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The recruitment of monocytes to the active endothelial cells is an early step in the formation of atherosclerotic lesions; therefore, the inhibition of monocyte–endothelial cells interactions may serve as a potential therapeutic strategy for atherosclerosis. Recent studies suggest that β-elemene can protect against atherosclerosis in vivo and vitro ; however, the mechanism underlying the anti-atherosclerotic effect by β-elemene is not clear yet. In this study, we aimed to investigate the effects of β-elemene on the monocyte–endothelial cells interactions in the initiation of atherosclerosis in vitro. Our results showed that β-elemene protects human umbilical vein endothelial cells (HUVECs) from hydrogen peroxide-induced endothelial cells injury in vitro . Besides, this molecule inhibits monocyte adhesion and transendothelial migration across inflamed endothelium through the suppression of the nuclear factor-kappa B-dependent expression of cell adhesion molecules. Further, β-elemene decreases generation of reactive oxygen species (ROS) and prevents the activation of mitogen-activated protein kinase (MAPK) signaling pathway in HUVECs. In conclusion, this study would provide a new pharmacological evidence of the significance of β-elemene as a future drug for prevention and treatment of atherosclerosis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the efficacy and safety of iguratimod (T-614) in combination with methotrexate (MTX) for active rheumatoid arthritis (RA) patients. Sixty active RA patients were enrolled according to the 2010 American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) classification criteria, and were randomized into MTX + T-614 group and MTX group. T-614 was orally administered at a dosage of 50 mg/day (25 mg twice daily) for 24 weeks. MTX was orally administered to RA patients at a stable weekly dosage of 10 mg/week for the first 4 weeks and subsequent 12.5 mg/week for the later 20 weeks. Clinical features at baseline and efficacy endpoints of the ACR 20 % response (ACR20), ACR50, ACR70, and adverse events at 24 weeks were evaluated, respectively. After 24 weeks of treatment, clinical features at baseline, including counts for tender joints and swelling joints, visual analog scale for pain, patient's and physician's global assessment, erythrocyte sedimentation rate, C-reactive protein, disease activity score 28, health assessment questionnaire, simplified disease activity index, and ACR50 in the MTX + T-614 group, showed statistically significant differences comparing with the MTX group ( P < 0.05). There was no significant increase in adverse events in the MTX + T-614 group comparing with the MTX group ( P > 0.05). The combination of MTX and T-614 therapy appeared to have a good efficacy and safety for active RA and was superior to MTX-alone therapy after 24 weeks of treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] Climate change is causing the surface temperature to rise and the extreme weather events to increase in frequency and intensity, which will pose potential threats to the survival and health of residents. Beijing is facing multiple challenges such as coping with climate change, urbanization, and population aging, which puts huge decision-making pressure on decision maker. However, few studies that systematically consider the health effects of climate change, urbanization, and population aging for China. Based on the distributed lag nonlinear model (DLNM) and 13 global climate models in the Coupled Model Intercomparison Project Phase 6 (CMIP6), this study obtained the temporal and spatial distribution of surface temperature through statistical downscaling methods, and comprehensively explored the independent and comprehensive effects of urbanization and population aging on the projection of future temperature-related cardiovascular disease (CVD) mortality in the context of climate and population change. The results showed that only improving urbanization can reduce future temperature-related CVD mortality by 1.7–18.3%, and only intensified aging can increase future temperature-related CVD mortality by 48.8–325.9%. Taking into account the improving urbanization and intensified aging, future temperature-related CVD mortality would increase by 44.1–256.6%, and the increase was slightly lower than that of only intensified aging. Therefore, the intensified aging was the biggest disadvantage in tackling climate change, which would obviously magnify the mortality risks of temperature-related CVD in the future. Although the advancement of urbanization would alleviate the adverse effects of the intensified aging population, the mitigation effects would be limited. Even so, Urbanization should be continued to reduce health risks for residents. These findings would contribute to formulate policies related to mitigate climate change and reduce baseline mortality rate (especially the elderly) in international mega-city - Beijing. In addition, relevant departments should improve the medical health care level and optimize the allocation of social resources to better cope with and adapt to climate change. [ABSTRACT FROM AUTHOR]

Treatment of diiron dithiolate complex, [(μ-SCH2)2CHC6H5]Fe2(CO)6(A), with one equivalent of bidentate phosphine-containing ligandN,N-bis(diphenylphosphine)butanamine [(Ph2P)2N-Bu-n] in refluxing xylene afforded the diphosphine-bridged complex [(μ-SCH2)2CHC6H5]Fe2(CO)4[(μ-PPh2)2N-Bu-n] (1) in high yield, while reaction ofAwith two equivalents of triphenylphosphine (PPh3) in the presence of decarbonylating agent Me3NO yielded the disubstituted complex [(μ-SCH2)2CHC6H5]Fe2(CO)4(PPh3)2(2) in low yield. Both complexes were characterized by spectroscopic methods and X-ray crystallography. In the solid state, two phosphines of (PPh2)2N-Bu-n bridge the two irons withcisbasal-basal conformation, while PPh3occupies an apical position of the square pyramidal geometries of each iron. The influence of coordination manner on the electrochemical properties of both complexes was investigated by cyclic voltammetry. [ABSTRACT FROM AUTHOR]

Skin is the largest organ in human body and works as biologically active barrier to provide critical preservation of body homeostasis. The skin is highly innervated by a plenitude of nerve fiber subpopulations, each carrying one or more neuronal mediators. Melanocyte itself also intimately contact with nerve fibers to form ‘synaptic-like structure’ and its functions may be directly regulated by the mediators contained in terminals of intra-epidermal nerve fibers. Clinical and biochemical studies have suggested that calcitonin gene-related peptide (CGRP) is involved in vitiligo skin. The present study was designed to investigate the effect of CGRP on epidermal melanocytes. After treatment with CGRP ranging from 0 to 500 ng/mL for 48 h, tyrosinase activity and melanogenesis were with little changes compared to treatment with medium only in B16F10 cells. Treatment with 500 ng/mL of CGRP cooperates with substance P (SP) (0.1–10 nM) to decrease tyrosinase activity and decrease melanin biosynthesis in B16F10 cells in a concentration-dependent manner. Furthermore, CGRP (8-37) antagonizes the synergistic effect of CGRP. The effect of CGRP on the cell apoptosis was examined. Treatments with 0–500 ng/mL of CGRP for 24 h, the expression levels of cleaved caspase-3, total caspase-3, cleaved caspase-9 and total caspase-9 were increased in a concentration-dependent manner. And 500 ng/mL of CGRP induced B16F10 cell apoptosis showed by TUNEL assay. In addition, Bax expression was up-regulated and Bcl-2 down-regulated in response to CGRP treatment. Hence, the Bax/Bcl-2 ratio was significantly increased. These in vitro observations indicate the pro-apoptotic impact of CGRP on B16F10 cell. [ABSTRACT FROM AUTHOR]

