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Abstract In deep‐ocean natural gas hydrate exploitation operation, the fatigue failure mechanism has attracted more and more attention from scholars, but it has not been effectively disclosed. Therefore, in this work, a multifield coupling and multiple‐nonlinear vibration model of lifting pipe is established, which can accurately determine the alternating stress of deep‐ocean lifting pipe. Second, according to Forman theory, the calculation method of crack propagation length and depth on the surface of a deep‐water riser is established, which is verified by the comparison between the experimental and theoretical model calculation results. The results demonstrate that, first, the effect of residual stress in the welded joint of deep‐ocean lifting pipe should be considered in the later parameter influence analysis. Second, the fatigue growth life of deep‐water pipe with small outflow velocity is mainly determined by tensile stress, and that is determined by both tensile stress and bending stress with large outflow velocity. Third, more attention should be paid to the vibration of the lower pipe on‐site to reduce its vibration frequency and vibration stress amplitude, which can effectively reduce the surface crack propagation state of the deep‐ocean pipe and improve the service life of the pipe. Fourth, properly adjusting the tension coefficient of the tensioner during field operation can effectively improve the safety of the pipe, and the optimal tension coefficient is related to the configuration of the deep‐ocean pipe system, which can be analyzed and determined by the model.

BackgroundThe therapeutic effects of vitamin D supplementation on Coronavirus disease 2019 (COVID-19) aggravation remain controversial and inconclusive. To probe into this contentious issue, we performed the present meta-analysis of randomized controlled trials (RCTs).MethodsLiterature published up to June 2023 was retrieved from Cochrane Library, PubMed, Web of Science and Embase. RCTs assessing mortality, intensive care unit (ICU) admission, mechanical ventilation (MV), length of hospitalization (LOH), and inflammatory markers containing C-reactive protein (CRP), D-dimer, interleukin-6 (IL-6), lactate dehydrogenase (LDH) were included. 19 RCTs were involved in the analysis and were conducted subgroup analyses on the baseline COVID-19 severity and vitamin D administration.ResultsIn the severity subgroup, statistically significant effects in moderate to severe group were observed in ICU admission (OR 0.43, 95% CI 0.23, 0.80; p = 0.008), MV (OR 0.44, 95% CI 0.27, 0.72; p = 0.001) and LOH (SMD –0.49, 95% CI –0.92, −0.06; p = 0.027). In the administration subgroup, effects of ICU admission (OR 0.39, 95% CI 0.16, 0.97; p = 0.044), MV (OR 0.18, 95% CI 0.07, 0.46; p = 0.000) and LOH (SMD –0.50, 95% CI –0.96, −0.04; p = 0.034) were more pronounced in patients supplied with multiple-dose vitamin D than single-dose. Although the result of mortality showed no statistically significant effect, it indicated a reduced trend (OR 0.87, 95% CI 0.63, 1.12; p > 0.05). The results of inflammatory markers reached no statistical differences.ConclusionThis meta-analysis revealed that moderate to severe COVID-19 patients supplied with multiple doses of vitamin D were less apt to need ICU admission, mechanical ventilation and have shorter hospital stays.

ObjectivePreeclampsia (PE) is a severe complication of unclear pathogenesis associated with pregnancy. This research aimed to elucidate the properties of immune cell infiltration and potential biomarkers of PE based on bioinformatics analysis.Materials and methodsTwo PE datasets were imported from the Gene ExpressioOmnibus (GEO) and screened to identify differentially expressed genes (DEGs). Significant module genes were identified by weighted gene co-expression network analysis (WGCNA). DEGs that interacted with key module genes (GLu-DEGs) were analyzed further by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The diagnostic value of the genes was assessed using receiver operating characteristic (ROC) curves and protein-protein interaction (PPI) networks were constructed using GeneMANIA, and GSVA analysis was performed using the MSigDB database. Immune cell infiltration was analyzed using the TISIDB database, and StarBase and Cytoscape were used to construct an RBP-mRNA network. The identified hub genes were validated in two independent datasets. For further confirmation, placental tissue from healthy pregnant women and women with PE were collected and analyzed using both RT-qPCR and immunohistochemistry.ResultsA total of seven GLu-DEGs were obtained and were found to be involved in pathways associated with the transport of sulfur compounds, PPAR signaling, and energy metabolism, shown by GO and KEGG analyses. GSVA indicated significant increases in adipocytokine signaling. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) indicated that the levels of activated B cells and T follicular helper cells were significantly increased in the PE group and were negatively correlated with GLu-DEGs, suggesting their potential importance.ConclusionIn summary, the results showed a correlation between glutamine metabolism and immune cells, providing new insights into the understandingPE pathogenesis and furnishing evidence for future advances in the treatment of this disease.

Abstract Background Compared with optimal blood pressure (BP), the prehypertension increases the risk of incident hypertension, cardiovascular (CV) events, and death. Moderate intensity of regular physical activity can reduce BP. However, aerobic exercise has some limitations. As a safe, low-impact, enjoyable, and inexpensive form of exercise that requires minimal equipment and space, Tai Chi is expected as a viable alternative to aerobic exercise. The study aimed to assess the effect of Tai Chi intervention program, compared with aerobic exercise, on the BP in prehypertension patients. Methods This study is a 12-month, two-center, single-blind, parallel, randomized controlled trial. Three hundred forty-two patients with prehypertension [with a systolic blood pressure (SBP) in the range of 120 mmHg to 139 mmHg and/or a diastolic blood pressure (DBP) in the range of 80 mmHg to 89 mmHg] are randomized to one of two intervention groups in a 1:1 ratio: Tai Chi or aerobic exercise. BP monitoring methods of office blood pressure, ambulatory blood pressure monitoring (ABPM), and home blood pressure monitoring (HBPM) are used at the same time to detect BP in multiple dimensions. The primary outcome is the comparison of SBP change from baseline to 12 months in Tai Chi group and SBP change from baseline to 12 months in aerobic exercise group. The secondary endpoints are as following: (1) the comparison of DBP of office blood pressure change from baseline to 12 months between Tai Chi group and aerobic exercise group, (2) the comparison of BP and the variability of BP assessed through ABPM change from baseline to 12 months between Tai Chi group and aerobic exercise group, (3) the comparison of BP assessed through HBPM change from baseline to 12 months between Tai Chi group and aerobic exercise group. Discussion This will be the first randomized controlled trial to specifically study the benefits of Tai Chi on the blood pressure control in patients with prehypertension. The successful completion of this study will help to provide evidence for whether Tai Chi is more desirable than aerobic exercise. Trial registration Trial registration number: Chinese Clinical Trial Registry, ChiCTR1900024368. Registered on 7 July 2019, http://www.chictr.org.cn/edit.aspx?pid=39478&htm=4

IntroductionPreventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in Traditional Chinese medicine (TCM) preparations can protect the myocardium by various mechanisms. Our meta-analysis aims to evaluate the efficacy of TCM saponins in treating myocardial ischemia-reperfusion injury (MIRI) and to summarize the potential molecular mechanisms further.MethodsWe conducted a literature search in six electronic databases [Web of Science, PubMed, Embase, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI)] until October 2022.ResultsSeventeen eligible studies included 386 animals (254 received saponins and 132 received vehicles). The random effect model is used to calculate the combined effect. The effect size is expressed as the weighted average difference (WMD) and 95% confidence interval (CI). Compared with placebo, saponins preconditioning reduced infarct size after MIRI significantly (WMD: −3.60,95% CI: −4.45 to −2.74, P

Post-pancreatitis diabetes mellitus—the most common sequela of pancreatitis—leads to poorer glycaemic control compared with type 2 diabetes. Because post-pancreatitis diabetes mellitus is an exemplar of secondary diabetes (with a clear underlying cause), much post-pancreatitis diabetes mellitus is preventable or treatable early. Earlier literature established the important role of dietary fibre in reducing plasma glucose in individuals with type 2 diabetes. The present review benchmarks available evidence on the role of habitual dietary fibre intake in pancreatitis and post-pancreatitis diabetes mellitus. It also paves the way for future research on the use of dietary fibre in the post-pancreatitis setting.

In this study, the effects of different fertilization methods and nitrogen forms on the root morphology and nitrogen accumulation of Pinus tabuliformis carr. were investigated, and the interaction mechanism between roots and nitrogen fertilizer was analyzed to provide a theoretical basis for the rational fertilization of Pinus tabuliformis. The total amount of nitrogen fertilizer applied to seedlings was 100 mg·plant−1; four nitrogen form treatments of ammonium nitrogen, nitrate nitrogen, ammonium nitrate 1:1, and amide nitrogen were set up; and two fertilization methods of conventional and exponential fertilization were applied, with a total of eight experimental treatments. By measuring root parameters, plant biomass, and nitrogen accumulation, the correlation between fertilization method and nitrogen form on the root index of seedlings was analyzed, and the effects of fertilization methods and nitrogen forms on the root growth of seedlings were discussed. Compared with conventional fertilization, exponential fertilization significantly promoted root growth and development, and amide nitrogen was the best nitrogen form. The total length, total surface area, total volume, average diameter, root tips, root/shoot ratio, root tissue density of seedlings’ roots, biomass, and nitrogen accumulation of seedlings in exponential fertilization with amide nitrogen EF3 treatment all increased substantially compared with the others, The effects of fertilization mode, nitrogen form, and their interaction on the partial growth of Pinus tabuliformis seedlings were significant (p < 0.05). The correlation analysis of each index showed that the correlation between nitrogen accumulation and biomass was strongest. Therefore, considering the morphological and structural characteristics of the root system and the nitrogen accumulation in the root system, amide nitrogen in the experimental fertilization can better promote the growth and development of the root system of seedlings.

Abstract Transformer internal thermal monitoring exists huge blind areas, and it is difficult for traditional methods to get fully distributed temperature in real time. In this contribution, the distributed optical fibre sensor was creatively applied inside an operating 35 kV oil‐immersed transformer which is also qualified for actual power grid operation through the ex‐factory tests. Furthermore, the full‐region temperature along the windings and iron limbs were firstly monitored in a spatiotemporally continuous manner and the hotspots were also closely traced, fluctuating at 90% of the high‐voltage winding height (80% for low‐voltage winding) during the whole process of the heat‐run test. Corresponding Finite Element Method (FEM) for thermo‐fluid field calculation was then utilized for deeper analysis. On the former basis, the actual detected temperature distributions (both spatial and temporal) were compared with the International Electrotechnical Commission traditional model and some modifications were suggested based on the real time measured data. This novel online monitoring application and the detailed internal thermal information may provide a solid reference for the delicate management of power transformers, which also offers a new horizon for the online monitoring in electrical apparatus industry.

The nonlinear dynamic response of a MEMS resonator with a triangular tuning comb is studied. The motion equation with dis-smooth tuning electrostatic force is derived according to Newton’s second law. The analytical solution of the periodic response is obtained using the harmonic balance method and section integral method. The singularity theory is then applied to investigate the bifurcation of the periodic response of the untuned system. The transition sets on the DC-AC voltage plane dividing the planes into several persistent regions are obtained. The bifurcation diagrams’ topological structures and jump phenomena corresponding to different parameter regions are analyzed. We explore the effects of tuning voltage on the response. This demonstrates that the amplitude–frequency curves present more hardening characteristics with increased tuning voltage. Many twists, bifurcation points, and unstable solutions appear, leading to complicated jump phenomena. Two bifurcation points exist on the response curves: the smooth and dis-smooth bifurcation points, with the latter occurring on the switching plane of non-uniform fingers.

To investigate the route choice behavior of travelers under unexpected accidents, this study designs four different scenarios of travelers’ route choice behavior experiments according to the severity of unexpected accidents. The bounded rationality characteristics of travelers, such as the time perception difference coefficient, psychological threshold effect coefficient, and scale effect, are introduced into the generalized random regret minimization (GRRM) model. An improved generalized random regret minimization (IGRRM) model is constructed based on travelers’ route choice behavior under unexpected accidents. The collected data of travelers’ route choice results under four different congestion-level scenarios are analyzed by the IGRRM model. The study finds that with the increase in congestion level, travelers are more willing to change the route; during the commute, travelers tend to choose the route with less travel time and angular cost; in the moderate and serious congestion scenarios, travelers no longer reject the detour route; attribute perception difference, scale effect, and psychological threshold effect; affect travelers’ route choice behavior. The IGRRM model based on the route choice behavior of travelers can more accurately characterize the route choice behavior of travelers under unexpected accidents, provide a basis for traffic flow distribution under unexpected accidents, and benefit traffic management departments to take traffic control and guidance measures to ease the traffic congestion caused by unexpected accidents.

