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Mechanisms underlying elevated blood pressure in dialysis patients are complex as a variety of non‐traditional factors are involved. We sought to explore the association of circulating betaine, a compound widely distributed in food, with blood pressure in dialysis patients. We used baseline data of an ongoing cohort study involving patients on hemodialysis. Plasma betaine was measured by high performance liquid chromatography in 327 subjects. Blood pressure level was determined by intradialytic ambulatory blood pressure monitoring. The mean age of the patients was 52.6 ± 11.9 years, and 58.4% were male. Average interdialytic ambulatory systolic and diastolic blood pressure were 138.4 ± 22.7 mm Hg and 84.4 ± 12.5 mm Hg, respectively. Mean plasma betaine level was 37.6 μmol/L. Multiple linear regression analysis revealed significant associations of betaine with both systolic blood pressure (β = −3.66, P = .003) and diastolic blood pressure (β = −2.00, P = .004). The associations persisted even after extensive adjustment for cardiovascular covariates. Subgroup analysis revealed that the association between betaine and blood pressure was mainly limited to female patients. Our data suggest that alteration of circulating betaine possibly contributes to blood pressure regulation in these patients.

Background: Renal fibrosis is a common outcome of nearly all kinds of chronic kidney disease (CKD) and eventually progresses to end-stage renal disease. The identification of an optimal biomarker of renal fibrosis to replace the invasive renal biopsy will have important clinical implications. Methods: We isolated urinary exosomes from 50 participants and examined the exosomal protein content and particle number in 38 CKD patients with different degrees of renal fibrosis and in 12 normal individuals. We examined the levels of exosomal microRNAs (miRNAs), namely, miR-200a, miR-200b, miR-200c, miR-141, miR-429, miR-29a, miR-29b, miR-29c, miR-192, and miR-21, by sorting the exosomes and comparing the levels of proximal tubular, non-proximal tubular, and total exosomal miR-200b. Results: The exosome content was higher in the CKD group, but no differences were evident among the mild, moderate, and severe fibrosis groups. Among the 10 exosomal miRNAs, miR-200b was lower in the CKD group than in the normal group and decreased more significantly with fibrosis progression as well as in IgA nephropathy and diabetic kidney disease. CD13+ CD63+ exosomes constituted 18.6% of all urinary exosomes. Sorting the proximal tubular exosomes with the CD13 protein marker revealed that miR-200b in the CD13+ group was extremely low; however, the result was significantly different in the CD13– group but not in the CD13+ group. The magnitude of the decline was greater in the CD13– groups than in the non-sorted whole groups between the fibrosis and normal patients. Conclusions: Non-proximal renal tubule-derived urinary exosomal miR-200b is a biomarker of renal fibrosis. Exosomes can be used as a liquid biopsy and may replace the traditional invasive renal biopsy in the diagnosis of renal fibrosis.

The strategic combination of the methylene bridged glycoluril dimer and triptycene skeletons delivers acyclic water soluble hybrid receptor 1 which is analogous to cucurbit[6]uril. The molecular recognition properties of host 1 toward hydrophobic cationic guests are investigated in detail by a combination of 1H NMR spectroscopy and isothermal titration calorimetry (ITC) studies. The fluorescence emission of 1 can be selectively and efficiently quenched upon the formation of 1·26 and 1·28 complexes.

A two-stage light gas gun is used to accelerate the sphere 6061 aluminum projectiles to a speed range of 2.3-6.3 km/s in an almost vacuum environment. Spectrometer and pyrometer are adopted to measure the time-frequency characteristics of the collision-generated spectra when 6061 aluminum projectiles impact on 6061 aluminum targets with thicknesses varying from 1 mm to 26 mm. Based on the thermal ionization, theories of the single and the secondary collision are established. Experimental spectra show that threshold velocities of evaporation and plasma phase transition are 2.45 km/s and 4.7 km/s when spherical aluminum alloy projectile impacts on aluminum alloy target. Theoretical calculation demonstrates that neither the single impact nor the secondary impact of debris or secondary compression in the oblique direction can explain the ionization at low-speed impact. The threshold velocity of ionization, however, calculated by the combined secondary collision both in the oblique and horizontal direction during the impact of spherical projectile colliding on the target is most reasonable to explain the plasma produced by relatively low-speed hypervelocity impact.

The characterization of externally solidified crystals (ESCs) and porosities in a high-pressure die-cast AlSi10MnMg alloy was investigated using optical microscope (OM) and computed tomography (CT) with particular attention on the effect of shot speeds on the ESCs and fracture behavior. Results showed that ESCs tended to agglomerate at the center region and changed from fine globular grains into large size dendrites from surface to center. The formation of the ESCs is found to be coarser as the "slow shot speed" in the first stage of high-pressure die casting (HPDC) or the "fast shot speed" in the second stage of HPDC is reduced, consequently, the corresponding ESC area fraction increased. From the fractured morphology, the plate specimen with a higher ESC content exhibited a rough fracture and a large volume fraction of shrinkage porosities was discovered beneath the fracture surface especially when a lower fast shot speed was applied. In in-situ tensile test, the large size shrinkage porosity served as a crack source and it further expanded in an inter-granular mode along ESC boundaries/other porosities (which caused a tortuous crack route) or in a trans-granular mode across the ESC grains/fine (α-Al)II grains (which caused a flat crack route). In addition, the gas porosities in the specimen promoted the crack propagation as a crack concentration area and experienced almost no deformation during the tensile process.

