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Although observational studies have linked primary aldosteronism (PA) with cardiovascular diseases (CVDs), the causality remains uncertain. In this study, we aimed to investigate whether PA is causally associated with CVD risk and cardiac magnetic resonance (CMR) parameters using the Mendelian randomization (MR) method. Independent and genome‐wide significant single nucleotide polymorphisms for PA were extracted from genome‐wide association study (GWAS) summary statistics. Genetic associations with the CVDs and CMR parameters were obtained from recent large‐scale GWASs or genetic consortia. Inverse‐variance weighted (IVW) method was utilized for the preliminary estimates, and multiple sensitivity analyses (including weighted median, Cochran's Q test, MR‐Egger, MR‐PRESSO, and leave‐one‐out analysis) were conducted to verify the robustness of the results. The MR analyses using the IVW method showed that genetically predicated PA was significantly associated with atrial fibrillation (OR = 1.046, 95% CI: 1.029–1.062, padj < 0.001), myocardial infarction (OR = 1.029, 95% CI: 1.005–1.053, padj = 0.027), heart failure (OR = 1.023, 95% CI: 1.004–1.042, padj = 0.027), any stroke (OR = 1.062, 95% CI: 1.031–1.095, padj < 0.001), any ischemic stroke (OR = 1.058, 95% CI: 1.022–1.095, padj = 0.004), and small vessel stroke (OR = 1.116, 95% CI: 1.041–1.196, padj = 0.004). Notably, PA also had a causal effect on adverse cardiac remodeling, including larger ventricular and atrial volumes, higher ventricular stroke volume, and reduced left atrial emptying fraction. Our findings support a causal role of PA in higher cardiovascular disease risk and adverse cardiac remodeling. Given the diagnostic delay and disease burden in PA, more attention should be paid to the screening and treatment of PA to reduce the incidence of cardiovascular outcomes. [ABSTRACT FROM AUTHOR]

Background: Copper is an essential trace element for biological systems, as it plays a critical role in the activity of various enzymes and metabolic processes. However, the dysregulation of copper homeostasis is closely associated with the onset and progression of numerous diseases. In recent years, copper‐induced cell death, a novel form of cellular demise, has garnered significant attention. This process is characterized by the abnormal accumulation of intracellular copper ions, leading to cellular dysfunction and eventual cell death. Copper toxicity occurs through the interaction of copper with acylated enzymes in the tricarboxylic acid (TCA) cycle. This interaction results in subsequent protein aggregation, causing proteotoxic stress and ultimately resulting in cell death. Despite the promise of these findings, the detailed mechanisms and broader implications of cuproptosis remain underexplored. Therefore, our study aimed to investigate the role of copper in cell death and autophagy, focusing on the molecular mechanisms of cuproptosis. We also aimed to discuss recent advancements in copper‐related research across various diseases and tumors, providing insights for future studies and potential therapeutic applications. Main Body: This review delves into the biological significance of copper metabolism and the molecular mechanisms underlying copper‐induced cell death. Furthermore, we discuss the role of copper toxicity in the pathogenesis of various diseases, emphasizing recent advancements in the field of oncology. Additionally, we explore the therapeutic potential of targeting copper toxicity. Conclusion: The study highlights the need for further research to explore alternative pathways of copper‐induced cell death, detailed mechanisms of cuproptosis, and biomarkers for copper poisoning. Future research should focus on exploring the molecular mechanisms of cuproptosis, developing new therapeutic strategies, and verifying their safety and efficacy in clinical trials. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096–1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07–11.99%), the fatty acid group (4.78–12.82%), and the cholesterol group (3.64–11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D. [ABSTRACT FROM AUTHOR]

A new working principle for multimodal excitation of a resonant bidirectional rotary inertial impact piezoelectric motor with a self-clamping structure was developed based on previous research on piezoelectric motors. Unlike previous piezoelectric motors that relied on single harmonic waves for unidirectional rotation, in this motor, we can simply change the driving signal characteristics of the motor without changing the structure of the piezoelectric motor to excite multiple vibration modes, thereby achieving rotation in both directions. Compared with other bidirectional resonant motors, the structure and control signal are simpler. The finite element simulation software COMSOL5.5 was used to simulate the working mode of the motor, and the results were in good agreement with the final experiment. During the experiments, the optimal operating frequency of the motor prototype was 900 Hz. The maximum output speed of the motor prototype was 3.9 rad/s, the maximum output torque was 15 N mm, and the maximum resolution was 0.248° under the conditions of 240 Vp-p voltage, 900 Hz frequency, and 7.8 N mm preload torque. [ABSTRACT FROM AUTHOR]

