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Deoxyribonucleic acid-protein (DNAP) of the cell nucleus was purified from developing wheat (

Carbon nanotubes (CNTs) are regarded as an excellent reinforcement for reinforcing metal matrix composites. However, they are extremely difficult to disperse since nano-scaled CNTs have large specific surface area, generally leading to agglomeration due to the large van der Waals attractive forces. In this study, CNTs as carbon sources were added into Ti6Al4V matrix, a dry jar-milling process without milling balls was performed to greatly reduce the structural damage of CNTs and simultaneously meet the requirements of dispersion homogeneity. In situ synthesized TiC and unreacted CNTs reinforced Ti6Al4V matrix composites (TMCs) were successfully prepared by the fast manufacturing process via spark plasma sintering. The microstructures and mechanical properties including microhardness, compressive yield strength, ultimate compressive strength and plastic strain of the Ti6Al4V alloy and the TMCs prepared by different CNTs content were studied to evaluate the strengthening effects of the reinforcements on Ti6Al4V matrix.

The contents of conjugated covalently polyamines (CC-PAs) and conjugated non-covalently polyamines (CNC-PAs) in embryo tonoplast, and the vacuole conformation were investigated using the embryos of developing maize (Zea mays L.) grains of two cultivars differing in drought-tolerance as experiment materials. The results indicated that after drought stress treatment for seven days, relative water content of embryo (RWCE) and relative increase rate of embryo dry weight (RIREDW) of the drought-sensitive cultivar ‘Xund-an no. 22’ decreased more significantly than those of the drought-tolerant ‘Zhengdan No. 958’. Furthermore, the changes in vacuole conformation of ‘Xundan no. 22’ were more marked. Meanwhile, the increases of the contents of CNC-spermidine (CNC-Spd) and CC-putrescine (CC-Put) in embryo tonoplast from ‘Zhengdan no. 958’ were more obvious than those from ‘Xundan no. 22’. Treatment with exogenous Spd not only alleviated the injury of drought stress to ‘Xundan no. 22’, but also enhanced the increases of CNC-Spd content and inhibited the changes in the vacuole conformation of this cultivar. The treatments of ‘Zhengdan no. 958’ with two inhibitors, methylglyoxyl-bis (guanylhydrazone) and phenanthrolin, significantly inhibited the drought stress-induced increases of CNC-Spd and CC-Put contents of the cultivar, respectively. Meanwhile, the treatments significantly aggravated the injury of drought stress to ‘Zhengdan no. 958’ and the changes in the vacuole conformation of this cultivar. All the results mentioned above suggest that the CNC-Spd and CC-Put in embryo tonoplast isolated from developing grains could enhance the tolerance of maize to drought stress by maintaining the vacuole conformation.

One of the most promising approaches to reach a high gain in inertial confinement fusion is the fast ignition scheme. In this scheme, a relativistic electron beam is generated; this passes through the imploded plasma and deposits parts of its energy in the core. However, the large angular spread of the relativistic electron beam and the poorly controlled compression of the target affect realization of the fast ignition technique. Here, we demonstrate that indirectly driven (that is, driven by X-rays generated inside a gold hohlraum) implosions with a ‘high-foot’ and a short-coast time of less than 200 ps allow us to tightly compress the shell. Furthermore, we show the ability to optimize the symmetry of the imploding shell by changing the hohlraum length, successfully tuning a suitable tube-shaped shell to compensate for the large angular spread of the relativistic electron beam and to enhance the electron-to-core coupling efficiency via resistive magnetic fields. Benefiting from those experimental techniques, a significant enhancement in neutron yield was achieved in our indirectly driven fast ignition experiments. These results pave the way towards high-coupling fast ignition experiments with indirectly driven targets similar to those at the National Ignition Facility. Experiments realizing the indirect-drive fast ignition scheme for inertial confinement fusion are reported. Enabled by a tightly compressed target, an increase of neutron yield is observed.

In this study, a new In(III)-based coordination polymer [In(cpt)](DMF)(H2O) (1, DMF = N,N-dimethylformamide) is prepared using a newly designed ligand 5-(4-carboxybenzyl)isophthalic acid (H3cpt). Complex 1 is characterized by single crystal and powder X-ray diffraction and the thermogravimetric analysis. The structure of 1 involves one-dimensional chain-like units containing In(III), further combined with cpt3-ligands to obtain a 3D framework structure. The ultrasonic treatment method is used to produce nanoparticles of 1 (nano 1). MTT assay was carried out to explore the cytotoxicity of nano 1 on HMEC-1 hemangioendothelioma cells, and RT-PCR was utilized to assess activation of the PTEN/PI3K/Akt pathway.