The van der Waals (vdW) heterostructures formed by stacking layered two-dimensional materials can improve the performance of materials and provide more applications. In our paper, six configurations of AlN/MoS2 vdW heterostructures were constructed, the most stable structure was obtained by calculating the binding energy. On this basis, the effect of external vertical strain on AlN/MoS2 heterostructure was analyzed, the calculated results show that the optimal interlayer distance was 3.593 Å and the band structure was modulated. Then the h-BN intercalation was inserted into the AlN/MoS2 heterostructure, by fixing the distance between h-BN and AlN or MoS2, two kinds of models were obtained. Furthermore, the electronic properties of AlN/MoS2 heterostructure can be regulated by adding h-BN intercalation layer and adjusting its position. Finally, the optical properties show that the absorption coefficient of AlN/MoS2 heterostructure exhibits enhancement characteristic compared with that of the individual monolayers. Meantime, compared with AlN/MoS2, the AlN/h-BN/MoS2 shows a redshift effect and the light absorption peak intensity increased, which indicated that h-BN intercalation layer can be used to regulate the electronic and optical properties of AlN/MoS2 heterostructure.

Heterostructures have attracted significant attention because of their interlayer van der Waals interactions, in this work, six stacking models of GeC/MoS2 heterostructure were constructed, the AB stacking model has the lowest energy and the most stable interlayer spacing between GeC and MoS2 is 3.81 A. Based on First-principles calculations, we explored the structural, electronic and optical properties of GeC/MoS2 heterostructure and its response to electric field and biaxial strain. The results show that built-in electric field formed at the GeC/MoS2 interface, which effectively separated photo-generated electrons and holes. Meantime, the absorption of GeC/MoS2 located at ~200 nm was enhanced compared with monolayers. When the electric field strength increased from −0.7 V/A to 0.65 V/A, the band gap value of GeC/MoS2 heterostructure increased from 0eV to 1.21eV linearly, then decreased continuously to 0eV with the electric field strength increasing from 0.65 V/A to 0.8 V/A. Lastly, with the biaxial strain increasing from −6% to 5%, the gap value of GeC/MoS2 heterostructure increased slowly from 0 eV to 1.19eV, then decreased rapidly to 0 eV when the biaxial strain increased from 5% to 8%, the transitions of direct-to-indirect band gap and N-to-P type characteristic occurred when biaxial strain was 3% and −2% respectively. Results show that the GeC/MoS2 heterostructure has application prospects in ultraviolet, nanoelectronic, and pressure sensitive devices.

The effect of substitutional doping at S site on the electronic properties of MoS2/Graphene (MoS2/G) was studied by First-principles calculations. Through the analysis on the energy band and density of states of MoS2/Graphene, it was found that the S vacancy in MoS2 monolayer caused the Dirac point shifted, and produced the defect energy levels at the Dirac point, which hindered the carrier transmission. Periods II-IV elements were doped at the S vacancy to improve the electronic properties and performance of MoS2/G. The calculated results show that the charge transfer of MoS2/G was greatly enhanced by the doping of N, P and As atoms. The current-voltage characteristic of N, P and As-doped G/MoS2/MoS2/G structure has higher drive-current and stable OFF-state current which can reduce device current consumption. For O-doped and Se-doped MoS2/G heterostructures, there is no impurity level introduced, and the Schottky barrier height increase (decrease) with the increase (decrease) of the biaxial strain, meantime the p-type Schottky contact, n-type Schottky contact and Ohmic contact characteristic can be converted mutually by adjusting biaxial strain or vertical external force. Our findings will be of great guiding significance for the designing of interface devices and explorations on nano-electronics.

The construction of van der Waals(vdW) heterostructures can not only enhance the properties of two-dimensional(2D) materials but also greatly expand their applications. In our works, bilayer/trilayer Blue Phosphorene/MoX2 (X=S, Se) vdW heterostructures with six different configurations were constructed. Through First-principles calculations, the mechanical stability and thermodynamic stability of all heterostructures are greatly improved compared with monolayers. In addition, the band structure and charge transfer of the heterostructures can also show the effect of the number of layers on electronic properties. When the external electric field or vertical strain was applied to the bilayer/trilayer heterostructures, the electronic properties of the structures can be well-modulated. Such good controllable properties inspired us to apply the heterostructures in electronic devices and piezoelectric devices. Finally, the optical properties and band alignments of the bilayer/trilayer heterostructures were improved, especially the change in the number of layers provides more possibilities. In addition, the excellent ability of heterostructures to accelerate the separation of photo-generated electron-hole pairs and the controllable values of power conversion efficiency (PCE) indicate that they have great potential for application in the field of photocatalysis and photovoltaics.

Ge2Sb2Te5 (GST) alloy has the ability to quickly transform between the amorphous phase and the crystalline phase; therefore, it can be used in non-volatile phase change storage. First-principles molecular dynamics was used to simulate the reversible phase change process of GST alloy, namely, amorphization and crystallization. The amorphous state was obtained by melting (∼3000 K) and cooling, and the amorphization process was characterized by the pair correlation function and bond angle distribution. The bond angles of amorphous GST were mainly distributed around 60°, 90°, and 110°, indicating the existence of octahedral and tetrahedral bonding configurations. The crystalline state was obtained by annealing at a temperature of 600 K, and the crystallization process was characterized by the pair correlation function, component disordered number, bond angle distribution, and dynamic atomic structure change. The results show that the bond angle of GST in crystallization is mainly distributed around 90°, and the structure mainly contains four-membered rings formed by Ge–Te and Sb–Te. By analyzing the optical properties, with the growth of crystallization time, the absorption coefficient, reflectivity, and conductivity of GST were significantly improved.

