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• We identified acevaltrate as an inhibitor of hypoxia-inducible factor-1α accumulation from the roots of Valeriana glechomifolia. • Acevaltrate inhibits HIF-1α protein synthesis and promotes degradation of HIF-1α protein. • Acevaltrate inhibits HIF-1α protein expression through suppression of mTOR/p70S6K/4E-BP1 signaling pathway. • Acevaltrate promotes apoptosis and inhibits proliferation by inhibiting HIF-1α. • Acevaltrate could be a valuable candidate for the intervention of hypoxia-inducible factor-1α-dependent anticancer activity. Acevaltrate is a natural product isolated from the roots of Valeriana glechomifolia F.G.Mey. (Valerianaceae) and has been shown to exhibit anti-cancer activity. However, the mechanism by which acevaltrate inhibits tumor growth is not fully understood. We here demonstrated the effect of acevaltrate on hypoxia-inducible factor-1α (HIF-1α) expression. Acevaltrate showed a potent inhibitory activity against HIF-1α induced by hypoxia in various cancer cells. This compound markedly decreased the hypoxia-induced accumulation of HIF-1α protein dose-dependently. Further analysis revealed that acevaltrate inhibited HIF-1α protein synthesis and promoted degradation of HIF-1α protein, without affecting the expression level of HIF-1α mRNA. Moreover, the phosphorylation levels of mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), and eIF4E binding protein-1 (4E-BP1) were significantly suppressed by acevaltrate. In addition, acevaltrate promoted apoptosis and inhibited proliferation, which was potentially mediated by suppression of HIF-1α. We also found that acevaltrate administration inhibited tumor growth in mouse xenograft model. Taken together, these results suggested that acevaltrate was a potent inhibitor of HIF-1α and provided a new insight into the mechanisms of acevaltrate against cancers. [ABSTRACT FROM AUTHOR]

High nitrogen steel welded joints are prone to problems such as porosity defects and coarse grain size. To address these issues, ultrasonic-assisted laser-arc hybrid welding experiments were conducted on 8 mm-thick high nitrogen steel plates. The effect of ultrasonic vibration on the porosity defects, microstructure, and properties of welded joints was studied. The results indicate that with the increase of ultrasonic power, the pore ratio of the weld first decreases and then increases. The effects generated due to ultrasound such as cavitation and sound flow caused grain refinement while weakening the directionality of grain growth. The refined microstructure of the weld increased the microhardness. However, when the ultrasonic power was 240 W, the microhardness of the welded joint decreased due to the low nitrogen content. As the ultrasonic power was increased, the tensile strength and impact toughness initially exhibited an enhancement followed by a declining trend. The best mechanical properties were obtained when the ultrasonic power was 180 W. In contrast, the worst performance was obtained when the ultrasonic power was 240 W, which was due to higher porosity and severe nitrogen loss. Ultrasonic impact can reduce welding residual stress and improve the corrosion resistance of welds, and the effect becomes more pronounced with the increase of ultrasound power. • Ultrasonic-assisted laser-arc hybrid welding experiments were conducted on 8 mm-thick high-nitrogen steel plates. • There exists an optimal ultrasonic power that can suppress weld porosity defects. • The effect of ultrasonic vibration on the microstructure, and properties of welded joints was studied. [ABSTRACT FROM AUTHOR]

Microbeam wide-angle X-ray diffraction (WAXD) experiments were carried out at different structural knot positions of SIOC and M4 fibers of ultra-high molecular weight polyethylene (UHMWPE). The optical microscope images revealed that SIOC fiber had bamboo-like structural knots, and M4 fiber had chaotic distribution of structural knots. WAXD patterns showed the monoclinic unit cell in the whole M4 fiber, but different lamellar orientations in the bamboo joint of SIOC fiber. In addition, small-angle X-ray scattering (SAXS) patterns confirmed that the SIOC fiber contained uniform distribution of shish structures, and differential scanning calorimetry (DSC) measurements showed that its less branched and short chains benefited the orthorhombic-hexagonal phase transformation. [ABSTRACT FROM AUTHOR]

A practical and economical process for the synthesis of perfluoroalkylated biphenyl derivatives has been developed. The three-component reaction of aromatic ketones, malononitrile and methyl perfluoroalk-2-ynoates gave the desired products in good to excellent yields via a one-pot two-step process. [ABSTRACT FROM AUTHOR]

• Both metallic Ag and Ag oxide exist in the coating. • A nano-sized Ag-rich layer exists at the substrate/coating interface. • PEO affects corrosion morphology and susceptibility of Mg-Ag alloy. • A sustained Ag+ release is achieved after PEO of Mg-Ag alloy. The application of biodegradable Mg alloys as implanted devices has been hindered by their low corrosion resistance and potential risk associated with microbial infection. In the present work, a rolled Mg-Ag alloy was studied, which was subjected to plasma electrolytic oxidation (PEO) to achieve a favoured balance between corrosion resistance and antimicrobial capability. The Ag distribution, corrosion resistance and Ag ionic release behaviour have been examined in details. It is revealed that PEO process leads to both incorporated Ag+ and Ag-rich nanoparticles in forms of metallic Ag and Ag oxide across the coating. In addition, a nano-sized Ag-enriched layer also exists at the substrate/coating interface. The microstructural modification associated with PEO process results in an increased corrosion resistance and a sustained Ag ionic release, indicating that it is a promising surface modification technique for antibacterial Mg-Ag alloy. [Display omitted] [ABSTRACT FROM AUTHOR]

The development of highly selective Janus Kinase 1 (JAK1) inhibitors is crucial for improving efficacy and minimizing adverse effects in the clinical treatment of autoimmune diseases. In a prior study, we designed a series of C-5 4-pyrazol substituted pyrrolopyridine derivatives that demonstrated significant potency against JAK1, with a 10 ∼ 20-fold selectivity over Janus Kinase 2 (JAK2). Building on this foundation, we adopted orthogonal strategy by modifying the C-5 position with 3-pyrazol/4-pyrazol/3-pyrrol groups and tail with substituted benzyl groups on the pyrrolopyridine head to enhance both potency and selectivity. In this endeavor, we have identified several compounds that exhibit excellent potency and selectivity for JAK1. Notably, compounds 12b and 12e , which combined 4-pyrazol group at C-5 site and meta -substituted benzyl tails, displayed IC 50 value with 2.4/2.2 nM and high 352-/253-fold selectivity for JAK1 over JAK2 in enzyme assays. Additionally, both compounds showed good JAK1-selective in Ba/F3-TEL-JAK1/2 cell-based assays. These findings mark a substantial improvement, as these compounds are 10-fold more potent and over 10-fold more selective than the best compound identified in our previous study. The noteworthy potency and selectivity properties of compounds 12b and 12e suggest their potential utility in furthering the development of drugs for autoimmune diseases. [Display omitted] • Three categories of pyrrolopyridine derivatives were synthesized as potent JAK1 inhibitors. • Orthogonal strategy revealed the SAR between "side chain" and benzyl "tail". • 12b / 12e showed 352-/253-fold selectivity for JAK1 over JAK2 in enzyme assay. [ABSTRACT FROM AUTHOR]

The Multi-purpose Time Projection Chamber (MTPC) is a gas-filled detector designed to measure cross sections of neutron-induced light-charged particle emission and fission reactions at the Back-streaming white neutron facility (Back-n) at the China Spallation Neutron Source. A prototype MTPC has been constructed with a drift volume, a resistive Micromegas charge amplification structure, and a high-density pixelated anode readout plane with 1519 hexagonal pads. Test measurements have been performed using a four-component alpha source. Alpha-particle track reconstruction is performed to obtain the deposited energy and length information of the trajectory. The performance test and characterization of the detector have served as the basis for the optimized design of the MTPC, which is currently undergoing commissioning at Back-n. [ABSTRACT FROM AUTHOR]

