Search

Abstract Aims Whether sodium‐glucose co‐transporter 2 inhibitors are effective for heart failure caused by ATTR‐CA (transthyretin cardiac amyloidosis) remains uncertain. The aim of this study is to investigate the cardiovascular prognosis in ATTR‐CA mice model with dapagliflozin treatment. Methods and results Humanized RBP4/TTRVal50Met and RBP4/TTR mice models were constructed with clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR‐Cas9) techniques and multiple generations breeding. A total of 6 RBP4/TTR mice received placebo treatment, when 12 RBP4/TTRVal50Met received dapagliflozin (1 mg/kg/day, 6 mice) and placebo (6 mice) treatment. Fasting glucose, intraperitoneal glucose tolerance test, and plasma brain natriuretic peptide (BNP) concentration were measured at Day 0, Week 2, and Week 4. BNP, transforming growth factor‐beta (TGF‐β), collagen type I alpha 1 (COL1A1) protein levels, and Cola1, TGFβ1, TNFα, IL‐1β, BNP relative quantities in cardiac, along with cardiac pathology examination including right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter were measured at Week 4 after treatment procedure. All 18 mice completed the experiment. The baseline characteristics were balanced among three treatment groups. In placebo‐treated mice, the cardiac BNP relative quantity was significantly higher in RBP4/TTRVal50Met mice than RBP4/TTR mice (RBP4[KI/KI], TTR [KI/KI]: 0.72 ± 0.46, RBP4[KI/KI], TTRVal50Met[KI/KI]: 1.44 ± 0.60, P = 0.043), indicating more significant heart failure progression in ATTR‐CA mice than normal mice. In ATTR‐CA mice, the cardiovascular prognosis measurements including heart failure (plasma BNP concentration and relative quantities of BNP), cardiac inflammation (relative quantities of Cola1, TGFβ1, TNFα, and IL‐1β), and pathological changes (right ventricular collagen percentage, ventricular septum thickness, left ventricular wall thickness, and left ventricular internal diameter) were statistically comparable between those under dapagliflozin and placebo treatment. Conclusions Dapagliflozin did not improve cardiovascular prognosis including the progression of heart failure, cardiac inflammation, and pathological changes in ATTR‐CA mice compared with placebo. The results of this study were not in support of dapagliflozin's therapeutic effects for ATTR‐CA. More pre‐clinical and clinical researches to validate these findings and demonstrate the underlying mechanisms are still required.

There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00–0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04–0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, −0.07units/kg/day, 95% CI, −0.11 to −0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, −0.11units/kg/day, 95% CI, −0.23 to −0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.

As a common method for preparing micron powder in industrial operations, the mechanical extrusion method simply pursues the particle size without considering the microstructure characteristics of sepiolite, which leads to problems such as bundles of sepiolite not being effectively dispersed, and thus the disruption of fibers is inevitably caused. In this work, a new micronization method for disaggregating these bundles while preserving the original structural integrity of the fibers is proposed based on steam pressure changes. The effects of steam pressure changes on the particle size distribution, microstructure, and properties of treated sepiolite are studied using X-ray fluorescence spectrometer (XRF), X-ray diffractometer (XRD), Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy (TEM), and a specific surface area and aperture analyzer (BET). The experimental results show that the particle size of sepiolite powder depends greatly on steam pressure, and sepiolite powder with mass ratio of 91.6% and a particle size D97 of 21.27 μm is obtained at a steam pressure of 0.6 MPa. Compared to the sepiolite after mechanical extrusion, the sepiolite treated with steam pressure changes can maintain the integrity of its crystalline structure. The specific surface area of sepiolite enhanced from 80.15 m2 g−1 to 141.63 m2 g−1 as the steam pressure increased from 0.1 to 0.6 MPa, which is about 1.6 times that of the sample treated with mechanical extrusion.

The invasion of exotic ant species in China presents significant challenges to ecosystems, agriculture, and the economy. This paper provides an in-depth analysis of China's ongoing battle with exotic ants, examining the factors contributing to their introduction and establishment. It explores the responses implemented by the decision makers, including capacity building, establishment of research institutions, and legislative measures. Limitations and gaps in the current strategies are identified, highlighting the need for regional collaboration, increased awareness, and strengthened early detection and response systems. Furthermore, the paper emphasizes the importance of conducting research to understand various exotic ant species' ecological and economic impacts, facilitating the development of targeted and effective management approaches. By adopting a comprehensive and coordinated approach, China can mitigate the impacts of ant invasions and safeguard its biodiversity, agriculture, and economy. This analysis underscores the significance of collective efforts in addressing the ongoing battle with exotic ants and preserving the well-being of ecosystems, economies, and the society.

Abstract Background The growth of rice is reduced by the slow decomposition of accumulated straw, which competes with rice for soil nitrogen nutrient. In recent year, straw-decomposing inoculants (SDIs) that can accelerate straw decomposition and ammonium nitrogen (N) fertilizer that can quickly generate available N is increasingly adopted in China. However, it is still unknown whether the N demand of straw decomposition and crop growth can be simultaneously met through the co-application of SDIs and ammonium N fertilizer. Results In this study, we investigated the effect of the co-application of SDIs and ammonium bicarbonate on decomposition rate of wheat straw, rice growth and rice yield over two consecutive years in rice-wheat rotation system. Compound fertilizer (A0) was used as control. The ratios of ammonium bicarbonate addition were 20% (A2), 30% (A3) and 40% (A4), respectively, without SDIs or with SDIs (IA2, IA3, IA4). Our results revealed that without SDIs, compared with A0, straw decomposition rate, rice growth and yield were improved under A2; However, under A3, rice yield was decreased due to the slow decomposition rate of straw and limited growth of rice during late growth stage. Combining SDIs and N fertilizer increased straw decomposition rate, rice growth rate and yield more than that of N fertilizer alone, especially under IA3. Compared with A0, straw decomposition rate, tiller number, aboveground biomass, leaf area index, root length, and nitrogen use efficiency were significantly increased by 16%, 8%, 27%, 12%, 17%, and 15% under IA3. Consequently, the average rice yield of IA3 was increased to 10,856 kg/ha, which was 13% and 9% higher, respectively, than of A0 and A2. Conclusion Our results indicated that ammonium bicarbonate application alone carried a risk of nutrient deficiency during late growth stage and yield decline. Therefore, the co-application of SDIs and 30% ammonium N fertilizer substitution can be a favorable practice to simultaneously accelerate straw decomposition and increase rice crop growth.

