Search

1,4-diaminobutane is widely used in the industrial production of polymers, pharmaceuticals, agrochemicals and surfactants. Owing to economic and environmental concerns, there has been a growing interest in using microbes to produce 1,4-diaminobutane. However, there is lack of research on the influence of cofactors pyridoxal phosphate (PLP) and NADPH on the synthesis of 1,4-diaminobutane. PLP serves as a cofactor of ornithine decarboxylase in the synthesis of 1,4- diaminobutane. Additionally, the synthesis of 1 mol 1,4-diaminobutane requires 2 mol NADPH, thus necessitating consideration of NADPH balance in the efficient synthesis of 1,4-diaminobutane by Escherichia coli. The aim of this study was to enhance the synthesis efficiency of 1,4-diaminobutane through increasing production of PLP and NADPH. By optimizing the expression of the genes associated with synthesis of PLP and NADPH in E. coli, cellular PLP and NADPH levels increased, and the yield of 1,4-diaminobutane also increased accordingly. Ultimately, using glucose as the primary carbon source, the yield of 1,4-diaminobutane in the recombinant strain NAP19 reached 272 mg/L·DCW, by increased 79% compared with its chassis strain. [ABSTRACT FROM AUTHOR]

This paper proposes a novel cloud computingbased parallel deep reinforcement learning (DRL) energy management strategy (EMS) for connected plug-in hybrid vehicles. First, a proximal policy optimization (PPO) algorithm is developed. Since the cloud computing can reduce the computational burden of the connected vehicles, the PPO is deployed in the proposed cloud computing-based EMS. In order to improve the strategy adaptation, a parallel mechanism is proposed to achieve the information interaction with multiple vehicles. Considering the real-time control requirements, thread pool is proposed and applied in the cloud computing based parallel EMS. The thread pool-based strategy provides an efficient real-time control ability and strategy improvement solution. To verify the PPO based EMS, the dynamic programming, deep Q-network and double deep Q-network strategies are developed for comparison. It is found that the PPO can achieve similar fuel efficiency improvement with the DP strategy among the three DRL algorithms. For parallel training of multiple connected vehicles, the cloud computing-based parallel EMS improves fuel economy by approximately 7.7%. Threadpool based parallel real-time EMS reduces average time for computational interactions by 20% and further improves the fuel efficiency. The proposed strategy has the advantages of realtime control, adaptability and continuous learning for improved fuel efficiency. [ABSTRACT FROM AUTHOR]

The M1-M5 muscarinic acetylcholine receptors constitute an important family of class A G-protein-coupled receptor (GPCRs) activated by the neurotransmitter, acetylcholine (1). Both the M1 and M4 receptors have been associated [...], Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the Ml and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high conservation of the acetylcholine-binding pocket has spurred current research into targeting allosteric sites on these receptors. Here we report the crystal structures of the Ml and M4 muscarinic receptors bound to the inverse agonist, tiotropium. Comparison of these structures with each other, as well as with the previously reported M2 and M3 receptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute to a role in drug selectivity at this important receptor family. We also report identification of a cluster of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new insight into how allosteric modulation may be transmitted between the two spatially distinct domains.

Mutation breeding is a significant means of increasing breeding efficiency and accelerating breeding process. In present study, we explored a new method for mutations inducing in rice (Oryza sativa L.) by using direct current electrophoresis bath (DCEB). The results showed that 20 mM NaCl solution is the optimal buffer, and the mortality of rice seeds followed an upward trend with increasing voltage and processing time of DCEB. By exploring the mutagenic effects of γ-irradiation and DCEB on seed vigor and physiological damages, we found that the physiological damages induced by DCEB on seed vigor were significant compared with that by γ-irradiation. We screened two mutants with low filled grain percentage and one mutant with abnormal hull from the M2 generations. These three mutants were confirmed to be authentic mutants based on 48 SSR markers followed by the protocol NY/T 1433–2014. Whole-genome resequencing detected a total of 503 and 537 polymorphisms in the two mutants, respectively, and the DCEB mutagenesis induced mainly InDel variants, while the exon region of mutant genes occupied a large proportion, especially the SNP variants, which occupied about 20% of the mutation sites in the exon region. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) and Parkinson’s disease (PD) are both age-related diseases of global concern being among the most common chronic metabolic and neurodegenerative diseases, respectively. While both diseases can be genetically inherited, environmental factors play a vital role in their pathogenesis. Moreover, DM and PD have common underlying molecular mechanisms, such as misfolded protein aggregation, mitochondrial dysfunction, oxidative stress, chronic inflammation, and microbial dysbiosis. Recently, epidemiological and experimental studies have reported that DM affects the incidence and progression of PD. Moreover, certain antidiabetic drugs have been proven to decrease the risk of PD and delay its progression. In this review, we elucidate the epidemiological and pathophysiological association between DM and PD and summarize the antidiabetic drugs used in animal models and clinical trials of PD, which may provide reference for the clinical translation of antidiabetic drugs in PD treatment. [ABSTRACT FROM AUTHOR]

