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Abstract: Estrogen-related receptor gamma (ERRγ), one of three members of the ERR family, is an inducible transcription factor. ERRγ has dual functions in different tissues. The decreased expression of ERRγ in the brain, stomach, prostate, and fat cells can cause neuropsychological dysfunction, gastric cancer, prostate cancer, and obesity. However, when ERRγ is present in the liver, pancreas, and thyroid follicular cells, ERRγ overexpression is related to liver cancer, type II diabetes, oxidative liver injury, and anaplastic thyroid carcinoma. Signaling pathway studies have confirmed that ERRγ agonists or inverse agonists can regulate ERRγ expression to treat related diseases. The collision between residue Phe435 and the modulator is a key factor determining the activation or inhibition of ERRγ. Although more than 20 agonists and inverse agonists of ERRγ have been reported, no clinical studies have been found in the literature. This review summarizes the important relationship between ERRγ-related signaling pathways and diseases, research progress, and the structure-activity relationship of modulators. These findings provide guidance for further study on new ERRγ modulators.

Abstract: Estrogen-related receptor alpha (ERRα), a member of the nuclear receptor superfamily, is strongly expressed in breast cancer cells. Its overexpression is associated with poor prognosis in triple-negative breast cancer (TNBC). ERRα expression could be inhibited by the downregulation of upstream oncogenic growth factors mTOR, HER2, and PI3K. Low expression of ERRα could suppress the migration and angiogenesis of tumor cells by inhibiting the activity of its downstream signals VEGF and WNT11. Studies have confirmed that ERRα inverse agonists can inhibit ERRα expression to treat breast cancer. Inverse agonists of ERRα could disrupt the interactions of ERRα with its coactivators and inhibit tumor development. Existing ERRα inverse agonists have shown moderate efficacy in inhibiting the growth of breast cancer cells. Clinical inverse agonists of ERRα have not been found in the literature. This review focuses on the research progress and the structure-activity relationship of ERRα inverse agonists, providing guidance for the research and discovery of new anti-tumor compounds for TNBC.

Cyclin-dependent kinase 12 (CDK12) is a transcription-associated CDK that plays key roles in transcription, translation, mRNA splicing, cell cycle, and DNA damage repair. Research has identified high expression of CDK12...

Aim: CDK4 is a promising target for breast cancer therapy. This study aimed to explore the structure–activity relationship of CDK4 inhibitor abemaciclib analogs and design potent CDK4 inhibitors for breast cancer treatment. Methods & results: A faithful 3D quantitative structure–activity relationship model was established by molecular docking, comparative molecular field analysis and comparative molecular similarity index analysis based on 56 abemaciclib analogs. Molecular dynamics simulation studies revealed the key residues of the interaction between CDK4 and inhibitors. Four novel inhibitors with satisfactory predicted binding affinity to CDK4 were designed. Conclusion: The 3D quantitative structure–activity relationship and molecular dynamics simulation studies provide valuable insight into the development of novel CDK4 inhibitors.

Cupric iodide and cuprous oxide as hole–transporting layer (HTL) materials in perovskite solar cells (PSCs) have been reported. However, the compositional instability and poor electrical conductivity of films in ambient air have limited their applications in PSCs. Cupric oxide (CuO) films may be used as a HTL material in PSCs due to their high electrical conductivity and high stability in ambient air even if their hole mobility is still required to further increase. Herein, single-phase monoclinic CuO films with p–type conduction were room-temperature prepared via direct–current reactive magnetron sputtering, thereby garnering low–cost advantage. CuO film prepared at 1:3 O2/Ar flow ratio (Ro/a) was best crystallized and preferred 〈−1 1 1〉 oriented, thereby resulting in a record mobility of 48.44 cm2/Vs and small electrical resistivity of 0.50 Ω∙cm. The PSCs with CuO as HTL material obtained 1.3% power conversion efficiency, indicating that CuO films with record hole mobility could be used as a HTL material in PSCs.

