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Abstract Prediabetes and related complications constitute significant public health burdens globally. As an indicator closely associated with abnormal glucose metabolism and atherosclerosis, the utility of Pulse Pressure Index (PPI) as a prediabetes risk marker has not been explored. We performed a retrospective cohort analysis to investigate this putative association between PPI and prediabetes hazard. Our analysis encompassed 183,517 Chinese adults ≥ 20 years registered within the Rich Healthcare Group 2010–2016. PPI was defined as (systolic blood pressure − diastolic blood pressure)/systolic blood pressure. The relationship between PPI and prediabetes risk was assessed via Cox proportional hazards regression modeling. Non-linearity evaluations applied cubic spline fitting approaches alongside smooth curve analysis. Inflection points of PPI concerning prediabetes hazard were determined using two-piecewise Cox models. During a median follow-up of 3 years (2.17–3.96 years), new-onset prediabetes was documented in 20,607 patients (11.23%). Multivariate regression analysis showed that PPI was an independent risk factor for prediabetes, and the risk of prediabetes increased by 0.6% for every 1% increase in PPI (Hazard Ratio [HR]: 1.006, 95% Confidence Interval [CI] 1.004–1.008, P

Abstract Background Ubiquitin-specific protease 38 (USP38), belonging to the USP family, is recognized for its role in controlling protein degradation and diverse biological processes. Ventricular arrhythmias (VAs) following heart failure (HF) are closely linked to ventricular electrical remodeling, yet the specific mechanisms underlying VAs in HF remain inadequately explored. In this study, we examined the impact of USP38 on VAs in pressure overload-induced HF. Methods Cardiac-specific USP38 knockout mice, cardiac-specific USP38 transgenic mice and their matched control littermates developed HF induced by aortic banding (AB) surgery. After subjecting the mice to AB surgery for a duration of four weeks, comprehensive investigations were conducted, including pathological analysis and electrophysiological assessments, along with molecular analyses. Results We observed increased USP38 expression in the left ventricle of mice with HF. Electrocardiogram showed that the USP38 knockout shortened the QRS interval and QTc, while USP38 overexpression prolonged these parameters. USP38 knockout decreased the susceptibility of VAs by shortening action potential duration (APD) and prolonging effective refractory period (ERP). In addition, USP38 knockout increased ion channel and Cx43 expression in ventricle. On the contrary, the increased susceptibility of VAs and the decreased expression of ventricular ion channels and Cx43 were observed with USP38 overexpression. In both in vivo and in vitro experiments, USP38 knockout inhibited TBK1/AKT/CAMKII signaling, whereas USP38 overexpression activated this pathway. Conclusion Our data indicates that USP38 increases susceptibility to VAs after HF through TBK1/AKT/CAMKII signaling pathway, Consequently, USP38 may emerge as a promising therapeutic target for managing VAs following HF.

Abstract:: Background: Atrial fibrillation (AF) emerges as a pivotal risk determinant for unfavorable outcomes in septic patients. Despite its recognized role, the enduring impact of AF on sepsis prognosis remains ambiguous. This investigation seeks to elucidate the connection between AF and both short and long-term outcomes in sepsis patients. Additionally, it aims to formulate a prognostic model for 1-year mortality utilizing pertinent clinical variables. Methods: A retrospective analysis encompassed sepsis patients admitted to Beth Israel Deacon Medical Center's intensive care unit. The evaluation encompassed the prevalence of AF and its influence on hospitalization duration, stays in the Intensive Care Unit (ICU), and mortality rates at distinct intervals. Propensity score matching was implemented to mitigate confounding factors. Machine learning techniques, including the Least Absolute Selection and Shrinkage Operator (LASSO) regression and random forest, were deployed for model development. Results: AF exhibited a correlation with heightened mortality rates at 7 days, 28 days, and 1 year. The resultant predictive model demonstrated superior efficacy compared to prevailing clinical critical illness scores in forecasting mortality risk. Crucial predictors in the model included variables such as RDW, weight, age, BUN, lactate, temperature, MCHC, MBP, ALP, and hemoglobin. Conclusions: AF emerges as a substantial peril for adverse outcomes in sepsis patients. The risk model, encompassing pertinent clinical variables, outperformed existing clinical critical illness scores in mortality prediction. This model furnishes valuable insights for risk stratification, augmenting prognostic precision in sepsis patients with concomitant AF.

