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Abstract Background The Chinese visceral adiposity index (CVAI) is a new index to evaluate visceral adipose tissue in the Chinese population. Arterial stiffness (AS) is a kind of degeneration of the large arteries, and obesity is an essential contributing factor to AS. Our study aimed to explore the longitudinal association between CVAI and the risk of AS and to compare the predictive power of CVAI, body mass index (BMI), and waist circumference (WC) for AS. Methods Between 2010 and 2020, a total of 14,877 participants participating in at least two brachial-ankle pulse wave velocity (baPWV) measurements from the Kailuan study were included. The Cox proportional hazard regression models were performed to evaluate the longitudinal association between CVAI and the risk of AS. The area under the receiver operating characteristic (ROC) curve was calculated to compare the predictive power of CVAI, BMI, and WC for AS. Results After adjusting for potential confounding factors, CVAI was significantly associated with the risk of AS. Compared with the first CVAI quartile, the hazard ratios (HR) and 95% CI of the second, third, and fourth quartiles were 1.30 (1.09–1.56), 1.37 (1.15–1.63), and 1.49 (1.24–1.78), respectively. The area under ROC curve of CVAI was 0.661, significantly higher than BMI (AUC: 0.582) and WC (AUC: 0.606). Conclusion CVAI may be a reliable indicator to identify high-risk groups of AS in the Chinese general population, and the predictive power of CVAI for AS was better than BMI and WC.

Abstract Recent studies have shown the crucial role of podocyte injury in the development of diabetic kidney disease (DKD). Deubiquitinating modification of proteins is widely involved in the occurrence and development of diseases. Here, we explore the role and regulating mechanism of a deubiquitinating enzyme, OTUD5, in podocyte injury and DKD. RNA-seq analysis indicates a significantly decreased expression of OTUD5 in HG/PA-stimulated podocytes. Podocyte-specific Otud5 knockout exacerbates podocyte injury and DKD in both type 1 and type 2 diabetic mice. Furthermore, AVV9-mediated OTUD5 overexpression in podocytes shows a therapeutic effect against DKD. Mass spectrometry and co-immunoprecipitation experiments reveal an inflammation-regulating protein, TAK1, as the substrate of OTUD5 in podocytes. Mechanistically, OTUD5 deubiquitinates K63-linked TAK1 at the K158 site through its active site C224, which subsequently prevents the phosphorylation of TAK1 and reduces downstream inflammatory responses in podocytes. Our findings show an OTUD5-TAK1 axis in podocyte inflammation and injury and highlight the potential of OTUD5 as a promising therapeutic target for DKD.

In the evolution of enterprises, the emergence of the information age and advancements in related technologies have significantly amplified the significance of financial data generated through enterprise activities for their overall development. As data processing and information technology continue to advance, enterprises are increasingly prioritizing the development of financial systems. The focus of attention is shifting towards leveraging data in the development and utilization of financial systems. This signifies a gradual transition towards a data-driven approach in the development and utilization of financial systems within enterprises. Some basic activities of data processing can be carried out on the network platform. For the development of an enterprise, the scale of production and operation of the enterprise and the technology of system development will directly affect the speed of enterprise development. In the context of the development of the new era, Internet technology has been developed at a deeper level. The development of Internet technology and the construction of network platforms have changed the way enterprises develop systems to a certain extent, providing more advanced technology for enterprise development systems. Embedded system can provide people with excellent human-computer interaction experience, and it also has very powerful data processing capabilities. It has been the focus of research by researchers in various countries in recent years. This article analyzes the use of embedded systems and genetic algorithms, and provides a new technical direction for enterprises to develop high-performance financial systems.

Abstract Heart failure with preserved ejection fraction (HFpEF) is a group of clinical syndromes that exhibit a remarkably heterogeneous phenotype, characterized by symptoms and signs of heart failure, left ventricular diastolic dysfunction, elevated levels of natriuretic peptides, and an ejection fraction greater than or equal to 50%. With the aging of the population and the escalating prevalence of hypertension, obesity, and diabetes, the incidence of HFpEF is progressively rising. Drug therapy options for HFpEF are currently limited, and the associated high risk of cardiovascular mortality and heart failure rehospitalization significantly impact patients' quality of life and longevity while imposing a substantial economic burden on society. Recent research indicates that certain device‐based therapies may serve as valuable adjuncts to drug therapy in patients with specific phenotypes of HFpEF, effectively improving symptoms and quality of life while reducing the risk of readmission for heart failure. These include inter‐atrial shunt and greater splanchnic nerve ablation to reduce left ventricular filling pressure, implantable heart failure monitor to guide diuresis, left atrial pacing to correct interatrial dyssynchrony, cardiac contractility modulation to enhance cardiac calcium handling, as well as renal denervation, baroreflex activation therapy, and vagus nerve stimulation to restore the autonomic imbalance. In this review, we provide a comprehensive overview of the mechanisms and clinical evidence pertaining to these devices, with the aim of enhancing therapeutic strategies for HFpEF.