Foam has been suggested to reduce laser imprint because of its low density. In this paper, the two-dimensional radiation hydrodynamic code FLASH is applied to investigate and characterize the strength of laser imprint through analyzing areal density perturbation. There are two important factors for the mitigation of laser imprint besides the thermal smoothing of the conduction region (between the ablation front and the critical density surface) and the mass ablation of the ablation front. First, radiation ablation dynamically modulates density distribution not only to increase the frequency of the perturbed ablation front oscillation but also to decrease the amplitude of oscillation. Second, a larger length of the shocked compression region reduces the amplitude of the perturbed shock front oscillation. The smaller the perturbation of both ablation front and shock front, the smaller the areal density perturbation. Based on the above physical mechanisms, the optimal way of mitigating laser imprint with foam is that the dynamically modulated density distribution further reduces the amplitude of perturbation reaching the solid CH when the areal density perturbation of foam oscillates to the first minimum value. The optimal ranges of foam parameters to mitigate laser imprint are proposed with the aid of dimensional analysis: the foam thickness is about 2~3 times the perturbation wavelength, and the foam density is about 1/2~3/2 times the mass density corresponding to the critical density.

An expert consensus on coronary artery bypass grafting (CABG) in patients with ischemic cardiomyopathy (ICM) was released by the American Association for Thoracic Surgery in May 2021, which contains a vast array of perioperative recommendations. During preoperative period, a comprehensive assessment on ICM including myocardial viability and valve function by a multi-disciplinary team (MDT) approach should be performed. In terms of intraoperative period, multiple arterial conduits and on-pump CABG using cold blood cardioplegia should be considered, meanwhile, other aspects involving concomitant management of mitral valve regurgitation and arrythmia, as well as active use of mechanical cardiac assist devices (e.g., intra-aortic balloon pump) should also be achieved. Finally, a range of postoperative interventions which includes standardized MDT management in intensive care unit (ICU), continuous use of cardiac assist devices, cardiac pacing, close follow-up within 90 days and drug treatment strictly guided by the guidelines after discharge from hospital should be conducted. The above-mentioned perioperative bundled care might reduce perioperative complications and operative mortality, and thus improve the prognosis of the patients with ICM.2021年5月美国胸外科协会发布了缺血性心肌病伴心力衰竭的冠状动脉旁路移植术（CABG）临床应用专家共识。该共识建议术前多学科参与，积极对缺血性心肌病进行评估，包括心肌活力、瓣膜功能等；术中采用多支动脉桥、含血心肌保护液行心脏停跳的CABG，同期积极处理二尖瓣关闭不全并重视心律失常处理，积极使用包括主动脉内球囊反搏在内的心脏机械辅助装置；术后采用多学科团队规范化重症监护病房的各项治疗，继续合理使用心脏辅助装置，重视心脏起搏治疗并在出院后90 d内密切随访等措施降低缺血性心肌病CABG 的手术死亡率，减少围手术期并发症并改善预后。.

In this study, a new In(III)-based coordination polymer [In(cpt)](DMF)(H2O) (1, DMF = N,N-dimethylformamide) is prepared using a newly designed ligand 5-(4-carboxybenzyl)iso­phthalic acid (H3cpt). Complex 1 is characterized by single crystal and powder X-ray diffraction and the thermogravimetric analysis. The structure of 1 involves one-dimensional chain-like units containing In(III), further combined with cpt3– ligands to obtain a 3D framework structure. The ultrasonic treatment method is used to produce nanoparticles of 1 (nano 1). MTT assay was carried out to explore the cytotoxicity of nano 1 on HMEC-1 hemangioendothelioma cells, and RT-PCR was utilized to assess activation of the PTEN/PI3K/Akt pathway.

慢性咳嗽是呼吸道疾病最常见的症状，对患者生活质量具有重大影响。新型冠状病毒肺炎（COVID-19）全球大流行有可能使原本患病率居高的慢性咳嗽再次激增。但目前慢性咳嗽的诊断和治疗仍具有巨大挑战，病因不明和治疗无效等情况占就诊人数的比例仍居高。对慢性咳嗽主要诱因、病因和治疗措施的最新研究，慢性咳嗽发生机制研究的新方向和新型止咳药的研发等相关内容在近年来不断更新，本文主要对慢性咳嗽的最新进展进行综述。.