Estrogen-related receptor α (ERRα), which is overexpressed in a variety of cancers has been considered as an effective target for anticancer therapy. ERRα inverse agonists have been proven to effectively inhibit the migration and invasion of cancer cells. As few crystalline complexes have been reported, molecular dynamics (MD) simulations were carried out in this study to deepen the understanding of the interaction mechanism between inverse agonists and ERRα. The binding free energy was analyzed by the MM-GBSA method. The results show that the total binding free energy was positively correlated with the biological activity of an inverse agonist. The interaction of the inverse agonist with the hydrophobic interlayer composed of Phe328 and Phe495 had an important impact on the biological activity of inverse agonists, which was confirmed by the decomposition of energy on residues. As Glu331 flipped and formed a hydrogen bond with Arg372 in the MD simulation process, the formation of hydrogen bond interaction with Glu331 was not a necessary condition for the compound to act as an inverse agonist. These rules provide guidance for the design of new inverse agonists.

ERRγinverse agonist is a powerful therapeutic target for the treatment of cancers and certain metabolic disorders. Until now, only GSK5814 was reported as selective ERRγinverse agonist. So 60 newly hydroxytamoxifen analogues were selected to perform molecular docking and 3D-QSAR study to design more selective inverse agonist of ERRγ. Both established CoMFA and CoMSIA models obtained high predictive and satisfactory value, demonstrated that bulky, hydrophobic and negative electrostatic substitutions are preferred at R2 position, and introducing hydrophilic and H-bond donor and acceptor groups at R1 and R4 positions is greatly important for improving binding activities. The obtained information will be useful to provide clues for rationally designing novel and high potency ERRγinverse agonists.

Preparation of single-phased indium-doped copper oxide (CuO:In) thin films with high quality at low temperature is crucial for the commercial application of CuO-based solar cells and light-emitting devices. Herein, direct-current magnetron sputtering assisted with high sputtering power and reactive pressure technique was used to prepare monoclinic CuO:In thin films at room temperature. The influence of sputtering power (Pspu) on the microstructure and the optical and electrical properties of the films were studied. The roles of indium in the CuO:In thin films were also proposed. CuO:In thin films are single-phased and monoclinic in structure. The crystallization and the preferred 〈−111〉 orientation of the films were enhanced with increased Pspu. The red shift of the film absorption edge was due to the decrease and increase of the lattice strains along crystal axes a and b with Pspu, respectively. A conducting transition from p type to n type of the films at 100 W Pspu was closely related to the increased substitution of copper by indium. The p- and n-type conductions of the films were mainly due to the copper vacancies and interstitials oxygen and to the effective substitution of copper by indium in the films, respectively. Increased Pspu increased the free carrier concentration and decreased the mobility of the films. The free carrier concentration reached the maxima of 9.333 × 1018 /cm3 at 100 W Pspu, whereas the mobility reached the maxima of 23.38 cm2/Vs at 60 W Pspu.

Perovskite MAPbI3 (MA = methylammonium, CH3NH3) films and solar cells have thoroughly been studied in recently years. However, the formation mechanism of MAPbI3 in the two-step sol-gel process is not reported and not well understood yet. Thus in this work, the cubic perovskite MAPbI3 films with preferred 〈110〉 orientation were fabricated on the glass substrates via the two-step sol-gel process. Impact of soaking time (tsoaking) of PbI2 in MAI in isopropyl alcohol (IPA) solution was thoroughly studied on the microstructure and the optical properties of the MAPbI3 films. The formation mechanism of MAPbI3 in the two-step sol-gel process was in particular proposed. The blue and red shifts of the absorption edge of the films with increase of tsoaking are attributed to the improved crystallization and to the weakened surface effect of the grains, respectively. An intermediate metal-organic frameworks (MOF) structure of PbI2:MAI:IPA is formed during the soaking due to Pb weakly coordinating with IPA organic molecules. The unstable MOF structure is collapsed during the following annealing, and PbI2 and ions I− from the hydrolyzed MAI form the stable PbI64− cubic frame. Ions (MA)+ diffuse to the interstice positions in the cubic frame structure under the electrostatic force, thus producing the ultimate MAPbI3.