This study explored the differences in the chemical and elemental composition, anti-nutritional factors, and nitrate content of cassava tender shoots (CTS) pickled vegetables under various traditional processes, such as Kimchi (KIM), sprouts pickles (SPP), vegetable pickled in sauce (SP), olives pickles (OP), hot Kimchi (HK) and salted pickles (SAP), using sensory evaluation, the index of nutritional quality (INQ), and principal component analysis (PCA). The aim was to identify the optimal process for producing high-quality CTS pickled vegetables. Results indicated that different pickling processes significantly affect the quality of CTS pickled vegetables. SPP had the highest protein content at 35.29 g/100 g, while SAP had relatively lower chemical composition. The mineral content in the CTS pickled vegetables decreased to varying degrees, with SPP having the most significant decrease (71.91% in Mn content, 70.72% in Zn, 59.20% in K, and 60.84% in Mg). The cyanide content of CTS pickled vegetables ranged from 32.62 mg/kg to 82.41 mg/kg, while tannin content ranged from 1.07 g tannic acid/100 g to 2.33 g tannic acid/100 g, with nitrate content lower than the national standard at 0.37 mg/kg to 1.02 mg/kg. Sensory evaluation showed that KIM had satisfactory freshness, texture, and appearance, ranking the highest among all. INQ evaluation indicated that SAP, KIM, and HK had higher nutritional value. PCA analysis showed that the cumulative contribution rate of the first three principal components was 83.949%, and the overall score showed that KIM, OP and HK had higher quality. After comprehensive evaluation of sensory evaluation, INQ evaluation, and PCA analysis, KIM using the pickle-making process was determined to be the best method, followed by HK and SAP.

Abstract Background High cardiovascular health (CVH) was associated with lower risk of cardiovascular disease (CVD) and longer life expectancy. However, whether life years lived without CVD could increase faster than or at least at the same pace as total lifespan remains unknown. We aimed to explore the associations of CVH status with total life expectancy and life years lived with and without CVD among middle-aged and elderly men and women. Methods We included 65,587 participants aged ≥ 45 years from Kailuan study, who were recruited during June 2006 to October 2007. CVH was scored and classified (low [0–49 points], moderate [50–79 points] and high [80–100 points]) with Life’s Essential 8, incorporating evaluations of health behaviors and factors. All-cause mortality and incident non-fatal CVD were recorded from baseline to December 31, 2020. The multi-state life table was adopted to explore the associations of CVH status with total life expectancy and life years lived with and without CVD. Results Six thousand fifty eight cases of incident non-fatal CVD and 10,580 cases of deaths were identified. Men aged 45 years with low, moderate, and high CVH had a life expectancy of 33.0, 36.5 and 38.5 years, of which 7.8 (23.6%), 6.0 (16.3%) and 3.7 years (9.6%) were spent with CVD. For women, the corresponding life expectancy was 36.6, 43.6 and 48.6 years, and the remaining life years lived with CVD were 7.8 (21.3%), 6.0 (13.7%) and 4.5 years (9.3%), respectively. The benefits of high CVH were persistent across lifespan from age 45 to 85 years and consistent when CVH was evaluated with health behaviors and factors alone. Conclusions High CVH compared with low CVH was associated with longer total life expectancy and fewer years spent with CVD, indicating that promoting CVH is of great importance for CVD prevention and healthy ageing in China.

