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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 non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. 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 non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 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 v. 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.
Early life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2) and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance.
Methods
The present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252).
Results
Higher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes.
Conclusions
The present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.
Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.
Having enterprises engaged in environmentally friendly behavior is an important part of reducing negative environmental impacts. This study makes a quantitative analysis against the backdrop of China's transitional economic system. The results show that politically-connected enterprises significantly reduce environmental expenditure, but this only holds for state-owned enterprises; private enterprises with political connections spend significantly more. Analysis of the efficiency of environmental expenditure indicates that, for private enterprises, environmental spending is used as a way to maintain political connections, with rent-seeking as the likely motivation. Politically-connected private enterprises have not reduced their emissions to the same extent as state-owned enterprises, despite increased expenditure. Given the scale of environmental degradation in China during a period of massive economic and social upheaval, the results of this analysis provide a quantitative case for policy change: governments should shift focus to the results that environmental spending produces.
This study aimed to identify clinical features for prognosing mortality risk using machine-learning methods in patients with coronavirus disease 2019 (COVID-19). A retrospective study of the inpatients with COVID-19 admitted from 15 January to 15 March 2020 in Wuhan is reported. The data of symptoms, comorbidity, demographic, vital sign, CT scans results and laboratory test results on admission were collected. Machine-learning methods (Random Forest and XGboost) were used to rank clinical features for mortality risk. Multivariate logistic regression models were applied to identify clinical features with statistical significance. The predictors of mortality were lactate dehydrogenase (LDH), C-reactive protein (CRP) and age based on 500 bootstrapped samples. A multivariate logistic regression model was formed to predict mortality 292 in-sample patients with area under the receiver operating characteristics (AUROC) of 0.9521, which was better than CURB-65 (AUROC of 0.8501) and the machine-learning-based model (AUROC of 0.4530). An out-sample data set of 13 patients was further tested to show our model (AUROC of 0.6061) was also better than CURB-65 (AUROC of 0.4608) and the machine-learning-based model (AUROC of 0.2292). LDH, CRP and age can be used to identify severe patients with COVID-19 on hospital admission.
Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear.
Methods.
The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations.
Result.
We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014).
Conclusions.
Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.
Cardiac fibroma is a rare benign primary tumour of the heart. In the paediatric population, it has been reported as the second most common benign cardiac tumour following rhabdomyoma. However, the prevalence of cardiac fibroma is rarely reported in the adult population. Signs and symptoms are nonspecific, including palpitations, cardiac murmur, arrhythmias, dyspnoea, cyanosis, chest pain, and sudden mortality, whereas, a number of patients with cardiac fibroma are asymptomatic. Surgical resection should be considered as the best option in symptomatic patients. This study reported four surgical cases of adults with cardiac fibroma arising from the left ventricle and a literature review regarding the clinical and pathological features, diagnostic modalities, therapeutic aspects, and prognosis of this rare entity.
Isolated congenital tricuspid regurgitation other than Ebstein’s anomaly was rare especially for children. The objective of this study was to investigate the clinical characteristics and to assess the results of tricuspid valvuloplasty for children with isolated tricuspid regurgitation.
Methods:
From January 2010 to June 2019, 10 consecutive patients with isolated tricuspid regurgitation who were unresponsive to drug therapy underwent tricuspid valvuloplasty in our hospital. Patients’ clinical data were analysed retrospectively.
Results:
Mean age at operation was 48.5 ± 31.0 (range: 9–106) months and mean weight at operation was 16.1 ± 6.9 (range: 8.6–33.0) kg. All patients presented severe isolated tricuspid regurgitation. According to pathological lesions, the main causes accounted for chordae tendinea rupture (3/10), leaflet cleft (2/10), mal-connected chordal tendinea to leaflets (2/10), elongated chordae (1/10) and chordae absent (1/10), and severe anterior leaflet dysplasia (1/10). Individualised tricuspid valvuloplasty was adapted to all of them successfully. Post-operative echocardiography showed no tricuspid regurgitation in two patients and mild regurgitation in eight patients. The cardiothoracic ratios on their chest roentgenograms decreased from 0.59 ± 0.05 to 0.54 ± 0.05. At the latest follow-up (50.4 ± 47.2 months), echocardiography showed that mild to moderate tricuspid regurgitation in seven patients, moderate tricuspid regurgitation in three patients, and no patient with severe tricuspid regurgitation. All patients were in NYHA functional class I.
Conclusions:
For patients with isolated tricuspid regurgitation who were not well responsive to drug therapy, individualised tricuspid valve repair can achieve an excellent result.