To investigate the 1.6 GeV high-energy proton beam detector utilized in the CSNS Phase-II upgrade project, a plastic scintillator detector presents a viable option due to its superior radiation hardness. This study investigates the effects of irradiation damage on a BC408 plastic scintillator induced by 80 MeV protons, including absorption and fluorescence spectroscopy, and light yield tests of BC408 pre- and post-proton irradiation, with a focus on determining the radiation resistance threshold of BC408. The results indicate that the performance of BC408 remains unimpaired at absorbed doses up to 5. 14 × 1 0 3 Gy , demonstrating its ability to absorb 1. 61 × 1 0 13 p/cm 2 1.6 GeV protons while maintaining stability. This suggests that BC408 could potentially be used as the 1.6 GeV high-energy proton beam detector in the CSNS Phase-II upgrade project. [ABSTRACT FROM AUTHOR]

Annular thermoelectric power generator has been increasingly considered in application of ambient energy harvesting owing to the advantages of simple structure and no pollution. To improve thermal stability and energy harvesting performance of this system, the latent heat of phase change materials to improve thermal management and the high thermal conductivity of the heat sink to enhance heat transfer with the ambient are harness to annular thermoelectric power generator. Motivated by this, a phase change material based annular thermoelectric energy harvester (PCM-ATEH) with fins is developed for ambient energy harvesting and its three-dimensional transient model is also built up through jointly with thermo-electric and phase change processes. This paper considers the influence of key parameters such as temperature fluctuation amplitude, temperature fluctuation period, height ratio of PCM and thermoelectric generator (TEG) and melting temperature on liquid fraction, temperature difference, voltage and power density. Moreover, the comparison of PCM-ATEH and PCM based thermoelectric energy harvester (PCM-TEH) with/without fins is further conducted in this study to explore thermal management and energy harvesting performance. The energy harvesting characteristics of PCM-ATEH with fins is developed concerning the combination of power generation of TEG and melting process of PCM. Based on the results, it is found that the temperature difference and power density of PCM-ATEH with fins vary periodically with the sinusoidal temperature boundary, and results show that increasing temperature fluctuation period is not always feasible. Additionally, the comparative results indicate that the peak power density and energy efficiency of PCM-ATEH with fins are increased by 0.126 W/m2 and 0.02 % compared with PCM-TEH with fins, and increased by 0.195 W/m2 and 0.041 % compared with PCM-ATEH without fins. The results of energy harvesting characteristics show that a maximum of 0.77$ per watt can be reached to power generation cost of PCM-ATEH with fins. This paper can provide theoretical guidance for thermal management and energy conversion of energy harvesting system. [ABSTRACT FROM AUTHOR]

Annular thermoelectric power generator has been increasingly considered in application of ambient energy harvesting owing to the advantages of simple structure and no pollution. To improve thermal stability and energy harvesting performance of this system, the latent heat of phase change materials to improve thermal management and the high thermal conductivity of the heat sink to enhance heat transfer with the ambient are harness to annular thermoelectric power generator. Motivated by this, a phase change material based annular thermoelectric energy harvester (PCM-ATEH) with fins is developed for ambient energy harvesting and its three-dimensional transient model is also built up through jointly with thermo-electric and phase change processes. This paper considers the influence of key parameters such as temperature fluctuation amplitude, temperature fluctuation period, height ratio of PCM and thermoelectric generator (TEG) and melting temperature on liquid fraction, temperature difference, voltage and power density. Moreover, the comparison of PCM-ATEH and PCM based thermoelectric energy harvester (PCM-TEH) with/without fins is further conducted in this study to explore thermal management and energy harvesting performance. The energy harvesting characteristics of PCM-ATEH with fins is developed concerning the combination of power generation of TEG and melting process of PCM. Based on the results, it is found that the temperature difference and power density of PCM-ATEH with fins vary periodically with the sinusoidal temperature boundary, and results show that increasing temperature fluctuation period is not always feasible. Additionally, the comparative results indicate that the peak power density and energy efficiency of PCM-ATEH with fins are increased by 0.126 W/m2 and 0.02 % compared with PCM-TEH with fins, and increased by 0.195 W/m2 and 0.041 % compared with PCM-ATEH without fins. The results of energy harvesting characteristics show that a maximum of 0.77$ per watt can be reached to power generation cost of PCM-ATEH with fins. This paper can provide theoretical guidance for thermal management and energy conversion of energy harvesting system. [ABSTRACT FROM AUTHOR]

Purpose: To explore the functional connectivity (FC) between the bilateral thalamus and the other brain regions in patients with vestibular migraine (VM). Methods: Resting-state fMRI and 3D-T1 data were collected from 37 patients with VM during the interictal period and 44 age-, gender-, and years of education-matched healthy controls (HC). The FC of the bilateral thalamus was analyzed using a standard seed-based whole-brain correlation method. Furthermore, the correlations between thalamus FC and clinical characteristics of patients were investigated using Pearson's partial correlation. Results: Compared with HC, VM patients showed decreased FC between the left thalamus and the left anterior cingulate cortex (ACC), bilateral insular and right supplementary motor cortex. We also observed decreased FC between the right thalamus and the left insular and ACC in VM patients. Furthermore, patients with VM also exhibited increased FC between the left thalamus and the right precuneus and middle frontal gyrus, between the right thalamus and superior parietal lobule. FC between the right thalamus and the left insular was negatively correlated with disease duration (p = 0.019, r = − 0.399), FC between the left thalamus and the left ACC was negatively correlated with HIT-6 score (p = 0.004, r = − 0.484). Conclusion: VM patients showed altered FC between thalamus and brain regions involved in pain, vestibular and visual processing, which are associated with specific clinical features. Specifically, VM patients showed reduced thalamo-pain and thallamo-vestibular pathways, while exhibited enhanced thalamo-visual pathway, which provided first insight into the underlying functional brain connectivity in VM patients. [ABSTRACT FROM AUTHOR]

An ultra-thin vapor chamber (UTVC) is an efficient heat transfer component that meets the heat dissipation requirement of miniaturized electronic devices. Heat dissipation is one of the most important issues for UTVCs. With decreasing thickness, the mechanical strength of heat pipes and vapor chambers drops dramatically, and inevitable surface damage occurs during conventional contact thermal testing. Here, we demonstrate a non-contact thermal testing method using laser heating and infrared temperature measurement to evaluate the thermal performance of UTVCs. This non-contact method allows UTVCs to reach a steady-state sooner than traditional contact methods. Use of the characteristic thermal resistance is proposed for more straightforward evaluation of the UTVC thermal performance in non-contact testing setups. This non-contact thermal testing method has proved to be an efficient testing method for UTVCs due to its rapidity, accuracy, and non-destructiveness. [ABSTRACT FROM AUTHOR]

The direct‐synthesis of conductive PbS quantum dot (QD) ink is facile, scalable, and low‐cost, boosting the future commercialization of optoelectronics based on colloidal QDs. However, manipulating the QD matrix structures still is a challenge, which limits the corresponding QD solar cell performance. Here, for the first time a coordination‐engineering strategy to finely adjust the matrix thickness around the QDs is presented, in which halogen salts are introduced into the reaction to convert the excessive insulating lead iodide into soluble iodoplumbate species. As a result, the obtained QD film exhibits shrunk insulating shells, leading to higher charge carrier transport and superior surface passivation compared to the control devices. A significantly improved power‐conversion efficiency from 10.52% to 12.12% can be achieved after the matrix engineering. Therefore, the work shows high significance in promoting the practical application of directly synthesized PbS QD inks in large‐area low‐cost optoelectronic devices. [ABSTRACT FROM AUTHOR]