The mitochondrion conformation and the contents of conjugated polyamines were investigated using the embryos of developing wheat (

Pancreatic cancer is considered to be the most malignant digestive tract tumor due to its high invasiveness, metastasis and recurrence rate. In recent years, neoadjuvant therapy has brought new insights to the treatment of pancreatic cancer. To date, the value of neoadjuvant therapy in pancreatic cancer has been widely recognized, but there is a lack of specific regimens. The superiority and inferiority of various regimens are still uncertain, therefore, the efficacy of neoadjuvant therapy can be evaluated combined with imaging, functional and biological markers.胰腺癌因具有高侵袭性、高转移性、高复发率等特点被认为是恶性程度极高的消化道肿瘤。近年来新辅助治疗给胰腺癌的治疗带来了新的曙光，如今新辅助治疗在胰腺癌的价值已被广泛认可，但缺乏特异性方案，各类方案孰优孰劣尚无定论，可联合影像学、功能学和生物学标记物评估新辅助治疗的效果。.

To elucidate the relationship between polyamines and anaerobic respiration of wheat (Triticum aestivum L.) seedling root under water-logging stress, the contents of polyamines (PAs), lactate and alcohol, and the activities of anaerobic respiration enzymes were investigated in seedling roots of two wheat cultivars, Yumai no. 18 and Yangmai no. 9. On the 5th day after water-logging treatment, spermidine (Spd) and spermine (Spm) contents increased significantly, pyruvate decarboxylase (PDC) activity increased and there was no difference between two cultivars. Alcohol dehydrogenase (ADH) activity and alcohol content in Yangmai no. 9 increased more markedly than Yumai no. 18, while lactate dehydrogenase (LDH) activity and the lactate content in the Yumai no. 18 increased more markedly than Yangmai no. 9. Treatments with exogenous Spd and Spm resulted in enhancing the increases in ADH activity, alcohol content, and the levels of Spd and Spm. This concomitantly inhibited the increases in LDH activity and lactate content in Yumai no. 18 under water-logging stress, alleviating stress-induced injury to the seedlings. Treatment with exogenous inhibitor methylglyoxyl-bis-guanylhydrazone (MGBG), resulted in reducing the increases in ADH activity, alcohol content, and Spd and Spm levels, promoting the increases in LDH activity and lactate content in Yangmai no. 9 under water-logging stress, and aggravating the stress-induced injury to the seedlings. The results suggested that under water-logging stress, increased Spd and Spm could facilitate the tolerance of wheat seedling to the stress by enhancing the increases in ADH activity and alcohol content, and inhibiting the increases in LDH activity and lactate content.

Recently a new nephelauxetic parameter β 1 = ( C C 0 ) 2 + ( B B 0 ) 2 , where B, C (B0, C0) are the Racah parameters of the transition metal ions in a crystal (free state), was introduced to rationalize the variations in the energy of the 2E-4A2 and 1E-3A2 spin-forbidden emission transitions that occur when ions with the d3 and d8 electron configurations are introduced as optically active impurities in a lattice. A critical analysis of the vast experimental data that is available in the archival literature shows that the energies of the above-mentioned transitions are linear functions of the β1 parameter. In this work, we further confirm this empirical finding and provide a derivation of the observed linear dependence by considering the Tanabe-Sugano matrices for the corresponding electron configurations.

