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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.
Mutation in CFAP43 leads to severe asthenozoospermia and multiple morphological abnormalities of the sperm flagellum (MMAF) in both human and mouse. Previous studies have shown that disruption of intra-manchette transport (IMT) caused failure of flagellum assembly and sperm head shaping. In a previous study, therefore, we postulated that disruption of IMT may contribute to the failure of sperm flagellum formation and result in MMAF, however the mechanisms underlying these defects are still poorly understood. Cfap43-deficient mice were studied here to reveal the cellular mechanisms of abnormal sperm head morphology and MMAF. Depletion of Cfap43 led to abnormal spermiogenesis and caused MMAF, sperm head abnormality and oligozoospermia. Furthermore, both abnormal manchette and disorganized ectoplasmic specialization (ES) could be observed at the elongated spermatids in Cfap43-deficient mice. Therefore, our findings demonstrated that, in mice, CFAP43-mediated IMT is essential for sperm head shaping and sperm flagellum formation.
Nanocrystalline metals possess high strength and outstanding resistance to irradiation damage. However, the high-density grain boundaries in nanocrystalline metals lead to low plasticity and poor thermal stability. In recent years, interface engineering has gradually become an important way to improve the comprehensive properties of nanocrystalline metals. In this paper, the interface structure, deformation mechanism, and physical properties of Cu–Nb nanolayered composites fabricated by physical vapor deposition and accumulative roll bonding are reviewed. Both Cu–Nb nanolayered composites possess semi-coherent interfaces. The nanolayered composites could achieve excellent resistance to irradiation damage since the interfaces are good sinks for the irradiation point defects. In addition, nanolayered metallic composites with abundant heterogeneous interfaces have better thermal stability compared to nanocrystalline metallic materials. Moreover, the interactions between dislocations and interfaces can be adjusted effectively through controlling the atomistic interface structure and alignment of slip systems across the interface, so as to achieve high strength and high plastic deformation ability simultaneously.
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.
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).
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.
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.
This study aimed to investigate the benefit of Bonebridge devices in patients with single-sided deafness.
Five patients with single-sided deafness who were implanted with Bonebridge devices were recruited in a single-centre study. Participants’ speech perception and horizontal sound localisation abilities were assessed at 6 and 12 months post-operatively. Speech intelligibility in noisy environments was measured in three different testing conditions (speech and noise presented from the front, speech and noise presented from the front and contralateral (normal ear) side separately, and speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side). Sound localisation was evaluated in Bonebridge-aided and Bonebridge-unaided conditions at different stimuli levels (65, 70 and 75 dB SPL).
All participants showed a better capacity for speech intelligibility in quiet environments with the Bonebridge device. The speech recognition threshold with the Bonebridge device was significantly decreased at both short- and long-term follow up in the speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side condition (p < 0.05). Additionally, participants maintained similar levels of sound localisation between the Bonebridge-aided and unaided conditions (p > 0.05). However, the accuracy of localisation showed some improvement at 70 dB SPL and 75 dB SPL post-operatively.
The Bonebridge device provides the benefit of improved speech perception performance in patients with single-sided deafness. Sound localisation abilities were neither improved nor worsened with Bonebridge implantation at the follow-up assessments.
No studies have reported on how to relieve distress or relax in medical health workers while wearing medical protective equipment in coronavirus disease 2019 (COVID-19) pandemic. The study aimed to establish which relaxation technique, among six, is the most feasible in first-line medical health workers wearing medical protective equipment.
This was a two-step study collecting data with online surveys. Step 1: 15 first-line medical health workers were trained to use six different relaxation techniques and reported the two most feasible techniques while wearing medical protective equipment. Step 2: the most two feasible relaxation techniques revealed by step 1 were quantitatively tested in a sample of 65 medical health workers in terms of efficacy, no space limitation, no time limitation, no body position requirement, no environment limitation to be done, easiness to learn, simplicity, convenience, practicality, and acceptance.
Kegel exercise and autogenic relaxation were the most feasible techniques according to step 1. In step 2, Kegel exercise outperformed autogenic relaxation on all the 10 dimensions among the 65 participants while wearing medical protective equipment (efficacy: 24 v. 15, no space limitation: 30 v. 4, no time limitation: 31 v. 4, no body position requirement: 26 v. 4, no environment limitation: 30 v. 11, easiness to learn: 28 v. 5, simplicity: 29 v. 7, convenience: 29 v. 4, practicality: 30 v. 14, acceptance: 32 v. 6).