AimsGlucokinase activators (GKAs) promote the activity of glucokinase (GK) and is under development for the treatment of diabetes. The efficacy and safety of GKAs require evaluation.MethodsThis meta-analysis included randomized controlled trials (RCTs) with a duration of at least 12 weeks conducted in patients with diabetes. The primary objective of this meta-analysis was the difference of hemoglobin A1c (HbA1c) change from baseline to study end between GKA groups and placebo groups. Risk of hypoglycemia and laboratory indicators were also evaluated. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for the continuous outcomes, and odds ratios (ORs) and 95% CI were calculated for the risk of hypoglycemia.ResultsData from 13 RCTs with 2,748 participants treated with GKAs and 2,681 control participants were analyzed. In type 2 diabetes, the level of HbA1c decreased greater in patients with GKA treatment compared with placebo (WMD = -0.339%, 95% CI -0.524 to -0.154%, P < 0.001). The OR comparing GKA versus placebo was 1.448 for risk of hypoglycemia (95% CI 0.808 to 2.596, P = 0.214). The WMD comparing GKA versus placebo was 0.322 mmol/L for triglyceride (TG) levels (95% CI 0.136 to 0.508 mmol/L, P = 0.001). When stratified by drug type, selectivity, and study duration, a significant difference was found between groups. In type 1 diabetes, the result of HbA1c change and lipid indicators showed no significant difference between the TPP399 group and the placebo group.ConclusionsIn patients with type 2 diabetes, GKA treatment was associated with a better glycemic control but a significant elevation in TG concentration in general. The efficacy and safety varied with drug type and selectivity.Systematic review registrationInternational Prospective Register of Systematic Reviews, identifier CRD42022378342.

Summary: Background: Curbing or reversing high glycated hemoglobin (HbA1c) and body mass index (BMI) are two essential parts in the clinical management of type 2 diabetes (T2D). We delineated the changing patterns of the baseline HbA1c and BMI in patients with T2D from placebo-controlled randomised trials to reflect the unmet clinical needs. Methods: PubMed, Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to December 19, 2022. Placebo-controlled trials of T2D with reports of baseline HbA1c and BMI were included, of which summary data from published reports were extracted. Pooled effect sizes of baseline HbA1c and BMI of from studies published in the same year were computed in Random-effects model due to the high level of heterogeneity among studies. The main outcome was correlations between the pooled baseline HbA1c, the pooled baseline BMI, and study years. This study was registered in PROSPERO as CRD42022350482. Findings: We identified 6102 studies, of which 427 placebo-controlled trials with 261, 462 participants were finally included in the study. Baseline HbA1c level declined with time (Rs = −0.665, P ＜ 0.0001, I2 = 99.4%). Baseline BMI increased over the past 35 years (R = 0.464, P = 0.0074, I2 = 99.4%), rising by around 0.70 kg/m2 per decade. Patients with BMI ≤25.0 kg/m2 dropped substantially from the half in 1996 to none in 2022. Patients with BMI ranging from 25 kg/m2 to 30 kg/m2 stabilized at 30–40% since 2000. Interpretation: A substantial decline in baseline HbA1c levels and a constant increase in baseline BMI levels was found in placebo-controlled trials through the past 35 years, which indicated the improvement in glycemic control and the urgency for the management of obesity in T2D. Funding: National Natural Science Foundation of China (No.81970698), Beijing Natural Science Foundation (No.7202216) and National Natural Science Foundation of China (No.81970708).

Erratic rainfall and misalignment between the rainy season and the growing season of winter wheat greatly limit rainfed winter wheat yield in the Loess Plateau of China. To increase the grain yield of winter wheat in this region, the effects of different agronomic practices, including adjusting planting pattern (NR, narrow row spacing), increasing seeding rate (high seeding rate, HS), decreasing basal nitrogen rate and increasing top-dressed nitrogen rate (DBN), and replacing an old cultivar with a new cultivar (NC) on wheat yield were investigated for two consecutive years. The results showed that the current grain yield of rainfed winter wheat in the Loess Plateau could be increased to 5879–7093 kg ha−1 by HS, DBN and NC practices relative to the practice of high-yielding farmers (PF). The increased yield due to HS, DBN and NC was attributed to the higher number of spikes ha−1, 1000-grain weight, and kernels spike−1. Before the flowering stage, HS increased soil water consumption (SWC) in 1–3 m subsoil due to the higher plant population compared with that of PF, whereas DBN decreased SWC in the 0–2 m soil layer compared with that of PF. After the flowering stage, HS, DBN, and NC increased SWC by 8–16 mm in 2–3 m subsoil compared to PF. The water use efficiency (WUE) was increased under DBN and NC in comparison with PF. However, the WUE did not increase under HS as it had the highest evapotranspiration among the five treatments. Increasing the use of subsoil water during the late growth stage by optimizing agronomic practices or applying new cultivars with expansive roots should be the primary approach to increase rainfed winter wheat yield in this region.

