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Background: Breast cancer is the leading cause of cancer death in women. The current methods of chemotherapy for breast cancer generally have strong adverse reactions and drug resistance. Therefore, the discovery of novel anti-breast cancer lead compounds is urgently needed. Objective: This study aimed to design and synthesize a series of 2-alkyl substituted fluorinated genistein analogues and evaluate their anti-breast cancer activity. Methods: Target compounds were obtained in a multistep reaction synthesis. The anti-tumor activity of compounds I-1~I-35 was evaluated with MCF-7, MDA-MB-231, MDA-MB-435, and MCF-10A cell lines in vitro, with tamoxifen as the positive control. Molecular docking was used to study the interaction between the synthesized compounds and PI3K-gamma. Results: A series of 2-alkyl substituted fluorinated genistein analogues was designed, synthesized, and screened for their bioactivity. Most of the compounds displayed better selectivity toward breast cancer cell lines as compared to tamoxifen. Among these analogues, I-2, I-3, I-4, I-9, I-15, and I-17 have the strongest selective inhibition of breast cancer cells. Compounds I-10, I-13, I-15, I-17, and I- 33 were found to have significant inhibitory effects on breast cancer cells. Molecular docking studies have shown that these compounds may act as PI3Kγ inhibitors and may further exhibit anti-breast cancer effects. Conclusion: Most of the newly synthesized compounds could highly, selectively inhibit breast cancer cell lines. The experimental results indicate that the synthesized analogs may also have obvious selective inhibitory effects on other malignant proliferation cancer cells.

Introduction: Although oxidative stress has been demonstrated to mediate acute ethanol-induced changes in autophagy in the heart, the precise mechanism behind redox regulation in acute ethanol heart disease remains largely unknown. Methods: Wild-type C57BL/6 mice were intraperitoneally injected with ethanol (3 g/kg/day) for 3 consecutive days. The effects of ethanol on cultured primary cardiomyocytes and H9c2 myoblasts were also studied in vitro. Levels of autophagic flux, cardiac apoptosis and function, reactive oxygen species (ROS) accumulation, NOX4, and NOX2 were examined. The NOX4 gene was knocked down with NOX4 siRNA. Results: In this study, we demonstrated that schisandrin B inhibited acute ethanol-induced autophagy and sequent apoptosis. In addition, schisandrin B treatment improved cardiac function in ethanol-treated mice. Furthermore, NOX4 protein expression was increased during acute ethanol exposure, and the upregulation of NOX4 was significantly inhibited by schisandrin B treatment. The knockdown of NOX4 prevented ROS accumulation, cell autophagy, and apoptosis. Conclusion: These results highlight that NOX4 is a critical mediator of ROS and elaborate the role of the NOX4/ROS axis in the effect of schisandrin B on autophagy and autophagy-mediated apoptosis in acute ethanol exposure, which suggests a therapeutic strategy for acute alcoholic cardiomyopathy.

A new salamo-type bisoxime compound H3L has been synthesized and exploited as a highly efficient chemosensor with multiple responses to Cu2+ and S2−. Chemosensor H3L exhibits highly selective and sensitive detection of Cu2+ and S2− simultaneously. The LODs of Cu2+ and S2− were calculated to be 1.5398 × 10−7 and 1.7274 × 10−7 M in DMF-water (9 : 1, v/v) solution, respectively. The color of the chemosensor H3L solution changed from light green to dark green after adding S2− under a 365 nm UV-lamp. The sensing mechanism of the chemosensor H3L was characterized using several methods, including ultraviolet spectroscopy, ESI-mass spectrometry, 1H-NMR and FT-IR spectroscopy. Meanwhile, the crystal structure of the Cu(II) complex, [Cu2(L)]ClO4·2CH3OH, has been determined by X-ray crystallographic analysis. Density Functional Theory (DFT) was employed to further understand the obtained experimental results.

Background: The efficacy of allergen-specific immunotherapy (AIT) is mainly depended on the tolerogenic immune responses elicited. Properly conjugated nano-vaccine has the advantages of both specific targeting and continuous and on-demand release of allergen. Objectives: The aim of this study is to investigate the effects of a dendritic cells (DCs)-targeting nano-vaccine for AIT. Methods: The nano-vaccine was produced by coupling polylactic-co-glycolic acid (PLGA)-encapsulated ovalbumin (OVA) with mannan. Allergen capture, human monocytes-derived DCs (hMoDCs) activation, and T cells responses were assessed by flow cytometry, confocal microscopy, quantitative real-time PCR, ELISA, and Cytometric Bead Array. Balb/c mice were immunized with the nano-vaccines, and the immune responses were analyzed. Results: OVA-PLGA nanoparticle (NP) displayed favorable safety profile. OVA-mannan-PLGA NP was captured more efficiently by hMoDCs than OVA-PLGA NP, which was mediated mainly through DC-specific intercellular adhesion molecule 3-grabbing nonintegrin. A tolerogenic phenotype of hMoDCs was induced by OVA-mannan-PLGA NP, but not OVA-PLGA NP, and increased number of regulatory T (Treg) cells was generated subsequently in in vitro coculture. Immunization of Balb/c mice with OVA-mannan-PLGA NP resulted in lower serum level of OVA-specific immunoglobulins and less production of pro-inflammatory cytokines in splenocytes culture than the mice immunized with OVA-PLAG NP, PLGA NP, or OVA, while the number of splenic Treg cells was higher in OVA-mannan-PLGA group than in other groups. Moreover, preimmunization with OVA-mannan-PLGA NP significantly inhibited the Th2 immune response induced by OVA sensitization. Conclusions: The biocompatible PLGA-encapsulated OVA coupling with mannan has augmented ability for tolerance induction and could be developed as a novel vaccine for AIT.