Single-phased n-type copper oxide (CuO) films were first prepared on glass substrates at a substrate temperature (Tsub) ≥ 500 °C by DC magnetron sputtering. The n-type conduction of the film is mainly attributed to the oxygen vacancies besides interstitial copper, due to the larger production probability of the oxygen vacancies than the interstitial copper. N-type CuO film with an optical absorption edge of ca. 1.9 eV has a maximum free-electron concentration of 1.457E19 cm−3 and a maximum electron mobility of 1.727 cm2−1s−1. The reduced mobility of n-type CuO films with increase of Tsub is mainly attributed to the enhancement of the point-defect scatterings.

Single-phased monoclinic CuO films with direct energy gap were deposited on the clean glass substrates by direct-current magnetron sputtering method. Effect of substrate temperature was in particular studied on the microstructure, and the optical and electrical properties of the films. With increase in substrate temperature, the crystallization of the polycrystalline CuO films is enhanced and thus the CuO film at substrate temperature of 600 °C has a clear preferred orientation. Substrate temperature has different effect on the stress along the crystal axis a, b, and c, indicating an anisotropic growth along different crystal axis. The absorption edge of the films in the vicinity of 1.88 eV first moves towards short wavelength direction and then towards long wavelength direction with substrate temperature, which can be explained by the quantum size effect of the crystallites. The conduction transition of the films from p to n type takes places at substrate temperature of 500 °C. The p-type conduction is attributed to the copper vacancies and interstice oxygen, while n-type conduction is to the oxygen vacancies and interstice copper. The CuO film deposited at high substrate temperature has a larger carrier concentration and a lower electrical resistivity.

Selecting optimum planting time (PT) in maize–soybean relay intercropping system (MSRI) is important to obtain higher intercrop yields because planting time decides the co‐growth duration and competitive ability of intercrop species in MSRI. However, little is known on how planting time (co‐growth duration) changes the interspecific interaction resulting in a seed‐yield difference between intercropping and sole cropping system. Therefore, this field study was initiated to determine the effects of changing co‐growth duration on competitive interactions, growth, and yield of intercrop species under MSRI. The sole soybean and relay‐cropped soybean were planted on PT1 (15–20 May, 90 days of co‐growth duration in MSRI); PT2 (5–10 June, 70 days of co‐growth duration in MSRI); and PT3 (25–30 June, 50 days of co‐growth duration in MSRI) to generate different size‐asymmetric competition between component crops in MSRI. Results showed that sole soybean produced the mean highest (2.93 t/ha) seed yield under PT2, and the mean lowest (2.51 t/ha) seed yield under PT1. However, in MSRI, PT3 increased the soybean yield by 29.1% and 13.3% compared to PT1 and PT2, respectively. The PT3 also increased the maize yield by 7.4% and 2.9% than PT1 and PT2, respectively, and it reduced the yield differences of maize and soybean between relay intercropping and sole cropping systems. In MSRI, decreased co‐growth duration promoted the soybean plants to achieve the higher crop growth rate, and biomass accumulation, which ultimately improved the soybean resilience toward size‐asymmetric competition created by maize plants. Furthermore, as compared to PT1 and PT2, planting time PT3 significantly increased the competitive ratio (by 10.1% and 17.3%, respectively) of soybean plants. Overall, the PT3 achieved the average highest land equivalent ratio of 1.63, which is significantly higher than PT1 (by 12.3%) and PT2 (by 10.6%). In conclusion, this study implied that in MSRI, the determination of proper soybean planting time (co‐growth duration) is one of the most critical factors to reduce the competition between the intercrops and to obtain higher crop yields.

Proanthocyanidin A2 (PA2), one of A-type proanthocyanidins, has been shown to harbor a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-HIV, anti-CDV and anti-?-glucosidase activities. However, little is known about the role for PA2 in regulating PDGF-induced VSMC proliferation and migration. In the present study, we investigated the possible effects of PA2 on PDGF-BB-induced proliferation, migration and inflammation in VSMCs in vitro to mimic a postangioplasty PDGF shedding condition. Herein, the data clearly show that PA2 markedly inhibited proliferation, migration and inflammatory responses at 0-30??g/ml concentration in VSMCs in vitro. 10-30??g/ml PA2 inhibited PDGF-mediated NAD(P)H oxidase activation and intracellular ROS formation in VSMCs. Furthermore, the effects exerted by PA2 involve the participation of KDR and Jak-2/STAT-3/cPLA2 signaling pathways. These data also highlight the possible therapeutic use of PA2 in vascular proliferative diseases, where abnormal proliferation and migration play important pathological roles.

