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In order to study the structural state of the bridge under the influence of time-varying effect, the response of the concrete self-anchored suspension bridge under vehicle load and temperature load during the 30-year operation period is studied, through field load test and finite element analysis based on ANSYS refined spatial solid model. The results show that with the increase of the service life of the bridge, the bottom plate of the box chamber of the main girder gradually tends to be tensioned in the longitudinal direction of the bridge, and the horizontal preload stress of the main girder gradually loses when the bridge is completed; The transverse bridge stress at the junction of the outermost bottom of the box chamber and the web tends to be tensile, while the transverse bridge stress at the measuring point of the inner bottom plate gradually increases. The change value of the cable force of the hanger is obviously affected by the restraint mode of the support. Affected by the main tower support, the cable force of the hanger adjacent to the main tower decreases greatly. During the operation of the bridge, the working conditions of the mid span and east span hangers shall be monitored.

The crystallographic alignment, microstructure and magnetic properties were studied for La0.6Ca0.6Sr0.1Fe12.4Co0.4O19 ferrite permanent magnets prepared with standard ceramic method. The effect of cold isostatic pressing (CIP) and sintering temperature on the structural and magnetic properties of the magnets were investigated. The CIP significantly improves the density of the green compact and final magnets, but undermines the crystallographic alignment of the magnets simultaneously. As a result, the remanence of the magnet achieves optimal value under the compromise between the increased density and the degraded alignment. Moreover, the coercivity of the magnet increases linearly with the increment of the CIP pressure due the fact that CIP processed samples bear more uniform and finer grains in favor of high coercivity. Under optimal CIP pressure and sintering temperature, the magnet obtains best magnetic properties of Br of 0.439 T, Hcj of 396 kA m−1, Hcb of 311 kA m−1, and (BH)maxof 35.8 kJ m−3.

In order to find good candidate materials for degradable fracturing ball applications, Mg-Al-Zn-Cu alloys with different contents of aluminum, zinc, and copper were prepared by ingot metallurgy. The effects of aluminum, zinc, and copper additions on the microstructure, compressive strength, and rapid decomposition properties of the alloys have been investigated using scanning electron microscopy, compressive tests, and immersion tests. The results show that the addition of high contents Al (15 to 20 wt pct) in pure magnesium promotes a large number of network-like β-Mg 17 Al l2 phases, which helps produce more micro-thermocouples to accelerate the corrosion process in 3 wt pct potassium chloride (KCl) at 366 K (93 °C). Adding different Zn contents improves the compressive properties of Mg-20Al alloys drastically. However, it decreases the decomposition rate in 3 wt pct KCl at 366 K (93 °C). Small amount of Cu will slightly reduce the compressive strength of Mg-20Al-5Zn alloy but dramatically increase its decomposition rate.

The crystallographic alignment, microstructure and magnetic properties were studied for La 0.6 Ca 0.6 Sr 0.1 Fe 12.4 Co 0.4 O 19 ferrite permanent magnets prepared with standard ceramic method. The effect of cold isostatic pressing (CIP) and sintering temperature on the structural and magnetic properties of the magnets were investigated. The CIP significantly improves the density of the green compact and final magnets, but undermines the crystallographic alignment of the magnets simultaneously. As a result, the remanence of the magnet achieves optimal value under the compromise between the increased density and the degraded alignment. Moreover, the coercivity of the magnet increases linearly with the increment of the CIP pressure due the fact that CIP processed samples bear more uniform and finer grains in favor of high coercivity. Under optimal CIP pressure and sintering temperature, the magnet obtains best magnetic properties of B r of 0.439 T, H cj of 396 kA m −1 , H cb of 311 kA m −1 , and (BH) max of 35.8 kJ m −3 .

The super τ-charm facility (STCF) is an electron−positron collider proposed by the Chinese particle physics community. It is designed to operate in a center-of-mass energy range from 2 to 7 GeV with a peak luminosity of 0.5 × 10 35 cm −2·s −1 or higher. The STCF will produce a data sample about a factor of 100 larger than that of the present τ-charm factory - the BEPCII, providing a unique platform for exploring the asymmetry of matter-antimatter (charge-parity violation), in-depth studies of the internal structure of hadrons and the nature of non-perturbative strong interactions, as well as searching for exotic hadrons and physics beyond the Standard Model. The STCF project in China is under development with an extensive R&D program. This document presents the physics opportunities at the STCF, describes conceptual designs of the STCF detector system, and discusses future plans for detector R&D and physics case studies.

