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Currently, ursodeoxycholic acid (UDCA) is the only clear medical treatment for primary biliary cholangitis (PBC). However, approximately 40% of patients are not sensitive to UDCA. In recent years, obeticholic acid (OCA) combined with UDCA has been used in the PBC patients who were not sensitive to UDCA, or as monotherapy for PBC adult patients who are intolerant to UDCA. Objective To develop and validate a specific, sensitive and reliable tandem mass spectrometry (UPLC-MS/MS) method for the determination of obeticholic acid (OCA) in rat plasma. Methods Plasma samples were treated with liquid–liquid extraction. Diazepam was selected as the internal standard (IS). Chromatographic separation was achieved by an Acquity BEH C18 column (2.1 mm × 50 mm, 1.7 μm) and a mobile phase consisting of acetonitrile and ultrapure water (containing 0.1% formic acid). The analyte was detected in positive ion mode by electrospray ionization mass spectrometry (ESI-MS). Multiple reaction monitoring (MRM) methods were used to detect specific precursor and product ions. The target ion pair of OCA was 419.38 → 401.22, and the IS was 285.05 → 193.02. Results The linear range of OCA in rat plasma was 0.05–50 μg/mL (R2 = 0.992); the recovery rate was 91.34%–97.37%. This assay showed good intra- and inter-day precision and accuracy. No significant matrix effects in this study. Conclusion A specific, sensitive and reliable quantitative analysis method was established to detect OCA after oral/intravenous administration in rat plasma via UPLC-MS/MS. It was appropriate for preclinical pharmacokinetic studies of OCA.

Human astrovirus non-structural protein nsP1a/4, located at the C-terminal end of nsP1a, is thought to be involved in regulating RNA replication. Here, we show that host protein CD63 interacts with the nsP1a protein. Further research showed that the large loop (LEL) domain of CD63 also interacts with nsP1a/4. Confocal microscopy showed that nsP1a/4 protein and CD63 co-localized in the cytoplasm of co-transfected cells. Co-localization of nsP1a/4 and CD63 was also observed in HAstV-1-infected cells. Overexpression of CD63 promoted replication of HAstV-1, whereas knockdown of CD63 reduced production of HAstV-1 viral progeny. These results suggest that CD63 plays a critical role in HAstV-1 replication, and provide an avenue to further understanding the interactions between host and virus proteins during replication and pathogenesis of HAstV.

This article is concerned with an electromagnetically semi-permeable elliptical crack embedded in a multiferroic composite medium. The multiferroic composite medium is infinite and subjected to combined magneto-electro-elastic loads applied symmetrically at infinity. The boundary integro-differential equations associated with this nonlinear problem are solved analytically, with the aid of the generalized method of potential theory. The complete and closed-form coupling field is obtained and expressed with two elliptic functions. In addition, the crucial quantities on the crack plane, including the generalized crack surface displacements, the behavior of normal stresses in the crack-tip field and the generalized stress intensity factors, are derived explicitly. Numerical calculation and the finite element analyses for a BaTiO3-CoFe2O4 composite medium are performed to verify the present analytical results and to illustrate the important parameters on the crack plane graphically.

Researchers in the field of teacher knowledge have been attempting to delineate pedagogical content knowledge (PCK) in different subjects and different levels of education. To date, there is a need to develop a nuanced understanding on the PCK of Early Childhood Education (ECE) teachers who teach English as a foreign language (EFL). This study used a qualitative method, stimulated recall classroom observation, to investigate the categories and subcategories of PCK of Chinese EFL teachers from Chinese/English bilingual kindergartens in China. Two novice EFL teachers with less than 2 years of post-qualification teaching experience participated in this study. The data revealed three categories of PCK of ECE EFL teachers in the Chinese context: knowledge of curriculum, knowledge of learners, and knowledge of teaching strategies and multiple representations. Influenced by knowledge of curriculum, and knowledge of teaching strategies and multiple representations, the teachers had commonalities in classroom practice which were the product-oriented pedagogy and the textbook-led syllabus in the Chinese context. The study has several implications for research and practice for ECE EFL teacher education, especially for those practicing in the Chinese context.

International audience; A B S T R A C T Phased-mission systems (PMSs) are widely used, especially in the aerospace industry. As in the outer space there are many kinds of cosmic rays, such as the Galactic Cosmic Rays (GCR), randomly hitting on these systems and causing significant impact on the electronics inside or outside the equipment, a reliability model for PMSs considering both finite and infinite random shocks is proposed in this paper. The modularization method is used to simplify the state space model for each phase and reduce the amount of system states, and the Markov regenerative process (MRGP) is used to describe the hybrid components' lifetime distributions and the dynamic behaviors within the modules. Then, two kinds of scenarios, finite and infinite random shocks effect, are both integrated into the dynamic modules. For demonstration, a phased altitude and orbit control system (AOCS) subjected to infinite random shocks is illustrated to demonstrate the procedure of the proposed Monte Carlo simulation. Thirdly, the evaluated system reliability under infinite random shocks is compared with the same system without considering random shocks. At last, a sensitivity analysis is also provided for completion.

