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Hyperlipidaemia is a major risk factor of atherosclerotic cardiovascular disease (ASCVD). Risk of cardiovascular events depends on cumulative lifetime exposure to low-density lipoprotein cholesterol (LDL-C) and, independently, on the time course of exposure to LDL-C, with early exposure being associated with a higher risk1. Furthermore, LDL-C fluctuations are associated with ASCVD outcomes2–4. However, the precise mechanisms behind this increased ASCVD risk are not understood. Here we find that early intermittent feeding of mice on a high-cholesterol Western-type diet (WD) accelerates atherosclerosis compared with late continuous exposure to the WD, despite similar cumulative circulating LDL-C levels. We find that early intermittent hyperlipidaemia alters the number and homeostatic phenotype of resident-like arterial macrophages. Macrophage genes with altered expression are enriched for genes linked to human ASCVD in genome-wide association studies. We show that LYVE1+resident macrophages are atheroprotective, and identify biological pathways related to actin filament organization, of which alteration accelerates atherosclerosis. Using the Young Finns Study, we show that exposure to cholesterol early in life is significantly associated with the incidence and size of carotid atherosclerotic plaques in mid-adulthood. In summary, our results identify early intermittent exposure to cholesterol as a strong determinant of accelerated atherosclerosis, highlighting the importance of optimal control of hyperlipidaemia early in life, and providing insights into the underlying biological mechanisms. This knowledge will be essential to designing effective therapeutic strategies to combat ASCVD.

The adaptive immune system plays an important role in the development and progression of atherosclerotic cardiovascular disease. B cells can have both proatherogenic and atheroprotective roles, making treatments aimed at modulating B cells important therapeutic targets. The innate-like B-cell response is generally considered atheroprotective, while the adaptive response is associated with mixed consequences for atherosclerosis. Additionally, interactions of B cells with components of the adaptive and innate immune system, including T cells and complement, also represent key points for therapeutic regulation. In this review, we discuss therapeutic approaches based on B-cell depletion, modulation of B-cell survival, manipulation of both the antibody-dependent and antibody-independent B-cell response, and emerging immunization techniques.

Regulatory T cells and type-2 innate lymphoid cells represent 2 subsets of immune cells, which have been shown in preclinical models to be important in atherosclerosis and myocardial repair. Regulatory T cells play a crucial role in immune homeostasis and tolerance via their interactions with effector T cells, dendritic cells, and monocytes/macrophages. They also utilize and secrete inhibitory cytokines, including interleukin 10 and transforming growth factor β, to regulate or suppress pathogenic immune responses. Type-2 innate lymphoid cells have an important role in type-2 immune responses and tissue repair through secreting interleukins 5 and 13, as well as a variety of biological mediators and growth factors. Intriguingly, interleukin-2 has emerged as a common cytokine, which can be harnessed to upregulate both cell types, and also has important translational consequences as clinical trials are ongoing for its use in cardiovascular disease. Here, we briefly review the biology of these regulatory immune cell types, discuss the preclinical and clinical evidence for their functions in cardiovascular disease, examine the prospects for clinical translation and current ongoing trials, and finally, postulate how overlap in the mechanisms of upregulation may be leveraged in future treatments for patients.

To investigate the differences in mRNA and protein expressions of MDM2(mouse double minute 2 homolog) and P73in cancer and cancer-adjacent tissues in patients with non-small-cell lung carcinoma (NSCLC).

Seismology illuminates physical processes occurring during underground explosions, not all yet fully understood. The thus‐far strongest North Korean test of 3 September 2017 was followed by a moderate seismic event (mL4.1) after 8.5 min. Here we provide evidence that this aftershock was a nontectonic event which radiated seismic waves as a buried horizontal closing crack. This vigorous crack closure, occurring shortly after the blast, is studied in the North Korea test site for the first time. The event can be qualitatively explained as rapid destruction of an explosion‐generated cracked rock chimney due to cavity collapse, although other compaction processes cannot be ruled out. North Korea detonated its strongest underground nuclear test in September 2017. It attracted the public interest worldwide not only due to its significant magnitude (6.3 mb) but also because it was followed 8.5 min later by a weaker event. Was the delayed shock a secondary explosion, an earthquake provoked by the shot, or something else? We answer these questions, thanks to unique data from near‐regional broadband stations. We basically solve a simple problem—fitting observed seismograms by synthetics. The good fit means that we understand why and how the seismic waves are radiated. According to our model, the explosion created a cavity and a damaged “chimney” of rocks above it. The aftershock was neither a secondary explosion nor a triggered tectonic earthquake. It occurred due to a process comparable to a “mirror image” of the explosion, that is, a rock collapse, or compaction, for the first time documented in North Korea's test site. Interestingly, shear fault motions, typical for natural earthquakes, were extremely small both in the explosion and in the aftershock. Small natural earthquakes also occur at the test site, and geotechnical works might trigger them. Thus, all studies related to rock stability of the site, and prevention of radioactive leakage, are important. Waveform analysis indicates that the explosion and its aftershock radiated seismic waves as crack opening and crack closing, respectivelyThe aftershock was a non‐shear event possibly resulting from deterioration of the cavity and the explosion‐damaged rock chimney

PurposeTo determine what impact rapid ascension to a high-altitude environment has on the retina with the aim of preventing and treating high-altitude oculopathy.Patients and methodsParticipants in the study were members of the Chinese military assigned to the high-altitude environment of the Tibetan plateau. Ninety-one participants were enrolled in the study. Optical coherence tomography was used to measure the thickness of retina-related indicators. Measurements were taken before and after exposure to the high-altitude environment and upon return to the baseline altitude.ResultsFollowing exposure to the high-altitude environment in Tibet, there was a significant increase in retinal nerve fiber layer (RNFL) thickness in the temporal and nasal quadrants of the optic disc, whilst a significant decrease in RNFL thickness in the inferior optic disc was also observed. A significant increase in RNFL thickness in the superior and inferior macula was also evident, along with a significant increase in the ganglion cell layer thickness in the superior macula. Upon return to the baseline altitude, all measurements returned to baseline levels except for the RNFL of the inferior macula, which was significantly thicker. Pathological changes were also documented in the eyes of nine participants upon returning to baseline altitude, including ischemic optic neuropathy, myopia, and cortical amaurosis.ConclusionsThe high-altitude environment can have a negative impact on the health of the retina and may contribute to the incidence of various eye diseases. This study deepens the understanding of what impact a high-altitude environment has on retina and provides reliable data for blindness prevention and treatment.

