-direction in structure, whether or not it owns edge states depends on the periodic zigzag-like morphology along the edges. Moreover, we propose a PNR-based z-shaped homogenous junction with scale $\sim$100 nm, where the central scattering region between two PNR electrodes is a phosphorene quantum dot (PQD) of PNR segment with various edge morphologies. Interestingly, the calculated conductance of the junction relies sensitively on the central PQD edge states, which exhibits a terrace with resonant oscillations near Fermi energy, otherwise the electron transport is blocked due to the absence of edge states. Remarkably, the number of oscillating peaks exactly matches to the number of sawtooth along an edge of PQD, since the discrete energy levels of the zigzag-like edge provide the transporting channels for electrons. The results here may be extended to the group-VA 2D materials for observing the electronic property of nanostructures.

As a potential drug/gene delivery system, the ultrasound-targeted microbubble destruction (UTMD) system can be used as a vehicle as well as increasing the permeability of biological barriers to enhance the effect of tumor treatment. However, the effect of UTMD in the tumor EMT process is unknown. In this study, we aimed to investigate the potential and mechanism of UTMD induced oxidative stress in inhibiting EMT of breast cancer. Human breast MDA231 cells were treated with microbubble (MB), ultrasound (US) and UTMD, respectively. The generation of oxidative stress, the levels of miR-200c, ZEB1 and vimentin, and the numbers of migratory cells were evaluated quantitatively and qualitatively by the measurement of intracellular reactive oxygen species (ROS), qRT-PCR, western blot assay, and transwell assay. Then, to evaluate the role of UTMD-induced oxidative stress and miR-200c in the epithelial-mesenchymal transition (EMT) inhibition, the ROS scavenger N-acetyl-L-cysteine (NAC) and miR-200c inhibitor were used before UTMD treatment. We found that UTMD induced oxidative stress, upregulated the expression of miR-200c, downregulated the expression of ZEB1 and vimentin and suppressed the MDA231 cell migration. The addition of NAC and miR-200c inhibitor had an opposite impact on the expression of miR-200c and ZEB1, thus hindered the effects of UTMD on MDA231 cells EMT. In conclusion, UTMD can inhibit the EMT characteristics of MDA231 cells. The mechanism may be related to the regulation of the miR-200c/ZEB1 axis through the generation of ROS induced by UTMD, which may provide a new strategy to prevent the tumor cells EMT under UTMD treatment.

Metabolic disorders of glucose and lipid were associated with some mineral elements, and data were warranted from various contexts to make the association more explicit.To investigate the relationships between the serum concentrations of six mineral elements (calcium, cobalt, copper, iron, magnesium, and selenium) and the risk of hyperglycemia and dyslipidemia in adults.The basic information and the over-night fasting serum samples of adults were randomly collected at a health examination center. The serum concentrations of glucose and lipids were measured with an automatic biochemical analyzer, and the mineral elements were measured with an inductively coupled plasma mass spectrometer. Data were analyzed between the hyperglycemia group (HGg) and the normal glucose group (NGg) as well as between the dyslipidemia group (DLg) and the normal lipid group (NLg).A total of 1466 adults aged 22-81 years (male/female = 1.8) were included, 110 in the HGg and 1356 in the NGg, or 873 in the DLg and 593 in the NLg. The serum element concentration medians [P50 (P25-P75)] significantly different between the HGg and the NGg were 0.83 (0.75-0.94) vs. 0.76 (0.68-0.87) mg/L for copper and 100 (90-110) vs. 94 (87-103) μg/L for selenium (P 0.001), while those between the DLg and the NLg were 99 (92-110) vs. 97 (90-106) mg/L for calcium, 0.78 (0.69-0.88) vs. 0.75 (0.66-0.85) mg/L for copper, 1.7 (1.4-2.0) vs. 1.6 (1.3-2.0) mg/L for iron, 24 (22-28) vs. 23 (22-27) mg/L for magnesium, and 97 (89-106) vs. 92 (84-100) μg/L for selenium (P 0.05). When the copper and selenium between the HGg and the NGg were analyzed by logistic regression with age, gender, body mass index, and mineral elements adjusted, only the highest quartile of selenium concentration had association with the increased risk of hyperglycemia [quartile (Q) 4 against Q1: OR = 2.9, 95 % CI = 1.5-5.5, P 0.001). When the five differed mineral elements between the DLg and the NLg were similarly analyzed, only iron and selenium had associations with the increased risk of dyslipidemia (e.g., Q4 against Q1: OR = 1.4, 95 % CI = 1.1-2.0 for iron and OR = 2.9, 95 % CI = 2.1-4.0 for selenium, P 0.05).In contrast to those of calcium, cobalt, copper, iron, and magnesium, the higher serum concentration of selenium increased the risk of both hyperglycemia and dyslipidemia in the study population of adult Chinese.