A nucleophile-catalyzed Michael addition/proton transfer/lactonization (NCMPL) organocascade process of chiral α,β-unsaturated acylammonium salts and indoline-2-thiones is described, which delivers the indolo[2,3-b]dihydrothiopyranone motifs in high yields (up to 97%) with good to excellent enantioselectivities (up to 98% ee).

Oceanic low level clouds strongly affect the atmospheric radiation budget. Uncertainties in their microphysical properties and cover currently limit the accuracy of climate predictions. Further, studies quantifying the relative importance of aerosol and dynamics on cloud properties in specific meteorological regimes are poorly constrained by observations in the Western North Atlantic boundary layer.Low level clouds were measured during the Aerosol Cloud meTereology Interactions oVer the western ATlantic Experiment (ACTIVATE) campaign in winter and summer 2020. The two NASA LaRC research aircraft HU-25 Falcon and UC-12 B-200 King Air conducted 35 simultaneous flights to investigate aerosol-cloud interactions of maritime clouds and their impact on radiation. Number concentration, liquid water content, ice water content, and particle size distribution in the size range of 3 µm to 1460 µm in diameter were measured with the fast forward scattering cloud probe (FCDP) and 2-dimensional optical array imaging probe (2D-S) onboard the Falcon. Here, we present an overview of late winter (February-March) and late summer (August-September) oceanic cloud properties in the region 65°W to 80°W and 30°N to 40°N. We compare cloud properties in these two seasons and investigate their dependence on meteorological parameters and aerosol abundance. In a case study, we present cloud observations in a cold air outbreak event on 1 March 2020 with a specific focus on mixed-phase clouds.

Glioblastoma (GBM) is the most common aggressive brain tumor and is associated with an extremely poor prognosis, as the current standard of care treatments have limited efficacy. Natural compounds have attracted increasing attention as potential anticancer drugs. Alantolactone (ATL) is a natural small molecule inhibitor, that has antitumor properties. In the present study, U87MG and U251 cells were treated ATL and changes in actin/G‑actin/F‑actin/cofilin pathway were detected in whole cells, in the cytoplasm and mitochondria by western blot analysis. Immunofluorescence and immunoprecipitation analysis identified changes in the expression levels of target proteins and interactions, respectively. A LIMK enzyme inhibitor was also applied to assess the effects of ATL on the migration and invasion of GBM cells. Flow cytometry was used to detect the levels of apoptosis of GBM cells. The expression of matrix metalloproteinase (MMP)‑2/MMP‑9, caspase‑3/caspase‑9/poly(ADP‑ribose) polymerase (PARP)/cytochrome c, were determined by western blot analysis to assess the effects of targeting LIMK. The in vitro findings were verified in vivo by characterizing changes in the expression of cofilin/LIMK in xenograft tumors in immunodeficient mice. It was found that ATL activated cofilin through the targeted inhibition of LIMK enzyme activity and it thus upregulated the ratio of G/F actin, and inhibited GBM cell migration and invasion. Conversely, the activation of cofilin and G‑actin could be co‑transferred to the mitochondria to initiate the mitochondrial‑cytochrome c pathway to induce apoptosis. On the whole, the findings of the present study further illustrate the molecular mechanisms through which ATL inhibits the metastatic phenotype of GBM cells and induces apoptosis. Given previous findings, it can be deduced that ATL can function through multiple pathways and has multiple targets in GBM models, highlighting its potential for use in clinical applications.

Background: Foaming in anaerobic digesters is considered a global concern due to significant impacts on process efficiency and operational costs. Although the importance of the organic loading rate on anaerobic foaming is now widely recognized, little is known about the key bacteria among the hundreds of species inducing foaming, especially the metabolite-microbiota correlation that influences foaming in anaerobic digesters.Results: Here, we show that the organic loading rate promotes foaming and decreases the performances of bench-scale batch digesters. Metabolomics analysis revealed distinct changes in the metabolic phenotype, including mainly short-chain fatty acids and amino acids, decreasing the surface tension and inducing foaming. Furthermore, the correlation analysis revealed that Clostridium clusters were the main microbes contributing to these metabolite foaming incidents.Conclusions: We provide the foaming microbes and metabolites in anaerobic digestion. Our findings elucidate the complex formation of foaming in anaerobic digestion and provide an effective early-warning for the control of foaming in full-scale digesters.