The gas-water distribution and production heterogeneity of tight gas reservoirs have been summarized from experimental and geological observations, but the charging and accumulation mechanisms have not been examined quantitatively by mathematical model. The tight gas charging and accumulation mechanisms were revealed from a combination of physical simulation of nuclear magnetic resonance coupling displacement, numerical simulation considering material and mechanical equilibria, as well as actual geological observation. The results show that gas migrates into tight rocks to preferentially form a gas saturation stabilization zone near the source-reservoir interface. When the gas source is insufficient, gas saturation reduction zone and uncharged zone are formed in sequence from the source-reservoir interface. The better the source rock conditions with more gas expulsion volume and higher overpressure, the thicker the gas saturation stabilization and reduction zones, and the higher the overall gas saturation. When the source rock conditions are limited, the better the tight reservoir conditions with higher porosity and permeability as well as larger pore throat, the thinner the gas saturation stabilization and reduction zones, but the gas saturation is high. The sweet spot of tight gas is developed in the high-quality reservoir near the source rock, which often corresponds to the gas saturation stabilization zone. The numerical simulation results by mathematical model agree well with the physical simulation results by nuclear magnetic resonance coupling displacement, and reasonably explain the gas-water distribution and production pattern of deep reservoirs in the Xujiaweizi fault depression of the Songliao Basin and tight gas reservoirs in the Linxing–Huangfu area of the Ordos Basin.

The composition and content of fatty acids in edible cassava flour not only affect its shelf life but also serve as important indicators for evaluating the nutritional quality of cassava flour. In this experiment, edible cassava flour was used as the sample. By optimizing the fatty acid methyl esterification method and gas chromatography conditions, a qualitative and quantitative detection method for fatty acids in edible cassava flour was established. The fatty acid composition in edible cassava flour of different varieties (strains) and different storage times was analyzed and detected. The results showed that gas chromatography could accurately analyze and quantify various fatty acids in edible cassava flour. There was a good linear relationship between the concentrations of palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid in the ranges of 20.0~1000.0, 4.0~400.0, 30.0~1500.0, 10.0~500.0 and 2.0~100.0 μg/mL, respectively, with coefficient of determination (R2) ranging from 0.9992 to 0.9999. The relative standard deviations (RSDs) of sample repeatability ranged from 0.5% to 3.2%. The RSDs of concentration changes after 24 hours of storage at room temperature ranged from 0.7% to 1.1%. The average recovery rates of the five fatty acids in the samples ranged from 88.0% to 105.4%, with average recovery rate RSD ranging from 3.4% to 10.4%, indicating good sample stability, method repeatability, and accuracy. The cassava flour prepared from different edible cassava varieties mainly contained palmitic acid, stearic acid, oleic acid, linoleic acid, and linolenic acid. There were significant differences in fatty acid content among different varieties, and the proportions of the five cassava flour fatty acids (SFA/MUFA/PUFA) were 1:(0.91~1.35):(0.12~0.39). Among them, the content of palmitic acid, oleic acid, linoleic acid, and linolenic acid in 'Huanan 9' cassava flour was significantly higher than other varieties (P

Cassava serves as a primary staple food for over one billion people worldwide. The quality of cassava flour is markedly affected by the oxidation and deterioration of lipids during storage. Despite its significance, the lipid composition of cassava flour and its alterations throughout storage periods have not been extensively studied. This study offers a comprehensive lipidomic analysis of cassava flour over storage periods using liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS). The results showed that 545 lipids from five classes and 27 subclasses were identified in cassava flour, including key substances such as free fatty acids (36 species), diglycerides (DGs) (31 species), and triglycerides (TGs) (259 species). Using Metware Cloud for statistical analysis, significant variations were observed in 50 lipid species over long-term storage, reflecting changes in lipid profiles due to storage. These lipids correlate with seven metabolic pathways, among which glycerolipid metabolism is the most affected. The metabolites associated with these pathways can differentiate cassava flour based on the length of storage. This study provides a theoretical basis and storage technology parameters for lipid changes during cassava flour storage.