Masked uncontrolled hypertension (MUCH) has been proven to be associated with increased cardiovascular risk in the general population. We performed the current analysis to determine its prevalence in dialysis patients and its association with pulse wave velocity (PWV). From 368 participants of another cohort study, we selected 145 subjects with controlled predialysis blood pressure (BP). All subjects underwent ambulatory BP monitoring and PWV measurement. MUCH was defined as controlled predialysis BP with daytime BP⩾135/85 mm Hg (definition-1); total ambulatory BP⩾130/80 mm Hg (definition-2); and either daytime BP⩾135/85 mm Hg or nighttime BP⩾120/70 mm Hg (definition-3). The prevalence of MUCH was 43.4% (definition-1), 55.9% (definition-2) and 74.5% (definition-3). Multivariable logistic regression analysis showed that the use of antihypertensive medication was the most consistent predictor of MUCH within all 3 definitions (all odds ratio (OR)⩾4.28, P0.001). Predialysis systolic BP (both OR1, P⩽0.04), predialysis diastolic BP (both OR1, P⩽0.001) and hemoglobin (both OR1, P=0.02) were all significantly associated with MUCH in two models. Interdialytic weight gain (OR=0.52, P=0.02) was associated with MUCH under definition-2, and BMI (OR=0.86, P=0.03) was associated with MUCH under definition-3. Patients with MUCH had significantly elevated PWV compared with their counterparts according to all three definitions with or without adjusting for covariates (all P⩽0.03). In conclusion, MUCH affects a large proportion of dialysis patients with controlled predialysis BP and is associated with increased PWV. Patients on antihypertensive medications and with higher predialysis BP are more likely to have MUCH.

We address the multiframe superresolution problem using the variational Bayesian method in this paper. In the variational Bayesian framework, the prior is crucial in transferring the ill-posed reconstruction problem to a well-posed one. We propose a prior combination method based on filter bank and l1 norm. Multiple filters are used in our prior model, and the corresponding combination coefficient vector can be estimated by the characteristics of the filtered image and noise. Furthermore, the local adaptive coefficients of every filter are more effective in removing noise and preserving image edges. Extensive experiments demonstrate the advantages of the proposed method.

The dysfunction of E3 ubiquitin ligases is important in the pathogenesis of many human diseases, as they play important roles in multiple cellular processes. In this review, we evaluated the structures, functions and clinical significance of two RING-type E3 ubiquitin ligases from the same subfamily, ring-finger protein 126 (RNF126) and breast cancer associated gene 2 (BCA2). Interestingly, the expression of RNF126 and BCA2 are regulated by multiple signaling pathways, including EGFR, ERK, AKT, and NF-κB. RNF126 and BCA2 appear to be functional mediators for not only DNA damage repair but also cancer development. Due to their significant functions in cell proliferation and DNA damage repair, RNF126 and BCA2 may be two potential diagnostic biomarkers and therapeutic targets for cancers.

Considering the influence of the preferential degree, the hesitation psychology of customers and the heterogeneity of underlying networks in preferential information spreading, we propose a novel model called AHFB (adherent–hesitator–forwarder–beneficiary) model to illustrate the dynamic behaviors of preferential information spreading on scale-free networks. The mean-field theory is adopted to describe the formulas of AHFB model. To begin with, we analyze the spreading dynamics of preferential information. Then we determine the basic reproductive number and equilibria by the next generation matrix method. The relationship among the basic reproductive number, preferential degree, and hesitation parameter is also analyzed. In addition, the globally asymptotical stability of information-eliminate equilibrium and the permanence of the preferential information spreading are proved in detail. Furthermore, a preferential information competition model is proposed, and the corresponding dynamic behaviors are studied. We have found that under certain conditions, a greater competitive advantage can be achieved by improving a certain range of preferential strengths. Numerical simulations are also presented to verify and extend theoretical results.

Human behaviors are known to spread through social contact, which means that knowledge transmission is a social process. In order to investigate the characteristics of knowledge transmission and heterogeneity of social networks, an ILSFI (ignoramus-learner-spreader-forgetter-ignoramus) model is presented on scale-free networks. The spreading dynamics of knowledge are analyzed in detail by using the theory of mean-field. The basic reproductive number R 0 is calculated by the next generation matrix method and two equilibria are derived. The theoretical analysis indicates that the basic reproductive number mainly depends on the knowledge transmission process and the topology of the underlying networks. Furthermore, the global stability of the knowledge loss equilibrium and the permanence of the knowledge transmission are also studied in detail. Finally, we analyze the interest degree and the benefit degree through numerical simulations.

Atherosclerotic cardiovascular disease remains a worldwide epidemic and one of the leading causes of death nowadays. Vessel wall imaging can be used to understand the development and progression of atherosclerosis, but it is rarely done because of the high cost. We recently identified the Osteoarthritis Initiative, a large prospective cohort study of knee osteoarthritis, which might serve as a valuable source for atherosclerosis research with its serial knee magnetic resonance imaging data. We have found that these images are suitable for vessel wall image analysis of the lower extremity arteries. Here, we will introduce the Osteoarthritis Initiative data set and explain why it could be used for cardiovascular research purposes. Also, we will briefly comment on peripheral artery atherosclerosis as it is covered in the Osteoarthritis Initiative image data set and review the use of vessel wall imaging for studying atherosclerosis. We think data mining of imaging studies, not originally designed on cardiovascular research, can not only maximize the value of the imaging data set but also boost our understanding of atherosclerosis.

