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The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in nonalcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD.
370 adult individuals with biopsy-proven NAFLD were studied. Appendicular skeletal muscle mass was measured by bioelectrical impedance. The association between the key exposure sarcopenia, and the outcome liver histological severity, was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology.
Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite NASH than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted odds ratio 2.79, 95%CI 1.31-5.95, p=0.008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43.8% vs. 17.2%, p=0.031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (p-value for interaction=0.006).
Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
Accumulating studies have found structural and functional abnormalities of the striatum in bipolar disorder (BD) and major depressive disorder (MDD). However, changes in intrinsic brain functional connectivity dynamics of striato-cortical circuitry have not been investigated in BD and MDD. This study aimed to investigate the shared and specific patterns of dynamic functional connectivity (dFC) variability of striato-cortical circuitry in BD and MDD.
Brain resting-state functional magnetic resonance imaging data were acquired from 128 patients with unmedicated BD II (current episode depressed), 140 patients with unmedicated MDD, and 132 healthy controls (HCs). Six pairs of striatum seed regions were selected: the ventral striatum inferior (VSi) and the ventral striatum superior (VSs), the dorsal-caudal putamen (DCP), the dorsal-rostral putamen (DRP), and the dorsal caudate and the ventral-rostral putamen (VRP). The sliding-window analysis was used to evaluate dFC for each seed.
Both BD II and MDD exhibited increased dFC variability between the left DRP and the left supplementary motor area, and between the right VRP and the right inferior parietal lobule. The BD II had specific increased dFC variability between the right DCP and the left precentral gyrus compared with MDD and HCs. The MDD had increased dFC variability between the left VSi and the left medial prefrontal cortex compared with BD II and HCs.
The patients with BD and MDD shared common dFC alteration in the dorsal striatal-sensorimotor and ventral striatal-cognitive circuitries. The patients with MDD had specific dFC alteration in the ventral striatal-affective circuitry.
In recent years, intracranial thrombectomy stent has been an important method to treat ischemic stroke caused by acute thrombosis. In this paper, a new intracranial thrombectomy stent with a fish scale-like structure was designed and its mechanical properties were studied by a finite element method. The porosity of all stents was more than 80%. The space occupation ratio (SOR) of the stents increased linearly with the increase of strut thickness, while the strut width had little effect on SOR. The maximum equivalent stress and strain, the directional deformation and overall radial load of the stent decreased with the increase of strut thickness, however, the strut width has little impact on these parameters. The stents with 0.2 mm strut width and the thickness of 0.15 and 0.20 mm had better radial load performance, and the stent with 0.2 mm strut width and 0.15 mm strut thickness had better contact performance with the vessel wall and displayed better flexibility. Therefore, the present study provides a theoretical basis for the design of new intracranial thrombectomy stent.
This study aimed to examine the efficacy of combining paroxetine and mirtazapine v. switching to mirtazapine, for patients with major depressive disorder (MDD) who have had an insufficient response to SSRI monotherapy (paroxetine) after the first 2 weeks of treatment.
This double-blind, randomized, placebo-controlled, three-arm study recruited participants from five hospitals in China. Eligible participants were aged 18–60 years with MDD of at least moderate severity. Participants received paroxetine during a 2-week open-label phase and patients who had not achieved early improvement were randomized to paroxetine, mirtazapine or paroxetine combined with mirtazapine for 6 weeks. The primary outcome was improvement on the Hamilton Rating Scale for Depression 17-item (HAMD-17) scores 6 weeks after randomization.
A total of 204 patients who showed early non-response to paroxetine monotherapy were randomly assigned to receive either mirtazapine and placebo (n = 68), paroxetine and placebo (n = 68) or mirtazapine and paroxetine (n = 68), with 164 patients completing the outcome assessment. At week 8, the least squares (LS) mean change of HAMD-17 scores did not significantly differ among the three groups, (12.98 points) in the mirtazapine group, (12.50 points) in the paroxetine group and (13.27 points) in the mirtazapine plus paroxetine combination group. Participants in the paroxetine monotherapy group were least likely to experience adverse effects.