Abstract Background The Chinese visceral adiposity index (CVAI), a simple surrogate measure of visceral fat, is significantly associated with cardiovascular disease (CVD) risk in the general population. This study aimed to evaluate the association of cumulative CVAI (cumCVAI) exposure and its accumulation time course with CVD risk among patients with hypertension. Methods This prospective study involved 15,350 patients with hypertension from the Kailuan Study who were evaluated at least three times in the observation period of 2006 to 2014 (2006–2007, 2010–2011, and 2014–2015) and who were free of myocardial infarction and stroke before 2014. The cumCVAI was calculated as the weighted sum of the mean CVAI for each time interval (value × time). The time course of CVAI accumulation was categorized by splitting the overall accumulation into early (cumCVAI06 − 10) and late (cumCVAI10 − 14) accumulation, or the slope of CVAI versus time from 2006 to 2014 into positive and negative. Results During the 6.59-year follow-up period, 1,184 new-onset CVD events were recorded. After adjusting for confounding variables, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD were 1.35 (1.13–1.61) in the highest quartile of cumCVAI, 1.35 (1.14–1.61) in the highest quartile of the time-weighted average CVAI, 1.26 (1.12–1.43) in those with a cumulative burden > 0, and 1.43 (1.14–1.78) for the group with a 10-year exposure duration. When considering the time course of CVAI accumulation, the HR (95% CI) for CVD was 1.33 (1.11–1.59) for early cumCVAI. When considering the combined effect of cumCVAI accumulation and its time course, the HR (95% CI) for CVD was 1.22 (1.03–1.46) for cumCVAI ≥ median with a positive slope. Conclusions In this study, incident CVD risk depended on both long-term high cumCVAI exposure and the duration of high CVAI exposure among patients with hypertension. Early CVAI accumulation resulted in a greater risk increase than later CVAI accumulation, emphasizing the importance of optimal CVAI control in early life.

In the automated modeling generated by oblique photography, various terrains cannot be physically distinguished individually within the triangulated irregular network (TIN). To utilize the data representing individual features, such as a single building, a process of building monomer construction is required to identify and extract these distinct parts. This approach aids subsequent analyses by focusing on specific entities, mitigating interference from complex scenes. A deep convolutional neural network is constructed, combining U-Net and ResNeXt architectures. The network takes as input both digital orthophoto map (DOM) and oblique photography data, effectively extracting the polygonal footprints of buildings. Extraction accuracy among different algorithms is compared, with results indicating that the ResNeXt-based network achieves the highest intersection over union (IOU) for building segmentation, reaching 0.8255. The proposed “dynamic virtual monomer” technique binds the extracted vector footprints dynamically to the original oblique photography surface through rendering. This enables the selective representation and querying of individual buildings. Empirical evidence demonstrates the effectiveness of this technique in interactive queries and spatial analysis. The high level of automation and excellent accuracy of this method can further advance the application of oblique photography data in 3D urban modeling and geographic information system (GIS) analysis.

With the deepening exploratory development, geological targets are gradually shifting from conventional reservoirs to unconventional ones. The sandstone reservoirs in the northeast margin of the Ordos Basin are stacked vertically and change quickly horizontally with thin thicknesses. Therefore, traditional inversion technology cannot satisfy the requirements of precise prediction of thin reservoirs. To solve this problem, this paper integrated geological, seismic and logging data based on the GR curve. A wave form simulation of the MG block in the eastern margin of Ordos Basin was conducted, and the distribution of sandstone reservoirs in the target bed was depicted. The results showed that the waveform indication simulation profiles had a high resolution both horizontally and vertically. They were also in line with the drilling well and strongly correlated with the seismic waveform, which could reflect the spatial variation in the reservoir and accord with the law of geological deposition in the study area. Therefore, as a more efficient inversion method, waveform indication simulation provided a strong support for the refined study of thin inter-bedded reservoirs and helped to maximize the development and utilization of gas resources.

To address the issue of traditional transmission line characteristic parameter testing methods being susceptible to external environmental interference. Proposed a method for processing geographic information data of transmission lines and physical simulation. Firstly, the parameters of the transmission line are tested, a model is established at both ends of the transmission line, and variable frequency signals are collected using 3D GIS technology to develop a lead control box for transmission line parameter testing. Then, the transmission line parameters are calculated online, and real-time voltage and current measurements are conducted at both ends of the transmission line. A zero sequence current simulation diagram of the transmission line is constructed, and circuit parameters are calculated based on the simulation results, Finally, measure the zero sequence parameters of the transmission line using electricity and obtain the zero sequence impedance value of the transmission line using the least squares method. The six zero sequence parameter values were measured in a disturbance environment. The results show that when the power line reaches a certain length, the error of the traditional method has reached 50%, and the testing error of the method studied by the author is less than 3%. The measurement error value of the transmission line characteristic parameter test method based on 3D GIS technology is less than that of the traditional method.