Reaction of the diiron propanedithiolate complex [ μ-(SCH)CHOCCH]Fe(CO) ( A) with bis-(diphenylphosphino)methane (dppm) in the presence of MeNO·2HO in MeCN yielded a mono-substituted complex [ μ-(SCH)CHOCCH]Fe(CO)( κ-dppm) ( 1), whereas in refluxing xylene gave a bridged complex [ μ-(SCH)CHOCCH]Fe(CO)( μ-dppm) ( 2). The structures of both complexes were fully characterized by spectroscopic methods and X-ray crystallography. In solid state, one phosphine atom of dppm in complex 1 occupies an apical position of the square pyramidal geometries of the Fe center or two phosphine atoms of dppm in complex 2 bridge two Fe centers in a cisoid dibasal conformation. The cyclic voltammograms of both complexes in the presence of HBF were investigated. [ABSTRACT FROM AUTHOR]

Aiming at the safety problems of trusted computing platform due to the Apps lack of trust, this paper presented a software identification distributing system, and introduced its function modules and workflow. Software identification acted as its safety carriers and authentication means, software behavior statement solved the problem of legitimacy and trust before distribution. It designed an authentication protocol to ensure the integrity of software during distribution, and provided a recommended strategies for choosing suitable software based on trustworthy behavior. Application examples demonstrate that the system has a higher research and practical value of enhancing the trustworthiness of the platform. [ABSTRACT FROM AUTHOR]

Reaction of the diiron propanedithiolate complex [μ-(SCH2)2CHO2CC6H5]Fe2(CO)6(A) with triphenylphosphine (PPh3) orcis-1,2-bis(diphenylphosphine)ethylene (cis-dppv) in the presence of one equivalent of Me3NO·2H2O yielded a mono-substituted complex [μ-(SCH2)2CHO2CC6H5]Fe2(CO)5(PPh3) (1) or an asymmetrically substituted complex [(μ-SCH2)2CHO2CC6H5]Fe2(CO)4(κ2-dppv) (2), respectively. The structures of both complexes were characterized by spectroscopic methods and X-ray crystallography. In the solid state, the PPh3ligand in1occupies an apical position of the square pyramidal geometries of the Fe2, while thecis-dppv in2coordinates Fe2 in an apical-basal manner. The electrochemistry of both complexes was investigated. The electron-withdrawing benzoate functionality on the bridgehead carbon of the propanedithiolate bridge shifts the oxidation and reduction potentials of1or2slightly. Both complexes can catalyze the reduction of protons from CF3COOH but with a higher efficiency for2. [ABSTRACT FROM AUTHOR]

A class of flavanone was found to improve melanogenesis in B16F10 mouse melanoma cell line, but little is known about its target. Herein we described the synthesis and bioevaluation of sixteen 3′,4′,7-trihydroxyflavanone analogues and further synthesized a novel fluorescent flavanone–BODIPY, which could improve melanogenesis in B16F10 cell line by selectively binding to its endoplasmic reticulum. The fluorescent flavanone–BODIPY was proved to be a valuable probe for studying the localization of intracellular flavanone on living cells. [ABSTRACT FROM AUTHOR]

Neuropeptide substance P (SP) and reactive oxygen species (ROS) have been demonstrated to play an important role in psychological stress-induced alteration of hair cycle, the underlying mechanism remains unknown. The present study aims to investigate possible contribution of SP and ROS in chronic restraint stress (CRS, a chronic psychological stress model) induced abnormal of hair cycle and induction of autophagy. Mouse CRS model was applied for 18 days with or without treatment antioxidant Tempol (a free radical scavenger) or SP receptor (NK1) antagonist (RP67580). After CRS procedure, hair growth cycle, oxidative stress markers and skin tissue autophagy levels were analyzed by ELISA or western blot. Our results revealed that CRS reduced body weight gain, distance of movement and times of standing, affected hair cycle by prolonging the telogen stage and delaying subsequent anagen and catagen stage. In addition, CRS resulted in increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and increase of autophagy markers (microtubule-associated proteins, light chain 3-II, LC3-II, and Beclin-1) in mice skin. Treatment with Tempol restored GSH-Px activity, and significantly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, as well as normalized hair cycle. In addition; RP67580 also restored SOD and GSH-Px activities, and markedly reduced increases of lipid peroxidation levels and LC3-II and Beclin-1 expressions, and normalized hair cycle. Our study provides the first strong evidence for SP and ROS play a role not only in alteration of hair cycle but also in induction of autophagy in psychological stress model, suggesting autophagy may contribute to psychological stress-induced abnormal of hair cycle. [ABSTRACT FROM AUTHOR]

Aims Luteolin is a falconoid compound that has an antioxidant effect, but its contribution to ROS-activated MAPK pathways in ischemia/reperfusion injury is seldom reported. Here, we have confirmed that it exhibits an antioxidant effect in myocardial ischemia/reperfusion injury (MIRI) by inhibiting ROS-activated MAPK pathways. Main methods We exposed rat hearts into the left anterior descending coronary artery (LAD) ligation for 30 min followed by 1 h of reperfusion. Observations were carried out using electrocardiography; detection of hemodynamic parameters; and testing levels of lactate dehydrogenase (LDH), creatine kinase (CK), total superoxide dismutase (T-SOD), and malondialdehyde (MDA). Mitogen-activated protein kinase (MAPK) pathway was measured by western blot and transmission electron microscopy was applied to observe the myocardial ultrastructure. Rat H9c2 cell in 95% N 2 and 5% CO 2 stimulated the MIRI. Oxidation system mRNA levels were measured by real-time PCR; mitochondrial membrane potential and apoptosis were measured by confocal microscopy and flow cytometry; western blot analysis was used to assay caspase-3, -8, and -9 and MAPK pathway protein expression; the MAPK pathway was inhibited using SB203580 (p38 MAPK inhibitor) and SP600125 (c-Jun NH 2 -terminal kinase inhibitor) before H9c2 cells were exposed to hypoxia/reoxygenation injury to show the modulation of the changes in ROS generation, cell viability and apoptosis. Key findings In vivo, luteolin can ameliorate the impaired mitochondrial morphology, regulating the MAPK pathway to protect MIRI. In vitro, luteolin can affect the oxidation system, mitochondrial membrane potential and MAPK pathway to anti-apoptosis. Significance These results reveal a ROS–MAPK mediated mechanism and mitochondrial pathway through which luteolin can protect myocardial ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

A novel sense amplifier is proposed to be suitable for the Multiple Time Programmable Nonvolatile Memory (MTP-NVM) of passive Radio-Frequency Identification (RFID). The circuit has superior performance such as low-power, high speed, reliability and highly sensitive without extra area overhead. The simulation based on GSMC 0.13μm-CMOS process shows that the new sense amplifier has high read speed and can work at low voltages (0.8V). When the voltage is 1.2V and the temperature is 27℃, the read delay is 10.5ns, the power consumption is 6.1μW@25MHz and the current difference it can identify accurately is about 33 nA. [ABSTRACT FROM AUTHOR]

