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Glucagon receptor plays an important role in the regulation of glucose metabolism. Studies have revealed that glucagon receptor antagonism is a potential effective treatment for diabetes. However, the functions of GCGR have not been fully illustrated. Although two Gcgr truncation knockout mice models have been widely used for GCGR function studies, truncated gene may remain neomorphic and/or dominant-negative function. In this study, we took the advantages of Crispr-Cas9 technique and generated a novel allele of GCGR in the mouse that yields complete loss of GCGR protein. Our studies reveal that complete deletion of Gcgr results in hyperglucagonemia, α-cell hyperplasia, improvement of glucose tolerance. These results are similar to the Gcgr-truncated mutation in mice. Hence, we provide a novel strain of GCGR knockout mice for the GCGR function studies.

An electronegativity-dominant high-entropy atomic environment regulation strategy was developed to manipulate the electrocatalytic properties by tailoring the competitive adsorption sites in HEA NPs.

Inductively coupled plasma-mass spectrometry (ICP-MS) with elemental labeling is a promising strategy for multiplex microRNA (miRNA) analysis. However, it is still challenging for specific analysis of multiple miRNAs with high homology, and the development of multiplex assays is always limited by the complexity of the sequence design. Herein, a simple and direct ICP-MS-based assay was developed for the simultaneous detection of three miRNAs by combining the lanthanide labeling strategy with entropy-driven catalytic (EDC) amplification. Owing to the specificity of EDC for nucleic acid recognition, it is able to differentiate miRNAs with single-base mutation in each EDC circuit. A universal biotin-labeled DNA strand was designed to hybridize with the DNA substrates for three EDC circuits, targeting miRNA-21, miRNA-155, and miRNA-10b, respectively. All the substrates were loaded on the surface of streptavidin magnetic beads. In the presence of target miRNA, the EDC reaction was initiated, and EDC substrates were dissociated, continuously releasing reporter strands that were labeled with lanthanides (Tb/Ho/Lu). After magnetic separation, the supernatant containing the released reporter strands was introduced into an ICP-MS system for simultaneous detection of

In order to meet the requirements of online fault detection for dry reactor, an online fault detection technology based on improved Kalman filter is proposed. The main content of the technology is based on the dry reactor detection technology, through the study of improved Kalman filter, the use of fault diagnosis and other methods, and finally through the experiments and analysis to build improved Kalman filter dry reactor online fault detection research means. The experimental results show that the maximum relative error of the improved Kalman filter is 6.039%, and the average relative error is 2.388%. The improved algorithm is very effective and greatly improves the prediction accuracy. The research based on improved Kalman filter can meet the demand of online fault detection of reactor.

Aim: To evaluate the efficacy and safety of corticosteroids for treating hospitalized COVID-19 patients. Materials & methods: Efficacy outcomes included time to negative SARS-CoV-2 tests, length of stay, duration and incidence of intensive unit care stay, incidence of mortality and duration and incidence of mechanical ventilation. Safety outcomes included the incidence of adverse events and severe adverse events, incidence of hyperglycemia and incidence of nosocomial infections. Results: Ninety-five randomized controlled trials (RCTs) and observational studies (n = 42,205) were included. Corticosteroids were associated with increased length of stay (based on RCT only), increased time to negative tests, decreased length of mechanical ventilation and increased odds of hyperglycemia. Conclusion: Corticosteroids should be considered in patients requiring mechanical ventilation, and glycemic monitoring may be needed when administering corticosteroids.

IntroductionThe concepts of health, illness, and disability as well as the perceptions of autism and quality of life (QoL) vary greatly across cultures and across time. This study sought to explore the interplay of culture on QoL and impact on parents caring for autistic children.MethodsWe used a transcultural dataset from seven countries (Australia, Hungary, Malaysia, Romania, Singapore, Spain, and the United Kingdom) with participating parents/carers reporting on the Quality of Life in Autism (QoLA) questionnaire. The QoLA questionnaire is a validated measure of QoL for parents of autistic children, with Part A subscale measuring parental QoL and part B subscale assessing the parental impact of the child’s autism spectrum disorder (ASD) symptoms or features. We used the Quade’s ranked analysis of covariance to determine significant differences between the countries in relation to QoLA Part A and Part B scores while adjusting for baseline differences using covariates such as parents’ gender, child’s age, and gender. Additionally, a post-hoc analysis with Bonferroni correction was also conducted to examine multiple pairwise comparisons.Results and conclusionWe found that while the effect of features of ASD (Part B subscale) stayed strongly comparable between cultures, the self-reported parental QoL was most likely determined by different aspects of culture in different countries. It is concluded that while the ASD symptoms or features appear to affect parents in the same way across different countries, the parental QoL may be a culturally informed construct.

