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The temporal variations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in 33 agricultural soil samples in the vicinity of a municipal solid waste incinerator (MSWI) in Eastern China were determined one year after the initial investigation in 2006. The soil PCDD/F concentrations in 2007 ranged from 73.6 to 377ngkg¿1 (0.60¿6.38ngI-TEQkg¿1). During 2006¿2007, the overall soil PCDD/F levels increased significantly, i.e., 33% and 39% for total concentration and I-TEQ (median value), respectively. Moreover, soils in the study area are proved to be almost free from previously suspected PCDD/F sources, i.e., pentachlorophenol/sodium penta-chlorophenate (PCP/PCP-Na) and 1,3,5-trichloro-2-(4-nitrophenoxy) benzene (CNP) contaminations. Furthermore, the results from a congener-specific factor analysis between soils (collected in two investigations) and dioxin emission sources suggest that diffuse sources including open burning of wastes, traffic and hot water boilers are major contributors that are responsible for the accumulation of PCDD/Fs in soils. By contrast, the impact of the presumably major PCDD/F source identified in our previous study, i.e., the MSWI, seems to be limited. [Copyright &y& Elsevier]

Abstract: Discrete element method (DEM) was employed in the research works presented in this paper to simulate the microscopic machining process of ceramics. A densely packed particle assembly system of the polycrystalline SiC has been generated in DEM software package PFC2D using bonded-particle model (BPM) in order to represent for the ceramic part numerically. Microscopic mechanical properties of SiC were calibrated by comparing the numerical tests in PFC2D with the equivalent experimental results, and introduced into the subsequent modeling of the ceramic machining process. The dynamic process of initiation and propagation of the micro-cracks under various machining conditions has been explicitly modeled in the DEM simulations. The numerical results from DEM modeling agreed well with the experimental observations and theoretical predictions. Rational relations between cracking damage of ceramics and cutting conditions have been established based on the analysis of simulation results. A generalized model of defining the range of inelastic zone has also been developed based on the numerical results. Moreover, this study has demonstrated the advantage of DEM model in its capability of revealing the mechanical details of machining process at micro-scale. [Copyright &y& Elsevier]

Ambient air monitoring of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) was performed to investigate their concentrations, profiles, and sources near a municipal solid waste incinerator (MSWI) in Eastern China. The PCDD/F concentrations varied over a factor of 51.4 from 0.059 to 3.03 pg I-TEQ m-3 (or over 41.4 from 3.96 to 164 pg m-3) and fell at the higher end of the range in recorded peer investigations around the world. Almost all ambient air samples show a unique TCDF-dominant homologue pattern, characterized by decreasing concentrations with increasing levels of chlorination (except for OCDD). By contrast, the dominant congener in terms of concentration profiles shows temporal and spatial variations among the OCDD, OCDF, and 1,2,3,4,6,7,8-HpCDF. The results from a congener-specific factor analysis between ambient air and PCDD/F emission sources, as well as U.S. EPA Chemical Mass Balance (CMB8.2) and Industrial Source Complex Short Term Version 3 (ISCST3) modeling, suggest that the deterioration of air quality in the study area is primarily attributed to open burning of wastes (OB), followed by hot water boilers (HWBs), traffic, and the MSWI. [ABSTRACT FROM AUTHOR]

Abstract: Pharmacophore modeling, including ligand- and structure-based approaches, has become an important tool in drug discovery. However, the ligand-based method often strongly depends on the training set selection, and the structure-based pharmacophore model is usually created based on apo structures or a single protein–ligand complex, which might miss some important information. In this study, multicomplex-based method has been suggested to generate a comprehensive pharmacophore map of cyclin-dependent kinase 2 (CDK2) based on a collection of 124 crystal structures of human CDK2–inhibitor complex. Our multicomplex-based comprehensive pharmacophore map contains almost all the chemical features important for CDK2–inhibitor interactions. A comparison with previously reported ligand-based pharmacophores has revealed that the ligand-based models are just a subset of our comprehensive map. Furthermore, one most-frequent-feature pharmacophore model consisting of the most frequent pharmacophore features was constructed based on the statistical frequency information provided by the comprehensive map. Validations to the most-frequent-feature model show that it can not only successfully discriminate between known CDK2 inhibitors and the molecules of focused inactive dataset, but also is capable of correctly predicting the activities of a wide variety of CDK2 inhibitors in an external active dataset. Obviously, this investigation provides some new ideas about how to develop a multicomplex-based pharmacophore model that can be used in virtual screening to discover novel potential lead compounds. [Copyright &y& Elsevier]

Abstract: A combined quantum mechanics and molecular mechanics (QM/MM) method has been employed to investigate binding energy contributions of the conserved bridging water molecules in CDK2-inhibitor complexes. Calculations to eight selected CDK2-inhibitor complexes with each one containing the same bridging water molecule WAT145 show that the energy contribution of WAT145 varies with ligands, indicating that the energy contribution depends on the characteristic of the corresponding ligand. Calculations to the CDK2-inhibitor complex containing two bridging water molecules show that different bridging water molecules in the same complex offer different binding energy contributions, which is due to the difference of their local environment. [Copyright &y& Elsevier]

Municipal solid waste (MSW) source-classified collection represents a change in MSW management in China and other developing countries. Comparative experiments were performed to evaluate the effect of a newly established MSW source-classified collection system on the emission of PCDDs/Fs (polychlorinated dibenzo-p-dioxins and dibenzofurans) and heavy metals (HMs) from a full-scale incinerator in China. As a result of presorting and dewatering, the chlorine level, heavy metal and water content were lower, but heat value was higher in the source-classified MSW (classified MSW) as compared with the conventionally mixed collected MSW (mixed MSW). The generation of PCDDs/Fs in flue gas from the classified MSW incineration was 9.28ng I-TEQ/Nm3, only 69.4% of that from the mixed MSW incineration, and the final emission of PCDDs/Fs was only 0.12ng I-TEQ/Nm3, although activated carbon injection was reduced by 20%. The level of PCDDs/Fs in fly ash from the bag filter was 0.27ng I-TEQ/g. These results indicated that the source-classified collection with pretreatment could improve the characteristics of MSW for incineration, and significantly decrease formation of PCDDs/Fs in MSW incineration. Furthermore, distributions of HMs such as Cd, Pb, Cu, Zn, Cr, As, Ni, Hg in bottom ash and fly ash were investigated to assess the need for treatment of residual ash. [Copyright &y& Elsevier]