Filtering methods have been widely used to improve the forecast performances of hydrological models. Although extensive research has been carried out on filtering methods in the hydrology literature, researchers have not treated the noise statistics of filtering methods in much detail. Wrongly specified noise statistics can lead to degraded state estimates and even filter divergence. A powerful approach for state estimation in the presence of unknown noise statistics is the interacting multiple model method (IMM), which solves the noise specification problem by combining the strengths of multiple filters with different noise statistics. The IMM method has received little to no attention in the hydrologic context. This paper proposes a novel approach (IMM‐CKF) for updating the states of hydrological models in the presence of unknown noise statistics by combining the cubature Kalman filter (CKF) with the IMM. The CKF is a popular nonlinear filter that has received little attention in the hydrology literature. The method is tested using a lumped hydrological model. The results of the synthetic case suggest the IMM‐CKF can yield an accurate estimate for the switch as well as the changed states when there are abrupt changes in the noise statistics of true noises, even if sub‐filter noise statistics are not equal to the real ones. The real case results (a forecast experiment) show that the IMM‐CKF has successfully combined the strengths of different sub‐filters and associated noise statistics. The IMM‐CKF can be useful for hydrological forecasting, especially when useful information about the true noise statistics is unavailable. A novel method for updating states of hydrological models in the presence of unknown noise statistics is proposedThe method can improve state estimation performance by combining the strengths of multiple filters with different noise statisticsThe method can improve the forecast performance of a hydrological model by state updating A novel method for updating states of hydrological models in the presence of unknown noise statistics is proposed The method can improve state estimation performance by combining the strengths of multiple filters with different noise statistics The method can improve the forecast performance of a hydrological model by state updating

ABSTRACTTitanium carbide–titanium diboride (TiC–TiB2) composite powders were synthesised through a carbothermal reduction method by using titanium dioxide, boric acid, and different carbon sources (namely, carbon black, sucrose, and glucose) as starting materials. The thermal decomposition behaviour of the precursors was studied by thermogravimetry–differential thermal analyser. Phase compositions and morphologies of the synthesised products were characterised by X-ray diffractometer and scanning electron microscope. When n(Ti):n(B):n(C) = 1.0:2.5:5.0, the blended stock mainly formed TiB2with sucrose or glucose as a carbon source, whereas the stock produced TiC when carbon black was the source. At an optimum reaction temperature, the particles of the powders synthesised from carbon black as a carbon source were the smallest at approximately 100 nm. With increasing amount of boric acid in the precursor, the morphologies of the samples changed into less spherical particles, and more flaky grains and small particles with irregular structures were observed.

ABSTRACTThe electric current pulse (ECP) was applied on the liquidus of 304 stainless steel during solidification and the pitting corrosion of the water-quenched specimens was explored in the present work. The results revealed that the utilisation of ECP can inhibit manganese sulphide from segregating around oxide inclusions during solidification and consequently, the pitting corrosion resistance of ECPed steel was significantly improved. Hence, the application of ECP during solidification might be an efficient way to improve the pitting corrosion resistance of the 304 stainless steel.This paper is part of a themed issue on Materials in External Fields.

Chronic lymphocytic leukemia (CLL) is a progressive malignancy of mature B-cells that involves the peripheral blood (PB), lymph nodes (LNs) and bone marrow (BM). Although the majority of CLL cells are in a resting state, small populations of proliferating cells exist; however, the anatomical site of active cell proliferation remains to be definitively determined. Based on findings that CLL cells in LNs have increased expression of B-cell activation genes, we tested the hypothesis that the fraction of ‘newly born’ cells would be highest in the LNs. Using a deuterium oxide (2H) in vivolabeling method in which patients consumed deuterated (heavy) water (2H2O), we determined CLL cell kinetics in concurrently obtained samples from LN, PB and BM. The LN was identified as the anatomical site harboring the largest fraction of newly born cells, compared to PB and BM. In fact, the calculated birth rate in the LN reached as high a 3.3% of the clone per day. Subdivision of the bulk CLL population by flow cytometry identified the subpopulation with the CXCR4dimCD5brightphenotype as containing the highest proportion of newly born cells within each compartment, including the LN, identifying this subclonal population as an important target for novel treatment approaches.