Opioid receptors have an important role in the central nervous system, regulating pain perception, hedonic homeostasis, mood and wellbeing (1). Thus, they have long been the focus of physiological and [...], The opioid receptor family comprises three members, the μ-, δ- and κ-opioid receptors, which respond to classical opioid alkaloids such as morphine and heroin as well as to endogenous peptide ligands like endorphins. They belong to the G-proteincoupled receptor (GPCR) superfamily, and are excellent therapeutic targets for pain control. The δ-opioid receptor (δ-OR) has a role in analgesia, as well as in other neurological functions that remain poorly understood (1). The structures of the μ-OR and κ-OR have recently been solved (2,3). Here we report the crystal structure of the mouse δ-OR, bound to the subtype-selective antagonist naltrindole. Together with the structures of the μ-OR and κ-OR, the δ-OR structure provides insights into conserved elements of opioid ligand recognition while also revealing structural features associated with ligand-subtype selectivity. The binding pocket of opioid receptors can be divided into two distinct regions. Whereas the lower part of this pocket is highly conserved among opioid receptors, the upper part contains divergent residues that confer subtype selectivity. This provides a structural explanation and validation for the 'message-address' model of opioid receptor pharmacology (4,5), in which distinct 'message' (efficacy) and 'address' (selectivity) determinants are contained within a single ligand. Comparison of the address region of the o-OR with other GPCRs reveals that this structural organization may be a more general phenomenon, extending to other GPCR families as well.

Opium extracts from the plant Papaver somniferum have been used for therapeutic and recreational purposes for thousands of years. Opioid alkaloids and related pharmaceuticals are the most effective analgesics for [...], Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled μ-opioid receptor (μ-OR) in the central nervous system. Here we describe the 2.8 Å crystal structure of the mouse μ-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the μ-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.

Author(s): Søren G. F. Rasmussen [sup.1] [sup.2] , Brian T. DeVree [sup.3] , Yaozhong Zou [sup.1] , Andrew C. Kruse [sup.1] , Ka Young Chung [sup.1] , Tong Sun Kobilka [...], G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The [beta].sub.2 adrenergic receptor ([beta].sub.2AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric [beta].sub.2AR and nucleotide-free Gs heterotrimer. The principal interactions between the [beta].sub.2AR and Gs involve the amino- and carboxy-terminal [alpha]-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the [beta].sub.2AR include a 14 Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an [alpha]-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the [alpha]-helical domain of G[alpha]s relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR. X-ray structure of a GPCR complex G-protein-coupled receptors (GPCRs) mediate the majority of a cell's responses to hormones and neurotransmitters, and to the senses of sight, olfaction and taste. This makes GPCRs potentially the most important group of drug targets in the human body. GPCRs are deeply embedded in the cell membrane, crossing it seven times, so structure determination for these complexes is particularly challenging -- as recounted in a recent News Feature (see http://go.nature.com/ftqnx4). The eagerly-awaited X-ray crystal structure of a GPCR transmembrane signalling complex has now been determined by Brian Kobilka's group. The structure presented is of an agonist-occupied monomer of the [beta].sub.2 adrenergic receptor in complex with G.sub.s, the stimulatory G protein for adenylyl cyclase. An accompanying paper reports the use of peptide amide hydrogen-deuterium exchange mass spectrometry to probe the protein dynamics of this signalling complex.

Introduction The [β.sub.2] adrenergic receptor ([β.sub.2]AR) has been a model system for the large and diverse family of G protein-coupled receptors (GPCRs) for over 40 years. It was one of [...], G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The [β.sub.2] adrenergic receptor ([β.sub.2]AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric [β.sub.2]AR and nucleotide-free Gs heterotrimer. The principal interactions between the [β.sub.2]AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the [β.sub.2]AR include a 14 Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.

GPCRs activated by diffusible ligands have a spectrum of functional states (1). A GPCR may activate more than one G protein isoform or a G-protein-independent pathway such as arrestin. In [...], G protein coupled receptors (GPCRs) exhibit a spectrum of functional behaviours in response to natural and synthetic ligands. Recent crystal structures provide insights into inactive states of several GPCRs. Efforts to obtain an agonist-bound active-state GPCR structure have proven difficult due to the inherent instability of this state in the absence of a G protein. We generated a camelid antibody fragment (nanobody) to the human [β.sub.2] adrenergic receptor ([β.sub.2]AR) that exhibits G protein-like behaviour, and obtained an agonist-bound, active-state crystal structure of the receptor-nanobody complex. Comparison with the inactive [β.sub.2]AR structure reveals subtle changes in the binding pocket; however, these small changes are associated with an 11Å outward movement of the cytoplasmic end of transmembrane segment 6, and rearrangements of transmembrane segments 5 and 7 that are remarkably similar to those observed in opsin, an active form of rhodopsin. This structure provides insights into the process of agonist binding and activation.