Kegel exercise seems a promising self-relaxation technique for first-line medical health workers while wearing medical protective equipment among COVID-19 pandemic.
The aim of this study was to explore the application of the flipped classroom approach in the training of Mass Casualty Triage (MCT) to medical undergraduate students.
In this study, 103 fourth-year medical students were randomly divided into a Flipped Classroom (FC) group (n = 51) and a Traditional Lecture-based Classroom (TLC) group (n = 52). A post-class quiz, simulated field triage (SFT) and feedback questionnaires were performed to assess both groups of students for their learning of the course.
In the post-quiz, the median (IQR) scores achieved by students from the FC and TLC groups were 42(5) and 39(5.5), respectively. Significant differences were found between the two groups. In the SFT, overall triage accuracy was 67.06% for FC, and 64.23% for TLC students. Over-triage and under-triage errors occurred in 18.43% and 14.50% of the FC group, respectively. The TLC group had a similar pattern of 20.77% over-triage and 15.0% under-triage errors. No significant differences were found regarding overall triage accuracy or triage errors between the two groups.
The FC approach could enhance course grades reflected in the post-quiz and improve students’ satisfaction with the class. However, there was no significant difference of competency between the two groups demonstrated in the SFT exercise.
Parabronema skrjabini is one of the most harmful nematodes to camels and is responsible for economic losses in animal husbandry industry. There is an urgent need for in-depth studies of potential vectors of the nematode due to its scant regarding information. As previous studies indicated that flies may be the vectors of P. skrjabini, we captured flies in the main camel-producing areas of Inner Mongolia. After autopsy of the specimens of two species of horn flies, we observed the morphology of the suspected nematode larvae found in them. Internal transcribed spacer ribosomal-DNA gene sequences were considered the best candidate to confirm the species of the larvae found. Our results showed that the homology compared with P. skrjabini was 99.5% in GenBank. Subsequently, we preliminarily identified two species of horn flies through morphological observation and then sequenced the mitochondrial-DNA-gene cytochrome oxidase subunit I obtained from two species of horn flies, with 100 and 99.2% similarity to sequences deposited in GenBank, respectively. Thus, we identified Haematobia titillans and Haematobia irritans and provided evidence for their potential role as vectors of parabronemosis. Our study provides reference for future research on the life history of the nematode and the vectors of parabronemosis.
Snow and ice were monitored by thermistor-string-based Snow and Ice Mass Balance Array (SIMBA) in Lake Orajärvi in northern Finland. An existing automatic SIMBA-algorithm was further developed to derive air/snow, snow/ice and ice/water interfaces based on the SIMBA environment temperature (ET) profiles. The identified interfaces agreed with in situ observations made in 2011/12 winter season. The method was capable to identify upward-moving snow/ice interface that was also visible from SIMBA heating temperature (HT) profiles, which responds to differences in the thermal diffusivities of air, snow, ice and water. The SIMBA data obtained in winters 2017/18 and 2018/19 were used to investigate snow and ice mass balance. An upward-moving snow/ice interface was detected as a result of meteoric ice (snow ice and superimposed ice) formation. Snow contributed to granular lake ice formation up to 40–55% of the total ice thickness on the seasonal mean. Heavy snowfalls and low air temperature in early winter are favourable for granular ice formation. The seasonal mean snow depth on nearby land was 2.7–2.9 times of that on the lake. The estimation of freeboard from snow and ice mass-balance measurement is sensitive to the snow density. Accurate ice freeboard calculation is still a challenge.
Soft robots can perform effectively inspecting than rigid robots in some special environments such as nuclear pipelines and high-voltage cables. This article presents a versatile quadruped soft rod-climbing robot (SR-CR) that consists of four bending actuators and a telescopic actuator. The bending actuator is composed of flexible bellows with multiple folding air chambers, elastic telescopic layer (ETL), and strain-limiting layer (SLL). The telescopic actuator provides the energy for the robot to climb forward. The SR-CR is activated by a control strategy that alternates the body deformation and feet pneumatic clenched for stable climbing. The robot can climb rods at 90°, with the maximum speed of up to 2.33 mm/s (0.018 body length/s). At 0.83 HZ, the maximum moving speed of the robot in climbing horizontally parallel rods can reach 18.43 mm/s. In addition, the SR-CR can also achieve multiple impressive functions, including turning around a corner at a rate of 7 mm/s (0.054 body length/s), carrying a payload of 3.7 times its self-weight on horizontal rods at a speed of 9 mm/s (0.069 body length/s).