Backgound and Aim: The best test to guide the choice of systemic therapy for breast cancer (BC) has not yet been identified. We did this study to identify factors that drive proliferation features in BC and assess their association with clinical outcomes after systemic therapy. Methods: We applied an artificial neural network-based integrative data mining approach to three cohorts of patients with untreated lymph node (LN)-negative BC (Wang et al; n=286, Desmedt et al; n=198 and Schmidt et al; n=200). The results were validated in four cohorts of BC patients (the Nottingham discovery cohort (n=171), Uppsala cohort (n=249), The Cancer Genome Atlas-Breast Cancer project [TCGA-BRCA; n= 970] and Molecular Taxonomy of Breast Cancer International Consortium [METABRIC cohort; n=1980]. Genes that featured prominently in our interactome map of proliferation have been chosen to take them forward to investigate their clinicopathological relevance of their gene copy number aberrations (CNAs), mRNA transcript expression, and protein expression and their associations with breast cancer-specific survival (BCSS), distant relapse-free survival (DRFS) and pathological complete response (pCR) in ten international cohorts of BC (n>12000 patients). Findings: ESR1, SPAG5, EGFR, BCL2, and FOXA1 were among the 39 common gene probes that were predictive across most proliferation features and datasets. In TCGA-BRCA cohort, SPAG5 gene mutation, gain/amplification and loss at the Ch17q11.2 locus were detected in 43 (4.4%), 177 (18.2%) and 180 (18.8%) of 970 patients, respectively and 65 (31%) of 479 ER-positive /HER-positive patients showed gain/amplification of SPAG5 gene. In multivariable analysis, high SPAG5 transcript and SPAG5 protein expression were associated with reduced BCSS compared with lower expression (METABRIC: HR 1·27, 95% CI 1·02–1·58, p=0·034; untreated LN-negative cohort: 2·34, 1·24–4·42, p=0·0090; and Nottingham-cohort: 1·73, 1·23–2·46, p=0·0020). In patients with ER-negative/HER2-negative or ER-positive/HER2-negative BC, high SPAG5 transcript expression was associated with an increased pCR compared with low SPAG5 transcript expression after receiving anthracycline neoadjuvant chemotherapy (AC-NeoACT) [(Multicentre phase 2 clinical trial cohort; n=136; OR 2·47, 95% CI 1·17–5·21, p=0.016) and (MD Anderson- taxane+AC-NeoACT cohort; n=287; OR 3·16, 95% CI 1·46–6·84, p=0.003); respectively]. In patients with ER-positive/HER2-negative BC who received taxane+AC-NeoACT followed by adjuvant tamoxifen (Adj-Tam) for 5 years (MD Anderson- taxane+AC-NeoACT cohort; n=287), high and low SPAG5 transcript expression had similar DRFS (HR 1·40, 95% CI 0.76–2·58, p=0.282). Whereas in ER-positive/HER2-negative BC patients who received only adj-Tam (n=298), high SPAG5 transcript expression was associated with reduced DRF at 5 years compared with lower expression (HR 1.98, 95% CI 1.19–3.27, p=0.008). Interpretation: The transcript and protein products of SPAG5 are independent prognostic and predictive biomarkers that might have clinical utility as biomarkers for combination cytotoxic chemotherapy sensitivity in ER-positive/HER-negative BC. Citation Format: Abdel-Fatah TMA, Agarwal D, Zafeiris D, Pongor L, Györffy B, Rueda OM, Moseley PM, Green AR, Liu D-X, Pockley AG, Rees RC, Caldas C, Ellis IO, Ball GR, Chan SYT. Identification of proliferation related derivers and their roles in precision medicine for breast cancers: A retrospective multidimensional comparative, integrated genomic, transcriptomic, and protein analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-16.

Three fluoroperovskites with the general formula XCaF3 (X = K, Rb, Cs) have been systematically studied using the first-principles methods. The structural, electronic, optical, elastic and thermodynamic properties of these three compounds were calculated at the ambient and elevated hydrostatic pressure. Variation of all these properties with pressure was analyzed; it was shown that the structural and elastic constants change linearly with increased pressure, whereas the calculated band gaps follow the quadratic dependence on pressure. Influence of the first cation variation (K – Rb – Cs) on these properties was discussed. Elastic anisotropy (directional dependence of the Young moduli) of these compounds was modeled and analyzed for the first time.

Ras mutations and overexpression of the Ras protein, p21Ras, are main causes of cancer development and progression, which has made the Ras gene and p21Ras important targets for therapy of Ras-driven cancers. We previously prepared recombinant adenovirus KGHV100 based on replication-defective adenovirus type 5, which could intracellularly express anti-p21Ras single chain fragment viable antibodies (scFv) and repress tumor growth in vitro and in vivo. However, the anti-tumor effects of this anti-p21Ras scFv were limited by short-term scFv expression due to a replication defect of KGHV100. To enhance the anti-tumor efficacy and safety of anti-p21Ras scFv, the present study constructed a dual-promoter-regulated recombinant adenovirus KGHV300 that carried anti-p21Ras scFv. In KGHV300, the expression levels of the essential replication genes E1a and E1b, were controlled by the human telomerase reverse transcriptase promoter and the hypoxia response element, respectively, and the anti-p21Ras scFv gene was controlled by the cytomegalovirus promoter. The conditional replication of KGHV300 and its antitumor efficacy were characterized in several tumor cell lines in vitro and in xenograft models of human breast cancer in nude mice. TCID50 assay demonstrated that KGHV300 could replicate in tumor cell lines but not in normal cell lines. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay indicated that the growth of tumor cells was effectively inhibited by KGHV300 infection. In MDA-MB-231 tumor xenograft models, KGHV300 effectively and significantly inhibited tumor growth and induced apoptosis of tumor cells. We concluded that the recombinant adenovirus KGHV300 may be a more potent and safer antitumor therapeutic for Ras-driven cancer biotherapy.

