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Qudong Lu,1 Yang Yang,1 Hengshuai Zhang,1 Cheng Chen,2 Jiang Zhao,1 Zhenxing Yang,1 Yi Fan,1 Longkun Li,1 Huan Feng,1 Jingzhen Zhu,1 Shanhong Yi1 1Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Burns, First Affiliated Hospital, Army Medical University, Chongqing, 400037, People’s Republic of ChinaCorrespondence: Jingzhen Zhu; Shanhong YiDepartment of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, People’s Republic of ChinaTel +86 23-68774453Email zhujz1114@163.com; 2644057844@qq.comPurpose: Hyperalgesia and bladder overactivity are two main symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS). Cannabinoid receptors participate in the modulation of pain and bladder function. GPR18, a member of the cannabinoid receptor family, also participates in the regulation of pain and bladder function, but its underlying mechanisms are unknown. In this work, we sought to study the role of GPR18 in IC/BPS.Methods: A rat model of IC/BPS was established with cyclophosphamide (CYP). Paw withdrawal threshold (PWT) measurement and cystometry were used to evaluate pain and bladder function, respectively. RT-PCR, Western blotting and immunofluorescence were used to assess the expression and distribution of GPR18. The role of GPR18 in pain and bladder function was studied by intrathecal injection of resolvin D2 (RvD2, a GPR18 agonist) and O-1918 (a GPR18 antagonist). Calcium imaging was used to study the relationship between GPR18 and TRPV1.Results: A rat model of IC/BPS, which exhibited a decreased PWT and micturition interval, was successfully established with CYP. The mRNA and protein expression of GPR18 was reduced in the bladder and dorsal root ganglia (DRG) in rats with CYP-induced cystitis. Intrathecal injection of RvD2 increased the PWT and micturition interval. However, O-1918 blocked the therapeutic effect of RvD2. GPR18 was present in bladder afferent nerves and colocalized with TRPV1 in DRG, and RvD2 decreased capsaicin-induced calcium influx in DRG.Conclusion: Activation of GPR18 by RvD2 alleviated hyperalgesia and improved bladder function, possibly by inhibiting TRPV1 in rats with CYP-induced cystitis.Keywords: interstitial cystitis/bladder pain syndrome, GPR18, TRPV1, hyperalgesia, bladder overactivity, resolvin D2, O-1918

Evidence suggests constipation precedes motor dysfunction and is the most common gastrointestinal symptom in Parkinson's disease (PD). 5-HT4 receptor (5-HT4R) agonist prucalopride has been approved to treat chronic constipation. Here, we reported intraperitoneal injection of prucalopride for 7 days increased dopamine and decreased dopamine turnover. Prucalopride administration improved motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. Prucalopride treatment also ameliorated intestinal barrier impairment and increased IL-6 release in PD model mice. However, prucalopride treatment exerted no impact on JAK2/STAT3 pathway, suggesting that prucalopride may stimulate IL-6 via JAK2/STAT3-independent pathway. In conclusion, prucalopride exerted beneficial effects in MPTP-induced Parkinson's disease mice by attenuating the loss of dopamine, improving motor dysfunction and intestinal barrier.

The effect of binding strength of counterions with the polyelectrolyte chain to the swelling of polyelectrolyte brushes is studied, by investigating the swelling of both the polycation and polyanion in response to the variation of the salt concentration under the change of counterion's identity. Two polyelectrolyte brushes grafted on solid substrates are adopted: the cationic poly [2-(methacryloyloxy)ethyltrimethyl ammonium] (PMETA-X, X = F, Cl, Br, and I) and the anionic polystyrene sulfonate (M-PSS, M = Li, Na, K, and Cs). The swelling change with the salt concentration is investigated by ellipsometry, quartz crystal microbalance with dissipation, and dielectric spectroscopy. It is discovered that although the thickness of PMETA-X brushes is larger than that of M-PSS brushes of similar grafting density, the former has much less solvent incorporated than the latter. Such a difference is attributed to the weaker interaction between the PMETA+ chain and its halide counterions than that between the PSS- chain and its alkali counterions, discovered by dielectric spectroscopy. This makes the original charges on the PMETA-X chain less neutralized and therefore have a higher charge density, compared with the M-PSS chain. The results demonstrate that the stronger binding of the counterions to the polyelectrolytes makes the main chains less charged, resulting in the weaker inter-chain electrostatic repulsion and less swelling of the brushes. Investigations into the effect of ion identity show the following order of binding strength: for the cationic PMETA+ chain, F- < Cl- < Br- < I- and for the anionic PSS- chain, Li+ < Na+ < K+ < Cs+.

Chondroitin sulfate (CS) is a kind of linear polysaccharide that is covalently linked to proteins to form proteoglycans. Chondroitin sulfate proteoglycans (CSPGs) consist of a core protein, with one or more CS chains covalently attached. CSPGs are precisely regulated and they exert a variety of physiological functions by binding to adhesion molecules and growth factors. Widely distributed in the nervous system in human body, CSPGs contribute to the major component of extracellular matrix (ECM), where they play an important role in the development and maturation of the nervous system, as well as in the pathophysiological response to damage to the central nervous system (CNS). While there are more than 30 types of CSPGs, this review covers the roles of the most important ones, including versican, aggrecan, neurocan and NG2 in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis and multiple sclerosis. The updated reports of the treatment of neurodegenerative diseases are involving CSPGs.

Human urine-derived stem cells (hUSCs) show multipotential differentiation ability and can differentiate into mesodermal cell lineages. Interstitial cells of Cajal-like cells (ICC-LCs) are crucial for the pace-making function of spontaneous contraction in the bladder. However, the mechanisms by which hUSCs generate ICC-LCs have not been elucidated. In this study, we developed a strategy for directional differentiation of hUSCs into ICC-LCs. hUSCs were transfected with lentiviral vectors encoding c-Kit, stem cell factor (SCF), hyperpolarization activated cyclic nucleotide gated potassium channel 4 (HCN4), and 5-azacytidine induced 2 (AZI2) genes, and the cells were cultured for an additional 7 days in specific medium. The expression of the surface marker c-Kit on ICC-LCs was determined at 7 days after transfection. hUSCs were successfully expanded and transfected with the four lentiviral vectors. hUSCs transfected with lentiviral-c-Kit, lentiviral-HCN4, and lentiviral-AZI2 showed higher expression of c-Kit 7 days after transfection, but only the lentiviral-HCN4-transfected cells showed morphological alterations in ICC-LCs. These cells also displayed visible HCN current amplitude and density. This approach may provide a new strategy for the treatment of underactive bladder.