Background: The pleiotropic efficacy of SGLT2is in patients with different eGFR levels has not been well-understood. This systematic review and meta-analysis assessed the disparities in the efficacy and safety of SGLT2i treatment across stratified renal function.Methods: We searched four databases from inception to December 2021. We included randomized controlled trials (RCTs) with reported baseline eGFR levels and absolute changes from baseline in at least one of the following outcomes: HbA1c, body weight, blood pressure, and eGFR. Continuous outcomes were evaluated as the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Categorical outcomes were evaluated as odds ratios (ORs) and accompanying 95% CIs.Results: In total, 86 eligible RCTs were included. SGLT2is produces a substantial benefit in glycemic control, weight control, and blood pressure control even in patients with impaired renal function. HbA1c and weight reductions observed in SGLT2i users were generally parallel with the renal function levels, although there was an augmented weight reduction in severe renal dysfunction stratum [HbA1c: −0.49% (−0.58 to −0.39%) for normal renal function, −0.58% (−0.66 to −0.50%) for mild renal function impairment, −0.22% (−0.35 to −0.09%) for moderate renal function impairment, and −0.13% (−0.67 to 0.42%) for severe renal function impairment (p < 0.001 for subgroup differences); weight: −2.12 kg (−2.66 to −1.59 kg) for normal renal function, −2.06 kg (−2.31 to −1.82 kg) for mild renal function impairment; −1.23 kg (−1.59 to −0.86 kg) for moderate renal function impairment; −1.88 kg (−3.04 to −0.72 kg) for severe renal function impairment (p = 0.002 for subgroup differences)]. However, the blood pressure reduction observed in SGLT2i users was independent of renal function. When compared with the placebo, the occurrence of hypoglycemia was more frequent in patients with favorable renal function rather than in those with substantial renal dysfunction.Conclusion: The HbA1c and body weight reductions observed in SGLT2i users were generally parallel with their baseline eGFR levels, while blood pressure reductions in SGLT2i users were independent of their baseline eGFR levels. Consistently, when compared with the placebo, hypoglycemia was more frequent in patients with favorable renal function, where the HbA1c reduction was profound.

AimsThe aim of the study was to evaluate the association between evening chronotype and social jetlag (SJL) with obesity, blood glucose and lipid levels in non-shift working adults.MethodsThe databases of MEDLINE, EMBASE and Cochrane Reviews were searched for studies analyzing the metabolic parameters among groups of different chronotypes or SJL until Feb 2022. Weighted mean difference (WMD) and 95% confidence intervals (CI) were used to analyze the association between these parameters and chronotypes or SJL.ResultsA total of 27 studies were included in this meta-analysis. Compared with morning chronotype, the participants with evening chronotype had higher body mass index (BMI) (WMD= 0.44 kg/m2, 95%CI, 0.30 to 0.57 kg/m2, p

The Scalloped (Sd) is a transcription factor that regulates organ size control in the Hippo-signaling pathway. Recent studies have showed that Hippo signaling also functions in the innate immune response. Although the Sd gene has been reported in many insects, their immune functions remain unexplored. In this study, the LsSd gene of Lasioderma serricorne, with a complete open reading frame that encodes a protein composed of 402 amino acids was identified. LsSd was predominantly expressed in early pupae. Tissue-specific analyses revealed that the highest concentrations of LsSd were detected in the midgut and brain. At 1–24 h after Escherichia coli infection, LsSd expression increased substantially. However, LsSd expression was downregulated 3–12 h after Staphylococcus aureus infection. RNA interference-mediated silencing of the LsSd transcript resulted in deformed, considerably smaller, and degenerated wings. Meanwhile, LsCycE, LsDiap1, and LsVg, which are involved in cell proliferation and wing development, were drastically reduced when LsSd was depleted. In a survival assay, the LsSd knockdown considerably decreased the susceptibility to S. aureus, a gram-positive bacterium. In addition, knockdown of LsSd remarkably downregulated the transcription of LsCact in response to S. aureus stimulation, while upregulating the expression of five immune-related genes. Our results provide conclusive proof for the important roles of LsSd in the immune response of L. serricorne.

The present study provides comprehensive analyses of a newly constructed passive energy-efficient building located in Harbin, China, which is a prime example of how to design a passive building that withstands the severe cold climate in northeast Asia. Conduction transfer functions of heat flux equilibrium are employed to simulate energy consumption characteristics of the paradigm passive building. The climatic conditions in severe cold region are analyzed, and the energy-saving designs in the studied engineering cases are summarized for their practical applications. Building physical models are established to perform numerical simulation analyses on the passive building paradigm in northeast Asian frigid zone. The dominant technical parameters of envelope structure affecting energy consumption in severe cold region, including thermal insulation thickness and heat transfer coefficient of building envelope, as well as window-to-wall ratio for each building facade, are taken into consideration as simulation variables to calculate cooling load, heating load, electricity consumption, and CO2 emission, which account for energy efficiency of passive buildings. The simulation results demonstrate the high energy-saving potential of the proposed passive building design and render the optimal energy-efficient parameters suitable for severe cold regions, which can reduce energy consumption and CO2 emission while ensuring comfort for occupants. The present study provides a theoretical reference for envelope structures of passive buildings in severe cold regions, which is of great significance to the development of green buildings and relevant policies.

An amendment to this paper has been published and can be accessed via the original article.