Tight sandstone gas reservoirs have the characteristics of poor physical properties of the reservoir， complex pore throat structure， strong anisotropy， and extensive coverage of initial water saturation， which lead to the complex flow mechanism of fluids in reservoirs and bring significant challenges to the accurate prediction and evaluation of gas well productivity. Therefore， based on the theory of gas-water two-phase non-Darcy flow， this study comprehensively considers the complex productivity factors， such as reservoir anisotropy， different degrees of stress sensitivity between reservoir matrix and fracture， two-phase starting pressure gradient， high-speed non-Darcy flow effect， gas slippage effect， finite conductivity of fracture， and inter-fracture interference. A new gas-water two-phase productivity prediction model for multistage fractured horizontal wells in anisotropic tight sandstone gas reservoirs is established by using coordinate transformation， perturbation ellipse theory， equivalent development rectangle theory， equivalent well diameter principle， pressure superposition principle， and hydropower similarity principle. Field examples verify the accuracy and practicability of the model. The gas-water two-phase productivity prediction curve is drawn， and the influence of sensitive parameters on productivity is evaluated. The results show that the open flow capacity of a fractured gas well increases with the increase in slippage effect， fracture conductivity， fracture half-length， fracture number， and the angles between the wellbore of the horizontal well and the main permeability of the formation. The open flow capacity of the fractured horizontal well decreases with the increase in reservoir anisotropy， reservoir stress sensitivity， fracture stress sensitivity， two-phase starting pressure gradient， and water-gas volume ratio. Water has an inhibitory effect on the flow of gas， and greater displacement pressure difference indicates a more significant inhibitory effect， so it is necessary to take waterproof and water control measures in advance. The research results further narrow the gap between the productivity prediction results of tight sandstone gas reservoirs and the actual production of the field， which is helpful for parameter evaluation， dynamic prediction， productivity evaluation， and exploration and development decision-making of tight sandstone gas reservoirs.

Abstract Aims Cardiovascular disease is the leading cause of death worldwide. Anxiety disorders are common psychiatric conditions associated with cardiovascular outcomes. This two‐sample Mendelian randomization (MR) study investigated the causal relationship between anxiety disorders and coronary heart disease (CHD), myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). Methods Single nucleotide polymorphisms (SNPs) associated with anxiety disorders (16 730 cases; 101 021 controls) were obtained from the UK Biobank genome‐wide association study (GWAS). Cardiovascular outcome data were derived from the FinnGen study (CHD: 21 012 cases and 197 780 controls; MI: 12 801 cases and 187 840 controls; HF: 23 397 cases and 194 811 controls; and AF: 22 068 cases and 116 926 controls). Inverse variance weighted (IVW), MR–Egger, weighted median, simple mode, and weighted mode analyses examined causality. Results IVW analysis demonstrated significant causal relationships between anxiety disorders and increased risk of CHD [odds ratio (OR): 4.496; 95% confidence interval (CI): 1.777–11.378; P = 0.002], MI (OR: 5.042; 95% CI: 1.451–17.518; P = 0.011), and HF (OR: 3.255; 95% CI: 1.461–7.252; P = 0.004). No relationship was observed with AF (OR: 1.775; 95% CI: 0.612–5.146; P = 0.29). Other methods showed non‐significant associations. Two‐way analysis indicated no reverse causality. Conclusions Anxiety disorders were causally associated with greater risk of CHD, MI, and HF but not AF among individuals of European descent. Further research on mediating mechanisms and in diverse populations is warranted.

In order to more accurately reflect the real contact stress on the tooth surface of beveloid gear, this paper constructs the tooth surface contact coefficient of beveloid gear, and verifies its rationality. Based on fractal contact theory and Hertz contact theory, a contact model of beveloid gear is established, which comprehensively considers the parameters such as gear tooth surface roughness, elastic deformation of contact point and material characteristics. The effectiveness of this method is contact strength of beveloid gear, which is compared with the finite element calculation results by calculating. The relation between load and area during gear meshing is obtained through fractal theory, and four basic parameters are simulated to analyze the effect of fractal contact model. The results show that the accuracy of fractal contact model is verified by numerical simulation and analysis of the relation between actual contact area and load. This paper is based on the finite element theory, Hertz contact theory and fractal theory, the tooth surface contact strength of beveloid gear is compared and analyzed, the correctness of calculating the contact stress of beveloid gear by fractal contact model is verified. The establishment of this model provides a certain theoretical basis for the design and strength check of beveloid gear.