Background/Objective:: Increasing dietary diversity is concurrent with an increasing prevalence of adiposity in China, but the association between these variables remains ambiguous. This study reveals an association between dietary diversity and body mass (underweight, overweight and obesity) in Chinese adults. Subjects/Methods:: Data from 17 825 participants (age, 18–65 years) were pooled from four survey waves (2004, 2006, 2009 and 2011) of the Chinese Health and Nutrition Survey. Anthropometric data and dietary intake information obtained through a 24-h dietary recall for 3 consecutive days were collected. Information on covariates, namely those regarding the socioeconomic status and lifestyle of each participant, were collected. The dietary diversity score (DDS) and entropy were used to represent dietary diversity. The association between dietary diversity and adiposity was analyzed by using multivariable-adjusted multinomial logistic regression. Results:: A positive association between dietary diversity and overweight was detected only in men (DDS: OR=1.09 (1.03–1.17); entropy: OR=1.60 (1.24–2.07)). The results were confirmed by analyzing the interaction between sex and diversity (DDS: OR=1.27 (1.17–1.37); entropy: OR=2.89 (2.11–3.89)). In contrast, no significant association was detected between dietary diversity and underweight/obesity (all P>0.05). Dietary consumption was compared between sexes to explain the different effects of dietary diversity on body mass in men and women. The results indicated that men typically had a higher consumption of meat (P<0.01). Conclusions:: Higher dietary diversity is positively associated with overweight in men. Additional preventive strategies that promote a healthy diet should focus on men.

The frequent typhoons in the northwest Pacific drive oceanic responses, for example, changes in sea surface temperature (SST) and chlorophyll‐a (Chl‐a). A composite analysis shows that SST (Chl‐a) around the typhoon center decreases (increases). The SST begins to decrease 3 days before the typhoon’s arrival and further decreases until 2 days following the typhoon’s passage. The Chl‐a increases rapidly after the typhoon’s arrival, and the maximum value is reached 3 days after the typhoon. Large oceanic responses are often associated with typhoons that have high wind speeds and slow translation speeds. From the perspective of the upper ocean structure, increasing changes in SST are identified with a shallower pre‐typhoon mixed layer depth (MLD). However, a significant dependence of the Chl‐a response on the pre‐typhoon MLD emerges only when the depth of typhoon‐induced mixing is greater than the pre‐typhoon MLD. This study helps to quantitatively describe typhoon‐induced changes with consideration of the determinant oceanic environment. Typhoons in the northwestern Pacific induce strong oceanic responses. Using 17 years of satellite observations, the impacts of typhoons on sea surface temperature (SST) and chlorophyll‐a (Chl‐a) are investigated. The SST time series shows that the SST begins to decrease 2 days before the typhoon’s arrival and continues to decrease until 2 days following the typhoon’s passage. The Chl‐a has a weak peak 2 days prior to the typhoon’s arrival, rapidly increases after the typhoon arrives, reaches the strongest response on the third day of the typhoon, and gradually decreases to a value slightly higher than the pre‐typhoon level. Prominent responses are associated with typhoons that have stronger intensity and slower translation speed. The pre‐typhoon upper ocean structure plays a dominant role in determining oceanic responses. Surface cooling is generally stronger where the pre‐typhoon mixed layer depth (MLD) is shallow. However, the change in Chl‐a shows a contrasting response in that the response prominently increases only when the depth of typhoon‐induced mixing exceeds the pre‐typhoon MLD. This study poses a quantitative approach to assess the influence of typhoons on the upper ocean from a statistical perspective with consideration of the upper ocean structure. Sea surface temperature and chlorophyll‐a changes are composited to assess their responses to the passage of typhoons in the northwest PacificLarge responses are introduced by strong and slow‐moving typhoons, and surface cooling increases with shallow mixed layer depth (MLD)Responses in chlorophyll‐a increase only when the depth of typhoon‐induced mixing exceeds the pre‐typhoon MLD Sea surface temperature and chlorophyll‐a changes are composited to assess their responses to the passage of typhoons in the northwest Pacific Large responses are introduced by strong and slow‐moving typhoons, and surface cooling increases with shallow mixed layer depth (MLD) Responses in chlorophyll‐a increase only when the depth of typhoon‐induced mixing exceeds the pre‐typhoon MLD

Hydrological models are widely used for flood forecasting, and proper initialization of hydrological models is essential. Although the unscented Kalman filter (UKF) has shown promise in the context of operational forecasting, it is limited by its intrinsic instability caused by the loss of positive semidefiniteness of the covariance matrix. Effective methods for tackling this problem have not been seen in the literature. The cubature Kalman filter (CKF) is a powerful nonlinear filter for state estimation, which has received little attention in the hydrologic context. In this paper, to overcome the instability problem of the UKF, a new modified UKF (UKF‐M) is proposed by modifying the default UKF tuning strategy, and a novel nonlinear filter (CKF) is introduced to update the states of hydrological models. The methods are tested using a lumped hydrological model. The results of the stability experiment suggest that both the UKF‐M and CKF can overcome the instability problem, while the original UKF can fail due to the loss of positive semidefiniteness of the covariance matrix. The results of a reforecast experiment in an operational context show that both filters can improve the forecast performance by updating the model state based on the observed discharge, with the UKF‐M achieving better forecast performances. The UKF‐M and CKF can be used to overcome the instability problem of the original UKF and are valuable methods for improving forecast performances of hydrological models by state updating. A new modified unscented Kalman filter is proposed to overcome the instability problem caused by the loss of positive semidefinitenessAn effective filter (cubature Kalman filter) is introduced to improve hydrological models’ forecast performances by state updatingBoth filters can improve the forecast performance, with the modified unscented Kalman filter achieving better forecast performance A new modified unscented Kalman filter is proposed to overcome the instability problem caused by the loss of positive semidefiniteness An effective filter (cubature Kalman filter) is introduced to improve hydrological models’ forecast performances by state updating Both filters can improve the forecast performance, with the modified unscented Kalman filter achieving better forecast performance

The evolution of teleost coloration is strongly linked with the fish-specific genome duplication (FSGD). Sepiapterin reductase (Spr) is commonly required in pteridine pigment synthesis and two paralogs are found in teleosts. However, the functions of spraand sprbin pigmentation have not been completely elucidated. Here we found that sprawas intensively expressed in skin, fins and scales of koi carp, while sprbwas ubiquitously expressed in all tissues.Then, the Spr enzyme activity inhibitor, sulfapyridine (SFD), was used to explore the phenotype and genes variation after sprinhibition. Following the administration of SFD, sprawas significantly suppressed but sprbwas up-regulated in skin. Additionally, the color phenotypes shifted from red to yellow due to a reduction in carotenoid concentration and the number of xanthophores/erythrophores in scales. Furthermore, the genes involved in carotenoid metabolism were influenced. However, pteridine metabolism-related genes rarely exhibited obvious changes. The results indicate that sprainhibition resulted in the dysregulation of carotenoid metabolism and pigment cells reduction, whereas sprbwas likely to maintain the conserved functions in pteridine synthesis for metabolic homoeostasis. This study provided evidences for the different functions of sprparalogs in carotenoid and pteridine metabolism and for better understanding of the relationship between genome duplication and color pattern diversification.

Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3–22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but ∼50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3–5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment- and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery.

The kidney-brain interaction has been a topic of growing interest. Past studies of the effect of kidney function on intracerebral hemorrhage (ICH) outcomes have yielded inconsistent findings. Although the second, main phase of the Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2) suggests the effectiveness of early intensive blood pressure (BP) lowering in improving functional recovery after ICH, the balance of potential benefits and harms of this treatment in those with decreased kidney function remains uncertain.

The aim of our study was to describe the impact of mid-urethral sling procedure for the treatment of stress urinary incontinence (SUI) on female sexual function. We used PubMed (updated March 2015) to conduct a literature electronic search that included peer-reviewed English language articles. We analyzed the studies about the impact of mid-urethral slings on female sexual function. There are different and contradictory results of the effects of mid-urethral sling on female sexual function. However, more papers show that women undergoing mid-urethral sling procedures report that their sexual function is improved or remains unchanged. The main mechanism of this improved sexuality is the complete relief from coital incontinence, reduction in anxiety and avoidance of sex, whereas the most common symptom related to worsened sexual activity is dyspareunia. Women undergoing sling procedures for SUI should be informed that their sexual activity is likely to remain unchanged or even improve after the operation, but that dyspareunia may occur.

Researching on fuel cells is an important direction of developing new energy in the twenty-first century. Fuel cells present broad application in the aerospace, military, power stations, electric vehicles and portable power applications due to their high power conversion efficiency (40–60%), environmental friendliness and reliability, small size, low noise and so on. This review gives an introduction into the fundamental, characteristics and applications of various fuel cells. In addition, the development of increasing use of polymers in fuel cells is also prospected.

To assess the crashworthiness of simple wrought magnesium structures, the axial deformation behaviour of different square tubes produced from magnesium alloys AZ31 and ZE10 were numerically investigated under quasi-static compressive loading conditions. Finite-element simulations were conducted to predict and assess the plastic buckling and crush behaviour. The necessary data to determine parameters for the plastic potential were taken from compression tests conducted along different orientations. The yield function Hill48 was selected, despite its inability to capture the strength differential effect. The modelling approach pursued is justified by considering the mechanical loading conditions, the fabrication process of the profiles and its implication on strain anisotropy, balancing achievable accuracy and computational efforts. The simulation results revealed that the material work hardening rates evidenced in uniaxial compression tests influenced the buckling modes as well as the energy dissipation.

AbstractThe linear micromorphic electroelastic theory is proposed to solve bending problems of piezoelectric micro-beam in this paper. The basic governing equations with the boundary conditions are derived through the variational principle. Both the cantilever piezoelectric micro-beam subjected to a concentrated load at the free end and the simply supported micro-beam subjected to a distributed load are analyzed. It is found that the predictions from the micromorphic electroelastic theory are remarkably different from those from the classical theory when the micro-beam thickness is approximate or equal to the characteristic length scale parameter, but their difference is slight when the micro-beam thickness is much larger than the characteristic length scale parameter. As a result, it is concluded that the size effect is significant when the micro-beam thickness is comparable to the characteristic length scale parameter.

In this study, a novel phosphorus-containing flame retardant (IFR) of spirocyclic pentaerythritol diphosphonate dinitroguanidine (SPDD) was successfully synthesized, which was characterized by 1H?NMR, 31P?NMR and FTIR spectra. At the same time, the SPDD was used in LLDPE to prepare flame-retardant materials whose flammability and thermal behavior were studied by thermogravimetric analysis (TGA), limiting oxygen index (LOI) and scanning electron microscopy (SEM). The TGA data showed that SPDD could effectively enhance the thermal stability and char residue of LLDPE/IFR composite. And with the increase of SPDD, the LOI value of LLDPE/IFR increases obviously. When SPDD reached 30?wt%, the LOI value of LLDPE/IFR reaches 31?%. The SEM also shows the surface of intumescent chars of LLDPE/IFR (30?%) has many sphere-like swollen bubbles.

A two-year field experiment with a split-split plot design was conducted to investigate the effects of soil N(0, 120 and 240 kg N·ha-1) and foliar Zn applications at different growth stages (jointing, flowering, early grain filling, and late grain filling) on Zn translocation and utilization efficiency in winter wheat grown on potentially Zn-deficient soil. Our results showed that foliar Zn application at the early grain filling stage significantly increased the Zn concentration in the grain (by 82.9% compared to control) and the Zn utilization efficiency (by 49% compared to jointing). The Zn concentration in the straw consistently increased with the timing of the foliar Zn application and was highest at late grain filling. However, the timing of the Zn application had little effect on Zn uptake in the grain and straw. A high N supply significantly increased the Zn concentration in and uptake by grain and straw, but it had little effect on the efficiency of Zn utilization. Consequently, a foliar Zn application at early grain filling causes Zn to re-translocate into grain from vegetative tissues, resulting in highly nutritional wheat grain. Finally, these practices improved the efficiency of Zn utilization in winter wheat and led to Zn-enriched straw, which may contribute to Zn recycling if it is returned to the field. The results also indicated that N nutrition is a critical factor in both the concentration and translocation of Zn in wheat.