In the ligand-free basal state, GPCRs exist in an equilibrium of conformations (6). Ligand binding modulates receptor function by stabilizing different intramolecular interactions and establishing a new conformational equilibrium. Activating [...], G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that mediate most cellular responses to hormones and neurotransmitters. They are the largest group of therapeutic targets for a broad spectrum of diseases. Recent crystal structures of GPCRs (1-5) have revealed structural conservation extending from the orthosteric ligand-binding site in the transmembrane core to the cytoplasmic G-protein-coupling domains. In contrast, the extracellular surface (ECS) of GPCRs is remarkably diverse and is therefore an ideal target for the discovery of subtype-selective drugs. However, little is known about the functional role of the ECS in receptor activation, or about conformational coupling of this surface to the native ligand-binding pocket. Here we use NMR spectroscopy to investigate ligand-specific conformational changes around a central structural feature in the ECS of the [β.sub.2] adrenergic receptor: a salt bridge linking extracellular loops 2 and 3. Small-molecule drugs that bind within the transmembrane core and exhibit different efficacies towards G-protein activation (agonist, neutral antagonist and inverse agonist) also stabilize distinct conformations of the ECS. We thereby demonstrate conformational coupling between the ECS and the orthosteric binding site, showing that drugs targeting this diverse surface could function as allosteric modulators with high subtype selectivity. Moreover, these studies provide a new insight into the dynamic behaviour of GPCRs not addressable by static, inactive-state crystal structures.

Aiming at the problems of low accuracy, low efficiency and low stability of traditional methods and recent developments in advanced technology incite the industries to be in sync with modern technology. With respect to various available techniques, this paper designs a fuzzy comprehensive evaluation model of the manufacturing industry for transferring risk based on economic big-data analytics. The big-data analysis method is utilized to obtain the data source of fuzzy evaluation of the manufacturing industry to transfer risk using data as the basis of risk evaluation. Based on the risk factors, the proposed model establishes the risk index system of the manufacturing industry and uses the expert evaluation method to design the scoring method of the evaluation index system. To ensure the accuracy of the evaluation results, the manufacturing industry's fuzzy comprehensive model is established using the entropy weight method, and the expert evaluation results are modified accordingly. The experimental results show that the highest efficiency of the proposed method is 96%, the highest accuracy of the evaluation result is 75%. The evaluation result's stability is higher than the other existing methods, which fully verifies the effectiveness and can provide a reliable theoretical basis for enterprise risk evaluation research. [ABSTRACT FROM AUTHOR]

This study was conducted to compare the growth-promoting and flesh quality -improving effects of three active compounds in Eucommia ulmoides (EU) on grass carp (Ctenopharyngodon idella). Four iso-nitrogenous diets supplemented with 400 mg/kg inclusion of geniposidic acid (GA), chlorogenic acid (CGA), geniposide (GP) and their combination (GA:CGA:GP = 1:1:1, the mixture) were prepared and fed to grass carp (47.1 ± 0.6 g) for 75 days. The results indicated that weight gain was increased by 5.22%, and feed conversion ratio decreased by 0.07 by dietary CGA (p < 0.05). In flesh quality, the four supplementations significantly increased muscle fibre density, total collagen and alkaline-insoluble collagen in skin, and reduced steaming loss of flesh. In addition, dietary CGA, GP and the active compounds mixture further increased total collagen, alkaline-insoluble collagen and amino acid in flesh. In collagen genes expression, the expression of COL1A1 in muscle and skin was significantly promoted by the supplementation of GA, CGA, GP and their combination (p < 0.05). In conclusion, the supplementation of GA, CGA, GP and their combination improved the flesh quality of grass carp, and the growth was increased by CGA. CGA played more important roles in growth-promoting and flesh quality-improving effects than GP and GA. [ABSTRACT FROM AUTHOR]

The catalytic activity of low-dimensional electrocatalysts is highly dependent on their local atomic structures, particularly those lesscoordinated sites found at edges and corners; therefore, a direct probe of the electrocatalytic current at specified local sites with true nanoscopic resolution has become critically important. Despite the growing availability of operando imaging tools, to date it has not been possible tomeasure the electrocatalytic activities fromindividual material edges and directly correlate those with the local structural defects. Herein, we show the possibility of using feedback and generation/collection modes of operation of the scanning electrochemical microscope (SECM) to independently image the topography and local electrocatalytic activity with 15-nm spatial resolution. We employed this operando microscopy technique to map out the oxygen evolution activity of a semi-2D nickel oxide nanosheet. The improved resolution and sensitivity enables us to distinguish the higher activities of the materials' edges from that of the fully coordinated surfaces in operando. The combination of spatially resolved electrochemical information with state-of-the-art electron tomography, that unravels the 3D complexity of the edges, and ab initio calculations allows us to reveal the intricate coordination dependent activity along individual edges of the semi-2D material that is not achievable by other methods. The comparison of the simulated line scans to the experimental data suggests that the catalytic current density at the nanosheet edge is ~200 times higher than that at the NiO basal plane. [ABSTRACT FROM AUTHOR]

Chimeric α.sub.2.-, β.sub.2.-Adrenergic Receptors: Delineation of Domains Involved in Effector Coupling and Ligand Binding Specificity THE ADRENERGIC RECEPTORS (Α.sub.1.-, α.sub.2.-, β.sub.1.-, AND β.sub.2.-), which mediate the physiological effects of catecholamines, [...]