Aims Lipid metabolic disorder involves multiple tissues and organs. Hepatic cholesterol metabolism is an important physiological process, which is tightly related to obesity and lipid metabolic disorders. In this study, we examined the direct effects of adipocytes on hepatic cholesterol metabolic factors and investigated the role of potential adipocytokines in it. Main methods Male SD rats were induced by a high-fat diet (HFD) and hepatic cholesterol metabolic factors, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) and ATP-binding cassette transporter A1 (ABCA1) were measured by immunoblotting. Then the effects of adipocytes on the expressions of hepatic cholesterol metabolism proteins were examined in the co-culture system. Finally, the concentrations of several adipocytokines were detected by ELISA and the effect of adiponectin (APN) on hepatic cholesterol metabolism was confirmed by short interference RNA (siRNA) in vitro. Key findings Our results showed that adipocytes significantly increased ABCA1 and decreased HMGR in hepatocytes after co-culture. Lipopolysaccharide (LPS) treatment in this co-culture system reversed cholesterol metabolism compared with the untreated group. APN, which also decreased in obese rats, had a significant positive correlation with ABCA1 and inversed correlation with HMGR in vitro. Co-culturing with APN-silenced adipocytes partially restored ABCA1 and HMGR levels. Significance The present study demonstrates that adipocytes regulate hepatic cholesterol metabolism partly via APN. [ABSTRACT FROM AUTHOR]

Reaction of the diiron propanedithiolate complex [ μ-(SCH)CHCH]Fe(CO) ( A) with 1,3-bis(diphenylphosphine)propane (dppp) in refluxing xylene yielded a chelated complex [( μ-SCH)CHCH]Fe(CO)(κ-dppp) ( 1) and a bridged isomer [( μ-SCH)CHCH]Fe(CO)( μ-dppp) ( 2), while in refluxing toluene or in hot MeCN in the presence of MeNO·2HO gave the chelated isomer 1 as the major or sole product. Protonation of complex 1 upon addition of HBF·EtO gave a bridging hydride ( μ-H)[( μ-SCH)CHCH]Fe(CO)(κ-dppp)(BF) ( 3). The structures of all complexes were fully characterized by spectroscopic methods and for complexes 1 and 2 by X-ray crystallography. In the solid state, the chelated complex adopts an apical-basal diphosphine arrangement and exhibits a six-membered ring in approximate chair conformation. The bridged isomer presents an expected cisoid dibasal geometry and the bond length of Fe-Fe is longer than that in chelated isomer, reaching to 2.61 Ǻ. The electrochemical investigation of both isomers in MeCN-[NBu][PF] in the presence of HBF showed that the catalytic efficiency of the bridged isomer is no less than that of the chelated isomer but better than that of the analogue [( μ-SCH)CHCH]Fe(CO)( μ-dppm). Interestingly, isomer 1 was converted to isomer 2 in refluxing xylene. An electron-transfer-catalyzed isomerization between one isomer and the other was not observed. [ABSTRACT FROM AUTHOR]

Forty β-elemene derivatives were prepared and their antioxidant activity in H 2 O 2 -treated human umbilical vein endothelial cells (HUVECs) was first investigated. Among which, the dimer compounds 5r and 5s exhibited the most potent antioxidant activity against reactive oxygen species production. Meanwhile, 5r and 5s led to a significant increase in superoxide dismutase and nitric oxide levels and decrease in malonyldialdehyde and lactate dehydrogenase contents. Furthermore, MTT assay showed that 5r and 5s did not produce obvious cytotoxicity and had significantly cytoprotective effects against oxidative damage on HUVECs. [ABSTRACT FROM AUTHOR]

A correction for the article "Characteristics of the Gut Microbiota and Metabolism in Patients With Latent Autoimmune Diabetes in Adults: A Case-Control Study" is presented, which is published in the previous issue of the periodical.

Chronic stress can affect skin function, and some skin diseases might be triggered or aggravated by stress. Stress can activate the central hypothalamic–pituitary–adrenocortical (HPA) axis, which causes glucocorticoid levels to increase. The skin has HPA axis elements that react to environmental stressors to regulate skin functions, such as melanogenesis. This study explores the mechanism whereby chronic stress affects skin pigmentation, focusing on the HPA axis, and investigates the role of glucocorticoids in this pathway. We exposed C57BL/6 male mice to two types of chronic stress, chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS). Mice subjected to either stress condition showed reduced melanogenesis. Interestingly, CRS and CUMS triggered reductions in the mRNA expression levels of key factors involved in the HPA axis in the skin. In mice administered corticosterone, decreased melanin synthesis and reduced expression of HPA axis elements were observed. The reduced expression of HPA axis elements and melanogenesis in the skin of stressed mice were reversed by RU486 (a glucocorticoid receptor antagonist) treatment. Glucocorticoids had no significant inhibitory effect on melanogenesis in vitro. These results suggest that, high levels of serum corticosterone induced by chronic stress can reduce the expression of elements of the skin HPA axis by glucocorticoid-dependent negative feedback. These activities can eventually result in decreased skin pigmentation. Our findings raise the possibility that chronic stress could be a risk factor for depigmentation by disrupting the cutaneous HPA axis and should prompt dermatologists to exercise more caution when using glucocorticoids for treatment. [ABSTRACT FROM AUTHOR]

Highlights: [•] Interleukin-6 receptor’s (IL-6R) functional organization is explained. [•] The signal transduction of interleukin-6 within hepatocytes is reviewed. [•] IL-6 as pro-inflammatory cytokine is evaluated in hepatic lipid disorders. [•] IL-6’s role in positively regulating hepatic lipids is analyzed. [•] Factors affecting IL-6 behavior in hepatic lipid regulation are discussed. [Copyright &y& Elsevier]

Steroidogenic factor 1 (SF-1), a transcriptional factor essential for estrogen biosynthesis, is undetectable in endometrial stromal cells and aberrantly expressed in endometriotic stromal cells. [ABSTRACT FROM PUBLISHER]

Peganum harmala L is an important medicinal plant that has been used from ancient time due to its alkaloids rich of ß-carbolines. Harmane is a naturally occurring ß-carboline extracted from Peganum harmala L, that exhibits a wide range of biological, psychopharmacological, and toxicological actions. The synthesis of novel derivatives with high anti-cancer activity and less side effects is necessary. In the present study, B-9-3—a semi-synthetic compound that is formed of two harmane molecules bound by a butyl group—showed a strong anti-cancer activity against a human lung cancer cell line, a human breast cancer cell line, and a human colorectal carcinoma cell line. B-9-3 anti-proliferative effect followed a similar pattern in the three cell lines. This pattern includes a dose-dependent induction of apoptosis, or necroptosis as confirmed by Hoechst staining, flow cytometry and western blot analyses, and the inhibition of cancer cells migration that was shown to be dependent on the drug׳s concentration as well. Moreover, B-9-3 inhibited tube formation in human umbilical vascular endothelial cell line (HUVEC), which indicates an anti-angiogenesis activity in vitro. In summary, B-9-3, a semi-synthetic derivative of ß-carboline, has an anti-proliferative effect against tumor cells via induction of apoptosis and inhibition of cell migration. [ABSTRACT FROM AUTHOR]