Background Incorporation of next-generation sequencing (NGS) technology into clinical utility in targeted and immunotherapies requires stringent validation, including the assessment of tumor mutational burden (TMB) and microsatellite instability (MSI) status by NGS as important biomarkers for response to immune checkpoint inhibitors. Materials and Methods We designed an NGS assay, Cancer Sequencing YS panel (CSYS), and applied algorithms to detect five classes of genomic alterations and two genomic features of TMB and MSI. Results By stringent validation, CSYS exhibited high sensitivity and predictive positive value of 99.7% and 99.9%, respectively, for single nucleotide variation; 100% and 99.9%, respectively, for short insertion and deletion (indel); and 95.5% and 100%, respectively, for copy number alteration (CNA). Moreover, CSYS achieved 100% specificity for both long indel (50–3,000 bp insertion and deletion) and gene rearrangement. Overall, we used 33 cell lines and 208 clinical samples to validate CSYS's NGS performance, and genomic alterations in clinical samples were also confirmed by fluorescence in situ hybridization, immunohistochemistry, and polymerase chain reaction (PCR). Importantly, the landscape of TMB across different cancers of Chinese patients (n = 3,309) was studied. TMB by CSYS exhibited a high correlation (Pearson correlation coefficient r = 0.98) with TMB by whole exome sequencing (WES). MSI measurement showed 98% accuracy and was confirmed by PCR. Application of CSYS in a clinical setting showed an unexpectedly high occurrence of long indel (6.3%) in a cohort of tumors from Chinese patients with cancer (n = 3,309), including TP53, RB1, FLT3, BRCA2, and other cancer driver genes with clinical impact. Conclusion CSYS proves to be clinically applicable and useful in disclosing genomic alterations relevant to cancer target therapies and revealing biomarkers for immune checkpoint inhibitors. Implications for Practice The study describes a specially designed sequencing panel assay to detect genomic alterations and features of 450 cancer genes, including its overall workflow and rigorous clinical and analytical validations. The distribution of pan-cancer tumor mutational burden, microsatellite instability, gene rearrangement, and long insertion and deletion mutations was assessed for the first time by this assay in a broad array of Chinese patients with cancer. The Cancer Sequencing YS panel and its validation study could serve as a blueprint for developing next-generation sequencing-based assays, particularly for the purpose of clinical application.

With the flourishing shale gas exploitation produces more oil based mud (OBM) drill cuttings, the hard-to-treat hazardous waste burden the local environment heavily. However, the problems of high energy consumption, high treating cost and high secondary contamination risk still remain unsolved for mainstream technologies such as thermal distillation, incineration and chemical extraction. Therefore, a new method and device based on cyclone desorption of high speed self-rotation to dispose of OBM drill cuttings are put forward to overcome the challenge.The working process includes: viscosity reduction in heated gas; cyclone deoiling; condensation and recycling of exhaust; separation of oil and water in coalescer. It is found that the self-rotation speed of solid particles in a 3-dimensional rotating turbulent flow field of cyclone is as high as 2,000 to 6,000 rad/s which coexists with revolution speed of 20 to 300 rpm. The remarkable pulsing centrifuge forces in the self-rotation and revolution coupling motion can enhance the desorption process of the oil so as to accomplish the separation and enrichment of oil and solid phase, and deep removal of organics from OBM drill cuttings.It turned out that the deoiling efficiency of OBM drill cuttings, a sample from Chongqing shale gas field, increased as the processing time longer and, to be exact, after 2.1 seconds the oil content fell from 17.9% to 0.16% which is about a half of the maximum allowable content of petroleum in pollutants, 0.3%, in GB 4284-84 "Control Standards for Pollutants in Agricultural Sludge".In general, the innovation of cyclone desorption of high speed self-rotation is the pulsing centrifuge force of self-rotation and revolution coupling motion, so it's free of chemical addition and high heating temperature. Therefore, the application of cyclone desorption of high speed self-rotation for OBM drill cuttings disposal is expected to lower treatment cost, enhance processing effect, and finally improve the environment of shale gas exploitation area and contribute to energy development.

A bidirectional three-level current-fed DC/DC converter is proposed for low voltage high current application. To reduce the peak current through high frequency (HF) transformer and switches at light load condition, a dual phase shift modulation is proposed and employed. Zero current switching of primary switches and zero voltage switching of secondary switches are achieved for a wide load range. The voltage across primary devices is naturally clamped at rather low reflected output voltage, enabling the use of low voltage rating devices. The total losses are reduced significantly and the converter performance is greatly improved. Simulation results and experimental results are presented to verify to the theoretical analysis.

Cognitive impairment is prevalent in patients with chronic kidney disease (CKD), but its underlying mechanisms are obscure. Here, we test the hypothesis that exaggerated orthostatic blood pressure reduction mediates the effects of renal failure on global cognition and memory. A total of 160 study subjects were recruited, including 80 dialysis patients and 80 controls. Global cognition was evaluated using the Montreal Cognitive Assessment (MoCA), and episodic memory was evaluated using the auditory verbal learning test (AVLT). Autonomic function was evaluated via the low-frequency to high-frequency ratio (LF/HF) through heart rate variability analysis. Compared with the controls, the dialysis patients had significantly lower MoCA and AVLT scores (including learning memory, short recall memory, and delayed recall memory) (all p 0.001). They also showed exaggerated orthostatic systolic blood pressure reductions (all p ≤ 0.001). The maximum orthostatic systolic blood pressure reduction was independently and negatively associated with short (β = -0.05, p = 0.029) and delayed (β = -0.05, p = 0.035) recall memory in dialysis patients but not in controls. Mediation analysis demonstrated that maximum orthostatic systolic blood pressure reduction mediates 13.8% of the effect of end-stage renal disease (ESRD) on short recall memory (p = 0.04). After adjustment for LF/HF, the negative association between maximum orthostatic blood pressure reduction and short recall score remained significant (p = 0.049), while the association between maximum orthostatic blood pressure reduction and delayed recall score became nonsignificant, with a marginal p value of 0.062. Our study reveals that exaggerated orthostatic blood pressure reduction is a possible explanation for ESRD-associated memory deficits.

Hypervelocity penetration experiments were performed on semi-infinite concrete targets with 7 mm-diameter 40CrNiMo steel long-rod projectiles at impact velocities ranging from 2117 m/s to 3086 m/s by using a two-stage combustion light-gas gun. After the experiments, the crater dimensions and penetration depth were carefully measured, also the residual projectiles were recovered. The depth of penetration was found to be greater than the hydrodynamic limit penetration depth. Numerical simulation was conducted to analyze the penetration process, and combined with the experimental results, it was obtained that the head of the long-rod projectile eroded and deformed into a hemisphere during hypervelocity penetration. According to the experimental and numerical simulation results, the penetration model of long-rod projectiles penetrating concrete targets at hypervelocity was constructed based on the Alekseevskii-Tate model. The penetration model was compared with the experimental depths of penetration, showing that the model had good applicability.

