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Heavy metals contamination is a serious problem of China. It is necessary to estimate bioavailability concentrations of heavy metals in agricultural soil for keeping the food security and human health. This study aimed to use hyperspectral data of rice (Oryza sativa) leaves as an indicator to retrieve the CaCl2-extractable concentrations of heavy metals in agricultural soil. Twenty-one rice samples, soil samples and reflectance spectra of rice leaves were collected, respectively. The potential relations between hyperspectral data and CaCl2-extractable heavy metals (E-HM) were explored. The partial least-squares regression (PLSR) method with leave-one-out cross-validation has been used to predict concentrations of CaCl2-extractable cadmium (E-Cd) and concentrations of CaCl2-extractable lead (E-Pb) in farmland soil. The results showed that the concentrations of E-Cd in soil had significant correlation with concentrations of Cd in rice leaves; the number of bands associated with E-Cd was more than that of E-Pb. Four indices (normalized difference vegetation index (NDVI), carotenoid reflectance index (CRI), photochemical reflectance index 2 (PRI2), normalized pigments chlorophyll ratio index (NPCI)) were significant (P R2 = 0.592 and RMSE = 0.046. We conclude that if the rice was sensitive to E-HM and/or the crop was stressed by the E-HM, the hyperspectral data of field rice leaves hold potentials in estimating concentration of E-HM in farmland soil. Therefore, this method provides a new insight to monitoring the E-HM content in agricultural soil.

As the most primordial signaling pathway in animal physiology, the Hippo pathway and innate immunity play crucial roles not only in sensing cellular conditions or infections, but also in various metabolite homeostasis and tumorigenesis. However, the correlation between cellular homeostasis and antiviral defense is not well understood. The core kinase LATS1/2, could either enhance or inhibit the anti-tumor immunity in different cellular contexts. In this study, we found that LATS2 can interact with PQBP1, the co-factor of cGAS, thus enhanced the cGAS-STING mediated innate immune response to HIV-1 challenge. LATS2 was observed to upregulate type-I interferon (IFN-I) and cytokines in response to HIV-1 reverse-transcribed DNA and inhibited HIV-1 infection. Due to the involvement of PQBP1, the function of LATS2 in regulating cGAS activity is not relying on the downstream YAP/TAZ as that in the canonical Hippo pathway. The related kinase activity of LATS2 was verified, and the potential phosphorylation site of PQBP1 was identified. Our study established a novel connection between Hippo signaling and innate immunity, thus may provide new potential intervention target on antiviral therapeutics.

Thermochemical conversion technology for the resource utilization of biomass can not only treat wastes polluting the environment but also efficiently generate hydrogen-rich gas for industrial appli...

The melting-flesh peach (Prunus persica, cv. 'Baihua') tends to rapidly decay after harvest in summer with a short after-ripening period. Although the use of preservatives can inhibit the growth of microorganisms, collisions during transportation greatly affect the shelf life for subsequent sales. To build a high-accuracy model to predict the inner physiological status of mechanically injured peaches during postharvest storage, visible/shortwave near-infrared (Vis/SWNIR) diffuse reflection spectra (300–1150 nm) were acquired for analysis. With 840 samples, two drop heights (30 cm and 60 cm) were applied to study the variations in total soluble solids (TSS) polyphenol oxidase (PPO), malondialdehyde (MDA) and relative electrolyte leakage (REL) by percussive tests. After multiplicative scatter correction and Savitzky-Golay smoothing pretreatments, optimal feature selections from a total of 1024 wavelengths were determined using genetic algorithm (GA) in PLS modeling. For TSS, the best correlation (rp) is 0.89, root mean square error of prediction (RMSEP) is 0.40 and relative percent deviation (RPD) is 2.94. For PPO, the best rp is 0.71, RMSEP is 20.34 and RPD is 2.75. For MDA, the best rp is 0.83, RMSEP is 0.17 and RPD is 1.90. For REL, the best rp is 0.92, RMSEP is 1.42 and RPD is 2.44. Through several verifications, the GA-PLS models showed good imitative effects and high precisions. They could predict the condition of peaches with minor injury, which are difficult to detect with the naked eye, to reduce loss in practical production.

The molybdenum cofactor, composed of molybdopterin and molybdenum, is a necessary compound for the catalytic activity of molybdenum enzymes. Molybdenum cofactor biosynthesis is a conserved multi-step process involving several enzymes. Molybdopterin synthase, a hetero-tetrameric enzyme composed of a pair of MoaE-MoaD subunits, catalyzes the generation of the cis-dithiolene group of molybdopterin in the second step of the process. The cis-dithiolene group can covalently bind molybdenum. Most mycobacterial species possess several genes encoding the full pathway of molybdenum cofactor biosynthesis. In M. smegmatis, the moaD2 and moaE2 genes encode the functional molybdopterin synthase. However, M. tuberculosis has genes encoding several molybdopterin synthase subunit homologs, including moaD1, moaD2, moaE1, moaE2, and moaX, which encodes a MoaD-MoaE fusion protein. Previous studies have shown that moaD2 and moaE2 encode functional molybdopterin synthase. Here, we report the crystal structures of two substrate-free molybdopterin synthases from two different mycobacterial pathogens, M. tuberculosis and M. smegmatis, at 2.1 A and 2.6 A resolutions, respectively. The overall structure of both molybdopterin synthases was hetero-tetrameric, consisting of a MoaE2 dimer flanked on either side by single MoaD2 subunits. The carboxyl-terminal domain of MoaD2 inserted into MoaE2, forming the active pocket. A comparison with previously reported molybdopterin synthase structures showed that substrate-binding and catalytic residues were conserved, despite low sequence similarity among these enzymes. The low sequence identity at the MoaE-MoaD heterodimer interface may provide the structural basis to explore mycobacterial inhibitors.