Abstract The consumption of alcohol reflects both societal norms and personal choices and has major clinical implications. Long‐term excess alcohol consumption leads to a domino effect of pathological outcomes and onset of chronic illness. However, the risks of alcohol consumption extend beyond long‐term health issues. Because habitual alcohol drinkers reach a state of systemic homeostasis, when they attempt withdrawal, they experience many negative physiological effects and may develop alcohol withdrawal syndrome. The complex interplay between alcohol consumption and withdrawal does not result solely in behavioral issues. Rather, a substantial number of important physiological adaptations and potential problems underly habitual drinking. Addressing these issues requires comprehensive medical observation and intervention. Here, we summarize the pathophysiological mechanisms, clinical diseases, and related treatment methods of alcohol consumption and withdrawal. The aim was to provide a reference to improve understanding of alcohol use and promote an informed approach to alcohol withdrawal.

Abstract Owing to issues such as time and cost, patients often show poor acceptance of and adherence to center-based cardiac rehabilitation (CBCR), which impacts the effectiveness of rehabilitation. Therefore, there is growing interest in home-based cardiac rehabilitation and cardiac telerehabilitation (CTR), which entail less time and cost than CBCR. This study aimed to compare the changes in physiological and psychological indicators, compliance, and satisfaction after CTR and CBCR. In this single-blind, randomized, controlled trial, the intervention group received CTR via the 5G Internet of Things platform, while the control group received CBCR. Data from 50 patients (age 66.28 ± 4.01 years) with acute myocardial infarction who underwent percutaneous coronary intervention were analyzed. After an intervention period of three months, the maximal oxygen uptake and metabolic equivalent of task were 5.53 ± 0.12 and 19.32 ± 0.17, respectively, in the intervention group, and 4.15 ± 0.13 and 16.52 ± 0.18, respectively, in the control group. After three months of intervention, there were significant differences between the two groups in all observed indicators (p 0.05). The use of a 5G Internet of Things platform cardiac rehabilitation model effectively improved outcomes in patients with acute myocardial infarction who underwent percutaneous coronary intervention. Trials registry: The study protocol was registered at Chinese Clinical Trials Registry (ChiCTR), first trial registration 07/08/2023, identification number ChiCTR2300074435.

Abstract Robotic 3D bin packing (R‐3dBPP), aiming to place deformed cases in various sizes in the container without fences, is a comprehensive application that includes perception, planning, execution, and hardware design. Traditional studies assume that the context of the real space must be accurately perceived and represented. However, disjunctions between the planner and reality are unavoidable in R‐3dBPP, especially with low‐cost sensors. As far as the author knows, there is no practical solution. In this paper, the above assumption is discarded and the typical types of uncertainties prevalent to guide the design of the algorithms are formulated. A new online bin‐packing algorithm is proposed, keeping deformed boxes stacked in close contact with each other, so that the whole pallet is kept stable by friction between the boxes and the container. In order to meet the requirement of close contact under the non‐negligible errors from sensors and planners, a compliant‐based motion planning system is introduced. It replaces the precision‐based feedback with a compliant end‐effector and accompanying motion strategies. Last but not least, a complete online bin‐packing robot system is developed and the system's performance under the influence of the uncertainties mentioned above through simulation and physical experiments is evaluated.

Abstract Background Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear. Methods In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms. Results Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent. Conclusions USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI.

Objective: Rheumatoid arthritis and Ankylosing spondylitis are two common autoimmune inflammatory rheumatic diseases that negatively affect activities of daily living and can lead to structural and functional disability, reduced quality of life. Here, this study utilized Fourier transform infrared (FTIR) spectroscopy on dried serum samples and achieved early diagnosis of rheumatoid arthritis and ankylosing spondylitis based on deep learning models. Method: A total of 243 dried serum samples were collected in this study, including 81 samples each from ankylosing spondylitis, rheumatoid arthritis, and healthy controls. Three multi-scale convolutional modules with different specifications were designed based on the multi-scale convolutional neural network (MSCNN) to effectively fuse the local features to enhance the generalization ability of the model. The FTIR was then combined with the MSCNN model to achieve a non-invasive, fast, and accurate diagnosis of ankylosing spondylitis, rheumatoid arthritis, and healthy controls. Results: Spectral analysis shows that the curves and waveforms of the three spectral graphs are similar. The main differences are distributed in the spectral regions of 3300–3250 cm−1, 3000–2800 cm−1, 1750–1500 cm−1, and 1500–1300 cm−1, which represent: Amides, fatty acids, cholesterol, proteins with a carboxyl group, amide II, free amino acids, and polysaccharides. Four classification models, namely artificial neural network (ANN), convolutional neural network (CNN), improved AlexNet model, and multi-scale convolutional neural network (MSCNN) were established. Through comparison, it was found that the diagnostic AUC value of the MSCNN model was 0.99, and the accuracy rate was as high as 0.93, which was much higher than the other three models. Conclusion: The study demonstrated the superiority of MSCNN in distinguishing ankylosing spondylitis from rheumatoid arthritis and healthy controls. FTIR may become a rapid, sensitive, and non-invasive means of diagnosing rheumatism.