We present a hybrid adaptive optics system for a kW-class solid-state slab master oscillator power amplifier laser that consists of both a low-order aberration corrector and a 59-actuator deformable mirror. In this system large defocus and astigmatism of the beam are first corrected by the low-order aberration corrector and then the remaining components are compensated by the deformable mirror. With this sequential procedure it is practical to correct the phase distortions of the beam (peak to valley up to 100 μm) and the beam quality β is successfully improved to 1.9 at full power.

A zonal decoupling algorithm used to control a dual deformable mirror (DM) is proposed. One of the two DMs is characterized with a large stroke (woofer), while the other one is characterized by a high spatial frequency (tweeter). A numerical model is used to compare the zonal decoupling algorithm with some traditional zonal decoupling algorithms. The simulation results indicate that the algorithm presented in this Letter improves the performance in suppressing the coupling error. An experimental system is built to prove the effectiveness of this algorithm. The experiments demonstrate that the phase aberrations could be effectively compensated and that the coupling error could also be suppressed.

Cognitive decline is a common non-motor symptom of Parkinson disease (PD), and cellular prion protein (PrPA total of 60 participants, which included 23 PD patients without cognitive impairment (the PD-NCI group), 17 PD patients with cognitive impairment (the PD-CI group) and 20 health controls were included in this study. All participants received a complete evaluation of motor symptoms as well as non-motor symptoms, which include devaluations of cognitive function(assessed with the Montreal Cognitive Assessment (MoCA)) and their psychiatric state(assessed with the Hamilton Anxiety Scale(HAM-A) and Hamilton Depression Scale(HAMD-17)). We used an enzyme-linked immunosorbent assay (ELISA) to measure the plasma exosomal prion protein level. The exosomal marker Heat shock protein 70 (HSP 70) was used to normalize the protein level to the exosome content.In PD patients, the plasma exosomal prion protein concentration was negatively correlated with the cognitive level. The plasma exosomal prion protein concentration was significantly higher in the PD-CI group than in the control group (p 0.05) and the PD-NCI group (p 0.05).Multivariate regression analysis indicated that plasma exosomal prion protein levels were significantly associated with the cognitive level (t=-3.185, P = 0.001) after adjusting for age, education, disease duration, HY stage and MDS-UPDRS-III scores.The plasma exosomal prion protein level is correlated with cognitive decline in PD patients and might be a potential biomarker for PD patients at risk for cognitive impairment.

Three types of multi-wall shielding were experimentally investigated for their performances under the high-velocity impact of a cm-size cylindrical projectile by using a two-stage light-gas gun. The three shields contained the same two aluminum bumpers but different rear walls, which were 7075-T651 aluminum (Al) plate, boron carbide (B4C)/Al 7075-T651/Kevlar composite plate and B4C/ultra-high molecular weight polyethylene (UHMW-PE) composite plate. The impact test was carried out using a cylindrical shape of 6 g mass 7075-T651 Al projectile in a speed range (1.6 to 1.9 km/s) to achieve an effective shield configuration. A numerical simulation was undertaken by using ANSYS Autodyn-3D and the results of this were in good agreement with the experimental results. Meanwhile, both the experimental and the numerical simulation results indicated that B4C/UHMW-PE composite plates performed a better interception of the high-velocity projectiles within the specific speed range and could be considered as a good configuration for intercepting large fragments in shielding design.

Multi-angle face detection, has a wide range of application needs in our lives. However, due to the large difference in facial features at different angles, it brings certain challenges for detection. In order to solve this problem more efficiently, we propose Step-by-Step Adjustment Networks(SAN) to perform multi-angle face detection in a coarse-to-fine manner. The method contains three stages, the first stage is that distinguish the target is human or cat's face or non-face. Then each candidate target's face orientation will be adjust to upright gradually. Initially, the position of bounding box need to be divided by several steps, and only predicting coarse orientations. Our SAN can achieve gradually decreasing the rotate ranges, and obtain accurately detect consequence with full 360? rotate angles. The experiments on Multi-Oriented FDDB and a challenging subset of WIDER FACE containing rotated facial include human and cat's, the result show that our SAN can achieve good performance.

ZnO-Bi2O3 based varistor ceramics doped with SnO2 or with SnO2, B2O3 and SiO2 were prepared by traditional solid–state reaction method respectively. The microstructure and properties of samples sintered at a low temperature range from 910 to 950°C were studied. Results show that: by low-temperature sintering, the sintering aids can improve the sample’s density and homogeneity, and therefore the overall properties of the samples. It was found that the samples sintered at 910°C with SnO2 as sintering aid possess the best performance, and the breakdown voltage is 1368 V/mm, nonlinear coefficient is 12.2, and the leakage current is less than 0.1 μA.

Nowadays, social media has increasingly become popular platforms for information dissemination and increasing incidents of cyber violence also have followed. In order to investigate the characteristics of cyber violence spreading and heterogeneity of online social networks, anSRCFE (susceptible–reader–commentator–forwarder–educatee) model is presented on scale-free networks. The spreading dynamics of cyber violence is analyzed in detail by using the mean-field theory. The basic reproductive number R 0 is calculated by the next generation matrix method and two equilibriums are derived. The theoretical analysis indicates that the basic reproductive number depends mainly on the educated degree and the topology of the underlying networks. The relationships between the basic reproductive number and human cognitive behaviors are studied. Furthermore, the global stability of the cyber violence free equilibrium is proved. The permanence of cyber violence spreading and the global attractivity of cyber violence prevailing equilibrium are also studied in detail. Finally, numerical simulations confirm the analytical results.