Thermal management has become a crucial problem for high-power-density equipment and devices. Phase change materials (PCMs) have great prospects in thermal management applications because of their large capacity of heat storage and isothermal behavior during phase transition. However, low intrinsic thermal conductivity, ease of leakage, and lack of flexibility severely limit their applications. Solving one of these problems often comes at the expense of other performance of the PCMs. In this work, we report core–sheath structured phase change nanocomposites (PCNs) with an aligned and interconnected boron nitride nanosheet network by combining coaxial electrospinning, electrostatic spraying, and hot-pressing. The advanced PCN films exhibit an ultrahigh thermal conductivity of 28.3 W m−1 K−1 at a low BNNS loading (i.e., 32 wt%), which thereby endows the PCNs with high enthalpy (> 101 J g−1), outstanding ductility (> 40%) and improved fire retardancy. Therefore, our core–sheath strategies successfully balance the trade-off between thermal conductivity, flexibility, and phase change enthalpy of PCMs. Further, the PCNs provide powerful cooling solutions on 5G base station chips and thermoelectric generators, displaying promising thermal management applications on high-power-density equipment and thermoelectric conversion devices.

Herein, we developed a novel fluorescent assay using spherical identification probes and toehold-mediated strand displacement reaction-initiated silver nanoclusters (AgNCs) "on-off" signal switch. In this strategy, the target was captured by the spherical probes to induce the activity of exonuclease III (Exo III), catalyzing the cyclic cleavage of substrates to produce a mass of trigger strands. After magnetic bead separation, the intermediates in the supernatant activated downstream toehold-mediated strand displacement reaction to change the structure of silver nanocluster templates, leading to fluorescence intensity reduction. Furthermore, it is demonstrated that the application of spherical identification probes could reduce the signal leakage and the limit of detection. In addition, AgNCs with perfect optical property were ingeniously combined to realize signal output, which reduced the cost and time of synthesis. Under the optimal conditions, the sensing method displayed a good linear range from 250 pM to 25 nM with a detectable minimum concentration of 250 pM. And the practical application potential in complex biological matrices was also evaluated. Considering these advantages, this constructed strategy opens a new path for nucleic acid detection with better performance. A simple, label- and hairpin-free fluorescent system based on spherical identification probe and toehold-mediated strand displacement reaction-initiated silver nanoclusters (AgNCs) "on-off" signal switch was successfully constructed to detect target DNA.

Sulfonated bis(4-methyl benzoate) phenylphosphine oxide (sBMPO) was synthesized by the sulfonation and esterification of bis(4-methylbenzoate)phenylphosphine oxide (BMPO).

Background China has undergone unprecedented urbanization in the past decades, with this rapid urbanization having profound and lasting impacts on human well-being. The aim of this study was to examine the association between urbanization and psychological well-being (PWB) in China. Methods Data was obtained from the 2015 China Health and Nutrition Survey and included 3,071 men and 3,385 women aged 50 years or older who lived in 288 communities across 12 provinces and municipalities. The urbanization index, summarizing 12 urbanization dimensions at community level, was categorized into tertiles representing low, medium and high levels of urbanization. PWB was assessed by scoring three self-reported questions. Gender-stratified multilevel analyses (level-1, individuals; level-2, communities; level-3: provinces/municipalities) were used to estimate the association between exposure to urbanization and PWB. Results The urbanization index was associated positively with PWB in middle-aged and elderly people after controlling for individual-level factors, with the association being stronger in women than in men. More specifically, an increase of one standard deviation in the score of community population density, economic activity, housing, education, sanitation, and diversity were associated significantly with PWB in both genders after adjustment for individual-level factors. In addition, the increase in the score of community communications, social services, transportation, and modern markets were also associated significantly with PWB in women, but not in men. Conclusions Urbanization has, on average, had an independent and positive effect on PWB in middle-aged and elderly Chinese populations, with many components of urbanization being separately and positively associated with PWB, especially in women. These findings provide novel insights for decision-makers on how to equitably allocate public resources to improve human well-being in the face of rapid urbanization.

Relaxor ferroelectric polymers display great potential in capacitor dielectric applications because of their excellent flexibility, light weight, and high dielectric constant. However, their electrical energy storage capacity is limited by their high conduction losses and low dielectric strength, which primarily originates from the impact-ionization-induced electron multiplication, low mechanical modulus, and low thermal conductivity of the dielectric polymers. Here a matrix free strategy is developed to effectively suppress electron multiplication effects and to enhance mechanical modulus and thermal conductivity of a dielectric polymer, which involves the chemical adsorption of an electron barrier layer on boron nitride nanosheet surfaces by chemically adsorbing an amino-containing polymer. A dramatic decrease of leakage current (from 2.4 × 10−6 to 1.1 × 10−7 A cm−2 at 100 MV m−1) and a substantial increase of breakdown strength (from 340 to 742 MV m−1) were achieved in the nanocompostes, which result in a remarkable increase of discharge energy density (from 5.2 to 31.8 J cm−3). Moreover, the dielectric strength of the nanocomposites suffering an electrical breakdown could be restored to 88% of the original value. This study demonstrates a rational design for fabricating dielectric polymer nanocomposites with greatly enhanced electric energy storage capacity.