The thiazole unit can exhibit both electron-deficient and electron-rich features, which provides more possibilities for shaping the photophysical and electroluminescence (EL) properties of the Ir(III) complex emitters. Herein, a series of cyclometalated Ir(III) complexes were synthesized from the 2-phenylthiazole-type ligands bearing fluorinated benzenesulfonyl moieties. Their thermal stabilities, photophysical and electrochemical properties and EL performances were fully studied. They can emit intense orange phosphorescence with peaks ranging from 577 to 590 nm, and the phosphorescence quantum yield (Φp) can be up to 0.89. Interestingly, when the number of fluorine atoms on the phenyl ring of the benzenesulfonyl moiety increases, their absorption and emission maxima both show red-shift effects, which were interpreted by the related theoretical calculation results. Besides, their LUMO levels follow a decreasing trend as the fluorine atoms increase, leading to good electron injection/transporting (EI/ET) properties. Finally, their EL performances were characterized by their solution processed OLEDs, which achieve the best EL efficiencies with a maximal current efficiency (ηL) of 27.5 cd A−1, a maximal power efficiency (ηp) of 17.3 lm W−1 and a maximal external quantum efficiency (ηext) of 12.3%, these results can outcompete the EL efficiencies of the reported solution processed OLEDs built by the thiazole-based Ir(III) complexes. All the concerned results should offer inspirations for Ir(III) complex functionalizations and reveal the great potential of 2-phenylthiazole ligands with fluoro-benzenesulfonyl moieties in developing high performance emitters.

The dense medium modulates the molecular structure and bioreactions in living cells via both noncovalent interactions and macromolecular crowding and confinement effects. However, the interplay between the volume effect and noncovalent interactions remains unclear. In this work, we studied in detail on how electrostatic interactions influence the crowding and confinement effect by comparing the formation and elongation of DNA nanotubes in branched dextran and charged hyaluronic acid (HA) solution of a broad concentration range, with and without 150 mM NaCl. In all the studied cases, three concentration regimes are identified: a crowding regime, a double-effect regime, and a confinement regime. In the crowding and double-effect regimes, the addition of 150 mM NaCl enhances the assembly of DNA tiles by screening the electrostatic repulsion, and a higher dextran solution is required to confine the DNA assembly into nanotubes. However, the screening effect on the HA network is more than that on the DNA assembly, so DNA tubes formed in HA solution at much lower concentrations. In the confinement regime, the electrostatic interaction exhibits a negligible effect on the DNA assembly in both dextran medium and HA medium. Our study demonstrates that the volume effect and noncovalent interactions are system specific and concentration dependent. Their interplay governs the living processes in crowded cells.

Background Controlling the blood glucose level is an effective method to reduce type 2 diabetes and prevent diabetes-related complications. Ursolic acid is a plant extract that can reduce postprandial hyperglycemia effectively. This study aimed to explore the inhibitory effect and interaction mechanism of ursolic acid against α-amylase and α-glucosidase. Results In this study, the effect of ursolic acid on glycosidase was studied in vitro, in vivo, and in silico. The half-maximal inhibitory concentration (IC50 ) of ursolic acid on α-amylase and α-glucosidase was 0.482 ± 0.12 mg mL-1 and 0.213 ± 0.042 mg mL-1 , respectively. The results of enzymatic kinetics showed that ursolic acid inhibited α-amylase and α-glucosidase activity in a non-competitive manner. The fluorescence spectrum showed that the combination of ursolic acid and glycosidase caused the intrinsic fluorescence quenching of glycosidase. The observation of starch granules revealed that the activity of α-amylase was inhibited and the hydrolysis of starch granules was prevented in the presence of ursolic acid. Molecular docking results showed that ursolic acid bound to the inactive site of α-amylase and α-glucosidase through the formation of ursolic acid-glucosidase complex. Ursolic acid interacted with α-amylase and α-glucosidase mainly through hydrogen bonding. The postprandial hypoglycemic effect of ursolic acid in C57BL/6J mice showed that the high concentration of ursolic acid could quickly reduce postprandial blood glucose level. Conclusion Ursolic acid can be considered as a natural ingredient in functional foods to control postprandial blood glucose levels and prevent diabetes by delaying the digestion of starch in foods. © 2019 Society of Chemical Industry.

Inhibition the activity of glycosidase is an effective method for the treatment and prevention of diabetes. In this study, enzymatic kinetics, fluorescence spectrum experiment, starch granule digestion, molecular docking studies and animal's studies were used to investigate the interaction mechanism of carnosic acid against two glycosidase (α-amylase and α-glucosidase). Enzymatic kinetics showed that carnosic acid inhibited α-amylase activity in a competitive manner and α-glucosidase activity in a non-competitive manner. The half inhibitory concentrations (IC50) of carnosic acid to α-amylase and α- glucosidase were (1.12 ± 0.31) and (0.08 ± 0.17), respectively. The fluorescence quenching experiments showed that the intrinsic fluorescence of α-amylase or α-glucosidase was quenched by forming a complex with carnosic acid, and there was only one binding site between carnosic acid and glycosidase. The starch granules were no longer hydrolyzed by α-amylase after the addition of carnosic acid, which indicated that carnosic acid inhibited the activity of α-amylase. Molecular docking study showed that carnosic acid binds to the amino acid residues of glycosidase through hydrogen bond and van der Waals force, which leads to the change of the molecular conformation of glycosidase and thus reduces the activity of glycosidase. The experiment on mice showed that carnosic acid could effectively reduce postprandial blood glucose in mice.

Aryl Hydrocarbon Receptor (AHR) is a ligand-activated transcription factor expressed in various brain regions. However, little is known about the role of AHR during neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Here, mice were sacrificed at day 4, day 6 and day 8 respectively after MPTP or saline treatment. Behavioral tests, Tyrosine hydroxylase (TH) expression, glial reaction, and AHR expression and activation were then assayed. As expected, mice treated with MPTP showed apparent behavioral dysfunctions and significantly reduced TH content. Immunofluorescence (IF) labeling showed an increased trend of phosphorylated AHR activation in the Substantia Nigra pars compacta (SNpc) and striatum after MPTP treatment. Western blot analysis demonstrated that MPTP treatment induced a significantly increased level of AHR at each time point tested, with the highest level observed at day 6 in the striatum. To determine exactly the AHR activation in relation to changes of glial cell reactivity, double IF labeling was performed for either IBA1 (microglia marker) and p-AHR, or GFAP (astrocyte marker) and p-AHR. The results demonstrated that MPTP treatment not only increases the number of p-AHR-positive IBA1-expressing cells in the striatum and the SNpc, but also increases that of p-AHR-positive GFAP-expressing cells in the striatum. Intriguingly, the increase of the number of cells co-expressing both p-AHR and IBA1 was highest at day 4 in response to MPTP in the striatum and at day 8 in the SNpc. The number of cells co-expressing both p-AHR and GFAP was increased at days 4, 6 and 8 in the striatum. In conclusion, our study suggests that AHR activation may facilitate PD diagnosis and serve as a target for the treatment of PD.

Nitrilase-mediated biocatalysis reactions have been continuously arousing wide interests by scholars and entrepreneurs in organic synthesis over the past six decades. Since regioselective nitrilases could hydrolyze only one cyano group of dinitriles into corresponding cyanocarboxylic acids, which are virtually impossible by chemical hydrolysis and of interest for a variety of applications, it becomes particularly appealing to synthetic chemists. The aim of the current review is to summarize the recent advancements on regioselective nitrilases concerning their fundamental researches and applications in synthesis of a series of high-value fine chemicals and pharmaceuticals. Carbon chain lengths and substituent group positions of substrates are found to be two crucial factors in affecting regioselectivity of nitrilase. Practical applications of regioselective nitrilases in synthesis of 1,5-dimethyl-2-piperidone (1,5-DMPD), atorvastatin, gabapentin, (R)-baclofen, and (S)-pregabalin were systematically reviewed. Future perspectives clearly elucidating the mechanism of regioselectivity and further molecular modifications of regioselective nitrilases integrating within silico technology for industrial applications were discussed.