Abstract: Isomer-specific data were investigated in order to identify the sources of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in agricultural soils, including Fluvo-aquic and paddy soils, in the vicinity of a Chinese municipal solid waste incineration (MSWI) plant. Homologue and isomer profiles of PCDD/Fs in soils were compared with those of potential sources, including combustion sources, i.e., MSWI flue gas and fly ash; and the impurities in agrochemicals, such as the pentachlorophenol (PCP), sodium pentachlorophenate (PCP–Na) and 1,3,5-trichloro-2-(4-nitrophenoxy) benzene (CNP). The results showed that the PCDD/F isomer profiles of combustion sources and agricultural soils were very similar, especially for PCDFs, although their homologue profiles varied, indicating that all the isomers within each homologue behave identically in the air and soil. Moreover, factor analysis of the isomer compositions among 33 soil samples revealed that the contamination of PCDD/Fs in agricultural soils near the MSWI plant were primarily influenced by the combustion sources, followed by the PCP/PCP–Na and CNP sources. This implication is consistent with our previous findings based on chemometric analysis of homologue profiles of soil and flue gas samples, and identifies PCP/PCP–Na as an additional important source of PCDD/Fs in the local area. This makes the similarities and differences of isomer profiles between Fluvo-aquic and paddy soils more explainable. It is, therefore, advisable to use isomer-specific data for PCDD/F source identifications where possible. [Copyright &y& Elsevier]

Abstract: PCDD/Fs have been become a serious issue because of their toxicological effects and associated adverse health implications. In this study, the gliding arc plasma was tested for treatment of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), which was synthesized from pentachlorophenol in atmospheric condition at 350°C with or without the catalysis of CuCl2. From the experiment, we found that the destruction efficiency of PCDD/F homologues after gliding was discharge ranged from 25% to 79%. This result demonstrates that gliding arc plasma is an effective technology to decompose PCDDs/Fs in flue gas. A plausible degradation mechanism for PCDD/Fs by gliding arc was discussed. Finally, a multistage reactor structure of gliding arc was proposed to upgrade removal efficiency for PCDD/Fs. [Copyright &y& Elsevier]

Ab initio calculations were performed to investigate the charge separation and charge recombination processes in the photoinduced electron transfer reaction between tetracyanoethylene and acenaphthylene. The excited states of the charge-balanced electron donor–acceptor complex and the singlet state of ion pair complex were studied by employing configuration interaction singles method. The equilibrium geometry of electron donor–acceptor complex was obtained by the second-order Møller–Plesset method, with the interaction energy corrected by the counterpoise method. The theoretical study of ground state and excited states of electron donor–acceptor complex in this work reveals that the S1 and S2 states of the electron donor–acceptor complexes are excited charge transfer states, and charge transfer absorptions that corresponds to the S0 → S1 and S0 → S2 transitions arise from π–π* excitations. The charge recombination in the ion pair complex will produce the charge-balanced ground state or excited triplet state. According to the generalized Mulliken–Hush model, the electron coupling matrix elements of the charge separation process and the charge recombination process were obtained. Based on the continuum model, charge transfer absorption and charge transfer emission in the polar solvent of 1,2-dichloroethane were investigated. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 23–35, 2003 [ABSTRACT FROM AUTHOR]

The authors report their experience with a new strategy for radioguided breast surgery that combines radioguided occult lesion localisation (ROLL) and sentinel lymph node (SLN) mapping. The study population comprised 38 women with non-palpable breast lesions suspicious for breast cancer (BI-RADS 4-5). On the day before surgery, 0.2 ml solution containing particles of dextran labelled with approximately 15 MBq of technetium99m was injected under stereotaxic guidance by mammography. All patients underwent open surgical biopsy guided by gamma probe, radiographic control of the surgical specimen and frozen section analysis. The rate of confirmation of lesion removal was 100% and the rate of simultaneous SLN mapping was 97.3% (37/38). Eleven cases of infiltrating carcinoma and eight of ductal carcinoma in situ (DCIS) were diagnosed intraoperatively. In the first eight invasive lesions, the SLN was biopsied and complete axillary lymph node dissection was performed; in the three other invasive lesions and in two aggressive cases of DCIS, only the SLN was dissected. The intraoperative results of SLN analysis and the definitive histopathological examinations of the SLN were always negative. It is concluded that ROLL and SLN can be employed simultaneously when dextran is used as a tracer; this technique allows frozen section diagnosis and intraoperative node analysis, and has many advantages over the conventional two-step procedure. [ABSTRACT FROM AUTHOR]

We review the experimental and computational data about the propagation of neural signals in myelinated axons in mice, cats, rabbits, and frogs published in the past five decades. In contrast to the natural assumption that neural signals occur one by one in time and in space, we figure out that neural signals are highly overlapped in time between neighboring nodes. This phenomenon was occasionally illustrated in some early reports, but seemed to have been overlooked for some time. The shift in time between two successive neural signals from neighboring nodes, defined as relay time τ, was calculated to be only 16.3 μs–87.0 μs, i.e., 0.8 %–4.4 % of the average duration of an action potential peak (roughly 2 ms). We present a clearer picture of the exact physical process about how the information transmits along a myelinated axon, rather than a whole action potential peak, what is transmitted is only a rising electric field caused by transmembrane ion flows. Here in the paper, τ represents the waiting time until the neighboring node senses an attenuated electric field reaching the threshold to trigger the open state. The mechanisms addressed in this work have the potential to be universal, and may hold clues to revealing the exact triggering processes of voltage-gated ion channels and various brain functions. [ABSTRACT FROM AUTHOR]

This paper presents a micromechanics-based 3D finite element model for predicting the damage initiation, propagation, and failure strength of TC33/Epoxy carbon fiber reinforced polymer (CFRP) unidirectional lamina under biaxial loadings. The finite element model is generated by introducing representative volume element (RVE) with a random distribution of fibers and a non-zero thickness, numerically identified interface phase via cohesive elements. In the finite element model, the carbon fibers are considered as elastic, while the elasto-plastic behavior and damage of the matrix are governed by extended Drucker–Prager plastic yielding model and ductile damage criterion. By imposing periodic boundary conditions to the RVEs, various cases subjected to uniaxial and biaxial loading conditions are carried out. During the combined transverse and in-plane shear stress states, a failure transition from compression- or tension-dominated to shear-dominated is captured, and the effects of the interfacial strength on the transition damage mechanisms are discussed. The corresponding failure locus is compared with the upper bound and lower bound predictions of three phenomenological failure criteria (Hashin, Tasi–Wu, and Puck failure criteria) for composites. It was found that in the interface-dominated failure of a CFRP lamina with a weak interface, the Hashin failure criterion performs best among the currently popular failure criteria. However, in the matrix-dominated failure with a strong interface, the Puck failure criterion performs best. Comparing these three criteria, it can be seen the Tsai–Wu may be generally better than both of others as it presents more neutral predictions in both of the examined cases. [ABSTRACT FROM AUTHOR]