ObjectiveTo construct a reliable nomogram available online to predict the postoperative survival of patients with perihilar cholangiocarcinoma.MethodsData from 1808 patients diagnosed with perihilar cholangiocarcinoma between 2004 and 2015 were extracted from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) database. They were randomly divided into training and validation sets. The nomogram was established by machine learning and Cox model. The discriminant ability and prediction accuracy of the nomogram were evaluated by concordance index (C-index), receiver operator characteristic (ROC) curve and calibration curve. Kaplan-Meier curves show the prognostic value of the associated risk factors and classification system.ResultsMachine learning and multivariate Cox risk regression model showed that sex, age, tumor differentiation, primary tumor stage(T), lymph node metastasis(N), TNM stage, surgery, radiation, chemotherapy, lymph node dissection were associated with the prognosis of perihilar cholangiocarcinoma patients relevant factors (P

Flax (Linum usitatissimum L.), as an important oil-producing crop, is widely distributed throughout the world, and its seeds are rich in polyunsaturated fatty acids (FAs). Previous studies have revealed that Arabidopsis thaliana ACETYL-CoA CARBOXYLASE (AtACCase) is vital for FA biosynthesis. However, the functions of L. usitatissimum AccD (LuAccD) on FA accumulation and seed germination remain unclear. In the present study, we cloned the LuAccD coding sequence from the flax cultivar ‘Longya 10’, identified conserved protein domains, and performed a phylogenetic analysis to elucidate its relationship with homologs from a range of plant species. Ectopic expression of LuAccD in A. thaliana wild-type background enhanced seed FA accumulation without altering seed morphological characteristics, including seed size, 1000-seed weight, and seed coat color. Consistently, the expression of key genes involved in FA biosynthesis was greatly up-regulated in the developing seeds of LuAccD overexpression lines. Additionally, we demonstrated that LuAccD acts as a positive regulator of salt and mannitol tolerance during seed germination in A. thaliana. These results provide important insights into the functions of LuAccD, which facilitates the oil quantity and abiotic stress tolerance of oil-producing crops through genetic manipulation.

Abstract Background Esophageal cancer (EC) is a malignant tumor with high mortality. Nomogram is an important tool used in clinical prognostic assessment. We aimed to establish a novel nomogram to predict the overall survival (OS) of EC patients after radical esophagectomy. Methods Data pertaining to the survival, demography, and clinicopathology of 311 EC patients who underwent radical esophagectomy were retrospectively investigated. The nomogram was established based on Cox hazard regression analysis. The calibration curves and Harrell's concordance index (C‐index) were used to verify the predictive accuracy and ROC curves were used to assess the efficacy of the nomogram. Kaplan–Meier curves showed the prognostic value of the related risk classification system. Pearson correlation test was performed to determine the correlation between the risk classification system and TNM staging. Results The median OS and 5‐year survival rates in the primary and validation cohorts were 44 months and 29.8%, and 52 months and 27.1%, respectively. We used six independent prognostic factors—age, Sex, AGR, PRL, N stage, and PNI—in the nomogram. The C‐index of nomogram was 0.75 and 0.70 in the primary and validation cohorts, respectively. Calibration curves indicated high consistency between actual and predicted OS. ROC curves showed that nomogram has a better efficacy compared with TNM staging in both cohorts. Patients were divided into three risk groups according to the total nomogram score, the median OS in each group was significantly different in both cohorts. Furthermore, the risk classification system was strongly correlated with the T and N staging system and exhibited a better OS prediction capability. Conclusions We established a novel and practical nomogram with a subordinate risk classification system to predict the OS of patients after radical esophagectomy. Compared with AJCC staging, this nomogram had preferable clinical capability in terms of individual prognosis assessment.

Based on a model with three-degree-of-freedom, the nonlinear coupled axial-torsional vibration of drill string is numerically studied considering a modified contact model of bit-rock interaction. The effects of driving angular velocities, nominal drilling pressures, and formation stiffness on response are discussed. The simulation results show that response can be periodic, quasi-periodic or chaotic motion with the variation of system parameters. Increasing driving angular velocity is helpful to reduce the duration of sticking and even make the system stick-slip free. However, bit-bounce may occur if driving angular velocity is too large. Increasing nominal drilling pressure can cause the system to be more prone to stick-slip, but it has dampening effect on bit-bounce. The larger the formation stiffness is, the smaller the amplitude of the axial vibration response of the system is, and the driving angular velocity corresponding to the maximum amplitude of the axial vibration response is also larger, whereas the variation of the amplitude of torsional vibration is smaller. Compared with the results from two-degree-of-freedom model, the amplitude of torsional vibration of the present model is remarkable greater. Meanwhile, the present model is more prone to stick-slip than the one with two-degree-of-freedom, and it is not easy to bit bounce.

In order to study the seismic response of liquid storage tank under bidirectional seismic excitation, the 15×104 m3 vertical unanchored liquid storage tank was taken as the object, and numerical analysis on seismic response of vertical unanchored tank was conducted with the finite element software ADINA, considering the contact nonlinear. The whole system was mainly divided into two parts, i.e., the basic isolation components and the liquid-structure interaction subsystem. The structure and liquid region of the tank were simulated with the shell element and potential fluid element respectively, and the three-dimensional isolation was equivalently replaced by a spring-damping system. Subsequently, analysis of uplift response, acceleration time history, liquid sloshing height, wall stress change, base shear and overturning moment was carried out for the liquid storage tank with Bathe integration method. The results show that: under the excitation of El-Centro seismic wave, the tank bottom is uplifted before seismic isolation and the uplift area is in the shape of "crescent", which disappears after seismic isolation. Installing a seismic isolation layer in the liquid storage tank could effectively reduce the dynamic response such as acceleration, wall stress, base shear force and overturning moment. However, liquid sloshing height of the liquid storage tank after seismic isolation increases. The research results could provide reference for the seismic isolation design of liquid storage tank.

Abstract Background Cardiac injury is now a common complication of coronavirus disease (COVID-19), but it remains unclear whether cardiac injury-related biomarkers can be independent predictors of mortality and severe disease development or intensive care unit (ICU) admission. Methods Two investigators searched the PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), Wanfang, MedRxiv, and ChinaXiv databases for articles published through March 30, 2020. Retrospective studies assessing the relationship between the prognosis of COVID-19 patients and levels of troponin I (TnI) and other cardiac injury biomarkers (creatine kinase [CK], CK myocardial band [CK-MB], lactate dehydrogenase [LDH], and interleukin-6 [IL-6]) were included. The data were extracted independently by two investigators. Results The analysis included 23 studies with 4631 total individuals. The proportions of severe disease, ICU admission, or death among patients with non-elevated TnI (or troponin T [TnT]), and those with elevated TnI (or TnT) were 12.0% and 64.5%, 11.8% and 56.0%, and 8.2% and. 59.3%, respectively. Patients with elevated TnI levels had significantly higher risks of severe disease, ICU admission, and death (RR 5.57, 95% CI 3.04 to 10.22, P