The stability of glass against crystallization is of importance in practical applications and theoretical understanding of the nature of glass materials. Annealing has complicated influences on glass stability. It induces either delayed or early crystallization, depending on detailed protocols and specific materials. By interrogating the thermal behaviors of twelve metallic glasses (MGs), we find that enhanced stability is correlated to another process: the so-called shadow glass transition and its evolution. Delayed crystallization can be observed when the shadow glass transition is shifted to cross the temperature of crystallization. Concurrently, the shadow glass transition evolves to an enthalpy overshoot. Molecular dynamics simulations support these findings and suggest that the suppressed string-like motion, relating to the shadow glass transition and the enthalpy overshoot, is likely the origin of the postponed nucleation ordering and enhanced glass stability.

IntroduceAnkylosing spondylitis (AS), rheumatoid arthritis (RA), and osteoarthritis (OA) are three rheumatic immune diseases with many common characteristics. If left untreated, they can lead to joint destruction and functional limitation, and in severe cases, they can cause lifelong disability and even death. Studies have shown that early diagnosis and treatment are key to improving patient outcomes. Therefore, a rapid and accurate method for rapid diagnosis of diseases has been established, which is of great clinical significance for realizing early diagnosis of diseases and improving patient prognosis.MethodsThis study was based on Fourier transform infrared spectroscopy (FTIR) combined with a deep learning model to achieve non-invasive, rapid, and accurate differentiation of AS, RA, OA, and healthy control group. In the experiment, 320 serum samples were collected, 80 in each group. AlexNet, ResNet, MSCNN, and MSResNet diagnostic models were established by using a machine learning algorithm.ResultThe range of spectral wave number measured by four sets of Fourier transform infrared spectroscopy is 700-4000 cm-1. Serum spectral characteristic peaks were mainly at 1641 cm-1(amide I), 1542 cm-1(amide II), 3280 cm-1(amide A), 1420 cm-1(proline and tryptophan), 1245 cm-1(amide III), 1078 cm-1(carbohydrate region). And 2940 cm-1 (mainly fatty acids and cholesterol). At the same time, AlexNet, ResNet, MSCNN, and MSResNet diagnostic models are established by using machine learning algorithms. The multi-scale MSResNet classification model combined with residual blocks can use convolution modules of different scales to extract different scale features and use resblocks to solve the problem of network degradation, reduce the interference of spectral measurement noise, and enhance the generalization ability of the network model. By comparing the experimental results of the other three models AlexNet, ResNet, and MSCNN, it is found that the MSResNet model has the best diagnostic performance and the accuracy rate is 0.87.ConclusionThe results prove the feasibility of serum Fourier transform infrared spectroscopy combined with a deep learning algorithm to distinguish AS, RA, OA, and healthy control group, which can be used as an effective auxiliary diagnostic method for these rheumatic immune diseases.

Abstract Aims Sodium‐glucose cotransporter 2 inhibitors (SGLT2is) have made considerable progress in the field of heart failure, but their application in arrhythmia remains to be in‐depth. Right heart disease (RHD) often leads to right heart dysfunction and is associated with atrial fibrillation (AF). Here, we explored the possible electrophysiologic effect of dapagliflozin (a type of SGLT2is) in the development of AF in rats with RHD. Methods and results Rats in the experimental group were intraperitoneally injected with a single dose of 60 mg/kg monocrotaline (MCT group, n = 32) on the first day of the experiment, whereas rats in the control group were injected with vehicle (CTL group, n = 32). Rats in the treatment subgroup were treated with dapagliflozin solution orally (MCT + DAPA and CTL + DAPA groups) for a total of 4 weeks, whereas rats in the rest of subgroups were given sterile drinking water. After 4 weeks, echocardiography demonstrated that MCT group rats developed obvious pulmonary arterial hypertension and right heart dysfunction. In addition, there were also obvious inflammatory infiltration, fibrosis, and muscularization in right atrial and pulmonary arteries. The P‐wave duration (17.00 ± 0.53 ms, vs. 14.43 ± 0.57 ms in CTL; 14.00 ± 0.65 ms in CTL + DAPA; 14.57 ± 0.65 ms in MCT + DAPA; P