Background The emergence of coronavirus disease 2019 (COVID-19) is a major healthcare threat. The current method of detection involves a quantitative polymerase chain reaction (qPCR)–based technique, which identifies the viral nucleic acids when present in sufficient quantity. False-negative results can be achieved and failure to quarantine the infected patient would be a major setback in containing the viral transmission. We aim to describe the time kinetics of various antibodies produced against the 2019 novel coronavirus (SARS-CoV-2) and evaluate the potential of antibody testing to diagnose COVID-19. Methods The host humoral response against SARS-CoV-2, including IgA, IgM, and IgG response, was examined by using an ELISA-based assay on the recombinant viral nucleocapsid protein. 208 plasma samples were collected from 82 confirmed and 58 probable cases (qPCR negative but with typical manifestation). The diagnostic value of IgM was evaluated in this cohort. Results The median duration of IgM and IgA antibody detection was 5 (IQR, 3–6) days, while IgG was detected 14 (IQR, 10–18) days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9%, respectively. In confirmed and probable cases, the positive rates of IgM antibodies were 75.6% and 93.1%, respectively. The detection efficiency by IgM ELISA is higher than that of qPCR after 5.5 days of symptom onset. The positive detection rate is significantly increased (98.6%) when combining IgM ELISA assay with PCR for each patient compared with a single qPCR test (51.9%). Conclusions The humoral response to SARS-CoV-2 can aid in the diagnosis of COVID-19, including subclinical cases. [ABSTRACT FROM AUTHOR]

Two new isopimarane diterpenoids, named 1α-hydroxy-7-oxoisopimara-8, 15-diene (1), 11β-hydroxy-7-oxoisopimara-8(14), 15-diene (2), together with six known compounds (3-8), were isolated from the medicinal plant Salacia cochinchinensis. All isolates were assayed for their cytotoxicity and α-glucosidase inhibitory activity. Results suggested compounds 1, 3 possessed significant cytotoxic activity against HepG2, HL60, and Hela cell lines with IC50 values ranging from 0.23 to 0.35 μM, and compounds 7, 8 exhibited noticeable α-glucosidase inhibitory ability with IC50 values of 0.25 and 0.31 μM, respectively. [ABSTRACT FROM AUTHOR]

Western flower thrip, Frankliniella occidentalis (Pergande), is among the most economically important agricultural pests globally, attacking a wide range of vegetable and horticultural crops. In addition to causing extensive crop damage, the species is notorious for vectoring destructive plant viruses, mainly belonging to the genera Orthotospovirus, Ilarvirus, Alphacarmovirus and Machlomovirus. Once infected by orthotospoviruses, thrips can remain virulent throughout their lifespan and continue transmitting viruses to host plants when and wherever they feed. These irruptive viral outbreaks in crops will permanently disrupt functional integrated pest management systems, and typically require a remedial treatment involving insecticides, contributing to further development of insecticide resistance. To mitigate against this continuing cycle, the most effective management is early and comprehensive surveillance of the pest species and recognition of plant viruses in the field. This review provides information on the pest status of F. occidentalis, discusses the current global status of the viruses vectored by this thrip species, examines the mechanisms involved in transmitting virus‐induced diseases by thrips, and reviews different management strategies, highlighting the potential management tactics developed for various cropping systems. The early surveillance and the utilization of potential methods for control of both F. occidentalis and viruses are proposed. [ABSTRACT FROM AUTHOR]

Static fatigue tests were conducted on core samples saturated with different phase CO 2 to evaluate the fatigue rate and bulk modulus under constant but stepped stress increment. There was re-appearance of primary fatigue at higher stress in all the samples. In the brine saturated sample, for a 4 MPa deviatoric stress increase, there was about 89% increase in primary fatigue rate with up to 16% more strain, up to 88% reduction in fatigue rate when fatigue goes from primary to secondary fatigue and a reduction in primary fatigue duration by 39% with a bulk modulus of 1.050 GPa. Also, the secondary fatigue rate in stress conditions that had the initial primary fatigue portion was up to 16% higher than the secondary fatigue rate for stress conditions that do not have a primary fatigue portion. Saturating the rock with different phase CO 2 -brine caused a significant change in the fatigue behaviour and bulk modulus depending on the phase of the CO 2. While the effect of CO 2 phase on bulk modulus is most pronounced in the supercritical CO 2 phase (decrease of 22%), change in fatigue rate is most pronounced on gaseous CO 2 phase (an increase of up to 45%) especially when it is combined with brine (an increase of up to 93%). The results of this study provide new insights into the deformation and response of rock's bulk moduli to different states of CO 2 -brine that could exist in a CO 2 storage site and will be useful for the future site selection and maintenance of the geological storage projects. • There is re-appearance of primary fatigue under higher stresses. • The effective stress in rock framework shield intragranular pores. • CO 2 phase affects fatigue behaviour and bulk modulus of reservoir rocks. • Increase in fatigue rate due to CO 2 was seen to be dominant at low stresses. [ABSTRACT FROM AUTHOR]

Actinosynnema species produce diverse natural products with important biological activities, which represent an important resource of antibiotic discovery. Advances in genome sequencing and bioinformatics tools have accelerated the exploration of the biosynthetic gene clusters (BGCs) encoding natural products. Herein, the completed BGCs of dnacin B1 were first discovered in two Actinosynnema pretiosum subsp. auranticum strains DSM 44131T (hereafter abbreviated as strain DSM 44131T) and X47 by comparative genome mining strategy. The BGC for dnacin B1 contains 41 ORFs and spans a 66.9 kb DNA region in strain DSM 44131T. Its involvement in dnacin B1 biosynthesis was identified through the deletion of a 9.7 kb region. Based on the functional gene analysis, we proposed the biosynthetic pathway for dnacin B1. Moreover, p-amino-phenylalanine (PAPA) unit was found to be the dnacin B1 precursor for the quinone moiety formation, and this was confirmed by heterologous expression of dinV, dinE and dinF in Escherichia coli. Furthermore, nine potential PAPA aminotransferases (APAT) from the genome of strain DSM 44131T were explored and expressed. Biochemical evaluation of their amino group transformation ability was carried out with p-amino-phenylpyruvic acid (PAPP) or PAPA as the substrate for the final product formation. Two of those, APAT4 and APAT9, displayed intriguing aminotransferase ability for the formation of PAPA. The proposed dnacin B1 biosynthetic machinery and PAPA biosynthetic investigations not only enriched the knowledge of tetrahydroisoquinoline (THIQ) biosynthesis, but also provided PAPA building blocks to generate their structurally unique homologues. [ABSTRACT FROM AUTHOR]

A pillar-layer pcu Zn (II) MOF exhibits ultrasensitive detection of nitroaniline with low detection limits. • A pillar-layer pcu Zn (II) MOF has been facilely synthesized through solvothermal condition. • This MOFexhibits ultrasensitive detection of nitroaniline. • The sensing mechanism has been investigated. A pillar-layer Zn (II) MOF (1), demonstrating a two-fold interpenetrating pcu topological net, has been facilely assembled from the mixed-ligand strategy. The result of tolerance towards organic solvents indicates MOF 1 shows an exceptional chemostability. The luminescence measurement reveals that MOF 1 is a promising luminescent chemosensor in the ultrasensitive detection of nitroaniline with low detection limits. Besides, the possible luminescent quenching mechanism of MOF 1 toward nitroaniline was investigated by the UV–Vis spectral overlap experiment. [ABSTRACT FROM AUTHOR]

