Search

Supplementary Figure S1. Complement regulates IL-10 production in CD8+ TILs. Supplementary Figure S2. Non-CD8+ T cell responses in tumor bearing mice. Supplementary Figure S3. T cell exhaustion markers expressed on CD8+ TILs after IL-10 culture. Supplementary Figure S4. Anaphylatoxins regulate IL-10 production through C3aR and C5aR.

Photo- or electroreduction of carbon dioxide into highly valued products offers a promising strategy to achieve carbon neutrality. Here, a series of polyoxometalate-based metal-organic frameworks (M-POMOFs) were constructed by metalloporphyrins [tetrakis(4-carboxyphenyl)-porphyrin-M (M-TCPPs)] and reductive POM for photo- and electrocatalytic carbon dioxide reductions (PCR and ECR, respectively), and the mysteries between the roles of single metal site and cluster in catalysis were disclosed. Iron-POMOF exhibited an excellent selectivity (97.2%) with high methane production of 922 micromoles per gram in PCR, together with superior Faradaic efficiency for carbon dioxide to carbon monoxide (92.1%) in ECR. The underlying mechanisms were further clarified. Photogenerated electrons transferred from iron-TCPP to the POM cluster for methane generation under irradiation, while the abundant electrons flowed to the center of iron-TCPP for carbon monoxide formation under the applied electric field. The specific multielectron products generated on iron-POMOF through switching driving forces to control electron flow direction between single metal site and cluster catalysis.

Glioblastoma (GBM) is a lethal cancer with limited therapeutic options. Dendritic cell (DC)-based cancer vaccines represent a promising approach for GBM treatment. Clinical studies suggest that other immunotherapeutic agents including anti-PD-1 and immune adjuvant poly I:C may be combined with DC vaccines to further enhance antitumor activity. Here we report a GBM case with combination immunotherapy consisting of DC vaccines, anti-PD-1 and poly I:C as well as a chemotherapeutic agent cyclophosphamide that were integrated with the standard chemoradiation therapy for > 5 years. The patient who received DC vaccines loaded with multiple forms of tumor antigens including mRNA-tumor associated antigens (TAAs), mRNA-neoantigens, and hypochlorous acid-oxidized tumor lysates. Furthermore, mRNA-TAAs were modified with a novel TriVac technology which fuses TAAs with a destabilization domain and inserts TAAs into a full-length LAMP-1 to enhance MHC class I and II antigen presentation, respectively. The treatment consisted of 42 DC cancer vaccine infusions, 26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions. The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells. No immunotherapy related adverse events were observed during the treatment. Robust anti-tumor CD4+ and CD8+ T cell responses were detected. The patient remains free of disease progression as of July, 2022. Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment. A large scale trial to validate these findings is warranted. Protocol numbers: 201708152377, 20202014-F-1