Background: Ibrutinib is an effective and well-tolerated treatment for B-cell lymphomas but is associated with an increased risk of atrial fibrillation (AF) by altering the structure of the atrium. 5-Methoxytryptophan (5-MTP) inhibits inflammatory and fibrotic processes. This study aimed to determine the effects and mechanisms of 5-MTP on the underlying mechanisms of AF caused by ibrutinib. Methods: The effect of 5-MTP on ibrutinib-related AF was investigated in male Sprague Dawley rats using echocardiographic, electrophysiological, immunofluorescent, Masson staining, and molecular analyses. Rusults: The ibrutinib+5-MTP group showed (1) a lower incidence and shorter duration of AF and accelerated atrial conduction; (2) a decreased left atrial mass and left atrial diameter; (3) decreased myocardial fibrosis in the left atrium; (4) lower atrial inflammation; (5) increased sarcoplasmic reticulum Ca2+-ATPase 2a protein expression, decreased phosphorylation of phospholamban at Thr17, and decreased sodium/calcium exchanger 1 protein expression and phosphorylation of ryanodine receptor 2 at S2814; and (6) decreased phosphorylation of CaMKII expression. 5-MTP treatment markedly activated the PI3K-Akt signaling. Inhibiting PI3K-Akt signaling significantly reversed the protective effect of 5-MTP on ibrutinib-related AF. Conclusions: These findings suggest that 5-MTP administration decreases the vulnerability of ibrutinib-related AF mainly caused by ameliorated maladaptive left atrial remodeling and dysregulation of calcium handling proteins. Mechanistically, 5-MTP treatment markedly enhanced the activation of cardiac PI3K-Akt signaling.

ABSTRACT Purpose: Oxidative stress and apoptosis contribute to the pathological basis of doxorubicin (DOX)-induced cardiotoxicity. Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Herein, we intended to explore the potential role and molecular basis of CBN in DOX-induced cardiotoxicity. Methods: C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity. CBN (10 mg/kg/day, i.p.) was administered for four week following DOX injection. Results: DOX administered markedly dampened cardiac function, increased cardiac injury, excessive reactive oxygen species (ROS) production, and cardiomyocyte loss. These alterations induced by DOX significantly alleviated by CBN treatment. Mechanistically, our results demonstrated that the CBN exerts cardioprotection role against DOX by up-regulating silent information regulator 1 (Sirt1) and decreasing acetylation of forkhead box O1 (FOXO1). Moreover, Sirt1 inhibition with Ex-527 significantly blunt the beneficial effect of CBN on DOX-induced cardiotoxicity, including cardiac dysfunction, ROS, and apoptosis. Conclusion: Collectively, CBN attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity through maintaining Sirt1/FOXO1 signaling pathway. Our results demonstrated that CBN might be used to treat DOX-related cardiotoxicity.

In this study, we employed a chemical precipitation method to successfully synthesize nanoparticles of gallium-doped hydroxyapatite (Ga-HAp). The microstructure of Ga-HAp was precisely tailored by modulating the concentration of gallium ions. Our findings unequivocally demonstrate that gallium ions exert a pronounced inhibitory influence on the growth of HAp crystals, and this inhibitory potency exhibits a direct correlation with the concentration of gallium. Furthermore, gallium ions facilitate the metamorphosis of HAp nanoparticles, transitioning them from nanoneedles to nanosheets. It is worth noting, however, that gallium ions exhibit a limited capacity to substitute for calcium ions within the crystal lattice of HAp, with the maximum substitution rate capped at 4.85%. Additionally, gallium plays a pivotal role in constraining the release of ions from HAp, and this behavior remains consistent across samples with varying Ga doping concentrations. Our in vitro experiments confirm that Ga-doped HAp amplifies both the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.