Conspectus: Electrochemistry at metal nanoparticles (NPs) is of significant current interest because of its applications in catalysis, energy conversion and storage, and sensors. The electrocatalytic activity of NPs depends strongly on their size, shape, and surface attachment. The use of a large number of particles in most reported kinetic experiments obscured the effects of these factors because of polydispersity and different NP orientations. Recent efforts to probe electrochemistry at single NPs included recording of the catalytically amplified current produced by random collisions of particles with the electrode surface, immobilizing an NP on the surface of a small electrode, and delivering individual NPs to electrode surfaces. Although the signals recorded in such experiments were produced by single NPs, the characterization issues and problems with separating an individual particle from other NPs present in the system made it difficult to obtain spatially and/or temporally resolved information about heterogeneous processes occurring at a specific NP. To carry out electrochemical experiments involving only one NP and characterize such an NP in situ, one needs nanoelectrochemical tools with the characteristic dimension smaller than or comparable to those of the particle of interest. This Account presents fundamentals of two complementary approaches to studying NP electrochemistry, i.e., probing single immobilized NPs with the tip of a scanning electrochemical microscope (SECM) and monitoring the collisions between one catalytic NP and a carbon nanopipette. The former technique can provide spatially resolved information about NP geometry and measure its electron transfer properties and catalytic activity under steady-state conditions. The emphasis here is on the extraction of quantitative physicochemical information from nanoelectrochemical data. By employing a polished disk-type nanoelectrode as an SECM tip, one can characterize a specific nanoparticle in situ and then use the same NP for kinetic experiments. A new mode of SECM operation based on tunneling between the tip and nanoparticle can be used to image the NP topography with a lateral resolution of ∼1 nm. An alternative approach employs carbon nanoprobes produced by chemical vapor deposition of carbon into quartz nanopipettes. One metal NP is captured inside the carbon nanocavity to probe the dynamics of its interactions with the electrode surface on the microsecond time scale. The use of high-resolution transmission electron microscopy is essential for interpreting the results of single-NP collision experiments. A brief discussion of the nanoelectrochemical methodology, recent advances, and future directions is included. [ABSTRACT FROM AUTHOR]

Twist1 is a basic helix-loop-helix transcription factor that strongly promotes epithelial-to-mesenchymal transition, migration, invasion, and metastasis of cancer cells. The MAPK-phosphorylated Twist1 on its serine 68 (Ser(P)68-Twist1) has a significantly enhanced stability and function to drive cancer cell invasion and metastasis. However, the phosphatase that dephosphorylates Ser(P)68-Twist1 and destabilizes Twist1 has not been identified and characterized. In this study, we screened a serine/threonine phosphatase cDNA expression library in HEK293T cells with ectopically coexpressed Twist1. We found that the small C-terminal domain phosphatase 1 (SCP1) specifically dephosphorylates Ser(P)68-Twist1 in both cell-free reactions and living cells. SCP1 uses its amino acid residues 43-63 to interact with the N terminus of Twist1. Increased SCP1 expression in cells decreased Ser(P)68-Twist1 and total Twist1 proteins, whereas knockdown of SCP1 increased Ser(P)68-Twist1 and total Twist1 proteins. Furthermore, the levels of SCP1 are negatively correlated with Twist1 protein levels in several cancer cell lines. SCP1-dephosphorylated Twist1 undergoes fast degradation via the ubiquitin-proteasome pathway. Importantly, an increase in SCP1 expression in breast cancer cells with either endogenous or ectopically expressed Twist1 largely inhibits the Twist1-induced epithelial-to-mesenchymal transition phenotype and the migration and invasion capabilities of these cells. These results indicate that SCP1 is the phosphatase that counterregulates the MAPK-mediated phosphorylation of Ser68-Twist1. Thus, an increase in SCP1 expression and activity may be a useful strategy for eliminating the detrimental roles of Twist1 in cancer cells. [ABSTRACT FROM AUTHOR]

Experiments at individual metal nanoparticles (NPs) can provide important information about their electrochemical and catalytic properties. The scanning electrochemical microscope (SECM) equipped with a nanometer-sized tip was recently used to image single 10 or 20 nm gold particles and quantitatively investigate electrochemical reactions occurring at their surfaces. In this Article, the theory is developed for SECM current vs distance curves obtained with a disk-shaped tip approaching a comparably sized, surface-bound conductive or insulating spherical NP. The possibility of evaluating the size of a surface-bound particle by fitting the experimental current-distance curve to the theory is shown for NPs and tips of different radii. The effects of the NP being partially buried into an insulating layer and the imperfect positioning of the tip with respect to the NP center are considered. The collection efficiency is calculated for redox species generated at the nanoparticle surface and collected at the tip. [ABSTRACT FROM AUTHOR]

Unlike macroscopic and micrometer-sized solid electrodes whose surface can be reproducibly cleaned by mechanical polishing, cleaning the nanoelectrode surface is challenging because of its small size and extreme fragility. Even very gentle polishing typically changes the nanoelectrode size and geometry, thus, complicating the replication of nanoelectrochemical experiments. In this letter, we show the possibility of cleaning nanoelectrode surfaces nondestructively by using an air plasma cleaner. The effects of plasma cleaning have been investigated by atomic force microscopy (AFM) imaging, voltammetry, and scanning electrochemical microscopy (SECM). A related issue, the removal of an insoluble organic film from the nanoelectrode by plasma cleaning, is also discussed. [ABSTRACT FROM AUTHOR]