After 8 weeks follow-up, paroxetine monotherapy, mirtazapine monotherapy and paroxetine/mirtazapine combination therapy were equally effective in non-improvers at 2 weeks. The results of this trial do not support a recommendation to routinely offer additional treatment or a switch in treatment strategies for MDD patients who do not show early improvement after 2 weeks of antidepressant treatment.
Few studies have examined the association of various types of Fe with colorectal cancer risk. The aim of this study was to investigate different forms and sources of Fe in relation to colorectal cancer risk in a Chinese population. A total of 2138 patients with colorectal cancer and 2144 sex- and age-matched (5-year interval) controls were recruited from July 2010 to November 2017. Dietary information was assessed by face-to-face interviews using a validated FFQ. Multivariable logistic regression was used to estimate the OR and 95 % CI on models. Intake of Fe from plants and Fe from white meat were inversely associated with the risk of colorectal cancer, while haem Fe and Fe from red meat were positively associated with colorectal cancer risk. The multivariable OR for the highest quartile v. the lowest quartile were 0·72 (95 % CI 0·59, 0·87, Ptrend<0·001) for Fe from plants, 0·54 (95 % CI 0·45, 0·66, Ptrend<0·001) for Fe from white meat, 1·26 (95 % CI 1·04, 1·53, Ptrend=0·005) for haem Fe and 1·83 (95 % CI 1·49, 2·24, Ptrend<0·001) for Fe from red meat intake, respectively. However, no significant association was found between the consumption of total dietary Fe, non-haem Fe, Fe from meat and colorectal cancer risk. This study showed that lower intake of Fe from plants and white meat, as well as higher intake of haem Fe and Fe from red meat, were associated with colorectal cancer risk in a Chinese population.
Identifying the relative importance of urban and non-urban land-use types for potential denitrification derived N2O at a regional scale is critical for quantifying the impacts of human activities on nitrous oxide (N2O) emission under changing environments. In this study we used a regional dataset from China including 197 soil samples and six land-use types to evaluate the main predictors (land use, heavy metals, soil pH, soil moisture, substrate availability, functional and broad microbial abundances) of potential denitrification using multivariate and pathway analysis. Our results provide empirical evidence that soils on farms have the greatest potential denitrifying ability (PDA) (10.92±6.08ng N2O-N·g–1 dry soil·min–1) followed by urban soil (6.80±5.35ng N2O-N·g–1 dry soil·min–1). Our models indicate that land use (low vs. high human activity), followed by total nitrogen (TN) and heavy metals (Cu, Zn, Pb, Cd) was the most important driver of PDA. In addition, our path analysis suggests that at least part of the impacts of land use on potential denitrification were mediated via microbial abundance, soil pH and substrates including TN, dissolved organic carbon and nitrate. This study identifies the main predictors of denitrification at a regional scale which is needed to quantify the impact of human activities on ecosystem functionality under changing conditions.
To produce pulses with good flat-top quality, pulse-forming lines (PFLs) have been widely used in the field of Tesla-type pulse generators. To shorten the physical length of the PFL, a double-width PFL (DWPFL) is proposed that doubles the output pulse width while maintaining flat-top quality. A repetitively 10 GW Tesla-type long-pulse generator producing pulses with flat-top width of about 110 ns was developed with a coaxial DWPFL to produce high-current electron beams. Electron beams of about 10 GW with flat-top widths of about 110 ns were obtained on a planar vacuum diode load. With this pulse generator and a C-band high-power microwave system, microwaves of ~2.2 GW power and full-width at half-maximum of 101 ns were generated. The experiment demonstrates the feasibility and ideal output waveform quality of the DWPFL.