Genistein is a phytoestrogen compound which possesses multiple biological activities such as anti-cancer, while its application is limited by poor pharmacokinetic properties. Structural modification is an effective approach to get genistein derivatives with better activities and approved pharmacokinetic properties. Based on previous research work, we synthesized two series of genistein derivatives bearing halogen substituents, and evaluated their inhibitory effects on the cancer cell lines MCF-7, MDA-MB-231, and MDA-MB-435. Among these derivatives, compound XI displayed the best inhibitory activity against MCF-7, MDA-MB-231 and MDA-MB-435 cell lines in vitro, which is worth further studies.

As a disease closely related to the metabolic syndrome, diabetes has become a public health issue that severely affects many people’s quality of life. The search for novel anti-diabetic agents remains the cornerstone to control this challenging disease. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin and leptin signaling pathways, has turned out to be a potential target of type II diabetes mellitus (T2DM) and obesity. In recent years, the development of novel anti-diabetic drugs based on PTP1B inhibitors has captured the attention of many researchers. Thiazole, a five-membered heterocycle containing sulfur and nitrogen atoms, has been considered as an essential core skeleton for various active compounds. Furthermore, thiazolidines, representing a series of compounds with saturated thiazole rings, widely exist in natural products and synthetic compounds with a variety of pharmacological activities. Here, we focus on the emphasis of PTP1B in diabetes and the development of PTP1B inhibitors based on thiazole and thiazolidine derivatives in the past decade. Many PTP1B inhibitors and their chemical structures, selectivity, potency, and structure-activity relationship have been elaborated. The great majority of PTP1B inhibitors containing thiazole and thiazolidine moieties described in this review exhibit preferable activities, which would be of importance for the rational design and efficient application of PTP1B inhibitors with anti-diabetes activity.

A large number of efficient cyanation methods have been developed because of the wide range of applications of nitriles, but conventional methods usually suffer from the need for a toxic cyanation reagent. Although difluorocarbene chemistry has received increasing attention, the use of difluorocarbene as a sources of the nitrile carbon for nitrile groups remains largely unexplored. We describe a difluorocarbene-based cyanation of aryl iodides promoted by a cheap copper source, Cu(NO3)2·2.5H2O, under an air atmosphere. Ph3P+CF2CO2 –, an easily available and shelf-stable difluorocarbene reagent, and NaNH2 are used as the carbon source and the nitrogen source for the nitrile group, respectively. The cyanation protocol is attractive because no toxic reagent is used and performing the reactions under an air atmosphere is operationally convenient.

Introduction Previous studies found that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with several inflammatory diseases. However, the relationship between VDR gene polymorphisms and chronic spontaneous urticaria (CSU) is not clear. Aim The purpose of our study was to explore the relationship between the polymorphism of VDR and the incidence of chronic spontaneous urticaria in the Chinese Han population. Meanwhile, the vitamin D levels in patients with chronic spontaneous urticaria were also detected and the effects of VDR gene polymorphism on vitamin D levels were detected. Material and methods The genotypes of four VDR polymorphisms (TaqI, BsmI, ApaI, and FokI) were studied using allele-specific PCR analysis in 90 CSU patients and 90 healthy controls. Results Compared to the control group, the mutant allele (C) of FokI were more common in patients with CSU (57.2% vs. 45%, p = 0.020, odds ratio (OR) = 0.612, 95% confidence interval (CI): 0.403-0.928). We found that serum vitamin D levels were significantly lower in CSU patients than in healthy controls (p = 0.023). However, the effect of VDR gene polymorphism on vitamin D levels was not found in patients of CSU. Conclusions We first reported the effect of VDR gene FokI (rs2228570) polymorphism on the incidence of chronic spontaneous urticaria in the Chinese Han population.

Atopic dermatitis (AD) is a recurrent chronic inflammatory skin disease affecting up to 30% of the children population, and immuno-regulatory therapy that could modify the course of disease is urgently needed. Probiotics have demonstrated therapeutic effects on AD and could potentially regulate the disease process. However, the efficacy of probiotics for AD is inconsistent among different studies, which is mainly due to the elusive mechanism and different species and (or) strains used. In this study, we designed a mixture of five strains of probiotics (named IW5) and analyzed the effect and mechanism of IW5 on calcipotriol (MC903)-induced AD-like dermatitis. We found that IW5 significantly alleviated skin inflammation of the MC903-induced AD in mice. Administration with IW5 induced increased production of regulatory T cells and regulatory dendritic cells (DCregs) in the mesenteric lymph nodes. We also found that the diversity of the gut microbiota in the mice with MC903-induced dermatitis was increased after IW5 administration, and the level of butyrate in the gut was elevated. In cell culture, butyrate induced the production of DCregs. Our study revealed the therapeutic effects of a newly designed probiotics mixture and uncovered a possible mechanism, providing a foundation for future clinical studies.

A facile oxalate co-precipitation method combined with solid-state sintering is used to synthesize layered LiNi0.6Co0.2Mn0.2O2 (NCM-622) as a low-cost cathode material for lithium ion batteries. Homogeneous Ni-Co-Mn oxalate precursors were obtained by adding oxalic acid into mixed metal acetates without the need of rigorous control of co-precipitation parameters. The effects of sintering temperature on the morphology, structure and electrochemical properties of the synthesized NCM-622 are studied. An intermediate sintering temperature of 850 °C is found to favor the integrity of the layered structure by compromising the solid-state reaction and Li loss, leading to a low degree of cation mixing. The as-synthesized NCM-622 delivers a capacity of 152 mA h g−1 after 100 cycles at 1 C (93.2% retention), and shows excellent rate capability with 76.8 mA h g−1 at 10 C, which is competitive to the materials prepared by the mainstream hydroxide co-precipitation method. Moreover, a solution-based surface modification was employed to further improve the cathode through self-adsorption of Al(OH)3 using Al2(SO4)3 precursor in order to form a Al2O3 coating. The facial surface modification has significantly improved the performance of NCM-622 under normal and high voltage conditions.