Background: X-linked inhibitor of apoptosis protein (XIAP) is the strongest member of the family of inhibitor of apoptosis protein. Studies found that the expression of XIAP in colon cancer tissue was significantly higher than that in adjacent tissues. Studies have shown that the expression of microRNA-215 (miR-215) was significantly lower than that of the adjacent tissues. This study investigated whether dysregulated miR-215 and XIAP play important roles in colon cancer cell apoptosis and the incidence of colon cancer. Materials and Methods: Forty-two patients with colorectal cancer (CRC) diagnosed and treated in the authors' hospital were selected. Human CRC cell line HCT116 and normal colonic mucosal epithelial cells (CMECs) were used. Luciferase reporter gene vector was constructed and dual-luciferase reporter gene assay was performed. HCT116 cells were cultured in vitro and divided into five groups: mimic normal control (NC) group, miR-215 mimic group, si-NC group, si-XIAP group, and miR-215 mimic + si-XIAP group. Western blot and polymerase chain reaction were conducted to examine XIAP and caspase-3. Apoptosis was detected by flow cytometry and cell proliferation was detected by cell counting kit-8 assay. Results: Compared with the adjacent tissues, the expression of miR-215 in colon cancer tissue was significantly lower, whereas the expression of XIAP in colon cancer tissue was significantly higher. The apoptosis rate and miR-215 expression level of HCT116 cells were lower than that of normal CMECs, whereas XIAP expression was significantly higher than that in normal colon mucosa epithelial cells. MiR-215 targeted the 3'-untranslated regions of XIAP and inhibited its expression. Overexpressing miR-215 and (or) silencing XIAP expression could significantly enhance the activity of caspase-9 and caspase-3, and promote the apoptosis of HCT116 cells. Conclusion: MiR-215 inhibited the expression of XIAP and promoted the apoptosis of HCT116 cells. [ABSTRACT FROM AUTHOR]

Investigations of in vivo corrosion behaviours of Ti-based orthopaedic implants are required for their clinical applications. In this work, C 10 H 12 CuN 2 Na 2 O 8 (Na 2 Cu-EDTA) has been applied to fabricate a Cu-rich TiO 2 ceramic layer on Ti substrate via micro-arc oxidation (MAO). The incorporation of Cu reduces the thickness and porosity of the resultant coating, which also affects its biological properties. With the addition of H 2 O 2 and/or albumin in NaCl solution to simulate the peri-implant conditions, Cu-rich TiO 2 ceramic layer displays a desirable chemical stability in simulated human environments whereas the synergistic effect of albumin and H 2 O 2 dramatically affects the electrochemical responses of bare Ti and Cu-free TiO 2 layer. Our present work illustrates the influence of in vivo chemical conditions on the corrosion properties of micro-arc oxidized titanium, which provides valuable guidance for its clinical application. • The synergetic effect of H 2 O 2 and albumin on the corrosion of micro-arc oxidized titanium was studied. • TiO 2 mainly acts as a physical barrier. • The incorporated Cu may alter the external chemical environment. • Cu is conducive to the bactericidal capability of TiO 2. [ABSTRACT FROM AUTHOR]

[Display omitted] • A uniform appearance is achieved by the introduction of ultrasound. • Ultrasound stimulates the formation of an amorphous Ca, P, Cu and O-rich layer. • Ultrasound is beneficial for corrosion and biological properties of the coating. To achieve a uniform surface layer with enhanced corrosion resistance, antibacterial capability and cytocompatibility on the titanium (Ti)-based orthopaedic implant, ultrasound-auxiliary micro-arc oxidation (UMAO) was carried out on Ti substrate to fabricate a Cu-incorporated TiO 2 coating. Instead of the co-existence of central brown area and peripheral black area in the Cu-incorporated TiO 2 coating fabricated by conventional micro-arc oxidation, a uniform brownish appearance could be achieved after the introduction of ultrasonic vibration (UV). The introduction of UV also significantly modifies the elemental composition, phase component and chemical configuration of the coating, which exhibits a bi-layered structure with the porous TiO 2 as the inner layer and the amorphous Ca, P, O and Cu component as the outer layer. Finally, electrochemical measurement and in vitro biological tests indicate that the introduction of UV is conducive to corrosion resistance, antibacterial capability and cytocompatibility of the Cu-incorporated TiO 2 coating. [ABSTRACT FROM AUTHOR]

Abstract: The possible involvement of the nitric oxide (NO)–cyclic GMP (cGMP)–protein kinase G (PKG) pathway on bovine lactoferrin (BLF)-induced spinal antihyperalgesic activity was elucidated in sciatic nerve injured rats. Intrathecal BLF reduced thermal hyperalgesia in a dose-dependent manner. Pretreatment with N G-l-nitro-arginine methyl ester (l-NAME, non-specific inhibitor of NO synthase), 7-nitroindazole (7-NI, neuronal NO synthase inhibitor), 1H-[1,2,4]-oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, guanylyl-cyclase inhibitor), (9S, 10R, 12R)-2,3,9,10,11,12-hexahydro-10-methoxy-2, 9-dimethyl-1-oxo-9, 12-epoxy-1H-diindolo-[1,2,3-fg:3′,2′,1′-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester (KT-5823, specific PKG inhibitor) or glybenclamide (ATP-sensitive K+ channel blocker), but not N G-d-nitro-arginine methyl ester (d-NAME, an inactive enantiomer of l-NAME), d-Phe-Cys-Tyr-d-Trp-Orn-Thr-NH2 (CTOP, selective μ-opioid receptor antagonist) or naloxone (nonselective opioid receptor antagonist) prevented BLF-induced antihyperalgesia. Data suggest that BLF-induced spinal antihyperalgesia could be due to activation of the NO–cGMP–PKG–K+ channel pathway and it is not mediated by μ-opioid receptor in a model of neuropathic pain. [Copyright &y& Elsevier]

Abstract: The water-soluble crude polysaccharide (CAP) was extracted from Angelica sinensis and was further fractionated by Sephacryl S-400 column chromatography, giving three polysaccharide fractions termed APF1, APF2 and APF3. The obtained results showed that the uronic acid linkages in the polysaccharides were more stable and resistant to thermal hydrolysis than neutral sugar linkages. APF2 exhibited higher thermal stability, followed by APF1, APF3 and CAP in decreasing order. APF1 contained the highest carbohydrate content (80.5%) and the lowest uronic acid content (28.4%) in comparison with APF2 (77.7% and 39.2%) and APF3 (70.1% and 34.6%). Further bioactive investigation showed that intraperitoneal administration of the polysaccharide fractions significantly induced peritoneal macrophage to release nitric oxide (NO), reactive oxygen species (ROS) and enhanced cellular lysosomal enzyme activity (p <.05) and the highest activity was achieved by APF2. Taken together, APF2 had the high thermal stability and immunostimulatory activity and so should be explored as a novel potential immunostimulants. [Copyright &y& Elsevier]

Main observation and conclusion: In searching for novel fungicidal leads, a series of pyrazole‐containing strobilurins were rationally designed, synthesized and characterized. Bioassay indicated that compound I‐7 displayed excellent fungicidal activity against a broad spectrum of plant pathogens such as Gibberella zeae, Rhizoctonia cerealis, Sclerotinia sclerotiorum, Phytophthora infestans, Physalospora piricola and Pellicularia sasakii with EC50 of 0.16, 0.02, 0.72, 0.07, 0.77 and 0.65 μg/mL, respectively, which were 3—10 times more potent than the positive control azoxystrobin against the corresponding pathogens. Moreover, like azoxystrobin and kresoxim methyl, I‐7, displayed excellent protective activity against P. sorghi. Molecular docking validated that I‐7 and azoxystrobin would share a similar binding mode with cytochrome bc1 complex. This study demonstrates that I‐7 is a promising fungicidal candidate for further development. [ABSTRACT FROM AUTHOR]