Herein, we report a tandem cycloisomerization/nucleophilic addition/cyclization of 2-amino chalcone with bifunctional nucleophiles driven by visible light. This cascade process is realized by the irradiation of a blue LED at room temperature, which provides a concise route to structurally diverse benzo[d][1,3]oxazocine scaffolds. Mechanistic studies show that the reaction is initiated with the E to Z isomerization of a C–C double bond upon the irradiation of visible light, followed by cyclization/rearomatization to generate a transient quinolinium intermediate, which is trapped by the nucleophile and cyclized to produce the polycyclic benzo[d][1,3]oxazocine. [ABSTRACT FROM AUTHOR]

This paper investigates the mechanical properties and permeability of chemically corroded rock during deep underground tunneling. Nuclear magnetic resonance tests are carried out to quantify the chemical damage of limestone samples at the microscopic scale. Coupled hydrostatic pressure-unloading tests at different unloading rates are also conducted on these chemically corroded limestone samples to investigate permeability changes and chemical effects on mechanical behaviours. Magnetic resonance imaging, T2 spectrum distribution and porosity of the samples are obtained, and the chemical micro damage is visualized and quantified. The relationship between permeability and mechanical behaviors of the rock under hydrochemical–mechanical coupled effects is investigated. The results show that the permeability development process of the chemical corroded samples can be divided into three stages: at the first stage, the permeability initially decreases, and the second stage starts at the inflection point of the permeability curve, from where the permeability begins to increase slightly. At the third stage, the permeability of the limestone increases dramatically until the sample is ruptured. Chemical corrosion and unloading rates have a combined and significant influence on the development of micro cracks in rocks, which is the root cause of the permeability changes. A stress-permeability model is proposed to describe the permeability and stresses in chemical-corroded limestone; this can be adopted for other sedimentary rocks. [ABSTRACT FROM AUTHOR]

Firstly, based on the research of intelligent manufacturing, the thesis analyses the birth and development goals of the Internet of Things and its application in intelligent manufacturing. It sorts out the existing IoT application technology problems in the manufacturing industry and explains the urgency of this research. The paper then analyses the characteristics of high-end assembly fault diagnosis and early warning system in the manufacturing IoT environment, and explains the connotation and characteristics of the system; constructs the overall operation framework, network environment and topology structure; and realizes system construction. Finally, the paper uses the actual case to simulate the application of the system, which verifies the feasibility and effectiveness of the research. [ABSTRACT FROM AUTHOR]

Non-thermal plasma (NTP) is a promising biomedical tool for application to wound healing. However, there is limited scientific evidence that confirms its efficacy to inhibit scar formation. This study aims to investigate the role of non-thermal plasma in scar formation. Two full-thickness dorsal cutaneous wounds of rats were treated with either a non-thermal helium plasma jet or helium. It was determined that the non-thermal plasma jet accelerated the wound healing process from 5 days after surgery (day 5: 41.27% ± 2.351 vs 54.7% ± 5.314, p < 0.05; day 7: 56.05% ± 1.881 vs 75.28% ± 3.914, p < 0.01; day 14: 89.85% ± 2.991 vs 98.07% ± 0.839, p < 0.05). The width of the scars for the NTP group was narrower than those of control group (4.607 ± 0.416 mm vs 3.260 ± 0.333 mm, p < 0.05). In addition, a lower level of TGF-β1, p-Smad2 and p-Smad3 were detected in the NTP treated wounds (p < 0.05, p < 0.01 and p < 0.01). As expected, α-SMA was also significantly decreased in the NTP treatment group (p < 0.01). Moreover, the expression of type I collagen and the proportion of type I to III collagen were lower in the NTP group (p < 0.05). The results of the study suggest that NTP may play a potential role in scar formation by inhibiting the TGF β1 signal pathway and reducing the levels of α-SMA and type I collagen, and may have clinical utility in the future. [ABSTRACT FROM AUTHOR]

Limited drug response and severe drug resistance confer the high mortality of non-small-cell lung cancer (NSCLC), a leading cause of cancer death worldwide. There is an urgent need for novel treatment against NSCLC. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is aberrantly overexpressed and participats in NSCLC development and EGFR-TKIs-induced drug resistance. Increasing evidences indicate that oncogenic ROR1 is a potential target for NSCLC therapy. However, nearly no ROR1 inhibitor was reported until now. Here, combining the computer-aided drug design and cell-based activity screening, we discover (R)-5,7-bis(methoxymethoxy)-2-(4-methoxyphenyl)chroman-4-one (ARI-1) as a novel ROR1 inhibitor. Biological evaluation demonstrates that ARI-1 specifically targets the extracellular frizzled domain of ROR1 and potently suppresses NSCLC cell proliferation and migration by regulating PI3K/AKT/mTOR signaling in a ROR1-dependent manner. Moreover, ARI-1 significantly inhibits tumor growth in vivo without obvious toxicity. Intriguingly, ARI-1 is effective to EGFR-TKIs-resistant NSCLC cells with high ROR1 expression. Therefore, our work suggests that the ROR1 inhibitor ARI-1 is a novel drug candidate for NSCLC treatment, especially for EGFR-TKIs-resisted NSCLC with high ROR1 expression. [ABSTRACT FROM AUTHOR]

For low-dimensional materials, size effect of a physical property is usually expected to occur when one (or more) of the dimension sizes decreases to that comparable to or smaller than one of the intrinsic characteristic lengths, e.g., the mean free path. We report here an unexpected size effect, that in centimeter-long stripes of 100-nm-thick metallic thin films, a reduction of the absolute value of thermopower occurs when the stripe width is in the order of 30-50 μm, which is 100-1000 times larger than the intrinsic mean free path of the material. When the stripe width is reduced to 1.5 μm, a relative reduction of thermopower up to 35% is measured in some metals. We suggest that the sidewall scattering due to rough edges of these stripes may be the origin of this unexpected phenomenon. The results may be applied to construct novel thermoelectric devices, such as thermocouples made from a single metal film. [ABSTRACT FROM AUTHOR]

The floating power generation and wave elimination system is getting more and more attention because of its multiple functions. The Savonius hydrokinetic turbine (SHT) can be used for wave elimination and power generation of offshore platforms due to its good self-start performance and simple structure. The wave elimination performance (WEP) and electricity generation performance (EGP) are closely related to the parameters of SHT, and these parameters are coupled with each other. Improving the performance of SHT under wave conditions and quickly analyzing the relationship between performance and parameters is a topic worth studying. In this paper, a multi-parameter multi-objective metamodel is established by CFD and RBFNN to meet the accuracy. And then coupled with NSGA –II algorithm to solve the Pareto front, quickly determining the optimized parameters of the SHT according to the decision criterion. Finally, a physical model is used for experimental verification, and the influence of each parameter on the performance is further analyzed. After optimization, the WEP is 0.3834 and the EGP is 0.2256. 55.7% and 28.6% improvement over the conventional structure, respectively. The metamodel is well representative within the optimization range. The optimized model still shows better performance in other conditions. • Constructed a metamodel of turbine for rapid analysis of performance. • The metamodel and fluid simulation are verified by experiments. • NSGA-II algorithm gives optimized parameters. • The metamodel combined with simulation gives the high performance interval of the parameters. • Verified that the optimized turbine still performs well under other conditions. [ABSTRACT FROM AUTHOR]