Certain ciliary transmembrane and membrane-tethered signaling proteins migrate from the ciliary tip to base via retrograde intraflagellar transport (IFT), essential for maintaining their ciliary dynamics to enable cells to sense and transduce extracellular stimuli inside the cell. During this process, the BBSome functions as an adaptor between retrograde IFT trains and these signaling protein cargoes. The Arf-like 13 (ARL13) small GTPase resembles ARL6/BBS3 in facilitating these signaling cargoes to couple with the BBSome at the ciliary tip prior to loading onto retrograde IFT trains for transporting towards the ciliary base, while the molecular basis for how this intricate coupling event happens remains elusive. Here, we report thatChlamydomonasARL13 only in a GTP-bound form (ARL13GTP) anchors to the membrane for diffusing into cilia. Upon entering cilia, ARL13 undergoes GTPase cycle for shuttling between the ciliary membrane (ARL13GTP) and matrix (ARL13GDP). To achieve this goal, the ciliary membrane-anchored BBS3GTPbinds and activates the ciliary matrix-residing ARL13GDPas an ARL13 guanine nucleotide exchange factor. At the ciliary tip, ARL13GTPbinds and recruits the ciliary matrix-residing and post-remodeled BBSome as an ARL13 effector to anchor to the ciliary membrane. This makes the BBSome spatiotemporally become available for the ciliary membrane-tethered phospholipase D (PLD) to couple with. Afterward, ARL13GTPhydrolyzes GTP for releasing the PLD-laden BBSome to load onto retrograde IFT trains. According to this model, hedgehog signaling defects associated withARL13bandBBS3mutations in humans could be satisfactorily explained, providing us a mechanistic understanding behind BBSome-cargo coupling required for proper ciliary signaling.Significance statementCertain signaling proteins export in a BBSome-dependent manner from cilia via retrograde IFT. As IFT cargoes, their coupling with the BBSome is mediated by ARL13 and BBS3. Here, we report that ARL13 in a GTP-bound state binds the membrane for diffusing into cilia followed by running GTPase cycle with BBS3 acting as an ARL13-specific guanine nucleotide exchange factor. ARL13GTPrecruits the IFT-shed BBSome as its effector to anchor to the membrane of the ciliary tip, making it spatiotemporally available for the ciliary membrane-tethered PLD to bind. Afterward, ARL13 GTP hydrolysis releases the PLD-laden BBSome for retrograde IFT train loading. ARL13 and BBS3 facilitate the cargo-BBSome coupling in such a way providing a regulatory mechanism for signaling protein export from cilia.

Porous heterostructured electrocatalysts with multifunctionality and synergistic effect have much benefit for efficient electrocatalytic CO

The high theoretical capacity of vanadium oxides makes them promising cathode candidates for the rechargeable lithium-ion batteries (LIBs). Nevertheless, the relatively poor electrical conductivity and capacity retention hinder the practical application and have to be overcome urgently for the increasing demand for storage technologies. Herein, a new BRG system composed of bimetallic oxide/rhodamine B (RB)/reduced graphene oxide (RGO) was prepared through the facile self-sacrificing template of the precursor polyoxometalate (POM) composites POMs/RB/RGO (PRG). RB not only acts as a cationic mediator to facilitate the loading of POMs on graphene for conversion to oxides but also promotes the formation of uniform nanorods on the RGO. The prepared composite FeV

Hepatocellular carcinoma (HCC) is a major cause of cancer‐related death worldwide, accounting for 90% of liver cancers. Effective systemic treatments for advanced stage HCC are limited. The recent clinical application of mutated neoantigens as immunotherapeutic targets in several human cancers demonstrated that boosting host T cell responses to these antigens may help control patient tumors. With increased enthusiasm for targeting mutated neoantigens as a strategy in cancer immunotherapy, many clinical trials were initiated to apply mutated neoantigens as targets for the therapy of HCC and other solid tumors. However, recent studies suggest that targeting mutated neoantigens for the immunotherapy of HCC and other solid tumors has pitfalls and may not achieve efficacy without strategic changes. Herein, we discuss the limits of using neoantigens as targets in HCC immunotherapy and suggest alternative strategies to overcome these limits. Importantly, similar limits and alternative strategies are likely applicable to other intermediate and low tumor mutation burden cancers.

Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4+ and/or CD8+ T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4+ and CD8+ T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).

According to the characteristics of submerged floating tunnel anchored by tension legs, simplifying the tube as point mass and assuming that the tension leg is a nonlinear beam model hinged at both ends, the nonlinear vibration equation of the tension leg is derived. The equation is solved by the Galerkin method and Runge-Kutta method. Subsequently, numerical analysis of typical submerged floating tunnel tension leg is carried out. It is shown that, the parametric vibration response of the submerged floating tunnel tension leg is related to the amplitude and frequency of the end excitation. Without considering axial resonance and transverse resonance, it is reasonable that higher order modes are abandoned and only the first three modes are considered. The axial resonance amplitude of the second or third order mode is equivalent to the first order mode axial resonance amplitude, which should not be ignored.