Electrochemical noise (EN) measurements were applied to detect the stress corrosion cracking (SCC) of API P110 low alloy steel in simulating CO2-containing downhole fluid during the slow strain rate test (SSRT). Several statistical parameters of potential and current transients were defined, and they were proven to be indicative of the metastable and stable pitting, as well as the initiation and propagation processes of microcracks. The EN results showed that the amplitude and lifespan of current transients increase with the CO2 concentration. The increasing SCC susceptibility of P110 steel is mainly attributed to the decreasing pH at the crack tip, which not only accelerated the rupture of passive film on crack walls but also prolonged the lifespan of cracks advance. EN measurement may be a promising technique for the early diagnosis of SCC. [ABSTRACT FROM AUTHOR]

Gyrotron, as a most likely practical high-power terahertz (THz) radiation source, has been widely applied to THz dynamic nuclear polarization-enhanced nuclear magnetic resonance (DNP-NMR) spectroscopy. In this article, an iris cavity with high-quality factor is theoretically designed for a frequency-tunable THz gyrotron, which could be tuned at three frequency regimes: 140, 250, and 263 GHz, respectively. Based on the self-developed nonlinear code, the beam wave interactions in the designed cavity are studied in detail when the corresponding high-order axial modes (HOAMs) are TE−6.1.q, TE0.4.q', and TE8.2.q. By tuning the applied magnetic field under the condition that the beam voltage U0 is 20 kV and beam current I0 is 0.10 A, the output power and frequency tuning ranges could achieve 0.75 kW and 1.15 GHz, 0.63 kW and 3.10 GHz, and 0.59 kW and 2.54 GHz. Meanwhile the calculation results are compared with the 3-D particle software CST, which have confirmed that the frequency and power tuning ranges of TE−6.1.q, TE0.4.q', and TE8.2.q'' could reach 0.46 kW and 1.07 GHz, 0.37 kW and 2.24 GHz, and 0.34 kW and 1.96 GHz. These results could be beneficial for the development of frequency-tunable gyrotron toward some up-and-coming novel THz applications. [ABSTRACT FROM AUTHOR]

Developing new scaffolds for highly potent and selective inhibitors of human Monoamine Oxidase B (h MAO-B) is a crucial objective in enhancing the efficacy and safety in the clinical treatment of neurodegenerative diseases. In this study, we have identified a series of C-3 isoxazole-substituted thiochromone S,S-dioxide derivatives that exhibit strong inhibitory activity against h MAO-B. The strategy of oxidizing thiochromone to thiochromone S,S-dioxide solves the key defect of extreme insolubility observed for thiochromone analogues. In addition, the sulfone group contributes extra hydrogen(H)-bonding interactions with Tyr435, which significantly increases the activity of thiochromone S,S-dioxide derivatives against h MAO-B. Furthermore, the presence of isoxazole group provides potential H-bonding interaction and electrostatic interaction with the residue of Tyr326, while the rigid aryl ring introduces a potential steric conflict with Phe208 of h MAO-A to improve both potency and selectivity. In our investigations, several compounds (9c , 10c , 10e , 10g , 10l and 10m) demonstrate remarkable single-digit nanomolar potency. These compounds exhibit favorable cytotoxicity profiles in both differentiated SH-SY5Y and HVSMC cells, without apparent cardiotoxic effects. Moreover, compounds 10e and 10h do not lead to an increase in ROS levels in differentiated SH-SY5Y cells, further demonstrating their potential as safe and effective h MAO-B inhibitors. These findings indicate that the C-3 isoxazole substituted thiochromone S,S-dioxide analogues are potential leading compounds for the development of selective inhibitors with high potency. [Display omitted] • C-3 Isoxazole thiochromone S,S-dioxide exhibit excellent potency against MAO-B. • Oxidizing of S atom to sulfone overcomes the defect of thiochromone in solubility. • The C-3 isoxazole group maintains activity against MAO-B. [ABSTRACT FROM AUTHOR]

Wafer fabrication is a highly complex manufacturing system. Using complex network models to portray the correlation between parameters is an effective tool for finding the key influencing factors associated with the cause of wafer defects. However, the complex network in a wafer fabrication system has many nonlinearities, non-normal distributions, coupling, and spurious correlations. Quantitative clarification of direct and indirect correlations in the complex network is the prerequisite for achieving explainable fault detection in smart manufacturing. Therefore, a Copula network deconvolution-based direct correlation disentangling framework is proposed in the context of explainable fault detection in semiconductor wafer fabrication. Firstly, The complex network correlation diagram of the parameters in the wafer fabrication process is constructed with each parameter as a node and the correlation coefficients between parameters as connected edges. Then, a nonlinear correlation metric model based on adaptive Copula function selection is designed to deal with the nonlinear correlation of complex network models. The adaptive selection of the Copula function is realized by the goodness-of-fit test method based on Euclidean distance. After that, considering the coupling and spurious correlation in the complex network model, a network deconvolution-based fault detection method is designed to identify direct correlation. Finally, a case study using the actual data from semiconductor wafer fabrication systems is conducted to compare the existing mainstream fault detection methods and validate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Accurate cross sections of neutron induced fission reactions are needed in the development of nuclear science and technology. The time projection chamber (TPC) is viewed as the potential detector to improve the measurement accuracy of the fission cross sections based on its track reconstruction and particle identification capabilities. The TPC developed by the back-streaming white neutron source (Back-n) team of China Spallation Neutron Source (CSNS) was introduced to verify its ability in measuring the cross section of fission reaction. Using our TPC, and based on the mono-energetic neutron source at Peking University and 232Th/238U samples, we have measured the cross section of the 232Th(n , f) reaction at 5.0 MeV. The fission events have been well distinguished from the background alpha events. The present cross section is consistent with the evaluation data from different libraries, which indicates that the fission cross section measurement using our TPC is feasible. By reducing the distance between the two fission samples, the large uncertainty of the present result will be reduced in future experiments. [ABSTRACT FROM AUTHOR]

l A novel design of microscale heat flux meter composed of a micro-hotwire and an infrared thermal microscopy is demonstrated. l By applied this microscale heat flux meter in heat-loss modified Angstrom method, low-dimensional thermal measurement for simultaneous measurement of thermal diffusivity, thermal conductivity and specific heat can be realized. l This microscale heat-flux meter is a general technique, which is promising for extensions to other thermal measurements. A microscale heat-flux meter is designed based on micro-hotwire and infrared thermal microscopy. Its feasibility in low-dimensional thermal measurement is verified by its application in heat-loss modified Angstrom method for simultaneous measurement of thermal diffusivity, thermal conductivity and specific heat. The hotwire and the sample under test are placed in a vacuum chamber. Through an observation window, the infrared microscopy can capture the thermal image including the hotwire and the sample. When the hotwire is heated, the temperature distribution along the wire is acquired by the readings extracted from the thermal image, which enables the determination of nonlinear and local temperature gradient. This gradient, according to Fourier's Law, can be used to calculate the local heat flux. When a sample is attached to the middle of the hotwire, the attached point is appeared to be a singularity in the temperature distribution along the hotwire, which poses a rigorous challenge to calculate the heat flux flowing into the sample. Here we tried some approaching strategies and verified that the local heat flux at second derivative minima around the singularity is a good enough approximation. The mathematical and physical origins for this approximating strategy are also discussed. This microscale heat-flux meter is a general technique, which is promising for an extension to other thermal measurements. [ABSTRACT FROM AUTHOR]