Argininosuccinate lyase (ASL) participates in arginine synthesis through catalysing a reversible reaction in which argininosuccinate (AS) converts into arginine and fumarate. ASL from Mycobacterium tuberculosis is essential for its growth. In this work, the crystal structure of the apo form of MtbASL was determined and reveals a tetrameric structure that is essential for its activity since the active sites are formed by residues from three different monomers. Subsequently, we determined the crystal structure of MtbASL-sulfate complex, and the ligand mimics the negatively charged intermediate. The complex structure and mutagenesis studies indicate that residues S282 and H161 might act as a catalytic dyad. A major conformational change in the MtbASL-SO4 complex structure could be observed upon sulfate binding, and this movement facilitates the interaction between substrate and the residues involved in catalysis. A different conformational change in the C-terminal domain could be observed in the MtbASL-SO4 complex compared with that in other homologues. This difference may be responsible for the lower activity of MtbASL, which is related to the slow growth rate of M. tuberculosis. The C-terminal domain is a potential allosteric site upon inhibitor binding. The various conformational changes and the diversity of the sequence of the potential allosteric site across the homologues might provide clues for designing selective inhibitors against M. tuberculosis.

Cadmium (Cd) contaminated rice has become a global food security issue. Hyperspectral remote sensing can do rapid and nondestructive monitoring of environmental stress in plant. To realize the nondestructive detection of Cd in brown rice before harvest, the leaf spectral reflectance of rice exposed to six different levels of Cd stress was measured during the whole life stages. In addition, the dry weight of rice grain and Cd concentrations in brown rice were measured after harvest. The impact of Cd stress on the quantity and the quality of rice grain and on the leaf reflectance of rice was analyzed, and hyperspectral estimation models for predicting the Cd content in brown rice during three growth stages were established. The results showed that rice plants can impact the quality of the brown rice seriously, even if the impact on the quantity was not significant. All the established models had the capability to estimate Cd concentrations in brown rice (R2 > 0.598), and the best performance model, with the R2 value of 0.873, was use first derivative spectrum of booting stage as variable. It was concluded that the hyperspectral of rice leaves provides a new insight to predict Cd concentration in brown rice before harvest.

Background Waist circumference is becoming recognized as a useful predictor of health risks in clinical research. However, clinical datasets tend to lack this measurement and self-reported values tend to be inaccurate. Predicting waist circumference from standard physical features could be a viable method for generating this information when it is missing or mitigating the impact of inaccurate self-reports. This study determined the degree to which the XGBoost advanced machine learning algorithm could build models that predict waist circumference from height, weight, calculated Body Mass Index, age, race/ethnicity and sex, whether they perform better than current models based on linear regression, and the relative importance of each feature in this prediction. Methods We trained tree-based models (via XGBoost gradient boosting) and linear models (via regression) to predict waist circumference from height, weight, Body Mass Index, age, race/ethnicity and sex (n = 60,740 participants). We created 10 iterations of each model, each using 90% of the dataset for training and the remaining 10% for testing performance (this group was different for each iteration). We calculated model performance and feature importance as an average across 10 iterations. We then externally validated the ensembled version of the top model. Results The XGBoost model predicted waist circumference with a mean bias ± standard deviation of 0.0 ± 0.04 cm and a root mean squared error of 4.7 ± 0.05 cm, with performance varying slightly by sex and race/ethnicity. The XGBoost model showed varying degrees of improvement over linear regression models. The top 3 predictors were Body Mass Index, weight and race (Asian). External validation found that on average this model overestimated waist circumference by 4.65 cm in the United Kingdom population (mainly due to overprediction in females) and underestimated waist circumference by 1.7 cm in the Chinese population. The respective root mean squared errors were 7.7 cm and 7.1 cm. Conclusions XGBoost-based models accurately predict waist circumference from standard physical features. Waist circumference prediction using this approach would be valuable for epidemiological research and beyond.

Additional file 2: Supplemental Figure 1. Example of one decision tree (out of 1000) in the first iteration of the gender-aggregated XGBoostmodel. Nodes contain cut-offs for the variable of interest and leaves contain output values.

Additional file 1: Supplemental Table 1. Training and testing statistics for sex-aggregated XGBoost model.

A thermal barrier coating (TBC), which is composed of a top coating (TC) and bond coating (BC), can keep a turbine engine working in high temperature. The TC is an insulated ceramic layer, and the BC is a conductive layer between the TC and engine blade. Owing to poor working conditions, some failures such as sintering, thinning of coating thickness, and oxide layer initiation will occur in the TBC. Once any part of the TBC fails, it will seriously threaten the safety of the aircraft. The quantitative detection of TBC parameters is realized with the electromagnetic/capacitive dual modality sensor in this paper. The measurement grid algorithm is used to inverse the thickness of the TC layer and the conductivity of the BC layer, and an analytical method is proposed to inverse the relative permittivity of the TC layer. According to the experiment, the inversion errors of these parameters are all less than 4%, which can meet the industry needs well.