Objective:To assess the potential efficacy of maggot debridement therapy (MDT) compared with standard care for diabetic foot ulcers (DFUs).Method:A meta-analysis was performed on the evidence for MDT for DFUs. Databases, including PubMed, Web of Science, the Cochrane library, EMbase, EBSCohost, Springer link, ScienceDirect and Ovid-Medline, were electronically searched for randomised controlled trials, case-control studies and controlled clinical trials, up to 31 December 2012, and relevant references of the included articles were also manually searched. the literature was screened, the data were extracted and the methodological quality of the included studies was assessed. meta-analyses were performed on the included data, for the outcomes healing rate, time to healing, incidence of infection, amputation rate and antibiotic-free days or antibiotics usage.Results:Overall, four studies comparing MDT with standard therapy on a total of 356 participants were included. the results of meta-analyses suggested that the MDT group was significantly superior to the control group in the percentage of DFUs to achieve full healing (RR=1.8, 95%CI=1.07; 3.02; p=0.03), amputation rate (RR=0.41, 95%CI=0.20; 0.85; p=0.02), time to healing (RR=–3.70, 95%CI=–5.76; –1.64; p=0.0004) and number of antibiotic-free days (126.8 ± 30.3 days vs 81.9 ± 42.1 days; p=0.001); however, collated differences in incidence of infection after intervention revealed no evidence of a difference between the MDT and control groups (RR=0.82, 95%CI=0.65; 1.04, p=0.10).Conclusion:Although MDT may be a scientific and effective therapy in treatment of DFUs, the evidence is too weak to routinely recommend it for treatment. large studies and sample sizes are needed to assess the efficacy and safety of MDT in the treatment of DFUs.Declaration of interest:There were no external sources of funding for this study. the authors have no conflicts of interest to declare with regard to this work or its contents. X. Tian and X.M. Liang contributed equally to this work.

Genetic mutations in GATA4, a transcriptional factor, have been found to cause congenital heart diseases. The underlying mechanism, however, remains largely unknown. We previously reported 7 heterozygous variants in patients with ventricular septal defects (VSD). Here we functionally characterized a de novo mutation p.S335X and demonstrated that this mutation led to the pre-termination of its translation, producing a truncated GATA4 lacking a conservative region at C-terminus. Truncated GATA4 did not disturb its subcellular localization; however, it delayed the cardiomyocyte differentiation in P19cl6 model and prohibited Bcl2 expression that led to apoptosis proved by fragmented genomic DNA and positive TUNEL staining in H9C2 cells. By ChIP assay, we showed that GATA4 without C-terminus reduced its DNA binding affinity and suppressed the expressions of its target genes. These findings suggest that C-terminus of GATA4 is critical to maintain DNA binding, and genetic mutations in this region may affect genes important for myocyte apoptosis and differentiation associated with congenital heart defects.

To investigate the effect of Zn fertilization on soil Zn fractions and grain Zn concentration in wheat grown on potentially Zn-deficient soil, a field experiment was carried out. The experimental design was split plot consisted of two varieties of wheat (Zhengmai 9023 and Xinong 889) with five Zn levels (0, 7.5, 15, 30 and 45 kg Zn/ha). Results showed that Zn fertilization had no significant effect on wheat yield and grain Zn concentration, and the recovery of Zn fertilizer was only 0.06% to 0.29%. However, the amount of soil DTPA-Zn was increased by 2.3-9.8-folds as Zn supplementation increases during the whole wheat growth stage as compared to the control (Zn0treatment). Besides, DTPA-Zn was positively correlated with both Loose organic matter bound Zn (LOM-Zn) and Exchange Zn (Ex-Zn), and their partial correlation coefficients were 0.558 and 0.119, respectively. Moreover, these two fractions also showed positive correlation with grain Zn concentration. The amount of LOM-Zn was firstly increased with increasing Zn fertilizer levels then gradually decreased as it get converted to mineral bound Zn (Min-Zn). Zn fertilization in this potentially Zn deficient soil increased the amount of DTPA-Zn in the whole wheat growth stage; however, grain Zn concentration cannot be significantly increased as Zn levels increase, thus suggesting that there are inhibitory factors for Zn absorption and translocation. Furthermore, the amount of soil DTPA-Zn perhaps cannot exactly reflect the capability of soil to supply Zn.

ABSTRACTA finite element method combined with three-dimensional anisotropic piezoelectric continuum damage mechanics is presented to simulate quasi-static crack propagation behavior in piezoelectric ceramics in this paper. In this method, the three-dimensional anisotropic piezoelectric damage constitutive model is utilized for characterizing the effects of mechanical and electrical damages on the fields near the crack tip, the combined-damage from the dominant mechanical and electrical damage components is regarded as the fracture criterion, and the gradient of combined-damage is assumed to control crack growth direction. A set of numerical simulations of the midspan crack propagation in a three-point bending PZT-4 beam are performed in various loading conditions. After the numerical results are validated by comparison with the corresponding experimental ones, the effects of mechanical and electrical loads on the cracking be havior are respectively evaluated. It is found from the obtained results that mechanical and electrical loads influence on the damage fields in the vicinity of the crack-tip, as well as the crack growth rate, in a significant way. With the increment in mechanical loading, the crack growth rate obviously increases. This means that positive and negative electric fields enhance and inhibit crack propagation, respectively.