The gut microbiota has been presumed to have a role in the pathogenesis of type 1 diabetes (T1D). Significant changes in the microbial composition of T1D patients have been reported in several case-control studies. This study is aimed at systematically reviewing the existing literature, which has investigated the alterations of the intestinal microbiome in T1D patients compared with healthy controls (HCs) using 16S ribosomal RNA-targeted sequencing. The databases of MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched until April 2019 for case-control studies comparing the composition of the intestinal microbiome in T1D patients and HCs based on 16S rRNA gene sequencing techniques. The Newcastle-Ottawa Scale was used to assess the methodological quality. Ten articles involving 260 patients with T1D and 276 HCs were included in this systematic review. The quality scores of all included studies were 6–8 points. In summary, a decreased microbiota diversity and a significantly distinct pattern of clustering with regard to β-diversity were observed in T1D patients when compared with HCs. At the phylum level, T1D was characterised by a reduced ratio of Firmicutes/Bacteroidetes in the structure of the gut community, although no consistent conclusion was reached. At the genus or species level, T1D patients had a reduced abundance of Clostridium and Prevotella compared with HCs, whereas Bacteroides and Ruminococcus were found to be more enriched in T1D patients. This systematic review identified that there is a close association between the gut microbiota and development of T1D. Moreover, gut dysbiosis might be involved in the pathogenesis of T1D, although the causative role of gut microbiota remains to be established. Further well-controlled prospective studies are needed to better understand the role of the intestinal microbiome in the pathogenesis of T1D, which may help explore novel microbiota-based strategies to prevent and treat T1D. [ABSTRACT FROM AUTHOR]

In the present work, the early-stage growth behaviour of titania on titanium (Ti) substrate during plasma electrolytic oxidation (PEO) process in an aqueous electrolyte rich in Ca and P was investigated. Microstructural characterization reveals the dramatic evolutions of morphology, porosity, phase component and chemical composition of titania during the early stage of PEO process. The PEO coating initially exhibits ultrafine pores with a completely amorphous structure after oxidation for 5 s, which displays a relatively low Ca/P ratio. With the extension of oxidation periods, titania gradually transforms to grooved morphology with an increased Ca/P ratio, which mainly consists of crystalline anatase phase. Finally, with the prolongation of oxidation period to 1 min, titania exhibits porous morphology typical for PEO coating, which comprises of both rutile and anatase crystals. Along with the prolongation of oxidation periods, the surface wettability of titania remains relatively stable whereas the corrosion resistance changes dramatically, which is closely associated with the combined effects of its porosity and thickness. The results of our present work advance the understanding of early-stage growth of titania during the PEO process, which offer theoretical guidance for the controllable synthesis of PEO coating on Ti and its alloys. • The growth behaviour of titania prior to dielectric breakdown was examined. • Titania initially displays ultrafine pores, transforms to grooved morphology and finally stabilizes as porous structure. • The initial titania is amorphous, which transforms to anatase and finally becomes the mixture of rutile and anatase. • The Ca/P ratio gradually increases with the prolongation of oxidation periods and finally reaches ~0.9. • The combined effect of porosity and thickness results in the dramatic modification of corrosion resistance in titania. [ABSTRACT FROM AUTHOR]

This study focuses on the problem of predicting nitrogen oxide (NO x) concentration at the inlet of selective catalytic reduction (SCR) reactors under variable load conditions of thermal power units. Some variables with strong correlation with NO x concentration at the SCR inlet were selected as auxiliary variables and the delay time between NO x concentration and auxiliary variables was determined by the mutual information method. Taking the delay time, dynamic time and prediction error into account, a real-time dynamic prediction model of NO x concentration based on the least square support vector machine was proposed. The model was tested using the actual historical data under variable load operating conditions of two thermal power units. Test results show that the proposed dynamic prediction model has high real-time prediction accuracy and satisfactory generalization ability. [ABSTRACT FROM AUTHOR]

Objectives. To investigate the risk factors for cognitive impairment in Chinese type 2 diabetes mellitus (T2DM) patients of advanced age and to identify effective biomarkers of mild cognitive impairment (MCI) in these patients. Methods. Chinese T2DM patients (n = 120) aged 50–70 years were divided into groups with impaired (mild, moderate, and severe) and normal cognitive function based on Montreal Cognitive Assessment and Mini-Mental State Examination scores. Data regarding demographic characteristics, clinical features of diabetes, biochemical markers, and metabolomics were collected. Results. Age, educational level, duration of diabetes, fasting blood glucose (FBG), HbA1c, total cholesterol (TC), triglyceride (TG), and 24-hour urine protein were significantly associated with cognitive impairment in T2DM patients of advanced age. The severity of fundus retinopathy and the incidence of macrovascular disease also differed significantly among the groups (P < 0.05). Metabolomics analysis suggested that increased levels of glutamate (Glu), phenylalanine (Phe), tyrosine (Tyr), proline (Pro), and homocysteine (Hcy) and a decreased level of glutamine (Gln) were significantly associated with cognitive impairment in the T2DM patients (P < 0.05). Receiver operating characteristic curve analysis demonstrated that Glu, Gln, Phe, and Pro levels were significant predictors of cognitive impairment in the T2DM patients. Conclusions. Age, educational level, duration of diabetes, and the levels of FBG, HbA1c, TC, TG, and 24-hour urine protein were considered as independent risk factors for cognitive impairment in older T2DM patients. Macrovascular and microvascular diseases also were closely associated with cognitive impairment in these patients. Together, Glu and Gln levels may represent a good predictive biomarker for the early diagnosis of cognitive impairment in T2DM patients. [ABSTRACT FROM AUTHOR]

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD. [ABSTRACT FROM AUTHOR]

In this work, a Cu-incorporated Al 2 O 3 coating has been successfully produced through the one-step plasma electrolytic oxidation (PEO) method. Unexpectedly, the resultant Cu-incorporated Al 2 O 3 coating displays a multi-layered structure, which exhibits significant variations in morphology, composition and crystallinity. Compared to the compact outer layer of the PEO coating, both medium and inner layers are highly porous even the average pore size of the medium layer is obviously higher than that of the inner layer. The medium layer has a higher Cu content in comparison to both outer and inner layers. And the outer layer mainly consists of crystalline γ-Al 2 O 3 phase whereas both medium and inner layers are in amorphous states. Further, it was found that Cu specie could exist as Cu 2 O and CuO in the Cu-incorporated PEO coating. Finally, it was revealed that the incorporation of Cu into the porous PEO coating significantly improves the antifouling property of Al metallic substrate against SRB, which successfully prevents the formation of SRB biofilm. Hence, PEO method is a promising surface modification technique for the fabrication of antifouling coating. [ABSTRACT FROM AUTHOR]

In the present work, Zn-incorporated TiO 2 coatings are prepared through a one-step micro-arc oxidation (MAO) method on a grade 4 pure titanium with the addition of either Na 2 Zn-EDTA solution or ZnO nanoparticles (NPs) as Zn sources. The microstructural features of both Zn-incorporated TiO 2 coatings were systematically examined. It is revealed that different Zn sources result in significant difference of phase component, chemical state, composition and morphology between the resultant Zn-incorporated MAO coatings. Zn species could be present as ZnO and Zn(OH) 2 in the coating when Na 2 Zn-EDTA was used as Zn source whereas the presence of ZnO nano-clusters is obvious on the coating surface with ZnO NPs as Zn source. The addition of ZnO NPs during the MAO process also leads to a lower Zn content of the resultant coating, which is more defective with increased thickness in comparison to that of Na 2 Zn-EDTA. Further, antibacterial property and osteogenic activity of both Zn-incorporated coatings were examined. Both Zn-incorporated coatings exhibit favourable bacterial inhibition ability and bone formability, suggesting the successful synthesis of bifunctional coatings through the facile one-step micro-arc oxidation method. [ABSTRACT FROM AUTHOR]