Background The American Heart Association recently proposed an updated definition of cardiovascular health (CVH) named as Life's Essential 8. We aimed to explore the association between this latest published CVH measurement and years lived without cardiovascular disease (CVD) among the Chinese population. Methods and Results We included 89 755 adults free of CVD at baseline from the Kailuan study. The CVH of each participant was scored (from 0 point to 100 points) and classified (low [0–49 points], moderate [50–79 points], and high [80–100 points]) according to Life's Essential 8, which incorporated 8 components covering health behaviors and health factors. Incident CVD was documented through follow‐ups from baseline (June 2006 to October 2007) until December 31, 2020. CVD‐free life years from age 30 to 80 years associated with different CVH scores were estimated using flexible parametric survival models. A total of 9977 incident CVDs were recorded. We observed a gradient relationship between CVH score and years lived without CVD. The age‐ and sex‐adjusted CVD‐free life years (95% CI) were 40.7 (40.3–41.0) years for low CVH, 43.3 (43.0–43.5) years for moderate CVH, and 45.5 (45.1–45.9) years for high CVH. Similar trends were noted when individual subtypes of CVD were investigated, and high CVH evaluated by health behaviors and health factors was also related to longer CVD‐free life years. Conclusions A higher CVH evaluated by the updated Life's Essential 8 metrics was significantly associated with a greater number of life years without CVD, indicating the importance of promoting CVH for healthy aging in China.

In order to understand the freezing characteristics and metabolites of cassava root, the edible cassava variety “South China 9” was taken as the research object, by measuring the freezing-law and related influencing factors at the head, middle and tail of cassava root, combined with non-targeted metabolomics to analyze the differential metabolite. The results showed that: The freezing temperature was from −0.6 to −1.1 ℃ in different parts of root, but the freezing time was different. The highest values of soluble solid content and starch content in different parts appeared in the head, which were 7.00% and 26.84% respectively, but there was no significant difference among different parts (P>0.05), while the highest value of water content appeared in the tail, which was 64.07%. Correlation analysis showed that freezing point was negatively correlated with soluble solids and water content, and positively correlated with starch content. Compared with control, 41 differential metabolites were screened under low treatment by the non-targeted metabolomics, and the enrichment degree of phenylalanine metabolic pathway was the highest, with a total of 9 significant differential metabolites. In this pathway, the expression of hippuric acid and benzoic acid was up-regulated, which might be related to the response of root tubers to low temperature. The results provide theoretical reference for low-temperature storage in the future.

Abstract Atherosclerosis is a chronic inflammatory disease with high morbidity and mortality rates worldwide. Doublecortin‐like kinase 1 (DCLK1), a microtubule‐associated protein kinase, is involved in neurogenesis and human cancers. However, the role of DCLK1 in atherosclerosis remains undefined. In this study, we identified upregulated DCLK1 in macrophages in atherosclerotic lesions of ApoE−/− mice fed an HFD and determined that macrophage‐specific DCLK1 deletion attenuates atherosclerosis by reducing inflammation in mice. Mechanistically, RNA sequencing analysis indicated that DCLK1 mediates oxLDL‐induced inflammation via NF‐κB signaling pathway in primary macrophages. Coimmunoprecipitation followed by LC–MS/MS analysis identified IKKβ as a binding protein of DCLK1. We confirmed that DCLK1 directly interacts with IKKβ and phosphorylates IKKβ at S177/181, thereby facilitating subsequent NF‐κB activation and inflammatory gene expression in macrophages. Finally, a pharmacological inhibitor of DCLK1 prevents atherosclerotic progression and inflammation both in vitro and in vivo. Our findings demonstrated that macrophage DCLK1 promotes inflammatory atherosclerosis by binding to IKKβ and activating IKKβ/NF‐κB. This study reports DCLK1 as a new IKKβ regulator in inflammation and a potential therapeutic target for inflammatory atherosclerosis.

CDK2 can drive the proliferation of cancer cells. Here, the authors screened for a non-ATP competitive inhibitor of the CDK2/cylinA complex and find that Homoharringtonine can disrupt the complex and promote the degradation of CDK2.