Abstract: Background: Interleukin-33 (IL-33) was recently recognized as a member of the IL-1 cytokine family. The triggers no matter environmental or endogenous that provoke IL-33 cellular release may be associated with inflammation, infection or tissue damage. However, to date, the regulatory role of IL-33 in the control of melanogenesis has not been elucidated. Objective: The present study was designed to investigate the effect of IL-33 on melanogenesis and to explore its underlying mechanisms. Methods: Melanocytes were exposed to IL-33. Then cell viabilities were measured by MTT assay. The improving activities of IL-33 were examined by melanin synthesis, tyrosinase (TYR) activity assay. The expressions of relative proteins were assessed by Western blotting. Results: IL-33 increased the TYR activity and melanin content in a dosage-dependent manner at concentrations of 1–10ng/ml. Treatment with 10ng/ml of IL-33 enhanced the expression of microphthalmia-associated transcription factor (MITF), TYR, tyrosinase-related protein 1 (TRP-1) and dopachrome tautomerase (DCT) in normal human foreskin-derived epidermal melanocytes (NHEM). Furthermore, IL-33 could remarkably promote the phosphorylation levels of p38 mitogen-activated protein kinases (MAPKs) and cyclic AMP-responsive element-binding protein (CREB). This pro-melanogenic effect could be partially reversed by the pre-treatment with the special p38 MAPK inhibitor, SB203580, and protein kinase A (PKA) inhibitor, H89. Conclusions: Our results collectively indicated that IL-33 improved melanin biosynthesis in NHEM. This function might be attributed to the fact that IL-33 stimulates the phosphorylation of p38 MAPK and CREB, increases the TYR, TRP-1 and DCT expression through MITF, finally resulting in the augment of melanogenesis. [Copyright &y& Elsevier]

Stress has been reported to induce alterations of skin pigmentary response. Acute stress is associated with increased turnover of serotonin (5-hydroxytryptamine; 5-HT) whereas chronic stress causes a decrease. 5-HT receptors have been detected in pigment cells, indicating their role in skin pigmentation. To ascertain the precise role of 5-HT in stress-induced pigmentary responses, C57BL/6 mice were subjected to chronic restraint stress and chronic unpredictable mild stress (CRS and CUMS, two models of chronic stress) for 21 days, finally resulting in abnormal pigmentary responses. Subsequently, stressed mice were characterized by the absence of a black pigment in dorsal coat. The down-regulation of tyrosinase (TYR) and tyrosinase-related proteins (TRP1 and TRP2) expression in stressed skin was accompanied by reduced levels of 5-HT and decreased expression of 5-HT receptor (5-HTR) system. In both murine B16F10 melanoma cells and normal human melanocytes (NHMCs), 5-HT had a stimulatory effect on melanin production, dendricity and migration. When treated with 5-HT in cultured hair follicles (HFs), the increased expression of melanogenesis-related genes and the activation of 5-HT1A, 1B and 7 receptors also occurred. The serum obtained from stressed mice showed significantly decreased tyrosinase activity in NHMCs compared to that from nonstressed mice. The decrease in tyrosinase activity was further augmented in the presence of 5-HTR1A, 1B and 7 antagonists, WAY100635, SB216641 and SB269970. In vivo, stressed mice received 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), a member of the class of selective serotonin reuptake inhibitors (fluoxetine; FX) and 5-HTR1A/1B agonists (8-OH-DPAT/CP94253), finally contributing to the normalization of pigmentary responses. Taken together, these data strongly suggest that the serotoninergic system plays an important role in the regulation of stress-induced depigmentation, which can be mediated by 5-HT1A/1B receptors. 5-HT and 5-HTR1A/1B may constitute novel targets for therapy of skin hypopigmentation disorders, especially those worsened with stress. [ABSTRACT FROM AUTHOR]

Highlights: [•] A novel fluorescein E-DNA biosensor was developed. [•] Gold nanoparticles were electrodeposited onto bare gold electrode surfaces. [•] Once hybridized with target DNA, electro-signal was changed. [•] The adsorption effect of nanogold enhanced the sensitivity of the sensor. [ABSTRACT FROM AUTHOR]

Successful mouse embryo implantation requires a receptive uterus and an activated blastocyst. A large number of genes, cytokines, and other factors are involved in the process. MicroRNAs (miRNAs) regulate the expression of many genes, and previous studies have investigated the relationship between miRNA expression and embryo implantation. In this study, we show that mmu-microRNA-200a (mmu-miR-200a) is expressed in a spatiatemporal manner during implantation in mouse uterus and found that phosphatase and tensin homolog (PTEN), SON, and programmed cell death 4 (Pdcd4) are the target genes of mmu-miR-200a by bioinformatics analysis. In vitro gain and loss of function experiments confirm that PTEN, a critical gene for cell proliferation and apoptosis, is the target gene of mmu-miR-200a. Our experiments also show that injection of the uterine horn with mmu-miR-200a lentivirus leads to a decreased implantation rate. Collectively, our results suggest that mmu-miR-200a affects embryo implantation by regulating PTEN protein expression. Thus, clarifying the physiological functions of uterine miRNAs will help to elucidate the embryo implantation process and may even contribute to curing infertility and inventing new contraceptives. [ABSTRACT FROM PUBLISHER]

A new binuclear zinc complex, namely [Zn(Salpn)4(1,3-btp)]n(1, H2salpn = N,N′- bis(salicylidene)-1,3-diaminopropane, while 1,3- btp = 1,3-bis (triazole) propane) has been synthesized under one-pot reaction conditions in high yield, and has been characterized by elemental analysis, IR spectroscopy, and single-crystal X-ray diffraction. The complex 1 crystallizes in the monoclinic system, space group ofC2/cwitha= 18.2270(17),b= 10.7435(10),c= 20.2896(19) Å,β= 92.9780(10)°. The two adjacent zinc-Salpn moieties were connected through the flexible 1,3-btp ligand into a binuclear unit. The bulk purity of the materials of 1 was confirmed through the powder X-ray diffraction (PXRD) experiments. Furthermore, the luminescent property of the complex 1 has also been investigated. Supplemental materials are available for this article. Go to the publisher's online edition ofSynthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal Chemistryto view the supplemental file. [ABSTRACT FROM AUTHOR]

We investigated the characteristics and sources of volatile organic compounds (VOCs) at a regional background station on the North China Plain from 12 October to 31 December 2017. This study is unique in that emission sources of VOCs and their influence on ozone formation were identified for the first time at a regional background site in North China. The average total mixing ratio of VOCs was 16.0 ± 10.0 ppbv before the heating period (NHP, 12 October to 14 November), and this value was 43% higher than that during the heating period (HP, November 15 to 31 December). Alkanes were the dominant contributors to total VOCs and ranged from 59.9% to 67.1% during the HP and NHP. Relative humidity (RH) and temperature (T) dependence were observed before the HP, and high VOC mixing ratios were observed at relatively low T (−4 °C to 5 °C) and high RH (>60%) conditions and medium T (5 °C < T < 14 °C) and low RH (< 60%) conditions. High mixing ratios of VOCs were observed under RH > 55% and T < −1 °C conditions during the HP. Through bivariate polar plots, medium or low mixing ratios of total VOCs (TVOCs) were found at low wind speeds (<2 m s−1) before the HP, whereas a high mixing ratio was found during the HP, highlighting the important role of local source emissions during the HP. In addition, southwest winds at high wind speeds (>4 m s−1) were essential for the regional transport of pollutants. The contributions of alkenes to L OH (OH radical loss rate) and OFP (ozone formation potential) before and during the HP were as high as 48.8%–62.9% and 49.7% -64.4%, respectively. The OFP and L OH of ethene presented higher levels before and during the HP, elucidating the significant role of alkenes in the formation of O 3 at SDZ site. Four emission sources of VOCs, including coal burning, liquefied petroleum gas (LPG) and natural gas (NG) usage, vehicular emissions and gasoline evaporation, were resolved using a positive matrix factorization (PMF) model, with contributions of 45.4%, 15.8%, 23.4% and 15.4%, respectively. The concentration weighted trajectory (CWT) analysis indicated that the main potential source regions were located to the south and southwest of Shangdianzi (SDZ) before the HP, and they were characterized by a narrow pollution band along Hengshui-Baoding-Langfang-Beijing. High CWT values were primarily distributed in a small region in southern SDZ during the HP, emphasizing the role of local emissions and transport from surrounding regions, especially urban areas of Beijing. [Display omitted] • Characteristics and sources of VOC were investigated at a regional background site. • Alkenes played a significant role on the formation of O 3. • Coal burning and vehicular emissions were the dominant VOC sources. • The CWT analysis indicated the regional transportation from southwestern. [ABSTRACT FROM AUTHOR]