A hollow cathode is an important component of the discharge circuit in Hall thruster. Different axial positions of the hollow cathode will cause the electrons emitted by the cathode to enter the discharge channel differently, thereby affecting the energy acquisition of the electrons and influencing the ignition of Hall thruster. Thus, a high-speed camera with a charge-coupled device was used to examine the plume features over time when the cathode was located at different axial positions. To better understand the changes in the plasma parameters in the discharge channel and plume during ignition, a two-dimensional axisymmetric fully kinetic particle-in-cell/Monte Carlo collision model was used to calculate the ion density and potential distribution at different times during the ignition process of Hall thruster. The results indicate that the ion density generated in the initial stage of ignition is larger at the exit of the discharge channel when the cathode axial position is close to the exit of the discharge channel. The electron avalanche ionization occurs earlier, and the peak value of the ignition pulse current is larger. These differences may occur because the energies of the electrons (emitted by the cathode) entering the discharge channel from different cathode axial positions differ. • The influence of cathode axial position change on the HET ignition is studied. • The CCD images of HET ignition under two different cathode positions are given. • A 2D-3V fully kinetic PIC-MCC model was used to calculate the plasma parameters. • The ion density and potential at different times during HET ignition are given. • The change of cathode position related to different energy acquisition of electrons. [ABSTRACT FROM AUTHOR]

The hydroxyapatite (HA)-based/TiO 2 -based composite coating was produced through plasma electrolytic oxidation (PEO) method in the present work. The microstructural evolution of the composite coating was examined as a function of PEO duration. It was observed that Ca P phase initially appears at the cracks of TiO 2 -based layer in form of plates of micrometre scales after PEO duration of 5 min and then transforms to the hybrid of plates and floccules, which finally convert to clusters composed of nano-sized plates by self-assembly. After 15 min oxidation, a two-layered composite coating was revealed, including TiO 2 -based inner layer and HA-based outer layer. It is also noticed that the thickness of HA-based layer continuously increases as the oxidation period extends whereas both the thickness of TiO 2 -based layer beneath the HA-based layer and the coverage rate of Ca P phase on TiO 2 -based layer remain relatively stable at the late stage of PEO process. The microstructural variation inevitably affects the biocompatibilities and corrosion properties of the composition coatings. With the extension of oxidation periods, an increased amount of Ca P phase was produced in the composite coating, which thus results in an improved corrosion resistance due to its insulation property, hydrophobicity and physical barrier effect. Meanwhile, the enhanced biocompatibility of the composite coating could also be achieved with the prolongation of PEO duration, which is associated with the high bioactivity of Ca P phase. • The hydroxyapatite/TiO 2 composite coating has been successfully produced through plasma electrolytic oxidation. • The formation of hydroxyapatite is closely associated with cracks in the TiO 2 -based layer. • The presence of hydroxyapatite retards the growth of underlying TiO 2. • The coverage rate of hydroxyapatite initially increases dramatically and finally remains stable at approximately 80%. • An increased amount of hydroxyapatite results in an improved corrosion resistance and biocompatibility of the coating. [ABSTRACT FROM AUTHOR]

Ruddlesden–Popper perovskite, (PEA)2PbBr4 (PEA = C8H9NH3), is a steady and inexpensive material with a broad bandgap and a narrow‐band emission. These features make it a potential candidate for deep‐blue light‐emitting diodes (LEDs). However, due to the weak exciton binding energy, LEDs based on the perovskite thin films usually possess a very low external quantum efficiency (EQE) of <0.03%. Here, for the first time, the construction of high‐performance deep‐blue LEDs based on 2D (PEA)2PbBr4 nanoplates (NPs) is demonstrated. The as‐fabricated (PEA)2PbBr4 NPs film shows a deep‐blue emission at 410 nm with excellent stability under ambient conditions. Impressively, LEDs based on the (PEA)2PbBr4 NPs film deliver a bright deep‐blue emission with a maximum luminance of 147.6 cd m−2 and a high EQE up to 0.31%, which represents the most efficient and brightest perovskite LEDs operating at deep‐blue wavelengths. Furthermore, the LEDs retain over 80% of their efficiencies for over 1350 min under ≈60% relative humidity. The steady and bright deep‐blue LEDs can be used as an excitation light source to realize white light emission, which shows the potential for light communication. The work provides scope for developing perovskite into efficient and deep‐blue LEDs for low‐cost light source and light communication. [ABSTRACT FROM AUTHOR]

Background Cervical spondylodiscitis with spinal epidural abscess (SEA) is not a rare medical condition and usually requires urgent decompression of neural structures and stabilization of the spine followed by antibiotic therapy for the prevention of severe neurologic deficits. Case Description In this report, we present a 43-year-old male patient with the chief complaint of neck pain and intermittent fever accompanying by slight dysphagia. After 2 weeks, he felt mild and transient numbness on the left upper limb. He had a history of esophageal intervention under endoscopy. Magnetic resonance imaging disclosed diffuse hyperintensity in the left paraesophageal and prevertebral tissues and a space-occupying lesion within the spinal canal. The esophagography revealed a saclike barium collection parallel to the upper esophagus herniating out from the posterior wall without evident leakage. Neither surgical decompression nor drainage was chosen by this patient; conservative treatment with antibiotic administration was managed to achieve a good neurologic recovery and remarkable resolution of the epidural abscess. During antibiotic therapy and dietary restriction, the symptoms of diverticulitis was also managed expectantly. Conclusions Physicians need to be aware of this rare case of SEA secondary to esophageal diverticulitis. An early diagnosis and prompt administration of antibiotics is a key factor to avoid neurologic deterioration for the treatment of SEA caused by diverticulitis. Endoscopic or surgical repair of diverticulum may be warranted to avoid the recurrence of such infection. Highlights • Esophageal diverticulitis can cause spinal epidural abscess in the cervicothoracic spine. • Early diagnosis and antibiotic treatment is important for a favorable outcome of spinal epidural abscess. • Surgical decompression should be considered if medical therapy for spinal epidural abscess fails. [ABSTRACT FROM AUTHOR]

Background: Studies showed that upregulation of Nav1.6 increased the neuronal excitability and participated in neuropathic pain in the dorsal root ganglion (DRG). However, the molecular mechanisms underlying Nav1.6 upregulation were not reported yet.Methods: The paw withdrawal threshold was measured in the rodents following lumbar 5 ventral root transection (L5-VRT). Then qPCR, western blotting, immunoprecipitation, immunohistochemistry, and chromatin immunoprecipitation assays were performed to explore the molecular mechanisms in vivo and in vitro.Results: We found that the levels of Nav1.6 and phosphorylated STAT3 were significantly increased in DRG neurons following L5-VRT, and TNF-α incubation also upregulated the Nav1.6 expression in cultured DRG neurons. Furthermore, immunoprecipitation and chromatin immunoprecipitation assays demonstrated that L5-VRT increased the binding of STAT3 to the Scn8a (encoding Nav1.6) promoter and the interaction between STAT3 and p300, which contributed to the enhanced transcription of Scn8a by increasing histone H4 acetylation in Scn8a promoter in DRG. Importantly, intraperitoneal injection of the TNF-α inhibitor thalidomide reduced the phosphorylation of STAT3 and decreased the recruitment of STAT3 and histone H4 hyperacetylation in the Scn8a promoter, thus subsequently attenuating Nav1.6 upregulation in DRG neurons and mechanical allodynia induced by L5-VRT.Conclusion: These results suggested a new mechanism for Nav1.6 upregulation involving TNF-α/STAT3 pathway activation and subsequent STAT3-mediated histone H4 hyperacetylation in the Scn8a promoter region in DRG, which contributed to L5-VRT-induced neuropathic pain. [ABSTRACT FROM AUTHOR]