To examine the independent risk factors of type-2 myocardial infarction (T2MI) elicited by acute upper gastrointestinal bleeding (AUGIB), and to establish a nomogram model for the prediction of AUGIB-induced T2MI.A nomogram model was established on the basis of a retrospective study that involved 533 patients who suffered from AUGIB in the Department of Critical Care Medicine (CCM) or Emergency Intensive Care Unit (EICU) of Renmin Hospital of Wuhan University, Wuhan, China, from January 2017 to December 2020. The predictive accuracy and discriminative power of the nomogram were initially evaluated by internal validation, which involved drawing the receiver operating characteristic (ROC) curve, calculating the area under the curve (AUC), plotting the calibration curve derived from 1000 resampled bootstrap data sets, and computing the root mean square error (RMSE). The predictive ability of the nomogram was further validated through the prospective and multicenter study conducted by the investigators, which enrolled 240 AUGIB patients [including 88 cases from Renmin Hospital of Wuhan University, 73 cases from Qilu Hospital of Shandong University (Qingdao), and 79 cases from Northern Jiangsu People's Hospital)], who were admitted to the Department of CCM or EICU, from February 2021 to July 2021.Among the 533 patients in the training cohort, 78 (14.6%) patients were assigned to the T2MI group and 455 (85.4%) patients were assigned to the non-T2MI group. The multivariate analysis revealed that age65, hemorrhagic shock, cerebral stroke, heart failure, chronic kidney disease, increased blood urea nitrogen, decreased hematocrit, and elevated D-Dimer were independent risk factors for AUGIB-induced T2MI. All these factors were incorporated into the nomogram model. The AUC for the nomogram for predicting T2MI was 0.829 (95% CI, 0.783-0.875) in the internal validation cohort and 0.848 (95% CI, 0.794-0.902) in the external validation cohort. The calibration curve for the risk of T2MI exhibited good consistency between the prediction by the nomogram and the actual clinical observation in both the internal validation (RMSE=0.016) and external validation (RMSE=0.020).The nomogram was proven to be a useful tool for the risk stratification of T2MI in AUGIB patients, and is helpful for the early identification of AUGIB patients who are prone to T2MI for early intervention, especially in emergency departments and intensive care units.