Valsartan is widely used for the treatment of moderate hypertension. However, previous studies have found that efficacy of the valsartan depends on the dose and intake. Cytochrome P450 (CYP) 2C9 metabolizes ∼15% of the clinical drugs. Genetic polymorphisms of CYP2C9 markedly affect the safety and effectiveness of many drugs, which might lead to adverse reactions and therapeutic failure. Twenty-four novel CYP2C9 variants (*36-*60) had been previously discovered via gene sequencing in the Han population. Our study aims to evaluate the impact of 38 CYP2C9 variants from the Chinese population on valsartan metabolism compared with CYP2C9*1 in vitro.Wild-type CYP2C9*1 and other CYP2C9 variants were expressed in Spodoptera frugiperda 21 insect cells. Incubations were performed at 37 °C with 20-2000 μM substrate for 30 min. The metabolite 4-OH valsartan was determined via UPLC-MS/MS.Among the 38 CYP2C9 variants, the enzymatic activities of most variants were significantly altered compared with the wild-type. Three variants (CYP2C9*27, *40 and *49) exhibited increased intrinsic clearance values (134-153% relative clearance). However, 12 variants (CYP *8, *13, *16, *19, *33, *36, *42, *43, *45, *52, *54, *58) caused90% decreases in the relative clearance of valsartan compared to CYP2C9*1.Our research provides systematic data for evaluating the effects of CYP2C9 variants on valsartan metabolism in the Chinese population. These results will expand our understanding of the impact of CYP2C9 genetic polymorphisms on valsartan metabolism and will contribute to precision medicine.

We show that the growth rate of dust grains in cold molecular clouds is enhanced by the high degree of compressibility of a turbulent, dilute gas. By means of high-resolution (10243) numerical simulations, we confirm the theory that the spatial mean growth rate is proportional to the gas-density variance. This also results in broadening of the grain-size distribution (GSD) due to turbulence-induced variation of the grain-growth rate. We show, for the first time in a detailed numerical simulation of hydrodynamic turbulence, that the GSD evolves toward a shape that is a reflection of the gas-density distribution, regardless of the initial distribution. That is, in case of isothermal, rotationally forced turbulence, the GSD tends to be a lognormal distribution. We also show that in hypersonic turbulence, decoupling of gas and dust becomes important and that this leads to an even further accelerated grain growth.

An outbreak of pneumonia named COVID-19 caused by a novel coronavirus in Wuhan is rapidly spreading worldwide. The objective of the present study was to clarify further the clinical characteristics and blood parameters in COVID-19 patients.Twenty-three suspected patients and 64 patients with laboratory-confirmed SARS-Cov-2 infection were admitted to a designated hospital. Epidemiological, clinical, laboratory, and treatment data were collected and analyzed.Of the 64 patients studied, 47 (73.4%) had been exposed to a confirmed source of COVID-19 transmission. On admission, the most common symptoms were fever (75%) and cough (76.6%). Twenty-eight (43.8%) COVID-19 patients showed leukopenia, 10 (15.6%) showed lymphopenia, 47 (73.4%) and 41 (64.1%) had elevated high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR), respectively, and 30 (46.9%) had increased fibrinogen concentration. After the treatment, the counts of white blood cells and platelets, and the level of prealbumin increased significantly, while aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and hsCRP decreased. COVID-19 patients with the hospital stay longer than 12 days had higher body mass index (BMI) and increased levels of AST, LDH, fibrinogen, hsCRP, and ESR.Results of blood tests have potential clinical value in COVID-19 patients.

To investigate the diagnostic value of contrast-enhanced three-dimensional (3D) T2-weighted turbo spin-echo SPACE (T2-SPACE) sequence in LNRC.A total of 90 surgically confirmed LNRC patients with 165 explored nerve roots were enrolled in this study. Diagnostic values were quantified using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. The consistency between 2D MRI and 3D T2-SPACE MRI was quantified using kappa test. The compression of specific branch in nerve root was evaluated on 2D MRI, 3D T2-SPACE MRI, and surgical findings. The pedicle height, vertebral body height (VH), proximal tilting angle of nerve root (PTA) were measured on MR images.The sensitivity, specificity, PPV, NPV, and accuracy by 2D MRI were 78.3%, 72.7%, 94.9%, 34.0%, and 77.6%, respectively. For 3D T2-SPACE MRI imaging, the sensitivity, specificity, PPV, NPV, and accuracy were 91.6%, 86.4%, 97.8%, 61.3%, and 90.9%, respectively. 2D MRI and 3D T2-SPACE MRI for detection of intra-foramen and extra-foramen nerve compression showed poor homogeneity (Kappa = 0.333, Kappa = 0.276, respectively). Smaller VHs and larger PTAs could be indicators for the diagnosis of foraminal nerve root compression.3D T2-SPACE MRI had a higher sensitivity, specificity, PPV, NPV, and accuracy than 2D MRI for detecting LNRC. The 3D T2-SPACE scan could be a good substitute to routine 2D MRI in LNRC diagnosis, especially for foraminal nerve root compression patients.III.