A new minimally invasive surgical (MIS) robot consisting of a spherical remote center motion (RCM) mechanism with modular design is proposed. A multi-objective dimensional synthesis model is presented to obtain the excellent performance indices. There are four objectives: a global kinematic index, a compactness index, a global comprehensive stiffness index, and a global dynamic index. Other indices characterizing the design requirement, such as workspace, mechanical parameter, and mass, are chosen as constraints. A new decoupled mechanism is raised to solve the coupled motion between the linear platform and the four degrees of freedom (DoF) of surgical instrument as a result of post-driving motors. Another new mechanical decoupled method is proposed to eliminate the coupled motion between the wrist and the forceps, enhance the dexterity of surgical instrument, and improve the independence of each motor. Then, a 7-DoF MIS robotic prototype based on optimization results has been built up. Experiment results validate the effectiveness of the two mechanical decoupled methods. The position change of the RCM point, accuracy, and repeatability of the MIS robot meet the requirements of MIS. Successful animal experiments validate the effectiveness of the novel MIS robot.
Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000–2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1–11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3–63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.
Elderly individuals with tuberculosis (TB) are more likely to have a non-specific clinical presentation of TB and high mortality. However, factors associated with mortality in elderly TB patients have not been extensively studied. This retrospective cohort study aimed to identify factors associated with death among elderly Taiwanese with TB. All elderly patients with TB from 2006 to 2014 in Taipei, Taiwan, were included in a study. Multiple logistic regression was used to identify the factors associated with death in elderly TB patients. The mean age of the 5011 patients was 79·7 years; 74·1% were men; 32·7% had mortality during the study follow-up period. After controlling for potential confounders, age ⩾75 years (reference: 65–74 years), male sex, end-stage renal disease (ESRD), malignancy, acid-fast bacilli-smear positivity, TB-culture positivity, pleural effusion on chest radiograph and notification by an ordinary ward or intensive care unit were associated with a higher risk of all-cause death; while high school, and university or higher education, cavity on chest radiograph and directly observed therapy were associated with a lower risk of all-cause death. This study found that the proportion of death among elderly patients with TB in Taipei, Taiwan, was high. To improve TB treatment outcomes, future control programmes should particularly target individuals with comorbidities (e.g. ESRD and malignancy) and those with a lower socio-economic status (e.g. not educated).
Wake vortex evolution of a square cylinder with a slot synthetic jet issuing from the cylinder’s rear surface has been experimentally investigated using the time-resolved particle image velocimetry technique. The Reynolds number based on the side length of the square cylinder is
. The excitation frequency normalized by the natural shedding frequency
varies from 0 to 6 at the dimensionless stroke length
. The distributions of the time-averaged Reynolds stresses present significant differences as the excitation frequency increases. With control, the mean streamwise velocity deficit of the wake recovers more quickly in comparison with the natural case, and the vertical velocity fluctuation intensity becomes weaker. Moreover, a drag reduction can be achieved for the control cases, especially, for
, a thrust instead of drag reduction can be obtained. The profiles of the mean streamwise velocity tend to have jet-like distributions. The wake vortex dynamics and its evolution with the excitation frequency are revealed. (i) For the low excitation frequency cases (
, 1, 2), no significant changes in the dominant frequency and the spanwise vortex structures are observed in comparison with the natural case. (ii) For the moderate excitation frequency case (
), the wake vortex shedding frequency is locked on half of the control frequency. In this case, the shear layer is divided into two parts by the synthetic jet vortex, and the wake vortices with smaller scales still shed asymmetrically and appear closer to the square cylinder. (iii) For the high excitation frequency case (
), the flow is governed by the synthetic jet. As a result of strong perturbations of the synthetic jet, the wake vortex shedding becomes symmetric with the shedding frequency consistent with the control frequency. And the separation is suppressed effectively. The different control effects of the slot synthetic jet on a square cylinder and a circular cylinder are also compared in detail. Generally speaking, the circular cylinder is easier to be controlled due to its non-fixed separation points.