Introduction Blood biomarkers are measured for their ability to characterise physiological and disease states. Much is known about linear relations between blood biomarker concentrations and individual vital signs or adiposity indexes (eg, BMI). Comparatively little is known about non-linear relations with these easily accessible features, particularly when they are modelled in combination and can potentially interact with one another. Methods In this study, we used advanced machine learning algorithms to create non-linear computational models for predicting blood biomarkers (cells, lipids, metabolic factors) from age, general adiposity (BMI), visceral adiposity (Waist-to-Height Ratio, a Body Shape Index) and vital signs (systolic blood pressure, diastolic blood pressure, pulse). We determined the predictive power of the overall feature set. We further calculated feature importance in our models to identify the features with the strongest relations with each blood biomarker. Data were collected in 2018 and 2019 and analysed in 2020. Results Our findings characterise previously unknown relations between these predictors and blood biomarkers; in many instances the importance of certain features or feature classes (general adiposity, visceral adiposity or vital signs) differed from their expected contribution based on simplistic linear modelling techniques. Conclusions This work could lead to the formation of new hypotheses for explaining complex biological systems and informs the creation of predictive models for potential clinical applications.

Because of β-lactamase–mediated resistance, β-lactam antibiotics were long considered ineffective drugs for tuberculosis (TB) treatment. However, some β-lactams, including meropenem and faropenem, are being re-evaluated in patients infected with TB. Penicillin-binding protein (PBP) 3, or ftsI, is an essential transpeptidase in Mycobacterium tuberculosis (Mtb) required for cell division, and thus it is an important drug target. Structures of apo MtbPBP3 and of complexes with five β-lactams, including meropenem and faropenem, reveal how they cause inactivation via formation of hydrolytically stable acyl-enzyme complexes. The structures reveal unique features of the antibiotic interactions, both in terms of differences in their binding to MtbPBP3 and in comparison with structures of other PBPs and serine β-lactamases, including the tautomerization status of the carbapenem-derived acyl-enzyme complexes. The results suggest that rather than hoping PBP inhibitors developed for other infections will work against TB, work should focus on developing PBP inhibitors specialized for treating TB. SIGNIFICANCE STATEMENT The structures of Mycobacterium tuberculosis penicillin-binding protein 3, an essential protein in M. tuberculosis, in complex with a number of widely used β-lactam antibiotics (e.g., meropenem, aztreonam, and amoxicillin) were solved. These data provide new insights for next-generation rational approaches to design tuberculosis (TB)-specific β-lactam or nonlactam antibiotics. This manuscript is a seminal article in the field of anti-TB drug discovery and suitable for the broad readership.

A novel microwave absorber of Fe

Thermochemical conversion technology can be employed for the utilization of biomass resource, which not only disposes of the waste polluting the environment but also produces biomass gas and bio-oil for industrial applications. In this work, CaO catalyst was used to catalyze the pyrolysis of herb residues to produce biobased gas. The mechanism of biomass pyrolysis with in-situ CO2 capture was studied by experimental investigation and thermodynamic simulation. The results of the thermogravimetric and infrared analysis showed that CaO could promote biomass pyrolysis, water gas shift reaction, methanation reaction, and macromolecular transformation, thus significantly improving the quality of catalytic cracking gas. The further mechanistic study indicated that in-situ CO2 capture promoted by CaO relieved the thermodynamic constraints of methanation at high temperature and achieved a high CH4 selectivity in the temperature range of biomass pyrolysis and tar catalytic cracking, which is consistent with the result of the thermodynamic analysis. Mechanistically, CaO promotes the water gas shift reaction by absorbing CO2, reduces the volume contents of CO2 and CO in gas and improves H2 and CH4 concentration to afford high-quality gas.

Objective: To investigate the clinical effect of microsurgical scleral drainage and trabeculectomy combined with scleral flap adjustable suture technique in the treatment of primary glaucoma. Methods: One hundred primary glaucoma patients (120 eyes) in Xinyu People’s Hospital of Jiangxi province were selected from July 2014 to June 2016. The patients were randomly divided into control group and study group. The control group was treated with compound trabeculectomy, while the study group was treated with microsurgical scleral drainage and trabeculectomy combined with scleral flap adjustable suture technique. In both groups of patients, intraocular pressure, functional filtering bleb formation, and complications before and after surgery were monitored for three days, one week, one month, three months, six months and one year, while anterior chamber depth was determined one week after operation. The extent of success of operation was compared between the two groups. Results: At three days, one week, one month, three months, six months and one year after surgery, intraocular pressure of study group was significantly lower than that of the control group (P

In order to investigate the effect of potassium carbonate on biomass pyrolysis properties, sawdust was used as raw material and different amounts of K2CO3 were added by impregnation method to carry out thermogravimetric and pyrolysis experiments. The effects of pyrolysis temperature and the amount of K2CO3 addition on the pyrolysis of sawdust were studied using a self-made fixed-bed pyrolysis furnace. Calculation of pyrolysis kinetics shows that the existence of K2CO3 catalyst changes the pyrolysis path of sawdust, so that the activation energy of pyrolysis sawdust decreases at low temperature and increases at high temperature. The pyrolysis experiments shows that the addition of K2CO3 and the increase of pyrolysis temperature both reduce the yield of the pyrolysis oil of sawdust and increase the yield of the pyrolysis syngas. However, K2CO3 catalyst promotes the yield of char, the increase of pyrolysis temperature decreases the yield of char. Analysis of the pyrolysis products finds that the addition of K2CO3 and the increase of pyrolysis temperature both improve quality of the pyrolysis oil, form more microporous surface of char, and increase the hydrogen content in the pyrolysis syngas. It is considered that the optimal process for producing pyrolysis syngas is 900 °C of pyrolysis temperature and 10% of K2CO3 addition.