Airway smooth muscle (ASM) is a prominent effecter in maintaining bronchial muscle contraction and responsible for airway hyper-responsiveness (AHR); the phenotype change and over-proliferation of airway smooth muscle cells (ASMCs) play key roles in the pathogenesis of asthma. The aim of this study was to investigate the anti-proliferation effects of Cortex Dictamni aqueous extract (CDAE) and ethanol extract (CDE) on ASMCs and the possible underline mechanisms. Cell proliferation rates were determined by MTT assay; matrix metalloproteinases-2 (MMP-2) activity was examined by gelatin zymography; cell proliferation and migration were appraised by in-vitro cell-gap closure assessment; protein expressions of p38, Bcl-2 and FAK of ASMCs were evaluated by western blotting and Ca2+ influx of cells was measured by confocal laser microscope. Our data demonstrated that the proliferation, migration and MMP-2 expressions of ASMCs were inhibited by CDAE or CDE; the protein expressions of p38, Bcl-2 and FAK in ASMCs were substantially reduced by CDAE and CDE detected by western blotting or immunocytochemistry; also the increased calcium influx has been observed instantaneously after ASMCs were stimulated by CDAE or CDE. These findings suggested that Cortex Dictamni extracts might have inhibitory effects on ASMCs over-proliferation which could be one of the underline mechanisms for the therapy of asthma.

Background Epstein-Barr virus (EBV) actively contributes to the pathological process of nasopharyngeal carcinoma (NPC) by enabling NPC cells to acquire various capacities required for their malignant biological actions. Our earlier works demonstrated that EBV-encoded latent membrane protein 1 (LMP1) enhanced vascular endothelial growth factor (VEGF)-mediated angiogenesis by boosting store-operated Ca2+ entry (SOCE) upon extracellular epidermal growth factor (EGF) stimulation. However, the antagonistic effects of SOCE blockage on EBV-promoted angiogenesis must be appropriately evaluated in vivo, and the global effect of EBV infection on the EGF-elicited cytosolic Ca2+ signaling, which regulates VEGF-mediated angiogenesis remains to be further clarified. Materials and methods Two EBV-infected NPC cell lines, CNE2-EBV and HK1-EBV, along with their parental cell lines were employed in the present study. Dynamic cytosolic Ca2+ changes were measured in individual fluorescent Ca2+ indicator-loaded cells. Amounts of VEGF production were determined by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs)-formed tube networks were quantitatively evaluated as an in vitro angiogenesis assay. A mouse model concurrently bearing EBV-positive/negative xenografts was utilized to evaluate the tumor growth and angiogenesis in vivo. Results EBV infection reliably promoted transplanted tumor growth while enhancing angiogenesis. Introduction of EBV into EBV-negative NPC cells increased the EGF-stimulated VEGF production while amplifying the EGF-evoked Ca2+ responses. Inhibition of the EBV-boosted Ca2+ signaling using 2-aminoethyl diphenylborinate (2-APB), a specific SOCE inhibitor, effectively antagonized the EBV-promoted VEGF production and endothelial tube formation in vitro. Pharmacological blockage of SOCE exhibited anti-angiogenic effect in the EBV-positive xenografts. Conclusion SOCE can serve as a candidate pharmacological target for treating NPC, as blockage of the Ca2+ signaling via SOCE is a feasible strategy to suppress the EBV-driven malignant profiles in NPC cells.

A sensitive, reliable, and rapid densitometric high-performance thin-layer chromatography (HPTLC) method has been developed for the quantification of hydroxysafflor yellow A (HSYA) in safflower. Chromatographic analysis was performed using the methanol extract of safflower. Polyamide TLC plates were used with the solvent system containing 3.6% hydrochloric acid, methanol, and ethyl acetate (7:3:1, v/v). Densitometric analysis of HSYA was performed at the absorbance mode of 399 nm. This system was found to give compact and dense spots for HSYA (RF value of 0.60 ± 0.03). The method showed a good linear relationship in the range of 61.0– 79.3 ng with r = 0.9991. The limit of detection, limit of quantification, and average recovery were 59 ng, 169 ng, and >95%, respectively. The proposed validated HPTLC method is an easy-to-use, accurate, and convenient method that can be successfully used for the standardization and quality analysis of herbal materials with different species of safflower.