This paper presents the modelling and failure analysis of 3D printed woven composite plates with a hole under tensile and shear loading. In the finite element (FE) software, woven cells are built using stacking sequences, which are then linked together to form the FE model of the woven laminate. According to the 3D printing experiments, tailored fibre placement is achieved in the simulation by altering the fibre orientation around a region to leave a hole. In order to compare this placement technique with that of a control group, 'drilled' samples with the notch removed via mechanical machining was proposed. Three cases, open-hole laminates under tensile loading and double-shear and single-shear loading, are studied to advance the understanding of the failure mechanisms. Good agreement between numerical and experimental results has been obtained, which exhibits a similar trend of strength improvement using new placement technique. The distribution of principal strain and displacement in the modelling are consistent with the results obtained from Digital Image Correlation (DIC) and Micro X-ray Computed Tomography (Micro-CT). It suggests that the avoidance of fibre breakage and the overlap of printed materials around the hole can dramatically increase the failure strength and prevent the propagation of cracks. Image 1 • Finite element models for 3D printed woven CFRP composites with holes were established. • Tailored fibre placement to leave a hole was considered and compared with traditional drilling method. • Avoidance of fibre breakage and overlap of printed materials increase the strength and prevent the propagation of cracks. • The numerical results are supported by the experimental results obtained from DIC and Micro-CT scanning. [ABSTRACT FROM AUTHOR]

A key issue faced by land management in China involves finding ways to prevent the degradation of the farmland system, which includes not only the scale and quality but also the ecological function of farmlands. This study uses a classification model of farmland landscapes that categorizes farmlands as core, boundary, perforation, corridor, edge patches, and discrete patches to propose a prime farmland protection zone delineation model that layer-by-layer excludes single factors based on a 'function, quality, ownership, and environmental identification' basis. Prime farmland protection zones are delineated based on the quality division of farmland, spatial ownership indicators, and geographic environmental determination. Finally, the spatial regulation of farmland boundaries from a 'two lines, two zones' perspective is determined based on conflict and coordination analysis between the prime farmland protection zones and built-up land. The spatial regulation method for farmland protection proposed by this study is based on the strict protection of prime farmland and the maintenance of its structural integrity, which can benefit farmland protection around the cities of China and achieve the goal of orderly urban expansion. This study provides theoretical guidance for protecting productive farmland resources, limiting disorderly urban expansion, and maintaining the heterogeneity of regional landscapes. • Spatial regulation method aiming to resolve the conflict of urban development and farmland protection was proposed. • A landscape structure classification model for farmland was developed to identify contiguous farmland patches. • The farmland protection zone based on 'function, quality, ownership, environmental identification' was proposed. [ABSTRACT FROM AUTHOR]

A zinc(II) triazolate framework comprised of [2 × 2] square grides is regarded as a chemosensor with high selectivity and excellent sensitivity for quantitative detection of dichromate anions in aqueous solution. • A zinc(II) triazolate framework comprised of [2 × 2] square grides has been facilely synthesized. • This MOF could serve as a promising luminescent chemosensor to selectively and sensitively probe dichromate anions in aqueous solution. A new zinc(II) triazolate framework, {[Zn 4 (Trz) 6 (HCOO) 2 } n (1) (Trz = 1 H -1,2,4-triazole) has been synthesized via solvothermal approach and structurally characterized by X-ray single-crystal diffraction associated with elemental analysis, infrared spectrum, thermogravimetric analysis and powder X-ray diffraction. The X-ray structural analysis reveals that the neighboring Zn(II) ions are bridged through the nitrogen atoms of triazole ligands to form a [2 × 2] square gride and the formate anions derived from the decomposition of N,N-dimethyformamide serve as terminal ligands. The [2 × 2] square grides can be further interconnected each other by the triazole groups to generate a 3D framework. Furthermore, 1 demonstrates luminescence response toward dichromate anion in aqueous solution with the average quenching K sv value of 9.72 × 103 L mol−1 and the detection limit of 5.82 × 10−4 mol L−1, indicating 1 is a promising luminescent chemosensor to selectively and sensitively probe dichromate anions in aqueous solution. [ABSTRACT FROM AUTHOR]

Abstract Surface wear is an inevitable damage of wire ropes used in winding hoist. It always reduces the service life of the wire rope and threatens the mine safety. The characteristics of the surface wear scar caused by sliding contact between ropes were discussed in a quantitative and qualitative method for this paper. A series of breaking tensile tests were carried out to investigate the effects of the wear characteristic parameters on the bearing capacity of the rope. Furthermore, the fracture failure behaviors of the rope with different wear scars were analyzed. Results show that the wear scar changes from distributing on one strand to evenly distributed on two adjacent strands as the sliding wear position changes from the strand peak to valley. When the wear region concentrates on one strand, the maximum wear depth increases from approximately 0.46 mm to approximately 0.64 mm with the increase of wear area. Broken wires seriously affect the elongation and breaking force of the rope. The maximum breaking force is approximately 42 KN and the maximum local elongation is approximately 1.5 mm under the condition of broken wires. Additionally, the external wires of the strand are easier to fracture caused by torsion and tension together. Furthermore, the shear lip and the fibre region on the fracture surface of the wires become not very obvious with the increase of the wear scar parameters. Graphical abstract Image 1 Highlights • The distribution of the wear scar is different with the change of sliding wear position. • The wear depth and wear area affect variation of force-elongation curves at different degrees. • The effect of the wire breaking on the elongation and breaking force of ropes most obviously. • The fracture of the outer wires was caused by torsion and tension together. • The plastic deformation and bearing capacity of ropes decrease with wear parameters. [ABSTRACT FROM AUTHOR]

Peptidyl‐prolyl cis‐trans isomerase Pin1 plays a crucial role in the development of human cancers. Recently, we have disclosed that Pin1 regulates the biogenesis of miRNA, which is aberrantly expressed in HCC and promotes HCC progression, indicating the therapeutic role of Pin1 in HCC therapy. Here, 7‐(benzyloxy)‐3,5‐dihydroxy‐2‐(4‐methoxyphenyl)‐8‐(3‐methylbut‐2‐en‐1‐yl)‐4H‐chromen‐4‐one (AF‐39) was identified as a novel Pin1 inhibitor. Biochemical tests indicate that AF‐39 potently inhibits Pin1 activity with an IC50 values of 1.008 μm, and also displays high selectivity for Pin1 among peptidyl prolyl isomerases. Furthermore, AF‐39 significantly suppresses cell proliferation of HCC cells in a dose‐ and time‐dependent manner. Mechanistically, AF‐39 regulates the subcellular distribution of XPO5 and increases miRNAs biogenesis in HCC cells. This work provides a promising lead compound for HCC treatment, highlighting the therapeutic potential of miRNA‐based therapy against human cancer. Neat as a pin: Prenylated flavonol AF‐39 was discovered as a novel and selective Pin1 inhibitor with an IC50 value of 1.008 μm. In hepatocellular carcinoma (HCC) cells, AF‐39 significantly suppresses HCC proliferation via restoring ERK‐phosphorylated exportin‐5 (XPO5) nucleus–cytoplasm distribution and upregulating microRNA biogenesis. [ABSTRACT FROM AUTHOR]