The in-situ CO2 removal pyrolysis of Chinese herb residue was studied by thermodynamic equilibrium simulation and experimental methods. The effects of temperature, pressure, and CaO loading on the gas composition, heating value and yield were determined. The simulation results indicate that the heating value of product gas increases with the increase of Ca/H and pressure, and slightly decreases with the increase of temperature. The simulation results were verified by the experiments conducted with a micro fixed-bed reactor. Under the simulated reaction conditions including atmospheric pressure, reaction temperature of 700 °C and the Ca/H of 0.65, the CO2 in the product gas was effectively removed, resulting the syngas with a high heating value. The product gas was mainly composed of H2, CO, CO2 and CH4 with the contents of 47.52, 22.04, 9.01 and 14.02 respectively by experiment. And the lower heating value of the product gas reached 18.1 MJ/Nm3.

Classical interpretation of cystic fibrosis (CF) lung disease pathogenesis suggests that infection initiates disease progression, leading to an exuberant inflammatory response, excessive mucus, and ultimately bronchiectasis. Although symptomatic antibiotic treatment controls lung infections early in disease, lifelong bacterial residence typically ensues. Processes that control the establishment of persistent bacteria in the CF lung, and the contribution of noninfectious components to disease pathogenesis, are poorly understood.To evaluate whether continuous antibiotic therapy protects the CF lung from disease using a ferret model that rapidly acquires lethal bacterial lung infections in the absence of antibiotics.CFTR (cystic fibrosis transmembrane conductance regulator)-knockout ferrets were treated with three antibiotics from birth to several years of age and lung disease was followed by quantitative computed tomography, BAL, and histopathology. Lung disease was compared with CFTR-knockout ferrets treated symptomatically with antibiotics.Bronchiectasis was quantified from computed tomography images. BAL was evaluated for cellular differential and features of inflammatory cellular activation, bacteria, fungi, and quantitative proteomics. Semiquantitative histopathology was compared across experimental groups. We demonstrate that lifelong antibiotics can protect the CF ferret lung from infections for several years. Surprisingly, CF animals still developed hallmarks of structural bronchiectasis, neutrophil-mediated inflammation, and mucus accumulation, despite the lack of infection. Quantitative proteomics of BAL from CF and non-CF pairs demonstrated a mucoinflammatory signature in the CF lung dominated by Muc5B and neutrophil chemoattractants and products.These findings implicate mucoinflammatory processes in the CF lung as pathogenic in the absence of clinically apparent bacterial and fungal infections.

1/f noise as well as nonlinear and hysteresis are the dominant restrictions of magnetoresistive (MR) sensors in detection ability. Modulation of the stimulating magnetic field of the MR sensors with microelectromechanical systems (MEMS) can reduce the 1/f noise by hundreds of times at low frequency, which gives a highlight for high-sensitive magnetic sensors. However, nonlinear response primarily caused by magnetic hysteresis is still a practical problem in modulated MR sensors, as well as unipolar response. In this paper, we propose a bidirection pulse magnetization method to reduce magnetic hysteresis, and in order to separate MR sensors from temperature influence, an integrated MEMS structure with low dissipation is developed to achieve pulse magnetization. Furthermore, this method is also used to achieve the bipolar magnetic field detection by distinguishing the response disparity under bidirection magnetization. The experimental results show that the modulated MR sensors can realize 90% reduction of hysteresis and 12.9% improvement of sensitivity with this method.

HCoV-229E spike (S) protein mediates virion attachment to cells and subsequent fusion of the viral and cellular membranes. This protein is composed of an N-terminal receptor-binding domain (S1) and a C-terminal trans-membrane fusion domain (S2). S2 contains a highly conserved heptad repeat 1 and 2 (HR1 and HR2). In this study, the HRs sequences were designed and connected with a flexible linker. The recombinant fusion core protein was crystallized and its structure was solved at a resolution of 2.45 Å. Then we characterized the binding of HR1s and HR2s via both sequence alignment and structural analysis. The overall structures, especially the residues in some positions of HR2 are highly conserved. Fourteen hydrophobic and three polar residues from each HR1 peptide are packed in layers at the coiled-coil interface. These core amino acids can be grouped into seven heptad repeats. Analysis of hydrophobic and hydrophilic interactions between HR2 helix and HR1 helices, shows that the HR1 and HR2 polypeptides are highly complementary in both shape and chemical properties. Furthermore, the available knowledge concerning HCoV-229E fusion core may make it possible to design small molecule or polypeptide drugs targeting membrane fusion, a crucial step of HCoV-229E infection.