Supramolecular polymerization is influenced by many factors, especially the stiffness of the polymers, which is directly related to cyclization of the polymers. We have proposed a supramolecular “ring opening” polymerization system with DNA molecules to study the ring-chain equilibrium of supramolecular polymerization. The molecular weight of the supramolecular polymers was characterized by Asymmetric Flow Field Flow Fractionation, and the diffusion coefficient of the supramolecular polymers was characterized by Fluorescent Correlation Spectra. Tuning the ratio of the “ring opening” strand, the length of the DNA monomers and temperature could change the ring-chain equilibrium, thus influence the molecular weight and diffusion coefficient. This strategy has offered us a useful platform to dig into the kinetic mechanism of supramolecular polymerization.

A self-healing hydrogel was synthesized via the multi-component reaction of azobenzene-methacrylamide, β-CD and 3-methacrylamido phenylboronic acid. The orthogonal method was applied to analyze the influence of host–guest inclusion complexation, cross-linker and phenylboronic acid monomers content on mechanical properties and healing efficiency of the hydrogel. The results indicated that hydrogel showed autonomic self-healing behavior. The hydrogel demonstrated light-switchable self-healing ability and pH-sensitive swelling ratio. It was found that hydrogel showed high elongation, excellent resilience and low elastic hysteresis. The design of the combined host–guest interactions and boronate esters on the hydrogel showed advantage for improving the mechanical, self-healing and recovery properties simultaneously.

The hydroformylation of long chain alkenes catalyzed by a water soluble Rh/TPPTS complex (TPPTS: sodium salt of sulfonated triphenylphosphine) in methanol was investigated. The mixture of rhodium precursor HRh(CO)(TPPTS)3, ligand TPPTS, methanol and a long chain alkene becomes a single phase under reaction conditions, which make the hydroformylation reaction proceed homogeneously. Both the conversion of long chain alkene and the selectivity to aldehydes (including the aldehydes forming methylacetals) could reach up to 97.8% and 97.6%, respectively, with 3323 h−1 of TOF (TOF: turnover frequency is defined as the moles of converted alkene per mole of Rh per hour). After the solvent methanol was removed under the reaction temperature, two phases were formed automatically. The colourless product phase could be efficiently separated from the precipitate rhodium catalyst phase by centrifuge. The catalyst was reused for five times without obvious loss of rhodium and the catalytic activity. The rhodium leaching in product mixture was less than 0.03% of the total rhodium.

Liquid chromatography coupled with mass spectrometry has been used as metabolomics profiling tool to discover and identify the metabolites in metabolic diseases. Osteoporosis (OP) syndrome is a chronic metabolic disease characterized by bone mass reduction and changes in bone microstructure. Psoralea corylifolia Linn. seeds (PCS) have a therapeutic effect on osteoporosis, but their action mechanism and therapeutic target are still unclear. This study aims to explore the metabolic changes of the urine profile in glucocorticoid-induced OP model rats and the therapeutic effect of PCS. High-throughput metabolomics based on the liquid chromatography coupled with mass spectrometry quadrupole time-of-flight mass spectrometry and multivariate data analysis were used to analyze the urine metabolites. The results showed that has an obvious separation between model and control groups. OPLS-DA was used to further analyze and discover substances that contributed to the separation. 42 potential biomarkers and 12 related metabolic pathways were identified in combination with network databases. After the intervention of PCS, 24 biomarkers were significantly regulated, mainly with glycone, serine and threonine metabolism, glutathione metabolism and purine metabolism and other metabolic pathways are related and discovered. This study has proved that PCS has therapeutic effect against OP by regulating that metabolic pathways disturbed in the OP. It provided a basis for the research and future development of new drugs for OP treatment.

The widespread adoption of genetically modified, glyphosate-tolerant corn and soybean varieties in US crop production has led to a dramatic increase in glyphosate usage. Though present at or below regulatory limits currently set for human foodstuffs, the concentration of glyphosate in companion animal feed is currently unknown. In the present study, 18 commercial companion animal feeds from eight manufacturers were analyzed for glyphosate residues using ELISA. Every product contained detectable glyphosate residues in the range of 7.83 × 101–2.14 × 103 μg kg−1 dry weight, with the average and medians being 3.57 × 102 and 1.98 × 102 μg kg−1 respectively. Three products were tested for within-bag variation and six were tested for lot to lot variation. Little within-bag variation was found, but the concentration of glyphosate varied by lot in half of the products tested. Glyphosate concentration was significantly correlated with crude fiber content, but not crude fat or crude protein. Average daily intakes by animals consuming feeds containing the median glyphosate concentration are estimated to result in exposures that are 0.68–2.5% of the Allowable Daily Intake (ADI) for humans in the US and EU, which are 1750 and 500 μg kg−1 respectively. Consumption of the most contaminated feed, however, would result in exposure to 7.3% and 25% of the above ADIs, though the relevance of such an exposure to companion animals is currently unknown. Companion animal feeds contained 7.83 × 101–2.14 × 103 μg kg−1 glyphosate which is likely to result in pet exposure that is 4–12 times higher than that of humans on a per Kg basis.

The thermal and mechanical properties of the chemically imidized polyimide (CIPI) films and thermally imidized polyimide (TIPI) films were investigated systematically. Experimental results indicated that the CIPI films show dramatically enhanced tensile strength and modulus with obviously reduced coefficient of thermal expansion (CTE) in comparison with TIPI films. These enhancements results from the high in-plane orientation and close packing of the CIPI backbones. Compared with thermal imidization which starts at about 140 °C, the chemical imidization activated by acetic anhydride and isoquinoline initiates the cyclization even at room temperature. The resulting imide rings restrict the mobility of polymer chains and lead to the in-plane orientation with solvent evaporation. Additionally, fewer small molecules remain in the films after treated at 120 °C by chemical imidization than by thermal imidization. The polymer chain plasticization caused by the evaporation of small molecules at high temperature is obviously restricted. Moreover, the partially imidized polymer inhibits the decomposition of mainchains that occurs at subsequent high temperature process, being beneficial to the formation of high molecular weight PI films. Hence, chemical imidization pathway shows apparent advantage to produce PI films with great combined properties, including high modulus, strength and toughness, as well as high thermal dimension stability etc.