OBJECTIVE: To investigate the changes of facial soft tissue before and after orthognathic surgery in patients with skeletal Class Ⅲ malocclusion. METHODS: Between August 2016 and April 2017, 30 patients with skeletal Class Ⅲ malocclusion who underwent maxillary LeFort Ⅰ osteotomy and sagittal split mandible osteotomy were selected as study subjects. Among them, 11 were male and 19 were female with an average age of 22.6 years (range, 18-35 years). Full head CT scan and facial soft tissue three-dimensional image scan were performed within 2 weeks before surgery and at 6 months after surgery. A three-dimensional facial image model was established using Artec Studio 11.0 and CMF Proplan 3.0 software to analyze the facial soft tissue changes before and after surgery. The soft tissue anatomical landmarks in each area of the face were measured and compared before and after surgery. RESULTS: The area of facial soft tissue change after surgery was the maxillary nose and the lower jaw area, and the two sides did not exceed the vertical boundary of the outer canthus. After surgery, the horizontal points of bilateral alar bases and bilateral cheeks changed significantly (P

Background C-type natriuretic peptide (CNP) is a member of the natriuretic peptide family and have been implicated to be involved in maintaining vascular homeostasis and acting as a cardiac chronotropic agent in experimental studies. However, clinical evidence of its participation in cardiovascular regulation is lacking, especially in patients with chronic kidney disease (CKD). We aimed to explore the association of circulating CNP with cardiovascular alterations in CKD. Methods Seventy-six subjects with CKD were recruited. Plasma CNP-22, the bioactive form of CNP in the circulation, was measured by an enzyme immunoassay. The patients also underwent several cardiovascular evaluations including measurement of blood pressure, endothelial function, heart rate variability (HRV) and pulse wave velocity. Results Mean (±standard deviation) age of the patients were 59.9 (±14.9) years and 56.6% were male. Average plasma CNP level was 790.8 ± 309.1 pg/ml. Plasma CNP level was not increased as estimated glomerular filtration rate declined. There was no significant difference of CNP between patients with or without endothelial dysfunction (with vs. without endothelial dysfunction: 844.6 ± 365.5 pg/ml vs. 738.3 ± 231.8 pg/ml, p = 0.14). Plasma CNP showed no association with blood pressure or pulse wave velocity, but was negatively associated with time-domain HRV parameters (SDNN, RMSSD, Triangular Index). The association of CNP with HRV persisted after adjustment for potential covariates. Conclusions Our data highlights a possible link between circulating CNP and autonomic dysfunction in CKD patients. Further studies are warranted to explore the mechanisms underlying this association, as well as evaluate the ability of circulating CNP in predicting adverse cardiovascular event in CKD patients. Electronic supplementary material The online version of this article (10.1186/s12882-018-0843-3) contains supplementary material, which is available to authorized users.

Dysfunction of microRNAs (miRs) has been implicated in the development and progression of various human cancers. Our previous study demonstrated that miR-101 inhibited bladder cancer cell proliferation and invasion through inhibition of c-FOS expression. As an miR generally has many targets, other targets of miR-101 may also serve important roles in bladder cancer progression. Reverse transcription-quantitative polymerase chain reaction and western blot analyses were used to examine mRNA and protein expression, respectively. Wound healing and Transwell assays were conducted to study cell migration and invasion, respectively. The luciferase reporter gene assay was performed to verify one of the targets of miR-101. The data in the present study indicate that the expression of miR-101 is significantly reduced in bladder cancer tissues compared with that in adjacent non-tumour tissues. In addition, miR-101 expression is also downregulated in bladder cancer cell lines compared with that in normal bladder epithelial cells. Furthermore, low expression of miR-101 was significantly associated with tumour metastasis, advanced clinical stage, and poor prognosis in bladder cancer. Frizzled class receptor 4 (FZD4) was identified as a novel target of miR-101 in bladder cancer cells. The expression of FZD4 was significantly upregulated in bladder cancer tissues and cell lines. Both miR-101 overexpression and FZD4 inhibition caused a significant reduction of the migration and invasion of bladder cancer cells, whereas overexpression of FZD4 reversed the suppressive effects of miR-101 on bladder cancer cell migration and invasion. In conclusion, it was demonstrated that miR-101 downregulation is associated with bladder cancer progression and that miR-101 can inhibit bladder cancer cell migration and invasion via directly targeting FZD4. The present study expands the understanding of the molecular mechanisms underlying bladder cancer progression.

Oxidative stress serves an important role in hypertensive brain damage. Peroxisome proliferator‑activated receptor γ (PPAR‑γ) agonists possess antioxidative and anti‑apoptotic effects. The present study verified the possibility that rosiglitazone serves a neuroprotective role by alleviating oxidative stress and cell apoptosis in the hippocampi of spontaneously hypertensive rats (SHRs). SHRs and age‑matched Wistar‑Kyoto (WKY; both 56 weeks old) rats received gavage administration of vehicle or rosiglitazone (5 mg/kg/day) for eight weeks. Systolic blood pressure (SBP) was measured by the indirect tail‑cuff method. The expression ratio of activated astrocytes was analyzed by glial fibrillary acidic protein immunohistochemistry. PPAR‑γ, inducible nitric oxide synthase (iNOS), gp47phox, B‑cell lymphoma 2 (Bcl‑2), Bcl‑2‑associated X protein (Bax) and caspase‑3 expression were investigated by quantitative polymerase chain reaction and western blot analysis. The number of apoptotic cells in the hippocampus of four groups was detected using the terminal deoxynucleotidyl transferase‑mediated dUTP end‑labeling (TUNEL) method. Compared with the WKY group, the SHR group exhibited decreased Bcl‑2 and PPAR‑γ expression, increased SBP, increased ratio of activated astrocytes and TUNEL‑positive cells, increased expression of iNOS, gp47phox, caspase‑3 and Bax. Rosiglitazone administration increased Bcl‑2 and PPAR‑γ expression, decreased the ratio of activated astrocytes and TUNEL‑positive cells, decreased iNOS, gp47phox, caspase‑3 and Bax expression in the hippocampi of SHRs. However, rosiglitazone did not significantly decreased SBP in the SHR group. Therefore, rosiglitazone exerts neuroprotective effect through antioxidative and anti‑apoptotic pathways, which was independent of blood pressure control.