During gas chromatography/mass spectrometry (GC-MS) analyses using water and methanol as injection solvents, hydrolysis reactions after injecting water control and alcoholysis reactions after injecting methanol control or ethanol into a GC-MS system were observed and studied. Two dominant hydrolysis/alcoholysis product series were detected, and were identified as being HO(CH3)2SiOR and HO(CH3)2SiO(CH3)2SiOR, where R=H, methyl, or ethyl, when pure water, methanol and ethanol were injected. The chemical structures of the reaction products were cross-checked by injecting H2O/D2O and H2O/MeOH/EtOH, and comparable EI mass fragmentation patterns were found. The water and alcohols injected reacted with silicones in septum particles which accumulated in the injection port liner after numerous injections, and both hydrolysis and alcoholysis reaction products gradually increased in concentration as the number of injections increased. Potential interferences from hydrolysis or alcoholysis reactions should be paid attention to, evaluated or eliminated when water or methanol was used as the GC or GC-MS solvent, and especially when underivatized methanol or ethanol was subject to GC and GC-MS analysis. [ABSTRACT FROM AUTHOR]

In nature, a sapling can grow into a big tree under irradiation of sunlight. In chemistry, a similar concept that a small molecule only exposing to sunlight grows into a hyperbranched macromolecule has not been realized by now. The achievement of the concept will be fascinating and valuable for polymer synthesis wherein sunlight is inexpensive, abundant, renewable, and nonpolluting. Herein, we report a new strategy in which small monomers can directly grow into big hyperbranched macromolecule under irradiation of sunlight without any catalyst. [ABSTRACT FROM AUTHOR]

Caspases are important in the life and death of immune cells and therefore influence immune surveillance of malignancies. We tested whether genetic variants in CASP8, CASP10 and CFLAR, three genes important for death receptor–induced cell killing residing in tandem order on chromosome 2q33, are associated with cancer susceptibility. Using a haplotype-tagging SNP approach, we identified a six-nucleotide deletion (−652 6N del) variant in the CASP8 promoter associated with decreased risk of lung cancer. The deletion destroys a stimulatory protein 1 binding site and decreases CASP8 transcription. Biochemical analyses showed that T lymphocytes with the deletion variant had lower caspase-8 activity and activation-induced cell death upon stimulation with cancer cell antigens. Case-control analyses of 4,995 individuals with cancer and 4,972 controls in a Chinese population showed that this genetic variant is associated with reduced susceptibility to multiple cancers, including lung, esophageal, gastric, colorectal, cervical and breast cancers, acting in an allele dose–dependent manner. These results support the hypothesis that genetic variants influencing immune status modify cancer susceptibility. [ABSTRACT FROM AUTHOR]

Various ionic and molecular activities in the extracellular environment are vital to plant cell physiological processes. A noninvasive microsensing system (NMS) based on either the scanning ion-selective electrode technique (SIET) or the scanning polarographic electrode technique (SPET) is able to obtain information regarding the transportation of various ions/molecules in intact samples under normal physiological conditions. The two-probe simultaneous test system (2STS) is an integrated system composed of SIET, SPET, and a Xu-Kunkel sampling protocol. In the present study, 2STS was able to simultaneously measure fluxes of H+ and O2 of the lily ( Lilium longiflorum Thunb. cv. Ace) pollen tube while avoiding interference between the two probes. The results indicate that the proton fluxes were effluxes, whereas the oxygen fluxes were influxes, and they were closely correlated to each other surrounding the constitutive alkaline band region. Specifically, when the proton effluxes increased, the oxygen influxes also increased. Therefore, the hypothesis of condensed active mitochondria existing in the alkalized area of the pollen tube proposed by Hepler's group is supported. (Managing editor: Wei Wang) [ABSTRACT FROM AUTHOR]

Background: The FAS receptor-ligand system is a key regulator of apoptotic cell death, and loss of FAS expression and gain of FAS ligand (FASL) expression play important roles in the development and progression of cancer. Single nucleotide polymorphisms in the promoter region of the FAS (G or A at position -1377 [FAS -1377G/A] and A or G at position -670 [FAS -670A/G]) and FASL (T or C at position -844 [FASL -844T/C]) genes alter the transcriptional activity of these genes. We examined the association between these polymorphisms and risk of the development and metastasis of esophageal squamous-cell carcinoma. Methods: Genotypes of 588 case patients with esophageal squamous cell carcinoma and 648 control subjects were determined by polymerase chain reaction-based restriction fragment length polymorphism. Associations with the risk of esophageal squamous-cell carcinoma were estimated by logistic regression. All statistical tests were two-sided. Results: We observed a statistically significantly increased risk of esophageal squamous-cell carcinoma associated with the FAS -1377AA (odds ratio [OR] = 1.79, 95% confidence interval [CI] = 1.29 to 2.48; P<.001) or FAS -670GG (OR = 1.72, 95% CI = 1.26 to 2.34; P<.001) genotype, which are in strong linkage disequilibrium compared with the FAS -1377GA or GG or the FAS -670AG or AA genotype, respectively. An increased risk of esophageal squamous-cell carcinoma was also associated with the FASL -844CC genotype (OR = 2.06, 95% CI = 1.64 to 2.59; P<.001) compared with the FASL -844CT or TT genotype. Gene-gene interactions of FAS and FASL polymorphisms increased the risk of esophageal squamous-cell carcinoma in a multiplicative manner (OR for the presence of both FAS -1377AA and FASL -844CC genotypes = 4.55, 95% CI = 2.75 to 7.48; P = .001, test for homogeneity). Statistically significant interactions were found between these polymorphisms in FAS and FASL and tobacco smoking. None of the polymorphisms was associated with risk of differentiation or metastasis of esophageal squamous-cell carcinoma at diagnosis. Conclusion: Genetic polymorphisms in the death pathway genes FAS and FASL appear to be associated with an increased risk of developing esophageal squamous-cell carcinoma. [ABSTRACT FROM AUTHOR]