Three homologous electrochromic conjugated polymers, each containing an asymmetric building block but decorated with distinct alkyl chains, were designed and synthesized using electrochemical polymerization in this study. The corresponding monomers, namely T610FBTT810, DT6FBT, and DT48FBT, comprise the same backbone structure, i.e., an asymmetric 5-fluorobenzo[c][1,2,5]thiadiazole unit substituted by two thiophene terminals, but were decorated with different types of alkyl chain (hexyl, 2-butyloctyl, 2-hexyldecyl, or 2-octyldecyl). The effects of the side-chain structure and asymmetric repeating unit on the optical absorption, electrochemistry, morphology, and electrochromic properties were investigated comparatively. It was found that the electrochromism conjugated polymer, originating from DT6FBT with the shortest and linear alkyl chain, exhibits the best electrochromic performance with a 25% optical contrast ratio and a 0.3 s response time. The flexible electrochromic device of PDT6FBT achieved reversible colors of navy and cyan between the neutral and oxidized states, consistent with the non-device phenomenon. These results demonstrate that subtle modification of the side chain is able to change the electrochromic properties of conjugated polymers.

Background Performance of existing atrial fibrillation (AF) risk prediction models in poststroke populations is unclear. We evaluated predictive utility of an AF risk model in patients with acute stroke and assessed performance of a fully refitted model. Methods and Results Within an academic hospital, we included patients aged 46 to 94 years discharged for acute ischemic stroke between 2003 and 2018. We estimated 5‐year predicted probabilities of AF using the Cohorts for Heart and Aging Research in Genomic Epidemiology for Atrial Fibrillation (CHARGE‐AF) model, by recalibrating CHARGE‐AF to the baseline risk of the sample, and by fully refitting a Cox proportional hazards model to the stroke sample (Re‐CHARGE‐AF) model. We compared discrimination and calibration between models and used 200 bootstrap samples for optimism‐adjusted measures. Among 551 patients with acute stroke, there were 70 incident AF events over 5 years (cumulative incidence, 15.2%; 95% CI, 10.6%–19.5%). Median predicted 5‐year risk from CHARGE‐AF was 4.8% (quartile 1–quartile 3, 2.0–12.6) and from Re‐CHARGE‐AF was 16.1% (quartile 1–quartile 3, 8.0–26.2). For CHARGE‐AF, discrimination was moderate (C statistic, 0.64; 95% CI, 0.57–0.70) and calibration was poor, underestimating AF risk (Greenwood‐Nam D’Agostino chi‐square, P

Intermittent fasting (IF) has gained attention as a promising diet for weight loss and dysmetabolic diseases management. This systematic review aimed to investigate the effects of IF on cardiometabolic risk factors (CMRFs). A systematic literature search was carried out using three electronic databases, namely PubMed, Embase, and the Cochrane Library, until October 2020. Randomized controlled trials that compared the IF intervention with a control group diet were included. Fourteen effect sizes were expressed as weighted mean difference (WMD) using a fixed-effects model and 95% confidence intervals (CI). Compared to the ones within control groups, participants exposed to the IF intervention reduced their body weight (WMD, −1.78 kg; 95% CI, −2.21 to −1.35; p

The inclination effect caused by fabrication errors on the periodic response of a symmetric MEMS gyroscope is investigated. The dynamic equation is established considering the inclination effect on support stiffness and electrostatic forces. The periodic response is obtained by the averaging method. The two-variable singularity theory is employed to study the bifurcation characteristics and give transition sets on the DC-AC voltage plane, which divide the plane into four persistent regions. The amplitude-frequency curves demonstrate that only the two persistent regions with low voltages are feasible for the gyroscope. Both over-etching and under-etching reduce the feasible region. The effect of parameters on the performance is present. The mechanical sensitivity and nonlinearity increase with the voltages. With the increase in the inclination angle, the mechanical sensitivity and nonlinearity decrease first and then increase. The full temperature stability of the mechanical sensitivity is also considered. The variation in mechanical sensitivity with temperature is small at a large voltage and negative inclination angle. Under-etching, which leads to small nonlinearity and good temperature stability, is more beneficial to the performance of the gyroscope than over-etching.

The dynamic behavior of a piezoelectric cantilever energy harvesting system with bi-stable state under elastic support is studied to reveal its complex phenomena. Based on the magnetic force model which can induce bi-stable phenomena, the mathematical model of the system with two degree of freedom under harmonic base motion is firstly established by using Newton's second law and Kirchhoff′s law. By the Routh-Hurwitz criterion, the static bifurcation of equilibrium points, is secondly analyzed for the dimensionless governing equations. At last, the amplitude variations of the displacement of piezoelectric cantilever beam and the variations of the output voltage with the system parameters and excitation parameters and their bifurcation diagrams are obtained by Matlab numerical simulations. The results show that the amplitude-frequency curves of the system are in hard characteristic, while the amplitude variations of the displacement of piezoelectric cantilever beam with mass ratio and stiffness ratio are in soft characteristic. That is, within some parameters intervals, the harmonic response of the system has bifurcation and leads to chaotic motion. The motion of the system can take place near the zero or non-zero equilibrium point, even jump with large amplitude between the two non-zero equilibrium points. For the same parameters, bi-stable systems have richer forms of motion compared to mono-stable ones, and significantly increase voltage output and response frequency band of the system. The research result may provide theoretical reference for how to optimize vibration energy collector in practice.

An improved homotopy analysis method (IHAM) is proposed to solve the nonlinear differential equation, especially for the case when nonlinearity is strong in this paper. As an application, the method was used to derive explicit solutions to the rotation angle of a cantilever beam under point load at the free end. Compared with the traditional homotopy method, the derivation includes two steps. A new nonlinear differential equation is firstly constructed based on the current nonlinear differential equation of the rotation angle and the auxiliary quadratic nonlinear differential equation. In the second step, a high-order non-linear iterative homotopy differential equation is established based on the new non-linear differential equation and the auxiliary linear differential equation. The analytical solution to the rotation angle is then derived by solving this high-order homotopy equation. In addition, the convergence range can be extended significantly by the homotopy–Páde approximation. Compared with the traditional homotopy analysis method, the current improved method not only speeds up the convergence of the solution, but also enlarges the convergence range. For the large deflection problem of beams, the new solution for the rotation angle is more approachable to the engineering designers than the implicit exact solution by the Euler–Bernoulli law. It should have significant practical applications in the design of long bridges or high-rise buildings to minimize the potential error due to the extreme length of the beam-like structures.