This research was supported by the Engineering & Physical Sciences Research Council (EPSRC) and the Biotechnology & Biological Sciences Research Council (BBSRC), UK (EP/D048559). AMB and EOJD were supported by graduate studentships from the BBSRC (BB/F01709X/1) and NJH and JEL were supported by graduate studentships from the EPSRC, and JEL after her DPhil by EP/D048559. AMB gratefully acknowledges her current fellowship support from the Royal Society and EPSRC for a Dorothy Hodgkin Fellowship (DH160004). JRH acknowledges support from the ARC (FT120100421) and the Centre for Advanced Imaging, The University of Queensland. Cytochrome P450 (CYP) monooxygenases catalyze the oxidation of chemically inert carbon-hydrogen bonds in diverse endogenous and exogenous organic compounds by atmospheric oxygen. This C–H bond oxy-functionalization activity has huge potential in biotechnological applications. Class I CYPs receive the two electrons required for oxygen activation from NAD(P)H via a ferredoxin reductase and ferredoxin. The interaction of Class I CYPs with their cognate ferredoxin is specific. In order to reconstitute the activity of diverse CYPs, structural characterization of CYP-ferredoxin complexes is necessary, but little structural information is available. Here we report a structural model of such a complex (CYP199A2-HaPux) in frozen solution derived from distance and orientation restraints gathered by the EPR technique of orientation-selective double electron-electron resonance (os-DEER). The long-lived oscillations in the os-DEER spectra were well modeled by a single orientation of the CYP199A2-HaPux complex. The structure is different from the two known Class I CYP-Fdx structures: CYP11A1-Adx and CYP101A1-Pdx. At the protein interface, HaPux residues in the [Fe2S2] cluster-binding loop and the α3 helix, and the C-terminus residue interact with CYP199A2 residues in the proximal loop and the C helix. These residue contacts are consistent with biochemical data on CYP199A2-ferredoxin binding and electron transfer. Electron-tunneling calculations indicate an efficient electron-transfer pathway from the [Fe2S2] cluster to the heme. This new structural model of a CYP-Fdx complex provides the basis for tailoring CYP enzymes for which the cognate ferredoxin is not known, to accept electrons from HaPux and display monooxygenase activity. Postprint

This cross-sectional study aimed to examine changes in thyroid-stimulating hormone (TSH) concentration over age in China and investigate relationship between TSH and risk factors for cardiovascular disease (CVD) among euthyroid subjects. TSH, free triiodothyronine (FT3), free thyroxine (FT4), blood lipid, and glucose were measured. 7,693 individuals were subdivided into different age groups. Associations between TSH and CVD risk factors [age, body mass index (BMI), systolic and diastolic blood pressure, total cholesterol (TC), triglycerides, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) and fasting plasma glucose (FPG)] were evaluated with Pearson correlation analysis. Results showed that 2.5th percentile for TSH was consistent across age groups, whereas 97.5th percentile increased in subjects older than 40 years with upper limit being 6.83 mIU/L in subjects aged 60-69 years and 8.07 mIU/L in those older than 70 years. The age-specific upper limits reclassification rate was higher in all age bands as compared to the common cut-off value. TSH was positively associated with age, SBP, DBP, TC and LDL-C and negatively with FT3 and FT4. Serum TSH within new reference range had a linear correlation with SBP, TC and LDL-C in subjects aged

Many Domain-Specific Modeling Languages (DSML) cannot formally define their semantics, leading to difficulties in identifying user-defined domain constraints. In this study, we propose a user-defined mechanism of domain constraints based on the formalization of structural semantics of DSML. First, we formally define concepts and decision methods of consistency and validity of domain constraints. Subsequently, we establish concepts and reasoning methods of domain-based model consistency. Thus, several domain constraint instances are defined and different models instances’ consistency are reasoned based on formalization of software architecture domain metamodel to illustrate our approach. Finally, our formal definition mechanism of domain constraint is added to our automatic translator for formalizing DSML and its models to automatically reason about domain constraints built based on DSML.

Background Previous national survey suggested that dyslipidemia is an increasing burden in China and more severe in urban population. In this study, we retrospectively analyzed the gender and age differences in lipids and lipoproteins in a large Chinese urban population in Nanjing city. Methods A total of 236, 945 adults (age ≥20 years old) who undertook a health check between 2009 and 2015 in our medical examination center were involved in the analysis. Fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride (TG) were measured by standard methods. Results The age-standardized estimates of serum total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride were 4.77 (4.76–4.79), 1.19 (1.18–1.19), 2.53 (2.52–2.54) and 1.74 (1.72–1.76) mmol/L in males (n=130954), and 4.79 (4.78–4.80), 1.46 (1.45–1.46), 2.44 (2.43–2.45) and 1.21 (1.19–1.22) mmol/L in females (n=105991), respectively. The prevalence of dyslipidemia was significantly elevated in females above 50 years old, and the peak prevalence of dyslipidemia in males was in the age group of 40–59 years, earlier as compared to females (peaked at 60–69 years old). In addition, an increasing secular trend was observed in LDL cholesterol levels from 2009 to 2015 in both males and females. Conclusions Dyslipidemia is an increasing epidemic in China, characterized by a rising trend of LDL cholesterol. The gender and age differences in serum levels of lipid profile as well as prevalence of dyslipidemia suggested that the middle-age men and postmenopausal women should be the prioritized target for better control of dyslipidemia and early prevention of cardiovascular disease.