Background Epicutaneous sensitization is an important route of immunization for allergens in atopic diseases; however, studies have also shown that application with protein on the intact skin induces antigen-specific tolerance. Langerhans cells (LCs) play an immunosuppressive role in several inflammatory skin diseases and mouse models, and the role of LCs in the skin-induced tolerance is not fully understood. Methods Langerin-DTA mice that were deficient in LCs were utilized to produce the model of skin-induced tolerance to ovalbumin (OVA). Binding of Langerin to OVA was analyzed by enzyme-linked immunosorbent assay, flow cytometry, and immunofluorescence. Homozygous Langerin-DTR mice that were deficient in Langerin were introduced to assess the role of Langerin in the skin-induced tolerance. Results Application with OVA onto the intact, but not tape-stripped, skin attenuated the production of OVA-specific IgE, IgG1, and IgG2a induced by subsequent subcutaneous immunization with OVA, and the inhibitory effects were abolished in Langerin-DTA mice. In contrast to the tape-stripped skin, the intact skin induced the production of IL-10 by LCs in draining lymph node after application with OVA. Langerin could bind OVA, and homozygous Langerin-DTR mice demonstrated similar humoral and cellular immune responses in the model of skin-induced tolerance compared to wide-type mice. Conclusion Our data suggested that LCs were critical in the intact skin-induced tolerance to protein antigen via Langerin, and LCs might be targeted via Langerin to regulate the immune responses in systemic and (or) skin inflammatory diseases.

Initial substrate chemical characteristics are the most important factor in the regulation of fine root decomposition. However, it remains unclear how nitrogen (N) deposition changes the decomposition process by affecting initial substrate chemical characteristics with different fine root diameter sizes. We compared the root decomposition processes across three diameter sizes (very fine roots, 0.05), but low N addition enhanced the correlation coefficients between initial chemical indexes and decomposition rates. (3) Low N addition increased the release rates of C and cellulose in the very fine roots but not intermediate fine and largest fine roots, while the medium and high N addition decreased the release rates of N, P, cellulose and lignin in the very fine and intermediate fine roots by affecting the initial C, N, P, starch, cellulose and lignin concentrations. (4) Release of compounds from large diameter fine roots is less responsive to N addition than that from the small ones. The initial substrate chemistry plays an important role during the N addition affecting fine root decomposition and release of chemical compounds. Our results suggest that N deposition may change the biogeochemical processes of forest ecosystems by affecting the release of compounds from fine roots.

In view of the potential application of NIR luminescence in biology, a series of four new 3,5-Heptanedione (β-diketonate) ytterbium complexes, e.g. [Yb(L)3(H2O)2] (1), [Yb(L)3(2,2′-bpy)] (2), [Yb(L)3(dpq)] (3) and [Yb(L)3(dppz)] (4) have been designed and isolated. Crystal structures analysis show that all complexes 1–4 exhibit the similar mononuclear structure, in which the central Yb3+ ion is eight-coordinated forming the square-anti-prismatic geometry. NIR luminescence of all complexes 1–4 shows strong characteristic emission of Yb3+ ions. To improve the mechanical and thermal stability, complex 1 was further doped into poly-(methyl methacrylate) (PMMA) for preparing a thin film (1@PMMA). Their thermal stability and NIR luminescence were essentially enhanced in contrast to that for complex 1. This NIR luminescent thin film may be of potential applications in biological dictation and luminescent probe.

In this study, bamboo flour (BF) was chemically modified using alkyl ketene dimer (AKD) or alkali treatment for the preparation of high-density polyethylene/bamboo flour (HDPE/BF) composites with or without compatibilizer maleic anhydride grafted high-density polyethylene (HDPE-g-MAH). The modified BF was characterized by Fourier transformation infrared (FTIR) spectroscopy and contact angle measurement, and the mechanical properties, morphology and water resistance of the HDPE/BF composites were investigated and compared. The results show that highly hydrophobic BF can be obtained by a simple procedure using a common paper sizing agent AKD. AKD can react with the hydroxyl groups in cellulose to form β-keto ester. The combination of AKD treatment and addition of HDPE-g-MAH is more effective in improving the mechanical properties of HDPE/BF composites than using them alone. The impact strength, flexural strength and modulus of HDPE/A-BF/MAH composite are increased by 100.0%, 197.1% and 61.8% compared with that of HDPE/U-BF composites, and the water absorption and thickness swelling are decreased by 87.7% and 87.4% after immersion in water for one week, respectively. These results indicate that HDPE/BF composites with good mechanical properties and high water resistance can be obtained by AKD treatment.

A new salamo-type fluorescence probe H2L was synthesized by a series of reactions and corroborated by single-crystal X-ray crystallography and 1H NMR spectra. Fluorescence of Co2+ selectively response showed “off” when cations were sequentially detected. The LOD of H2L to Co2+ was calculated to be 3.73 × 10-7 M in DMF/water (9:1, v/v) solution system. Meanwhile, the single crystal of the Co2+ complex with H2L was obtained by solvent evaporation. The structure of the complex [Co3(L)2(MeOH)2(μ-OAc)2]·2MeOH was validated by single-crystal X-ray diffraction, IR, and elemental analyses, and the mechanism of recognition of Co2+ by H2L was got. Density functional theory (DFT) and Hirshfeld surface analyses were investigated to further understand the experimental results observed.