In order to evaluate the efficacy and side effects of the non-insulin antidiabetes medications as an adjunct treatment in type 1 diabetes mellitus (T1DM), we conducted systematic searches in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials published between the date of inception and March 2020 to produce a systematic review and meta-analysis. Overall, 57 studies were included. Compared with placebo, antidiabetes agents in adjunct to insulin treatment resulted in significant reduction in glycosylated hemoglobin (weighted mean difference [WMD], –0.30%; 95% confidence interval [CI], –0.34 to –0.25%; P

Abstract Background To exam the associations between the use of sodium glucose co-transporter 2 inhibitor (SGLT2i) and the risk of lower limb complications, and to analyze the associated factors. Methods Pubmed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from the inception to November 2020. Randomized controlled trials of SGLT2i conducted in population containing diabetic patients with reports of amputation, peripheral arterial disease (PAD) and diabetic foot (DF) events were included. Random-effect model, fixed-effect model and meta-regression analysis were accordingly used. Result The numbers of SGLT2i users versus non-SGLT2i users in the analyses of amputation, PAD and DF were 40,925/33,414, 36,446/28,685 and 31,907/25,570 respectively. Compared with non-SGLT2i users, the risks of amputation and PAD were slightly increased in patients with canagliflozin treatment (amputation: OR = 1.60, 95% CI 1.04 to 2.46; PAD: OR = 1.53, 95 % CI 1.14 to 2.05). Meta-regression analyses indicated that greater weight reduction in SGLT2i users was significantly associated with the increased risks of amputation (β = − 0.461, 95% CI − 0.726 to − 0.197), PAD (β = − 0.359, 95% CI − 0.545 to − 0.172) and DF (β = − 0.476, 95% CI − 0.836 to − 0.116). Lower baseline diastolic blood pressure (β = − 0.528, 95% CI − 0.852 to − 0.205), more systolic blood pressure reduction (β = − 0.207, 95% CI − 0.390 to − 0.023) and more diastolic blood pressure reduction (β = − 0.312, 95% CI − 0.610 to − 0.015) were significantly associated with the increased risks of amputation, PAD and DF respectively in patients with SGLT2i treatment. Conclusions The risks of amputation and PAD were slightly increased in patients with canagliflozin treatment. Reductions in body weight and blood pressure were associated with lower limb complications in patients with SGLT2i treatment.

Abstract Background The placebo response in patients with diabetes mellitus is very common. A systematic evaluation needs to be updated with the current evidence about the placebo response in diabetes mellitus and the associated factors in clinical trials of anti-diabetic medicine. Methods Literature research was conducted in Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies published between the date of inception and June 2019. Randomized placebo-controlled trials conducted in type 1and type 2 diabetes mellitus (T1DM/T2DM) were included. Random-effects model and meta-regression analysis were accordingly used. This meta-analysis was registered in PROSPERO as CRD42014009373. Results Significantly weight elevation (effect size (ES) = 0.33 kg, 95% CI, 0.03 to 0.61 kg) was observed in patients with placebo treatments in T1DM subgroup while significantly HbA1c reduction (ES = − 0.12%, 95% CI, − 0.16 to − 0.07%) and weight reduction (ES = − 0.40 kg, 95% CI, − 0.50 to − 0.29 kg) were observed in patients with placebo treatments in T2DM subgroup. Greater HbA1c reduction was observed in patients with injectable placebo treatments (ES = − 0.22%, 95% CI, − 0.32 to − 0.11%) versus oral types (ES = − 0.09%, 95% CI, − 0.14 to − 0.04%) in T2DM (P = 0.03). Older age (β = − 0.01, 95% CI, − 0.02 to − 0.01, P

Generative Adversarial Networks (GANs) have achieved impressive results in various image synthesis tasks, and are becoming a hot topic in computer vision research because of the impressive performance they achieved in various applications. In this paper, we introduce the recent research on GANs in the field of image processing, including image synthesis, image generation, image semantic editing, image-to-image translation, image super-resolution, image inpainting, and cartoon generation. We analyze and summarize the methods used in these applications which have improved the generated results. Then, we discuss the challenges faced by GANs and introduce some methods to deal with these problems. We also preview some likely future research directions in the field of GANs, such as video generation, facial animation synthesis and 3D face reconstruction. The purpose of this review is to provide insights into the research on GANs and to present the various applications based on GANs in different scenarios.

Wireless power transmission (WPT) technique has advanced rapidly in the past two decades. For wireless power transmission distances from 40 to 200 mm, the resonance coupling WPT (R-WPT) technique has surpassed its original inductive coupling counterpart in terms of transmission efficiency. Nevertheless, the power transfer efficiency of a R-WPT system is still lower than that of a wired power transfer system. To increase the power transfer efficiency of a R-WPT system, metamaterial (MM) slabs are inserted between the transmitter and receiver. Moreover, it has recently been validated that a hybrid MM (HMM) slab with different resonance frequency unit cells behaves better than a homogeneous MM slab with identical resonance frequency unit cells in a R-WPT application. However, in the existing HMM slab designs for WPT applications, a trial and error approach, is commonly used to decide the physical and circuit parameters of the HMM slab due to the overwhelmingly high computational cost of numerical simulations using three-dimensional (3-D) finite element method. To overcome the deficiencies of the existing designing methodology and to fully automate the design process, a design-of-experiment (DOE) assisted sequential refinement methodology is proposed by introducing an adaptive surrogate model with tabu search method, for design optimizations of HMM slabs in R-WPT applications. Compared with the existing refinement searching procedures, the salient feature of the proposed one is its bi-directional characteristics, which can refine the searches in the promising sub spaces by intensifying sampling points; and use coarse searches or even discarding the exploitations in the worst sub spaces using some adaptive upper and lower limits of the decision parameters. To validate the feasibility and show the advantages of the proposed methodology, detailed numerical and experimental studies on a case study of a four-coil WPT system working at 13.88 MHz are conducted, and the results have shown that the HMM slab optimized by using the proposed methodology does have better performance in WPT applications when compared to its homogenous counterparts.

Biomass, the only globally available, renewable feedstock of organic carbon, is considered a viable alternative to fossil fuels. It can be efficiently utilized to produce various building blocks in accordance with green and sustainable chemistry principles. In this review, recent progress, such as the transformation of carbohydrates (C5 or C6 sugar, inulin, and cellulose) and their derivatives (furfural, hydroxymethylfurfural) into significant platform chemicals over polyoxometalates, zeolites, non-noble metals, and ionic liquids in single or multiphase, is evaluated.