PTP1B serving as a key negative regulator of insulin signaling is a novel target for type 2 diabetes and obesity. Modification at ring B of N-{4-[(3-Phenyl-ureido)-methyl]-phenyl}-methane-sulfonamide template to interact with residues Arg47 and Lys41 in the C site of PTP1B by molecular docking aided design resulted in the discovery of a series of novel high potent and selective inhibitors of PTP1B. The structure activity relationship interacting with the C site of PTP1B was well illustrated. Compounds 8 and 18 were shown to be the high potent and most promising PTP1B inhibitors with cellular activity and great selectivity over the highly homologous TCPTP and other PTPs.

Zanthoxylum bungeanum meal (ZBM) is the by-product of Z. bungeanum seeds after pressing. It is restricted as a feed additive because it contains stimulating and potentially harmful substances, which are alkylamides and alkaloids. This study described the use of Lactobacillus paracasei and L. acidipiscis isolated from ZBM in solid-state fermentation of ZBM to reduce the concentration of undesirable alkylamides and alkaloids. By optimizing the substrate and fermentation conditions, the minimum contents of alkylamide and alkaloid were 2.96 and 3.20 mg/g, and the degradation rates reached 51.86% and 39.59%, respectively. Moreover, the biotransformation pathways of hydroxyl-α-sanshool and chelerythrine were established by identifying the metabolites. Bacterial diversity was shift significantly, and the relative abundance of Lactobacillus increased from 0.10% to 99.0% after fermentation. In conclusion, this study introduced a reliable strategy for processing ZBM as a feed additive.

Unlike other breast cancer subtypes, targeted therapies for triple negative breast cancer (TNBC) have yet to progress past clinical trial stage to approval. Accumulating evidences demonstrated that expression of estrogen-related receptor alpha (ERRα) indicated worse prognosis and correlated with poor outcome in breast cancers including TNBC. Therefore, ERRα modulators/regulators may be potential in the therapeutic treatment of breast cancers. In the current study, we presented a novel compound LingH2-10 that bound to ERRα, as identified using a time-resolved fluorescence resonance energy transfer assay (TR-FRET) with the IC50 value of 0.64±0.12μM. Further, functional activity was determined by transient transfection luciferase reporter assay in order to validate the utility of the binding affinity in a cellular context. LingH2-10 showed selective inhibition on ERRα transcriptional activity with the IC50 value of 0.58±0.09μM in cell-based luciferase reporter assay. Moreover, representative in vitro results showed that LingH2-10 suppressed the proliferation of various human cancer cells, and inhibited the migration of triple negative breast cancer cell MDA-MB-231. In addition, our results demonstrated that well known ERRα target genes such as PDK4, Osteopontin and pS2, were all significantly down modulated by LingH2-10. In vivo experiments showed that LingH2-10 (30mg/kg, every other day) observably suppressed the growth of MDA-MB-231 xenograft tumors by 42.02% compared to untreated xenograft tumors. Taken together, all these data suggested that LingH2-10, as a selective inverse agonist of ERRα, was a lead compound of anti-cancer agents for treating TNBC patients.

The estrogen-related receptor α (ERRα) is an orphan receptor and a novel target for solid tumor therapy, conceivably through effects on the regulation of tumor cell energy metabolism associated with energy stress within solid tumor micro environments. Here we describe the discovery of novel potent inverse agonists of ERRα. In vitro, compound 11 potently inhibits ERRα’s transcriptional activity by preventing endogenous PGC-1α and ERRα binding and suppresses the proliferation of different human cancer cell lines and the migration of breast cancer cells (MDA-MB-231). In vivo, compound 11 demonstrates a strong inhibitory effect on the growth of human breast cancer xenografts (MDA-MB-231) and the tumor growth is inhibited by 40.9% after treating with compound 11 (30 mg/kg). The binding mode shows that compound 11 interacts with the binding pocket of ERRα through hydrogen interactions with the residue Gly397 and hydrophobic interactions with the hydrophobic residues. All these results suggest that compound 11 represents a novel potent ERRα inverse agonist and is promising in the discovery of antitumor compounds for the treatment of triple negative breast cancer.