Background: The incidence of cancer, diabetes, and autoimmune diseases has been increasing. Furthermore, there are more and more patients with solid organ transplants. The survival rate of these immunocompromised individuals is extremely low when they are severely hit-on. In this study, we established cardiac arrest cardiopulmonary resuscitation (CPR) model in severe combined immunodeficient (SCID) mice, analyzed the expression and activation of mitochondrial autophagy and NLRP3 inflammasome/caspase-1, and explored mitochondrial repair and inflammatory injury in immunodeficiency individual during systemic ischemia-reperfusion injury. Methods: A potassium chloride-induced cardiac arrest model was established in C57BL/6 and nonobese diabetic/SCID (NOD/SCID) mice. One hundred male C57BL/6 mice and 100 male NOD/SCID mice were randomly divided into five groups (control, 2 h post-CPR, 12 h post-CPR, 24 h post-CPR, and 48 h post-CPR). A temporal dynamic view of alveolar epithelial cells, macrophages, and neutrophils from bronchoalveolar lavage fluid (BALF) was obtained using Giemsa staining. Spatial characterization of phenotypic analysis of macrophages in the lung interstitial tissue was analyzed by flow cytometry. The morphological changes of mitochondria 48 h after CPR were studied by transmission electron microscopy and quantified according to the Flameng grading system. Western blotting analysis was used to detect the expression and activation of the markers of mitochondrial autophagy, NLRP3 inflammasome, and caspase-1. Results: (1) In NOD/SCID mice, macrophages were disintegrated in BALF, and many alveolar epithelial cells were shed at 48 h after resuscitation. Compared with C57BL/6 mice, the ratio of macrophages/total cells peaked at 12 h and was significantly higher in NOD/SCID mice (31.17 ± 4.13 vs. 49.69 ± 2.43, t = 14.46, P= 0.001). After 24 h, the results showed a downward trend. Furthermore, a large number of macrophages were disintegrated in the BALF. (2) Mitochondrial autophagy was present in both C57BL/6 and NOD/SCID mice after CPR, but it began late in the NOD/SCID mice. Compared with C57BL/6 mice, phos-ULK1 (Ser327) expression was significantly lower at 2 h and 12 h after CPR (2 h after CPR: 1.88 ± 0.36 vs. 1.12 ± 0.11, t= −1.36, P< 0.01 and 12 h after CPR: 1.52 ± 0.16 vs. 1.05 ± 0.12, t= −0.33, P< 0.01), whereas phos-ULK1 (Ser757) expression was significantly higher at 2 h and 12 h after CPR in NOD/SCID mice (2 h after CPR: 1.28 ± 0.12 vs. 1.69 ± 0.14, t = 1.7, P< 0.01 and 12 h after CPR: 1.33 ± 0.10 vs. 1.94 ± 0.13, t = 2.75, P< 0.01). (3) Furthermore, NLRP3 inflammasome/caspase-1 activation in the pulmonary tissues occurred early and for only a short time in C57BL/6 mice, but this phenomenon was sustained in NOD/SCID mice. The expression of the NLRP3 inflammasome increased modestly in the C57 mice, but the increase was higher in the NOD/SCID mice than in the C57BL/6 mice, especially at 12, 24, 48 h after CPR (48 h after CPR: 1.46 ± 0.13 vs. 2.97 ± 0.19, t = 5.34, P= 0.001). The expression of caspase-1-20 generally followed the same pattern as the NLRP3 inflammasome. Conclusions: There is a regulatory relationship between the NLRP3 inflammasome and mitochondrial autophagy after CPR in the healthy mice. This regulatory relationship was disturbed in the NOD/SCID mice because the signals for mitochondrial autophagy occurred late, and NLRP3 inflammasome- and caspase-1-dependent cell injury was sustained. Key words: Autophagy; Cardiopulmonary Resuscitation; Immunodeficiency; Macrophage; Mitochondria; NLRP3 Inflammasome

The antibacterial peptide mytichitin-CB has been highly expressed in Pichia pastoris. In this study, we aim to investigate its potential for application in pork preservation. P. pastoris-derived mytichitin-CB exhibited broad and potent antibacterial activity against four common foodborne bacterial pathogens and two food spoilage bacteria of Pseudomonas spp. with low minimal inhibition concentrations of 0.23–1.24 μg/mL. Mytichitin-CB effectively suppressed the growth of the microflora and significantly reduced the increases in pH, drip loss, total volatile basic nitrogen (TVB-N), and thiobarbituric acid reactive substances (TBARS) of fresh pork during storage at 4 °C. Consequently, the fresh pork maintained its desirable sensory properties. Mytichitin-CB could also effectively inhibit the growth of Staphylococcus aureus, Escherichia coli O157, and Pseudomonas fluorescens in a pork spoilage model. Combining mytichitin-CB with chitosan and nisin at the optimal proportion further enhanced the antibacterial activity and effects of food preservation on fresh pork, as evidenced by improved sensory properties, lowered drip loss and TVB-N production, and reduced change in pH during storage. However, combining these three agents failed to further increase antioxidant activity against lipid oxidation. Overall, the combination of 4 mg/L of mytichitin-CB with 10 g/L of chitosan incorporated with 300 mg/L of nisin exhibited the best performance in fresh pork preservation. The combined findings suggest that treatment with mytichitin-CB alone or in combination with chitosan and nisin has considerable potential in the preservation of fresh meat products to extend the shelf life and assure the quality and safety of meat.