Virtual enterprise (VE) is a new type of cooperation mode and has attracted considerable attention in the global manufacturing environment. Success of the VE is highly dependent on participators, and thus selection of partners becomes a crucial issue. Partner selection can be considered as a multi-attribute decision-making problem involving variable criteria and a large number of alternatives. However, decision makers are usually uncertain of their preferences owing to changeable types of criteria and incomplete information on candidates. Therefore, an integrated approach is presented in this paper. First, a decision matrix is flexibly established according to the requirements, and then attribute weights of the decision matrix are calculated using the combination weighting method. Subsequently, the preference-order of candidates is provided to enable decision makers to choose suitable partners using grey relational analysis. Finally, an illustrative example is used to explain an application of the proposed approach.

Three field experiments were conducted to determine the effect of soil Zn, foliar Zn, and soil N application on Zn and phytic acid concentrations in wheat grain grown on potentially Zn-deficient soil. Results showed significant genotypic variation in grain Zn concentrations among fifteen wheat cultivars commonly grown in northwest China. Soil Zn application had mixed effects, increasing grain Zn concentrations of some cultivars by as much as 21%, but reducing grain Zn concentrations of other cultivars by as much as 14%. In comparison, foliar Zn application increased grain Zn concentrations by 26 to 115%. Grain Zn concentrations were 14% larger in the combined (foliar Zn + soil Zn) treatment compared to the foliar Zn treatment, but the added cost of soil Zn application may not be economically justifiable. Wheat grain phytic acid concentrations and phytic acid: Zn molar ratios were less in the foliar Zn and (foliar Zn + soil Zn) treatments compared to the soil Zn and the unfertilized treatments. This indicated that foliar Zn increased Zn bioavailability. Best results were obtained when foliar Zn was applied at early grain filling. Overall, these findings indicate that foliar Zn application to Zn-efficient cultivars could reduce human Zn deficiency in regions with potentially Zn-deficient soil.

Using ionic liquid (IL) [C2MIM][PF6] as an additive could remarkably improve the performance of the acetonitrile (CAN) process, which is the most widely used distillation process to produce 1,3‐butadiene (1,3‐BT). In this work, a rigorous simulation of a new IL process to produce 1,3‐BT was carried out to evaluate the performance of IL additive on an industrial scale, using UNIFAC as the global thermodynamic model. Based on the simulation models, some key operation parameters, such as solvent ratio and reflux ratio, were determined by sensitivity analysis. Furthermore, a multi‐objective optimization was proposed and performed considering both the energy consumption and environmental impact (green degree) of the new process. A nonlinear mathematical model was established to express this multi‐objective optimization problem, which includes six decision variables and involves maximizing the green degree of the process, the purity and the recovery of 1,3‐BT, and minimizing the energy consumption of the process. The optimization results showed that the energy consumption of the IL‐containing process could be reduced by 22 % and that its green degree could be improved by 9.2 %.

The self-assembly of perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA) on graphene with coverage in the range of 0.3−3 monolayers (MLs) is characterized by a DFT-based ab initiocalculation method. For α modification mode, with a critical thickness of 1 ML, the growth of PTCDA on graphene follows the Stranski−Krastanov (SK) mode. For β modification mode, the PTCDA can form two complete MLs on a graphene substrate. From the thermodynamic viewpoint, α modification mode is more stable than β modification mode. At 1 ML, the PTCDA follows a planar configuration on graphene, which is also almost unperturbed by typical defects in the graphene sheet. The PTCDA adlayer remains its planar and continuous herringbone structure on graphene with three typical defects. For α modification mode with 2 or 3 ML coverage, the molecular planes incline to the substrate plane with angles around 9° and 13°, respectively, which indicates that a bulk-like phase appears. This also enhances the lateral intrinsic charge transport characteristics. For α modification mode, the total amount of charge transfer between PTCDA and graphene per 5√3 × 5 super cell at 2 MLs saturates with 0.42e, which is 0.1 and 0.06elarger than those of 1 and 3 MLs, respectively.

MDAM technology is a brand-new and low-cost machining technology. Based on the brief introduction of MDAM system, the generator structure and additional anode access method are in-depth studied. The results show that the cost of consumable parts can be reduced to a minimum of only 10.9% of the original design for optimized generator based on cost reduction, but have the problems of lifespan reduction and frequently replacement. Cost and efficiency are considered comprehensively in the design of final optimized generator, which not only extends the lifespan of consumable pieces about 4 times and improves machining efficiency, but also reduces the cost to only 36.4% of the original design. So it is adopted by the system. On the choice of additional anode access methods, through comprehensive comparison, the method of additional anode attaching with the nozzle directly is ascertained, which is simple and easy realized, and reduces the damage to the surface and sub-surface during the machining of ceramics and other brittle materials. The results lay a solid foundation for further technology promotion.

Tetraploid (4N) complementation assay is regard as the most stringent characterization test for the pluripotency of embryonic stem (ES) cells. The technology can generate mice fully derived from the injected ES cell (ES-4N) with 4N placentas. However, it remains a very inefficient procedure owing to a lack of information on the optimal conditions for ES incorporation into the 4N embryos. In the present study, we injected ES cells from embryos of natural fertilization (fES) and somatic cell nuclear transfer (ntES) into 4N embryos at various stages of development to determine the optimal stage of ES cells integration by comparing the efficiency of full-term ES-4N mouse generation. Our results demonstrate that fES/ntES cells can be incorporated into 4N embryos at 2-cell, 4-cell and blastocyst stages and full-term mice can be generated. Interestingly, ntES cells injected into the 4-cell group resulted in the lowest efficiency (5.6%) compared to the 2-cell (13.8%, P> 0.05) and blastocyst (16.7%, P< 0.05) stages. Because 4N embryos start to form compacted morulae at the 4-cell stage, we investigated whether the lower efficiency at this stage was due to early compaction by injecting ntES cells into artificially de-compacted embryos treated with calcium free medium. Although the treatment changed the embryonic morphology, it did not increase the efficiency of ES-4N mice generation. Immunochemistry of the cytoskeleton displayed microtubule and microfilament polarization at the late 4-cell stage in 4N embryos, which suggests that de-compaction treatment cannot reverse the polarization process. Taken together, we show here that a wide developmental range of 4N embryos can be used for 4N complementation and embryo polarization and compaction may restrict incorporation of ES cells into 4N embryos.