A simple and effective technique for strain-independent temperature measurement has been demonstrated using the peak wavelengths of both type-I and type-IIA fiber Bragg gratings written without hydrogen loading in the same fiber, this having been specially fabricated with a high concentration of germanium in the core composition. The device is also capable of monitoring strain and temperature simultaneously and can be used to measure temperature over the range of 25–300 °C with a strain range of 0–500 μ[variant_greek_epsilon], achieving a temperature-dependent sensitivity of 0.53 and 0.31 pm/°C for strain-independent temperature measurement with root mean square errors of 2.4 and 4.1 °C at 25 and 300 °C, respectively. © 2004 American Institute of Physics. [ABSTRACT FROM AUTHOR]

The α2 and β2 adrenergic receptors, both of which are activated by epinephrine, but which can be differentiated by selective drugs, have opposite effects (inhibitory and stimulatory) on the adenylyl cyclase system. The two receptors are homologous with each other, rhodopsin, and other receptors coupled to guanine nucleotide regulatory proteins and they contain seven hydrophobic domains, which may represent transmembrane spanning segments. The function of specific structural domains of these receptors was determined after construction and expression of a series of chimeric α2-,β2-adrenergic receptor genes. The specificity for coupling to the stimulatory guanine nucleotide regulatory protein lies within a region extending from the amino terminus of the fifth hydrophobic domain to the carboxyl terminus of the sixth. Major determinants of α2- and β2-adrenergic receptor agonist and antagonist ligand binding specificity are contained within the seventh membrane spanning domain. Chimeric receptors should prove useful for elucidating the structural basis of receptor function. [ABSTRACT FROM AUTHOR]

Considering the role of glycolysis inhibition as a novel therapeutic strategy for cancer, including breast cancer (BC), we wondered whether glycolysis could affect BC progression by regulating transmembrane O-mannosyltransferase-targeting cadherins 3 (TMTC3). Following the intervention, lactic acid production in BC cells was monitored, and viability, proliferation, and apoptosis assays were performed. The expressions of TMTC3 and endoplasmic reticulum (ER) stress- and apoptosis-related factors Caspase-12, C/EBP homologous protein (CHOP), glucose-regulated protein 78 (GRP78), B-cell lymphoma-2 (Bcl-2), and Bcl-2 associated X (Bax) were quantified. TMTC3 was lowly expressed in BC tissue and cell. The promotion of glycolysis via glucose represses TMTC3 expression and apoptosis yet enhances lactic acid production and growth of BC cell, along with promoted levels of Caspase-12, CHOP, GRP78, and Bcl-2 yet repressed level of Bax, while the contrary results were evidenced after 2-deoxyglycouse intervention. Overexpressed TMTC3 additionally abrogated the effects of glycolysis on increasing the viability and proliferation yet inhibiting the apoptosis of BC cells, with the increased expressions of Caspase-12, CHOP, and GRP78, and Bcl-2 yet decreased level of Bax. Collectively, inhibiting glycolysis restrained the growth and attenuated the ER stress of BC cell by regulating TMTC3. [ABSTRACT FROM AUTHOR]

The Daqing River Basin has long been seriously threatened by floods. The construction of Xiong'an New Area has put forward higher requirements for the flood control system of the basin. Researches on the characteristics of the flood control system in the Daqing River Basin, the causes of the flood and the historical flood were conducted with the purpose to have a clear understanding of the deficiency of the existing flood control system in the Drainage Basin and figure out the countermeasures to improve the flood control capacity of the Drainage Basin by taking the development process of the flood control system in the Drainage Basin into consideration. Analysis was conducted on the causes, flood process, the process of regulation and storage of reservoirs and depressions as well as flood disaster with the flood occurred in August 1963 as the major research object. Besides, the deficiency of flood control system of the Drainage Basin in terms of flood control system and the flood occurred in August 1963 (also called 63.8 Flood). According to the research, the major problems in the current flood control system of the Daqing River Basin are mainly concentrated on Baiyang Lake with blocked internal water transmission and insufficient drainage capacity, which makes it difficult to cope with the flood exceeding the designed level. The great change of water level will also destroy the ecological balance of Baiyang Lake itself. In addition, during the construction of the New District, some flood storage and detention areas in Baiyang Lake will be deprived of the capability in regulation and storage, which will increase the difficulty of flood control in the downstream areas. Combined with the existing flood control system and aiming at the construction of Xiong'an New Area, the concepts of flood control system such as developing the Xiaoguan flood diversion way, rebuilding the new housing hub and strengthening the dredging of downstream river are put forward. • Developing the Xiaoguan flood diversion way. • Analysis was conducted on flood process, regulation process, storage of reservoirs, etc. • Building the new housing hub and strengthening the dredging of downstream river. • Figured the countermeasures to improve flood control capacity of Drainage Basin. [ABSTRACT FROM AUTHOR]