Extreme learning machine (ELM) is suitable for nonlinear soft sensor development. Yet it faces an overfitting problem. To overcome it, this work integrates bound optimization theory with variational Bayesian (VB) inference to derive novel L1 norm-based ELMs. An L1 term is attached to the squared sum cost of prediction errors to formulate an objective function. Considering the nonconvexity and nonsmoothness of the objective function, this article uses bound optimization theory, and constructs a proper surrogate function to equivalently convert a challenging L1 norm-based optimization problem into easy one. Then, VB inference is adopted for optimizing the converted problem. Thus, an L1 norm-based ELM can be efficiently optimized by an alternating optimization algorithm with a proved convergence. Finally, a soft sensor is developed based on the proposed algorithm. An industrial case study is carried out to demonstrate that the proposed soft sensor is competitive against recent ones.

Multitask optimization (MTO) is a new optimization paradigm that leverages useful information contained in multiple tasks to help solve each other. It attracts increasing attention in recent years and gains significant performance improvements. However, the solutions of distinct tasks usually obey different distributions. To avoid that individuals after intertask learning are not suitable for the original task due to the distribution differences and even impede overall solution efficiency, we propose a novel multitask evolutionary framework that enables knowledge aggregation and online learning among distinct tasks to solve MTO problems. Our proposal designs a domain adaptation-based mapping strategy to reduce the difference across solution domains and find more genetic traits to improve the effectiveness of information interactions. To further improve the algorithm performance, we propose a smart way to divide initial population into different subpopulations and choose suitable individuals to learn. By ranking individuals in target subpopulation, worse-performing individuals can learn from other tasks. The significant advantage of our proposed paradigm over the state of the art is verified via a series of MTO benchmark studies.

Yuan Chen,1,* Yiheng Chen,2,* Chonghui Tang,3 Qian Zhao,1 Tailin Xu,1 Qi Kang,1 Bin Jiang,2 Li Zhang4 1Department of Endocrinology, The First People’s Hospital of Zunyi, Zunyi, Guizhou, 563000, People’s Republic of China; 2Department of Hand and Plastic Surgery, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325000, People’s Republic of China; 3Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 315300, People’s Republic of China; 4Department of Neurosurgery, China-Japan Friendship Hospital, Beijing, 100029, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li ZhangDepartment of Neurosurgery, China-Japan Friendship Hospital, No. 2 Yinghua East Road, District of Chaoyang, Beijing, 100029, People’s Republic of ChinaEmail ftzy73129@sina.comAim: Endothelial dysfunction is a key pathological basis for diabetes mellitus complications, including diabetic nephropathy, diabetic retinopathy, and diabetic cardiomyopathy. This study aimed to reveal the functional role of ribosomal protein S4 Y-linked 1 (RPS4Y1) in endothelial dysfunction.Methods: Human umbilical vein endothelial cells (HUVECs) were subjected to high glucose. The expression of RPS4Y1 in cells was overexpressed or silenced by plasmid or siRNA transfection. MTT assay, flow cytometry, JC-1 probe, scratch test, tube formation, and ELISA were conducted to assess the effects of RPS4Y1 on cell. Western blot was performed to assay the downstream signaling of RPS4Y1. The inhibitors of p38, ERK, and Jnk were used to treat cells to validate the involvement of them in RPS4Y1-mediated endothelial dysfunction.Results: RPS4Y1 was upregulated in HUVECs in response to high glucose in both dose- and time-dependent manners. Overexpression of RPS4Y1 induced viability loss, apoptosis, and inflammation, but inhibited cell migration and tube formation. Silence of RPS4Y1 impacted these aspects in a contrary trend. The phosphorylation of p38 rather than ERK and Jnk was activated by RPS4Y1. In addition, the dysfunction of HUVECs mediated by RPS4Y1 was attenuated by SB203580 (a specific inhibitor of p38 signaling).Conclusion: The highly expressed RPS4Y1 in endothelial cells may contribute to high glucose-induced dysfunction through regulating p38 MAPK signaling. RPS4Y1 might be a potential therapeutic target for treating diabetes mellitus complications.Keywords: RPS4Y1, HUVEC, diabetes mellitus, high glucose, p38 MAPK signaling