Abstract Aims Myeloid differentiation protein 1 (MD1) is expressed in the mammalian heart and exerts an anti‐arrhythmic effect. Atrial fibrillation (AF) is closely related to heart failure with preserved ejection fraction (HFpEF). The potential impact of MD1 on AF vulnerability in an HFpEF model is not clear. Methods and results MD1 knock‐out and wild‐type (WT) mice were subjected to uninephrectomy and continuous saline or d‐aldosterone infusion and given 1% sodium chloride drinking water for 4 weeks. Echocardiographic and haemodynamic measurements, electrophysiological studies, Masson staining, and molecular analysis were performed. Aldosterone‐infused WT mice develop HFpEF with left ventricular hypertrophy, moderate hypertension, pulmonary congestion, and diastolic dysfunction. Aldosterone infusion increased the vulnerability of WT mice to AF, as shown by a prolonged interatrial conduction time, shortened effective refractory period, and higher incidence of AF. In addition, aldosterone infusion increased myocardial fibrosis and inflammation, decreased sarcoplasmic reticulum Ca2+‐ATPase 2a protein expression and the phosphorylation of phospholamban at Thr17, and increased sodium/calcium exchanger 1 protein expression and the phosphorylation of ryanodine receptor 2 in WT mice. All of the above adverse effects of aldosterone infusion were further exacerbated in MD1 knock‐out mice compare with WT mice. Mechanistically, MD1 deletion increased the activation of the toll‐like receptor 4/calmodulin‐dependent protein kinase II signalling pathway in in vivo and in vitro experiments. Conclusions MD1 deficiency increases the vulnerability of HFpEF mice to AF. This is mainly caused by aggravated maladaptive left atrial fibrosis and inflammation and worsened dysregulation of calcium handling, which is induced by the enhanced activation of the toll‐like receptor 4/calmodulin‐dependent protein kinase II signalling pathway.

Multi-pass hot extrusion was used to prepare the Al2O3/AZ31 composite.The microstru-cture was characterized by optical microscopy, scanning electron microscopy, transmission electron microscopy, and mechanical properties were tested by Vickers hardness tester and electron universal strength tester. The results show that Al2O3 particles are uniformly distributed in AZ31 magnesium matrix by multi-pass hot extrusion. The grain refining effect of Al2O3 particles on the matrix is enhanced, and the grain size of the composite decreases significantly with the increase of the pass. During the hot extrusion process, the dislocation density around the Al2O3 particles increases, and the high-density dislocation region facilitates the dynamic recrystallization nucleation, so that the grains of the Al2O3/AZ31 composite are significantly refined. The Al2O3 particles are gradually distributed into a long strip from the initial island distribution, then distributed in a linear pattern, and finally distributed uniformly in the form of particles in the AZ31 magnesium matrix. After fourth-pass hot extrusion, the mechanical properties of Al2O3/AZ31 composite are significantly improved, and hardness, tensile strength and yield strength are 89HV, 305MPa and 198MPa, respectively. The hardness, tensile strength and yield strength increase by 19.2%, 14.8%, and 14.1%, respectively, compared with the first-pass hot extrusion.

Pulmonary fibrosis: Moving signals down a notch might help A cell membrane protein called Notch1, which binds to signaling molecules outside cells and then alters the activity of genes inside the cells, might be a promising target for drugs to treat the lung damage of pulmonary fibrosis. This condition, generally of unknown cause, involves thickening, stiffening and scarring of lung tissue. It can lead to serious breathing difficulties and eventually death, especially in people aged over 70. Hui Wang and colleagues at Central South University, Changsha, investigated the significance of the Notch1 signaling pathway by examining lung tissue from patients and manipulating the activity of the pathway in mouse cells. They conclude that Notch1 signaling is activated in pulmonary fibrosis. Drugs that could inhibit the pathway, for example by binding to the Notch1 protein, might open a promising new avenue toward treatment.

Background Cardiac remodeling predisposes individuals to heart failure if the burden is not solved, and heart failure is a growing cause of morbidity and mortality worldwide. The cardiac extracellular matrix not only provides structural support, but also is a core aspect of the myocardial response to various biomechanical stresses and heart failure. MFAP4 (microfibrillar‐associated protein 4) is an integrin ligand located in the extracellular matrix, whose biological functions in the heart remain poorly understood. In the current study we aimed to test the role of MFAP4 in cardiac remodeling. Methods and Results MFAP4‐deficient (MFAP4−/−) and wild‐type mice were subjected to aortic banding surgery and isoproterenol to establish models of cardiac remodeling. We also evaluated the functional effects of MFAP4 on cardiac hypertrophy, fibrosis, and cardiac electrical remodeling. The expression of MFAP4 was increased in the animal cardiac remodeling models induced by pressure overload and isoproterenol. After challenge of 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol, MFAP4−/− mice exhibited lower levels of cardiac fibrosis and fewer ventricular arrhythmias than wild‐type mice. However, there was no significant effect on cardiomyocyte hypertrophy. In addition, there was no significant difference in cardiac fibrosis severity, hypertrophy, or ventricular arrhythmia incidence between wild‐type‐sham and knockout‐sham mice. Conclusions These findings are the first to demonstrate that MFAP4 deficiency inhibits cardiac fibrosis and ventricular arrhythmias after challenge with 8 weeks of aortic banding or 2 weeks of intraperitoneal isoproterenol but does not significantly affect the hypertrophy response. In addition, MFAP4 deficiency had no significant effect on cardiac fibrosis, hypertrophy, or ventricular arrhythmia in the sham group in this study.