Background Coronavirus disease 2019 (COVID‐19) has become a worldwide public health emergency. This study aimed to investigate the clinical significance of liver blood tests in COVID‐19 patients. Methods The analysis included clinical data of 23 patients with suspected COVID‐19 and 66 patients with confirmed COVID‐19 from January 25 to February 20, 2020. The relationship between liver blood test results, liver condition (HBsAb positive, HBcAb positive, and fatty liver disease), and duration of hospital stay among COVID‐19 patients was analyzed. Results The median hospital stay of COVID‐19 patients was 6 days. Serum albumin (Alb) level was lower in patients with COVID‐19 confirmed on admission than in patients with suspected COVID‐19 (40.08 g/L vs 42.50 g/L, P = .016), while the level of aspartate aminotransferase (AST) was higher (23 U/L vs 18 U/L, P = .005). Abnormal results of liver blood tests in patients with COVID‐19 included increased levels of alanine transaminase (ALT) (21.2%, 14 patients), AST (15.2%, 10 patients), and gamma‐glutamyl transpeptidase (GGT) (22.7%, 15 patients). After 5‐10 days of treatment, levels of Alb and AST in COVID‐19 patients were significantly decreased (P .05). In addition, only levels of AST were positively correlated with the duration of hospital stay (r = .334, P = .007). Conclusion Abnormal results of the liver blood test were found in COVID‐19 patients. The COVID‐19 patients on admission with the higher levels of AST might have longer hospital stays.

The coronavirus disease (COVID-19) is currently prevalent worldwide. We analysed the occurrence of diarrhoea of these patients after treatment. All patients were treated with nebulised α-interferon and oral administration of Lopinavir/Ritonavir tablets. Of the 62 patients, 38 (61.3%) developed diarrhoea after treatment. Of these 38 cases, 63.2% (24/38 cases) had their first diarrhoea within 24 hours after medication. Only 13.2% (5/38 cases) had more than 5 bowel movements per day with a maximum of 10 per day. Patients with diarrhoea had lower white blood cell counts. Leukopenia was a risk factor for the development of diarrhoea. We conclude that COVID-19 patients had a relatively high rate of diarrhoea after treatment. Lopinavir/Ritonavir was speculated to contribute to diarrhea, which is a common adverse drug reaction to Lopinavir/Ritonavir. Patients with reduced white blood cell counts at admission may be more likely to develop diarrhoea after admission.

Coagulation driven by supersonic turbulence is primarily an astrophysical problem because coagulation processes on Earth are normally associated with incompressible fluid flows at low Mach numbers, while dust aggregation in the interstellar medium for instance is an example of the opposite regime. We study coagulation of inertial particles in compressible turbulence using high-resolution direct and shock-capturing numerical simulations with a wide range of Mach numbers from nearly incompressible to moderately supersonic. The particle dynamics is simulated by representative particles and the effects on the size distribution and coagulation rate due to increasing Mach number is explored. We show that the time evolution of particle size distribution mainly depends on the compressibility (Mach number). We find that the average coagulation kernel ⟨Cij⟩ scales linearly with the average Mach number ℳrms multiplied by the combined size of the colliding particles, that is, 〈Cij〉∼〈(ai+aj)3〉 ℳrmsτη−1, which is qualitatively consistent with expectations from analytical estimates. A quantitative correction 〈Cij〉∼〈(ai+aj)3〉(vp,rms/cs)τη−1 is proposed and can serve as a benchmark for future studies. We argue that the coagulation rate ⟨Rc⟩ is also enhanced by compressibility-induced compaction of particles.

As a common chronic respiratory disease, the incidence of asthma is increasing in recent years worldwide. Airway remodeling is the primary pathological basis of refractory asthma, but the studies about the underlying mechanism of airway remodeling was a lack. In the study, we aimed to investigate the effects and mechanisms of miR‐326 on airway remodeling in airway smooth muscle cells (ASMCs). The results showed that transforming growth factor‐β1 (TGF‐β1) accelerated matrix protein deposition by increasing the expression levels of collagen I and fibronectin, and promoted proliferative ability of ASMCs. However, miR‐326 was significantly downregulated in TGF‐β1‐treated ASMCs. MiR‐326 mimics robustly decreased the collagen I and fibronectin levels and inhibited cell proliferation of TGF‐β1‐treated ASMCs. Luciferase assay investigated that tumor necrosis factor superfamily member 14 (TNFSF14) was a direct target of miR‐326. The expression of TNFSF14 was negatively regulated by miR‐326. Moreover, exogenous TNFSF14 effectively reversed the inhibitory effects of miR‐326 overexpression on the expression levels of collagen I and fibronectin, and promoted cell proliferation of TGF‐β1‐treated ASMCs. In conclusion, miR‐326 suppressed matrix protein deposition and cell proliferation of TGF‐β1‐treated ASMCs via inhibiting TNFSF14. MiR‐326 might be a promising novel therapeutic target for asthma.