The EGFR is one of the most popular targets for anticancer therapies and many drugs, such as erlotinib and gefitinib, have got enormous success in clinical treatments of cancer in past decade. However, the efficacy of these agents is often limited because of the quick emergence of drug resistance. Fundamental structure researches of EGFR in recent years have generally elucidated the mechanism of drug resistance. In this review, based on systematic resolution of full structures of EGFR and their variants via single crystal x-ray crystallography, the working and drug resistance mechanism of EGFR-targeted drugs are fully illustrated. Moreover, new strategies for avoiding EGFR drug resistance in cancer treatments are also discussed.

RhoA/p27Kip1 and β-Catenin/Wnt4 signaling processes play central roles in proliferation and migration in vascular smooth muscle cells (VSMCs). ERRα, a member of orphan nuclear receptors, is a potent prognostic factor in breast, ovarian, colon and other types of tumors. However, biological significance of ERRα in VSMCs as well as the molecular mechanisms remains largely unknown. Therefore, the present study was designed to investigate whether ERRα is involved in the proliferation and migration of VSMCs in vitro and neointimal formation in vivo. The specific ERRα inverse agonist XCT790 (or ERRα shRNA) resulted in a significant inhibition of proliferation and phenotypic switch in cultured rat aortic SMCs (RASMCs). Furthermore, cycle progression, cell cycle protein transcription as well as hyperphosphorylation of the retinoblastoma protein (Rb) in RASMCs were prevented by downregulation of ERRα. Transwell assay demonstrated that migratory capacity of RASMCs was also inhibited the treatment of XCT790 (or ERRα shRNA). At the molecular levels, RhoA/p27Kip1 and β-Catenin/Wnt4 signaling pathways are involved in ERRα-mediated RASMCs growth and migration. Finally, inhibition of ERRα significantly attenuated neointimal formation in rat artery after balloon injury. These results help to further understand vascular remodeling and suggest that ERRα might be a potential target for the treatment of vascular proliferative diseases.

Protein tyrosine phosphatase1B (PTP1B), a significant negative regulator in insulin and leptin signaling pathways, has emerged as a promising drug target for Type II diabetes mellitus and obesity. Numerous potent PTP1B inhibitors have been discovered within both academia and pharmaceutical industry. However, nearly all medicinal chemistry efforts have been severely hindered because a vast majority of them demonstrate poor membrane permeability and low-selectivity, especially over T-cell protein tyrosine phosphatase (TCPTP). To search the rules about the selectivity over TCPTP and membrane permeability of PTP1B inhibitors, based on the PTP1B/inhibitor crystal complexes, the development PTP1B inhibitors defined as AB, AC, ABC and ADC types have been concluded in the review.

CuO is p-type conductive in nature because of its native point defects, and thus n-type, highly conductive CuO is difficult to obtain due to these native point defects. The introduction of trivalent metallic ions into CuO may deal with the problem. Thus in this work, non-stoichiometric n-type CuO:In3+ thin films are magnetron reactively sputtered at 25 °C (room temperature) and at different reactive pressures (Preact). Compared with CuO thin films, the CuO:In3+ thin films have considerably small electrical resistivity, thereby making CuO:In3+ film a potential candidate of light-absorbing materials in heterojunction solar cells. The high Preact helps improve the crystallization and mobility of the films by the weakened bombardment upon the film surface from the sputtered particles, and by the reduction of the free carrier concentration, respectively. The introduction of In3+ into CuO is more favorable to form n-type and high conduction by partial substitution of Cu by In3+. In addition, a conducting transition from n type to p type is observed at 1.8 Pa Preact. The 1.2 Pa Preact is more suitable for n-type CuO:In3+ for utilization in the photovoltaic application.

Protein tyrosine phosphatase 1B (PTP1B) which plays an important role in the negative regulation of insulin and leptin pathway has emerged as a novel promising therapeutic target for the treatment of type 2 diabetes mellitus and obesity. Upon careful study, a series of novel scaffold and simple synthesis method inhibitors were discovered based on the analysis of X-ray crystal structures of PTP1B/inhibitor complexes and docking simulations. Among them, compound P7 exhibited high inhibitory activity (IC50=222 nM) with moderate selectivity (8-fold) over T-cell PTPase (TCPTP) through interacting with the A, B and C binding sites of PTP1B enzyme. Further studies on cellular activities revealed that compound P7 could enhance insulin-mediated IRβ phosphorylation and insulin-stimulated glucose uptake.