Shensong Yangxin (SSYX) is a traditional Chinese medicine, which has been proven to improve the clinical symptoms of arrhythmia. However, the role of SSYX in metabolic syndrome (MetS)-induced electrical remodeling remains to be fully elucidated. Here, we sought to clarify whether SSYX can alter the electrophysiological remodeling of cardiac myocytes from MetS rats by regulating transient outward potassium current (Ito) and calcium current (ICa-L). Male Wistar rats were subjected to 16 weeks of high-carbohydrate, high-fat to produce a MetS model group. SSYX (0.4 g/kg) was administrated by daily gavage 8 weeks following high-carbohydrate, high-fat for 8 weeks. In vivo electrophysiological study was performed to evaluated ventricular arrhythmias (VA) vulnerability and electrophysiological properties. The potential electrical mechanisms were estimated by whole-cell patch-clamp and molecular analysis. The H9C2 cells were used to verify the protective role of SSYX in vitro. After 16-week high-carbohydrate, high-fat feeding, MetS model rats showed increased body weight (BW), blood pressure (BP), blood sugar (BS), heart rate (HR) and heart weights to tibia length (HW/TL) ratio. Furthermore, MetS rats depicted increased VA inducibility, shortened effective refractory period (ERP) and prolonged action potential duration (APD). Lower ICa-L and Ito current densities were observed in MetS rats than CTL rats. Additionally, MetS rats exhibited significantly increased cardiac fibrosis, decreased Cx43 expression and protein levels of Cav1.2, Kv4.2, Kv4.3 than CTL group. As expected, these MetS-induced effects above were reversed when SSYX was administrated. Mechanistically, SSYX administrated significantly down-regulated the TLR4/MyD88/CaMKII signaling pathway both in vivo and in vitro. Collectively, our data indicated that the electrical remodeling induced by MetS contributed to the increased VA susceptibility. SSYX protects against MetS-induced VA by inhibiting electrical remodeling through TLR4/MyD88/CaMKII signaling pathway.

Subject: This study was to evaluate whether a special lecture on the Chinese Guideline for Blood Pressure Measurement (CGBPM) improves end-digit preference (EDP) of blood pressure (BP) recordings in primary care clinics. Methods: In 2012, the doctors working in a clinic received a lecture, which emphasizes that when mercurial sphygmomanometer was used, only 0, and even numbers could be recorded as BP end-digit. In 2016, we collected the BP recordings (2011–2015) of 462 hypertensive patients followed in the educated clinic or in another no-educated clinic. The percentages of 0, 2, 4, 6, 8 in BP end-digit were calculated for evaluating zero EDP, and the percent decline in each year was calculated on the formula: (baseline percentage – actual percentage in a year)/baseline percentage. Results: In 2011, the percentage of zero end-digit was over 75% for SBP or DBP in both clinics. Against the no-educated clinic, the educated clinic had significant higher percent decline of zero EDP on SBP (31.5% vs −2.6%) and DBP (36.9% vs −14.3%) in 2013, and in 2014 (SBP 38.0% vs 11.6%; DBP 42.8% vs −4.0%). In 2015, the educated clinic still had higher percent decline of zero EDP on DBP (43.3% vs 29.3%). Furthermore, the percentages of zero end-digit for SBP (43.6% vs 49.2%) or for DBP (43.5% vs 59.0%) were lower in the educated clinic in 2015. Conclusion: Education on BP measurement and recording could improve the quality of BP recordings, and this effect may last for three years.

The phosphorus-rich sediments, including phosphate nodules and phosphate rock, at the bottom of the Lower Cambrian, are widespread in China. These sediments are also considered as one of the most important chemical symbol layers in early Cambrian and also indicate the great change of the Earth's surface system in the transitional period of Cryptozoic to Phanerozoic. Phosphorus sources and the enrichment mechanism remains a matter of debate. In order to better understand the depositional mechanism of these phosphorus-rich sediments, Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) was used to perform in situ multi-element imaging in the micro areas of phosphate nodules from the black shale of the Niutitang Formation in the Jinsha area of Guizhou Province. The results show that the enrichment of each element in phosphorus tuberculosis clearly records the trend of the microenvironment during the formation of phosphorus tuberculosis. Ca and P are enriched and Si is depleted in the inner layer of the phosphate nodule, which means that the enrichment of P was due to the formation of authigenic apatite. P is derived from organic matter containing oxygen or anaerobic degradation release. The co-enrichment of Mn, Zn with P in the interior indicates an oxic bottom water layer during the formation of the phosphate nodule. The enrichment of As, Mo, V in the surrounding rocks or black shale implies that the reduced bottom water ended the growth of the phosphate nodule. This study shows that LA-ICP-MS in situ multi-element imaging technology can reveal rich geochemical information in the micro-area, which can provide high-precision visualization evidence, and will be widely used in geological exploration and paleo-environmental research.