The energy level diagrams are theoretically constructed for the di-, tri-, tetravalent lanthanide and actinide ions, using the Hartree–Fock calculated parameters of the Coulomb and spin–orbit interactions within f N ( N =1…13) electron configurations. These diagrams are analogous to Dieke's diagram, which was obtained experimentally. They can be used for an analysis of the optical spectra of all considered groups of ions in various environments. Systematic variation of some prominent energy levels (especially those ones with a potential for emission transitions) along the isoelectronic 4f/5f ions is considered.

For the first time the structural, elastic and bonding properties of 15 elpasolite crystals Cs 2 NaLnCl 6 (Ln denotes all lanthanides from La to Lu) were calculated systematically using the CRYSTAL09 program. Several trends in the variation of these properties in relation to the atomic number Z of the Ln ions were found; in particular, the lattice parameter of these compounds decreases with Z (which can lead to the increased crystal field splittings of the 5d states for the heavier Ln ions), whereas the elastic constants and Debye temperature increase. The degree of covalency of the Ln–Cl chemical bonds is increased toward the end of the lanthanide series.

Several alkaline earth sulfides doped with Eu2+ and Er3+ ions have been synthesized and shown to be potential phosphors for applications in the visible spectral range. The excitation and emission spectra corresponding to the 4f–5d interconfigurational transitions of Eu2+ were analyzed with an aim of extraction of the main parameters of the electron-vibrational interaction. The values of the Huang–Rhys factor, effective phonon energies, and zero-phonon line positions were systematically compared for all studied materials; physical trends were discussed. As a test for the validity of the obtained parameters, the Eu2+ 5d–4f emission bands were modeled to yield good agreement with the experimental spectra.

We present the first experimental evidence supported by simulations of kinetic effects launched in the interpenetration layer between the laser-driven hohlraum plasma bubbles and the corona plasma of the compressed pellet at the Shenguang-III prototype laser facility. Solid plastic capsules were coated with carbon-deuterium layers; as the implosion neutron yield is quenched, DD fusion yield from the corona plasma provides a direct measure of the kinetic effects inside the hohlraum. An anomalous large energy spread of the DD neutron signal (∼282 keV) and anomalous scaling of the neutron yield with the thickness of the carbon-deuterium layers cannot be explained by the hydrodynamic mechanisms. Instead, these results can be attributed to kinetic shocks that arise in the hohlraum-wall-ablator interpenetration region, which result in efficient acceleration of the deuterons (∼28.8 J, 0.45% of the total input laser energy). These studies provide novel insight into the interactions and dynamics of a vacuum hohlraum and near-vacuum hohlraum.

Two pairs of enantiomers, (−) and (+)-securidanes A ( 1 and 2 ) and B ( 3 and 4 ) featuring unprecedented triarylmethane (TAM) skeletons, were isolated from Securidaca inappendiculata . Their structures were established by spectroscopic data, X-ray crystallography, and CD analysis. A plausible biosynthetic pathway for 1 − 4 based on the co-isolated precursors was proposed. Bioinspired total synthesis of 1 − 4 was completed in high yield, which in turn corroborated the biosynthetic hypothesis. Compounds 1 − 4 showed good inhibition against protein tyrosine phosphatase 1B (PTP1B). The molecular docking demonstrated that the strongest inhibitor 3 (IC 50 = 7.52 μ M) reaches deeper into the binding pocket and has an additional H-bond.

This paper proposed a new general framework for intelligent optimization based on organizing tactics rather than probability rules. Compared with the existing intelligent optimization algorithms, like Particle Swarm Optimization, this framework has several significant advantages. First, the “intelligence” does not depend on the probability rules of the operators, but their organizing tactics. Thus there are no probability equations that need to be updated, and involved control parameters are fewer, so it is easier to use in practice. Second, synergistic coexistence and automatic balance of the exploration and the exploitation are achieved in the running. Third, population diversity has been kept during the running. Fourth, most useless and ineffective repetitious operations are avoided, and thus the needed consumption of storage space and running time are lessened largely.