Xiaobin Luo,1 Bin Zhao,2 Baoxia Chen,2 Hongyu Chen,1 Tao Han,1 Najeeb Bassam Najeeb Bsoul,1 Hede Yan1 1Department of Orthopedics (Division of Hand Surgery), The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Key Laboratory of Orthopedics of Zhejiang Province, The Second School of Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, 325027, People’s Republic of China; 2Department of Post Anaesthesia Care Unit, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, People’s Republic of ChinaCorrespondence: Hede YanDepartment of Orthopaedics (Division of Hand Surgery), The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, West Xueyuan Road 109#, Wenzhou, 325027, Zhejiang Province, People’s Republic of ChinaEmail yanhede@hotmail.comBackground: The application of random pattern skin flaps is limited in plastic surgery reconstruction due to necrosis. Trans-cinnamaldehyde has antibacterial, anticancer, and antioxidant properties. In this study, we aimed to investigate the effect of trans-cinnamaldehyde on skin flap survival and its possible mechanism regarding nitric oxide.Materials and Methods: One hundred forty male Sprague-Dawley rats were randomly divided into seven groups (n = 20 each group). After the dorsal flap was raised, different doses of trans-cinnamaldehyde (10, 20, and 30 mg/kg) were immediately given by oral gavage in the three different groups. To assess the possible involvement of the nitric oxide system, NG-nitro-L-arginine methyl ester (L-NAME, a nonselective nitric oxide synthase inhibitor) was used in this study. All flap samples were incised on postoperative day 7.Results: Our results showed that flap survival was increased significantly in the 20 mg/kg (P < 0.001) trans-cinnamaldehyde (TC) group compared to the control group or 30 mg/kg TC group. This protective function was restrained by coadministration of L-NAME with 20 mg/kg TC. The results of histopathology, laser Doppler, arteriography mediated with oxide–gelatine, and fluorescent staining all showed a significant increase in capillary count, collagen deposition, angiogenesis, and flap perfusion. Immunohistochemistry results revealed a significant increase in the expression of CD34, eNOS, and VEGF.Conclusion: Trans-cinnamaldehyde increased flap survival through the nitric oxide synthase pathway and contributed to angiogenesis. A concentration of 20 mg/kg trans-cinnamaldehyde was recommended in this study.Keywords: random pattern flap, flap necrosis, trans-cinnamaldehyde, angiogenesis, flap perfusion

This study investigated the influence of the exogenous application of vitamin B2 (VB2), B12 (VB12), biotin (VH), and nicotinic acid (VPP) on oxygen production in maize (Zea mays L.) seedlings at 5 °C for day 1, 3, 5 and 7. The seeds were soaked in VB2, VB12, VH, and VPP solutions for 24 h at the concentration of 100 mg/L, and control was soaked in distilled water. A total of 50 seeds were used for each treatment in germination boxes was repeated three times. The germination box was placed in a hypothermic incubator for 1, 3, 5, and 7 days in the dark at 5 °C, then moved to a plant growth room and kept for seven days. Compared with the VH and VPP treatments, the VB2 and VB12 treatments had higher thiobarbituric acid reactive substances, proline, and soluble sugars. The VB2 and VB12 treatments also increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) than other treatments. The VB2 and VB12 treatments reduced the contents of hydrogen peroxide (H2O2–), superoxide anion (O2–), and the damage of reactive oxygen species (ROS) to cells, increased the stability of the cell membrane and the content of cell osmoregulation substances. Moreover, VB2 and VB12 had higher seedling growth, germination rate, and index. Treatments VB2 and VB12 could promote maize seed germination and growth under low-temperature stress. Exogenous vitamins in crop production can be a valuable tool for protecting plants against low-temperature stress.

Many experiments show that vitrification significantly reduces the fertilization capacity of mammalian oocytes, restricting the application of vitrified oocytes. It has been proven that the JUNO protein plays a vital role in mammalian oocytes fertilization. However, little information is available about the effects of vitrification on the JUNO protein and the procedure to protect it in bovine oocytes. Here, the present study was designed to investigate the effect of vitrification on the JUNO protein level in bovine oocytes. In this study, MII oocytes were treated with cholesterol-loaded methyl-β-cyclodextrin (CLC; 0, 10, 15, 20 mM) for 45 min before vitrification and methyl-β-cyclodextrin (MβCD; 0, 2.25, 4.25, 6.25 mM) for 45 min after thawing (38-39°C). Then, the expression level and function of JUNO protein, cholesterol level in the membrane, the externalization of phosphatidylserine, sperm binding capacity and the developmental ability of vitrified bovine oocytes were examined. Our results showed that vitrification significantly decreased the JUNO protein level, cholesterol level, sperm binding capacity, development ability, and increased the promoter methylation level of the JUNO gene and apoptosis level of bovine oocytes. Furthermore, 15 mM CLC + 4.25 mM MβCD treatment significantly improved the cholesterol level and increased sperm binding and development ability of vitrified bovine oocytes. In conclusion, the combination treatment of cholesterol-loaded methyl-β-cyclodextrin and methyl-β-cyclodextrin significantly improves the fertilization capacity of vitrified bovine oocytes by protecting fertilization protein JUNO.

The helicopter transmission system generally employs oil injection lubrication, while the tooth surface often operates under mixed lubrication. In the case of mixed lubrication, the relationship among the fluid flow, rough contact, and material wear renders it quite difficult to establish a predictive model for wear and lubrication coupling. The present study involved, in consideration of the effect of tooth surface micro-morphology, establishing a coupling analysis model for the wear characteristics of involute gear mixed lubrication. The effects of the mixture of squalane base oil and 15% (by weight) polyisoprene(SQL+PIP), polyalphaolefin oil (PAO6) and mineral SN100 on the distribution of lubrication performance parameters and the wear characteristics were analyzed. The results revealed that the film thickness of SQL+PIP was higher than that of PAO6 and SN100, and the coefficient of friction is lower. In addition, the increase in lubricant viscosity was conducive to reducing the contact area and load ratios of direct rough contact, which was, in turn, beneficial to reducing wear.

In this study, a novel, high surface area iron phosphonate (IP) for highly efficient adsorption of uranyl ion in acidic medium was described. The as-prepared IP was amorphous with its specific surface area and total pore volume as high as 268 m2/g and 1.04 cm3/g, respectively. Particularly, the as-prepared IP with ferrous ions and oxygen, nitrogen-bearing functional groups prove excellent U(VI) adsorption capacity (154.6 mg/g) as compared to that of amorphous FePO4 (67.3 mg/g) and Fe3(PO4)2(H2O)8 (33.8 mg/g). Surprising, the saturation adsorption capacity could achieve up to 353.9 mg/g. Besides, the IP also had a fast adsorption rate for attaining adsorption equilibrium within 20 min, and followed pseudo-second-order kinetic and Freundlich models. Moreover, both the Dubinin-Radushkevich isotherm adsorption model and the value of enthalpy indicated a chemisorption process. Otherwise, the Na+-independent U(VI) adsorption on IP and the adsorption-desorption isotherm studies revealed that inner-layer surface complexation is the control step for U(VI) adsorption process, and the adsorbent featured an irreversible adsorption process. The structure and functional groups of the adsorbent remained unchanged after capture of U(VI). Further, X-ray photoelectron spectra (XPS) analysis demonstrated that the capture mechanism of U(VI) on IP from acidic aqueous solution was due to not only redox reaction, but also ascribed to the coordinated chemical adsorption.

The structural parameters of 23 ionic liquids were calculated by the Hartree–Fock ab initio method. The relationship between the antiwear properties of ionic liquids dissolved in dimethyl sulfoxide and the structural parameters of the ionic liquids was studied using multiple linear regression analysis. A quantitative structure tribo-ability relationship model with good fitting and prediction ability was established. The results show that entropy is the most important structural parameter affecting the antiwear performance of ionic liquid-dimethyl sulfoxide systems. The entropy of the ionic liquid is related to the hydrogen bonding in the system, and an orderly arrangement of this hydrogen bonding is beneficial in terms of improving antiwear performance.