To evaluate the efficacy of acellular collagen scaffold (ACS) in combination with basic fibroblast growth factor (bFGF) for the repair of traumatic tympanic membrane (TM) perforation in a rat model.A prospective controlled animal study in a rat model of traumatic TM perforation.Tertiary medical center.Sprague-Dawley rats (N = 84) with unilateral traumatic perforation of the right TMs were randomized to receive ACS, bFGF, ACS in combination with bFGF (ACS/bFGF), or nothing (spontaneous healing without any interventions as a control group). The healing outcomes were evaluated by otoscopy, optical coherence tomography, histology, and transmission electron microscopy at 1, 2, and 4 weeks postoperatively. The hearing outcomes were assessed with auditory brainstem response testing.ACS/bFGF resulted in higher perforation closure rates at an earlier stage than spontaneous healing, ACS, and bFGF. Based on histology, optical coherence tomography, and transmission electron microscopy, a trilaminar structure and uniform thickness with mature, densely packed collagen fibers were seen in the ACS/bFGF group. Auditory brainstem response evaluation also showed that ACS/bFGF treatment promoted faster functional hearing recovery as compared with the control group.ACS is an effective TM scaffold and a carrier for bFGF. ACS/bFGF improves the TM closure rate, results in better-reconstructed TMs, and improves hearing. ACS/bFGF serves as a potential substitute for TM perforations in clinical settings.

To provide feasible methods for the extraction of valuable metals from spent batteries or low-grade primary ores, the extraction behavior of some representative acidic phosphorus-containing compounds (APCCs) as extractants is evaluated from the perspective of experimental and theoretical investigations in this work. Aqueous solutions containing five metal ions, Ca(II), Co(II), Mg(II), Mn(II), and Ni(II), were made to simulate leaching liquids, and the extraction of these metals was investigated. A simplified calculated model was used to evaluate the interaction between each extractant and metal ions. The calculation results agree well with the experimental tests in trend. This work not only provides potential extractants for the extraction of valuable metals from spent batteries or low-grade primary ores but also demonstrates the practicability of the simplified calculation model.

Background Skin commensal bacteria play important roles in skin homeostasis. Langerhans cells (LCs) are epidermis-resident dendritic cells that sense environmental stimuli and are critical in the induction of immune tolerance to allergen and bacterial skin flora. However, response of LCs to the metabolites of the skin microbiota is not clear. Objective To explore the effects of the skin microbial metabolites on LCs activation. Methods LCs derived from CD34+ hematopoietic stem cells in the cord blood were treated with a microbial metabolite of tryptophan, indole-3-aldehyde (IAId). Activation aryl hydrocarbon receptor (AhR) signaling, production of IL-10, and expression of receptor activator of NF-κB (RANK) / receptor activator of NF-κB ligand (RANKL) in LCs or keratinocytes were analyzed using quantitative PCR, western blotting and flow cytometry. LCs maturation induced by IAId and CD4+ T cell response induced by IAId-conditioned LCs were also investigated. Results IAId induced the production of indoleamine 2,3-dioxygenase (IDO) and IL-10 in LCs through the activation of AhR. IAId promoted the expression of RANK and RANKL on LCs and keratinocytes in an AhR-dependent manner respectively, which might result in activation of NF-κB signaling and production of IL-10. Moreover, a mature phenotype of LCs was induced by IAId, and IAId-activated LCs inhibited CD4+ T cell proliferation and induced IL-10 secretion. Conclusions Our study revealed a negatively regulatory function of a tryptophan metabolite on LCs through the activation of AhR, and the microbial metabolites could be utilized in future treatment for inflammatory skin diseases.

Sorafenib is currently the standard chemotherapy drug for treatment of advanced hepatocellular carcinoma (HCC). But its efficacy requires improvement, it is imperative to seek therapeutic strategies that combine sorafenib with other anticancer agents. In this study we investigated the synergistic anticancer effect of combining sorafenib and artesunate, an anti-malaria drug derivative, against HCC in vitro and in vivo. We first showed that artesunate (1–100 μM) alone dose-dependently inhibited the proliferation of five HCC cell lines tested with IC(50) values of around 100 μM. Artesunate treatment dose-dependently increased the ROS level in both HuH7 and Hep3B cells; addition of NAC significantly ameliorated the antiproliferation effect of artesunate against HuH7 and Hep3B cells. Then we demonstrated that combination of sorafenib and artesunate exerted synergistic antiproliferation effect and induced synergistic apoptosis in HCC cell lines. In nude mice bearing Hep3B xenografts, combined administration of sorafenib and artesunate significantly enhanced the suppression on tumor growth. We further revealed that sorafenib dose-dependently decreased the levels of p-ERK and p-STAT3, whereas artesunate markedly increased the levels of p-ERK and p-STAT3 in HuH7 and Hep3B cells. When used in combination, sorafenib abolished artesunate-elevated levels of p-STAT3 and p-ERK. Moreover, pharmacological inhibition of ERK by inhibitor PD0325901 or STAT3 by inhibitor Stattic markedly enhanced the anticancer activity of artesunate, suggesting that suppression of ERK and STAT3 signaling by sorafenib contributes to the synergistic anticancer activity against HCC caused by combination of sorafenib and artesunate. Taken together, our results provide an evidence for possible use of sorafenib plus artesunate or artemisinin analogs for treatment of HCC in the future.

Resveratrol is a natural phytoestrogen produced by plants to protect themselves from injury, UV irradiation, and fungal attack. The main active structure is E-resveratrol, which has many pharmacological activities. As the structure of resveratrol is similar to the natural estrogen 17β-estradiol and the synthetic estrogen E-diethylstilbestrol, resveratrol is used in reducing the incidence of breast cancer. However, the therapeutic application of resveratrol is limited due to its low bioavailability. To improve its bioavailability and pharmacological activity, some resveratrol derivatives have been designed and synthesized by substitutions of methoxy, hydroxyl, and other functional groups or heterocyclic esterification either on the "A" or "B" ring, and double bonds were replaced by imine bonds and isometric heterocycles such as naphthyl and imidazole, or synthetic resveratrol oligomers. The structures, synthetic routes, and evaluation of the biological activities of these compounds are discussed. These are aimed at providing some references for the study of resveratrol derivatives in anti-breast cancer treatment.