Refractory chronic GVHD (cGVHD) is an important complication after allogeneic hematopoietic SCT and is prognostic of poor outcome. MSCs are involved in tissue repair and modulating immune responses in vitro and in vivo . From April 2005 to October 2008, 19 patients with refractory cGVHD were treated with MSCs derived from the BM of volunteers. The median dose of MSCs was 0.6 × 10 6 cells per kg body weight. Fourteen of 19 patients (73.7%) responded well to MSCs, achieving a CR ( n =4) or a PR ( n =10). The immunosuppressive agent could be tapered to less than 50% of the starting dose in 5 of 14 surviving patients, and five patients could discontinue immunosuppressive agents. The median duration between MSC administration and immunosuppressive therapy discontinuation was 324 days (range, 200–550 days). No patients experienced adverse events during or immediately after MSC infusion. The 2-year survival rate was 77.7% in this study. Clinical improvement was accompanied by the increasing ratio of CD5+CD19+/CD5−CD19+ B cells and CD8+CD28−/CD8+CD28+ T cells. In conclusion, transfusion of MSCs expanded in vitro , irrespective of the donor, might be a safe and effective salvage therapy for patients with steroid-resistant, cGVHD.

Genetic polymorphisms of CYP2C9 significantly influence the pharmacokinetics and pharmacodynamics of some drugs, which might result in adverse drug effects and therapeutic failure. Several studies have been performed on CYP2C9 genetic polymorphisms in Han Chinese populations. However, these studies only focused on two commonly investigated alleles, *2 and *3 , in relatively small sample sizes. To scale up the gene-scanning region and determine relatively precise data on the genetic distribution pattern in Chinese populations, unrelated healthy Han Chinese volunteers from Zhejiang Province ( n =1127) and Hebei ( n =1000) Province were recruited as subjects for the direct sequencing of all exons of CYP2C9 . As a result, 14 previously reported alleles were detected in this work, and 8 of these alleles ( *14 , *16 , *19 , *23 , *27 , *29 , *33 and *34 ) were described for the first time in Chinese populations. In addition, 37 novel mutations were also detected, of which 22 variants were non-synonymous, and 21 new alleles, *36-*56 , were designated by the Human CYP Allele Nomenclature Committee. In vitro functional analysis of these 22 novel CYP2C9 variants revealed that 17 mutations had a significant influence on the protein’s catalytic activity. Our study provides the most accurate data on CYP2C9 polymorphisms in Han Chinese populations and detects the largest number of novel allelic variants existing to date. These new alleles will greatly enrich the current knowledge of naturally occurring CYP2C9 variants in Chinese populations.

The insecticidal and repellent activities of the essential oil extracted from Zingiber purpureum Roscoe rhizomes were evaluated against Tribolium castaneum (Herbst) and Lasioderma serricorne (L.) adults. During our screening program for agrochemicals from Chinese medicinal herbs and wild plants, the essential oil of Z. purpureum rhizomes was found to possess strong contact toxicity against T. castaneum and L. serricorne adults, with LD50 values of 39.0 and 16.3 µg per adult, respectively, and also showed strong fumigant toxicity against the two grain storage insects with LC50 values of 13.6 and 9.3 mg/liter of air, respectively. The essential oil obtained by hydrodistillation was investigated by gas chromatography-mass spectrometry. The main components of the essential oil were identified to be sabinene (48.1%), terpinen-4-ol (25.1%), and γ-terpinene (6.7%), followed by α-terpinene (4.3%), β-thujene (3.4%), and α-phellandrene (2.7%). Sabinene, terpinen-4-ol, and γ-terpinene were separated and purified by silica gel column chromatography and preparative thin-layer chromatography. Terpinen-4-ol showed the strongest contact toxicity against T. castaneum and L. serricorne (LD50 = 19.7 and 5.4 µg per adult, respectively) and also the strongest fumigant toxicity against T. castaneum and L. serricorne (LC50 = 3.7 and 1.3 mg/liter of air, respectively). Otherwise, sabinene and terpinen-4-ol were strongly repellent against T. castaneum as well as the essential oil, while γ-terpinene exhibited weaker repellency against T. castaneum compared with the positive control, DEET (N, N-diethyl-3-methylbenzamide). Moreover, only the essential oil exhibited strong repellency against L. serricorne, the three compounds exhibited weaker repellency against L. serricorne relative to DEET.