In this paper two Nb-silicide-based alloys with nominal compositions (at.%) Nb-12Ti-18Si-6Ta-2.5W-1Hf-2Sn-2Ge (JZ1) and Nb-12Ti-18Si-6Ta-2.5W-1Hf-5Sn-5Ge (JZ2) were studied. The alloys were designed using the alloy design methodology NICE to meet specific research objectives. The cast microstructures of both alloys were sensitive to solidification conditions. There was macro-segregation of Si in JZ1 and JZ2. In both alloys the &beta, Nb5Si3 was the primary phase and the Nbss was stable. The A15-Nb3X (X = Ge,Si,Sn) was stable only in JZ2. The Nbss+&beta, Nb5Si3 eutectic in both alloys was not stable as was the Nb3Si silicide that formed only in JZ1. At 800 &deg, C both alloys followed linear oxidation kinetics and were vulnerable to pesting. At 1200 &deg, C both alloys exhibited parabolic oxidation kinetics in the early stages and linear kinetics at longer times. The adhesion of the scale that formed on JZ2 at 1200 &deg, C and consisted of Nb and Ti-rich oxides, silica and HfO2 was better than that of JZ1. The microstructure of JZ2 was contaminated by oxygen to a depth of about 200 &mu, m. There was no Ge or Sn present in the scale. The substrate below the scale was richer in Ge and Sn where the NbGe2, Nb5(Si1-xGex)3, W-rich Nb5(Si1-xGex)3, and A15-Nb3X compounds (X = Ge,Si,Sn) were formed in JZ2. The better oxidation behavior of JZ2 compared with JZ1 correlated well with the decrease in VEC and increase in &delta, parameter values, in agreement with NICE. For both alloys the experimental data for Si macrosegregation, vol.% Nbss, chemical composition of Nbss and Nb5Si3, and weight gains at 800 and 1200 &deg, C was compared with the calculations (predictions) of NICE. The agreement was very good. The calculated creep rates of both alloys at 1200 &deg, C and 170 MPa were lower than that of the Ni-based superalloy CMSX-4 for the same conditions but higher than 10&minus, 7 s&minus, 1.

Polyborosiloxane gel (PBS-gel) with shear hardening properties was prepared by cross-linking boric acid and hydroxyl-terminated polydimethylsiloxane through B&ndash, O&ndash, Si dynamic covalent bonding. The prepared PBS gel was mixed with methyl vinyl silicone rubber (MVQ), and a benzoyl peroxide (BPO) cross-linking agent was added to vulcanize the silicone rubber. At the same time, the gel molecules were co-vulcanizing with MVQ to produce molecular cross-linking. The effects of PBS-gel on the damping properties of silicone rubber were analyzed by dynamic rheological test, Fourier transform infrared spectroscopy and dynamic mechanical analysis. The results demonstrated that the damping performance of MVQ/PBS rubber is greatly improved and the rubber has a tan&delta, &gt, 0.3 in the range of &minus, 25~125 &deg, C. The shear-hardening gel is uniformly dispersed in the system, due to the combined action of covalent bonds and intermolecular forces, which act as an active molecular chain that can efficiently dissipate and transfer energy inside the silicone rubber.

The correlation between the water content and protein adsorption on the surface of polymer brushes is investigated quantitatively. Using a number of model systems such as poly N-isopropylacrylamide (PNIPAM), polyethylene glycol (PEG), poly(2-(methacryloyloxy)ethyl phosphorylcholine) (PMPC), poly(2-hydroxyethyl methacrylate) (PHEMA), and poly(2,2,3,4,4,4-hexafluorobutyl)methacrylate (PHFBMA) polymer brushes with various grafting densities, the amount of water hydrodynamically coupled inside the brushes and its correlation with protein adsorption (BSA and Fg proteins as model systems) were determined by quartz crystal microbalance with dissipation (QCM-D) and surface plasma resonance (SPR). The results demonstrate the negative correlation between the water content and protein adsorption - the more water is coupled inside the brushes, the more protein adsorption is suppressed. In particular for PNIPAM brushes with a high enough grafting density and with a water content greater than 250 ng cm-2, the protein adsorption is negligible.

The fertilization capacity of sex-sorted sperms is seriously decreased, which inhibits its wide application. However, little information is still available about the effect of vitamin C (VC) and lycopene (Lyc) on the fertilization capacity of sex-sorted bull sperm. In this study, the washing medium and fertilization medium of sex-sorted sperm from three bull individuals were supplemented with different concentrations of VC (0, 1 × 10-3 , 1 × 10-4 , 1 × 10-5 , 1 × 10-6 M) or Lyc (0, 1 × 10-4 , 1 × 10-5 , 1 × 10-6 , 1 × 10-7 ). After washing twice and incubation for 1.5 hr, the malondialdehyde (MDA) level, phosphatidylserine (PS) translocation, membrane potential (Δψm) and IVF (in vitro fertilization) ability of sex-sorted sperm were investigated. For the sex-sorted sperm of bulls A, B and C, 1 × 10-3 M VC or 1 × 10-4 M Lyc treatment significantly decreased their MDA levels and PS translocation and increased their Δψm levels and cleavage rates after IVF. When blastocysts were concerned, 1 × 10-4 M Lyc significantly improved the blastocyst rates and their IFN-tau expression of bulls A and C. In conclusion, supplementation of 1 × 10-3 M VC or 1 × 10-4 M Lyc in washing and fertilization medium contributed greatly to improving the fertilization capacity of sex-sorted bull sperm during IVF procedure.

To investigate the effects of dietary supplementation of WGBR on lipid metabolism, C57BL/6J mice were fed a normal chow diet, a high-fat diet based on corn starch, a high-fat diet based on white rice, and low or high dosage of black rice for 12 weeks. WGBR alleviated high-fat diet-induced increase in body weight and visceral weight; reduced serum TC, TG, and non-HDL-C/HDL-C levels; and increased fecal sterols and fat excretion. Furthermore, WGBR decreased hepatic TG and TC contents through the pathway of AMPK. This, in turn, decreased PPARγ, SREBP-1c, FASN, ACC, and HMGCOR-A and increased LXRα, PPARα, and CPT1α at the gene level. Further, it lowered PPARγ and elevated PPARα, p-ACC/ACC, and p-AMPKα/AMPKα at the protein level. Additionally, WGBR treatment decreased gene expression of NPC1L1, ACAT2, MTTP, which regulated lipid absorption in the intestine and preserved CYP7A1, ABCG5/8 that transported cholesterol from the liver and enterocytes to the intestinal lumen.

Kinetics of the imidization reaction of poly (amic acid) (PAA) film based on pyromellitic anhydride (PMDA) and 4,4′-diaminodiphenyl ether (ODA) was studied by infrared spectroscopy. Attention is paid to the effect of solvent content inside the sample to the reaction kinetics. The results show that the presence of solvent favors the imidization reaction, rendering a much higher reaction kinetics than the case of without solvent. The data indicates that there is almost one NMP solvent molecule lost per imidization reaction. The kinetics of isothermal imidization reaction exhibits huge heterogeneity and is well-fitted by the Kohlraush-Williams-Watts (KWW) equation, from which the characteristic reaction time and the stretching exponent are determined. Both of them decrease with the increasing of the imidization reaction temperature, demonstrating the reaction is retarded with the proceeding of the reaction together with the creation of bigger dynamical heterogeneity.