The five-level active neutral-point (NP)-clamped (ANPC) converter is a newly emerging topology which can overcome the drawbacks of traditional NP-clamped and flying-capacitor multilevel converters. This paper presents a comprehensive theoretical analysis of the NP potential balancing issue and demonstrates that the NP potential can be naturally balanced under ideal and steady conditions. An NP potential balancing method based on zero-sequence voltage injection is presented. By calculating the average NP currents of all key zero-sequence voltages, the most appropriate zero-sequence voltage is selected to generate the demanded NP current, which can also limit the switching frequency of the series-connected insulated-gate bipolar transistors to the fundamental frequency. A three-phase five-level ANPC inverter prototype is built up, and both steady and dynamic experimental results are presented to verify the validity of this method. [ABSTRACT FROM PUBLISHER]

Background. Hypoxia up-regulated expression of tissue factor (TF) may facilitate tumor cell metastasis, but transcriptional mechanisms remain undefined. Material and methods. To verify the role of Egr-1 in hypoxia-induced TF expression in breast cancer cells, quantitative PCR and Western blot analysis were performed. The secretion of VEGF under hypoxia was detected by enzyme-linked immunosorbent assay (ELISA). Egr-1 and HIF-1α siRNA were transiently transfected into breast cancer cells to evaluate their specific roles. Results. The increased Egr-1 expression occurring in hypoxic breast cancer cells can up-regulate TF expression and stimulating protein 1(Sp1) was not responsible for the hypoxia-induced expression of TF. HIF-1α mediated the hypoxia-induced up-regulation of TF expression through vascular endothelial growth factor (VEGF). The regulatory effects of Egr-1 on TF under hypoxia were independent of HIF-1α. Either Egr-1 or HIF-1α was responsible for hypoxic induction of tumor cells adhesion. HIF-1α, but not Egr-1, had a pivotal role in human breast cancer cells invasion. Both Egr-1 and HIF-1α were critical to angiogenesis induced by hypoxic conditions in MDA-MB-231 and HUVEC co-cultures. In nude mice, both Egr-1 and HIF-1α small interfering RNA (siRNA) could decrease extravasation of MDA-MB-435 cells in the lung after tail vein injection. Conclusions. Hypoxia-induced expression of TF in human breast cancer cells depends on Egr-1 and HIF-1α, and both of these proteins may play an important role in breast cancer metastasis, either directly or indirectly through the TF pathway. [ABSTRACT FROM AUTHOR]

Background. Hypoxia up-regulated expression of tissue factor (TF) may facilitate tumor cell metastasis, but transcriptional mechanisms remain undefined. Material and methods. To verify the role of Egr-1 in hypoxia-induced TF expression in breast cancer cells, quantitative PCR and Western blot analysis were performed. The secretion of VEGF under hypoxia was detected by enzyme-linked immunosorbent assay (ELISA). Egr-1 and HIF-1α siRNA were transiently transfected into breast cancer cells to evaluate their specific roles. Results. The increased Egr-1 expression occurring in hypoxic breast cancer cells can up-regulate TF expression and stimulating protein 1(Sp1) was not responsible for the hypoxia-induced expression of TF. HIF-1α mediated the hypoxia-induced up-regulation of TF expression through vascular endothelial growth factor (VEGF). The regulatory effects of Egr-1 on TF under hypoxia were independent of HIF-1α. Either Egr-1 or HIF-1α was responsible for hypoxic induction of tumor cells adhesion. HIF-1α, but not Egr-1, had a pivotal role in human breast cancer cells invasion. Both Egr-1 and HIF-1α were critical to angiogenesis induced by hypoxic conditions in MDA-MB-231 and HUVEC co-cultures. In nude mice, both Egr-1 and HIF-1α small interfering RNA (siRNA) could decrease extravasation of MDA-MB-435 cells in the lung after tail vein injection. Conclusions. Hypoxia-induced expression of TF in human breast cancer cells depends on Egr-1 and HIF-1α, and both of these proteins may play an important role in breast cancer metastasis, either directly or indirectly through the TF pathway. [ABSTRACT FROM AUTHOR]

Backgrounds: Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP) mediated immune response, the role of reactive oxygen species (ROS) in brain-skin-axis regulation system remains unknown. Objectives: The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress) which induced abnormal of hair cycle. Methods and Results: Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in CRS mice skin. In addition, SP receptor antagonist (RP67580) reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation. Conclusions: Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss. [ABSTRACT FROM AUTHOR]

Abstract: The reactions in mixtures of water–ethanol between lanthanide salts and nitrogen N-hetrocyclic carboxylic acid, in the presence of ammonium oxalate, result in two interesting lanthanide–organic coordination polymers, formulated as, {[Sm4(Hmimda)4(μ4-C2O4)2·6H2O]·8H2O} i (1), [Eu4(Hmimda)4(μ4-C2O4)2·6H2O]·4H2O} n (2), (H3mimda=1H-2-methyl-4, 5-imidazole-dicarboxylic acid). The polymers 1 and 2 are isostructural, and are both built from zig-zag 1D chains constructed from Ln-Hmimda moieties bridged by oxalate, as the secondary building unit (SBU). The Hmimda ligand further is interconnected the 1D chains to form the 3D framework. Variable-temperature magnetic susceptibility measurements indicate that the μ4-k 4 O bridging fashion of oxalate results in the possible antiferromagnetic interactions occurring between the adjacent lanthanide(III) centers. The photo-luminescent and thermalgravimetric analyses of the polymers were also determined. [Copyright &y& Elsevier]