The dynamics of vortical structures in flow over a circular cylinder in the vicinity of a flat plate is investigated using particle image velocimetry (PIV). The cylinder is placed above the flat plate with its axis parallel to the wall and normal to the flow direction. The Reynolds number
based on the cylinder diameter
is 1072 and the gap
between the cylinder and the flat plate is varied from gap-to-diameter ratio
. The flow statistics and vortex dynamics are strongly dependent on the gap ratio
. Statistics show that as the cylinder comes close to the wall (
), the cylinder wake becomes more and more asymmetric and a boundary layer separation is induced on the flat plate downstream of the cylinder. The wake vortex shedding frequency increases with decreasing
until a critical gap ratio (about
) below which the vortex shedding is irregular. The deflection of the gap flow away from the wall and its following interaction with the upper shear layer may be the cause of the higher shedding frequency. The vortex dynamics is investigated based on the phase-averaged flow field and virtual dye visualization in the instantaneous PIV velocity field. It is revealed that when the cylinder is close to the wall (
), the cylinder wake vortices can periodically induce secondary spanwise vortices near the wall. As the cylinder approaches the wall (
) the secondary vortex can directly interact with the lower wake vortex, and a further approaching of the cylinder (
) can result in more complex interactions among the secondary vortex, the lower wake vortex and the upper wake vortex. The breakdown of vortices into filamentary debris during vortex interactions is clearly revealed by the coloured virtual dye visualizations. For
, the lower shear layer is strongly inhibited and only the upper shear layer can shed vortices. Investigation of the vortex formation, evolution and interaction in the flow promotes the understanding of the flow physics for different gap ratios.
Evolution of Lagrangian coherent structures (LCS) in a flat plate boundary layer transition induced by the wake of a circular cylinder is investigated. Both hydrogen bubble visualization and particle image velocimetry (PIV) techniques are used. It is found that downstream of the cylinder, the disturbance in the boundary layer experiences a fast growth followed by a slow decay in the transition. Lagrangian coherent structures are revealed by qualitative hydrogen bubble visualizations and quantitative finite-time Lyapunov exponents (FTLE) fields derived from the PIV data. The evolution of the LCS is considered from the very beginning of the transition up to when the boundary layer becomes fully developed turbulent flow. The mean convection velocity and average inclination angle of the LCS are first extracted from the FTLE fields. The streamwise length of the low-speed streaks seems to increase, while their spanwise distance decreases in the boundary layer transition. Proper orthogonal decomposition (POD) of the PIV data shows that low-speed streaks associated with the hairpin vortices and hairpin packets are the dominant coherent structures close to the wall in the transitional and turbulent boundary layer. The POD modes also reveal a variety of scales in the turbulent boundary layer. Moreover, it is found that large-scale coherent structures can modulate the amplitude of the small-scale ones.
Autophagy process in Toxoplasma gondii plays a vital role in regulating parasite survival or death. Thus, once having an understanding of certain effects of autophagy on the transformation of tachyzoite to bradyzoite this will allow us to elucidate the function of autophagy during parasite development. Herein, we used three TgAtg proteins involved in Atg8 conjugation system, TgAtg3, TgAtg7 and TgAtg8 to evaluate the autophagy level in tachyzoite and bradyzoite of Toxoplasma in vitro based on Pru TgAtg7-HA transgenic strains. We showed that both TgAtg3 and TgAtg8 were expressed at a significantly lower level in bradyzoites than in tachyzoites. Importantly, the number of parasites containing fluorescence-labelled TgAtg8 puncta was significantly reduced in bradyzoites than in tachyzoites, suggesting that autophagy is downregulated in Toxoplasma bradyzoite in vitro. Moreover, after treatment with drugs, bradyzoite-specific gene BAG1 levels decreased significantly in rapamycin-treated bradyzoites and increased significantly in 3-MA-treated bradyzoites in comparison with control bradyzoites, indicating that Toxoplasma autophagy is involved in the transformation of tachyzoite to bradyzoite in vitro. Together, it is suggested that autophagy may serve as a potential strategy to regulate the transformation.