1H-NMR, 13C-NMR and HPLC

Table S1. Sensitivity analysis excluding patients with coronary artery disease. (DOCX 17Â kb)

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of TP53, CDKN2A, NFE2L2, CHEK2, NOTCH1, FAT1, and FBXW7. Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

A series of high energy density compounds (HEDCs) based on N-nitrourea were designed and their theoretical performances were calculated using the Gaussian programs. The predicted values of the energy density of these compounds are in the range 1.848–1.93 g cm−3, and their calculated VODs are in the range 6700–8305 m s−1. Tetranitrodiglycoluril (TNDGU) (1) and tetranitrotriglycoluril (TNTGU) (2) were synthesized and characterized by NMR (1H, 13C) and IR spectroscopy as well as elemental analyses. The structure of the aminolysis product (7) of TNDGU was further confirmed by single-crystal X-ray diffraction, which indicated that the structure belongs to P21/c space group in the monoclinic system.

The solubility of 3,7-dinitro-1,3,5,7-tetraazabicyclo [3.3.1] nonane (DPT) was measured in ethanenitrile, methanol, 1,1-dichloroethane, dimethyl sulfoxide (DMSO), acetone, ethyl acetate, ethyl acetate and methanol mixture, and acetonitrile and water mixture from 288.15 K to 308.15 K. In this paper, the determination method of DPT was first established by high-performance liquid chromatography (HPLC) with optimized chromatographic conditions. The solubility of DPT in all solvents was measured upon this chromatographic method. Experimental results show that the order of solubility can be represented as DMSO > acetonitrile > ethyl acetate > ethyl acetate/methanol (9:1, v/v) > ethyl acetate/methanol (7:3, v/v) > acetone > acetonitrile/water (9:1, v/v) > ethyl acetate/methanol (5:5, v/v) > acetonitrile/water (7:3, v/v) > 1,1 - dichloroethane > methanol. Moreover, its solubility increased with raising the temperature. The thermodynamic properties of DPT, such as solution enthalpy, have also been calculated.

Ethylene responsive factors (ERFs) are plant-specific transcription factors that are involved in a variety of biological processes. We previously demonstrated that an ERF gene from Tamarix hispida, ThERF1, encodes a protein binding to GCC-box and DRE motifs and negatively modulates abiotic stress tolerance. In the present study, microarray analysis was performed to study the genes regulated by ThERF1 on a genomic scale. There were 154 and 307 genes (respectively representing 134 and 260 unique genes) significantly up- and downregulated by ThERF1 under salt stress conditions, respectively. A novel motif, named TTG, was identified to be recognized by ThERF1, which commonly presents in the promoters of ThERF1-targeted genes. The TTG motif is also bound by other ERFs of a different subfamily from T. hispida and Arabidopsis, indicating that it is commonly recognized by ERF proteins. The binding affinities of ERFs to the TTG motif are significantly induced by salt stress. The TTG motif is more enriched than the GCC-box and DRE motifs in the promoters of ThERF1-targeted genes. Taken together, these studies suggested that the TTG motif plays an important role in the gene expression regulated by ERFs in response to salt stress.

NRAS mutation at codons 12, 13, or 61 is associated with transformation; yet, in melanoma, such alterations are nearly exclusive to codon 61. Here, we compared the melanoma susceptibility of an NrasQ61R knock-in allele to similarly designed KrasG12D and NrasG12D alleles. With concomitant p16INK4a inactivation, KrasG12D or NrasQ61R expression efficiently promoted melanoma in vivo, whereas NrasG12D did not. In addition, NrasQ61R mutation potently cooperated with Lkb1/Stk11 loss to induce highly metastatic disease. Functional comparisons of NrasQ61R and NrasG12D revealed little difference in the ability of these proteins to engage PI3K or RAF. Instead, NrasQ61R showed enhanced nucleotide binding, decreased intrinsic GTPase activity, and increased stability when compared with NrasG12D. This work identifies a faithful model of human NRAS-mutant melanoma, and suggests that the increased melanomagenecity of NrasQ61R over NrasG12D is due to heightened abundance of the active, GTP-bound form rather than differences in the engagement of downstream effector pathways. Significance: This work explains the curious predominance in human melanoma of mutations of codon 61 of NRAS over other oncogenic NRAS mutations. Using conditional “knock-in” mouse models, we show that physiologic expression of NRASQ61R, but not NRASG12D, drives melanoma formation. Cancer Discov; 4(12); 1418–29. ©2014 AACR. This article is highlighted in the In This Issue feature, p. 1355

Somatic inactivation of the serine/threonine kinase gene STK11/LKB1/PAR-4 occurs in a variety of cancers, including ∼10% of melanoma. However, how the loss of LKB1 activity facilitates melanoma invasion and metastasis remains poorly understood. In LKB1-null cells derived from an autochthonous murine model of melanoma with activated Kras and Lkb1 loss and matched reconstituted controls, we have investigated the mechanism by which LKB1 loss increases melanoma invasive motility. Using a microfluidic gradient chamber system and time-lapse microscopy, in this paper, we uncover a new function for LKB1 as a directional migration sensor of gradients of extracellular matrix (haptotaxis) but not soluble growth factor cues (chemotaxis). Systematic perturbation of known LKB1 effectors demonstrated that this response does not require canonical adenosine monophosphate–activated protein kinase (AMPK) activity but instead requires the activity of the AMPK-related microtubule affinity-regulating kinase (MARK)/PAR-1 family kinases. Inhibition of the LKB1–MARK pathway facilitated invasive motility, suggesting that loss of the ability to sense inhibitory matrix cues may promote melanoma invasion.