We herein report a novel strategy for multi-walled carbon nanotube (MWCNT)-supported PtCo nanocatalysts, which are synthesized in deep eutectic solvents (DESs) by a chemical reduction route. The X-ray diffraction (XRD) and transmission electron microscopy (TEM) results indicate that the alloyed PtCo nanoparticles of ca. 2.4 nm are deposited on the surface of MWCNTs with less aggregation in larger clusters. X-ray photoelectron spectroscopy (XPS) measurements reveal the strong charge transfer interaction between Pt and Co atoms in the PtCo/MWCNT catalyst. The electrochemical tests illustrate that the PtCo/MWCNT exhibits much higher electrocatalytic activity, stability and CO tolerance ability than the Pt/MWCNT catalyst for the methanol oxidation reaction (MOR). This study implies that the method based on DESs will be potential in design and fabrication of the highly efficient electrocatalysts for DMFCs applications.

Based on the displacement potential functions, considering submarine rock and soil as elastic half-space, seawater as ideal fluid, anchors as springs, the formulae for determining the hydrodynamic pressure on submerged floating tunnel were deduced while the P-wave was incident. Subsequently, effects of different submarine rock and soil parameters (such as shear modulus, Poisson ratio) and different spring constants and spaces of the anchors on the hydrodynamic pressures were discussed. It could be concluded that for normal incidence, the shear modulus and the Poisson ratio of submarine rock and soil have no influence on the amplitude of the hydrodynamic pressure on SFT for. The peak value of the amplitude of the hydrodynamic pressure on SFT increases as the Poisson ratio of submarine rock and soil and the spring constant of anchor increases, decreases as the spacing of the anchor increases.

In contrast to its inhibitory effects on many cells, IL10 activates CD8+ tumor-infiltrating lymphocytes (TIL) and enhances their antitumor activity. However, CD8+ TILs do not routinely express IL10, as autocrine complement C3 inhibits IL10 production through complement receptors C3aR and C5aR. CD8+ TILs from C3-deficient mice, however, express IL10 and exhibit enhanced effector function. C3-deficient mice are resistant to tumor development in a T-cell– and IL10-dependent manner; human TILs expanded with IL2 plus IL10 increase the killing of primary tumors in vitro compared with IL2-treated TILs. Complement-mediated inhibition of antitumor immunity is independent of the programmed death 1/programmed death ligand 1 (PD-1/PD-L1) immune checkpoint pathway. Our findings suggest that complement receptors C3aR and C5aR expressed on CD8+ TILs represent a novel class of immune checkpoints that could be targeted for tumor immunotherapy. Moreover, incorporation of IL10 in the expansion of TILs and in gene-engineered T cells for adoptive cell therapy enhances their antitumor efficacy. Significance: Our data suggest novel strategies to enhance immunotherapies: a combined blockade of complement signaling by antagonists to C3aR, C5aR, and anti–PD-1 to enhance anti–PD-1 efficacy; a targeted IL10 delivery to CD8+ TILs using anti–PD-1–IL10 or anti-CTLA4–IL10 fusion proteins; and the addition of IL10 in TIL expansion for adoptive cellular therapy. Cancer Discov; 6(9); 1022–35. ©2016 AACR. See related commentary by Peng et al., p. 953. This article is highlighted in the In This Issue feature, p. 932

ZnO light-emitting diodes (LEDs) have an enormous potential in lighting applications. The major issue to be resolved is the generating and control of light emissions. This issue arises from the variation and combination in LED wavelength. We found that defect luminescence of ZnO has a varied wide range of wavelength, which suits to an application of LED for white-light generation. We have shown both experimentally and theoretically that defect emission can be used in ZnO systems. This type of defect has the advantage of not requiring extensive and costly factory systems comparing with traditional doped materials and others. We not only propose potential application of native defect luminescence of Zinc Oxide film for white LEDs-flat light sources, but also have some methods to control defect origins, a certain center position and broad range of the emission band of ZnO film in the initial stage. According to different preparing method and certain experiment conditions, variant white such as whitish and bluish-white etc., primary and important colors- blue bands (455, 458 nm), green bands (517, 548 nm), red bands (613, 569 nm) are obtained respectively. This proved that it is a better road to one white light LED with one kind of material -ZnO.