The contents of cyanogenic glycosides (Cyanogenic Glycosides, CNGs) are very important to evaluate the safety of sweet cassava roots and their products. Using cassava roots and cassava products as test materials in this study, a method for rapid extraction and high performance liquid chromatography-evaporative light scattering (HPLC-ELSD) detection of two kinds of cyanogenic glycosides was established. The content of CNGs in different varieties of cassava roots, cassava flour, and their products were analyzed. The results showed that the optimal extraction concentrations of sulfuric acid solution for these two GNSs from cassava roots and flour were 0.025 and 0.100 mol/L, respectively. The HPLC-ELSD method was effective in the separation of linamarin and lotaustralin. The linear correlation was good in the range of 4.1 to 820.0 mg/L and 2.5 to 250.0 mg/L, which correlation coefficients (r) reached 0.9996 and 0.9993 respectively. The LOD was 2.1 and 0.5 mg/L, and the LOQ was 8.2 and 2.0 mg/kg, respectively. The relative standard deviation (RSD) of repeatability and sample stability are both less than 5.0%. The average recovery rates of two CNGs in cassava roots and cassava products were between 89.3%~96.3% and 107.5%~114.9%, respectively. And the RSD of the repeatability of the recovery was less than 3.4%. The results of sample verification showed that the content of CNGs in different cassava varieties were quite different, The content of CNGs was lower in cassava flour which was prepared from cassava grown for 8~9 months, and the cooking method could effectively remove CNGs in cassava food. This method was simple, stable and accurate, and had a strong application prospect in the analysis and evaluation of CNGs in sweet cassava roots and their products.

Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local “burst” release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6–6.3 μg mL−1), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.

Membrane-disruptive peptides/peptidomimetics (MDPs) are antimicrobials or anticarcinogens that present a general killing mechanism through the physical disruption of cell membranes, in contrast to conventional chemotherapeutic drugs, which act on precise targets such as DNA or specific enzymes. Owing to their rapid action, broad-spectrum activity, and mechanisms of action that potentially hinder the development of resistance, MDPs have been increasingly considered as future therapeutics in the drug-resistant era. Recently, growing experimental evidence has demonstrated that MDPs can also be utilized as adjuvants to enhance the therapeutic effects of other agents. In this review, we evaluate the literature around the broad-spectrum antimicrobial properties and anticancer activity of MDPs, and summarize the current development and mechanisms of MDPs alone or in combination with other agents. Notably, this review highlights recent advances in the design of various MDP-based drug delivery systems that can improve the therapeutic effect of MDPs, minimize side effects, and promote the co-delivery of multiple chemotherapeutics, for more efficient antimicrobial and anticancer therapy.

To further improve the operational performance of a phononic crystal air-coupled ultrasonic transducer while reducing the number of simulations, an intelligent optimization design strategy is proposed by combining finite element simulation analysis and artificial intelligence (AI) methods. In the proposed strategy, the structural design parameters of 1–3 piezoelectric composites and acoustic impedance gradient matching layer are sampled using the optimal Latin hypercube sampling (OLHS) method. Moreover, the COMSOL software is utilized to calculate the performance parameters of the transducer. Based on the simulation data, a radial basis function neural network (RBFNN) model is trained to establish the relationship between the design parameters and the performance parameters. The accuracy of the approximation model is verified through linear regression plots and statistical methods. Finally, the NSGA-II algorithm is used to determine the design parameters of the transducer. After optimization, the band gap widths of the piezoelectric composites and acoustic impedance gradient matching layer are increased by 16 kHz and 13.5 kHz, respectively. Additionally, the −6 dB bandwidth of the transducer is expanded by 11.5%. The simulation results and experimental results are consistent with the design objectives, which confirms the effectiveness of the design strategy. This work provides a feasible strategy for the design of high-performance air-coupled ultrasonic transducers, which is of great significance for the development of non-destructive testing technology.

Atherosclerotic cardiovascular disease and subsequent heart failure threaten global health and impose a huge economic burden on society. MicroRNA-132 (miR-132), a regulatory RNA ubiquitously expressed in the cardiovascular system, is up-or down-regulated in the plasma under various cardiac conditions and may serve as a potential diagnostic or prognostic biomarker. More importantly, miR-132 in the myocardium has been demonstrated to be a master regulator in many pathological processes of ischemic or nonischemic heart failure in the past decade, such as myocardial hypertrophy, fibrosis, apoptosis, angiogenesis, calcium handling, neuroendocrine activation, and oxidative stress, through downregulating target mRNA expression. Preclinical and clinical phase 1b studies have suggested antisense oligonucleotide targeting miR-132 may be a potential therapeutic approach for ischemic or nonischemic heart failure in the future. This review aims to summarize recent advances in the physiological and pathological functions of miR-132 and its possible diagnostic and therapeutic potential in cardiovascular disease.