Three novel AuI polyynes have been prepared in high yield by copolymerization between an AuI complex precursor and different ethynyl aromatic ligands. The investigation of their photophysical behavior has indicated that forming polyynes through polymerization not only maintains the high transparency of the corresponding AuI polyynes similar to those of their corresponding small molecular AuI acetylides, but also effectively enhances their triplet (T1) emission ability. Critically, owing to their enhanced T1 emission ability, all the AuI polyynes exhibit a stronger optical power limiting (OPL) ability against a 532 nm laser than the corresponding small molecular AuI acetylides. The AuI polyynes based on fluorene and triphenylamine ligands show even better OPL performance than the state-of-the-art OPL material C60, indicating their great potential in the field of laser protection. More importantly, in a prototype OPL device made by doping the fluorene-based AuI polyyne into a polystyrene (PS) solid matrix, substantially improved OPL activity has been observed compared with that in the solution, demonstrating its great potential for practical application. All these results have provided a new strategy to achieve a balance between high OPL activity and good transparency for OPL materials, representing a valuable attempt towards developing new OPL materials with high performance to cope with the key problems in the field of nonlinear optics.

The effective charge and evolution of single chains of a DNA i-motif during its unfolding process are investigated at the single molecule level. Using fluorescence correlation spectroscopy and photon counting histograms, the single chain dimensions and electrical potential of cytosine-rich human telomeric oligonucleotides are monitored, during their unfolding from the i-motif to the random coil state. It is discovered that the effective charge density of the DNA chain is very sensitive to conformation changes and the results remarkably expose the existence of an intermediate state of the unfolding process. A huge difference in pH value exists in the vicinity of the DNA chain and the bulk solution, depending on the salt concentration, as reflected by a down-shift in the pH value of unfolding. The presence of an external salt in the solution helps to stabilize the i-motif structure at low pH values due to the reduction of the effective charge density. It can also destabilize the folded structure in the pH range of the conformation transition due to the elevation of the local pH value, encouraging the deprotonation of the cytosine groups. These results provide new information for understanding the structure and stability of i-motif DNA, and its biological function, as well as the building blocks for smart nanomaterials.

Two simple salicylaldehyde-based sensors BDQ and BQ were developed, which had been applied in anion sensing and anti-counterfeiting. Their chemical structures were determined by the 1H, 13C NMR and mass spectra. In the anion sensing investigations, F− ions exhibited more competitive response over the others, thus the related detecting limits, anti-interference ability, stoichiometry and sensing mechanism had been carefully carried out. Impressively, once the F− ions were added, the color of the sensor solutions obviously transformed from colorless to yellow, directly recognizing by naked eyes. On the other hand, these sensors were almost non-emissive in solutions, the green fluorescence were successfully turned on after adding fluoride anions. Moreover, the F− ion detection limits achieved by these sensors were as low as 7.5 × 10−7 M, much lower than that of World Health Organization (WHO) permission level. Most importantly, the mechanism of colorimetric change and turn-on fluorescence was safely attributed to the excited-state proton transfer (ESPT) process coming from the sensor-F− complex constructed by the hydrogen bond, which had been deeply interpreted by the NMR and mass titration experiments as well as the theoretical calculations. Finally, the practical application of these sensors for fluoride ion detections in real environment were conducted as well. Meanwhile, considering the reversible fluorescence transformation from blue to green, the high-level and repeatable anti-counterfeiting patterns were developed. Based on all of the results, it's expected that this contribution could provide useful clues for design the high-performance chemo-sensors and anti-counterfeiting materials.

The present study investigated the effects of melatonin on bovine oocyte maturation and subsequent embryonic development in vitro. Results showed that the nuclear and cytoplasmic maturation, characterized by first polar body extrusion, normal distribution of cortical granules and mitochondria, as well as increased mitochondrial membrane potential, were significantly improved in 10-9 mol/L melatonin-treated oocytes. Melatonin supplementation reduced intracellular reactive oxygen species level and enhanced glutathione production. Meanwhile, the presence of melatonin (10-9 mol/L) during oocyte maturation resulted in a decreased early apoptotic rate in oocytes. After in vitro fertilization, oocytes receiving melatonin supplementation exhibited a significantly higher blastocyst formation rate and yielded a markedly lower number of apoptotic cells. Mechanistic explorations showed that addition of 10-9 mol/L melatonin to in vitro maturation media significantly attenuated the transcript level of caspase-3, while the expressions of BCL-2, XIAP, CAT and HSP70 were significantly reinforced in the resultant embryos. Taken together, melatonin ameliorates bovine oocyte maturation potential, and the beneficial effects can affect subsequent embryonic development. The protective role of melatonin may be due to its anti-apoptotic and anti-oxidative activities.

The application of polyethylene glycol (donated as PEG), as an environmentally benign solvent instead of water, in rhodium catalyzed hydroformylation of long chain alkenes by using water soluble phosphine BISBIS or TPPTS (TPPTS: sodium salt of sulfonated triphenylphosphine, BISBIS: sodium salt of sulfonated 2,2′-bis(diphenylphosphinomethyl)-1,1′-biphenyl) is herein reported. The conversion of long chain alkenes in PEG-200 could reach above 95.0% after a short reaction time (15 min). In addition, an efficient phase separation and recycling of PEG-200 and catalyst were achieved. The leaching of rhodium into product phase detected by ICP-AES was less than 0.06 wt% of the initial amount.

Tunable optical diffusers have attracted attention because of the rapid development of next generation stretchable optoelectronics and optomechanics applications. Flexible wrinkle structures have the potential to change the light path and tune the diffusion capability, which is beneficial to fabricate optical diffusers. The generation of wrinkles usually depends on an external stimulus, thus resulting in complicated fabricating equipment and processes. In this study, a facile and low-cost method is proposed to fabricate wrinkle structures by the self-wrinkling of thermal-cured polymer for tunable optical diffusers. The uncured polydimethylsiloxane (PDMS) precursors were exposed to UV/ozone to obtain hard silica layers and then crosslinked via heating to induce the wrinkle patterns. The wrinkle structures were demonstrated as strain-dependent tunable optical diffusers and the optical diffusion of transmitted light via the deformable wrinkle structures was studied and adjusted. The incident light isotropically diffused through the sample at the initial state. When the wrinkle structures deformed, it showed a more pronounced isotropic optical diffusion with uniaxial tensile strain. The optical diffusion is anisotropical with a further increase in uniaxial tensile strain. The proposed method of fabricating wrinkles by UV/ozone-assisted self-wrinkling of thermal-cured polymer films is simple and cost-effective, and the obtained structures have potential applications in tunable optical diffusers.

The inhibition of glycosidase activity is regarded as an effective treatment for diabetes mellitus. Bilberry (Vaccinium myrtillus L.) fruit has a high content of anthocyanins with various biological activities. The objective of this study was to investigate the inhibitory activity of anthocyanin-rich bilberry extract (BE) on α-glucosidase and α-amylase and their interaction mechanisms in vitro. The IC50 values of BE with regard to α-glucosidase and α-amylase inhibition were 0.31 ± 0.02 and 4.06 ± 0.12 mg/mL, respectively. The enzyme kinetics revealed that BE acts as a mixed-type inhibitor against α-glucosidase and α-amylase. Moreover, the fluorescence of two glucosidases showed significant quenching by BE. FTIR spectra and differential scanning calorimetry (DSC) indicated that BE changed the enzyme structure and decreased its stability. A morphological observation of starch granules found that BE inhibited the activity of α-amylase to postpone the hydrolysis of starch. Furthermore, the in vivo study further showed that BE had a hypoglycaemic effect. The most suitable conformation (main anthocyanidins of BE) and optimal binding site (α-glucosidase, α-amylase) were assayed by molecular docking. In conclusion, this study revealed that BE could be a potential glycosidase inhibitor.