Leg weakness (LW) issues are a great concern for pig breeding industry. And it also has a serious impact on animal welfare. To dissect the genetic architecture of limb-and-hoof firmness in commercial pigs, a genome-wide association study was conducted on bone mineral density (BMD) in three sow populations, including Duroc, Landrace and Yorkshire. The BMD data were obtained by ultrasound technology from 812 pigs (including Duroc 115, Landrace 243 and Yorkshire 454). In addition, all pigs were genotyped using genome-by-sequencing and a total of 224 162 single-nucleotide polymorphisms (SNPs) were obtained. After quality control, 218 141 SNPs were used for subsequent genome-wide association analysis. Nine significant associations were identified on chromosomes 3, 5, 6, 7, 9, 10, 12 and 18 that passed Bonferroni correction threshold of 0.05/(total SNP numbers). The most significant locus that associated with BMD (P value = 1.92e−14) was detected at approximately 41.7 Mb on SSC6 (SSC stands for Sus scrofa chromosome). CUL7, PTK7, SRF, VEGFA, RHEB, PRKAR1A and TPO that are located near the lead SNP of significant loci were highlighted as functionally plausible candidate genes for sow limb-and-hoof firmness. Moreover, we also applied a new method to measure the BMD data of pigs by ultrasound technology. The results provide an insight into the genetic architecture of LW and can also help to improve animal welfare in pigs.
This paper presents a soft robot which can imitate the crawling locomotion of an earthworm. Locomotion of the robot can be achieved by expanding and contracting the body that is made of flexible material. A link of the earthworm-like robot is combined with three modules, and a multi-cavity earthworm-like soft robot is combined with multiple links. The multiple links of the earthworm-like soft robot are fabricated by silicone in the three-dimensional printed customized molds. Experiments on a single module, two-links, and three-links show that the soft robot can move and bend on condition of modules extension and contraction in a specified gait. The development of the earthworm-like soft robot shows a great prospect in many complicated environments such as pipeline detection.
Psychiatric disorders are a group of complex psychological syndromes with high prevalence. Recent studies observed associations between altered plasma proteins and psychiatric disorders. This study aims to systematically explore the potential genetic relationships between five major psychiatric disorders and more than 3,000 plasma proteins.
Methods.
The genome-wide association study (GWAS) datasets of attention deficiency/hyperactive disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), schizophrenia (SCZ) and major depressive disorder (MDD) were driven from the Psychiatric GWAS Consortium. The GWAS datasets of 3,283 human plasma proteins were derived from recently published study, including 3,301 study subjects. Linkage disequilibrium score (LDSC) regression analysis were conducted to evaluate the genetic correlations between psychiatric disorders and each of the 3,283 plasma proteins.
Results.
LDSC observed several genetic correlations between plasma proteins and psychiatric disorders, such as ADHD and lysosomal Pro-X carboxypeptidase (p value = 0.015), ASD and extracellular superoxide dismutase (Cu-Zn; p value = 0.023), BD and alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase 6 (p value = 0.007), MDD and trefoil factor 1 (p value = 0.011), and SCZ and insulin-like growth factor-binding protein 6 (p value = 0.011). Additionally, we detected four common plasma proteins showing correlation evidence with both BD and SCZ, such as tumor necrosis factor receptor superfamily member 1B (p value = 0.012 for BD, p value = 0.011 for SCZ).
Conclusions.
This study provided an atlas of genetic correlations between psychiatric disorders and plasma proteome, providing novel clues for pathogenetic and biomarkers, therapeutic studies of psychiatric disorders.
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.
Methods
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.
Results
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.
Conclusions
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.
Single-shot laser-induced damage threshold (LIDT) measurements of multi-type free-standing ultrathin foils were performed in a vacuum environment for 800 nm laser pulses with durations τ ranging from 50 fs to 200 ps. The results show that the laser damage threshold fluences (DTFs) of the ultrathin foils are significantly lower than those of corresponding bulk materials. Wide band gap dielectric targets such as SiN and formvar have larger DTFs than semiconductive and conductive targets by 1–3 orders of magnitude depending on the pulse duration. The damage mechanisms for different types of targets are studied. Based on the measurement, the constrain of the LIDTs on the laser contrast is discussed.
High-index ferroelectric thin films show excellent dielectricity, piezoelectricity and switching behaviors. Understanding the misfit strain relaxation behavior may prove beneficial to gaining insights into the high-quality growth of high-index ferroelectric films. In this study, ferroelectric PbTiO3 thin films were deposited on the (101)-oriented (La, Sr)(Al, Ta)O3 substrate by pulsed laser deposition and were investigated using (scanning) transmission electron microscopy. Two types of misfit dislocations with line directions of 〈111〉 and [010] were found at the interface. The 〈111〉 dislocation exhibited Burgers vectors of a[011] or
$a\left[ {0\bar{1}1} \right]$
, while the [010] dislocation featured Burgers vectors of
$a\left[ {\bar{1}01} \right]$
. The former might be generated by gliding, and the latter by climbing. We propose that the misfit strain relaxation in this film system basically results from the formation of dislocations and the residual misfit strain is relaxed via the formation of 90° ac domains.