The evolution of melt ponds on Arctic sea ice in summer is one of the main factors that affect sea-ice albedo and hence the polar climate system. Due to the different spectral properties of open water, melt pond and sea ice, the melt pond fraction (MPF) can be retrieved using a fully constrained least-squares algorithm, which shows a high accuracy with root mean square error ~0.06 based on the validation experiment using WorldView-2 image. In this study, the evolution of ponds on first-year and multiyear ice in the Canadian Arctic Archipelago was compared based on Sentinel-2 and Landsat 8 images. The relationships of pond coverage with air temperature and albedo were analysed. The results show that the pond coverage on first-year ice changed dramatically with seasonal maximum of 54%, whereas that on multiyear ice changed relatively flat with only 30% during the entire melting period. During the stage of pond formation, the ponds expanded rapidly when the temperature increased to over 0°C for three consecutive days. Sea-ice albedo shows a significantly negative correlation (R = −1) with the MPF in melt season and increases gradually with the refreezing of ponds and sea ice.
The Wulian complex is located on the northern margin of the Sulu orogenic belt, and was formed by collision between the North China Craton (NCC) to the north and South China Craton (SCC) to the south. It consists of the metasedimentary Wulian Group, gneissic granite and meta-diorite. The U–Pb analyses for the detrital zircons from the Wulian Group exhibit one predominant age population of 2600–2400 Ma with a peak at c. 2.5 Ga and several secondary age populations of > 3000, 3000–2800, 2800–2600, 2200–2000, 1900–1800, 1500–1300 and 1250–950 Ma; some metamorphic zircons have metamorphic ages of c. 2.7, 2.55–2.45, 2.1–2.0 and 1.95–1.80 Ga, which are consistent with magmatic-metamorphic events in the SCC. Additionally, the Wulian Group was intruded by the gneissic granite and meta-diorite at c. 0.76 Ga, attributed to Neoproterozoic syn-rifting bimodal magmatic activity in the SCC and derived from partial melting of Archaean continental crust and depleted mantle, respectively. The Wulian Group therefore has tectonic affinity to the SCC and was mainly sourced from the SCC. The detrital zircons have positive and negative ϵHf(t) values, indicating that their source rocks were derived from reworking of both ancient and juvenile crustal rocks. The major early Precambrian crustal growth took place during c. 3.4–2.5 Ga with a dominant peak at 2.96 Ga and several secondary peaks at 3.27, 2.74 and 2.52 Ga. The two oldest zircons with ages of 3307 and 3347 Ma record the recycling of ancient continental crust (> 3.35 Ga) and crustal growth prior to c. 3.95 Ga in the SCC.
This paper studies the parameter estimation for Ornstein–Uhlenbeck stochastic volatility models driven by Lévy processes. We propose computationally efficient estimators based on the method of moments that are robust to model misspecification. We develop an analytical framework that enables closed-form representation of model parameters in terms of the moments and autocorrelations of observed underlying processes. Under moderate assumptions, which are typically much weaker than those for likelihood methods, we prove large-sample behaviors for our proposed estimators, including strong consistency and asymptotic normality. Our estimators obtain the canonical square-root convergence rate and are shown through numerical experiments to outperform likelihood-based methods.
To identify the association of the glucokinase gene (GCK) rs4607517 polymorphism with gestational diabetes mellitus (GDM) and determine whether sweets consumption could interact with the polymorphism on GDM in Chinese women.
We conducted a case–control study at a hospital including 1015 participants (562 GDM cases and 453 controls). We collected the data of pre-pregnancy BMI, sweets consumption and performed genotyping of the GCK rs4607517 polymorphism. Logistic regression was performed to test the association between the rs4607517 polymorphism and GDM, and the stratified analyses by sweets consumption were conducted, using an additive genetic model.
A case–control study of women at a hospital in Beijing, China.
One thousand and fifteen Chinese women.
The GCK rs4607517 A allele was significantly associated with GDM (OR 1·35, 95 % CI 1·03, 1·77; P = 0·028). Furthermore, stratified analyses showed that the A allele increased the risk of GDM only in women who had a habitual consumption of sweet foods (sweets consumption ≥ once per week) (OR 1·61, 95 % CI 1·17, 2·21; P = 0·003). Significant interaction on GDM was found between the rs4607517 A allele and sweets consumption (P = 0·004).
This study for the first time reported the interaction between the GCK rs4607517 polymorphism and sweets consumption on GDM. The results provided novel evidence for risk assessment and personalised prevention of GDM.