ABSTRACT The effects of n-propyl gallate ( nPG) on postharvest ripening of tomato have been studied. Mature green (MG) stage tomatoes were harvest and treated with 0.5 mM nPG at 25 ± 1C for 12 h. Following the nPG treatment, fruit ripening was delayed by at least 7 days. Cyanide-resistant respiration and ethylene production were suppressed significantly at the first 7 days. nPG treatment decreased levels of H2O2 and increased activities of antioxidant enzymes and chemicals, particularly for superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (GPX) and ascorbic acid (AsA). The decreases of flesh firmness and total chlorophylls were inhibited, and the production of soluble sugars and lycopene were suppressed by nPG either. Alternative oxidase (AOX) and cyanide-resistant respiration play important roles in fruit climacteric and may be correlated with system 2 ethylene production. nPG could be used as an efficient inhibitor to tomato fruit ripening. PRACTICAL APPLICATIONS Control of fruit ripening is of enormous commercial importance. Generally, tomato fruit ripening is controlled through the use of gas, temperature and humidity control. This research has focused on the application of n-propyl gallate ( nPG) on postharvest ripening of tomato fruit. The results of the study have implied that nPG treatment could obviously prolong the shelf life and keep the postharvest quality of tomato fruits, and the firmness loss, respiration rate and ethylene production could be better suppressed compared with the control fruits, which shows that nPG is a potentially effective and safe inhibitor for climacteric fruits ripening, such as tomato. Utilization of the results of this research is likely to benefit for the storage technological improvement. [ABSTRACT FROM AUTHOR]

The additional eddy loss in the solid strand of the formed coil is an important part of windings copper loss in the superpower direct drive permanent magnetic synchronous motor (PMSM). This eddy loss produces due to the uneven leakage magnetic field in the stator slot region. The traditional windings transposition technology is difficultly applied to the multi-turn and less-strand formed coil, because of the limited slot fill factor. Therefore, aiming to reduce the additional eddy loss, this paper proposes a new end windings transposition technology and it was used in a 2 MW low-speed and high-torque multi-unit PMSM prototype. The additional eddy loss inhibitory excellent effect is verified by finite element analysis. It should be emphasized that this technology can be directly used in the permanent magnetic direct drive wind generator. [ABSTRACT FROM PUBLISHER]

In this letter, asymmetric simple exclusion processes with off-ramp on the boundaries have been studied by asymmetric simple exclusion processes (ASEPs). In this model, particles can only detach from a single off-ramp on the boundaries of the system. The phase diagrams and density profiles are calculated by approximate mean field theory and have shown good agreement with the extensive Monte Carlo computer simulations. [ABSTRACT FROM AUTHOR]

Abstract: Colchicine is an alkaloid that has been widely used to treat gout. It also has a curative effect on cancer. Although many studies have shown that its effect on cell apoptosis was mediated by the activation of caspase-3, the pathways involved in the process remained obscure. Here we show some evidence regarding the missing information using human normal liver cells L-02 in our study. The effect of colchicine on apoptosis in L-02 cells and the apoptosis-associated signaling pathways were determined using different tests including cell viability assay, Annexin V and propidium idodide binding, PI staining, Hoechst 33342 staining, mitochondrial membrane potential assay, caspase activity assay and Western blot analysis. We found that colchicine-induced a dose-dependent drop of cell viability in L-02 cells; early apoptosis happened when cells were treated with 0.1μM of colchicine. The colchicine-induced loss of mitochondrial membrane potential, activation of caspase-3 and 9, up-regulation of Bax and down-regulation of Bcl-2 showed an evidence for the colchicine activity on apoptosis, at least, by acting via the intrinsic apoptotic pathway. [Copyright &y& Elsevier]

Abstract: A unique lanthanide coordination polymer, formulated as {[Pr3(Heimda)2(μ 2-HCOO) (μ 2-C2O4)2·5H2O]}n (H3eimda=2-ethyl-1H‐imidazole‐4,5‐dicarboxylic acid, H2C2O4 =oxalic acid) (1), has been hydrothermally synthesized by using lanthanide(III) nitrate, H3eimda acid at the presence of two kinds of carboxylate as coligands. The polymer was characterized by elements analysis, IR spectroscopy, thermogravimetry, variable-temperature magnetic susceptibility and single‐crystal X-ray diffraction study. Polymer 1 possesses three-dimensional (3-D) framework with Pcu topology, containing the original 1D zig-zag chain composed of [Pr-HCOO]2+ moieties. Variable temperature magnetic susceptibility measurements indicate that depopulation of the Stark levels or possible antiferromagnetic interactions within polymer 1 leads to the continuous decrease of χ M T when the samples are cooled from 300 to 2K, and the photoluminescence properties of polymer 1 were also investigated. [Copyright &y& Elsevier]

This paper studies the exciton--longitudinal-optical-phonon coupling in InGaN/GaN single quantum wells with various cap layer thicknesses by low temperature photoluminescence (PL) measurements. With increasing cap layer thickness, the PL peak energy shifts to lower energy and the coupling strength between the exciton and longitudinal-optical (LO) phonon, described by Huang--Rhys factor, increases remarkably due to an enhancement of the internal electric field. With increasing excitation intensity, the zero-phonon peak shows a blueshift and the Huang--Rhys factor decreases. These results reveal that there is a large built-in electric field in the well layer and the exciton--LO-phonon coupling is strongly affected by the thickness of the cap layer. [ABSTRACT FROM AUTHOR]

Abstract: A novel 3d–4f heterometallic coordination polymer, namely, {[Sm2(PBDA)2·2H2O][Zn2(PBDA)2(Cl)2]}n (1), (H2PBDA=3 -(pyridin-3-yl-oxy) benzene −1,2-dicarboxylic acid) has been hydrothermally synthesized by using samarium(III) nitrate, H2PBDA acid and zinc chloride as raw materials, and characterized by elemental analysis, FT-IR, TG analysis and single crystal X-ray diffraction. Polymer 1 possesses two-dimensional (2D) network containing the original 1D heterometallic chain composed of [Sm2Zn2(PBDA)2] moieties. Variable temperature magnetic susceptibility studies reveal that 1 displays possible weak antiferromagnetic coupling between the neighboring Sm(III) ions, and the photoluminescent properties of polymer 1 as well as free H2PBDA ligand were also investigated. [Copyright &y& Elsevier]

Abstract: Genetic and physiological studies have revealed evidence for multiple signaling pathways by which the plastid exerts retrograde control over photosynthesis associated nuclear genes (PhANGs). It has been proposed that the tetrapyrrole pathway intermediate Mg-protoporphyrin IX (Mg-proto IX) acts as the signaling molecule in the pathways and accumulates in the chloroplasts and cytosol of the cell after treatment with the herbicide Norflurazon (NF). However, the role of Mg-Proto IX in plastid signaling has been challenged by two recent reports. In this paper, new evidence is presented supporting Mg-Proto IX as a plastid-signaling molecule in mature Arabidopsis seedlings. Fluorescence HPLC and confocal microscope observation verified that a short-term (<96h) NF treatment resulted in a large accumulation of Mg-Proto IX accompanying with Lhcb repression, whereas the long-term NF treatments caused marked changes of tetrapyrrole pools, while Lhcb expression was continuously repressed. These results may explain the discrepancies among different reports. Reactive oxygen species (ROS) eliminator treatments only partly reversed the NF-induced repression of Lhcb. Therefore, the NF generates both ROS signals and Mg-Proto IX signals. Furthermore, our data suggested that plastid signal transduction through plastid GUN1 protein is independent of tetrapyrrole export from the plastid. [Copyright &y& Elsevier]