Ion-exchange is a widely used purification technology in the heparin manufacturing process. To improve the rate and efficiency, the cationic monomer Acryloxyethyltrimethyl ammonium chloride (DAC) was grafted on silica gel particles by using a surface-initiated graft-polymerization technique, and a novel adsorption polymer of PDAC/SiO2 was prepared. The adsorption experiments of PDAC/SiO2 for heparin show that there are strong electrostatic interactions between heparin with a high density of negative charges and PDAC/SiO2 that exists in many quaternary ammonium cations. Comparing the adsorption kinetics of PDAC/SiO2 with D201 anionic strong alkali exchange resin, PDAC/SiO2 shows higher adsorption capacity and faster adsorption rate. The pH and temperature of solutions have a great influence on the adsorption amount, and there is a maximum adsorption capacity of 121mg/g when pH=7 at 25 °C. The adsorption of PDAC/SiO2 for heparin is an exothermic process and driven by entropy.

A post-synthetic modification method was developed to prepare fluorescent metal organic frameworks by the covalent interaction of ethoxycarbonyl isothiocyanate with amine functionalized UMCM-4. X-ray diffraction spectrometry, X-ray photoelectron spectrometry, elemental analysis, Fourier-transformed infrared spectroscopy, nuclear magnetic resonance spectrometry, thermogravimetric analysis/derivative thermogravimetry analysis, and nitrogen sorption isotherms were employed to characterize the modified metal organic frameworks. With high emission efficiency and excellent fluorescence stability, the sensing properties of Fe 3+ were studied. Possible mechanisms of energy and electron transfers between the target and the fluorescent probe were demonstrated. Effects of response time, Fe 3+ concentration, and other metal ions on the fluorescence intensity were also studied.

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Cystic fibrosis (CF) is a multiorgan disease caused by mutations in the cystic fibrosis transmembrane conductance regulator ( CFTR ). In patients with CF, abnormalities initiate in several organs before birth. However, the long-term impact of these in utero pathologies on disease pathophysiology is unclear. To address this issue, we generated ferrets harboring a VX-770 (ivacaftor)–responsive CFTR G551D mutation. In utero VX-770 administration provided partial protection from developmental pathologies in the pancreas, intestine, and male reproductive tract. Homozygous CFTR G551D/G551D animals showed the greatest VX-770–mediated protection from these pathologies. Sustained postnatal VX-770 administration led to improved pancreatic exocrine function, glucose tolerance, growth and survival, and to reduced mucus accumulation and bacterial infections in the lung. VX-770 withdrawal at any age reestablished disease, with the most rapid onset of morbidity occurring when withdrawal was initiated during the first 2 weeks after birth. The results suggest that CFTR is important for establishing organ function early in life. Moreover, this ferret model provides proof of concept for in utero pharmacologic correction of genetic disease and offers opportunities for understanding CF pathogenesis and improving treatment.

To provide guidance for the study of risk factors of cardiovascular disease in China, we analyze and compared the research hotspots and frontiers of cardiovascular risk factors in China and outside China in this paper. The CiteSpace software is used to visualize the research literature on cardiovascular risk factors from Cnki(China Knowledge Network Internet) and Web of Science core collection database from 2010-2018, and to draw the knowledge map of high-frequency words, research institutions and countries. In this project, a total of 318 Chinese literatures and 9,009 English literatures were screened out as research objects. The number of annual publications assumes an increasing tendency, most of which are concentrated in developed countries or regions. Study of cardiovascular risk factors outside China is significantly taken more seriously than in China. This study shows that the research frontier has already been extended to lifestyle, particulate air pollution, socioeconomic status, depression, stroke and breast cancer, etc. Moreover, children, adolescents and women have been more concerned in the target population. In consideration of the main reasons for cardiovascular disease---Hypertension, diabetes, coronary heart disease, obesity, atherosclerosis and metabolic syndrome, etc., we should pay close attention to the influence on the risk of cardiovascular disease produced by psychological state, living habits, regional differences, air pollution and so on. Meanwhile, we also need to take the screening and prevention of cardiovascular risk more seriously among adolescents.

Organophosphates (OPs) have been used widely as insecticides for protecting the agricultural crops from the pests. These compounds are highly toxic because they can cause the irreversible damage to human nervous system. Phosphotriesterases (PTEs), widely exist in many different kinds of bacteria, insects and mammals, can hydrolyze phosphotriesters (one major kind of OP) sufficiently. The phosphotriesterase-activities of PTEs are considered to derive from the lactonase-activities during the evolution, and phosphotriesterase-like lactonase family (PLL), is the closest protein family to PTE family based on protein-protein blast results. But members of PLL family exhibit higher lactonase activities than the phosphotriesterase activities, while the best substrates for PTEs are phosphotriesters. In this paper, the X-ray crystal structure of phosphotriesterase from M. tuberculosis (mPHP) was solved at a resolution of 2.3 A. The structure reveals that the mPHP is a dimer with a typical distorted (β/α)8 barrel structure like other structures of PLL family and PTE family. The architecture of active pocket of mPHP coordinates with 2 metal ions which is also similar to other PLLs and PTEs. The activity assay proved the mPHP is biological active form and the Atomic Absorption Spectroscopy assay gave the evidence that the two metal ions bound to the active pocket were Zinc cations. The structural comparison between mPHP and other homologues concluded that the mPHP should belong to PLL family, not PTE family.