Mesoporous Cu 2 O particles with different morphologies were synthesized via simple one-pot reactions. Effects of reducing agents, dispersant, template, and temperature on the structure of the prepared materials were investigated. Mesoporous flower-shaped Cu 2 O materials were obtained at 70 ℃ using glucose as a reductant . Different hollow microsphere shapes of Cu 2 O could be prepared at 40 ℃ using another type of reductant, ascorbic acid . The results indicated that the uniform morphology of synthesized Cu 2 O with mesopores presented a maximum specific surface area of 45.3 m 2 /g. Furthermore, the as-prepared Cu 2 O particles showed good photodegradation efficiencies of methyl orange in the range of 86.0–93.7%, depending on their morphologies.

A series of charged dinuclear Cu(I) complexes were developed by functionalization of both central bipyrimidine-based ligands and organic phosphine ligands. The chemical modification of the ligands can effectively affect the absorption, emission and thermal stability properties of the Cu(I) complexes. The decomposition temperatures ( T d ) are improved by using bulky ligands. Interestingly, the complexes with the triphenylamine group on the bipyrimidine ligand show higher photoluminescence quantum yield (PLQY) than the complexes bearing the triphenylphosphine oxide group, while the complexes having the triphenylamine group on the phosphine ligand display lower PLQY. The functional groups also show an obvious influence on the redox behaviors of these complexes. Most importantly, the organic light-emitting diodes (OLEDs) based on selected dinuclear Cu(I) complexes show impressive EL features. The best performance is achieved by the device based on complex Cu-MD-1 with the maximum external quantum efficiency (EQE) of 6.09%, current efficiency (CE) of 12.78 cd A −1 and power efficiency (PE) of 5.93 lm W −1 , representing the state-of-the-art EL efficiencies reported for the charged Cu(I) complexes. In addition, the OLEDs based on these Cu(I) complexes can emit warm white light with Color Rendering Index (CRI) as high as 88 and Commission Internationale Ed I'eclairage (CIE) coordinates close to (0.40, 0.46), showing the great potential of these Cu(I) complexes in fabricating single-emitter warm WOLEDs.

The effect of strengthening of interaction between single fluorescent probes and polymer matrix to the probes' dynamics is investigated using single molecule fluorescence defocus microscopy. By introducing multiple hydroxyl groups to the fluorescent probes (perylene diimide derivatives) which builds up hydrogen bonds between the probe and polymer matrix, the dynamics is discovered to be retarded. This is evidenced by the lowering of the frequency of the vibrational modes in the power spectra of the rotation trajectories of individual fluorescent probes, and also by the decrease in population of rotating probes. The results show that by strengthening the probe-matrix interaction, the local dynamics detected by the probes is equivalent to that detected by a bigger probe, due to the enhanced friction between the probe and the polymer matrix.

Two homoleptic thiazole-based IrIII phosphorescent emitters, Ir-3Tz1F and Ir-3Tz2F, with fluorinated 2-phenylthiazole-type ligands were designed and prepared. Their thermal stability, and photophysical and electrochemical properties, as well as electroluminescent (EL) performances in both monochromic OLEDs and solution-processed WOLEDs were investigated. When doped in monochromic OLEDs made by vacuum deposition, Ir-3Tz1F gave the maximum EL efficiencies with ηL of 56.2 cd A−1, ηext of 15.8% and ηp of 50.2 lm W−1. Critically, solution-processed WOLEDs based on Ir-3Tz1F with three primary colors could achieve an excellent trade-off among the stable balanced white EL spectra, a high EL efficiency and a high color rendering index (CRI). The optimized solution-processed WOLED exhibited very attractive EL efficiencies of 33.4 cd A−1, 16.5% and 30.6 lm W−1, while maintaining both a high CRI of ca. 80 and very stable Commission Internationale de L’Eclairage (CIE) coordinates in a wide driving voltage range from 4 V to 11 V.

Functional PtII ppy-type complexes (ppy = 2-phenylpyridine anion) with pyridine and chloride monodentate ligands are prepared, which show high electroluminescence efficiencies.

Encouraged by the high photoluminescence (PL) of the bis-ZnII salphen complexes, a series of coordination polymers have been successfully developed through metal–ligand interactions between the bis-ZnII salphen complexes and functional ditopic ligands. These bis-ZnII salphen coordination polymers can exhibit high thermal stability up to 433 °C. Their PL spectra show an emission maximum peaking at ca. 570 nm in solution and ca. 580 nm in neat films. The PL investigation of the neat films for these bis-ZnII salphen coordination polymers has indicated that the functional ditopic ligands can restrain the molecular packing among the bis-ZnII salphen units for enhancing their PL intensity. Hence, the functional ditopic ligands should exhibit great potential in avoiding exciton quenching in the emission layer formed by these bis-ZnII salphen coordination polymers in polymer light-emitting diodes (PLEDs). Benefiting from such a molecular design, these bis-ZnII salphen coordination polymers can exhibit a peak luminance (Lmax) of 8658 cd m−2, a maximum external quantum efficiency (ηext) of 3.18%, a maximum current efficiency (ηL) of 6.2 cd A−1 and a maximum power efficiency (ηP) of 4.4 lm W−1. These attractive results represent the state-of-the-art EL performances ever achieved by Schiff base ZnII coordination polymers, which would provide significant clues for developing high performance PLEDs based on Schiff base ZnII coordination polymers.

A cyclometalating ligand containing a 9-phenyl-9-phosphafluorene oxide (PhFlPO) moiety has been synthesized and used to construct asymmetric tris-heteroleptic cyclometalating IrIII complexes in combination with other ppy-type (Hppy = 2-phenylpyridine) ligands containing a functional group with a different charge carrier injection/transporting character. Their photophysical properties, electrochemical behaviors, and electroluminescent (EL) performances have been characterized in detail. Time-dependent density functional theory (TD-DFT) and natural transition orbital (NTO) calculation were carried out to gain insight into the photophysical properties of these complexes. The NTO results show that the characters of the lowest triplet excited states (T1) can be delicately manipulated through the combination of different cyclometalating ligands. In addition, the strong electron injection/transporting (EI/ET) ability associated with the PhFlPO moiety can confer EI/ET properties to the asymmetric tris-heterolepti...