Perovskite solar cells are poised to be a game changer in photovoltaic technology with a current certified efficiency of 25.2%, already surpassing that for multicrystalline silicon solar cells. On the path to higher efficiencies and much needed higher stability, however, interfacial and bulk defects in the active material should be carefully engineered or passivated. Post-treatment techniques show great potential to address defect issues (e.g., by coarsening the perovskite grains or establishing an interfacial heterogeneous layer). In this article, we summarize current fundamental understanding of the major energy-loss routes in perovskite materials and devices, including bulk/interfacial defects mediated nonradiative recombination and band mismatch-induced recombination. This is followed by a survey of the important post-treatment techniques developed over the past few years to minimize energy loss in perovskite solar cells, including solvent annealing, amine halide solution dripping-induced Ostwald ripening, three-dimensional–two-dimensional interface layer from phenethylammonium iodide (PEAI) dripping, and wide bandgap interface layer engineering from n-hexyl trimethylammonium bromide washing. Finally, we provide a prospective view about further developments of post-treatment techniques.
OBJECTIVES/GOALS: The desmoplastic reaction in PDAC involves a significant accumulation of immune cells and fibroblasts.The functional diversity of carcinoma associated fibroblasts (CAFs) remains largely unknown, and identification of immune regulating subsets would have a substantial impact in augmentation of immunotherapy efficacy. METHODS/STUDY POPULATION: Employing histology, FACs, multiplex immunohistochemistry, single cell RNA sequencing (sc-RNA-seq) and genetically engineered mouse models, we demonstrate that aSMA+ cells are a dominant CAF population in PDAC with tumor restraining properties (TS-CAFs), as opposed those of the FAP+ CAFs, which demonstrate tumor promoting activity (TP-CAFs). RESULTS/ANTICIPATED RESULTS: Analysis of bulk tumor depleted of either TS-CAFs or TP-CAFs showed that TS-CAFs predominantly modulate extracellular matrix (ECM) production, facilitate cell-ECM adhesion and regulate adaptive immunity, while TP-CAFs exhibit a lineage that is skewed towards a pro-inflammatory, chemokine secreting phenotype. Further, scRNA-Seq analyses demonstrate that CAFs share distinct gene expression profiles characteristic of lymphocytic and myeloid lineages. Together our data distinguish two populations of CAFs, one which is tumor suppressing with roles in ECM remodeling and another which is tumor promoting with roles in cytokine production, both with immune modulating capabilities. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study identifies a complex network of functionally heterogeneous fibroblasts during PDAC progression with significant immunotherapeutic implication. The identification of distinct fibroblast subsets will allow us to discriminately target fibroblast populations to augment immunotherapy efficacy in pancreatic cancer.
The coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, spread rapidly throughout China and gradually to some countries abroad. How is the development of an epidemic controlled? Early diagnosis is one of the important contents in prevention and control. COVID-19 patients with early mild pneumonia often lack typical evidence to make a definitive diagnosis. Based on the analysis of the cases of 4 patients, this article finds that early diagnosis requires a combination of epidemiology, clinical manifestations, imaging, and etiology, with particular emphasis on epidemiology history and chest computed tomography (CT) manifestations.
High sugar-sweetened beverage (SSB) intake has been shown to correlate with a higher risk for CVD and metabolic disorders, while the association between SSB intake and the risk of metabolic syndrome (MetS) remains unclear. The present study aimed to explore the association between SSB intake and MetS among children and adolescents in urban China.
A cross-sectional study involving 7143 children and adolescents was conducted in urban China. MetS definition proposed by the International Diabetes Federation was adopted. Data on SSB intake, diet, physical activity and family environment factors were obtained through questionnaires. Logistic regression models with multivariable adjustment were adopted to analyse the association between SSB intake and the risk of MetS and its components.
Primary and secondary schools in three urban cities of China.
Children and adolescents (n 5258) aged 7–18 years.
Among the participants, 29·9 % of them had high SSB intake (at least 0·3 servings/d) and the overall MetS prevalence was 2·7 %. Participants with high SSB intake were at higher risk for MetS (OR = 1·60; 95 % CI 1·03, 2·54) and abdominal obesity (OR = 1·55; 95 % CI 1·28, 1·83) compared with their counterparts with no SSB intake (0 servings/d).
High SSB intake is significantly associated with increased MetS and abdominal obesity risk among children and adolescents in urban China. These results suggest that strong policies focusing on controlling SSB intake might be effective in preventing MetS and abdominal obesity.