Macrophages play an important role in clearing necrotic myocardial tissues, myocardial ischemia–reperfusion injury, and ventricular remodeling after myocardial infarction. M1 macrophages not only participate in the inflammatory response in myocardial tissues after infarction, which causes heart damage, but also exert a protective effect on the heart during ischemia. In contrast, M2 macrophages exhibit anti-inflammatory and tissue repair properties by inducing the production of high levels of anti-inflammatory cytokines and fibro-progenitor cells. Interleukin (IL)-38, a new member of the IL-1 family, has been reported to modulate the IL-36 signaling pathway by playing a role similar to that of the IL-36 receptor antagonist, which also affects the production and secretion of macrophage-related inflammatory factors that play an anti-inflammatory role. IL-38 can relieve myocardial ischemia–reperfusion injury by promoting the differentiation of M1 macrophages into M2 macrophages, inhibit the activation of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome, and increase the secretion of anti-inflammatory cytokines, such as IL-10 and transforming growth factor-β. The intact recombinant IL-38 can also bind to interleukin 1 receptor accessory protein-like 1 (IL-1RAPL1) to activate the c-jun N-terminal kinase/activator protein 1 (JNK/AP1) pathway and increase the production of IL-6. In addition, IL-38 regulates dendritic cell-induced cardiac regulatory T cells, thereby regulating macrophage polarization and improving ventricular remodeling after myocardial infarction. Accordingly, we speculated that IL-38 and macrophage regulation may be therapeutic targets for ameliorating myocardial ischemic injury and ventricular remodeling after myocardial infarction. However, the specific mechanism of the IL-38 action warrants further investigation. [ABSTRACT FROM AUTHOR]

Piezoelectric impact motor (PIM) with high power driving capability has attracted extensive attention. This paper presents a new resonant-type PIM based on inertial drive mechanism. Architecture construction, dynamic modeling, and prototype experiment of the proposed motor are conducted. With sinusoidal driving voltages of 24 Vp-p at 435 Hz and 18 Vp-p at 870 Hz in the resonant mode, the prototype motor achieves an average no-load velocity of 26.1 mm s−1, a stalling drag force of 350 mN, and a power output capacity of 2.55 mW, while it also provides a stable step displacement of 0.67 μm with saw-tooth wave driving voltage of 20 Vp-p, 10 Hz in the stepping mode. Experiment results are consistent with the theoretical analysis, which confirms an effective approach to guide the structure design and further optimization for resonant-type PIMs. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to clarify the specific mechanism by which GARP affects the atherosclerotic plaques in ApoE−/- mice and the effect of GARP-tDC on atherosclerosis. Methods: The mice were randomly divided into three groups: the control group, the GARP-overexpressed group and the GARP-inhibited group. After 12 weeks, all the mice were euthanized, and the specimens were collected. In vitro, experiments were conducted to observe the effect of GARP on DC phenotype and the changes of the proportion of CD4+CD25+Foxp3+ Treg cells when GARP-tDCs were co-cultured with CD4+ T cells. Furthermore, adoptive transmission of GARP-tDCs was used to observe the effect on atherosclerotic plaque in mice. Results: The GARP-overexpressed group enhanced the biological activity of Foxp3+ CD4+CD25+ Tregs and resulted in increased expression of LAP in T cells. In addition, the GARP-overexpressed group significantly suppressed the function of Th1 and Th17, and decreased the secretion of INF-γ and IL-17A. Thus, GARP had a protective effect on atherosclerosis. In vitro, we found that GARP-tDC had a tolerance-inducing phenotype, and GARP-tDC also had the ability to induce tolerance when co-cultured with CD4+ T cells. More importantly, adoptive transmission of GARP-tDCs reduced the size of atherosclerotic plaques. Conclusion: GARP and the GARP-tDC play protective roles in atherosclerosis. The protective effect of GARP on atherosclerosis is achieved by increasing CD4+CD25+Foxp3+ Treg cells and inhibiting the production of IFN-γ and IL-17A. [ABSTRACT FROM AUTHOR]