Objective: Aberrantly expressed exosomal circular RNAs (circRNAs) have been reported in various human cancers. Nevertheless, it remains elusive in cutaneous squamous cell carcinoma (cSCC). Herein, based on RNA-seq, we systematically uncovered the expression and implication of exosomal circRNAs in cSCC.Methods: Plasma exosomes derived from cSCC and healthy subjects were characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and western blot. Differentially expressed exosomal circular RNAs (circRNAs) were screened by RNA-seq analysis, which were validated by RT-qPCR. Among them, the biological structure of circ-CYP24A1 was validated by Sanger sequencing and RNase R digestion. Si-circ-CYP24A1 was transfected into exosomes, followed by incubation with A431 and SCL-1 cells. Then, viability, apoptosis, migration, and invasion were evaluated by CCK-8, TUNEL staining and migration assays.Results: This study identified 25 up- and 76 down-regulated exosomal circRNAs in cSCC than healthy subjects. Among them, circulating circ-CYP24A1 was confirmed to be up-regulated in cSCC. Circ-CYP24A1 had a covalently closed circular structure and was not sensitive to RNase R digestion. After incubation with si-circ-CYP24A1-transfected exosomes, proliferation, migration, and invasion were lowered while apoptosis was enhanced in A431 and SCL-1 cells. Meanwhile, si-circ-CYP24A1-transfected exosomes significantly decreased the expression of downstream targets CDS2, MAVS, and SOGA in cSCC cells.Conclusion: Collectively, our study identified that targeting exosomal circ-CYP24A1 could suppress cSCC progression by weakening tumor malignant behaviors, which might provide a promising therapeutic target and non-invasive diagnostic biomarker for cSCC.

ObjectiveGraves’ disease (GD) and autoimmune thyroiditis (AIT) are two major causes of thyrotoxicosis that require correct diagnosis to plan appropriate treatment. The objectives of this study were to evaluate the usefulness of thyroid-related parameters for distinguishing GD from AIT and identify a novel index for differential diagnosis of thyrotoxicosis.DesignThis retrospective study was performed using electronic medical records in Peking University People’s Hospital (Beijing, China).MethodsIn total, 650 patients with GD and 155 patients with AIT from December 2015 to October 2019 were included in cohort 1. Furthermore, 133 patients with GD and 14 patients with AIT from December 2019 to August 2020 were included in cohort 2 for validation of the novel index identified in cohort 1. All patients were of Chinese ethnicity and were newly diagnosed with either GD or AIT. Thyroid-related clinical information was collected before intervention by reviewing the patients’ electronic medical records. Receiver operating characteristic curve analysis was used to identify the optimal cutoff for distinguishing GD from AIT.ResultsIn cohort 1, thyroid-stimulating hormone (TSH) receptor antibody was identified as the best indicator for distinguishing GD from AIT. The area under the receiver operating characteristic curve was 0.99(95% confidence interval: 0.98–0.99, p

ObjectiveWhether hypoglycemic treatments with weight-alternating effects influence the incidence of neoplasm in type 2 diasbetes (T2D) remains uncertain. Therefore, we performed a meta-analysis to assess the association between the weight alteration and incidence of neoplasm in patients with T2D.Research Design and MethodsSystematic searches were conducted for studies published between the inception of 1950s and September 2019. Randomized controlled trials conducted in T2D patients with at least 48-week follow-up, significant weight change difference between treatment arms and reports of neoplasm events were included. Fixed-effects model and meta-regression analysis were accordingly used.ResultsIn all, 46 studies were included. Analysis indicated weight reduction was not associated with a decreased incidence of neoplasm (OR = 1.01, 95% CI, 0.96 to 1.07, I2 = 17%) and weight elevation was not associated with an increased incidence of neoplasm (OR = 0.91, 95% CI, 0.76 to 1.09, I2 = 0%). Meta-regression analysis showed a slower weight reduction rate (β = −5.983, 95% CI, −11.412 to 0.553, P = 0.03) instead of weight change difference (β = −0.030, 95% CI, −0.068 to 0.007, P = 0.115) was significantly associated with reduced risk of neoplasm in patients with T2D. Moreover, a decreased incidence of prostate, bladder, and uterine neoplasm was observed in T2D patients with weight reduction difference while an increased incidence of thyroid neoplasm was found in glucagon-like peptide-1 receptor analog (GLP-1RA) users with weight reduction difference.ConclusionsAdditional weight change achieved by current hypoglycemic agents or strategies in short and medium periods was not associated with incidence of most neoplasm in patients with T2D. However, a decreased incidence of prostate, bladder, and uterine neoplasm was shown in T2D patients with weight reduction difference while an increased risk of thyroid neoplasm was observed in T2D patients on GLP-1RA treatments with weight reduction difference. A more sustained and persistent weight reduction process may confer reduced risk of neoplasm in patients with T2D.

Biomass is a potential non-food, carbon-neutral, and abundant resource, which can be used as an alternative to fossil fuels during the sustainable preparation of various platform chemicals. Alkyl levulinates (ALs) have found widespread application as flavorings, plasticizing agents, and fuel additives, as well as synthetic precursors to various building blocks. Several processes have been investigated to transform biomass and its derivatives into ALs, which mainly include: (i) direct esterification of levulinic acid (LA) with alkyl alcohols and (ii) alcoholysis reactions of renewable biomass feedstocks and their derivatives, including furfuryl alcohol (FAL), chloromethyl furfural (CMF), and saccharides. This review focuses on illustrating the effects of the biomass pretreatment step, catalyst texture, possible mechanisms, acidities, and intermediates on the synthesis of ALs from sustainable resources covering a wide range of intermediates, including diethyl ether (DEE), 4,5,5-triethoxypentan-2-one (TEP), ethoxymethylfuran (EMF), ethyl-D-fructofuranoside (EDFF), and ethyl-D-glucopyranoside (EDGP).