In this work, we have identified a significantly improved variant (S131Y/Q252I) of the natural ϵ-keto ester reductase CpAR2 from Candida parapsilosis for efficiently manufacturing (R)-8-chloro-6-hydroxyoctanoic acid [(R)-ECHO] through co-evolution of activity and thermostability. The activity of the variant CpAR2S131Y/Q252I towards the ϵ-keto ester ethyl 8-chloro-6-oxooctanoate was improved to 214 U mg-1 -from 120 U mg-1 in the case of the wild-type enzyme (CpAR2WT )-and the half-deactivating temperature (T50 , for 15 min incubation) was simultaneously increased by 2.3 °C in relation to that of CpAR2WT . Consequently, only 2 g L-1 of lyophilized E. coli cells harboring CpAR2S131Y/Q252I and a glucose dehydrogenase (GDH) were required in order to achieve productivity similar to that obtained in our previous work, under optimized reaction conditions (530 g L-1 d-1 ). This result demonstrated a more economical and efficient process for the production of the key (R)-α-lipoic acid intermediate ethyl 8-chloro-6-oxooctanoate.

Reactions of N,N'-bis (salicylidene)-1,2-cyclohexanediamine (H2 L) with mixed lanthanide counterions of LnCl3 ·6H2 O and Ln (NO3 )3 ·6H2 O afford six H2 L lanthanide coordination polymers, e.g. {[Pr(H2 L)2 (NO3 )2 Cl]·2CH2 Cl2 }n (1); {[Ln(H2 L)1.5 (NO3 )3 ]2 ·5CHCl3 ·mCH3 OH}n [Ln = Sm (2), Eu (3), Gd (4), Tb (5) and Yb (6); m = 1 (2-5); m = 0 (6)]. X-ray crystallographic analysis reveals that complex 1 exhibits three-dimensional diamondoid topologic structure and complexes 2-6 are of two-dimensional structure. Luminescent spectra show that complexes 1 and 6 have characteristic near-infrared (NIR) emission of praseodymium (III) and ytterbium (III) ions and complexes 2-5 emit luminescence in the visible region. Complexes 3 and 6 reveal sensitive luminescence responses to formaldehyde.

Objective To evaluate the effect of atmospheric fine particulate matter (PM2.5) on the expression of skin barrier-associated proteins and proinflammatory cytokines in human keratinocytes. Methods Atmospheric PM2.5 samples were given by Professor Yufeng Zhou in Children′s Hospital of Fudan University. Human primary keratinocytes were isolated from circumcised foreskins of 5 males, and subjected to culture. These human primary keratinocytes were divided into several groups to be stimulated with PM2.5 at different concentrations of 0 (control group) , 10, 50, 100, 200 mg/L for 24 hours, and cell counting kit (CCK) -8 assay was performed to determine the survival rates of keratinocytes. Fluorescence-based quantitative PCR and Western blot analysis were conducted to determine the mRNA and protein expression of filaggrin, keratin-14 and claudin-1 in these keratinocytes respectively, and enzyme-linked immunosorbent assay (ELISA) was performed to detect levels of interleukin (IL) -1α, thymic stromal lymphopoietin (TSLP) and IL-33 in the culture supernatant of these keratinocytes. Statistical analysis was carried out with SPSS13.0 software by using one-way analysis of variance, least significant difference (LSD) -t test and Pearson correlation analysis. Results After 24-hour treatment with different concentrations of PM2.5, there was no significant difference in the survival rate of keratinocytes between the 10-mg/L PM2.5 group and control group (P > 0.05) , while the survival rates of keratinocytes were significantly lower in the 50-, 100-, 200-mg/L PM2.5 groups than in the control group (all P 0.05) . The 10-, 50-, 100- and 200-mg/L PM2.5 groups showed significantly increased keratin-14 expression compared with the control group (all P < 0.05) . The claudin-1 expression did not differ between the 10-mg/L PM2.5 group and control group (P = 0.87) , but significantly higher in the 50-, 100- and 200-mg/L PM2.5 groups than in the control group (all P < 0.05) . The stimulation with PM2.5 at 10, 50, 100 and 200 mg/L could induce an increase in the supernatant levels of TSLP, IL-1α and IL-33 (all P < 0.01) . Pearson correlation analysis showed that the supernatant levels of the proinflammatory cytokines TSLP, IL-1α and IL-33 were positively correlated with the concentration of PM2.5 (r = 0.57, 0.67, 0.91 respectively, all P < 0.05) . Conclusion The exposure to PM2.5 can induce decreased survival rate of keratinocytes, aberrant expression of filaggrin, keratin-14 and claudin-1, and elevated secretion of the proinflammatory cytokines TSLP, IL-1α and IL-33, which may lead to impaired skin barrier function. Key words: Keratinocytes; Particulate matter; Cell survival; Keratin-14; Claudins; Interleukin-1alpha; PM2.5; Barrier-associated proteins; Filaggrin; Interleukin-33; Thymic stromal lymphopoietin

Firstly discovered in 1980s, human immunodeficiency virus (HIV) continues to affect more and more people. However, there is no effective drug available for the therapy of HIV infection. Betulinic acid existing in various medicinal herbs and fruits exhibits multiple biological effects, especially its outstanding anti-HIV activity, which has drawn the attentions of many pharmacists. Among the derivatives of betulinic acid, some compounds exhibited inhibitory activities at the nanomolar concentration, and have entered phase II clinical trials. This paper summarizes the current investigations on the anti-HIV activity of betulinic acid analogues, and provides valuable data for subsequent researches.

A series of isomorphic lanthanide metal–organic frameworks (Ln-MOFs), namely [Ln(dcbba)(DMF)2]n·H2O·0.5DMF [Ln = La (1), Eu (2) and Tb (3); H3dcbba = 4-(3, 5-dicarboxylatobenzyloxy)benzoic acid; DMF = N,N′-dimethylformamide] have been designed and synthesized by the solvothermal reactions of H3dcbba and La(NO3)3·6H2O. Single-crystal X-ray diffraction analysis reveals that the complexes 1–3 exhibit a (3,6)-connected open framework structure with binuclear [Ln2(COO)6]n secondary building units as 6-connected nodes and H3dcbba ligands as 3-connected nodes. The isostructural mixed La/Eu/Tb-dcbba (4) was obtained via the in-suit doping of different Ln3+ ions into the host framework, which is able to emit pure orange, white, and blue light when excited at 300, 305, and 350 nm, respectively. Subsequently, a novel and multifunctional sensing process was designed based on the excitation wavelength sensitive color tunable luminescent sample 4, which can detect HS– ions, THF (tetrahydrofuran), and Ag+ ions via diffe...