Cucumber seedlings (Cucumis sativus Jinyou 35) were used to study the effects of high temperature (HT: 42 ℃/32 ℃) and sub-high temperature (SHT: 35 ℃/25 ℃) on its photosynthesis and growth. The results showed that the growth of cucumber seedlings was dramatically inhibited by the high and sub-high temperature stresses. The photosynthetic rate (P以‘津优35号’黄瓜幼苗为试材,研究高温(HT: 42 ℃/32 ℃)和亚高温(SHT: 35 ℃/25 ℃)胁迫对黄瓜幼苗光合作用及生长量的影响.结果表明: 高温、亚高温明显抑制幼苗生长.随着胁迫时间的延长,黄瓜幼苗叶片的光合速率(

Herein, we report a novel electrocatalyst consisting of Pt nanoparticles supported on a polyindole (PIn)-functionalized multi-walled carbon nanotube (MWCNT) composite (Pt/PIn-MWCNT) for use in the methanol oxidation reaction (MOR). The PIn-MWCNT support is synthesized via in situ chemical polymerization of indole on the MWCNT surface. The transmission electron microscopy (TEM) images indicated that the Pt nanoparticles were approximately 3.0 nm in size and were uniformly deposited on the surface of PIn-MWCNTs with no aggregation into larger clusters. X-ray photoelectron spectroscopy (XPS) measurements confirm the strong electron interaction between the Pt nanoparticles and the PIn-MWCNT support as well as the formation of the Pt–N bond. The electrochemical tests demonstrate that the Pt/PIn-MWCNT composite exhibits much higher electrocatalytic activity, durability and CO tolerance than the Pt/MWCNT and commercial Pt/C catalysts toward MOR. The results indicate that the as-prepared Pt/PIn-MWCNTs are promising for use as an anode electrocatalyst in direct methanol fuel cells (DMFCs).

We report on a novel electrochemical dopamine (DA) sensor based on a glassy carbon electrode (GCE) modified with a hybrid material composed of Cu(I) oxide hollow microspheres and carbon black. The hybrid material was synthesized in a mixed solvent composed of water and the deep eutectic solvent choline chloride/urea, and by in-situ reduction of Cu(II) by ascorbic acid. The surface morphology and structure of the materials were characterized by scanning electron microscopy, transmission electron microscopy and X-ray diffraction. Cyclic voltammetry and chronoamperometry were used to evaluate the electrocatalytic properties of the modified GCE toward DA oxidation in phosphate buffer solution of pH 5.7. The sensor displays a higher electrocatalytic activity toward DA oxidation compared to other modified electrodes. At a working potential of 0.25 V (vs. SCE), the sensor exhibits a rapid response (

The hydrothermal synthesis of a novel Pd electrocatalyst using copper phthalocyanine-3,4′,4″,4′″-tetrasulfonic acid tetrasodium salt (TSCuPc) functionalized multi-walled carbon nanotubes (MWCNTs) composite as catalyst support for Pd nanoparticles is reported. The prepared nanocomposites were characterized by UV–vis absorption spectroscopy, Fourier transform infrared (FTIR) spectroscopy, Raman spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and electrochemical tests. It is found that Pd nanoparticles are uniformly deposited on the surface of TSCuPc-MWCNTs, and their dispersion and electrochemical active surface area (ECSA) are significantly improved. Studies of cyclic voltammetry and chronoamperometry demonstrate that the Pd/TSCuPc-MWCNTs exhibits much higher electrocatalytic activity and stability than the Pd/AO-MWCNTs catalyst for formic acid oxidation. This study implies that the as-prepared Pd/TSCuPc-MWCNTs will be a promising candidate as an anode electrocatalyst in direct formic acid fuel cell (DFAFC).