Based on a lumped parameter model with two degrees of freedom, the periodic response of the coupled axial-torsional nonlinear vibration of drill strings is studied by HB-AFT (harmonic balance and alternating frequency/time domain) method and numerical simulations. The amplitude-frequency characteristic curves of axial relative displacement and torsional relative angular velocity are given to reveal the mechanism of bit bounce and stick-slip motion. The stability of periodic response is analyzed by Floquet theory, and the boundary conditions of bifurcation of periodic response are given when parameters such as nominal drilling pressure, angular velocity of turntable, and formation stiffness are varied. The results show that the amplitude of the periodic response of the system precipitates a spontaneous jump and Hopf bifurcation may occur when the angular velocity of the turntable is varied. The variation of parameters may lead to the complex dynamic behavior of the system, such as period-doubling motion, quasiperiodic motion, and chaos. Bit bounce and stick-slip phenomenon can be effectively suppressed by varying the angular velocity of turntable and nominal drilling pressure.

The dynamic response and its stability of a blade rotor with coupled rubbing in the labyrinth seal and tip seal are investigated. The dynamic equations are established based on the Hertz contact rubbing force at the labyrinth seal and the tip rubbing force considering both the contact deformation of the tip seal and the bending deformation of the blade. Numerical simulations show that the coupled rubbing response includes periodic motions, almost periodic motions, and chaotic motions. Compared with the single rubbing fault, coupled rubbing increases the range of rotation velocity of contact. A new continuation shooting method is used in the solution and stability analysis of the periodic response to give the bifurcation diagrams. The paths of the system for entering and exiting chaos are analyzed.

Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain–gut and kidney–gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.

Abstract Defect or intermediate states within the band gap of ferroelectric oxides are known to impact functional characteristics such as saturated polarization. However, depending upon their respective position, such levels can also induce a substantial photoelectrical response under appropriate illumination and severely impact the conduction mechanism of an otherwise highly insulating material system. Sub‐band‐gap illumination is used to highlight the activity of these levels in epitaxially grown and ferroelectric Pb(Zr0.2Ti0.8)O3 thin films. Large transient effects are observed in relation to ferroelectric polarization and conductivity after illumination. In the case of polarization, light induces a “leaky” character, which eventually decays over a period of nearly 1.5 h. In conjunction, persistent photoconductivity is observed as the enhanced conductivity attained under illumination gradually decays over several minutes after removal of illumination. Thermally stimulated currents are measured to probe the presence of sub‐band gap states and analyze their effect over a wide range of temperature. The trapping nature of the states and their role in the conduction is found to be the underlying origin.

Atherosclerosis and its associated cardiovascular diseases (CVDs) are serious threats to human health and have been reported to be associated with the gut microbiota. Recently, the role of berberine (BBR) in atherosclerosis and gut microbiota has begun to be appreciated. The purposes of this study were to observe the effects of high or low doses of BBR on atherosclerosis and gut microbiota modulation, and to explore their correlation in ApoE–/– mice fed a high-fat diet. A significant decrease in atherosclerotic lesions was observed after treatment with BBR, with the effect of the high dose being more obvious. Both BBR treatments significantly reduced total cholesterol, APOB100, and very low-density lipoprotein cholesterol levels but levels of high/low-density lipoprotein cholesterol and lipoprotein (a) were only reduced by high-dose BBR. Decreased pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6 and increased anti-inflammatory IL-10 and adiponectin levels were observed in the high-dose BBR group, but no decrease in IL-6 or increase in IL-10 was evident using the low-dose of BBR. 16S rRNA sequencing showed that BBR significantly altered the community compositional structure of gut microbiota. Specifically, BBR enriched the abundance of Roseburia, Blautia, Allobaculum, Alistipes, and Turicibacter, and changed the abundance of Bilophila. These microbiota displayed good anti-inflammatory effects related to the production of short-chain fatty acids (SCFAs) and were related to glucolipid metabolism. Alistipes and Roseburia were significantly enriched in high-dose BBR group while Blautia and Allobaculum were more enriched in low-dose, and Turicibacter was enriched in both BBR doses. Metagenomic analysis further showed an elevated potential for lipid and glycan metabolism and synthesis of SCFAs, as well as reduced potential of TMAO production after BBR treatment. The findings demonstrate that both high and low-dose BBR can improve serum lipid and systemic inflammation levels, and alleviate atherosclerosis induced by high-fat diet in ApoE–/– mice. The effects are more pronounced for the high dose. This anti-atherosclerotic effect of BBR may be partly attributed to changes in composition and functions of gut microbiota which may be associated with anti-inflammatory and metabolism of glucose and lipid. Notably, gut microbiota alterations showed different sensitivity to BBR dose.

Atrial fibrillation (AF) occurs in up to 11% of cancer patients treated with ibrutinib. The pathophysiology of ibrutinib promoted AF is complicated, as there are multiple interactions involved; the detailed molecular mechanisms underlying this are still unclear. Here, we aimed to determine the electrophysiological and molecular mechanisms of burst-pacing-induced AF in ibrutinib-treated mice. The results indicated differentially expressed proteins in ibrutinib-treated mice, identified through proteomic analysis, were found to play a role in oxidative stress-related pathways. Finally, treatment with an inhibitor of NADPH oxidase (NOX) prevented and reversed AF development in ibrutinib-treated mice. It was showed that the related protein expression of reactive oxygen species (ROS) in the ibrutinib group was significantly increased, including NOX2, NOX4, p22-phox, XO and TGF-β protein expression. It was interesting that ibrutinib group also significantly increased the expression of ox-CaMKII, p-CaMKII (Thr-286) and p-RyR2 (Ser2814), causing enhanced abnormal sarcoplasmic reticulum (SR) Ca2+ release and mitochondrial structures, as well as atrial fibrosis and atrial hypertrophy in ibrutinib-treated mice, and apocynin reduced the expression of these proteins. Ibrutinib-treated mice were also more likely to develop AF, and AF occurred over longer periods. In conclusion, our study has established a pathophysiological role for ROS signaling in atrial cardiomyocytes, and it may be that ox-CaMKII and p-CaMKII (Thr-286) are activated by ROS to increase AF susceptibility following ibrutinib treatment. We have also identified the inhibition of NOX as a potential novel AF therapy approach. Keywords: Reactive oxygen species, Ibrutinib, Atrial fibrillation, Electrical remodeling, Structural remodeling

Explicit solutions to vertical and horizontal displacements are derived for large deformation of a cantilever beam under point load at the free end by an improved homotopy analysis method (IHAM). Quadratic and cubic nonlinear differential equations are adopted to construct more proficient nonlinear equations for vertical and horizontal displacements respectively combined with their currently available nonlinear displacement equations. Higher-order nonlinear iterative homotopy equations are established to solve the vertical and horizontal displacements by combining simultaneous equations of the constructed nonlinear equations and the auxiliary linear equations. The convergence range of vertical displacement is extended by the homotopy-Páde approximation. The explicit solutions to the vertical and horizontal displacements are in favorable agreements with the respective exact solutions. The convergence ranges for a relative error of 1% by the improved homotopy analysis method for vertical and horizontal displacements increases by 60% and 7%, respectively. These explicit formulas are helpful in practical engineering design for very slender structures, such as high-rise buildings and long bridges.