Polypyrrole (PPy) is a highly conductive polymer and promising pseudocapacitive material for energy storage. However, the poor stability of PPy based supercapacitors (SCs) limits their applications. Here we demonstrate a facile dipping process to uniformly grow 4-butylbenzenesulfonate modified PPy film on a filter paper substrate. The flexible and free-standing PPy paper electrode demonstrated excellent cycling stability with capacitance retention of ~84.8% after 200,000 cycles. We believe that the 4-butylbenzenesulfonate modification could increase the order degree of PPy via layer-by-layer stacked α-α coupled chains, leading to a robust structure under the charging and discharging progress. This work pushes the cycling limitation of PPy based SCs and realizes their potentials for practical applications.

A series of four β-diketone mononuclear Dy(iii) complexes, namely Dy(Hthd)3(MeOH)·2,5-Py (1), Dy(Hthd)3(Tppo) (2), Dy(Hthd)3(PyNO) (3), and Dy(Hthd)3(4-PyNO) (4) (Hthd = 2,2,6,6-tetramethyl-3,5-heptanedione, 2,5-Py = 2,5-pyridine, Tppo = triphenylphosphine oxide, PyNO = pyridine N-oxide, 4-PyNO = 4-methylpyridine N-oxide), have been isolated by reactions of Hthd, DyCl3·6H2O and an auxiliary ligand. X-ray crystallographic analysis revealed that complexes 1-4 are all seven-coordinated mononuclear structures with C2v or C3v local symmetry. The magnetic measurements of complexes 1-4 revealed their field-induced single-ion magnet (SIM) behavior, due to mixed low-lying states. The crystal field parameters and orientations of the magnetic easy axes were obtained from simulations of the DC magnetic data and an electrostatic model calculation. The magneto-structural correlation of seven-coordinated Dy(iii) SIMs with low-symmetry coordination environments was further discussed.

Four mononuclear dysprosium complexes, namely, [Dy(thd)3(MeOH)2] (1), [Dy(thd)3(Phen)] (2), [Dy(thd)3(Dpq)] (3) and [Dy(thd)3(Dppz)] (4) (thd = 2,2,6,6-tetramethyl-3,5-heptanedione; Phen = 1,10-phenanthroline; Dpq = dipyrazine[2,3-f:2′,3′-h]quinoxaline; and Dppz = dipyrido[3,2-a:2′,3′-c]phenazine), have been designed and isolated by reactions of Hthd with DyCl3·6H2O and corresponding auxiliary capping ligands such as Phen, Dpq and Dppz. The crystal structure analysis exhibits that Dy(III) ions in complexes 1–4 adopt distorted square antiprism geometry with D4d symmetry. Magnetic analysis reveals that all complexes 1–4 exhibit slow magnetic relaxation with the barrier heights (Ueff/kB) of 45.1 K, 98.4 K, 128.9 K and 89.4 K, respectively. The butterfly magnetic hysteresis loops were observed up to 5 K for complex 2. The co-relationship between the barrier heights and the structure in terms of the Dy–Oβ-diketone bond lengths, the quantify distortion degree (σα2 or σΦ2) and the deviation angles (θ) of magnetic easy axes for the SAP coordination environment were investigated and discussed.

In this work, commercial LiCoO 2 is modified with a glassy B 2 O 3 by solution mixing with H 3 BO 3 followed by post-calcination in order to enhance its high-voltage electrochemical performance. The glassy B 2 O 3 coating/additive is believed to serve as an effective physiochemical buffer and protection between LiCoO 2 and liquid electrolyte, which can suppress the high-voltage induced electrolyte decomposition and active material dissolution. During the early cycling and due to the electrochemical force, the as-coated B 2 O 3 glasses which have 3D open frameworks tend to accommodate some mobile Li + and form a more chemically-resistant and ion-conductive lithium boron oxide (LBO) interphase as a major component of the solid electrolyte interphase (SEI), which consequently enables much easier Li + diffusion/transfer at the solid-liquid interfaces upon further cycling. Due to the synergetic effects of B 2 O 3 coating/modification, the high-voltage capacity and energy density of the B 2 O 3 -modified LiCoO 2 cathode are promisingly improved by 35% and 30% after 100 cycles at 1 C within 3.0–4.5 V vs. Li/Li + . Meanwhile, the high-rate performance of the B 2 O 3 -modified electrode is even more greatly improved, showing a capacity of 105 mAh g −1 at 10 C while the bare electrode has dropped to no more than 30 mAh g −1 under this rate condition.

An adsorption–coagulation–microfiltration (A–C–MF) hybrid process using copper ferrocyanide (CuFC) as the adsorbent was developed in this study for the removal of cesium from water. The effect of coagulant on cesium removal by CuFC adsorption was investigated. A simpler calculation method for determining the CuFC dosage was established based on the Freundlich adsorption isotherms. Although the volume of treated water was 1.32 times higher for the A–C–MF process than the adsorption–microfiltration (A–MF) process, the cake layer and membrane pore resistances in the former were both lower than those in the latter due to the coagulation process.

A series of four new Salen-type lanthanide coordination polymers, e.g. [Ln(H2L)1.5Cl3]n (Ln = Tb (1), Dy (2), Ho (3), and Er (4); H2L = N,N′-bis(salicylidene)-1,4-butanediamine) have been synthesized by self-assembly and characterized by X-ray crystallography. Complexes 1–4 are isomorphic and exhibit one-dimensional alternating single/double ligand-bridge helix-like chain structures in which metal ion is six-coordinated in a slightly distorted octahedral geometry. Detailed magnetic studies suggest that the coordination polymer, especially complex 2, exhibits a typical single-molecule magnet behavior with the energy barrier of 24.4 K.