Polyacrylonitrile nanofiber (PANN) membrane fabricated by electrospinning was adopted for the first time as the reactive medium to remove metal ions from the contaminated soils. Characteristics of metal ion remediation by electrokinetics/PANN permeable reactive barrier (EK/PANNPRB) were investigated. Applied voltages, initial metal ion concentrations and soil pH were changed to explore the adsorb and complexion behavior of PANN with metal ions. The results showed EK/PANNPRB had higher removal efficiency than EK without PRB. The metal ion removal efficiencies by PANNPRB decreased when the applied voltage was increased. The lower the initial metal ion concentrations and soil pH, the better were the removal rates. At the applied voltage of 25 V, metal ion concentrations of 5, 10, and 100 mg L −1 and pH of 1.2, the removal rates of Zn 2+ , Fe 3+ , and Ca 2+ were 99.15%, 98.03%, and 99.73%, respectively. The results indicated that EK/PANNPRB system was suitable for the remediation of soil contaminated by metal ions with removal rates much higher than those exhibited by the EK system without modified PRB.

High–quality p–type NiO films are crucial for NiO–based heterojunction solar cells. Herein, a series of face-centered cubic, p–type NiO films was prepared at room temperature through DC reactive magnetron sputtering. The increased sputtering power (SP) improves the film crystallization. The film's lattice strain is increased and a microstress transition from compressive to tensile stress occurs with increased SP. The film's lattice strain reduces the LO and 2LO phonon frequency. The blueshifted optical absorption edge with increased SP is caused by the improved film crystallization. The film's free hole concentration is slightly increased and subsequently reduced with increased SP. The former is mainly due to the increased number of the nickel vacancies, whereas the latter to the improved film crystallization that reduces the content of the nickel vacancies and interstitial oxygen. The hole mobility is strongly affected by the scatterings by the crystal lattice and point defects.

Single-phase NiO films with high carrier mobility and low electrical resistivity are crucial for NiO-based heterojunction solar cells. Herein, a series of face-centered cubic (fcc) nickel oxide (NiO) films was room-temperature prepared at different O2/Ar flow ratio (Roa) values through low-cost DC reactive magnetron sputtering. With increase of Roa, the film crystallization is initially improved, and the film's free carrier concentration increases, thereby resulting in a slight blue shift in optical absorption edge. The oxygen-rich state in the form of nickel vacancies and interstitial oxygen enlarges the film's lattice distortion and thus leads to a red shift in optical absorption edge. The reduced film transmittance with increase of Roa is due to the enhanced point defect scattering. The free carrier concentration of the films reaches the maxima of 3.17 × 1019/cm3 at 3:1 Roa and the hole mobility reaches the maxima of 1.53 cm2/Vs at 2:1 Roa.

Cupric oxide (CuO) films with high electrical conductivity are crucial to their potential application in heterojunction solar cells. However, intrinsic CuO films usually have low electrical conductivity. The doping of proper ions into CuO is effective for the improved electrical conductivity. Herein, a series of monoclinic, indium-doped cupric oxide (CuO:In) films was prepared at different substrate temperature (Tsub) values via low-cost DC reactive magnetron sputtering. The influence of Tsub was intensively studied on the film’s microstructure, optical and electrical behaviors. A conducting transition from p type to n type occurs at 400 °C Tsub for CuO:In films rather than 500 °C Tsub for intrinsic CuO films. The decrease in critical transition temperature is mainly caused by the substitution of copper by indium. With increase of Tsub, the film crystallization is enhanced and the point defect content is reduced in the films, thereby increasing the film’s mobility and free carrier concentration. Increased Tsub helps the effective substitution of copper by indium and thus forms the n-type conduction. Compared with undoped CuO film, the CuO:In films have quite low mobility, improved electrical conductivity and large optical absorption edge. This finding indicates that CuO:In films can be used as absorption layer material in heterojunction solar cells rather than as hole-transporting layer material in perovskite solar cells.