In this paper, we investigate the bifurcation characteristics of a comb drive MEMS resonator. The method of averaging and the residue theorem are used to get a more accurate analytical solution for the periodic response. Then, the singularity theory is employed to give the transition sets on the DC-AC voltage plane and the lateral separation-quality factor plane, which divide the planes into 9 persist regions. The corresponding bifurcation diagrams are present to discuss the jump phenomena of the periodic response, and the influences of the parameters on the amplitude-frequency response are studied. We also attempt to analyze the feasibility for the resonators working in the nonlinear regions and give the available frequency range and the available maximum amplitude of the nonlinear response. With the increase of the DC voltage, the amplitude-frequency curves change from hardening to softening, and the lateral separation has the opposite effect. The amplitude-frequency curves increase along the backbone curves with the AC voltage and quality factor. The response curves of softening or hardening characteristics have enough available frequency range and large available amplitudes, which may be more appropriate for the operation of the resonator than those of the mixture characteristics.

Cardiovascular disease (CVD) is the leading cause of death worldwide, especially in developed countries, and atherosclerosis (AS) is the common pathological basis of many cardiovascular diseases (CVDs) such as coronary heart disease (CHD). The role of the gut microbiota in AS has begun to be appreciated in recent years. Trimethylamine N-oxide (TMAO), an important gut microbe-dependent metabolite, is generated from dietary choline, betaine, and L-carnitine. Multiple studies have suggested a correlation between plasma TMAO levels and the risk of AS. However, the mechanism underlying this relationship is still unclear. In this review, we discuss the TMAO-involved mechanisms of atherosclerotic CVD from the perspective of inflammation, inflammation-related immunity, cholesterol metabolism, and atherothrombosis. We also summarize available clinical studies on the role of TMAO in predicting prognostic outcomes, including major adverse cardiovascular events (MACE), in patients presenting with AS. Finally, since TMAO may be a novel therapeutic target for AS, several therapeutic strategies including drugs, dietary, etc. to lower TMAO levels that are currently being explored are also discussed.

The nod-like receptor family pyrin domain containing 3 (NLRP3) is currently the most widely studied inflammasome and has become a hot topic of recent research. As a macromolecular complex, the NLRP3 inflammasome is activated to produce downstream factors, including caspase-1, IL-1β, and IL-18, which then promote local inflammatory responses and induce pyroptosis, leading to unfavorable effects. A growing number of studies have examined the relationship between the NLRP3 inflammasome and cardiovascular diseases (CVDs). However, some studies have shown that the NLRP3 inflammasome is not involved in the occurrence of certain diseases. Therefore, identifying the mechanism of action of the NLRP3 inflammasome and its potential involvement in the pathological process of disease progression is of utmost importance. This review discusses the mechanisms of NLRP3 inflammasome activation and the relationship between the inflammasome and CVDs, including coronary atherosclerosis, myocardial ischemia/reperfusion, cardiomyopathies, and arrhythmia, as well as CVD-related treatments.

Background:SCN5A with Brugada syndrome (BrS) is not commonly considered as an independent risk marker for subsequent cardiac events. However, the risk of SCN5A combined with other clinical characteristics has not been fully investigated.Objectives: The aim of this study is to investigate and evaluate risk stratification and related risk factors of SCN5A in BrS.Methods: The databases of PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI) and Wanfang Data were searched for related studies published from January 2002 to May 2018 followed by meta-analysis. The BrS patients who underwent SCN5A gene tests were included. The prognosis and risk stratification of SCN5A combined with symptoms and asymptoms diagnosis in BrS, electrophysiology study (EPS) were then investigated and evaluated. Outcomes were defined as ventricular tachycardia/fibrillation (VT/VF), sudden cardiac death (SCD).Results: Eleven suitable studies involving 1892 BrS patients who underwent SCN5A gene tests were identified. SCN5A (+) was not considered to be a significant predictor of future cardiac events (95% CI: 0.89–2.11; P = 0.15; I2 = 0%). However, SCN5A (+) patients with symptoms at diagnosis revealed a higher prevalence of future VT/VF, SCD compared to SCN5A (–) patients with symptoms at diagnosis. (95% CI: 1.06–3.70; P = 0.03 I2 = 0%) Among asymptomatic patients, the risk did not significantly differ between SCN5A (+) patients and SCN5A (–) patients. (95% CI: 0.51–4.72; P = 0.45 I2 = 0 %). In an investigation involving patients in EPS (–) BrS electrocardiogram (ECG), the risk of SCN5A (+) is higher than that of SCN5A (–) (P < 0.001).Conclusions: In BrS patients with symptoms at diagnosis or EPS (–), the meta-analysis suggests that SCN5A (+) are at a higher risk of arrhythmic events than SCN5A (–).

Aims: Risk stratification of patients with Brugada syndrome (BrS) is vital for accurate prognosis and therapeutic decisions. Spontaneous Type 1 ST segment elevation is generally considered to be an independent risk factor for arrhythmic events. Other risk factors include gender, syncope, sudden cardiac arrest (SCA), and positive electrophysiological study (EPS). However, the further risk stratification of spontaneous type 1 combined with the other risk factors remains unclear. The present study pooled data from 4 large trials aiming to systematically evaluate the risk of spontaneous Type-1 ECG when combined with one or more of these other recognized risk factors.Methods: We searched for related studies published from November 2, 2002 to February 10, 2018 in PubMed, EMBASE, Cochrane Library, MEDLINE, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Databases. The pooled data were evaluated combining each risk factor with the presence of a spontaneous Type-1 ECG. All analyses were performed using Review Manager, version 5.0.12.Results: Four eligible studies involving 1,338 patients (85% males, mean age: 48.1 ± 18.1 years) were enrolled. Spontaneous Type-1 ECG was associated with higher risk for ventricular tachycardia/fibrillation (VT/VF) than cases with non-Type 1 ECG in males (odds ratio: 95% CI: 1.84–5.17; P < 0.0001), but not in females (P = 0.29). Among spontaneous Type-1 cases with syncope or with positive EPS, the difference was not statistically significant (P = 0.06 and 0.07, respectively). Patients with Type-1 ECGs and positive EPS were at higher risk than those with negative EPS (95% CI: 1.10–5.04; P = 0.03). Pooled analysis showed an association of Spontaneous Type-1 ECG, Type-1 ECGs combined with male, and Type-1 ECGs combined with positive EPS between increased risk of arrhythmic events.Conclusion: Our results indicate that in BrS patients, a spontaneous Type-1 ECG is an independent risk factor for SCD in males, but not in females. A spontaneous Type-1 BrS is associated with a worse prognosis when combined with positive EPS