Phased mission systems (PMSs) have wide applications in engineering practices, especially in aerospace industry such as man-made satellite and spacecraft. To achieve high reliability in a PMS, certain critical parts in the system are designed to have a redundant architecture, such as cold standby (structural or functional). State-space models such as Markov processes have been widely used in previous studies to evaluate the reliabilities of these systems. But in practice, many real systems consist of mechanical components or mechatronics whose lifetime follow non-exponential distributions like the Weibull distribution. In this type of system, the Markov process is not capable of modeling the system behavior. In this paper, the SMP (Semi-Markov Process) is applied to solve the problem that the components’ lifetime in dynamic systems follows non-exponential distributions. An approximation algorithm for the SMP is proposed to assess the reliability of the PMSs consisting of non-exponential components. Furthermore, the accuracy and calculation efficiency of the approximation algorithm are explored. At last, the reliability assessment of a complex multi-phased altitude and orbit control system (AOCS) in a man-made satellite is presented to illustrate the method.

This work aims to study the free and forced transverse vibrations of a nanowire on elastic substrate, in a systematic way. To this end, the governing equations are obtained from an updated mechanical model integrating the effects of surface and elastic substrate. The Winkler, Pasternak and Generalized substrate models are taken into consideration to characterize various substrates. The characteristic equations, mode shapes and effective Young’s moduli are determined for nanowires with three typical boundary conditions: simply supported, clamped-clamped and clamped-free. The Laplace transform is employed to derive the exact solutions for forced vibrations of the three typical nanowires. Numerical calculations are performed to validate the proposed solutions and to analyze the effects of surface and elastic substrates on the free and forced vibrations.

Cu(I)-Catalyzed diastereoselective carboboration of α-alkyl-substituted α,β-unsaturated carboxylic esters to produce β-boryl-α-quaternary carbon esters was developed. The carbon skeletons of dialkyl sulfates, primary allyl halides, and benzyl bromides were transferred to the α-position of the substrates to provide products in moderate to good yields with a diastereoselectivity of >95% in most cases. Substrates bearing a β-(hetero)aryl substituent gave higher diastereoselectivities than those bearing a linear β-alkyl substituent. The crystal structure of the potassium trifluoroborate derivative shows that the reactions probably go through a copper(I) enolate intermediate and the diastereoselectivity arises from the electrophilic attack of electrophiles to the less hindered side of the enolates.

Background TMEM16A is a critical component of Ca2+-activated chloride channels (CaCCs) and mediates basilar arterial smooth muscle cell (BASMC) proliferation in hypertensive cerebrovascular remodeling. CaMKII is a negative regulator of CaCC, and four CaMKII isoforms (α, β, γ and δ) are expressed in vasculature; however, it is unknown which and how CaMKII isoforms affect TMEM16A-associated CaCC and BASMC proliferation.Methods and Results:Patch clamp and small interfering RNA (siRNA) knockdown of different CaMKII isoforms revealed that only CaMKIIγ inhibited native Ca2+-activated chloride currents (ICl.Ca) in BASMCs. The TMEM16A overexpression evoked TMEM16A Cl-current and inhibited angiotensin II (Ang II)-induced proliferation in BASMCs. The co-immunoprecipitation and pull-down assay indicated an interaction between CaMKIIγ and TMEM16A protein. TMEM16A Cl-current was modulated by CaMKIIγ phosphorylation at serine residues in TMEM16A. Serine525 and Serine727 in TMEM16A were mutated to alanine, and only mutation at Ser727 (S727A) reversed the CaMKIIγ inhibition of the TMEM16A Cl-current. Phosphomimetic mutation S727D markedly decreased TMEM16A Cl-current and reversed TMEM16A-mediated suppression of BASMC proliferation, mimicking the inhibitory effects of CaMKIIγ on TMEM16A. A significant increase in CaMKIIγ isoform content was observed in parallel to the decrease of TMEM16A and ICl.Cain basilar artery proliferative remodeling in Ang II-infused mice. Conclusions Serine 727 phosphorylation in TMEM16A by CaMKIIγ provides a new mechanism for regulating TMEM16A CaCC activity and Ang II-induced BASMC proliferation.