To capture more nutrients, root systems of maize (Zea mays L.) and soybean (Glycine max L.) exhibit morphological and physiological plasticity to a localized supply of phosphorus (P). However, the mechanisms of the interaction between light intensity and P affecting root morphological and physiological alterations remain unclear. In the present study, the regulation of P uptake capacity of maize and soybean by light intensity and localized P supply was investigated in a low solar radiation area. The plants were grown under continual and disrupted light conditions with homogeneous and heterogeneous P supply. Light capture of maize and soybean increased under the disrupted light condition. Plant dry weight and P uptake were increased by more light capture, particularly when plants were grown in soil with heterogeneous P supply. Similarly, both localized P supply and disrupted light treatment increased the production of fine roots and specific root length in maize. Both homogeneous P supply and disrupted light treatment increased the malate and citrate exudation in the root of soybean. Across all of the experimental treatments, high root morphological plasticity of maize and root physiological plasticity of soybean were associated with lower P concentrations in leaves and greater sucrose concentrations in roots. It is suggested that the carbon (C), exceeded shoot growth capabilities and was transferred to roots as sucrose, which may serve as both a nutritional signal and a C-substrate for root morphological and physiological changes.

Proanthocyanidin A2 (PA2), one of A-type proanthocyanidins, has been shown to harbor a broad spectrum of pharmacological activities, including anti-inflammatory, antioxidant, anti-HIV, anti-CDV and anti-?-glucosidase activities. However, little is known about the role for PA2 in regulating PDGF-induced VSMC proliferation and migration. In the present study, we investigated the possible effects of PA2 on PDGF-BB-induced proliferation, migration and inflammation in VSMCs in vitro to mimic a postangioplasty PDGF shedding condition. Herein, the data clearly show that PA2 markedly inhibited proliferation, migration and inflammatory responses at 0-30??g/ml concentration in VSMCs in vitro. 10-30??g/ml PA2 inhibited PDGF-mediated NAD(P)H oxidase activation and intracellular ROS formation in VSMCs. Furthermore, the effects exerted by PA2 involve the participation of KDR and Jak-2/STAT-3/cPLA

Fragment-docking-oriented de novel design for both the catalytic site and the C phosphotyrosine binding site led to the discovery of novel scaffold and chemical easy N-(2,5-diethoxy-phenyl)-methanesulfonamide based phosphotyrosine mimetics that when incorporated into ureas are high potent and selective inhibitors of protein tyrosine phosphatase 1B. Among them, compound 15 was shown to be the most potent PTP1B inhibitor with great selectivity over the highly homologous T-cell protein tyrosine phosphatase.

An efficient route to the synthesis of 3-amino-2-ethoxycarbonyl imidazo[1,2-a]pyridine derivatives starting from ethyl α-benzotriazolyl-α-morpholinoacetate has been developed. By the reactions between primary heterocyclic amidines and isocyanides catalyzed by Ga(OTf)3, target compounds were obtained in moderate to good yields. This in turn will set the stage for the wide application of this useful reaction for the synthesis of 3-amino-2-carbonylimidazo[1,2-a]pyridines based on imidazo[1,2-a]pyridine privileged structures.

In the title polymer, [Hg2(SCN)4(C26H16N2)]n, the two equivalent HgIIatoms are coordinated by one N atom of a bridging 4,4′-bis(pyridin-3-ylethynyl)-1,1′-biphenyl ligand, two S atoms of two thiocyanates and one N atom of a thiocyanate, giving rise to a distored tetrahedral coordination environment. Two thiocyanate ligands bridge symmetry-related metal atoms to form a polymeric chain extending parallel to [001], and another bridging mode is accomplished by the organic ligand that is located about an inversion centre. The dihedral angle between the coordinating pyridine ring and the benzene ring is 11.4 (2)°, and the two coordinating pyridine rings in the organic ligand are parallel by symmetry. The point group of the ligand in the compound is thus close toC2h. The result of the mode of the organic ligands is the formation of zigzag sheets connectedviabridging thiocyanate ligands.