The detection and recognition of arrow markings is a basic task of autonomous driving. To achieve all-day detection and recognition of arrow markings in complex environment, we propose a hybrid model by exploiting the advantages of biologically visual perceptual model and discriminative model. Firstly, the arrow markings are extracted from the complex background in the region of interest (ROI) by the biologically visual perceptual model using the frequency-tuned (FT) algorithm. Then candidates for road markings are detected as maximally stable extremal regions (MSER). In recognition stage, biologically visual perceptual model calculates the sparse solution of arrow markings using sparse learning theory. Finally, discriminative model uses the Adaptive Boosting (AdaBoost) classifier trained by sparse solution to classify arrow markings. Experimental results show that the hybrid model achieves detection and recognition of arrow markings in complex road conditions with the precision, recall, and F-measure being 0.966, 0.88, and 0.92, respectively. The hybrid model is robust and has some advantages compared with other state-of-the-art methods. The hybrid model proposed in this paper has important theoretical significance and practical value for all-day detection and recognition in complex environment. [ABSTRACT FROM AUTHOR]

Application of micro-pattern gaseous detectors to gaseous photomultiplier tubes has been widely investigated over the past two decades. In this paper, we present a double micro-mesh gaseous structure that has been designed and fabricated for this application. Tests with X-rays and UV laser light indicate that this structure exhibits an excellent gas gain of > 7 × 1 0 4 and good energy resolution of 19% (full width at half maximum) for 5.9 keV X-rays. The gas gain can reach up to 1 0 6 for single electrons while maintaining a very low ion-backflow ratio down to 0.0005. This structure has good potential for other applications requiring a very low level of ion backflow. [ABSTRACT FROM AUTHOR]

As a potent bronchodilator, the anti-inflammatory effects of tiotropium and its interaction with budesonide against cadmium-induced acute pulmonary inflammation were investigated. Compared to values obtained in rats exposed to cadmium, cytological analysis indicated a significant decrease of total cell and neutrophil counts and protein concentration in bronchoalveolar lavage fluid (BALF) in rats pretreated with tiotropium (70μg/15ml or 350μg/15ml). Zymographic tests showed a decrease of MMP-2 activity in BALF in rats pretreated only with high concentration of tiotropium. Histological examination revealed a significant decrease of the severity and extent of inflammatory lung injuries in rats pretreated with both tested concentrations of tiotropium. Though tiotropium (70μg/15ml) or budesonide (250μg/15ml) could not reduce cadmium-induced bronchial hyper-responsiveness, their combination significantly decreased bronchial contractile response to methacholine. These two drugs separately decreased the neutrophil number and protein concentration in BALF but no significant interaction was observed when both drugs were combined. Although no inhibitory effects on MMP-2 and MMP-9 was observed in rats pretreated with budesonide alone, the combination with the ineffective dose of tiotropium induced a significant reduction on these parameters. The inhibitory effect of tiotropium on lung injuries was not influenced by budesonide which alone induced a limited action on the severity and extent of inflammatory sites. Our findings show that tiotropium exerts anti-inflammatory effects on cadmium-induced acute neutrophilic pulmonary inflammation. The combination of tiotropium with budesonide inhibits cadmium-induced inflammatory injuries with a synergistic interaction on MMP-2 and MMP-9 activity and airway hyper-responsiveness. [ABSTRACT FROM AUTHOR]

Ketol-acid reductoisomerase (KARI) is an NAD(P)H and Mg2+-dependent enzyme of the branched-chain amino acid (BCAA) biosynthesis pathway. Here, the first crystal structures of Staphylococcus aureus (Sa) KARI in complex with two transition state analogues, cyclopropane-1,1-dicarboxylate (CPD) and N-isopropyloxalyl hydroxamate (IpOHA) are reported. These compounds bind competitively and in multi-dentate manner to KARI with Ki values of 2.73 μm and 7.9 nm, respectively; however, IpOHA binds slowly to the enzyme. Interestingly, intact IpOHA is present in only ≈25 % of binding sites, whereas its deoxygenated form is present in the remaining sites. This deoxy form of IpOHA binds rapidly to Sa KARI, but with much weaker affinity (Ki=21 μm). Thus, our data pinpoint the origin of the slow binding mechanism of IpOHA. Furthermore, we propose that CPD mimics the early stage of the catalytic reaction (preceding the reduction step), whereas IpOHA mimics the late stage (after the reduction took place). These structural insights will guide strategies to design potent and rapidly binding derivatives of these compounds for the development of novel biocides. [ABSTRACT FROM AUTHOR]

The pre-stretched gel-spinning ultra-high molecular weight polyethylene fibers with low concentration solution obtained from industrial production line were used to study the structural transition from shish-kebab to fibrillar crystals during hot-stretching process via in-situ small-angle X-ray scattering, wide-angle X-ray diffraction measurements, and scanning electron microscopy. With the increase of hot-stretching strain, the kebab crystals (lamellae) undergo stress-induced fragmentation and recrystallization at 90, 100, and 110 °C and melting and recrystallization at 120 °C to transform to fibrillar crystals. Furthermore, the shish length of pre-stretched fibers at all stretching temperatures first increase and then gradually decrease with the strain, but the number of shish continuously increase and the shish diameter increase firstly and finally keep almost constant. The degree of crystal orientation for all stretching temperatures is as high as above 0.9 during the whole stretching process. These results indicate that the shish-kebab crystals of ultra-high molecular weight polyethylene fibers prepared from low concentration solution can smoothly transform to fibrillar crystals through the hot stretching process. [ABSTRACT FROM AUTHOR]

Autophagy plays a dual role in the development of cancer, acting as both a tumor suppressor and a cell survival inducer. Ophiopogon japonicus (L.f) Ker-Gawl (OJ), as a traditional Chinese medicine, specially possesses remarkable anti-cancer activity in the clinical. Previously, studies have indicated that flavonoids (FOJ) and steroidal saponins (SSOJ) are the main active substances of OJ. However, the effects of FOJ and SSOJ on autophagy of A549 cells have not been fully elucidated. In this study, we found that the expressions of autophagy-related mediators (LC3-II/LC3-I ratio, Atg-3, Atg-7 and Beclin-1) were increased in A549 cells by the treatment with FOJ (7.9 mg crude drug/mL) and SSOJ (12.2 mg crude drug/mL). Meanwhile, FOJ or SSOJ could induce the up-regulation of LC3-II at both protein and mRNA levels. Moreover, we observed the cytoplasmic vaculoes which formed double-layered membranes and only some cytoplasmic organelles or myelin figures remained in FOJ or SSOJ-treated A549 cells for 24 h by Transmission Electron Microscopy (TEM). Further detection about the PI3K/Akt/mTOR signaling pathway showed that the levels of PI3K, Akt and mTOR were significantly suppressed with the FOJ or SSOJ treatment. The 3-MA (an autophagy inhibitor) and LY294002 (a PI3K inhibitor) further confirmed the underlying mechanism in the FOJ or SSOJ-induced autophagy of A549 cells. Additionally, the pretreatment with FOJ and SSOJ increased the level of p53, whereas decreased the expression of Ki67. These findings suggested that FOJ or SSOJ could activate the autophagy of A549 cells, wherein the mechanism might be associated with their inhibition of PI3K/Akt/mTOR signaling pathway. Thus, FOJ or SSOJ could be a potential autophagy inducer to prevent the process of lung cancer. [ABSTRACT FROM AUTHOR]