Nucleic acid oxidation plays an important role in the pathophysiology progress of a variety of diseases. 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn) and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), which originate from DNA and RNA oxidation, were the most widely used indicators for oxidative stress. The study investigated the relation between 8-oxo-dGsn, 8-oxo-Gsn, and CKD. 146 patients with CKD were divided into five disease stages, and their fasting blood and morning urine were collected. The levels of 8-oxo-dGsn and 8-oxo-Gsn in plasma and urine were quantified by LC-MS/MS. The ratio of urinary 8-oxo-Gsn to creatinine increased from stages 1 to 4 corresponding to the increased severity of CKD, but it decreased in stage 5. And plasma 8-oxo-Gsn gradually increased with the decline of renal function. In particular, the increased ratio of plasma and urine 8-oxo-Gsn in stage 5 exceeded the concentration of creatinine. This trend was similar to the estimated glomerular filtration rate (eGFR), which indicates that 8-oxo-Gsn could be an appropriate indicator for renal function. Our finding indicates that as the disease progresses, RNA oxidation is increased. The significant increase in the ratio of plasma and urinary 8-oxo-Gsn is a novel evaluation index of end-stage renal disease.

Coleoptera are visible members of food webs in tea plantations, with high species richness and abundance. Many tea pests, as well as natural enemies, are members of this order, so a knowledge of how groundcovers affect beetles can aid pest management. We collected beetles in a replicated field experiment in the Wuyi Mountains, Fujian Province, China. Tea was intercropped with Paspalum notatum or Chamaecrista rotundifolia, or rows were cleared to bare ground, or in the control they were left unmanaged to allow weeds to grow naturally. Sampling, done by sweep netting and vegetation beating, was conducted monthly, between May 2006 and April 2008, and Coleoptera abundance, biomass, species richness and assemblage structures were compared between groundcover treatments. Total beetle abundance and species richness were significantly higher in tea intercropped with C. rotundifolia and bare ground than in naturally grown weedy control. Whilst there was no difference between predator assemblages among treatments for any measure, herbivores were more abundant, weighed more, and were more diverse in C. rotundifolia treatments than in weedy control. Biomass and species richness were also greater in plots with P. notatum groundcover than those in weedy control. We found that beetle assemblages varied both seasonally and with ground cover treatment, but the potential pest control impact of more species-rich beetle assemblages was mixed, and further work is needed to gain information on trophic groups with potential benefits for use in non-insecticidal pest management. This work was supported by the National Natural Science Foundation of China (No. 31501650), National Key R & D Program of China (No. 2016YFD0200900), Fujian Agriculture and Forestry University Construction Project for Technological Innovation and Service System of Tea Industry Chain (No. K1520005 A03), Fujian Spark Program (No. 2018S0019), “111” Program: Innovation Center for Ecologically Based Pest Management of Subtropical Crops (No. D16012). info:eu-repo/semantics/publishedVersion

Recently, phased mission systems (PMSs) have been widely studied due to their wide range of applications, such as man-made satellites or spacecraft. The lifetime of the PMSs can be separated into several phases, in which their tasks, system configurations, and failure criteria could be different. Meanwhile, the randomly occurred shocks, such as the space radiation from outer space, will cause additional wear and fatal damage on the electronic devices in these systems, which will obviously affect the system reliability. To consider these shocks’ effect in the reliability modeling of the PMSs, a Markov regenerative process (MRGP) based model is proposed in this paper. Firstly, shock models for components and the basic conceptions of MRGP are introduced. Then, a simple cold standby system is used to show the proposed MRGP model for systems under mixed shocks. And a Monte Carlo simulation procedure is applied to verify the results. At last, by integrating the proposed MRGP model and the modular method for PMSs, the reliability of an AOCS in a spacecraft is assessed to show the proposed method.

The saturated reactor is used in the DC converter valve to protect thyristors. A fluid-solid coupling heat dissipation model was established for the saturated reactor in this study, which included water cooling, heat conduction, heat convection and heat radiation. By the means of finite element method, the temperature and flow field distribution were calculated, which indicated that the low thermal conductivity of epoxy resin hinders the heat dissipation of the saturated reactor. To research effects of thermal conductivity on heat dissipation, the heat dissipation performance of saturated reactor with different epoxy resins was numerical simulated by using this model. The results showed that the heat dissipation performance of the saturated reactor can be effectively improved by the rise of the thermal conductivity of epoxy resin, but the marginal benefit of increasing the thermal conductivity of epoxy resin is gradually reduced. Meanwhile, high-thermal conductivity epoxy resin could have the longer service life under the same operation conditions.

Fragile X syndrome (FXS) is the most frequently inherited form of intellectual disability and prevalent single-gene cause of autism. A priority of FXS research is to determine the molecular mechanisms underlying the cognitive and social functioning impairments in humans and the FXS mouse model. Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate a majority of fast excitatory neurotransmission in the central nervous system and are critically important for nearly all aspects of brain function, including neuronal development, synaptic plasticity, and learning and memory. Both preclinical and clinical studies have indicated that expression, trafficking, and functions of AMPARs are altered and result in altered synapse development and plasticity, cognitive impairment, and poor mental health in FXS. In this review, we discuss the contribution of AMPARs to disorders of FXS by highlighting recent research advances with a specific focus on change in AMPARs expression, trafficking, and dependent synaptic plasticity. Since changes in synaptic strength underlie the basis of learning, development, and disease, we suggest that the current knowledge base of AMPARs has reached a unique point to permit a comprehensive re-evaluation of their roles in FXS.