Background Langerhans cells (LCs) are epidermis-resident dendritic cells that sense and mediate stimuli from skin and outside world, and participate in various skin diseases, playing either pro-inflammatory or regulatory roles. However, the exact function of LCs in the pathogenesis of psoriasis remains unclear, and the conclusions of previous studies are controversial. Objectives To explore the role of LCs in mouse model of imiquimod (IMQ)-induced psoriasis-like dermatitis using langerin-diphtheria toxin A (DTA) mice that are constitutively deficient in LCs. Methods IMQ (Aldara) was painted on the skin of mice to produce psoriasis-like dermatitis, and inflammation was evaluated by gross ear thickness, histopathology, flow cytometry and cytokine production. Bone marrow transplantation and fluorescein isothiocyanate tracing were applied to access the migration of LCs. Results The severity of IMQ-induced dermatitis in langerin-DTA mice was significantly lower than that of wild-type mice, as evidenced by decreased level of ear thickness, inflammatory cell infiltration (γδ T cells and neutrophils) and inflammatory cytokine expression (IL-17, IL-22, IL-23 and tumor necrosis factor-α). After application with IMQ, LCs expanded in epidermis and showed increased expression of CD80 and CD86, and migrated to draining lymph node within 48 h. LCs in the lymph node 48 h after application with IMQ expressed increased level of CD80, CD86, CD40 and CC chemokine receptor 7. Conclusion LCs were activated upon application with IMQ, and promoted the inflammatory responses in psoriasis-like dermatitis.

Introduction Cockroach allergen exposure elicits cockroach sensitization and poses an increased risk for asthma. However, the major components in cockroach allergen and the mechanisms underlying the induction of cockroach allergen-induced allergy and asthma remain largely elusive. We sought to examine the role of cockroach-associated glycan in regulating human basophil function. Methods N-linked glycans from naturally purified cockroach allergen Bla g 2 were characterized by MALDI-TOF mass spectrometry. Binding of cockroach allergen to serum IgE from cockroach allergic subjects was determined by solid-phase binding immunoassays. Role of cockroach associated glycan in histamine release and IL-4 production from human basophils was examined. Expression of C-type lectin receptors (CLRs) and their role in mediating glycan-uptake in the basophils was also investigated. Results MALDI-TOF mass spectrometric analysis of N-glycan from Bla g 2 showed complex hybrid-types of glycans that terminated with mannose, galactose, and/or N-acetyl glucosamine (GlcNAc). Deglycosylated Bla g 2 showed reduced binding to IgE and was less capable of inducing histamine release from human basophils. In contrast, N-glycan derived from Bla g 2 significantly inhibited histamine release and IL-4 production from basophils passively sensitized with serum from cockroach allergic subjects. An analysis of CLRs revealed the expression of DC-SIGN and DCIR, but not MRC1 and dectin-1, in human basophils. Neutralizing antibody to DCIR, but not DC-SIGN, significantly inhibited Bla g 2 uptake by human basophils. A dose-dependent bindings of cockroach allergen to DCIR was also observed. Conclusions These observations indicate a previously unrecognized role for cockroach allergen-associated glycans in allergen-induced immune reactions, and DCIR may play a role in mediating the regulation of glycan on basophil function.

With the increasing demand for high energy density in portable-device Li-ion batteries (LIBs), efforts are devoted to increase and stabilize the capacity of LiCoO2 at high operation voltages. Herein, we report a low-cost and eco-friendly wet-chemical method to coat Al2O3 on LiCoO2, using only aluminium sulphate and water as source materials. A nanoscale oxide layer is coated on the surface of LiCoO2 particles through hydrogen-bonding assisted adsorption of the hydrolysed Al(OH)3 nanoparticles. The as-proposed Al2O3-coating provides excellent physico-chemical protection and kinetically-favourable interfaces for the LiCoO2 electrode, resulting in remarkable improvements of the electrode's cycling stability and rate capability when tested at high cutoff voltages up to 4.7 V (vs. Li/Li+). The synergetic effects of the oxide coating, e.g. alleviated electrolyte decomposition and reduced generation of irreversible solid electrolyte interphase (SEI) constituents (LiF/Li2CO3 and organics), are attributed to the improvements. At the cutoff voltage of 4.5 V, the modified LiCoO2 electrode in this work exhibits excellent cycling stability (147 mA h g−1, 82.6% retention after 500 cycles at 1C) and competitive rate capability (130 mA h g−1 at 10C), which are some of the best results reported so far. The outstanding high-voltage electrode performance and the simple and scalable coating approach show great promise of LiCoO2 cathodes in future high-energy and high-power LIBs.

A white-light-emitting LnCP is effectively applied to the detection of Ag+ and Mn2+ ions with high selectivity and sensitivity via luminescence-colour change.

A series of Hdmh mononuclear dysprosium complexes, namely [Dy(dmh)3(MeOH)] (1), [Dy(dmh)3(2,2′-bpy)]2 (2), and [Dy(dmh)3(phen)] (3), and analogue complexes of complex 2 [Lu(dmh)3(2,2′-bpy)]2 (4) (Hdmh = 2,6-dimethyl-3,5-heptanedione, 2,2′-bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline), have been isolated by reaction of Hdmh and LnCl3·6H2O with 2,2′-bpy/phen auxiliary ligands. X-ray crystallographic analysis reveals that all complexes 1–4 are mononuclear complexes. Complex 1 is seven-coordinated by three dmh ligands and one methanol. Complexes 2, 3 and 4 are all eight-coordinated by three dmh ligands and one 2,2′-bpy or phen. Magnetic studies indicate that complexes 2 and 3 exhibit slow relaxation at zero field but complex 1 does not. Strikingly, complex 2 exhibits mainly single slow relaxation under zero dc field and double slow relaxation under optimized dc field. In contrast, complex 3 exhibits double slow relaxation under zero dc field and single slow relaxation under optimized dc field. The origins of the double slow relaxation modes of complex 2 have been verified by dilution sample of complex 4.