AbstractDeriving histocompatible embryonic stem (ES) cells by somatic cell nuclear transfer (SCNT) and parthenogenetic activation (PA) requires fresh oocytes, which prevents their applications in humans. Here, we evaluated the efficiency of deriving ES cells from mature metaphase II (MII) and immature metaphase I (MI) vitrified oocytes, by PA or SCNT, in a mouse model. We successfully generated ES cell lines from PA (MII and MI) and SCNT (MII and MI) blastocysts. These cell lines expressed genes and antigens characteristic of pluripotent ES cells and produced full-term pups upon tetraploid embryo complementation. This study established an animal model for efficient generation of patient-specific ES cell lines using cryopreserved oocytes. This is a major step forward in the application of therapeutic cloning and parthenogenetic technology in human regenerative medicine and will serve as an important alternative to the iPS cell technology in countries/regions where these technologies are permitted.

AbstractOocytes contain a maternal store of the histone variant MacroH2A, which is eliminated from zygotes shortly after fertilization. Preimplantation embryos then execute three cell divisions without MacroH2A before the onset of embryonic MacroH2A expression at the 16-cell stage. During subsequent development, MacroH2A is expressed in most cells, where it is assembled into facultative heterochromatin. Because differentiated cells contain heterochromatin rich in MacroH2A, we investigated the fate of MacroH2A during somatic cell nuclear transfer (SCNT). The results show that MacroH2A is rapidly eliminated from the chromosomes of transplanted somatic cell nuclei by a process in which MacroH2A is first stripped from chromosomes, and then degraded. Furthermore, MacroH2A is eliminated from transplanted nuclei by a mechanism requiring intact microtubules and nuclear envelope break down. Preimplantation SCNT embryos express endogenous MacroH2A once they reach the morula stage, similar to the timing observed in embryos produced by natural fertilization. We also show that the ability to reprogram somatic cell heterochromatin by SCNT is tied to the developmental stage of recipient cell cytoplasm because enucleated zygotes fail to support depletion of MacroH2A from transplanted somatic nuclei. Together, the results indicate that nuclear reprogramming by SCNT utilizes the same chromatin remodeling mechanisms that act upon the genome immediately after fertilization.

We evaluated short echo time two-dimensional 1H magnetic resonance spectroscopy (2D-1HMRS) with the point-resolved spatial selection (PRESS) protocol in temporal lobe epilepsy (TLE) patients with negative magnetic resonance imaging (MRI) findings and described the characteristics of 2D-1HMRS in the epileptic focus. Thirty-eight TLE patients with negative conventional MRI findings and 10 healthy controls were studied by 2D-1HMRS. A 128-channel prolonged video-electroencephalographic (EEG) method was used as the standard for epileptogenic focus localization to evaluate N-acetyl aspartate/(choline + creatine + phospho - creatine) (NAA/[Cho + Cr–PCr]), glutamate + glutamine/creatine (Glx/Cr–PCr) and myo-inositol/Cr–PCr ratios in patients with negative MRI findings. The 2D-1HMRS showed that 32/38 patients and all healthy controls had stable baselines and good signal-to-noise ratios. Compared with the healthy controls, 32 patients showed abnormal NAA/(Cho + Cr–PCr) ratios in the hippocampus and, in 25 of these patients, focus lateralization agreed with the EEG. It is concluded that short echo time 2D-1HMRS with the PRESS protocol can help find abnormalities in lateralization of temporal epilepsy in patients with negative MRI findings.

This study included 93 patients with renal masses who underwent standard partial nephrectomy or tumor enucleation. After surgery, parenchymal mass loss caused by devascularization resulted in more damage to renal function than excised parenchymal mass loss. Surgeons should seek better techniques to decrease devascularization during reconstruction.

Papillary thyroid cancer (PTC) is a common malignancy and has a good prognosis after appropriate treatment. PTC cells spread mainly by lymph node metastasis (LNM), but the mechanism is not well understood. Expression of vascular endothelial growth factor C (VEGF-C) and matrix metalloproteinase 2 (MMP-2) protein was studied immunohistochemically from the archived specimens of 65 PTC patients who initially presented without LNM. In this retrospective study, the frequency of expression differed significantly between thyroid cancer tissue and adjacent normal follicular epithelium (VEGF-C 78.5% and 20.0%, respectively; MMP-2 81.5% and 36.7%, respectively). LNM developed in 35 of the patients during 5–15 years of follow-up, by the end of which the frequencies of expression of VEGF-C and MMP-2 protein expression were 91.4% and 94.3%, respectively. Both VEGF-C and MMP-2 protein expression were significantly more frequent in PTC with LNM than without LNM. VEGF-C and MMP-2 protein expression levels were significantly correlated with LNM and it is, therefore, feasible that VEGF-C and MMP-2 may be useful as tumour markers of PTC with cervical LNM.