Abstract: Three water-soluble dicobalt(III) complexes, [Co2 L 2(µ-OH)2](ClO4)2·5H2O (1), [Co2 L 2(µ-OH)2](ClO4)2·CH3OH·H2O(2); [Co2 L 2(µ-OH)2](ClO4)2·4H2O(3) (L =1,4,7-triazacyclononane-N-acetate monoanion), were prepared to serve as nuclease mimics. The complexes were characterized by X-ray, IR and UV–vis spectroscopy as well as ESI-MS. Three complexes exhibit similar structures, just with different solvent molecules. The electrospray mass spectrum of 1 in solution indicates that dinuclear ion [Co2 L 2(µ-OH)2-H+] + (4) is the active species. In the absence of any reducing agent, the complexes cleave plasmid pBR322 DNA was performed and its hydrolytic mechanism was demonstrated with radical scavengers, anaerobic reaction and T4 ligase. The kinetic aspects of DNA cleavage under pseudo- or true-Michaelis–Menten conditions are also detailed, kinetic parameters (k cat, K M) were calculated to be 3.57h−1, 6.92×10−4 M; 0.28h−1, 1.9×10−5 M for 4, respectively. [Copyright &y& Elsevier]

In this work, a chloro-bridged trinuclear copper complex {[Cu(bpea)Cl]2CuCl4} (1) (bpea = N,N-bis(2-pyridylmethyl)ethylamine) has been synthesized and structurally characterized. In 1, two mononuclear [Cu(bpea)Cl]+ are linked by one [image omitted], generating a sandwich-like trinuclear unit. A crystallographic C2 axis passes through the Cu of the connecting [image omitted]. Susceptibility data of 1 indicate weak intratrimer ferromagnetic coupling with J = 5.16 cm-1. Elemental analysis, infrared, UV spectra, and electrochemistry of the complex were also determined. [ABSTRACT FROM AUTHOR]

Abstract: It has been proven that isoliquiritigenin could inhibit the proliferation of some kinds of cancer cell lines and has a strong antioxidative activity. The purpose of this study is to investigate whether the antioxidant isoliquiritigenin affects the proliferation and redifferentiation in HL-60 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) colorimetric method and trypan blue staining were used to measure cell proliferentiation and survival. The morphological changes, nitroblue tetrazolium chloride (NBT) reductive activity, and the CD11b and CD14 surface antigens were used as the biomarkers of redifferentiation of HL-60 cells. The intracellular reactive oxygen species (iROS) level was detected by a fluorescent probe, 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA). Isoliquiritigenin (ISL) inhibited the cell proliferation and decreased the iROS levels in a dose-dependent manner, while the treatment did not increase the lethality rate. After 72 h treatment with 10 μg/ml ISL, a typical differentiated morphology was observed in HL-60 cells, including the decrease of karyoplasmic ratio and the increase of kidney-shape nuclear cells. The positive rate (%) of CD11b (26.4±3.90 vs 7.70±1.04, P <0.01) and CD14 (20.4±2.30 vs 2.63±0.133, P <0.01) cells increased significantly. The NBT reductive activity increased 2.3-fold as compared to that of the control group. As an antioxidant, ISL decreased the iROS formation in a dose-dependent manner. All the results indicate that the antioxidant ISL is able to induce the monocytic differentiation in leukemia cells. ISL has the potential as a drug to cure leukemia with fewer side effects. [Copyright &y& Elsevier]

Abstract: Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heterocycle amine-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, synthesized and evaluated as multiple targets agents in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds inhibited c-Src and iNOS well. The best compound 8 inhibited both enzymes with the IC50 values of 34.8nM and 26.7μM. Several compounds also showed moderate anti-proliferation at 10μM against colon and liver cancer cell lines. [Copyright &y& Elsevier]

Depression is the most frequent affective disorder and is the leading cause of disability worldwide. In order to screen antidepressants and explore molecular mechanisms, a variety of animal models were used in experiments, but there is no reliable high-throughput screening method. Zebrafish is a common model organism for mental illness such as depression. In our research, we established chronic unpredictable mild stress (CUMS) models in C57BL/6 mice and zebrafish; the similarities in behavior and pathology suggest that zebrafish can replace rodents as high-throughput screening organisms. Stress mice (ip., 1 mg/kg/d, 3 days) and zebrafish (10 mg/L, 20 min) were treated with reserpine. As a result, reserpine caused depression-like behavior in mice, which was consistent with the results of the CUMS mice model. Additionally, reserpine reduced the locomotor ability and exploratory behavior of zebrafish, which was consistent with the results of the CUMS zebrafish model. Further analysis of the metabolic differences showed that the reserpine-induced zebrafish depression model was similar to the reserpine mice model and the CUMS mice model in the tyrosine metabolism pathway. The above results showed that the reserpine-induced depression zebrafish model was similar to the CUMS model from phenotype to internal metabolic changes and can replace the CUMS model for antidepressants screening. Moreover, the results from this model were obtained in a short time, which can shorten the cycle of drug screening and achieve high-throughput screening. Therefore, we believe it is a reliable high-throughput screening model. [ABSTRACT FROM AUTHOR]

Unprecedented travel restrictions due to the COVID-19 pandemic caused remarkable reductions in anthropogenic emissions, however, the Beijing area still experienced extreme haze pollution even under the strict COVID-19 controls. Generalized Additive Models (GAM) were developed with respect to inter-annual variations, seasonal cycles, holiday effects, diurnal profile, and the non-linear influences of meteorological factors to quantitatively differentiate the lockdown effects and meteorology impacts on concentrations of nitrogen dioxide (NO 2) and fine particulate matters (PM 2.5) at 34 sites in the Beijing area. The results revealed that lockdown measures caused large reductions while meteorology offset a large fraction of the decrease in surface concentrations. GAM estimates showed that in February, the control measures led to average NO 2 reductions of 19 μg/m3 and average PM 2.5 reductions of 12 μg/m3. At the same time, meteorology was estimated to contribute about 12 μg/m3 increase in NO 2 , thereby offsetting most of the reductions as well as an increase of 30 μg/m3 in PM 2.5 , thereby resulting in concentrations higher than the average PM 2.5 concentrations during the lockdown. At the beginning of the lockdown period, the boundary layer height was the dominant factor contributing to a 17% increase in NO 2 while humid condition was the dominant factor for PM 2.5 concentrations leading to an increase of 65% relative to the baseline level. Estimated NO 2 emissions declined by 42% at the start of the lockdown, after which the emissions gradually increased with the increase of traffic volumes. The diurnal patterns from the models showed that the peak of vehicular traffic occurred from about 12pm to 5pm daily during the strictest control periods. This study provides insights for quantifying the changes in air quality due to the lockdowns by accounting for meteorological variability and providing a reference in evaluating the effectiveness of control measures, thereby contributing to air quality mitigation policies. [Display omitted] • Generalized Additive Models quantified lockdown and meteorology impacts on PM 2.5 and NO 2. • NO 2 decreased by 19 μg/m3 due to the lockdown which was offset by a 12 μg/m3 increase due to meteorology. • PM 2.5 decreased by 12 μg/m3 due to the lockdown which was offset by a 30 μg/m3 increase due to meteorology. • Changes in vertical mixing had the largest impact on NO 2 , and changes in humidity for PM 2.5. • Downtown Beijing experienced larger reductions that lasted longer compared with suburban areas. [ABSTRACT FROM AUTHOR]