Originally recognized as a regulator of axon guidance in the nervous system, Semaphorin 4D (Sema4D, CD100) also participates in various immune responses and many immune-related diseases. However, whether Sema4D is involved in the pathogenesis of contact hypersensitivity (CHS) remains unclear. In this study, we explored the role of Sema4D in oxazolone-induced CHS using Sema4D knockout (KO) mice. We found that Sema4D KO mice developed attenuated CHS responses, as indicated by milder ear-swelling, lower expression of IL-1β, IL-6, CXCL2 and CXCL5, and decreased recruitment of neutrophils, CD8+ T cells and CD4+ T cells. CHS was impaired in the wide type (WT) mice reconstituted with bone marrow from Sema4D KO mice, indicating that deletion of Sema4D gene in hematopoietic cells played a key role in the alleviated CHS in Sema4D KO mice. CHS was also attenuated in the WT mice transferred with draining lymph nodes (dLNs) cells from oxazolone-sensitized Sema4D KO mice, and the activation and differentiation of hapten-specific CD8+ T cells were impaired in Sema4D KO mice. Furthermore, Sema4D KO mice expressed less IL-1β and CXCL2 than WT mice after oxazolone sensitization, and after transferred with dLNs cells from oxazolone-sensitized WT mice, naive Sema4D KO mice showed attenuated CHS responses upon oxazolone challenge, indicating that the innate immune response of CHS in Sema4D KO mice was also abrogated. Taken together, our findings revealed for the first time that Sema4D positively regulated both the adaptive and innate immune responses in CHS.

To use copper ferrocyanide (CuFC) more efficiently in wastewater treatment, the method of isotope carrying used in 137Cs removal was investigated. A calculation model based on Freundlich isotherm was established to determine the optimum initial cesium concentration, at which the highest decontamination factor (DF) could be obtained at a certain CuFC dosage. An accurate DF prediction model was developed to describe synergistic effects of sodium and potassium. A novel index called volumetric distribution coefficient (K vd) was proposed to evaluate adsorption performance in terms of DF and concentration factor.

The introduction of oxygen vacancy for transition metal oxide is an effective method to tune their conductivity. Here, microwave combustion method is used to quickly synthesize reduced metal oxides and graphene hybrid composite in several minutes. Among these as-synthesized composites, the reduced orthorhombic Nb2O5 and graphene oxide (rNb2O5/rGO) composite demonstrates great electrochemical performance with a reversible specific capacity of 726.2 C g−1 at 2 mV s−1 in organic electrolyte as well as a good capacity retention of 87% after 3000 cycles at 10 A g−1. It is believed that this strategy can be a common route to quickly produce oxygen vacancy in oxides and satisfy much more application requirements even for the possibility of industrialization.

A simple imine based receptor NA-1 has been synthesized for detection of Zinc ions. Probe NA-1 showed the selective colorimetric changes with Zinc (II) ions whereas other metal ions didn't showed any observable colorimetric changes. The probe showed the very selective turn-on fluorescence response with Zn(II) ions among other rival metal ions like Cd(II) and Hg(II). The mode of binding was studied by 1H-nmr titrations and fluorescence spectroscopy. Jobs plot analysis confirming that the probe NA-1 forms 1:1 complex with Zn(II). The observed fluorescence and absorption change further supported by theoretical calculations. The turn-on fluorescence of the probe NA-1 is probably attributable to the interruption of intramolecular charge transfer as well as ESIPT. The limit of detection of the probe for Zn(II) sensing is in the range of 14 nano molar. Cytotoxicity (MTT) assay of the probe in live HeLa cells is showing that the probe is least toxic to cells. The probe NA-1 is effectively applied to detect Zn(II) ions in HeLa cells and suggesting the probe is NA-l permeable to cell wall and viable for Zinc(II) ions imaging in live cells.

Hepatocellular carcinoma (HCC) is a prevalent and refractory cancer in the world and very few drugs are available for the disease treatment currently. Programmed cell death protein-1 (PD-1) monoclonal antibodies including nivolumab and pembrolizumab has received accelerated approval for treatment of advanced HCC based on phase 1/2 clinical trials. However, the recently disclosed results of phase 3 clinical trials showed that both nivolumab and pembrolizumab as monotherapy failed to meet the primary objectives, which might overshadow the prospect of PD-1 inhibitors as monotherapy in treatment of advanced and unresectable HCC. The feasibility of PD-1 inhibitors in combination with other therapies or in other HCC settings requires further verification in the future.

Three new multi-nuclear Cu(II) complexes, [Cu4(L)2(CH3OH)2](NO3)2·2CH3OH (1), [Cu4(L)2(CH3OH)(CH3CN)](ClO4)2·2CH3OH (2) and [Cu4(HL)2(μ2-Cl)2Cl2(CH3CH2OH)2][CuCl2]·CHCl3 (3) have been successfully synthesized by the one-pot reaction of a bis(salamo)-based ligand H3L with Cu(NO3)2·3H2O, Cu(ClO4)2·6H2O and CuCl2·2H2O, respectively. Complexes 1 and 2 are monoclinic systems including four Cu(II) atoms with two completely deprotonated ligand (L)3- units, which form centrosymmetric helical molecules. Complex 3 is triclinic system including five Cu(II) atoms with two incompletely deprotonated ligand (HL)2- units, which forms an expanded structural molecule. Complexes 1–3 have been characterized by elemental analyses, IR, UV–Vis spectroscopy and single crystal X-ray crystallography. In addition, supramolecular interactions, Hirshfeld surfaces analyses, effects of counteranions and fluorescence properties were also investigated.