The residual stress detection based on eddy current method belongs to weak signal detection. Aiming at the problems of sensor output signal with many channels, large amount of data, wide frequency range and low signal-to-noise ratio, a weak magnetic signal detection system is designed and implemented with Zynq-7020 (ARM+ FPGA) as the development board and peripheral hardware circuit. Among them, FPGA controls the peripheral chip to complete the signal source excitation and 8-channel high-speed data acquisition and preprocessing, and then the data is transmitted to ARM through AXI bus. ARM extracts the signal characteristics through digital orthogonal lock-in amplification technology according to the control parameters provided by the upper computer, and feeds back the results to the upper computer. The test results show that the system has high stability and detection accuracy, and meets the overall requirements of the system.

A novel microwave absorber of Fe3O4/carbonized cellulose micro-nano hybrid with self-assembly porous structure has been fabricated through a facile process of loading of hydrolyzed Fe3+ polymers, freeze drying and annealing. Annealing temperature has effect on the microstructural defects and growth of Fe3O4 and graphite nanocrystals, and further affects the dielectric properties of Fe3O4/carbonized cellulose micro-nano hybrid. The Fe3O4/carbonized cellulose micro-nano hybrid annealed at 700 ℃ (FC-700) presents the most excellent microwave absorption properties. The effective adsorption bandwidth of FC-700 reaches up to 6.72 GHz with the thickness of 2.3 mm. The minimum reflection loss of FC-700 reaches -42.25 dB in frequency of 12.27 GHz. The delta-function method proves the Fe3O4/carbonized cellulose micro-nano hybrid has good impedance match with the free space. Cole-Cole plots validate the polarization relaxation. The novel carbon- based micro-nano hybrid with excellent performance, easy fabrication, and low cost has good prospects for microwave absorption application.

Telomere repeat factor 1 (TRF1) is a subunit of shelterin (also known as the telosome) and plays a critical role in inhibiting telomere elongation by telomerase. Tankyrase 1 (TNKS1) is a poly(ADP-ribose) polymerase that regulates the activity of TRF1 through poly(ADP-ribosyl)ation (PARylation). PARylation of TRF1 by TNKS1 leads to the release of TRF1 from telomeres and allows telomerase to access telomeres. The interaction between TRF1 and TNKS1 is thus important for telomere stability and the mitotic cell cycle. Here, the crystal structure of a complex between the N-terminal acidic domain of TRF1 (residues 1–55) and a fragment of TNKS1 covering the second and third ankyrin-repeat clusters (ARC2-3) is presented at 2.2 Å resolution. The TNKS1–TRF1 complex crystals were optimized using an `oriented rescreening' strategy, in which the initial crystallization condition was used as a guide for a second round of large-scale sparse-matrix screening. This crystallographic and biochemical analysis provides a better understanding of the TRF1–TNKS1 interaction and the three-dimensional structure of the ankyrin-repeat domain of TNKS.

The radiation resistance performance of nanoporous (NP) gold is investigated by cascade simulations of a gold nanowire using molecular dynamics. The role of the surface on primary defect production was clarified: the mean size of the vacancy clusters (VCs) near the surface in the nanowire becomes larger compared to that of a single crystal. In the surface region, the reduction of the formation and migration energies of point defects leads to a continuous flux of point defects towards the free surface, which retards the formation and growth of defect clusters, resulting in a good anti-radiation performance. In the cascade region, however, the retained vacancies tend to form larger sessile VCs due to their low migration energies and large attractive forces, resulting in radiation damage. The competition between these two factors determines the anti-radiation behavior of NP gold.

Objective: Gallstone formation is a pathological process of mineralization in the human body. Determination of the morphology and ultrastructure of gallstones holds the key to understanding the pathophysiology of gallbladder disease. Synchrotron radiation phase-contrast Xray microtomography is a novel technology, which is designed for comprehensive analysis of gallstone ultrastructure. Materials and Methods: Nine human gallstones were obtained from the Department of Pathology, Qingpu branch of Zhongshan Hospital Affiliated to Fudan University (China), and scanned by synchrotron radiation µCT (SR µCT). The imaging data generated by SR µCT scan were analyzed. Results: The three-dimensional ultrastructure of human gallstones corresponding to their cholesterol and bile pigment composition was determined. Conclusions: The ultrastructure of gallstones exhibits considerable diversity and complexity. The synchrotron radiation phase-contrast X-ray microtomography is a valuable tool for in-depth study of human gallstones.

An agricultural drought disaster was analyzed with the new insight of rescaled statistics (R/S) and wavelet analysis in this study. The results showed that: (1) the Hurst index of the agricultural disaster area, the inundated area of agricultural drought disaster, and the grain loss was 0.821, 0.874, and 0.953, respectively, indicating that the process of the agricultural drought disaster had stronger positive continuity during the study period, (2) based on the Morlet analysis of the agricultural disaster area, the inundated area of the agricultural drought disaster, and the grain loss of China from 1950 to 2016, the time series of the agricultural drought had multiple time scale features with the periodic variation on a large scale containing the periodic variation on a small scale, and (3) in the last 67 years, the strong wavelet energy spectrum of the agricultural disaster area, the inundated area of the agricultural drought disaster, and the grain loss was at the time scale of &asymp, 22&ndash, 32 years, &asymp, 24&ndash, 32 years, and &asymp, 25&ndash, 32 years, respectively. In addition, the first major period in the agricultural drought disaster area, the inundated area of agricultural drought disaster, and the grain loss had average periods of approximately 16 years, 16 years, and 18 years, respectively.