This paper investigates the problem of an infinite multiferroic composite medium weakened by a penny-shaped crack, which is symmetrically subjected to four pairs of generalized loads on the upper and lower surfaces. These loads could be mechanical pressures, electric displacements, magnetic inductions and temperature increments. In view of the magneto-electric properties of the crack surfaces, four mixed boundary problems are formulated. Based on the general solution, the three-dimensional thermo-magneto-electro-elastic coupling field variables in the three-dimensional full space for various boundary cases are explicitly obtained by means of the generalized potential theory method. Some important physical quantities in fracture mechanics, such as the generalized stress intensity factors and the generalized crack surface displacements, are presented as well. Numerical calculations are performed to validate the present solutions and to show the distributions of the 3D coupled fields. The influences of the magneto-electric properties of the crack surfaces on the generalized stresses and stress intensity factors are revealed.

A highly efficient chiral amidine derivative-catalyzed tandem Michael addition/lactonization of carboxylic acids and o-quinone methides (o-QMs) has been developed that enables the asymmetric synthesis of cis-3,4-dihydrocoumarins bearing contiguous tertiary stereogenic centers in high yields with excellent stereoselectivities.

The performance of the up-flow anaerobic sludge blanket (UASB) is significantly governed by the hydrodynamics of the reactor. Though the influence of hydrodynamics on mass transfer, granular size distribution, and biogas production was well studied, the interaction between biogas bubbles and anaerobic granular sludge (AGS) is poorly understood. This study used the impinging-jet technique and bubble probe atomic force microscope (AFM) to investigate the attachment and adhesion force between biogas bubbles (CH4 and CO2) and AGS. The fluxes of normalized CH4 or CO2 bubble-attachment on two kinds of AGS were directly affected by gas velocity and decreased with an increase in the Reynolds number ranged from 40 to 140. The bubble-attachment had a positive linear relationship with the contact angles, ratio of exopolymeric protein and polysaccharide, and hydrophilic functional groups of AGS. A bubble probe AFM was used to explore the adhesion force between a single bubble and AGS. The results indicated that the adhesion force between the bubbles and the two kinds of AGS also decreased with increasing approach velocity. Overall, these results contribute to a new insight into the understanding of interaction between biogas bubbles and AGS in UASB reactors.

Rationale: Transmembrane member 16A (TMEM16A) is a component of calcium-activated chloride channels that regulate vascular smooth muscle cell (SMC) proliferation and remodeling. Autophagy, a highly conserved cellular catabolic process in eukaryotes, exerts important physiological functions in vascular SMCs. In the current study, we investigated the relationship between TMEM16A and autophagy during vascular remodeling. Methods: We generated a transgenic mouse that overexpresses TMEM16A specifically in vascular SMCs to verify the role of TMEM16A in vascular remodeling. Techniques employed included immunofluorescence, electron microscopy, co-immunoprecipitation, and Western blotting. Results: Autophagy was activated in aortas from angiotensin II (AngII)-induced hypertensive mice with decreased TMEM16A expression. The numbers of light chain 3B (LC3B)-positive puncta in aortas correlated with the medial cross-sectional aorta areas and TMEM16A expression during hypertension. SMC-specific TMEM16A overexpression markedly inhibited AngII-induced autophagy in mouse aortas. Moreover, in mouse aortic SMCs (MASMCs), AngII-induced autophagosome formation and autophagic flux were blocked by TMEM16A upregulation and were promoted by TMEM16A knockdown. The effect of TMEM16A on autophagy was independent of the mTOR pathway, but was associated with reduced kinase activity of the vacuolar protein sorting 34 (VPS34) enzyme. Overexpression of VPS34 attenuated the effect of TMEM16A overexpression on MASMC proliferation, while the effect of TMEM16A downregulation was abrogated by a VPS34 inhibitor. Further, co-immunoprecipitation assays revealed that TMEM16A interacts with p62. TMEM16A overexpression inhibited AngII-induced p62-Bcl-2 binding and enhanced Bcl-2-Beclin-1 interactions, leading to suppression of Beclin-1/VPS34 complex formation. However, TMEM16A downregulation showed the opposite effects. Conclusion: TMEM16A regulates the four-way interaction between p62, Bcl-2, Beclin-1, and VPS34, and coordinately prevents vascular autophagy and remodeling.