Poyang Lake wetland plays an important ecological service function. Frequent drought events have caused significant changes in the distribution pattern of wetland plants. This study analyzed the changes in the distribution elevation of wetland plants in Poyang Lake from 2000 to 2020, including the optimal elevation, and upper and lower limit elevations, and revealed the impacts of drought on the ecological niches of typical wetland plants. The results showed that the wetland plants were distributed in a regular strip pattern according to the elevation gradient. The Polygonum hydropiper-Phalaris arundinacea (PP), Carex cinerascens (Cc), Phragmites australis-Triarrhena lutarioriparia (PT), and Artemisia selengensis (As) communities were mainly distributed at elevations of 8.70-13.62 m, 10.35-14.99 m, 12.00-16.28 m, and 11.82-18.46 m, with optimal elevations of 11.16, 12.67, 14.14, and 15.14 m, respectively. Although the optimal elevations and upper limit elevations of four typical wetland plants exhibited different changing trends, their lower limit elevations showed the significant downward trends, especially for Cc and PP communities. Moreover, drought caused a varying degree of decrease (0.16-0.34 m) in the optimal elevations of four typical wetland plants, the upper and lower limit elevations of most wetland plants had also decreased in dry years. [ABSTRACT FROM AUTHOR]

Analysis of Ligand Binding Specificity of Receptor Chimeras The elegant studies of Kobilka et al. define the effects of exchange of individual transmembrane segments of α.sub.2.- and β.sub.2.-adrenergic receptors on [...]

Nowadays, people are paying increasing attention to the rational exploitation of geothermal resources. To develop and utilize geothermal resources in a scientific way, it is important to understand the change patterns of key geohydrological parameters such as seepage velocity and temperature. As part of the effort, this paper analyzes and studies the influencing mechanism of geothermal fluids on the dynamic changes of groundwater flow and heat transfer temperature. First, a differential equation of heat conduction of geothermal fluids and a groundwater flow-geothermal fluids thermal coupling model were constructed to study the seepage state and the heat transfer of groundwater flow in the energy extraction process. Then, an analytical model for the influence of groundwater seepage on heat transfixion was established, directly showing the relevant mechanism. The experimental results proved the effectiveness of the constructed model. [ABSTRACT FROM AUTHOR]

Inhaled drugs, including long-acting muscarinic antagonists (LAMAs), long-acting β2-agonists (LABAs) and inhaled corticosteroids (ICSs), are the main therapeutic options for patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis to compare the efficacy and safety of LAMA+LABA+ICS, LAMA+LABA and LABA+ICS therapies. The Pubmed, Embase and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing the efficacy (moderate-to-severe exacerbations, lung function and quality of life) and safety (adverse events (AEs), severe adverse events (SAEs), withdrawals due to AEs, deaths and pneumonia) of LAMA+LABA+ICS, LAMA+LABA and LABA+ICS in COPD patients. Two investigators independently searched eligible studies and extracted relevant information. The data were analyzed using the Review Manager software, and the quality of included studies was assessed using the Cochrane risk of bias tool. A total of 27 studies were included, and majority of the studies showed low risk of bias. Moderate-to-severe exacerbations were lower after LAMA+LABA+ICS therapy compared with the LABA+ICS (RR = 0.66; 95% CI: 0.59-0.74) and LAMA+LABA therapies (RR = 0.88; 95% CI: 0.82-0.94). Lung function was significantly improved after LAMA+LABA+ICS compared with LAMA+ICS treatment. FEV1, peak FEV1 and trough FEV1 were significantly increased by 100 mL, 150 mL and 120 mL, respectively, in LAMA+LABA+ICS therapy compared with LAMA+ICS. In addition, LAMA+LABA therapy resulted in increased FEV1, peak FEV1 and trough FEV1 by 80 mL, 90 mL and 70 mL, respectively, compared with LAMA+ICS. SGRQ-total score was used to assess quality of life of COPD patients, which indicated that LAMA+LABA+ICS therapy was associated with slightly greater decrease compared with LABA+ICS (MD = -1.33; 95% CI: -2.35 to -0.30). No significant differences were found across all three treatment combinations in term of AEs, SAEs, withdrawals due to AEs and deaths. However, the risk of pneumonia was higher in the triple therapy group than that in the LABA+ICS (RR = 1.16; 95% CI: 1.01-1.33) or LAMA+LABA (RR = 1.31; 95% CI: 1.06-1.62) groups, and significantly lower in the LAMA+LABA group compared with LABA+ICS (RR = 0.64; 95% CI: 0.54--0.76). LAMA+LABA+ICS therapy offered greater efficacy and comparable safety compared with the LAMA+LABA or LABA+ICS therapies. However, triple therapy could increase the risk of pneumonia compared with LAMA+LABA or LABA+ICS therapies. People who have higher risk of pneumonia should carefully consider the use of triple therapy. LAMA+LABA therapy offered greater efficacy and lower risk of pneumonia to LABA+ICS therapy. Collectively, LAMA+LABA therapy might be a better choice than LABA+ICS. [ABSTRACT FROM AUTHOR]

A response by Tong Sun and colleagues to a letter to the editor about their article on a promoter polymorphism in the CASP8 gene which is not associated with cancer risk is presented.