Abstract: Because both c-Src and iNOS are key regulatory enzymes in tumorigenesis, a new series of 4-heteroarylamino-3-quinolinecarbonitriles as potent dual inhibitors of both enzymes were designed, prepared, and evaluated for blocking multiple signaling pathways in cancer therapy. All compounds were evaluated by two related enzyme inhibition assays and an anti-proliferation assay in vitro. The results showed that most compounds could inhibit both enzymes, and several of them showed potent inhibition activity against different cancer cell lines. The best compound 20 (CPU-Y020) showed the IC50 values of 6.58 and 7.61μM toward colon cancer HT-29 and liver cancer HepG2 cell lines. [Copyright &y& Elsevier]

Abstract: A long-acting (basal) insulin capable of delivering flat, sustained, reproducible glycemic control with once daily administration represents an improvement in the treatment paradigm for both type 1 and type 2 diabetes. Optimization of insulin pharmacodynamics is achievable through structural modification, but often at the expense of alterations in receptor affinity and selectivity. A series of isoelectric point (pI)-shifted insulin analogs based on the human insulin sequence or the GlyA21 acid stable variant were prepared by semi-synthetic methods. The pI shift was achieved through systematic addition of one or more arginine (Arg) or lysine (Lys) residues at the N terminus of the A chain, the N terminus of the B chain, the C terminus of the B chain, or through a combination of additions at two of the three sites. The analogs were evaluated for their affinity for the insulin and IGF-1 receptors, and aqueous solubility under physiological pH conditions. Notably, the presence of positively charged amino acid residues at the N terminus of the A chain was consistently associated with an enhanced insulin to IGF-1 receptor selectivity profile. Increased IGF-1 receptor affinity that results from Arg addition to the C terminus of the B chain was attenuated by cationic extension at the N terminus of the A chain. Analogs 10, 17, and 18 displayed in vitro receptor selectivity similar to that of native insulin and solubility at physiological pH that suggested the potential for extended time action. Accordingly, the in vivo pharmacokinetic and pharmacodynamic profiles of these analogs were established in a somatostatin-induced diabetic dog model. Analog 18 (A0:Arg, A21:Gly, B31:Arg, B32:Arg human insulin) exhibited a pharmacological profile comparable to that of analog 15 (insulin glargine) but with a 4.5-fold more favorable insulin:IGF-1 receptor selectivity. These results demonstrate that the selective combination of positive charge to the N terminus of the A chain and the C terminus of the B chain generates an insulin with sustained pharmacology and a near-native receptor selectivity profile. [Copyright &y& Elsevier]

From 1993 to 1995, with a conventional fluorescence spectrophotometer (CFS) (convenient) and working in a synchronous scan model (easy-to-use), Pasternack et al. proposed the resonance light-scattering (RLS) technique, to efficiently characterize self-assemblies or self-aggregations of chromophores with good electronic coupling. Incident wavelengths were specially considered within their absorption envelopes (rather unorthodox), and their amplified signals were observed (good sensitivity and selectivity). Due to these absorbing benefits, RLS technique, as a novel readout method, commenced on its exciting analytical tours soon after Liu et al. and especially Li et al., separately, set out their corresponding pioneering investigations from 1995 to 1997. From then on, it has received an increasing attention by analysts, as a consequence exhibiting more and more fascinating analytical applications. Moreover, various attractive RLS-derived techniques have been developed successively to improve it or to enlarge its possibilities. Later on, Liu et al. and Li et al., Tabak et al., Yguerabide et al., Huang et al., Lakowicz et al. and Fernández Band et al. have made their outstanding contributions. In this review, we concentrate on major achievements of RLS in analytical chemistry for over a decade, involving the developments and analytical applications of RLS derived techniques treated as an impacting progress of RLS technique in analytical chemistry. Finally, an indication of future directions of RLS technique in analytical chemistry is provided. [ABSTRACT FROM AUTHOR]

NAFLD (non-alcoholic fatty liver disease) is one of the most prominent liver diseases in the world. As a metabolic-related disease, the development of NAFLD is closely associated with various degrees of lipid accumulation, oxidation, inflammation, and fibrosis. Ilex chinensis Sims is a form of traditional Chinese medicine which is used to treat bronchitis, burns, pneumonia, ulceration, and chilblains. Kaempferol-3-O-glucuronide (K3O) is a natural chemical present in Ilex chinensis Sims. This study was designed to investigate the antioxidative, fat metabolism-regulating, and anti-inflammatory potential of K3O. A high-cholesterol diet (HCD) was used to establish steatosis in larval zebrafish, whereby 1mM free fatty acid (FFA) was used to induce lipid accumulation in HepG2 cells, while H2O2 was used to induce oxidative stress in HepG2. The results of this experiment showed that K3O reduced lipid accumulation and the level of reactive oxygen species (ROS) both in vivo (K3O, 40 μM) and in vitro (K3O, 20 μM). Additionally, K3O (40 μM) reduced neutrophil aggregation in vivo. K3O (20 μM) also decreased the level of malondialdehyde (MDA) and significantly increased the level of glutathione peroxidase (GSH-px) in both the HCD-induced larval zebrafish model and H2O2-exposed HepG2 cells. In the mechanism study, keap1, nrf2, tnf-α, and il-6 mRNA were all significantly reversed by K3O (20 μM) in zebrafish. Changes in Keap1 and Nrf2 mRNA expression were also detected in H2O2-exposed HepG2 cells after they were treated with K3O (20 μM). In conclusion, K3O exhibited a reduction in oxidative stress and lipid peroxidation, and this may be related to the Nrf2/Keap1 pathway in the NAFLD larval zebrafish model. [ABSTRACT FROM AUTHOR]

To investigate a possible methodology of exploiting herbal medicine and design polytherapy for the treatment of skin depigmentation disorder, we have made use of Vernonia anthelmintica (L.) Willd., a traditional Chinese herbal medicine that has been proven to be effective in treating vitiligo. Here, we report that the extract of Vernonia anthelmintica (L.) Willd. effectively enhances melanogenesis responses in B16F10. In its compound library, we found three ingredients (butin, caffeic acid and luteolin) also have the activity of promoting melanogenesis in vivo and in vitro. They can reduce the accumulation of ROS induced by hydrogen peroxide and inflammatory response induced by sublethal concentrations of copper sulfate in wild type and green fluorescent protein (GFP)-labeled leukocytes zebrafish larvae. The overall objective of the present study aims to identify which compatibility proportions of the medicines may be more effective in promoting pigmentation. We utilized the D-optimal response surface methodology to optimize the ratio among three molecules. Combining three indicators of promoting melanogenesis, anti-inflammatory and antioxidant capacities, we get the best effect of butin, caffeic acid and luteolin at the ratio (butin:caffeic acid:luteolin = 7.38:28.30:64.32) on zebrafish. Moreover, the effect of melanin content recovery in the best combination is stronger than that of the monomer, which suggests that the three compounds have a synergistic effect on inducing melanogenesis. After simply verifying the result, we performed in situ hybridization on whole-mount zebrafish embryos to further explore the effects of multi-drugs combination on the proliferation and differentiation of melanocytes and the expression of genes (tyr, mitfa, dct, kit) related to melanin synthesis. In conclusion, the above three compatible compounds can significantly enhance melanogenesis and improve depigmentation in vivo. [ABSTRACT FROM AUTHOR]