To establish a method for the analysis of methcathinone in urine by gas chromatography-mass spectrometry （GC-MS）.Proadifen hydrochloride （internal standard） and buffer solution （pH=9） were added into the urine samples, and methcathinone was extracted by ethyl acetate. The extract was volatilized in 50 ℃ nitrogen gas flow and the remnant was dissolved by methanol and analysed by GC-MS.The methcathinone in urine showed a good linear relationship in the mass concentration range of 0.02-2.00 μg/mL. The linear equation wasThe method is convenient and sensitive, which can be applied to the forensic identification of methcathinone in urine.

During the crack propagation, crack tip contains stress odd singularity and has specific yield range. As the cycling loading continuing, the crack grows in the plastic zone. So the plastic zone is crucial to crack propagation action. In this paper, the crack propagation route was observed in different microstrctures, the deformation characteristic of plastic zone was analyzed for equiaxed structure and lamellar structure. The results show that crack propagation path is more straighter in equiaxed structure than that in lamellar structure. There were more tiny cracks near the crack surface in the lamellar structure during the crack growth, which shows that lamellar structure has a bigger plastic zone during the deformation.The plastic deformation need absorb the energy, which hinders the crack propagation.

Hot-mixed asphalt (HMA) concrete has been extensively used in the concrete box-girder bridge deck pavement due to its excellent performance and driving comfort. Nevertheless, during HMA concrete construction, the high paving temperature may disturb the thermal field of the bridge, thereby causing the significant thermal response throughout the box girder. Therefore, this research aims to investigate the temperature behavior and thermal stress of a reinforced concrete box girder segment during HMA concrete paving. The transient thermal field theory and element deletion method were first adopted to establish a three-dimensional finite element model of a reinforced concrete box girder segment and simulate the dynamic paving process, respectively. Subsequently, the bridge monitoring data was used to validate the thermal field model and then the temperature distribution analysis was conducted. Finally, the thermal stress in the bridge was studied in cross-sectional area. Results demonstrate that the vertical temperature of the concrete box-girder during the paving process is declined with the increasing vertical distance to SFRC leveling layer, and its highest value occurs at 36min after starting to paving. Furthermore, in the vertical direction, the west web-plate is subjected to compressive stress at locations of two ends and tensile stress at locations of the middle. Meanwhile, the thermal stresses undergo a decline trend after short-term growth both in the box and flange slab in the transversal direction.

Produced water from polymer flooding was much more difficult to be treated than that from water flooding. The mechanisms of polymer stabilizing the oil-in-water emulsion were the decreases of interfacial tension and electric conductivity, and the increases of zeta potential and bulk phase viscosity. Inorganic flocculant, the combination of inorganic flocculant and polymer degradation agent, and the combination organic flocculant and coagulant were used to break the oil-in-water emulsion stabilized with polymer. It was the most effective way to use the combination of organic flocculant and coagulant for treating polymer stabilizing oil-in-water emulsion.

To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations.In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015.As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study.INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

Toll-like receptor 3 (TLR3) mediates antiviral response by recognizing double-stranded RNA. Its cytoplasmic domain is tyrosine phosphorylated upon ligand binding and initiates downstream signaling via the adapter TIR-containing adaptor inducing interferon–β (TRIF). However, the kinase responsible for TLR3 phosphorylation remains unknown. We show here that Bruton's tyrosine kinase (BTK)-deficient macrophages failed to secrete inflammatory cytokines and IFN-β upon TLR3 stimulation and were impaired in clearing intracellular dengue virus infection. Mutant mice were also less susceptible to d -galactosamine/p(I:C)-induced sepsis. In the absence of BTK, TLR3-induced phosphoinositide 3-kinase (PI3K), AKT and MAPK signaling and activation of NFκB, IRF3, and AP-1 transcription factors were all defective. We demonstrate that BTK directly phosphorylates TLR3 and in particular the critical Tyr759 residue. BTK point mutations that abrogate or led to constitutive kinase activity have opposite effects on TLR3 phosphorylation. Loss of BTK also compromises the formation of the downstream TRIF/receptor-interacting protein 1 (RIP1)/TBK1 complex. Thus, BTK plays a critical role in initiating TLR3 signaling.