The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays an important role in apoptosis, metastasis, and proliferation and is recognized as an important potential therapeutic target for cancer. Six series of 3(5)-(6-methylpyridin-2-yl)-4-(quinolin-4-yl)pyrazoles (11a-d, 12a-d, and 18a-d) and 3(5)-(6-methylpyridin-2-yl)-4-(2-phenyl-pyridin-4-yl)pyrazoles (19a-d, 20a-d, and 21a-d) were synthesized and evaluated for activin receptor-like kinase 5 (ALK5) and HIF-1α inhibitory activity at the enzyme and cell levels. The effect of the lead compound 20d (J-1012) on HIF-1α activation in HCT116 cells was investigated. J-1012 markedly decreased the hypoxia-induced or TNF-induced accumulation of HIF-1α protein dose-dependently. Analysis revealed that J-1012 inhibited HIF-1α protein synthesis, without affecting the degradation of HIF-1α protein. Furthermore, by inhibiting the activation of HIF-1α, J-1012 suppressed the metastasis and proliferation and promoted apoptosis of HCT116 cells. These results suggest that J-1012 may be a potential therapeutic agent against human colon cancer.

User authentication for an accurate biometric system is the demand of the hour in today’s world. When somebody attempts to take on the appearance of another person by introducing a phony face or video before the face detection camera and gets illegitimate access, a face presentation attack usually happens. To effectively protect the privacy of a person, it is very critical to build a face authentication and anti-spoofing system. This paper introduces a novel and appealing face spoof detection technique, which is primarily based on the study of contrast and dynamic texture features of both seized and spoofed photos. Valid identification of photo spoofing is anticipated here. A modified version of the DoG filtering method, and local binary pattern variance (LBPV) based technique, which is invariant to rotation, are designated to be used in this paper. Support vector machine (SVM) is used when feature vectors are extracted for further analysis. The publicly available NUAA photo-imposter database is adapted to test the system, which includes facial images with different illumination and area. The accuracy of the method can be assessed using the false acceptance rate (FAR) and false rejection rate (FRR). The results express that our method performs better on key indices compared to other state-of-the-art techniques following the provided evaluation protocols tested on a similar dataset.

In modern industry, engineered systems are generally required to work under complex operational conditions to complete specific missions. But most of existing data-driven prognostic methods still lack an effective model that can utilize operational conditions data to predict remaining useful life (RUL) of engineered systems. To fill these practical gaps, this paper develops a novel prognostic method based on Bi-Directional Long Short-Term Memory (BLSTM) network. The proposed method can effectively integrate multiple sensors data with operational conditions data for RUL prediction of engineered systems. In the proposed prognostic framework, multiple raw sensors data, operational conditions data, and inspection time epoch are preprocessed to form the desired sequences data with fixed length, and then are taken as main inputs and auxiliary inputs to fed into proposed BLSTM based network. And the labeled RUL are used as actual output for training the proposed model. Different from other deep learning (DL) based prognostic methods, the developed method can simultaneously model both sensors data and operational conditions data in a consolidated framework. The proposed approach is validated through a case study on aircraft turbofan engine, and comparisons with other existing state-of-the-art methods are also included.

The effect of path loss on the reliability of wireless communication in Military C4ISR (Command, Control, Communication, computer, Intelligence, Surveillance and Reconnaissance) Architectures has drawn much attention. Previous work were focused on the reliability assessment of infrastructure, but its link reliability has not been fully considered. This paper puts forward a new method for the reliability assessment of the C4ISR communication through the analysis of the traditional suburban Millimeter Waves (MMW) path loss models. To evaluate the effects of the path loss on the link reliability, we used the lognormal distribution to fit the random distribution curve of the communication distance. Derived by formula, the PDF (Probability Distribution Function) and the CDF (Cumulative Distribution Function) of the path loss value on different communication distance have been obtained. Finally, the C4ISR communication reliability at different frequencies are calculated based on the threshold of the path loss value. The advantage of this method is that it can reflect the effects of the environmental factors and carrier frequency on the reliability of the C4ISR wireless communication.

The transforming growth factor-&beta, (TGF-&beta, ), in which overexpression has been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Thirty-two quinoxaline-derivatives of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a&ndash, d, 15a&ndash, d, 16a&ndash, d, 17a&ndash, d, 18a&ndash, d, 19a&ndash, d, 25a, 25b, 25d, 26a, 26b, 26d, 27b, and 27d were synthesized and evaluated for their activin TGF-&beta, type I receptor kinase and p38&alpha, mitogen activated protein (MAP) kinase inhibitory activity in enzymatic assays. Among these compounds, the most active compound 19b inhibited TGF-&beta, type I receptor kinase phosphorylation with an IC50 value of 0.28 &micro, M, with 98% inhibition at 10 &micro, M. Compound 19b also had good selectivity index of &gt, 35 against p38&alpha, MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). A molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.