The association between intake of dietary fibre and glucose metabolism has been extensively investigated in numerous metabolic disorders. However, little is known about this association in individuals after an attack of acute pancreatitis (AP). The aim was to investigate the associations between intake of dietary fibre and markers of glucose metabolism in individuals with new-onset prediabetes or diabetes after acute pancreatitis (NODAP), pre-exiting type 2 prediabetes or diabetes, and normoglycaemia after acute pancreatitis. This cross-sectional study was nested within the parent prospective longitudinal cohort study. The studied markers of glucose metabolism were fasting plasma glucose and glycated haemoglobin. Habitual intake of dietary fibre was determined using the EPIC-Norfolk food frequency questionnaire. Multivariable linear regression analyses were conducted. The study included a total of 108 individuals after AP. In the NODAP group, increased intakes of total fibre (β = −0.154, p = 0.006), insoluble fibre (β = −0.133, p = 0.01), and soluble fibre (β = −0.13, p = 0.02) were significantly associated with a reduction in fasting plasma glucose. Increased intakes of vegetables (β = −0.069, p = 0.004) and nuts (β = −0.039, p = 0.038) were significantly associated with a reduction in fasting plasma glucose. Increased intake of nuts (β = −0.054, p = 0.001) was also significantly associated with a reduction in glycated haemoglobin. None of the above associations were significant in the other study groups. Habitual intake of dietary fibre was inversely associated with fasting plasma glucose in individuals with NODAP. Individuals after an attack of AP may benefit from increasing their intake of dietary fibre (specifically, vegetables and nuts) with a view to preventing NODAP.

The bifurcation of the periodic response of a micro-machined gyroscope with cubic supporting stiffness and fractional electrostatic forces is investigated. The pull-in phenomenon is analyzed to show that the system can have a stable periodic response when the detecting voltage is kept within a certain range. The method of averaging and the residue theorem are employed to give the averaging equations for the case of primary resonance and 1:1 internal resonance. Transition sets on the driving/detecting voltage plane that divide the parameter plane into 12 persistent regions and the corresponding bifurcation diagrams are obtained via the singularity theory. The results show that multiple solutions of the resonance curves appear with a large driving voltage and a small detecting voltage, which may lead to an uncertain output of the gyroscope. The effects of driving and detecting voltages on mechanical sensitivity and nonlinearity are analyzed for three persistent regions considering the operation requirements of the micro-machined gyroscope. The results indicate that in the region with a small driving voltage, the mechanical sensitivity is much smaller. In the other two regions, the variations in the mechanical sensitivity and nonlinearity are analogous. It is possible that the system has a maximum mechanical sensitivity and minimum nonlinearity for an appropriate range of detecting voltages.

Dietary intake of iron is known to be associated with impaired glucose metabolism. However, its involvement in derangements of glucose metabolism after acute pancreatitis (AP) is not completely understood. The aim was to investigate the association between dietary iron intake and markers of glucose metabolism in individuals after an attack of AP. Fasting blood samples were collected to analyse markers of glucose metabolism (fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)). The EPIC-Norfolk food frequency questionnaire was used to determine the habitual intake of dietary iron (total, haem, and non-haem). Multivariable linear regression analyses were conducted and six statistical models were built to adjust for covariates. A total of 109 individuals after AP were studied in a cross-sectional fashion. Total iron (β (95% confidence interval) = −0.19 (−0.35, −0.05); p = 0.01 in the most adjusted model) and non-haem iron (β (95% confidence interval) = −0.19 (−0.33, −0.04); p = 0.03 in the most adjusted model) were significantly associated with FPG, consistently in all adjusted model. Total iron and non-haem iron did not have consistent significant associations with HbA1c. Dietary haem iron intake was not associated with either FPG or HbA1c. Habitual intake of dietary iron is inversely associated with FPG in individuals after an attack of AP and may be involved in the pathogenesis of new-onset diabetes after pancreatitis. Prospective longitudinal studies are now warranted to unveil the specific mechanism underlying the involvement of dietary iron.

To accurately detect and monitor the internal temperature of an operating power transformer, the distributed optical fiber sensor (DOFS) was creatively applied inside an oil-immersed 35 kV transformer through high integration with the winding wire. On the former basis, the power transformer prototype with a completely global internal temperature sensing capability was successfully developed and it was also qualified for power grid operation through the ex-factory type tests. The internal spatially continuous temperature distribution of the operating transformer was then revealed through a heat-run test and the numerical simulation was also applied for further analysis. Hotspots of windings were continuously located and monitored (emerging at about 89%/90% height of low/high voltage winding), which were furtherly compared with the IEC calculation results. This new nondestructive internal sensing method shows a broad application prospect in the electrical equipment field. Also, the revelation of transformer internal distributed temperature can offer a solid reference for both researchers and field operation staff.

Traditional monitoring methods cannot obtain the overall thermal information for power transformers. To solve this problem, a distributed fiber optic sensor (DFOS) was creatively applied inside an operating 35 kV power transformer by highly integrating with the electromagnetic wires. Then, the transformer prototype with totally global sensing capability was successfully developed and it was qualified for power grid application through the strict ex-factory tests. The as designed optical fiber sensor works stably all the time with a temperature accuracy of ±0.2 °C and spatial positioning accuracy of 0.8 m. Based on the obtained internal temperature distribution, Gaussian convolution was further applied for the signal processing and hereby, the hotspots for all the windings and iron cores could be accurately traced. The hottest points were located at 89.1% (55 °C) of the high voltage winding height and 89.7% (77.5 °C) of the low voltage winding height. The actual precise hotspot location corrected the traditional cognition on the transformer windings and it would serve as an essential reference for the manufactures. This new nondestructive internal sensing and condition monitoring method also exhibits a promising future for the DFOS applying in the high-voltage electrical apparatus industry.