Ti/Mo and Cr/Mo metallic multilayer films with different periodicities were synthesised on a Ti–6Al–4V alloy surface by ion beam enhanced magnetron sputtering deposition process. The structure, bonding strength, microhardness and ductility of the multilayer films were measured. The effects of Ti/Mo and Cr/Mo metallic multilayer films on wear and fretting fatigue (FF) resistance of Ti–6Al–4V were studied. The results show that the wear resistance of Ti–6Al–4V alloy is improved by the Ti/Mo and Cr/Mo multilayer films which exhibit high density, fine grain, high bonding strength and obvious superhardness phenomenon. Ti/Mo multilayer films with a 200 nm periodicity exhibit strong adhesion, high hardness, good toughness and excellent fatigue resistance, which bring a 30% increase in FF life of Ti–6Al–4V alloy. However, Cr/Mo multilayer films have only a minor effect on the FF resistance of the Ti–6Al–4V alloy due to their high hardness and low ductility.

Coronavirus (CoV) 3C-like proteinase (3CLpro), located in nonstructural protein 5 (nsp5), processes the replicase polyproteins 1a and 1ab (pp1a and pp1ab) at 11 specific sites to produce 12 mature nonstructural proteins (nsp5 to nsp16). Structural and biochemical studies suggest that a conserved Gln residue at the P1 position is absolutely required for efficient cleavage. Here, we investigate the effects of amino acid substitution at the P1 position of 3CLpro cleavage sites of infectious bronchitis virus (IBV) on the cleavage efficiency and viral replication by in vitro cleavage assays and reverse genetic approaches. Our results demonstrated that a P1-Asn substitution at the nsp4-5/Q2779, nsp5-6/Q3086, nsp7-8/Q3462, nsp8-9/Q3672, and nsp9-10/Q3783 sites, a P1-Glu substitution at the nsp8-9/Q3672 site, and a P1-His substitution at the nsp15-16/Q6327 site were tolerated and allowed recovery of infectious mutant viruses, albeit with variable degrees of growth defects. In contrast, a P1-Asn substitution at the nsp6-7/Q3379, nsp12-13/Q4868, nsp13-14/Q5468, and nsp14-15/Q5989 sites, as well as a P1-Pro substitution at the nsp15-16/Q6327 site, abolished 3CLpro-mediated cleavage at the corresponding position and blocked the recovery of infectious viruses. Analysis of the effects of these lethal mutations on RNA synthesis suggested that processing intermediates, such as the nsp6-7, nsp12-13, nsp13-14, nsp14-15, and nsp15-16 precursors, may function in negative-stranded genomic RNA replication, whereas mature proteins may be required for subgenomic RNA (sgRNA) transcription. More interestingly, a mutant 3CLpro with either a P166S or P166L mutation was selected when an IBV infectious cDNA clone carrying the Q6327N mutation at the nsp15-16 site was introduced into cells. Either of the two mutations was proved to enhance significantly the 3CLpro-mediated cleavage efficiency at the nsp15-16 site with a P1-Asn substitution and compensate for the detrimental effects on recovery of infectious virus.

Manipulation of the coronavirus genome to accommodate and express foreign genes is an attractive approach for gene delivery and vaccine development. By using an infectious cloning system developed recently for the avian coronavirus infectious bronchitis virus (IBV), the enhanced green fluorescent protein (EGFP) gene, the firefly luciferase gene and several host and viral genes (eIF3f, SARS ORF6, Dengue virus 1 core protein gene) were inserted into various positions of the IBV genome, and the effects on gene expression, virus recovery, and stability in cell culture were studied. Selected viruses were also inoculated into chicken embryos for studies of foreign gene expression at different tissue level. The results demonstrated the stability of recombinant viruses depends on the intrinsic properties of the foreign gene itself as well as the position at which the foreign genes were inserted. For unstable viruses, the loss of expression of the inserted genes was found to result from a large deletion of the inserted gene and even IBV backbone sequences. This represents a promising system for development of coronavirus-based gene delivery vectors and vaccines against coronavirus and other viral infections in chicken.