Background Glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) have shown their beneficial effects on cardiovascular outcomes and multiple cardiovascular risk factors, including hypertension. However, the mechanism of blood pressure (BP)–lowering effects of these agents has not been elucidated. This study aims to evaluate the effect of hemoglobin A1c reduction or body weight reduction with GLP‐1RA treatment and SGLT2i treatment on BP changes in patients with type 2 diabetes mellitus. Methods and Results Studies were identified by a search of MEDLINE, EMBASE, and the Cochrane Central Register until June 2019. Meta‐regression analysis was performed to evaluate the association between hemoglobin A1c reduction or body weight reduction and changes of BP. A total of 184 trials were included. Both GLP‐1RA and SGLT2i led to significant reductions in systolic BP (weighted mean difference, −2.856 and −4.331 mm Hg, respectively; P

Atrial fibrillation (AF) is a common abnormal heart rhythm disease. Therefore, the development of an AF detection system is of great significance to detect critical illnesses. In this paper, we proposed an automatic recognition method named CNN-LSTM to automatically detect the AF heartbeats based on deep learning. The model combines convolutional neural networks (CNN) to extract local correlation features and uses long short-term memory networks (LSTM) to capture the front-to-back dependencies of electrocardiogram (ECG) sequence data. The CNN-LSTM is feeded by processed data to automatically detect AF signals. Our study uses the MIT-BIH Atrial Fibrillation Database to verify the validity of the model. We achieved a high classification accuracy for the heartbeat data of the test set, with an overall classification accuracy rate of 97.21%, sensitivity of 97.34%, and specificity of 97.08%. The experimental results show that our model can robustly detect the onset of AF through ECG signals and achieve stable classification performance, thereby providing a suitable candidate for the automatic classification of AF.

The tomato leaf miner, Tuta absoluta is a destructive pest of tomato. The leaf-mining activities of its larvae can cause significant yield losses. Real-time quantitative polymerase chain reaction (RT-qPCR) is commonly used to measure gene expression, and the selection of stable reference genes for calibration and standardization is critical for accurate use of RT-qPCR. We studied the stable expression of nine common housekeeping genes in T. absoluta. These were examined at different developmental stages, in larval tissues, as well as those induced by exposure to 20E and insecticides. Four dedicated algorithms (geNorm, BestKeeper, NormFinder, and ΔCt method) and online tool (RefFinder) were used to analyze and rank the tested reference genes. Based on the standardized gene expression data of target gene ecdysone receptor (EcR), the applicability of specific reference genes was verified. The results clarify that the optimal internal reference genes vary greatly under different experimental conditions. GAPDH and RPS11 were the best reference genes for developmental stages; RPL28 and RPL10 for different tissues; EF1α and RPL28 for 20E treatment; EF1α and RPL7A for insecticide treatments. The most suitable reference genes in all experimental conditions are EF1α and RPL28.

Pests not only attack field crops during the growing season, but also damage grains and other food products stored in granaries. Modified or controlled atmospheres (MAs or CAs) with higher or lower concentrations of atmospheric gases, mainly oxygen (O2), carbon dioxide (CO2), ozone (O3), and nitric oxide (NO), provide a cost-effective method to kill target pests and protect stored products. In this review, the most recent discoveries in the field of MAs are discussed, with a focus on pest control as well as current MA technologies. Although MAs have been used for more than 30 years in pest control and play a role in storage pest management, the specific mechanisms by which insects are affected by and adapt to low O2 (hypoxia) and high carbon CO2 (hypercapnia) are not completely understood. Insect tolerance to hypoxia/anoxia and hypercapnia involves a decrease in aerobic metabolism, including decreased NADPH enzyme activity, and subsequently, decreases in glutathione production and catalase, superoxide dismutase, glutathione-S-transferase, and glutathione peroxidase activities, as well as increases in carboxyl esterase and phosphatase activities. In addition, hypoxia induces energy and nutrient production, and in adapted insects, glycolysis and pyruvate carboxylase fluxes are downregulated, accompanied with O2 consumption and acetate production. Consequently, genes encoding various signal transduction pathway components, including epidermal growth factor, insulin, Notch, and Toll/Imd signaling, are downregulated. We review the changes in insect energy and nutrient sources, metabolic enzymes, and molecular pathways in response to modified O2, CO2, NO, and O3 concentrations, as well as the role of MAs in pest control. This knowledge will be useful for applying MAs in combination with temperature control for pest control in stored food products.

Background. To develop a decision-support software according to the Chinese Diabetes Society guideline in order to improve the standard care in type 2 diabetes. Methods. Firstly, we developed a decision-support software for healthcare professionals. It was an independent software on a tablet to record the data of patients and treatments given by their physicians. A major function of the software was to remind doctors when and how they should implement the standard care as recommended by the Chinese Diabetes Society guideline. Secondly, we compared the baseline data of standard care including statin and aspirin usage with data from a previous “3B study” to see whether there was an improvement of these standard cares. Finally, we further compared the data during four quarters of the whole year to evaluate whether there was a continuous improvement. Results. During the first quarter, 27,291 cases and 27,352 cases were collected with complete information about statin and aspirin usage, respectively. The percentage of patients treated with statins and aspirin in our study was significantly higher than that reported in the 3B study (59.6% vs. 19.9% and 59.8% vs. 18.5%, P0.05). Conclusion. Our decision-support software has been shown to be effective in continuously improving the standardization of comprehensive treatment in type 2 diabetes.

The memetic algorithms which employ population information spreading mechanism have shown great potentials in solving complex three-dimensional black-box problems. In this paper, a newly developed memetic meta-heuristic optimization method, known as shuffled frog leaping algorithm (SFLA), is modified and applied to topology optimization of electromagnetic problems. Compared to the conventional SFLA, the proposed algorithm has an extra local search step, which allows it to escape from the local optimum, and hence avoid the problem of premature convergence to continue its search for more accurate results. To validate the performance of the proposed method, it was applied to solving the topology optimization of an interior permanent magnet motor. Two other EAs, namely the conventional SFLA and local-search genetic algorithm, were applied to study the same problem and their performances were compared with that of the proposed algorithm. The results indicate that the proposed algorithm has the best trade-off between the results of objective values and optimization time, and hence is more efficient in topology optimization of electromagnetic devices.