Some well-established immunotherapy, radiotherapy, postoperation, anticancer drugs such as anthracyclines, antimetabolites, human epidermal growth factor receptor 2 blockers, tyrosine kinase inhibitors, alkylating agents, checkpoint inhibitors, and angiogenesis inhibitors, are significantly linked to cardiotoxicity. Cardiotoxicity is a common complication of several cancer treatments. Some studies observed complications of cardiac arrhythmia associated with the treatment of cancer, including atrial fibrillation (AF), supraventricular arrhythmias, and cardiac repolarization abnormalities. AF increases the risk of cardiovascular morbidity and mortality; it is associated with an almost doubled risk of mortality and a nearly 5-fold increase in the risk of stroke. The occurrence of AF is also usually researched in patients with advanced cancer and those undergoing active cancer treatments. During cancer treatments, the incidence rate of AF affects the prognosis of tumor treatment and challenges the treatment strategy. The present article is mainly focused on the cardiotoxicity of cancer treatments. In our review, we discuss these anticancer therapies and how they induce AF and consequently provide information on the precaution of AF during cancer treatment.

Background: Male gender has been consistently shown to be a risk factor for a greater number of arrhythmic events in patients with Brugada Syndrome (BrS). However, there have been no large-scale comprehensive pooled analyses to statistically and systematically verify this association. Therefore, we conducted a pooled analysis on gender differences in prognosis and risk stratification of BrS with a largest sample capacity at present.Methods: We searched PubMed, Embase, Medline, Cochrane Library databases, Chinese National Knowledge Infrastructure, and Wanfang Data for relevant studies published from 2002 to 2017. The prognosis and risk stratification of BrS and risk factors were then investigated and evaluated according to gender.Results: Twenty-four eligible studies involving 4,140 patients were included in the analysis. Male patients (78.1%) had a higher risk of arrhythmic events than female patients (95% confidence interval: 1.46–2.91, P < 0.0001). Among the male population, there were statistical differences between symptomatic patients and asymptomatic patients (95% CI: 2.63–7.86, P < 0.00001), but in the female population, no statistical differences were found. In the female subgroup, electrophysiological study (EPS) positive patients had a tendency toward a higher risk of arrhythmic events than EPS-negative patients (95% CI: 0.93–29.77, P = 0.06).Conclusions: Male patients are at a higher risk of arrhythmic events than female patients. Within the male population, symptomatic patients have a significantly higher risk profile compared to asymptomatic patients, but no such differences are evident within the female population. Consequently, in the female population, the risk of asymptomatic patterns cannot be underestimated.

Anthracyclines are effective agents generally used to treat solid-tumor and hematologic malignancies. The use of anthracyclines for over 40 years has improved cancer survival statistics. Nevertheless, the clinical utility of anthracyclines is limited by its dose-dependent cardiotoxicity that adversely affects 10–30% of patients. Anthracycline-induced cardiotoxicity may be classified as acute/subacute or chronic/late toxicity and leads to devastating adverse effects resulting in poor quality of life, morbidity, and premature mortality. Traditional Chinese medicine has a history of over 2,000 years, involving both unique theories and substantial experience. Several studies have investigated the potential of natural products to decrease the cardiotoxic effects of chemotherapeutic agents on healthy cells, without negatively affecting their antineoplastic activity. This article discusses the mechanism of anthracycline-induced cardiotoxicity, and summarizes traditional Chinese medicine treatment for anthracycline-induced heart failure (HF), cardiac arrhythmia, cardiomyopathy, and myocardial ischemia in recent years, in order to provide a reference for the clinical prevention and treatment of cardiac toxicity.

Curbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo. Importantly, inhibition of PD-1 signaling during the carcinogenesis process (immediately after 4NQO challenge) significantly reduced and delayed de novo formation of both pre-cancerous and cancerous lesions in vivo, in conjunction with effective PD-1 down-modulation in the tumor infiltrating leukocyte and peripheral lymph organs. Lastly, reduction of carcinogen-induced lesions upon PD-1 mAb treatment in vivo was accompanied by reduction of potent immunosuppressive myeloid-derived suppressor cells (MDSCs), and increase in “activated” T cell accumulations in the lesion-microenvironment (127% increase) and peripheral lymph nodes (25% increase). These data support PD-1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy and reduce canceration rate in premalignant lesions.

Asymmetric triangulation is an interesting method combined with concentric pleating to obtain a 3D shape without stretching or tearing. There exists some geometric properties in the process of folding to help realize extension and contraction, which can be used in parametric modeling of different regular polygons. To facilitate design and modeling, adequate computational modeling methods are indispensable. This paper proposes a new mathematical idea and presents a feasible way to build the parameterized models in the digital environment of Rhinoceros, utilizing the Kangaroo plugin in Grasshopper. Designers can directly observe the models’ kinematic deployment and calculate the folding efficiency. It is concluded that the tendencies of folding efficiency in different regular polygons are not the same. To realize rigid folding, each polygon has a limited folding angle.

The principal parametric resonance of two van der Pol oscillators under coupled position and velocity feedback control with time delay is investigated analytically and numerically on the assumption that only one of the two oscillators is parametrically excited and the feedback control is linear. The slow-flow equations are obtained by the averaging method and simplified by truncating the first term of Taylor expansions for those terms with time delay. It is found that nontrivial solutions corresponding to periodic motions exist only for one oscillator if no feedback control is applied although the two oscillators are nonlinearly coupled. Based on Levenberg-Marquardt method, the effects of excitation and control parameters on the amplitude of periodic solutions of the system are graphically given. It can be seen that both of the two oscillators can be excited in periodic vibration with proper feedback. However, the amplitudes of the periodic vibrations are independent of the sign of feedback gains. In addition, the influence of time delay on the response of the system is periodic. In terms of numerical simulations, it is shown that both of the two oscillators can also have quasi-periodic motions, periodic motions about a new equilibrium position and other complex motions such as relaxation oscillation when feedback control is considered.

In this paper, the dynamics of Duffing-van der Pol oscillators under linear-plus-nonlinear position feedback control with two time delays is studied analytically and numerically. By the averaging method, together with truncation of Taylor expansions for those terms with time delay, the slow-flow equations are obtained from which the trivial and nontrivial solutions can be found. It is shown that the trivial solution can be stabilized by appropriate gain and time delay in linear feedback although it loses its stability via Hopf bifurcation and results in periodic solution for uncontrolled systems. And the stability of the trivial solution is independent of nonlinear feedback. Different from the case of the trivial solution, the stability of nontrivial solutions is also associated with nonlinear feedback besides linear feedback. Non-trivial solutions may lose their stability via saddle-node or Hopf bifurcation and the resulting response of the system may be quasi-periodic or chaotic. The feedback gains and time delays have great effects on the amplitude of the periodic solutions and their bifurcation control. The simulations, obtained by numerically integrating the original system, are in good agreement with the analytical results.