A compact linear-rotary impact motor based on a single piezoelectric tube actuator is proposed. The motor can realize independent linear and rotary motions. With two independent electrodes, the piezoelectric actuator has an outer diameter of 6 mm, a thickness of 0.5 mm, and a length of 25 mm. The actuator produces a maximum axial displacement of 2.17 µm with a driving voltage of 720 Vp-p (peak-to-peak driving voltage), and it produces a maximum torsional angle of 599.98 µrad with a driving voltage of 720 Vp-p. The prototype motor can achieve the independent linear velocities of 6263.45 µm/s and −6331.58 µm/s in the positive and negative directions of motions under the saw-shaped driving voltage of 560 Vp-p at 8 kHz. The motor can realize the independent rotary velocities of 1.22 × 106µrad/s and −1.21 × 106µrad/s in the two motions under the saw-shaped driving voltage of 560 Vp-p at 9 kHz. The maximum output force of the motor is 0.45 N, and the maximum output torque is 0.80 mN m for linear and rotary motions, respectively. [ABSTRACT FROM AUTHOR]

Chronic cerebral hypoperfusion (CCH) is a main cause of vascular dementia and is also an etiological factor of neurological diseases and mental disorders. However, few treatments are available for CCH, and new medications are needed. In the present study, we employed a rat model of CCH that was based on bilateral common carotid artery occlusion and investigated the therapeutic effects of resveratrol and its detailed mechanism of action. We evaluated neurological deficit scores and performed the Morris water maze test, hematoxylin and eosin staining, TUNEL staining, enzyme-linked immunosorbent assays, and Western blot. Resveratrol reduced neurological deficit scores in CCH rats and reduced pathological damage in the frontal cortex and hippocampus. Resveratrol activated autophagy and inhibited the expression of AKT/mechanistic target of rapamycin (mTOR) signaling pathway-related proteins. Treatment with a phosphoinositide-3 kinase inhibitor reversed the protective effect of resveratrol. These findings suggest that resveratrol improves cognitive function in a rat model of CCH and reduces oxidative stress-induced neuronal damage in the frontal cortex and hippocampus by activating autophagy and inhibiting neuronal apoptosis. These effects may be regulated by the AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Resonant-type piezoelectric impact motors can improve the output capability effectively. A new construction of asymmetric inertial masses is proposed to synthesize approximate saw-tooth wave resonant vibration with matched anti-phase and in-phase modes. A prototype is designed, manufactured, and tested. With 40 Vp–p, 400 Hz exciting voltage for the anti-phase mode and 16 Vp–p, 800 Hz exciting voltage for the in-phase mode, the prototype provides a maximum no-load velocity of 17.2 mm/s and a maximum output power of 0.72 mW with 100 mN load. The velocity and output power of the prototype in the proposed resonant state are near three orders of magnitude higher than those in the traditional quasi-static state. [ABSTRACT FROM AUTHOR]

A novel impact two-degree-of-freedom (2-DOF) motor based on the decomposed screw-type motion of a piezoelectric actuator (PA) has been proposed. The fabricated prototype motor has a maximum diameter of 15 mm and a length of 100 mm which can produce a maximum torsional angle of about 1000 μrad and a maximum longitudinal displacement of about 1.03 μm under a saw-shaped driving voltage with 720 Vp-p (peak-to-peak driving voltage). When the axial prepressure generated by the spring is about 1N and the radial prepressure generated by the snap ring is about 14 N, the fabricated motor realizes rotary motion with the driving frequency from 200 Hz to 4 kHz. When the axial prepressure generated by the spring is about 11.7 N and the radial prepressure generated by the snap ring is about 21.1 N, the fabricated motor realizes linear motion with the driving frequency from 2 kHz to 11 kHz. In the experiments, the prototype motor can achieve 9.9 × 105 μrad/s rotary velocity at 2 kHz and it can achieve 2.4 mm/s linear velocity at 11 kHz under the driving voltage of 720 Vp-p. [ABSTRACT FROM AUTHOR]