Aims/Introduction The aims of the present study were to evaluate the diagnostic value of fasting plasma glucose, 2-h postload plasma glucose and glycosylated hemoglobin (HbA1c) measurements in the screening of diabetes and prediabetes, and to determine the cut-off point of HbA1c in the diagnosis of diabetes and prediabetes in a Chinese population. Materials and Methods A total of 7,611 individuals aged 40 years or older, who did not have a prior history of diabetes, were randomly selected in the Changchun area. For each participant, a questionnaire was completed, and a physical examination and an oral glucose tolerance test were carried out. The values of fasting plasma glucose, 2-h postload plasma glucose and HbA1c were compared by area under the receiver operating characteristic curves. The Youden index was used to identify the optimal cut-off point of HbA1c in the diagnosis of diabetes and prediabetes. Results The prevalence of newly diagnosed diabetes and prediabetes was 12.71% and 29.39%, respectively. In participants with newly diagnosed diabetes, the area under the receiver operating characteristic curve was 0.8368 for fasting plasma glucose, 0.9330 for 2-h postload plasma glucose and 0.8064 for HbA1c; whereas for prediabetes, these values were 0.8022, 0.9288 and 0.6895, respectively. In addition, an HbA1c threshold of 6.3% showed the highest Youden index (0.4799) for detecting diabetes; furthermore, an HbA1c threshold of 5.8% showed the highest Youden index (0.2866) for detecting prediabetes. Conclusions HbA1c ≥6.3% (45 mmol/mol) and between 5.8% and 6.2% (40-44 mmol/mol) were the optimal cut-off values for the diagnosis of diabetes and prediabetes, respectively, in a Chinese population. [ABSTRACT FROM AUTHOR]

Supercritical OTB (once-through boiler) units with high steam temperature and pressure have been widely used in modern power plants due to their high cycle efficiency and less emissions. To ensure the effective operation of such power generation systems, it is necessary to build a model for the design of the overall control system. There are already detailed models of once-through boilers; however, their complexity prevents them from being applied in the controller design. This study describes a lumped parameter dynamic model that has a relatively low complexity while faithfully capturing the essential overall plant dynamics. The model structure was derived by fundamental physical laws utilizing reasonable simplifications and data analysis to avoid the phase transition position problem. Parameter identification for the model structure was completed using operational data from a 1000 MW ultra-supercritical OTB. The model was determined to be reasonable by comparison tests between computed data and measured data for both steady and dynamic states. The simplified model is verified to have appropriate fidelity in control system design to achieve effective and economic operation of the unit. [ABSTRACT FROM AUTHOR]

The counting rate capability of a resistive micro-pattern gas detector (MPGD) is limited due to the effect of flowing current and accumulated charge on the resistive layer when evacuating the multiplied electrons to the ground. Thus, the design and optimization of new detector structures that evacuate the electrons to the ground nearby, but not via long-distance transmission on the resistive layer, are essential for the development of the detector rate capability. This type of MPGD design is known as fast grounding. In this study, systematic simulations for the rate capability with various fast grounding designs are conducted, including simulation of the flowing current and charge accumulation effects of the resistive layer. By comparing with experimental results based on strip-grounded, double layer resistive (DLR) and point-grounded micro-resistive WELL (μ -RWELL) detectors, the accuracy of the simulations is validated and demonstrated. These simulations can also be used to optimize the fast grounding design of MPGDs with a resistive layer. Our study indicates that the point-grounded fast grounding design has a good gain performance at a high counting rate and can achieve a compromise between detector performance, manufacturing difficulty and detector dead area. The simulation and experimental results also indicate that the gain decrease can be controlled within ∼ 5.2% at 1 MHz/cm 2 of 8.1 keV X-ray irradiation, with ideal grounded point arrays with a 5 mm pitch and a 0.5 mm radius. [ABSTRACT FROM AUTHOR]

Background The aim of the present study was to compare correlation coefficients between anthropometric indices and blood glucose level, and to determine optimal cutoff points of obesity indices in a Chinese population. Methods 2419 males and 5140 females participated in this study in Changchun city. Weight, height, WC (waist circumference) and hip circumference were measured; and BMI (body mass index), WHtR (waist height ratio), WHR (waist hip ratio) and BAI (body adiposity index) were calculated by formulas. FPG (fasting plasma glucose), PPG (post-load plasma glucose), HbA1c (glycosylated hemoglobin) and FSI (fasting serum insulin) were measured. Results WHtR had the highest partial correlation coefficients with blood glucose and HbA1c in both males and females; however, BAI had the lowest coefficients. AUC (area under receiver operating characteristic curves) for WHtR in screening type 2 diabetes mellitus were higher than other indices. We confirmed that the optimal cutoff points of obesity for WHtR, WHR, WC, BMI and BAI were 0.55, 0.92, 88.1, 25.9 and 28.1 in males, and 0.52, 0.85, 81.6, 24.6 and 31.0 in females, respectively. Conclusions Central obesity correlates more closely to glucose metabolism in Chinese population than general obesity. WHtR is the best index to predict type 2 diabetes mellitus in Chinese adults. [ABSTRACT FROM AUTHOR]

Background: Bacillus (B.) anthracis is the pathogen that causes fatal anthrax. Guizhou Province is an old foci of anthrax in the southwest of China. Human anthrax has also been frequently reported in Guizhou in recent year. However, there is limited information on the genetic background of local B. anthracis isolates in Guizhou Province. Strain-specific detection of this bacterium using molecular approaches has enhanced our knowledge of microbial genetics. In the present study, we employed Multiple Locus Variable Number Tandem Repeats (VNTR) Analysis (MLVA) assay to analyze the genetic characteristics of B. anthracis strains isolated in Guizhou Province and their relationships to worldwide distributed isolates. Results: A total of 32 isolates of B. anthracis from soil, human, cattle, dog and water of different anthrax epidemics in Guizhou Province from 2006 to 2011 were confirmed with phage lysis test, penicillin inhibition test and PCR. MLVA-8 discriminated them into 28 unique MLVA types (MT G1 - G28), which were novel MTs compared with the previous reports. Cluster tree based on 32 isolates from Guizhou Province and 76 worldwide distributed isolates (30 MTs) showed they were divided into three clusters, designated A, B and C. All the 32 isolates were distributed in cluster A, which were further grouped into A1, A2, A3 and A4 sub-clusters. 32 isolates from Guizhou Province were closely grouped in each of the sub-clusters, respectively. Minimum Spanning Tree (MST) based on the MLVA data showed that the 28 MLVA profiles of isolates from Guizhou Province and 30 MLVA profiles of worldwide distributed isolates formed three clonal complexes (CCs) and ten singletons. Conclusions: 28 novel MTs of B. anthracis from Guizhou were revealed and their relationships to worldwide isolates were showed. The results will provide important information for prevention of anthrax and also enhances our understanding of genetic characteristics of B. anthracis in China. [ABSTRACT FROM AUTHOR]

Title compounds (IV) are synthesized by a Knoevenagel condensation followed by Michael addition and cyclization reactions in good to excellent yields. [ABSTRACT FROM AUTHOR]

Among all the security risks, the sharing of resources and data communication in virtual machines are most concerned. This paper proposed an access control security model which combined the Chinese Wall and BLP model. It introduced BLP with corresponding adoption with PCW security model. This model could be used to control the resources usage and event behaviors in virtual machines. The experimental results show its effectiveness and safety. [ABSTRACT FROM AUTHOR]