RhoA/p27

Southwest of China is one of the major soybean (Glycine max L.) production regions in China with low availability of soil phosphorus (P). Whereas little information is available on assessment of P-efficient soybean genotypes in this region, even though use of P-efficient soybean genotypes is a sustainable P management strategy for enhancing yield and P use efficiency. To assess the genetic variation on P use efficiency, 274 soybean genotypes were employed to compare the yield and P acquisition potentials in the field. Additionally, 10 representational genotypes (5 P-efficient genotypes and 5 P-inefficient genotypes) were grown in hydroponic media containing low P treatment (0.05 mM L-1) and high P treatment (0.25 mM L-1) to further investigate P assimilation characteristics and the related mechanisms of P-efficient soybean genotypes. In the field trial the models described the relationships between yield and seed P concentration (R2= 0.85), shoot P accumulation (R2= 0.84), HI (R2= 0.82) well. The yield, seed P concentration and shoot P accumulation ranged from 5.5 to 36.0 g plant-1, concentration from 0.045 to 0.93 % and accumulation from 0.065 to 0.278 mg plant-1, respectively. In the hydroponic trial, P-efficient genotypes under low P treatment showed significantly greater plant growth and higher P accumulation than P-inefficient genotypes. Simultaneously, total root length, specific root length, root surface area and root volume of P-efficient were significantly greater than P-inefficient under low P treatment. Higher rate of organic acid exudation and acid phosphatase activities were observed in the P-efficient soybean genotypes under low P condition when compared to the P-inefficient soybean genotypes. It indicated that significant genetic variation for P use efficiency existed in this region, and the P-efficient soybean genotypes, especially E311 and E141, demonstrated great tolerance to P deficiency, which could be potential materials using in improving production and P use efficiency in low availability of soil P region.

Fermented soybean foods have been shown to reduce incidence of diabetes and improve insulin sensitivity. 6-Hydroxydaidzein (6-HD) is a bioactive ingredient isolated from fermented soybean. In this study, we examined the effects of 6-HD on adipocyte differentiation and insulin-stimulated glucose uptake, as well as the mechanisms involved. In our experiments, 6-HD enhanced 3T3-L1 adipocyte differentiation and insulin-stimulated glucose uptake in a dosage-dependent manner. In addition, 6-HD increased peroxisome proliferator-activated receptor gamma (PPARγ) gene expression and PPARγ transcriptional activity. 6-HD increased CCAAT/enhanced binding protein alpha (C/EBPα) expression as well. Although having no effects on glucose transporter type 4 (GLUT4) gene expression, 6-HD facilitated GLUT4 protein translocation to the cell membranes. Our results indicate that 6-HD exhibited the actions of promoting adipocyte differentiation and improving insulin sensitivity by increasing the expression of C/EBPα and facilitating the translocation of GLUT4 via the activation of PPARγ, suggesting that 6-HD can be promising in diabetes management.

The estrogen-related receptor α (ERRα) is an orphan nuclear receptor that plays a primary role in the regulation of cellular energy homeostasis and osteogenesis. It is reported that ERRα is widely expressed in a range of tissues and accumulating evidence has supported that the high expression of ERRα correlates with poor prognosis of various human malignancies, including breast, endometrium, colon, prostate and ovary cancers. Herein is described the discovery of a novel selective inverse agonist (HSP1604) of ERRα, but not of ERRβ and ERRγ, as determined using transient transfection luciferase reporter assay and a time-resolved fluorescence resonance energy transfer (TR-FRET) co-activator assay. HSP1604 potently inhibits ERRα transcriptional activity with IC50=1.47±0.17μM in cell-based luciferase reporter assay and also decreases the protein level of ERRα and the mRNA levels of its downstream target genes such as pyruvate dehydrogenase kinase 4 (PDK4), pS2 and osteopontin. HSP1604 has also suppressed the proliferation of different human cancer cell lines and the migration of breast cancer cells with high expression of ERRα. Representative in vivo results show that HSP1604 suppresses the growth of human breast cancer xenograft in nude mice as doses at 30mg/kg or 100mg/kg administered every other day during 28-day period. HSP1604 thus has the potential both as a new agent to inhibit the growth of tumors and as a chemical probe of ERRα biology.