A recycling magnetic flocculation membrane filtration (RMFMF) process integrating circulating coagulation, magnetic enhanced flocculation and membrane filtration was investigated for the treatment of surface water micro-polluted by tetracycline, one of the typical pharmaceutical and personal care products. A bench-scale experiment was conducted and several water quality parameters including turbidity, ultraviolet absorbance at 254 nm (UV 254 ), total organic carbon and tetracycline concentration were evaluated, taking coagulation membrane filtration and magnetic flocculation membrane filtration processes as reference treatments. The experimental results showed that at the optimum doses of 20 mg·L −1 ferric chloride (FeCl 3 ), 4 mg·L −1 magnetite (Fe 3 O 4 ) and 6 mg·L −1 reclaimed magnetic flocs in RMFMF processes, removal efficiencies of above evaluated parameters ranged from 55.8% to 92.9%, which performed best. Simultaneously, the largest average particle size of 484.71 μm and the highest fractal dimension of 1.37 of flocs were achieved, which did not only present the best coagulation effect helpful in enhancing the performance of removing multiple contaminants, but also lead to the generation of loose and porous cake layers favouring reduced permeate flux decline and membrane fouling.

In this Letter, we present an adaptive aberration correction system to simultaneously compensate for aberrations and reshaping the beams. A low-order aberration corrector is adapted. In this corrector, four lenses are mounted on a motorized rail, whose positions can be obtained using a ray tracing method based on the beam parameters detected by a wavefront sensor. After automatic correction, the PV value of the wavefront is reduced from 26.47 to 1.91 μm, and the beam quality β is improved from 18.42 to 2.86 times that of the diffraction limit. After further correction with a deformable mirror, the PV value of the wavefront is less than 0.45 μm, and the beam quality is 1.64 times that of the diffraction limit. To the best of our knowledge, this is the highest performance from such a high-power, high-pulse repetition rate Nd:YAG solid-state laser ever built.

OBJECTIVE Ambulatory arterial stiffness index (AASI) is a parameter derived from ambulatory blood pressure (ABP) readings. It is calculated as 1 minus the linear slope of DBP on SBP. We tested its value in assessing arterial stiffness in dialysis patients. METHODS We performed a cross-sectional analysis of the baseline data from a cohort study. A total of 344 patients on maintenance hemodialysis from six tertiary hospitals were included. All patients underwent ABP monitoring and carotid-femoral pulse wave velocity (cfPWV) measurement. Clinical determinants of AASI were analyzed, and the ability of AASI for assessing arterial stiffness was compared with ambulatory pulse pressure (PP). RESULTS Multiple regression analysis revealed that ambulatory PP (β = 0.003), current smoker (β = -0.069), age (β = 0.003) and ambulatory SBP (β = 0.001) were independent determinants of AASI. Ambulatory PP correlates better with cfPWV than AASI (r = 0.28 for AASI and 0.59 for PP; P for difference

Previous studies suggested that the reactive hyperemia index (RHI) is a promising cardiovascular risk predictor. We aimed to evaluate clinical determinants of RHI and its association with circulating endothelial injury and cardiac markers in hemodialysis patients. Among 368 patients recruited, RHI was evaluated by peripheral arterial tonometry (PAT) on a midweek nondialysis day. Clinical determinants of RHI were explored by multiple stepwise regression analysis and associations between RHI and circulating markers were evaluated by general linear models. The major cause of a failed PAT test was poor signal (82.1%). Intraclass correlation coefficient for reproducibility evaluation was 0.74. Multiple regression analysis showed traditional clinical factors only explained 7% of the variance of natural logarithm RHI (LnRHI) in the patients. In association analyses, LnRHI showed significant positive associations with Von Willebrand factor (vWF) (p = 0.04) and tissue factor (p = 0.047). It also associated positively with troponins (p ≤ 0.02 for both). In conclusion, performance of the PAT test was acceptable in dialysis patients and traditional clinical variables had very limited influence on RHI in these subjects. Among a panel of conventional endothelial injury markers, RHI showed very modest associations with only vWF and tissue factor. RHI associated positively with troponins in the patients.

Background: Recent data suggest that there is a pathogenic role for CXC ligand 16 (CXCL16) in cardiovascular diseases. Little is known about circulating CXCL16 in patients with kidney dysfunction. We explored the relationships of plasma CXCL16 with cardiac injury markers in a group of dialysis patients. Methods: Plasma CXCL16 and C-reactive protein (CRP) were measured in 366 patients who were on maintenance hemodialysis. Cardiac injury was evaluated via measurements of the circulating B-type natriuretic peptide (BNP), N-terminal prohormone of brain natriuretic peptide (NT proBNP), Troponin I (TnI), and Troponin T (TnT). Sixty healthy subjects who were frequency matched with the patients on the basis of age and gender were recruited as healthy controls. Results: The mean age of the patients was 52.5 ± 12.1 years and 56.3% were male. Circulating CXCL16 was significantly higher in the patients than in the controls (patients vs. controls: 477.3 (367.0-647.1) pg/mL vs. 229.5 (203.8-254.5) pg/mL; p < 0.001). The log-transformed (log-) CXCL16 level was correlated with all 4 cardiac markers (log-BNP, log-NTproBNP, log-TnI, and log-TnT) with high levels of significance (all p < 0.001), even after extensive controls for the covariates. In contrast, CRP was correlated only with BNP (marginally) and NT proBNP and was not correlated with troponins. Conclusion: We showed, for the first time, highly significant relationships of circulating CXCL16 level with cardiac injury markers in dialysis patients. Our data suggest that circulating CXCL16 is possibly involved in the pathological process of cardiovascular damage in dialysis patients and may serve as a therapeutic target for cardiac protection in these patients.