This paper investigates the effect of supplementary cementitious materials (SCMs) on the fresh and mechanical properties of nano-silica modified cement-based materials (NSMCBM) based on the response surface method (RSM). Fly ash (FA), ground granulated blast-furnace slag (GGBFS), and silica fume (SF) were selected and the Box-Behnken design (BBD) method was used to design mix proportion. Besides, the quadratic term model was used to describe the relationship between independent variables and responses including fluidity, yield stress, plastic viscosity, thixotropy, and 3, 7, 28, and 56 d compressive strength. Based on the quadratic term model, the response surface of each response was drawn to understand the influence of SCMs. Results showed that FA had significant effect on fluidity and thixotropy while three kinds of SCMs had extremely significant effect on plastic viscosity. Response surface plot showed that NS could increase the plastic viscosity of NSMCBM to 1.445 Pa•s (M16). However, the addition of FA and GGBFS decreased the plastic viscosity to 0.9 Pa•s, which was comparable with the reference sample (M17). Such value was 37.7% lower than that of M16. Meanwhile, NS complemented the reduction of compressive strength caused by SCMs. Thus, the synergy effect of SCMs and NS could improve both fresh and mechanical properties. At last, multi-objective optimization was utilized to optimize the proportion of SCMs considering the interaction between SCMs to achieve desirable parameters.

Objectives: To investigate the effect and mechanism of sacubitril/valsartan on myocardial fibrosis in rats following experimental myocardial infarction and in TGF-β1-treated myocardial fibroblasts.Methods: Male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle, valsartan (Val, 32 mg/kg, once-daily) or sacubitril/valsartan (Sac/Val, 68 mg/kg, once-daily) for 4 weeks. In parallel, myocardial fibroblasts (MFs) isolated from neonatal SD rats were exposed to hypoxia and treated with TGF-β1 (5 ng/ml) plus vehicle, Val (107–10–5 M) or Sac/Val (107–105 M). Rat cardiac function and fibrosis were measured by echocardiography and histological method, respectively. MFs viability and collagen synthesis were determined by cell counting kit-8 and enzyme-linked immunosorbent assay, respectively. Protein expressions of TGF-β1, Smad3, phosphorylated Smad3 (p-Smad3), and p-Smad3 subcellular localization were detected by immunoblotting and immunocytochemistry.Results: Sac/Val significantly improved cardiac structure and function in rats after myocardial infarction, including decreased left ventricular end-diastolic diameter and interventricular septal thickness, increased ejection fraction, and reduced myocardial collagen volume fraction and type Ⅰ and type Ⅲ collagen levels, and this effect was superior to that of Val. Besides, Sac/Val inhibited myocardial TGF-β1 and p-Smad3 protein expression better than Val. Mechanically, Sac/Val significantly attenuated TGF-β1-induced proliferation and collagen synthesis of MFs, and inhibit Smad3 phosphorylation and nucleus translocation, and this effect outperformed Val. Overexpression and silencing of Smad3 enhanced and reversed the inhibitory effects of Sac/Val on TGF-β1-induced collagen synthesis by MFs, respectively.Conclusions: Sacubitril/valsartan improves cardiac function and fibrosis in rats after experimental myocardial infarction, and this effect is related to the inhibition of collagen synthesis in myocardial fibroblasts by inhibiting the TGF/Smads signaling pathway.

Influenza virus infects the host and transmits through the respiratory tract (i.e., the mouth and nose); therefore, the development of intranasal influenza vaccines that mimic the natural infection, coupled with an efficient mucosal adjuvant, is an attractive alternative to current parenteral vaccines. However, with the withdrawal of cholera toxin and Escherichia coli heat-labile endotoxin from clinical use due to side effects, there are no approved adjuvants for intranasal vaccines. Therefore, safe and effective mucosal adjuvants are urgently needed. Previously, we reported that one derivative of α-Galactosylceramide (α-GalCer), 7DW8-5, could enhance the protective efficacy of split influenza vaccine by injection administration. However, the mucosal adjuvanticity of 7DW8-5 is still unclear. In this study, we found that 7DW8-5 promotes the production of secret IgA antibodies and IgG antibodies and enhances the protective efficacy of the split influenza vaccine by intranasal administration. Furthermore, co-administration of 7DW8-5 with the split influenza vaccine significantly reduces the virus shedding in the upper and lower respiratory tract after lethal challenge. Our results demonstrate that 7DW8-5 is a novel mucosal adjuvant for the split influenza vaccine.