Featured Application: This study provides theoretical and technical references for the practical development of a parallel piezoelectric impact drive mechanism. A controllable complex curve motion can be realized by the method of using coupled motions. A two-degrees-of-freedom (2-DOF) linear piezoelectric impact drive mechanism (PIDM) is actuated by two independent piezoelectric actuators (PAs). The coupled motion interactions of a two orthogonal DOF linear PIDM with a single friction interface are introduced and analyzed. A complete dynamic model of the 2-DOF PIDM is established with the Karnopp friction model considering the distribution of friction in the x-axis and y-axis. The output displacements of the 2-DOF PIDM and two corresponding independent 1-DOF PIDMs are investigated numerically. When the two input exciting signals of a 2-DOF PIDM have the same driving voltage of 100 V with a duty ratio of 98% at 10 Hz and two 1-DOF PIDMs are driving under the same conditions, the step displacements in the two axes of 2-DOF PIDM are improved compared to the corresponding 1-DOF PIDM. When the two input exciting signals of a 2-DOF PIDM have the same driving voltages of 100 V with a duty ratio of 98% but the driving frequency is 10 Hz in the x-axis and 20 Hz in the y-axis, the results show that the displacement of high frequency achieves a slight decrease and displacement of low frequency shows a large increase compared to the two corresponding 1-DOF PIDMs. [ABSTRACT FROM AUTHOR]

A two-axis optical scanner was designed and fabricated from stainless-steel substrate and piezoelectric sheets. Metal substrate with four cantilevers was bonded with eight piezoelectric sheets forming four bimorphs to enable two-axis scanning of the mirror. With a 5 mm × 5 mm square mirror, following scanning angles and frequencies were achieved at two orthogonal vibration modes: 35.2° at 861.5 Hz with a driving voltage of 100 Vp-p and 10.9° at 2485 Hz with a driving voltage of 200 Vp-p. The developed technique offers alternative to MEMS scanners providing scanning ability with large mirror size and scanning angles at middle frequency range. [ABSTRACT FROM AUTHOR]

A new design is presented to decrease the contact wear between a piezoelectric transformer and its heat transfer structure by inserting a layer of polypropylene membrane between them. Without significant degradation of performance, the wear problem is well suppressed with notable extension of working life. Compared with the former wear rate of 2.72% per day on the electrodes in the first 2.5 working days, the wear rate with polypropylene membrane is decreased to only 0.03% per day within an accumulated working time of 110 days. Moreover, with the insulating layer, structure design and package become more flexible as the metal electrodes and radiator are isolated. [ABSTRACT FROM AUTHOR]

We develop a novel approach to match harmonics and vibration modes based on the mechanism of multiple tuning fork structure (MTFS), through which it is promising to realize arbitrary periodical vibrations in the resonant state. A prototype three-layer MTFS with first three harmonics is presented to verify the feasibility of the proposed principle. The matching process and experimental results confirm the unique advantages of MTFS, as discussed in the theoretical analysis. Typical periodical motions, including sawtooth, square, half-wave rectified, and full-wave rectified waveforms, are achieved by the syntheses of resonant harmonics. [ABSTRACT FROM AUTHOR]

The construction of piezoelectric motors using multiple piezoelectric tubes is proposed in this paper. The static and dynamic characteristics of an eight-tube actuator are studied. The formulas of the bending deflection, moment, and resonant frequency are given. A prototype two-phase traveling wave piezoelectric motor using such a structure is studied. The stator that is composed of eight piezoelectric tubes produces a wobbling motion when excited in a certain pattern. Both the static and dynamic characteristics of the stator were measured. The rotor's angular speed possesses a good linearity with the driving voltage amplitude. With a driving voltage of 200 Vp–p at 5.0 kHz, the motor can rotate at the highest angular speed of 319 rpm and produce a maximum stall torque of 1.6 mN·m. With an applied voltage of 160 Vp–p and a preload of 0.3 N, the motor's working efficiency reached about 12%. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI), a severe outcome of cardiovascular disease, poses a serious threat to human health. Uncontrolled inflammation and excessive cardiomyocyte death, following an infarction event, significantly contribute to both the mortality rate and complications associated with MI. The protein IL-4-induced gene 1 (IL4I1 or FIG1) serves as a natural inhibitor of innate and adaptive immunity, playing a crucial role in CD4+ T cell differentiation, macrophage polarization, and ferroptosis inhibition. Previous studies have linked IL4I1 to acute MI. This review summarizes evidence from both basic and clinical research, highlighting IL4I1 as a critical immunoregulatory enzyme that not only regulates inflammatory responses, but also potentially mitigates MI-induced damage., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Background: Asthma is a common chronic disease among children, especially preschoolers. Some evidence suggests that diet may play a role in asthma, but the current findings are contradictory. The objective of our study was to determine the association between dietary intake and asthma in preschool children aged 2-5 years., Methods: We selected preschool children aged 2-5 years with complete data on asthma diagnosis, diet, and body mass index (BMI) from the national health and nutrition examination survey (NHANES) database. In a selected population, children with self-reported asthma were included in the final sample. In children without self-reported asthma, we further used propensity score matching (PSM) to match age and sex for sampling, maintaining a ratio of 1:4 for cases. Lasso regression was used to identify dietary factors affecting asthma in preschoolers., Results: A total of 269 children with self-reported asthma and 1,076 children without self-reported asthma were included in our study. Univariate analysis showed that there were significant differences in ethnicity and dietary zinc intake between asthmatic children and children without asthma. After adjusting for all dietary and demographic variables, the results of logistic Lasso regression analysis showed that non-Hispanic black (β = 0.65), vitamin B12 (β = 0.14), and sodium (β = 0.05) were positively associated with childhood asthma, while Vitamin K (β = -0.04) was negatively associated with childhood asthma., Conclusion: In conclusion, our study confirms that non-Hispanic black and dietary sodium intake are associated with a higher risk of asthma in preschoolers. In addition, our study found that dietary vitamin B12 was positively associated with childhood asthma, while vitamin K was negatively associated with childhood asthma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Qu, Pan, Guo and Wu.)