The spike (S) protein of the coronavirus (CoV) infectious bronchitis virus (IBV) is cleaved into S1 and S2 subunits at the furin consensus motif RRFRR 537 /S in virus-infected cells. In this study, we observe that the S2 subunit of the IBV Beaudette strain is additionally cleaved at the second furin site (RRRR 690 /S) in cells expressing S constructs and in virus-infected cells. Detailed time course experiments showed that a peptide furin inhibitor, decanoyl-Arg-Val-Lys-Arg-chloromethylketone, blocked both viral entry and syncytium formation. Site-directed mutagenesis studies revealed that the S1/S2 cleavage by furin was not necessary for, but could promote, syncytium formation by and infectivity of IBV in Vero cells. In contrast, the second site is involved in the furin dependence of viral entry and syncytium formation. Mutations of the second site from furin-cleavable RRRR/S to non-furin-cleavable PRRRS and AAARS, respectively, abrogated the furin dependence of IBV entry. Instead, a yet-to-be-identified serine protease(s) was involved, as revealed by protease inhibitor studies. Furthermore, sequence analysis of CoV S proteins by multiple alignments showed conservation of an XXXR/S motif, cleavable by either furin or other trypsin-like proteases, at a position equivalent to the second IBV furin site. Taken together, these results suggest that proteolysis at a novel XXXR/S motif in the S2 subunit might be a common mechanism for the entry of CoV into cells.

The isothermal section of the Dy–Co–Ti system at 500 °C has been investigated in the whole composition range by means of X-ray diffraction, thermal analysis, scanning electron microscopy and energy dispersive X-ray spectroscopy. The only ternary phase DyTi x Co 12− x is of ThMn 12 -type structure, space group I 4/ mmm , and shows a small homogeneity range of 1 ≤ x ≤ 1.6. The lattice parameters for DyTi x Co 12− x with 1 ≤ x ≤ 1.56 are a = 0.8336(4)–0.8402(1) nm and c = 0.4691(3)–0.4727(1) nm. Along a constant Dy concentration, the solid solubilities of Ti in the compounds Dy 2 Co 17 , DyCo 3 , DyCo 2 and Dy 3 Co are about 2.0, 2.0, 3.0 and 4.0 at.%, respectively. The TiCo phase has a homogeneity range of 50–54 at.% Co at 500 °C and dissolves up to 2.0 at.% Dy.

Recently, a dengue virus-induced apoptosis p53- and mitochondria-mediated were reported in human and animal cells. To understand further the underlying mechanisms, a p53-deficient cell line, H1299, and a p53-knockin cell line, H273, were infected with dengue type 1 virus and the cellular gene expression profiles at the mRNA level were analyzed by affymetrix array analysis. The results showed 183 genes with at least twofold increase at mRNA expression level in dengue virus-infected cells. Among the 183 genes, 68 genes were up-regulated in both H1299 and H273 cells and 78 genes were found to be up-regulated in only H273 cells. Eleven selected genes, mainly involved in IFN-pathway, cell cycle, signal transduction, and ubiquitin-proteasome pathways were confirmed using qualitative and quantitative PCR. Interestingly, an approximately 32-fold increase in caspase-1 expression was observed in the p53-knockin cell line, H273. Gene silencing of caspase-1 or inhibition of caspase-1 activity led to reduction in dengue virus-induced apoptosis with minimal effect on virus replication.

The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM alpha-helical bundle. We have shown previously that the topology of the alpha-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM alpha-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric alpha-helical bundle model.

Viruses depend heavily on host cells for replication and exploit the host translation machinery for its gene expression using various unorthodox translation mechanisms. According to the conventional scanning model, only the 5'-proximal gene in the viral RNA is accessible to the ribosomes whereas other genes are silent. In this study, we use a model plant RNA virus, Hibiscus chlorotic ringspot virus (HCRSV), to investigate various translation mechanisms involved in regulation of the expression of internal genes. The 3'-end 1.2kb region of HCRSV genomic and subgenomic RNAs were shown to encode four polypeptides of 38, 27, 25 and 22.5kDa. Mutagenesis studies revealed that a CUG codon ((2570)CUG) is the initiation codon for p27, the longest of the three co-C-terminal products (p27, p25 and p22.5), and translation of p25 and p22.5 was initiated at (2603)AUG and (2666)AUG, respectively. Translation initiation of the p27 expression at the (2570)CUG codon regulates the expression of p38, the viral coat protein through a leaky scanning mechanism and mutational analysis of an upstream open reading frame (ORF) demonstrated that initiation of the p27 expression at this CUG codon (instead of an AUG) may play a role in maintaining the ratio of p27 and p38. In addition, a previously identified internal ribosome entry site was shown to control the expression of p27 and p38 in the subgenomic RNA 2.