Influenza virus only encodes a dozen of viral proteins, which need to use host machinery to complete the viral life cycle. Previously, KAP1 was identified as one host protein that potentially interacts with influenza viral proteins in HEK 293 cells. However, the role of KAP1 in influenza virus replication in human lung alveolar epithelial cells and the underlying mechanism remains unclear. In this study, we first generated KAP1 KO A549 cells by CRISPR/Cas9 gene editing. KAP1 deletion had no significant effect on the cell viability and lack of KAP1 expression significantly reduced the influenza A virus replication. Moreover, we demonstrated that KAP1 is involved in the influenza virus entry, transcription/replication of viral genome, and viral protein synthesis in human lung epithelial cells and confirmed that KAP1 interacted with PB2 and NS1 viral proteins during the virus infection. Further study showed that KAP1 inhibited the production of type I IFN and overexpression of KAP1 significantly reduced the IFN-β production. In addition, influenza virus infection induces the deSUMOylation and enhanced phosphorylation of KAP1. Our results suggested that KAP1 is required for the replication of influenza A virus and mediates the replication of influenza A virus by facilitating viral infectivity and synthesis of viral proteins, enhancing viral polymerase activity, and inhibiting the type I IFN production.

Previous studies have found that the polymorphisms of tumor necrosis factor-α induced protein 3 (TNFAIP3) were associated with several autoimmune diseases. However, the role of TNFAIP3 polymorphisms in type-1 autoimmune hepatitis (AIH-1) remained unclear. The present study aimed to clarify the association of TNFAIP3 polymorphisms with AIH-1 risk in a Chinese Han population. The TaqMan SNP genotyping assay was used to determine the distribution of TNFAIP3 polymorphisms in 432 AIH-1 patients and 500 healthy controls. The association of TNFAIP3 polymorphisms and clinical characteristic was further evaluated. Five TNFAIP3 polymorphisms (rs2230926, rs5029939, rs10499194, rs6920220, rs582757) were analyzed in the present study. No significant association could be observed between rs2230926, rs5029939, rs6920220, rs582757 and the susceptibility to AIH-1 in Chinese Han population. Compared with wild-type genotype CC at rs10499194, individuals carrying CT genotype had a significantly increased risk for developing AIH-1 (OR = 2.32, 95%CI 1.44-3.74). Under a dominant model, CT/TT carriers have a 140% increased risk of AIH-1 than CC carriers (OR = 2.40, 95%CI 1.50-3.87). The rs10499194 T allele was also found to be significantly associated with AIH-1 risk (OR = 2.41, 95%CI 1.51-3.82). In addition, higher serum ALT, AST levels and more common cirrhosis were observed in AIH-1 patients with T allele (CT/TT) than those with CC genotype. In conclusion, TNFAIP3 rs10499194 T allele and CT genotype were associated with an increased risk for AIH-1, suggesting rs10499194 polymorphism as a candidate of susceptibility locus to AIH-1.

To investigate the effects of glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on endothelial dysfunction in LDL receptor-deficient (LDLR-KO) mice and ox-LDL-challenged human umbilical vein endothelial cells (HUVECs) and its possible mechanism. LDLR-KO mice were randomly treated with normal saline, liraglutide, or liraglutide plus a GLP-1R antagonist exendin-9 for four weeks. In parallel, HUVECs were cultured with ox-LDL alone or combined with liraglutide, in the presence or absence of lectin-like ox-LDL receptor-1(LOX-1) overexpression or GLP-1R knockdown. Endothelial-dependent relaxation and LOX-1 protein expression of thoracic aorta, circulating levels of oxidative and inflammatory markers in mice, and cell survival, reactive oxygen species production, and expression of adhesion molecules and signal regulators in ox-LDL cultured endothelial cells were measured. liraglutide effectively enhanced acetylcholine-induced vasodilation, reduced LOX-1 expression in aortas, and decreased circulatory oxidative and inflammatory levels in LDLR-KO mice, which were abolished by cotreatment with exendin-9. HUVECs exposed to ox-LDL exhibited reduced cell viability, increased reactive oxygen species production and apoptosis, and elevated protein expression of ICAM-1, VCAM-1, LOX-1, NOX4, and NF-κB, which were markedly ameliorated by liraglutide treatment. The protective effects of liraglutide against ox-LDL-induced cell injury were abrogated in HUVECs overexpressing LOX-1 or silencing GLP-1R. Liraglutide improved oxidized LDL-induced endothelial dysfunction via GLP-1R-dependent downregulation of LOX-1-mediated oxidative stress and inflammation. [ABSTRACT FROM AUTHOR]