Purpose: This study aims to clarify the specific mechanism by which GARP affects the atherosclerotic plaques in ApoE -/- mice and the effect of GARP-tDC on atherosclerosis., Methods: The mice were randomly divided into three groups: the control group, the GARP-overexpressed group and the GARP-inhibited group. After 12 weeks, all the mice were euthanized, and the specimens were collected. In vitro, experiments were conducted to observe the effect of GARP on DC phenotype and the changes of the proportion of CD4 + CD25 + Foxp3 + Treg cells when GARP-tDCs were co-cultured with CD4 + T cells. Furthermore, adoptive transmission of GARP-tDCs was used to observe the effect on atherosclerotic plaque in mice., Results: The GARP-overexpressed group enhanced the biological activity of Foxp3 + CD4 + CD25 + Tregs and resulted in increased expression of LAP in T cells. In addition, the GARP-overexpressed group significantly suppressed the function of Th1 and Th17, and decreased the secretion of INF-γ and IL-17A. Thus, GARP had a protective effect on atherosclerosis. In vitro, we found that GARP-tDC had a tolerance-inducing phenotype, and GARP-tDC also had the ability to induce tolerance when co-cultured with CD4 + T cells. More importantly, adoptive transmission of GARP-tDCs reduced the size of atherosclerotic plaques., Conclusion: GARP and the GARP-tDC play protective roles in atherosclerosis. The protective effect of GARP on atherosclerosis is achieved by increasing CD4 + CD25 + Foxp3 + Treg cells and inhibiting the production of IFN-γ and IL-17A., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Cai et al.)

This paper presents a novel impact rotary motor based on a piezoelectric tube actuator with helical interdigitated electrodes which has a compact structure and high resolution. The assembled prototype motor has a maximum diameter of 15 mm and a length of 65 mm and works under a saw-shaped driving voltage. The LuGre friction model is adopted to analyze the rotary motion process of the motor in the dynamic simulations. From the experimental tests, the first torsional resonant frequency of the piezoelectric tube is 59.289 kHz with a free boundary condition. A series of experiments about the stepping characteristics of different driving voltages, duty cycles, and working frequencies are carried out by a laser Doppler vibrometer based on a fabricated prototype motor. The experimental results show that the prototype rotary motor can produce a maximum torsional angle of about 0.03&deg; using a driving voltage of 480 V p-p (peak-to-peak driving voltage) with a duty ratio of 0% under a small friction force of about 0.1 N. The motor can produce a maximum average angle of about 2.55 rad/s and a stall torque of 0.4 mN∙m at 8 kHz using a driving voltage of 640 V p-p with a duty ratio of 0% under a large friction force of about 3.6 N. The prototype can be driven in forward and backward motion and is working in stick-slip mode at low frequencies and slip-slip mode at high frequencies.

Piezoelectric tubes with film electrodes on their outer and inner surfaces can be used to compose multitube actuators. The actuator of four piezoelectric tubes can substitute the traditional single-tube actuator with quartered electrodes which has been widely used in scanning probe microscopy and piezoelectric motors. In this article, the static deflection, static bending moment, resonant frequency, and dynamic deflection of the four-tube actuator are all studied in detail. The comparison between this actuator and the traditional single-tube actuator is also done and the results show that the four-tube actuator has better performances under certain conditions. The experiment results of a prototype actuator testified the validation of the analysis.