Intra-uterine growth restriction (IUGR) impairs postnatal growth and skeletal muscle development in neonatal infants. This study evaluated whether dietary β-hydroxy-β-methylbutyrate Ca (HMB-Ca) supplementation during the early postnatal period could improve muscle growth in IUGR neonates using piglets as a model. A total of twelve pairs of IUGR and normal-birth-weight (NBW) male piglets with average initial weights (1·85 (sem 0·36) and 2·51 (sem 0·39) kg, respectively) were randomly allotted to groups that received milk-based diets (CON) or milk-based diets supplemented with 800 mg/kg HMB-Ca (HMB) during days 7–28 after birth. Blood and longissimus dorsi (LD) samples were collected and analysed for plasma amino acid content, fibre morphology and the expression of genes related to muscle development. The results indicate that, regardless of diet, IUGR piglets had a significantly decreased average daily weight gain (ADG) compared with that of NBW piglets (P<0·05). However, IUGR piglets fed HMB-Ca had a net weight and ADG similar to that of NBW piglets fed the CON diet. Irrespective of body weight (BW), HMB-Ca supplementation markedly increased the type II fibre cross-sectional area and the mRNA expression of mammalian target of rapamycin (mTOR), insulin-like growth factor-1 and myosin heavy-chain isoform IIb in the LD of piglets (P<0·05). Moreover, there was a significant interaction between the effects of BW and HMB on mTOR expression in the LD (P<0·05). In conclusion, HMB-Ca supplementation during the early postnatal period could improve skeletal muscle growth and maturity by accelerating fast-twitch glycolytic fibre development in piglets.
Mussels are typical macrofouling organisms in the world. In this study, the interaction between the settlement of Mytilus coruscus plantigrades and bacterial community on coloured substrata was determined. Bacterial communities in biofilms developed on seven coloured substrata were analysed by Illumina Miseq sequencing. The mussel settlement response to coloured substrata with no biofilms was also examined. Flavobacteria, Alphaproteobacteria and Gammaproteobacteria were the first, second and third most dominant groups in seven biofilm samples. The results suggest that the inducing activities of these biofilms on plantigrade settlement varied with coloured substrata and the lowest percentage of settlement was observed on biofilms on the green substratum. High-throughput sequencing showed that bacterial community in biofilms also changed with the substratum colour. No significant difference in the inducing activity on plantigrade settlement was observed between the coloured substrata with no biofilms. Thus, difference in plantigrade settlement response may be correlated to the changes in bacterial community on coloured substrata. This finding extends current knowledge of interaction among mussel settlement and bacterial community variability.
One-dimensional carbon nanomaterials (1-DCNMs), as one of the most promising one-dimension nanomaterials due to its unique microstructure, peculiar chemical, mechanical, thermal, and electronic properties, have long been considered as an important building block to construct micro-nano-electrics and devices. The growth controllability in direction, morphology and microstructure may provide a straightforward platform for fabricating high performance 1-DCNMs-based devices. Recently, electric and magnetic fields have emerged as key techniques to control the 1-DCNMs' growth direction, morphology and microstructure. In this paper, we focus explicitly on the 1-DCNMs preparations with assistance of a magnetic field, and the main problems that should be solved in the future are also discussed.
The need for higher energy density batteries has spawned recent renewed interest in alternatives to lithium ion batteries, including multivalent chemistries that theoretically can provide twice the volumetric capacity if two electrons can be transferred per intercalating ion. Initial investigations of these chemistries have been limited to date by the lack of understanding of the compatibility between intercalation electrode materials, electrolytes, and current collectors. This work describes the utilization of hybrid cells to evaluate multivalent cathodes, consisting of high surface area carbon anodes and multivalent nonaqueous electrolytes that are compatible with oxide intercalation electrodes. In particular, electrolyte and current collector compatibility was investigated, and it was found that the carbon and active material play an important role in determining the compatibility of PF6-based multivalent electrolytes with carbon-based current collectors. Through the exploration of electrolytes that are compatible with the cathode, new cell chemistries and configurations can be developed, including a magnesium-ion battery with two intercalation host electrodes, which may expand the known Mg-based systems beyond the present state of the art sulfide-based cathodes with organohalide-magnesium based electrolytes.