In order to arrive at the scene of the fire in the shortest time dealing with the accident, considering two fires occurred at the same time, taking optimal allocation of resources at the center of the fire fighting and the least time of driving to fireground as objective functions, based on automobile brake model and two-stage scheduling mechanism, to build the total time optimal model and resource allocation optimization model. Models obtain vehicle shortest transit time and the optimal resource allocation amount, it can effectively solve routing problem of the emergency rescue vehicle, resources shortage also can be solved when many accidents happen at the same time, to avoid the waste of resources and to ease the pressure of maintenance cost.

Taking the free vibration system of a submerged floating tunnel tether as research object, the non-linear free vibration equation was set up. By means of Galerkin method, the partial differential equation was transformed into a set of ordinary ones. The damping ratios of the first four modes were obtained after complex eigenvalue analysis. Subsequently, effects of inclination, sag, initial tension force and length of tether on its modal damping ratios were analyzed. The results show that inclination and sag of tether merely affect the damping ratio of first in-plane mode; they have no effect on the damping ratios of higher order in-plane modes and out of plane modes; the first in-plane modal damping ratio of tether is in direct proportion to its inclination, whereas in inverse proportion to its sag; the first modal damping ratio of tether (both in-plane and out of plane) is in direct proportion to its length, whereas in inverse proportion to its initial tension.

Cycloastragenol (CAG), a bioactive triterpenoid sapogenin isolated from the Chinese herbal medicine Radix astragali , was reported to promote the phosphorylation of extracellular signal-regulated protein kinase (ERK). Here we investigated the effect of CAG on adipogenesis. The image-based Nile red staining analyses revealed that CAG dose dependently reduced cytoplasmic lipid droplet in 3T3-L1 adipocytes with the IC 50 value of 13.0 μM. Meanwhile, cytotoxicity assay provided evidence that CAG was free of injury on HepG2 cells up to 60 μM. In addition, using calcium mobilization assay, we observed that CAG stimulated calcium influx in 3T3-L1 preadipocytes with a dose dependent trend, the EC 50 value was determined as 21.9 μM. There were proofs that elevated intracellular calcium played a vital role in suppressing adipocyte differentiation. The current findings demonstrated that CAG was a potential therapeutic candidate for alleviating obesity and hyperlipidemia.

To study the vibration response of submerged floating tunnel tether under the combined action of vortex-induced vibration and parametric vibration, a non-linear vibration equation based on wake oscillator model is set up taking the geometric nonlinearity of tether into account, in which effect of tube on tether is simplified as axial excitation. An approximate numerical solution of planning submerged floating tunnel tether is obtained by applying Galerkin method and Runge-kutta method. The variation degree of mid-span displacement response and axial force of tether is analyzed when the vortex-induced resonance and parametric resonance occur. The results show that, when vortex-induced resonance and parametric resonance occur simultaneously, the mid-span displacement and axial force of tether increase dramatically; the tether sag effect results in the asymmetry of tether mid-span vibration amplitude.

To study the nonlinear mechanical characteristics of reinforced concrete shear wall structures under rare earthquakes, a single reinforced concrete shear wall model is established in SAP2000 program, which is simulated by nonlinear multi-layer shell element. Nonlinear static pushover analysis of the model is presented by uniform acceleration lateral load pattern and inverted triangle lateral load pattern. The relationship curve between base shear and top displacement of shear wall, and the stress distribution diagrams of the concrete layer and rebar layer are obtained. It may be concluded that, the yielding of rebar layer and the cracking of the concrete layer may be observed by stress distribution diagrams. SAP2000 program is feasible to nonlinear simulation of shear wall structures.

The V2O5films were prepared by the (radio frequency)RF sputtering. The transmission of the samples under different deposition pressures and different Ar/O2flow ratios was investigated to determine the fundamental preparation condition for the further analysis. On the fundamental condition, the security volt of V2O5was determined. It is concluded that the annealing makes the V2O5films have a good reversibility but lowers the electrochromic property.

In this paper, the ZnO/Cu2S/ZnO complex films were fabricated by Radio Frequency (RF) magnetron sputtering, and their transparent, conductive and photocatalytic properties have been investigated. The results show the properties of ZnO/Cu2S/ZnO complex films vary when the top layer ZnO thickness changes.