Apple phlorizin has many biological activities, such as antioxidant and liver protection. The present study aimed to evaluate the roles of apple phlorizin against hydrogen peroxide (H2 O2 )-induced oxidative damage in HepG2 cells. In this study, treatment with apple phlorizin (100 and 150 μg/ml) decreased the production of reactive oxygen species and alleviated apoptosis as well as DNA damage in H2 O2 -induced HepG2 cells. These effects were associated with the increased activity of antioxidant enzymes, enhanced the ARE-driven phase II antioxidant gene expression and its upstream Nrf2 protein expression, and decreased apoptosis-related gene expression. However, the phase II antioxidant gene expression and Nrf2 protein expression upregulated by phlorizin were reversed by Nrf2 shRNA transfection. These results showed that phlorizin relieves oxidative stress, DNA damage, and apoptosis in H2 O2 -induced HepG2 cells, at least partially, by regulating the expression of Nrf2 protein and apoptosis-related genes. PRACTICAL APPLICATIONS: Apple phlorizin is a polyphenol compound extracted from apple or apple juice. This report highlighted a protective effect of phlorizin on antioxidant stress, DNA damage, and apoptosis in H2 O2 -induced HepG2 cells. These results suggested that phlorizin may be developed for functional foods.

This study aimed to investigate the lipid lowering effects of lutein and explore the specific regulatory mechanism of lutein in HepG2 cells. The experimental results showed that compared with free fatty acids (FFAs)-treated group, 16 μM lutein showed a significant lipid-lowering effect, decreased TG and TC levels, and alleviated oxidative stress. In addition, lutein decreased the gene expression levels related to adipose synthesis, while increased the expression levels of genes related to lipid oxidation, but can be reversed by compound C. Furthermore, 16 μM lutein increased the activity of AMPK, the ratio of AMP/ATP and the expression of AMPK phosphorylated protein. The docking results showed the interaction of lutein with the γ-subunit of AMPK protein. These results together suggested that lutein attenuated oxidative stress and liver fat accumulation induced by FFAs by activating AMPK.

Esophagus cancer is the seventh cause of cancer-related deaths globally. In this study, we analyzed interleukin 6 (IL-6) gene expression in human esophagus cancer patients and showed that IL-6 mRNA levels are significantly higher in tumor tissues and negatively correlated with overall survival, suggesting that IL-6 is a potential therapeutic target for esophagus cancer. We further demonstrated that apigenin, a nature flavone product of green plants, inhibited IL-6 transcription and gene expression in human esophagus cancer Eca-109 and Kyse-30 cells. Apigenin significantly and dose-dependently inhibited cell proliferation and promoted apoptosis while stimulating the cleaved PARP (poly ADP-ribose polymerase) (C-PARP) and caspase-8 expression. It suppressed VEGF (Vascular endothelial growth Factor) expression and tumor-induced angiogenesis. Pretreatment of cells with IL-6 could completely reverse apigenin-induced cellular changes. Finally, using a preclinical nude mice model subcutaneously xenografted with Eca-109 cells, we demonstrated the in vivo antitumor activity and mechanisms of apigenin. Taken together, this study revealed for the first time that apigenin is a new IL-6 transcription inhibitor and that inhibiting IL-6 transcription is one of the mechanisms by which apigenin exhibits its anticancer effects. The potential clinical applications of apigenin in treating esophagus cancer warrant further investigations.

Pancreatic ductal adenocarcinoma (PDAC) includes two molecular subtypes, of which the basal-like subtype is associated with the shortest survival and is highly resistant to chemotherapy. The basal-like subtype is defined by a 25-gene signature; however, the role of these genes in promoting tumor aggression remains unexplored. Here, we set out to uncover the mechanisms of chemoresistance and explore targeted therapies for this subtype. We focused on studying an oncofetal antigen, keratin 17 (K17), which is the most overexpressed hallmark gene of the basal-like PDAC. We manipulated the expression of K17 and found that in multiple in vitro and in vivo models of PDAC, spanning human and murine PDAC cells and orthotopic xenografts, K17 expression resulted in a greater than two-fold increase in resistance to Gemcitabine (Gem) and 5-fluorouracil, the major chemotherapeutic agents in standard-of-care treatments. To uncover the mechanisms associated with K17-induced chemoresistance, we performed unbiased metabolomic studies in isogenic PDAC cell lines and found that compared to control cells, K17 increases intracellular levels of deoxycytidine (dC) by four-fold that promote Gem (dC analogue) resistance. Based on previous findings that K17 enters nucleus to regulate gene expression, we explored whether K17 triggers metabolic reprogramming at the transcriptional level and found that enzymes involved in pyrimidine biosynthesis are positively correlated with K17 expression in PDAC cells. Given that it is still poorly understood how K17 regulates gene expression, we performed domain-prediction analyses. We discovered and validated a novel chromatin remodeling domain on K17 that is required for metabolic reprogramming. We are now performing ChIP-Seq and RNA-Seq to understand how this domain alters pyrimidine biosynthesis. To identify small molecules that could target K17-expressing PDACs potentially by disrupting metabolic reprograming, we performed an unbiased high-throughput drug screen and found that Podophyllotoxin (PPT), a microtubule inhibitor, significantly and selectively killed K17-positive compared to K17-negative PDAC cells. In the clinic, another microtubule inhibitor, Paclitaxel (PTX), is used in combination with Gem as a first line chemotherapy. Surprisingly, when combined with Gem, PPT but not PTX, was synergistic in inhibiting the viability of K17-expressing PDAC cells and enhanced survival of mice bearing K17-expressing PDACs. Currently, we are exploring the role of PPT in regulating pyrimidine biosynthesis. In summary, we identified a novel pathway of chemoresistance and a compound that could result in developing a biomarker-based personalized therapy. Citation Format: Chun-Hao Pan, Yuka Otsuka, BanuPriya Sridharan, Melissa Woo, Cindy V. Leiton, Sruthi Babu, Mariana Torrente Gonçalves, Ryan R. Kawalerski, Ji Dong K. Bai, Richard A. Moffitt, Jiang Zhao, David K. Chang, Andrew V. Biankin, Tim Duong, Pankaj K. Singh, Louis Scampavia, Timothy Spicer, Kenneth R. Shroyer, Luisa F. Escobar-Hoyos. Targeting a novel rewired pathway of nucleotide metabolism that drives chemoresistance in the most lethal molecular subtype of pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-023.

This study demonstrates that the conformation transition of single polymer molecules can be adjustable by applying external irradiation. By choosing poly N-isopropylacrylamide as the model system, its coil-to-globule conformation transition temperature is shifted with application of external UV irradiation, due to the photo-isomerization of the azobenzene moiety attached to the chain end. The investigation was conducted at single molecular level by fluorescence correlation spectroscopy, using hydrodynamic radius as the measure of chain dimension. It is discovered that the coil-to-globule transition temperature of the PNIPAM-azo can be controlled up to a difference of 12 °C upon external irradiation, due to the difference in polarity of the azobenzene end group.

Lateral diffusion of cyclic polystyrene at the interface between fused silica and dichloromethane is investigated at the single-molecular level. Narrowly distributed cyclic polystyrene (c-PS) of high purity with molecular weights spanning nearly an order of magnitude is prepared via atom transfer radical polymerization (ATRP) and Cu-catalyzed azide/alkyne cycloaddition (CuAAC) click reaction. The diffusion coefficients (D) of c-PS and its linear analogue (l-PS) on the surface are measured by fluorescence correlation spectroscopy (FCS). The diffusion coefficient of c-PS is discovered to have an inverse dependence on molecular weight, D ∼ M−1, in contrast to the case of linear polystyrene, which reproduces a stronger molecular weight dependence, D ∼ M−3/2. The slower interfacial motion of cyclic chains is attributed to their stronger binding to the surface and more importantly, the unique surface diffusion mechanism due to the absence of free chain ends.