Polyurethane modified with polylactic acid microcapsules were fabricated for controlled release of chlorpyrifos (one of the high usage solid phosphorous insecticides) via interfacial polymerisation with diphenylmethane diisocyanate, polyether triol, 1,4-butanediol and polylactic acid as modifier. The structure, morphology and release properties of synthesised microcapsules were characterised by Fourier transform infra-red spectroscopy, thermogravimetric analyser, scanning electron microscope, particle size analyser and high-performance liquid chromatography. More benign solvents, namely ethyl acetate and n-butyl acetate were used as replacement for toxic solvents commonly used in the preparation of polyurethane microcapsules, namely xylene. The spherical microcapsules prepared in this study were 1–20 μm in diameter. Fourier transform infra-red spectroscopy indicated that polylactic acid had successfully participated in the interfacial polymerisation of polyurethane. Encapsulation efficiency of microcapsules can amount up to 71.0% w/w with a loading efficiency of 26.2% w/w. The microcapsules exhibited a sustained release period above 60 days. Combining polylactic acid into the soft segment of polyurethane proves to effectively accelerate the release rate. [ABSTRACT FROM AUTHOR]

A numerical study of the effects of friction conditions on the formation of dead metal zone (DMZ) is presented. The friction conditions are classified as three different cases in the form of coefficient: (1) constant coefficient of friction, (2) “smooth” and “sharp” change of the friction coefficient and (3) time-dependent friction coefficient. These friction cases are numerically investigated using the finite element (FE) code ABAQUS/Explicit. A FE model based on the arbitrary-Lagrangian-Eulerian approach is developed to simulate the cutting process and investigate the influences of the friction conditions. The simulated results, for a wide range of friction conditions, are obtained, analyzed and compared with previously published experimental/numerical data. It has been found that the friction coefficient has a direct effect on the amount and shape of DMZ, the sharp change of coefficient has a larger effect on the DMZ formation than the smooth one and the formation of DMZ is more determined by the value of the friction coefficient than its duration. [ABSTRACT FROM AUTHOR]

Abstract Nuclear Magnetic Resonance (NMR) imaging in combination with mechanical tests are carried out to investigate the influence of chemical solutions on porosity change, micro damage and macro mechanical property degradation of limestone samples under external stress. The NMR images and T 2 values for compression stage, micro damages emergence stage, micro damages development stage and fracture and collapse stage are obtained and analysed. The results of the corrosive influence of chemical solutions with different pH values and immersion periods on the mechanical property degradation of limestone samples are investigated. By choosing porosity as the damage variable, the micro damage of the samples during triaxial compression are calculated. It can be concluded that pH values of the chemical solutions change the porosity and micro damage evolution of the rock, which is the root reason for its mechanical properties degradation. The chemical erosion also has a significant influence on the micro crack propagation in the limestone samples under triaxial compression. [ABSTRACT FROM AUTHOR]

This paper presents an assessment of three different particle based approaches for 3D modelling of fibre reinforced polymer (FRP) composite laminates with anisotropic elasticity, namely 3D Discrete Lattice model, 3D Hexagonal Close Packing model and Extended 2D Hexagonal and Square Packing model. These approaches are compared and evaluated against experimental results using a 0 ∘ ply lamina case. It has been confirmed that the Extended 2D Hexagonal and Square modelling approach in Discrete Element Method (DEM) is capable of modelling 3D composite laminates with better efficiency. Angle-ply lamina and two different laminates are modelled with the chosen particle approach. Good agreements between DEM, Finite Element and theoretical results prove the capability of this developed DEM approach for modelling the elastic behaviour of general FRP composite lamina and laminates. [ABSTRACT FROM AUTHOR]

Micro damage evolution in chemical corroded limestone samples subjected to cyclic loads is investigated using Nuclear Magnetic Resonance (NMR) system. Based on the experimental data of Magnetic Resonance Imaging (MRI), T 2 values and porosity, the micro damage evolution process is visualized and analyzed. It is found that the porosity and micro cracking of the corroded limestone samples increase with the cyclic loading, and the micro damage evolution process consists of three distinct stages: micro crack emergence stage, micro damage development stage and damage development accelerated stage. Chemical erosion is found to have a significant influence on the propagation of micro cracks and accelerate the damage development of the limestone samples under cyclic loading. With the same number of load cycles, the chemical corroded samples always have lower peak strength than that of the water softened samples. Before the inflection point in the micro damage-loading cycles curve, the main damage is caused by new micro cracks increase inside the limestone; while after this point, the new micro crack emergence is being restrained, and the existed micro cracks connect into rupture bands. A damage model is finally proposed to quantify the damage evolution of the chemical corroded rocks subjected to cyclic loads. [ABSTRACT FROM AUTHOR]

Catalytic oxidation is regarded an effective technique to control the emissions of chlorinated benzenes (CBzs) and polychlorinated dibenzo- p -dioxins and dibenzofurans (PCDD/Fs) from waste incinerators. Among the numerous factors affecting the degradation efficiency of CBzs and PCDD/Fs, limited attention has been paid to the impact of hydrochloric acid (HCl) present in the flue gas. This study investigates how HCl affects the catalytic degradation of 1,2-dichlorbenzene (1,2-DCBz) at different reaction times and temperature regimes. The results showed that the removal efficiency of 1,2-DCBz, which was achieved by the V 2 O 5 /WO 3 -TiO 2 (VWTi) catalyst, decreased the largest by 10% in the presence of HCl. Furthermore, it was found that the increasing concentration of water vapor hindered the degradation efficiency of 1,2-DCBz. No relationship between the process temperature and the destruction efficiency of PCDD/Fs was observed in the presence of HCl. Potential increasing of the removal efficiency of 1,2-DCBz was confirmed by adding different amount of activated carbon (AC) in the presence of HCl. [ABSTRACT FROM AUTHOR]