Mesoporous Ce0.65Zr0.35O2 composites are synthesized by co-precipitation method and a series of novel MnOx/Ce0.65Zr0.35O2 monolithic catalysts with different content of manganese oxides are prepared for toluene catalytic oxidation. The results show that the catalytic activity of Ce0.65Zr0.35O2 is promoted by introduction of manganese and influenced remarkably by the amount of MnOx. In particular, the catalyst with 15 wt.% MnOx loading performs best activity in view of the lowest complete conversion temperature of 250 °C at a GHSV of 12000 h−1. According to the characterizations of N2 adsorption-desorption, XRD, SEM-EDX, H2-TPR, O2-TPD and XPS analyses, the superior catalytic activity could be attributed to the well-dispersed MnOx species, good low-temperature redox property, more Mn4+ species and more available surface and lattice oxygen species. Additionally, the optimized catalyst shows high stability during the thermal aging experiment and long-term testing experiment, and it also shows a good activity under the condition of high gas hourly space velocity, which presents a well application prospect.

MnOx–CeO2/La–Al2O3 catalysts prepared by the deposition–precipitation method, impregnation method and a combination of the two methods were investigated for toluene oxidation. The results showed that the MnOx–CeO2/La–Al2O3 catalyst prepared by the deposition–precipitation method showed the best catalytic activity by achieving the complete conversion of toluene at 300 °C with a GHSV of 12 000 h−1. N2 adsorption–desorption, XRD, SEM-EDX, H2-TPR, O2-TPD, Toluene-TPD and XPS were employed for catalyst characterization. The characterization results revealed that the MnOx–CeO2/La–Al2O3 catalyst prepared by the deposition–precipitation method had richer surface oxygen species, a higher proportion of Mn4+ and good low-temperature redox properties, which resulted in a superior catalytic activity toward complete oxidation of toluene.

Previously, we have reported that the dysregulation of ketogenesis plays an important role in the carcinogenesis of clear cell renal cell carcinoma (ccRCC). Here, we demonstrate decreased expression of the HMGCS2 gene in ccRCC, a critical enzyme for the synthesis of the ketone body β-hydroxybutyrate (β-OHB). We found that the reduced transcription of the HMGCS2 gene in ccRCC cells was significantly correlated to a higher relative methylation rate in its promotor region. The higher methylation rate in the region of the transcription start site and 1st exon of the HMGCS2 gene was, in turn, correlated with a worse clinical outcome for patients. The transcription of HMGCS2 was possible to restore by treatment with 5-aza-2'-deoxycytidine and with the histone deacetylase inhibitor β-OHB. Therefore, the low levels of the HMGCS2 enzyme in ccRCC may be the consequence of hypermethylation of the HMGCS2 promotor. The ensuing reduction in the ketone body levels further suppresses the transcription of HMGCS2 via a feedback loop. Ectopic expression of HMGCS2 attenuates the migration and invasion of ccRCC but does not affect the proliferative capacity of ccRCC cells in vitro. In addition, we showed that ectopic expression of HMGCS2 boosts the intracellular levels of β-OHB and that exogenously applied β-OHB suppresses the motility and invasion of ccRCC. Our study reveals crosstalk between genes that regulate metabolism and their metabolites, thus providing a better understanding of the epigenetic mechanism involved in ccRCC carcinogenesis and suggesting opportunities for metabolic therapy of tumors. Initially, we suggest that the mRNA level of HMGCS2 could serve as a potentially valuable diagnostic (AUC = 0.918, p 0.001) and prognostic biomarker.

Ce0.65Zr0.35O2 was prepared by co-precipitation method and a series of Mn1-yCoy/Ce0.65Zr0.35O2 catalysts with different Mn/Co molar ratio were synthesized via the co-impregnation method. These catalysts were applied for gaseous toluene oxidation, which showed that the catalytic activity was significantly improved by the addition of Mn and Co. In particular, Mn–Co(1:1)/Ce0.65Zr0.35O2 with Mn/Co molar ratio of 1:1 displayed the best result with the lowest complete conversion temperature of 242 °C under a GHSV of 12,000 h−1. The as-prepared catalysts were characterized by X-ray diffraction, H2 temperature-programmed reduction, N2 adsorption–desorption, X-ray photoelectron spectroscopy and O2 temperature-programmed desorption. These characteristics revealed that the coexistence of Mn and Co could enhance the redox property and generate more surface adsorbed oxygen, thereby improving the performance of the catalysts for toluene low-temperature oxidation. The Mn–Co(1:1)/Ce0.65Zr0.35O2 exhibited the best catalytic activity and high stability. The excellent catalytic activity of the Mn–Co(1:1)/Ce0.65Zr0.35O2 could be ascribed to a greater amount of surface adsorbed oxygen species and Mn4+ on the catalyst surface.