Plasma ion implantation and deposition of polymeric materials has gained substantial interest in recent years. This paper will present numerical results on initial potential on top surface and some examples on ion implantation of thin polymer foils. The results demonstrate that the thickness and permittivity of treated samples have a critical influence on initial potential drop across the insulating objects. The smaller thickness and larger permittivity are beneficial for ion implantation. Duplex films of Al2O3/SiO2have been fabricated using arc plasma ion implantation and deposition. The films may substantially increase atomic-oxygen resistance of Kapton foils, which have been frequently utilized in satellites in low-earth-orbit (LEO) environment. The mass loss of treated samples may decrease by one quarter of magnitude compared to that of control sample. The PET foils have also been implanted using C2H2plasma ion implantation. The experimental results show that ion implantation may effectively enhance the gas barrier capability. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

The immobilization of metal nanoparticles in the framework of porous carbon for heterogeneous catalysis may avoid particle aggregation, movement, and leaching, thus leading to a high catalyst efficiency. In this Full Paper, an approach to prepare Ru nanoparticles incorporated into the pore walls of porous carbon to form a sandwiched Ru/C nanostructure for heterogeneous hydrogenation is demonstrated. Physical adsorption of nitrogen, X‐ray diffraction, thermogravimetric analysis, field‐emission transmission electron microscopy, field‐emission scanning electron microscopy, and energy dispersive X‐ray spectroscopy techniques are employed to study the structure and morphology of the catalysts. Catalytic results show that the Ru nanoparticles sandwiched in the pore walls of porous carbon display a remarkably high activity and stability in the hydrogenation of benzene. An enhanced hydrogen spillover effect is believed to play a significant role in the hydrogenation reaction because of the intimate interfacial contact between Ru nanoparticles and the carbon support. The catalyst system described in this work may offer a new concept for optimizing catalyst nanostructures.

1,4‐di(4′‐N,N‐diphenylaminostyryl)benzene (DPA‐DSB) is a well known compound with a large two‐photon absorption (TPA) section and strong fluorescence in solution. However, the ease with which it crystallizes results in the formation of discontinuous crystalline phases during vacuum deposition processes, thereby greatly limiting its applicability in solid‐state devices. A cruciform dimer of DPA‐DSB, 2,5,2′,5′‐tetra(4′‐N,N‐diphenylaminostyryl)biphenyl (DPA‐TSB) is reported, wherein two DPA‐DSB molecules are linked through a central biphenyl bond. The DPA‐TSB molecules take on a cruciform configuration because of the steric crowding around the central biphenyl core, which has the effect of efficiently suppressing crystalline and intermolecular interactions. The neat DPA‐TSB solid shows strong green–blue fluorescence because of both steady‐state absorption as well as TPA. The DPA‐TSB solid exhibits a photoluminescence (PL) efficiency (ηsolid) of 29 % and a solid‐state two‐photon action cross section (δηsolid) of 954 GM (1 GM = 1 × 10–50cm4s photon–1molecule–1), which is much greater than for the model compound DPA‐DSB (ηsolid= 16 % and δηsolid= 150 GM, where δ is the TPA cross section and η is the fluorescence quantum yield). Based on its high PL efficiency, good film‐forming ability, and strong TPA, DPA‐TSB seems to be a good candidate for applications in solid‐state optical devices.

The friction and wear of the silicon carbide (SiC) and hot pressed silicon nitride (Si3N4) against zirconia (Y–TZP) sliding under dry friction and room temperature conditions were investigated with pin-on-disk tribometer at sliding speed of 0.56 m·s-1 and normal load of 50 N, 80 N and 120 N, respectively. It was found that, the coefficient of friction and wear rate are dependent on the test duration as well as the normal load. Through analyzing and comparing, the wear rates of the two frictional couples both are in the 10-6 mm3 (N·m)-1. Based on the variety regulation of the wear maps, the wear mechanisms of the two couples were analyzed. Between the two couples, the friction and wear characteristics of the SiC/ZrO2 couple are better than the Si3N4/ZrO2 couple’s.

Premature chromosome condensation (PCC) was believed to promote nuclear reprogramming and to facilitate cloning by somatic cell nuclear transfer (NT) in mammalian species. However, it is still uncertain whether PCC is necessary for the successful reprogramming of an introduced donor nucleus in cattle. In the present study, fused NT embryos were subjected to immediate activation (IA, simultaneous fusion and activation), delayed activation (DA, activation applied 4 h postfusion), and IA with aged oocytes (IAA, activation at the same oocyte age as group DA). The morphologic changes, such as nuclear swelling, the occurrence of PCC, and microtubule/aster formation, were analyzed in detail by laser-scanning confocal microscopy. When embryos were subjected to IA in both IA and IAA groups, the introduced nucleus gradually became swollen, and a pronuclear-like structure formed within the oocyte, but PCC was not observed. In contrast, delaying embryo activation resulted in 46.5%–91.2% of NT embryos exhibiting PCC. This PCC was observed beginning at 4 h postcell fusion and was shown as one, two, or multiple chromosomal complexes. Subsequently, a diversity of pronuclear-like structures existed in NT embryos, characterized as single, double, and multiple nuclei. In the oocytes exhibiting PCC, the assembled spindle structure was observed to be an interactive mass, closely associated with condensed chromosomes, but no aster had formed. Regardless of whether they were subjected to IA, IAA, or DA treatments, if the oocytes contained pronuclear-like structures, either one or two asters were observed in proximity to the nuclei. A significantly higher rate of development to blastocysts was achieved in embryos that were immediately activated (IA, 59.1%; IAA, 40.7%) than in those for which activation was delayed (14.2%). The development rate was higher in group IA than in group IAA, but it was not significant (P= 0.089). Following embryo transfer, there was no statistically significant difference in the pregnancy rates (Day 70) between two of the groups (group IA, 11.7%, n = 94 vs. group DA, 12.3%, n = 130; P> 0.05) or live term development (group IA, 4.3% vs. group DA, 4.6%; P> 0.05). Our study has demonstrated that the IA of bovine NT embryos results in embryos with increased competence for preimplantational development. Moreover, PCC was shown to be unnecessary for the reprogramming of a transplanted somatic genome in a cattle oocyte.