The control of cutoffs is of great interest in designs of circular waveguides. In this paper, this topic is investigated for pure transverse-electric (TE) and transverse-magnetic (TM) modes by taking advantage of anisotropic reactance lining loadings. It is found that the cutoffs of TE and TM modes are determined by the reactance in the azimuthal and axial directions, respectively. When the reactance values are positive, the cutoff frequencies are lower than those of a normal conducting waveguide with the same cross-section. However, in contrast to the claim made in the previous literature that the negative reactance values caused the same reducing effect on the cutoffs as the positive values did, the cutoffs are found to be increased by the negative reactances. The theoretical results are validated by the simulations using commercial software, where a delicate model with an approximate curved anisotropic impedance boundary is proposed for the first time. By lowering the TE cutoffs and raising the TM ones, some intriguing applications, such as single-mode bandwidth extension and degenerate mode avoidance, are predicted, which would pave a way for designs of novel waveguide devices.
The overuse of antibiotics and the rapid emergence of antibiotic resistance prompted the launch of an antimicrobial stewardship programme in 2011. This study aimed to investigate the trends and correlations between antibiotic consumption and resistance of Staphylococcus aureus in a tertiary hospital of northwest China from 2010 to 2016. Trends were analysed by linear regression, and correlations were assessed by an autoregressive integrated moving average model. The total consumption of antibiotics halved during the 7-year study period, while the rates of resistance of S. aureus decreased significantly or remained stable; methicillin-resistant S. aureus (MRSA) declined markedly, from 73.3% at the beginning of the study to 41.4% by the end. This latter decrease was significantly correlated with the consumption of several classes of antibiotics. In conclusion, reduction in antibiotic use impacted significantly on resistance rates and contributed to a decline in MRSA prevalence.
For instrumented spherical indentation, the presence of equibiaxial residual stress in a material will lead the indentation load–depth curve to shift upward or downward. The load differences between the stressed and stress-free curves were used to estimate the equibiaxial residual stress. Using dimensional analysis and finite element simulations, the equibiaxial residual stress was related to the elastic–plastic parameters and the relative load difference at a fixed normalized indentation depth (h/R = 0.1). Based on these expressions, and together with the method for determining elastic–plastic parameters established in our previous work, an integrated method was proposed to estimate the equibiaxial residual stress and elastic–plastic parameters of metals simultaneously via instrumented spherical indentation. This method avoids preknowledge of the yield strength and measuring the contact area. Applications were illustrated on Al 2024, Al 7075, and Ti Grade 5 with introduced stresses. By comparing the results determined by this integrated method with the reference values, the maximum relative error is generally within ±10% for the yield strength, within ±15% for the elastic modulus, and within ±20% for the equibiaxial residual stress.
To investigate the effects of heat stress on broiler metabolism, we assigned 144 broilers to normal control (NC), heat stress (HS) or pair-fed (PF) groups and then monitored the effects using growth performance, carcass characteristics, biochemical assays and GC-MS-based metabolomics. The up-regulation of cloacal temperature confirmed that our experiment was successful in inducing chronic heat stress. The average daily gain and average daily feed intake of the HS group were significantly lower than those of the NC group, by 28·76 and 18·42 %, respectively (P<0·001), whereas the feed:gain ratio was significantly higher, by 14·49 % (P=0·003), and heat stress also increased leg proportion (P=0·027) and intramuscular fat proportion (P<0·001) and decreased breast proportion (P=0·009). When comparing the HS and NC groups and HS and PF groups, our metabolomics approach identified seventy-eight and thirty-four metabolites, respectively, with significantly different levels (variable importance in the projection values >1 and P<0·05). The greater feed:gain ratio of the HS group was significantly positively correlated with the leg, abdominal fat, subcutaneous fat and intramuscular fat proportions and levels of some free amino acids (proline, l-cysteine, methionine and threonine) but was negatively correlated with breast proportion and levels of some NEFA (stearic acid, arachidonic acid, palmitic acid and oleic acid). These findings indicated that the heat-stressed broilers were in negative energy balance and unable to effectively mobilise fat, thereby resulting in protein decomposition, which subsequently affected growth performance and carcass characteristics.
An investigation of symmetry breaking and naturally occurring instabilities over thin slender delta wings with sharp leading edges was carried out in a water tunnel using particle image velocimetry (PIV) measurements. Time-averaged location, strength and core radius of conical vortices vary almost linearly with chordwise distance for three delta wings with
$75^{\circ }$
,
$80^{\circ }$
and
$85^{\circ }$
sweep angles over a wide range of angles of attack. Properties of the time-averaged vortex pairs depend only on the similarity parameter, which is a function of the angle of attack and the sweep angle. It is shown that time-averaged vortex pairs develop asymmetry gradually with increasing values of the similarity parameter. Vortex asymmetry can develop in the absence of vortex breakdown on the wing. Instantaneous PIV snapshots were analysed using proper orthogonal decomposition and dynamic mode decomposition, revealing the shear layer and vortex instabilities. The shear layer mode is the most periodic and more dominant for lower values of the similarity parameter. The Strouhal number based on the free stream velocity component in the cross-flow plane is a function of only the similarity parameter. The dominant frequency of the shear layer mode decreases with the increasing similarity parameter. The vortex modes reveal the fluctuations of the vorticity magnitude and helical displacement of the cores, but with little periodicity. There is little correlation between the fluctuations in the cores of the vortices.