Many studies have shown a close association between Nogo-B and inflammation-related diseases. However, uncertainty does exist, regarding Nogo-B function in the pathological progression of cerebral ischemia/reperfusion (I/R) injury. Middle cerebral artery occlusion/reperfusion (MCAO/R) model was utilized in C57BL/6L mice to mimic ischemic stroke in vivo. Using oxygen-glucose deprivation and reoxygenation (ODG/R) model in microglia cells (BV-2) to establish cerebral I/R injury in vitro. Various methods, including Nogo-B siRNA transfection, mNSS and the rotarod test, TTC, HE and Nissl staining, immunofluorescence staining, immunohistochemistry, Western blot, ELISA, TUNEL and qRT-PCR were employed to probe into the effect of Nogo-B downregulation on cerebral I/R injury and the potential mechanisms. A small amount of Nogo-B expression (protein and mRNA) was observed in cortex and hippocampus before ischemia, then Nogo-B expression increased significantly on day 1, reaching the maximum on day 3, remaining stable on day 14 after I/R, and decreasing gradually after 21 days, but it still rose significantly compared with that observed preischemia. Nogo-B down-regulation could markedly reduce the neurological score and infarct volume, improve the histopathological changes and neuronal apoptosis, lower the number of CD86+/Iba1+ cells and the levels of IL-1β, IL-6, and TNF-α, and raise the density of NeuN fluorescence, the number of CD206+/Iba1+ cells, and the level of IL-4, IL-10 and TGF-β in brain of MCAO/R mice. Treatment with Nogo-B siRNA or TAK-242 in BV-2 cells could obviously decrease the CD86 fluorescence density and the mRNA expression of IL-1β, IL-6 and TNF-α, increase CD206 fluorescence density and the mRNA expression of IL-10 after OGD/R injury. In addition, the expression of TLR4, p-IκBα and p-p65 proteins significantly increased in the brain after MCAO/R and BV-2 cells exposed to OGD/R. Treatment with Nogo-B siRNA or TAK-242 prominently reduced the expression of TLR4, p-IκBα and p-p65. Our findings suggest that the down-regulation of Nogo-B exerts protective effect on cerebral I/R injury by modulating the microglia polarization through inhibiting TLR4/NF-κB signaling pathway. Nogo-B may be a potential therapeutic target for ischemic stroke. • Downregulation of Nogo-B has an evident protection on cerebral I/R injury. • Downregulation of Nogo-B inhibits neuroinflammatory response after cerebral I/R injury. • Downregulation of Nogo-B promotes microglia polarization from M1 to M2 through inhibiting the TLR4/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Developing a convenient and accurate temperature detection method is of great importance in industrial production, biochemical processes and scientific research. As a noncontact optical temperature sensing technique, luminescence thermometry has been attracted increasing interest. Here we present two Zn(II) metal-organic frameworks (MOFs) with the formulas of {(H 3 O)[Zn 2 (btca) 2 (taz-NH 2) x (taz-CH 3) 1-x ]·H 2 O} n (x ​= ​1 (1); x ​= ​0 (2)) (H 2 btca ​= ​benzotriazole-5-carboxylic acid, Htaz-NH 2 ​= ​5-amino-1H-tetrazole and Htaz-CH 3 ​= ​5-methyl-1H-tetrazole) by virtue of the mixed-ligand approach for photoluminescence sensors as luminescence thermometries over tunable temperature range. Two MOFs exhibit 1D hexagonal nano-channels along the [100] direction, occupied by lattice water molecules. The temperature dependent photoluminescent characteristic of 1 and 2 reveal that the luminescence signals can be decreased as temperature rises from 120 to 400 ​K, thereby achieving the non-destructive temperature detection. Furthermore, linear correlations are presented between the luminescence intensities and the low temperatures for 1 and 2. Satisfying relative sensitivities of 0.49% K−1 for 1 and 0.61% K−1 for 2 , and small temperature uncertainties of 0.062 ​K for 1 and 0.049 ​K for 2 ​at 400 ​K could be acheieved. Notably, the intensity-based luminescent thermometer measurements reveal that 2 shows extremely more linear with temperature and wider temperature range than those of 1 , indicating that 2 is a more considerable luminescence thermometry over tunable temperature range. Two isoreticular zinc(II) metal-organic frameworks luminescent thermometers over tunable temperature range have been facilely fabricated. [Display omitted] • Two 3D Zn(II) MOFs have been facilely synthesized by virtue of the mixed-ligand approach. • The MOFs can be exploited as photoluminescence sensors as luminescence thermometries over tunable temperature range. • 2 shows extremely more linear with temperature and wider temperature range than those of 1. [ABSTRACT FROM AUTHOR]

Recently telecom fraud has become a serious problem especially in developing countries such as China. At present, it can be very difficult to coordinate different agencies to prevent fraud completely. In this paper we study how to detect large transfers that are sent from victims deceived by fraudsters at the receiving bank. We propose a new generative adversarial network (GAN) based model to calculate for each large transfer a probability that it is fraudulent, such that the bank can take appropriate measures to prevent potential fraudsters to take the money if the probability exceeds a threshold. The inference model uses a deep denoising autoencoder to effectively learn the complex probabilistic relationship among the input features, and employs adversarial training that establishes a minimax game between a discriminator and a generator to accurately discriminate between positive samples and negative samples in the data distribution. We show that the model outperforms a set of well-known classification methods in experiments, and its applications in two commercial banks have reduced losses of about 10 million RMB in twelve weeks and significantly improved their business reputation. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effect of dietary lysine level on performance, egg quality and serum biochemical indices of laying pigeons, with the aim of discussing the lysine requirements of laying pigeons. A total of 2,400 healthy pigeons (average body weight: 583 ± 77g) with the age of 40 wk were randomly allocated to 6 treatment groups of 5 replicates with 80 female pigeons each (housed 2 per cage). A 16L:8D light cycle was used. The control group fed the basal diet which was primarily composed of corn-soybean meal with a low lysine level of 0.64%. The lysine levels of the other 5 treatment groups were 0.68%, 0.72%, 0.76%, 0.80%, and 0.84% achieved by adding supplemental lysine to the basal diet. The study had lasted for 12 wk after a 1-wk adaptive phase. The results showed that laying rate and average egg weight of the entire experimental period were significantly influenced by dietary lysine level (P < 0.05), laying rate showed a significant quadratic response to increasing dietary lysine level (maximum response = 0.784), egg weight showed a significant linear response. Dietary lysine level had significant effects on eggshell thickness and yolk color (P<0.05), both showing significant linear response. Eggshell thickness showed a downward trend while yolk color showed an opposite trend. Dietary lysine level had significant effects on the concentration of calcium (Ca), phosphorus (P), total cholesterol, and total protein (P < 0.05) in serum. The concentration of Ca and total cholesterol showed significant linear responses; Ca showed an upward trend, and total cholesterol showed the opposite trend. The content of P showed a significant quadratic response, and showed an upward trend in the range of dietary lysine levels. In conclusion, taking laying rate as the main assessment index and then considering egg quality and serum biochemical indices secondly, the optimal lysine level of dietary was 0.78% for laying pigeons. [ABSTRACT FROM AUTHOR]

Objective. Up to 62% of perimenopausal women have depression symptoms. However, there is no efficacy treatment. The aim of this study is to compare the clinical efficacy and safety of EA therapy and escitalopram on perimenopause women with mild-moderate depressive symptom. Method. A multicenter, randomized, positive-controlled clinical trial was conducted at 6 hospitals in China. 242 perimenopause women with mild-moderate depressive symptom were recruited and randomly assigned to receive 36 sessions of EA treatment or escitalopram treatment. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome measures include menopause-specific quality of life (MENQOL) and serum sexual hormones which include estrogen, follicle-stimulating hormone, and luteinizing hormone. Results. 221 (91.3%) completed the study, including 116 in the EA group and 105 in the escitalopram group. The baseline levels of demographic and outcome measurements were similar in the two groups. In the intervention period, there was no difference between two groups. However, in the follow-up, both HAMD-17 and MENQOL were significantly decreased, and at week 24 the mean differences were −2.23 and −8.97, respectively. There were no significant differences in the change of serum sexual hormones between the two groups. No serious adverse events occurred. Conclusion. EA treatment is effective and safe in relieving depression symptom and improving the quality of life in the perimenopausal depression. Further research is needed to understand long-term efficacy and explore the mechanism of this intervention. This study is registered with ClinicalTrials.gov NCT02423694. [ABSTRACT FROM AUTHOR]