Saving water resources plays an important role in the sustainable utilization of water resources.Based on relevant data of water resources in Zhongshan City from 2000 to 2017,this paper analyzes the sustainable development of water resources in Zhongshan City after carrying out water-saving work by the analysis methods of water ecological footprint and sustainable utilization evaluation.The results show that after the water-saving work was carried out in Zhongshan City in 2011,in overall,the water ecological footprint per capita decreased,the intensity of water resources utilization decreased sharply,the ecological pressure index of water resources reduced,the ecological carrying capacity of water resources per capita increased,and the ecological surplus of water resources per capita increased;with nearly 89% sustainable utilization state of water resources in Zhongshan,water resources have changed from a weak unsustainable state to a weak and medium sustainable state.The level of sustainable utilization of water resources is effectively improved.

The Neoproterozoic to Early Cambrian period is a very important era in the history of earth evolution. Research on stratigraphic framework, paleo-oceanography, palaro-atmospheric, and paleoclimatology are focuses of international geosciences. As a new stratigraphic dating method, Re-Os isotopic dating was developed rapidly in the last decades. It has dual advantages of dating and tracing the paleoenvironment for the organic-rich black shale deposited at the important timing turning points during Neoproterozoic to Early Cambrian. Taking the Neoproterozoic to Early Cambrian strata as an example, the application of the Re-Os isotopic dating method in chronostratigraphy is described in this paper and the reliability of the Re-Os dating method by comparison with numerous precise zircon U-Pb ages is confirmed. This method has played an important role in the research of the building order in the Doushantuo Formation and the sedimentary time of the Liuchapo Formation. Combining previous Sr isotope curves with the initial 187Os/188Os ratios of Neoproterozoic to Early Cambrian strata, the role of Os isotopes in the interpretation of the paleoenvironment and tracing the source of Ni-Mo-V polymetallic layers is discussed. Sr isotope analysis is difficult to conduct on black shales, while initial 187Os/188Os can complement this defect. Therefore, the mutual combination of these two methods can contribute to the exploration of the paleoenvironment during Neoproterozoic to Early Cambrian. Finally, with the development of Re-Os isotope analysis technology and establishment of more experiment processes, it will produce a significant effect on the study of future chronostratigraphy, especially on the age-determination of the older strata.

This paper presents a planning system based on semantic reasoning for a general-purpose service robot, which is aimed at behaving more intelligently in domains that contain incomplete information, under-specified goals, and dynamic changes. First, Two kinds of data are generated by Natural Language Processing module from the speech: (i) action frames and their relationships; (ii) the modifier used to indicate some property or characteristic of a variable in the action frame. Next, the task’s goals are generated from these action frames and modifiers. These goals are represented as AI symbols, combining world state and domain knowledge, which are used to generate plans by an Answer Set Programming solver. Finally, the plan’s actions are executed one by one, and continuous sensing grounds useful information, which makes the robot use contingent knowledge to adapt to dynamic changes and faults. For each action in the plan, the planner gets its preconditions and effects from domain knowledge, so during the execution of the task, the environmental changes, especially those conflict with the actions, not only the action being performed but also the subsequent actions, can be detected and handled as early as possible. A series of case studies are used to evaluate the system and verify its ability to acquire knowledge through dialogue with users, solve problems with the acquired causal knowledge, and plan for complex tasks autonomously in the open world.

This paper reports the project of a shopping mall service robot, named KeJia , which is designed for customer guidance, providing information and entertainments in a real shopping mall environment. The background, motivations, and requirements of this project are analyzed and presented, which guide the development of the robot system. To develop the robot system, new techniques and improvements of existing methods for mapping, localization, and navigation are proposed to address the challenge of robot motion in a very large, complex, and crowded environment. Moreover, a novel multimodal interaction mechanism is designed by which customers can conveniently interact with the robot either in speech or via a mobile application. The KeJia robot was deployed in a large modern shopping mall with the size of 30,000 m 2 and more than 160 shops; field trials were conducted for 40 days where about 530 customers were served. The results of both simulated experiments and field tests confirm the feasibility, stability, and safety of the robot system.