Considering the prevalence of cardiovascular disease in public health and the limited validated therapeutic options, this study aimed to find novel compounds targeting the angiotensin II type 1 receptor, accepted as a therapeutic target in cardiovascular disease. A small library consisting of 89 compounds from 39 Chinese herbs was profiled using a cell-based calcium mobilization assay which was developed and characterized for high-throughput screening. [6]-Gingerol derived from Zingiber officinale Roscoe (ginger) was identified as a novel angiotensin II type 1 receptor antagonist, with an IC50 value of 8.173 µM. The hit was further tested by a specificity assay indicating that it had no antagonistic effects on other evaluated GPCRs, such as endothelin receptors. The major ingredient of ginger, [6]-gingerol, could inhibit angiotensin II type 1 receptor activation, which partially clarified the mechanism of ginger regulating blood pressure and strengthening heart in the cardiovascular system.

A mathematical equation for vibration of submerged floating tunnel tether under the effects of earthquake and parametric excitation is presented. Multi-step Galerkin method is used to simplify this equation and the fourth-order Runge-Kuta integration method is used for numerical analysis. Finally, vibration response of submerged floating tunnel tether subjected to earthquake and parametric excitation is analyzed in a few numerical examples. The results show that the vibration response of tether varies with the seismic wave type; the steady maximum mid-span displacement of tether subjected to seismic wave keeps constant when parametric resonance takes place; the transient maximum mid-span displacement of tether is related to the peak value of input seismic wave acceleration.

This study surveyed and collected the urban trunk traffic flow data of Bayi South/North Street in Jinhua. The section between two crossings-- Fengting Rd. VS Bayi North St. and Huixi St. VS Bayi North St. (World Trade Hotel) was set as a representative example. It analyzed sections and intersection traffic flow characteristics at the weekday evening peak hour (5:00 to 6:00 pm), evaluated the congestion situation, proposed the further improve measures. Then the effectiveness of the promote measures were evaluated by applying software VISSIM simulation of trunk road traffic. The results will benefit to raise the urban trunk traffic system capacity, better the traffic jams situation, optimize transportation planning and management measures, and further the sustainable development along the urban trunk.

ZnO film and Cu2S/ZnO bilays on the glass substrate were fabricated by RF magnetron sputtering. We carried out the experiments by adjusting the thickness of Cu2S on ZnO layer. The performance of Cu2S/ZnO on the transparency, conduction and photocatalysis were investigated. The photocatalytic experiments showed a good photocatalytic activity for photodegradation of methyl orange.

Genes of selenoproteome have been increasingly implicated in various aspects of neurobiology and neurological disorders, but remain largely elusive in Parkinson's disease (PD). In this study, we investigated the selenotranscriptome (24 selenoproteins in total) in five brain regions (cerebellum, substantia nigra, cortex, pons and hippocampus) by real time qPCR in a two-phase manner using a mouse model of chronic PD. A wide range of changes in selenotranscriptome was observed in a manner depending on selenoproteins and brain regions. While Selv mRNA was not detectable and Dio1& 3 mRNA levels were not affected, 1, 11 and 9 selenoproteins displayed patterns of increase only, decrease only, and mixed response, respectively, in these brain regions of PD mice. In particular, the mRNA expression of Gpx1-4 showed only a decreased trend in the PD mouse brains. In substantia nigra, levels of 17 selenoprotein mRNAs were significantly decreased whereas no selenoprotein was up-regulated in the PD mice. In contrast, the majority of selenotranscriptome did not change and a few selenoprotein mRNAs that respond displayed a mixed pattern of up- and down-regulation in cerebellum, cortex, hippocampus, and/or pons of the PD mice. Gpx4, Sep15, Selm, Sepw1, and Sepp1 mRNAs were most abundant across all these five brain regions. Our results showed differential responses of selenoproteins in various brain regions of the PD mouse model, providing critical selenotranscriptomic profiling for future functional investigation of individual selenoprotein in PD etiology.