Purpose: Wound healing, especially of extensive full-thickness wounds, is one of the most difficult problems in clinical studies. In this study, we prepared a novel substance P (SP)-delivery system using zeolite imidazolate framework-8 (ZIF-8) nanoparticles. Methods: We synthesized ZIF-8 nanoparticles using a modified biomimetic mineralization method. We then coated SP-loaded ZIF-8 nanoparticles (SP@ZIF-8) with polyethylene glycol-thioketal (PEG-TK) to fabricate SP@ZIF-8-PEG-TK nanoparticles, and encapsulated them in injectable hydrogel composed of sodium alginate and pectin and cross-linked using calcium chloride. The final hydrogel wound dressing containing SP@ZIF-8-PEG-TK nanoparticles was called SP@ZIF-8-PEG-TK@CA. Results: The fabricated ZIF-8 nanoparticles had high SP-loading efficiency. SP-release assay showed that the SP@ZIF-8-PEG-TK nanoparticles maintained drug activity and showed responsive release under stimulation by reactive oxygen species. The SP@ZIF-8-PEG-TK nanoparticles promoted proliferation of human dermal fibroblasts, up-regulated expression levels of inflammation-related genes in macrophages, and exhibited favorable cytocompatibility in vitro. Full-thickness excision wound models in vivo confirmed that SP@ZIF-8-PEG-TK@CA dressings had excellent wound-healing efficacy by promoting an early inflammatory response and subsequent M2 macrophage polarization in the wound-healing process. Conclusion: In conclusion, these findings indicated that SP@ZIF-8-PEG-TK@CA dressings might be useful for wound dressing applications in the clinic.

Despite therapeutic advances in HER2-positive metastatic breast cancer, resistance to trastuzumab inevitably develops. In the PHOEBE study, we aimed to assess the efficacy and safety of pyrotinib (an irreversible pan-HER inhibitor) plus capecitabine after previous trastuzumab. This is an open-label, randomised, controlled, phase 3 trial done at 29 hospitals in China. Patients with pathologically confirmed HER2-positive metastatic breast cancer, aged 18–70 years, who had an Eastern Cooperative Oncology Group performance status of 0 or 1, and had been previously treated with trastuzumab and taxanes were randomly assigned (1:1) to receive oral pyrotinib 400 mg or lapatinib 1250 mg once daily plus oral capecitabine 1000 mg/m2 twice daily on days 1–14 of each 21-day cycle. Randomisation was done via a centralised interactive web-response system with a block size of four or six and stratified by hormone receptor status and previous lines of chemotherapy for metastatic disease. The primary endpoint was progression-free survival according to masked independent central review. Efficacy and safety were assessed in all patients who received at least one dose of the study drugs. Results presented here are from a prespecified interim analysis. This study is registered with ClinicalTrials.gov, NCT03080805. Between July 31, 2017, and Oct 30, 2018, 267 patients were enrolled and randomly assigned. 134 patients received pyrotinib plus capecitabine and 132 received lapatinib plus capecitabine. At data cutoff of the interim analysis on March 31, 2019, median progression-free survival was significantly longer with pyrotinib plus capecitabine (12·5 months [95% CI 9·7–not reached]) than with lapatinib plus capecitabine (6·8 months [5·4–8·1]; hazard ratio 0·39 [95% CI 0·27–0·56]; one-sided p<0·0001). The most common grade 3 or worse adverse events were diarrhoea (41 [31%] in the pyrotinib group vs 11 [8%] in the lapatinib group) and hand–foot syndrome (22 [16%] vs 20 [15%]). Serious adverse events were reported for 14 (10%) patients in the pyrotinib group and 11 (8%) patients in the lapatinib group. No treatment-related deaths were reported in the pyrotinib group and one sudden death in the lapatinib group was considered treatment related. Pyrotinib plus capecitabine significantly improved progression-free survival compared with that for lapatinib plus capecitabine, with manageable toxicity, and can be considered an alternative treatment option for patients with HER2-positive metastatic breast cancer after trastuzumab and chemotherapy. Jiangsu Hengrui Medicine and National Key R&D Program of China. For the Chinese translation of the abstract see Supplementary Materials section.