Friction and impact between steel wire rope always exist in multi-layer winding hoist during the winding-in process, in particular for an ultra-deep coal mine. To understand the friction and wear mechanisms of wire rope among the layers in the winding hoist, a series of sliding friction experiments were carried out using a self-made friction test rig. The results show that the coefficient of friction (COF) of the wire rope changes little with increasing load and stabilizes at approximately 0.73, but decreases with the sliding velocity under dry-friction condition. However, under lubrication condition, there is almost no effect of the contact load and sliding velocity on the COF, which stabilizes at approximately 0.35. Additionally, the temperature rise is concentrated at the contact area, and it increases with the load and the sliding velocity. The maximum temperature rise with the lubrication is much lower, approximately 10 °C, than that under the condition of dry-friction, which is approximately 103 °C. Furthermore, the maximum of the COF under the impact load is significantly lower than that for the stable contact friction. With the impact and sliding velocities increase, the maximum COF under the impact load experiences a slight increase and reaches a maximum value of approximately 0.36. As the impact load increases, the COF changes little, but the impact process occurs more than once. [ABSTRACT FROM AUTHOR]

The RET tyrosine kinase is an important therapeutic target for medullary thyroid cancer (MTC), and drug resistance mutations of RET, particularly V804M and V804L, are a main challenge for the current targeted therapy of MTC based on RET inhibitors. In this investigation, we report the structural optimization and structure-activity relationship studies of N -phenyl-7,8-dihydro-6 H -pyrimido[5,4-b][1,4]oxazin-4-amine derivatives as a new class of RET inhibitors. Among all the obtained kinase inhibitors, 1-(5-( tert -butyl)isoxazol-3-yl)-3-(4-((6,7,8,9-tetrahydropyrimido[5,4-b][1,4]oxazepin-4-yl)amino)phenyl)urea ( 17d) is a multi-kinase inhibitor and potently inhibits RET and its drug resistance mutants. It showed IC 50 (half maximal inhibitory concentration) values of 0.010 μM, 0.015 μM, and 0.009 μM against RET-wild-type, RET-V804M, and RET-V804L, respectively. 17d displayed significant anti-viability potencies against various RET-driving tumor cell lines. In a xenograft mouse model of NIH3T3-RET-C634Y, 17d exhibited potent in vivo anti-tumor activity, and no obvious toxicity was observed. Mechanisms of action were also investigated by Western blot and immunohistochemical assays. Collectively, 17d could be a promising agent for the treatment of MTC, hence deserving a further investigation. [ABSTRACT FROM AUTHOR]

The 4 properties of Chinese materia medica refer to cold, hot, warm, and cool. In the present study, the effects of the Coptis, the prepared aconite root, and dried ginger rhizome were compared with regard to the rectal and skin temperature changes of the related body surface acupuncture points (Dazhui, Zhiyang, Mingmen, Zhongwan, and Shenque). The investigation aimed to explore the thermal sensitive points, which can reflect the cold and hot properties of the Chinese herbs. This study showed that the prepared aconite root and dried ginger rhizome exhibited a warming effect on the body temperature, whereas the warming sensitive points were Zhongwan, Shenque, Dazhui, and Zhiyang. Coptis exhibited both a warming and a cooling effect on the body temperature, and the cooling sensitive point was Dazhui. The concomitant effect of these three Chinese herbs on the regulation of the body temperature was reflected by Dazhui. However, there are still some limitations and one-sidedness. For instance, the cold and hot property of some herbs cannot be fully reflected through relevant acupoints on the conception and governor vessels. More detecting sites such as ears and internal organs will be selected for further exploration of Chinese herbs’ cold and hot property. [ABSTRACT FROM AUTHOR]

Motivation: Genetic and gene expression variations within and between populations and across geographical regions have substantial effects on the biological phenotypes, diseases, and therapeutic response. The development of precision medicines can be facilitated by the OMICS studies of the patients of specific ethnicity and geographic region. However, there is an inadequate facility for broadly and conveniently accessing the ethnic and regional specific OMICS data. Results: Here, we introduced a new free database, HEROD, a human ethnic and regional specific OMICS database. Its first version contains the gene expression data of 53 070 patients of 169 diseases in seven ethnic populations from 193 cities/regions in 49 nations curated from the Gene Expression Omnibus (GEO), the ArrayExpress Archive of Functional Genomics Data (ArrayExpress), the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Geographic region information of curated patients was mainly manually extracted from referenced publications of each original study. These data can be accessed and downloaded via keyword search, World map search, and menu-bar search of disease name, the international classification of disease code, geographical region, location of sample collection, ethnic population, gender, age, sample source organ, patient type (patient or healthy), sample type (disease or normal tissue) and assay type on the web interface. [ABSTRACT FROM AUTHOR]

Background: Dengue was regarded as a mild epidemic in mainland China transmitted by Aedes albopictus. However, the 2014 record-breaking outbreak in Guangzhou could change the situation. In order to provide an early warning of epidemic trends and provide evidence for prevention and control strategies, we seek to characterize the 2014 outbreak through application of detailed cases and entomological data, as well as phylogenetic analysis of viral envelope (E) gene. Methods: We used case survey data identified through the Notifiable Infectious Disease Report System, entomological surveillance and population serosurvey, along with laboratory testing for IgM/IgG, NS1, and isolation of viral samples followed by E gene sequencing and phylogenetic analysis to examine the epidemiological and molecular characteristics of the outbreak. Results: The 2014 dengue outbreak in Guangzhou accounted for nearly 80% of total reported cases that year in mainland China; a total of 37,376 cases including 37,340 indigenous cases with incidence rate 2908.3 per million and 36 imported cases were reported in Guangzhou, with 14,055 hospitalized and 5 deaths. The epidemic lasted for 193 days from June 11 to December 21, with the highest incidence observed in domestic workers, the unemployed and retirees. The inapparent infection rate was 18.00% (135/750). In total, 96 dengue virus 1 (DENV-1) and 11 dengue virus 2 (DENV- 2) strains were isolated. Phylogenetic analysis indicated that the DENV-1 strains were divided into genotype I and V, similar to the strains isolated in Guangzhou and Dongguan in 2013. The DENV-2 strains isolated were similar to those imported from Thailand on May 11 in 2014 and that imported from Indonesia in 2012. Conclusions: The 2014 dengue epidemic was confirmed to be the first co-circulation of DENV-1 and DENV-2 in Guangzhou. The DENV-1 strain was endemic, while the DENV-2 strain was imported, being efficiently transmitted by the Aedes albopictus vector species at levels as high as Aedes aegypti. [ABSTRACT FROM AUTHOR]