Conformance control and water plugging are a widely used EOR method in mature oilfields. However, majority of conformance control and water plugging agents are unavoidable dehydrated situation in high-temperature and high-salinity low permeability reservoirs. Consequently, a novel conformance control system HPF-Co gel, based on high-temperature stabilizer (CoCl2.H2O, CCH) is developed. The HPF-Co bulk gel has better performances with high temperature (120 ℃) and high salinity (1×105 mg/L). According to Sydansk coding system, the gel strength of HPF-Co with CCH is increased to code G. The dehydration rate of HPF-Co gel is 32.0% after aging for 150 d at 120 ℃, showing excellent thermal stability. The rheological properties of HPF gel and HPF-Co gel are also studied. The results show that the storage modulus (G') of HPF-Co gel is always greater than that of HPF gel. The effect of CCH on the microstructure of the gel is studied. The results show that the HPF-Co gel with CCH has a denser gel network, and the diameter of the three-dimensional network skeleton is 1.5-3.5 μm. After 90 d of aging, HPF-Co gel still has a good three-dimensional structure. Infrared spectroscopy results show that CCH forms coordination bonds with N and O atoms in the gel amide group, which can suppress the vibration of cross-linked sites and improve the stability at high temperature. Fractured core plugging test determines the optimized polymer gel injection strategy and injection velocity with HPF-Co bulk gel system, plugging rate exceeding 98%. Moreover, the results of subsequent waterflooding recovery can be improved by 17%. [ABSTRACT FROM AUTHOR]

We report a method to modulate the photoluminescence (PL) of SrTiO3(001) at room temperature by fluorhydric (HF) acid etching and Ar+ion bombardment. The PL of the virgin sample is in the blue/green range, which can be enhanced in intensity by a factor of 7.2 after being fully etched in HF acid with the peak shape being unchanged. Ar+ion bombardment of SrTiO3can blueshift the overall PL, and the peak maximum becomes centred at 403 nm. After fully etching the ion-bombarded sample in HF, the PL peak stays in the blue light range, but its intensity increases to 17.5 times that of the virgin one. Oxygen vacancies assumed to be produced on the lateral sides of SrTiO3nanograins are responsible for the PL emissions, and their variations in number and nature are attributed to the PL modulation. [ABSTRACT FROM AUTHOR]

Presents a response to a letter to the editor on gene polymorphisms.

Cr/Fe-bearing sludge is a hazardous solid waste, produced at mass production in smelting, plating and surface finishing industries. Such waste is commonly treated by chemical detoxification and safety landfill, whereas only a few Cr-rich sludge is recycled as a tanning reagent. In this study, a novel route was developed to recycle Cr/Fe-bearing sludge as erdite-bearing flocculant for wastewater treatment. Results showed that two sludges were irregular aggregates, one of which contained 1.6 wt.% Cr (short for LS) and the other contained 4.2 wt.% Cr (HS). After hydrothermal treatment, stable Cr(III)/S-bearing product was formed from the Cr(VI) reduction in the sludges. Conversely, erdite was generated in nanorod form with diameter and length of 200 nm and 0.5–1 μm from LS, respectively, whereas grew radially to 1.5–2.5 μm for HS. The two erdite-bearing products were spontaneously hydrolysed to Fe/S-bearing flocs and showed similar performance in the treatment of real electroplating effluent with 91.55, 1.94 and 0.25 mg/L of Zn, Ni and Cr, respectively. For instance, by adding 1 g/L product of LS, the release of Cr from the products did not occur, and the residual Zn, Ni and Cr in the effluent was 0.25, 0.65 and 0.17 mg/L, respectively, which met the discharge standard of the electroplating industry. With the two converted products, the residual Zn/Ni/Cr concentrations were apparently lower than those of the raw sludges and other common reagents (e.g. polymeric ferric sulphate, activated carbon and diatomite). Thus, such erdite-bearing products could serve as a flocculant and then be applied in electroplating wastewater treatment. Highlights: Aggregated sludge was converted to nanorod erdite-bearing flocculant; Hydrothermal detoxication of Cr(VI) as Cr(III) also occurred; Nanorod flocculant was superior for Zn/Ni/Cr removal compared with PFS; Cr(III) was stable in the flocculated deposit without release to wastewater. [ABSTRACT FROM AUTHOR]

This paper describes the background of large multi-shaker test facility's application. There are three major different methods to deal with the synchronous vibration control issues for these facilities. They are including using digital phase unit, analog phase unit and mimo-vibration controller. Finally, specific engineering application examples in the field of aerospace were given. The test results show that different methods have their own strength and weakness and choices have to be made to resolve the in-phase vibration control problems according to the multi-shaker test facilities' configuration. [ABSTRACT FROM AUTHOR]