The effects of exogenous application of melatonin (MEL) on promoting plant growth and alleviating environmental stresses are already known, but the potential value in crop production is still poorly understood. In this study, the effects of seed pre-soaking with MEL on winter wheat (Triticum aestivum L.) growth and yield were investigated in a continuous two-year pot experiment and another year of field experimentation. Results showed that seed pre-soaking with different concentrations of MEL (10, 100 and 500 μM) for 24 h increased grain yields per plant from 29% to 80% in pot experiment and increased grain yield per area from 4−19% in field experiment, compared with the controls. Further analysis showed that the beneficial effects of MEL on improving wheat grain yield can be ascribed to: (1) increased spike number by enhancing tiller number; (2) enhanced carbon assimilation capacity by maintaining large leaf area, high photosynthetic rate and delaying leaf senescence; (3) promoted growth in root system. The result of this study suggests that MEL could be considered as an effective plant growth regulator for improving grain production in winter wheat.

The walnut weevil, Alcidodes juglans Chao (Coleoptera: Curculionidae), is an important agricultural pest and distributed widely in China. The complete mitochondrial genome of A. juglans is 15,638 bp long, and consists of 13 protein-coding genes (PCGs), two ribosomal RNA genes, 21 transfer RNA (tRNA) genes and a putative control region (GenBank accession No. MH819192). The trnI gene has not been observed in the A. juglans mitogenome. The nucleotide composition is significantly biased (A, G, C, and T was 38.35%, 10.02%, 14.96%, and 36.67%, respectively) with A + T contents of 75.02%. All of the 21 tRNAs have the typical cloverleaf structure, with an exception for trnS1 (AGN). All PCGs are initiated by ATN codons, except for cox1 with AAT instead. Ten PCGs use a common stop codon of TAA or TAG, whereas the remaining three were terminated with a single T. The phylogenetic relationships based on neighbour-joining method showed that A. juglans is closely related to Naupactus xanthographus, which is in accordance with the traditional morphological classification.

The complete mitochondrial genome of Cheliceroides longipalpis Zabka (Araneae: Salticidae) is a circular DNA molecule of 14,334 bp in length (GenBank accession number MH891570), and contains a standard set of 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA (tRNA) genes, and an A + T-rich region. The gene orientation of C. longipalpis was similar to those found in other spider mitogenomes. The overall nucleotide composition is 36.5% A, 8.1% C, 12.9% G, and 42.5% T. Twenty reading frame overlaps and seven intergenic regions were found in the mitogenome of C. longipalpis. Thirteen tRNAs lack the potential to form the cloverleaf-shaped secondary structure. Ten PCGs start with ATN codons, two genes (cox2 and cox3) begin with TTG, and cox1 use AGA as initiation codon. Nine PCGs use usual termination codon of TAA or TAG, whereas the remaining four had an incomplete termination codon (T). The phylogenetic relationships of 14 spider mitogenomes based on the concatenated amino acid sequences of 13 PCGs showed that C. longipalpis is closely related to Plexippus paykulli, which is consistent with the traditional taxonomy.

The complete mitochondrial genome of Epeus alboguttatus (Araneae: Salticidae) is 14,625 bp in length (GenBank accession number MH922026). It was predicted to consist of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA genes, and a putative control region. The gene composition and orientation of E. alboguttatus were identical to those found in other spider mitogenomes. The nucleotide composition shows heavily biased towards As and Ts, accounting for 77.59%. Twenty-two genes were in majority strand and 15 genes were in minority strand. ATT, ATA, TTA, and TTG were initiation codons, and TAA, TAG, and T were termination codons. Twenty-two reading frame overlaps and four intergenic regions were found in the mitogenome of E. alboguttatus. Ten tRNA genes lost the TΨC arm stems and had unpaired amino acid acceptor arms, whereas three tRNAs lacked the dihydrouracil (DHU) arm. Phylogenetic analysis indicated that E. alboguttatus is nested with Salticidae and recovered as sister to other five salticids.

The complete mitochondrial genome of the orb-weaving spider Neoscona scylla was characterized in this study. The circular molecule is 14,092 bp in length (GenBank accession no. MK086023), containing 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region. The nucleotide composition is asymmetric (35.27% A, 9.82% C, 15.55% G, 39.36% T), with an overall A + T content of 74.63%. The gene arrangement of N. scylla is identical to that observed in other spiders. Nine PCGs are initiated with typical ATN start codons, three genes (cox2, cox3, and nad6) begin with TTG, and cox1 use TTA as initiation codon. Twelve PCGs stop with complete termination codon TAA and TAG, while nad3 uses incomplete termination codon (T). Twenty-five reading frame overlaps and five intergenic regions are found in the mitogenome of N. scylla. Seven tRNAs lose TΨC arm stems, whereas three lack the dihydrouracil (DHU) arm. The phylogenetic relationships based on 13 PCGs show that N. scylla clusters closest to 5 species of Araneidae.

The complete mitochondrial genome of an orb-weaving spider Neoscona multiplicans was determined. The circular mitogenome is 14,074 bp in length (GenBank accession number MK052682), consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, two ribosomal RNA genes, and an A + T-rich region. The gene arrangement and orientation of N. multiplicans are identical to those found in other known spiders. The nucleotide composition is significantly biased toward A + T content at 74.82% (A: 35.44%; C: 9.53%; G: 15.65%; T: 39.38%). ATT, ATA, TTA, TTG were initiation codons and TAA, TAG, T were termination codons. Six intergenic regions and 24 reading frame overlaps were found in the mitogenome of N. multiplicans. The A + T-rich is 483 bp with an A + T content of 77.23%. Eleven tRNAs lack the potential to form the cloverleaf-shaped secondary structure. Phylogenetic tree based on 13 PCGs showed that N. multiplicans is closely related to Araneus ventricosus, which is consistent with the conventional classification.