Furan resin and fir powder pretreated by FeCl3 and aqueous ammonia solution were used to fabricate α-Fe/Fe3C/woodceramic nanocomposite. The bands of the pretreated wood powder were characterized by Fourier transform infrared spectroscopy (FTIR). The structural characterization of the nanocomposites was performed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The microwave absorption of the nanocomposites was measured by a vector network analyzer in the range of 2–18 GHz. The mechanical properties of the composites were also investigated. XRD and SEM results show that the α-Fe and Fe3C nanoparticles are in-situ generated and disperse in the matrix of the woodceramic. The diameters of these nanoparticles increase with the increasing of concentration of FeCl3 solution. The experimental results show that both the complex permittivity and the complex permeability of α-Fe/Fe3C/woodceramic nanocomposites increase as the concentration of FeCl3 solution increases. The composites pretreated with 0.60 mol·L−1 FeCl3 have the best absorption properties. The maximum value of reflection loss (RL) at 3 mm thickness reaches −25.60 dB at 10.16 GHz and the bandwidth below −10 dB is about 2.5 GHz. Compared to woodceramic, the bending strength and compressive strength of α-Fe/Fe3C/woodceramic nanocomposites increase by 22.5% and 18.7% at most, respectively.

Endonuclease IV is a typical endonuclease of the apurinic-apyrimidinic (AP) or abasic endonuclease superfamily. It repairs damaged DNA through base excision repair by cleaving the DNA backbone immediately 5′ of an AP site. In Mycobacterium tuberculosis, endonuclease IV is the major AP endonuclease. This enzyme is absent from mammalian cells, making it an attractive target for anti-tuberculosis drug development. In this study, the structure of the recombinant endonuclease IV from M. tuberculosis (MtbEndo IV) was determined at a high resolution of 1.18 A. MtbEndo IV was found to have a classical α8β8-fold TIM barrel with loops on its surface connecting the α-helices and β-strands that constitute a groove for DNA binding. Three zinc ions were identified at the active site. A comparison between the structures of MtbEndo IV and Escherichia coli End IV suggested that Gln32 of MtbEndo IV may plays a role in regulating substrate binding.

Background: Adult obesity has become a serious human health issue. However, no existing study has explored the relationship between obesity and climatic conditions at the time of birth. To determine whether the birth month and climatic conditions at birth correlate with the prevalence of obesity and obesity-related diseases. Methods: This observational study included 264,574 Chinese participants. All participants were enrolled between 2008 and 2014 .Initially, 382,325 Chinese participants were selected from a population-based sample, after which 264,574 participants were randomly selected by the complete data and appropriate age. All data were measured by the same observers who were blinded to patient groupings. Findings: Individuals born in June, July, and August had the lowest risks of obesity and hypertension. Therefore, the prevalence of adult obesity may be significantly affected by climatic conditions during the birth month. Our research indicates a new direction for exploration of the contributions of climatic factors and time of birth to adult obesity. Interpretation: Participants born in June had the lowest body mass index and prevalence of overweight and obesity among all participants. The highest prevalence of these categories was observed in February and September, which yielded a clear V-type trend curve. Similar trends were observed for obesity-related diseases such as hypertension. Adult obesity correlated linearly with the average temperature, precipitation, and atmospheric pressure of the birth month (P

Magnetic modulation methods especially Micro-Electro-Mechanical System (MEMS) modulation can improve the sensitivity of magnetoresistive (MR) sensors dramatically, and pT level detection of Direct Current (DC) magnetic field can be realized. While in a Low Frequency Alternate Current (LFAC) magnetic field measurement situation, frequency measurement is limited by a serious spectrum aliasing problem caused by the remanence in sensors and geomagnetic field, leading to target information loss because frequency indicates the magnetic target characteristics. In this paper, a compensation field produced with integrated coils is applied to the MR sensor to remove DC magnetic field distortion, and a LFAC magnetic field frequency estimation algorithm is proposed based on a search of the database, which is derived from the numerical model revealing the relationship of the LFAC frequency and determination factor [defined by the ratio of Discrete Fourier Transform (DFT) coefficients]. In this algorithm, an inverse modulation of sensor signals is performed to detect jumping-off point of LFAC in the time domain; this step is exploited to determine sampling points to be processed. A determination factor is calculated and taken into database to figure out frequency with a binary search algorithm. Experimental results demonstrate that the frequency measurement resolution of the LFAC magnetic field is improved from 12.2 Hz to 0.8 Hz by the presented method, which, within the signal band of a magnetic anomaly (0.04-2 Hz), indicates that the proposed method may expand the applications of magnetoresistive (MR) sensors to human healthcare and magnetic anomaly detection (MAD).

There is intense interest in late‐stage catalytic CH bond functionalization as an integral part of synthesis. Effective catalysts must have a broad substrate range and tolerate diverse functional groups. Drug molecules provide a good test of these attributes of a catalyst. A library of P450BM3 mutants developed from four base mutants with high activity for hydrocarbon oxidation produced human metabolites of a panel of drugs that included neutral (chlorzoxazone, testosterone), cationic (amitriptyline, lidocaine) and anionic (diclofenac, naproxen) compounds. No single mutant was active for all the tested drugs but multiple variants in the library showed high activity with each compound. The high conversions enabled full product characterization that led to the discovery of the new P450 reaction type of oxidative decarboxylation of an α‐hydroxy carboxylic acid and the formation a protected imine from an amine, offering a novel route to α‐functionalization of amines. The substrate range and varied product profiles suggest that this library of enzymes is a good basis for developing late‐stage CH activation catalysts.