The complete mitochondrial genome of the leafhopper Chlorotettix nigromaculatus was described in this study. The circular molecule is 15,011 bp in length (GenBank accession no. MK234840), consisted of 13 protein-coding genes (PCGs), 22 tRNA genes, two rRNA genes, and a putative control region. The base composition values for the mitogenome were 42.4, 13.3, 10.4, and 33.9% for A, C, G, and T, respectively. All the 22 tRNAs have the typical cloverleaf structures, except for trnS1 which lacked the dihydrouridine arm. All the 13 PCGs initiated with ATN codons and most of them terminated with TAG or TAA codons, whereas cox2, nad1, and nad4 used a single T residue. The rrnL and rrnS genes were 1220 and 745 bp in length, respectively. Phylogenetic analysis using amino acid sequences of 13 PCGs showed that C. nigromaculatus was clustered with six Deltocephalinae species, which was consistent with the conventional classification.

The prevalence of type 2 diabetes is increasing rapidly in the young population. The clinical characteristics and risk factors for young type 2 diabetes patients with atherosclerosis are not fully explicated. The aim of the present study was to investigate various clinical and biochemical characteristics of young type 2 diabetic patients with atherosclerosis.This was a cross-sectional study. The study involved 2199 hospitalized patients with type 2 diabetes. The young patients were classified into the atherosclerotic group or the non-atherosclerotic group, and we also enrolled an older group with peripheral atherosclerosis disease and an age of at least 45 years. Comparisons were made between the different groups to investigate the cardiovascular and metabolic risk profiles of young type 2 diabetes patients with atherosclerosis. We also used logistic regression models to assess the atherosclerosis risk factors for young patients.Compared to older type 2 diabetes patients with atherosclerosis, young patients with atherosclerosis had more deleterious profiles of weight and hyperlipidemia. Only age and diabetes duration were found to be significant independent risk factors for atherosclerosis in young patients. The ratio of the presence of atherosclerosis in the lower extremity arteries alone was significantly higher in young patients than older patients (26.4% vs. 14.0%, P = 0.000).Young type 2 diabetes patients with atherosclerosis have more adverse cardiovascular risk profiles and inadequate control of these risk factors. Lower extremity examination is of high importance in young patients.

The aim of this study is to compare the effects of hypoglycemic treatments in groups of patients categorized according to the mean baseline body mass indexes (BMIs).Studies were identified by a literature search and all the studies were double blind, placebo-controlled randomized trials in type 2 diabetes patients; study length of ≥12 weeks with the efficacy evaluated by changes in HbA1c from baseline in groups. The electronic search was first conducted in January 2015 and repeated in June 2015.227 studies were included. Treatment with sulfonylureas was compared with placebo in overweight patients and resulted in a significantly greater change in the HbA1c levels (weighted mean difference (WMD), -1.39%) compared to obese patients (WMD, -0.77%)(p0.05). Treatment with alpha glucosidase inhibitors in normal weight patients was associated with a HbA1c change (WMD, -0.94%) that was comparable that in overweight (WMD, -0.72%) and obese patients (WMD, -0.56%)(p>0.05). Treatment with thiazolidinediones in normal weight patients was associated with a HbA1c change (WMD, -1.04%) that was comparable with that in overweight (WMD, -1.02%) and obese patients (WMD, -0.88%)(p>0.05). Treatment with DPP-4 inhibitors in normal weight patients was associated with a HbA1c change (WMD, -0.93%) that was comparable with that in overweight (WMD, -0.66%) and obese patients (WMD, -0.61%)(p>0.05). In total, of the seven hypoglycemic agents, regression analysis indicated that the mean baseline BMI was not associated with the mean HbA1c changes from baseline.In each kind of hypoglycemic therapy in type 2 diabetes, the baseline BMI was not associated with the efficacy of HbA1c changes from baseline.

Context: Challenges exist in the management of Glucokinase–maturity-onset diabetes of the young (GCK-MODY), especially during pregnancy. Objective: This work aimed to evaluate the prevalence of congenital anomaly in newborns from GCK-MODY mothers, and the relationship between fetus genotype and the risk of congenital malformation as well as other adverse pregnancy outcomes. Methods: Electronic databases including PubMed, EMBASE, and Cochrane database last updated July 16, 2022, were searched. We included observational studies conducted in GCK-MODY complicated by pregnancy, and reporting at least one pregnancy outcome. We extracted data in duplicate, and the risk of bias was evaluated by the Newcastle-Ottawa Quality Assessment Scale (NOS). All statistical analysis was performed by Cochrane Review Manager. Results: Eight studies were selected in the meta-analysis. Five were of high quality and 3 were of medium quality evaluated by NOS. A total of 257 GCK-MODY mothers and 499 offspring were enrolled. Among them, 370 offspring were divided into 2 groups: GCK-affected offspring (GCK+, n = 238) and GCK-unaffected offspring (GCK−, n = 132). The percentage of congenital malformations in GCK pregnant women’s offspring was 2.4%. The risk of congenital malformations was similar between the GCK+ and GCK− group (odds ratio = 0.56; 95% CI, 0.07- 4.51; I² = 0%; P = .59). The risk of macrosomia/large for gestational age, neonatal hypoglycemia, and combined adverse neonatal outcome was significantly lower in offspring with the GCK mutation compared with non–GCK mutation carriers. Conclusion: The percentage of congenital malformations was 2.4% in GCK-MODY pregnant women’s offspring, and newborns with the GCK mutation have lower birth complication than non–GCK mutation carriers. [ABSTRACT FROM AUTHOR]