Stenus-inspired, swift, and agile untethered insect-scale soft propulsors.

Mimicking living creatures, soft robots exhibit incomparable adaptability and various attractive new features. However, untethered insect-scale soft robots are often plagued with inferior controllability and low kinetic performance. Systematically inspired by the swift swingable abdomen, conducting canals for secretion transport, and body setae of Stenus comma, together with magnetic-induced fast-transformed postures, herein, we present a swift, agile untethered millimetre-scale soft propulsor propelling on water. The demonstrated propulsor, with a body length (BL) of 3.6 mm, achieved a recorded specific speed of ~201 BL/s and acceleration of ~8,372 BL/s2. The comprehensive kinetic performance of this propulsor surpasses those of previous ones at similar scales by several orders. Notably, we discovered momentum-transfer-induced over-biological on-demand braking (deceleration ~-5,010 BL/s2) and elucidated the underlying hydrodynamics. This work offers new insights into systematically bio-inspired artificial insect-scale soft robots, enabling them to push boundaries in performance, and potentially revolutionizing robot design, optimization, and control paradigms.

Synergistical Mechanical Design and Function Integration for Insect-Scale On-Demand Configurable Multifunctional Soft Magnetic Robots.

Meso- or micro-scale(or insect-scale) robots that are capable of realizing flexible locomotion and/or carrying on complex tasks in a remotely controllable manner hold great promise in diverse fields, such as biomedical applications, unknown environment exploration, in situ operation in confined spaces, and so on. However, the existing design and implementation approaches for such multifunctional, on-demand configurable insect-scale robots are often focusing on their actuation or locomotion, while matched design and implementation with synergistic actuation and function modules under large deformation targeting varying task/target demands are rarely investigated. In this study, through systematical investigations on synergistical mechanical design and function integration, we developed a matched design and implementation method for constructing multifunctional, on-demand configurable insect-scale soft magnetic robots. Based on such a method, we report a simple approach to construct soft magnetic robots by assembling various modules from the standard part library together. Moreover, diverse soft magnetic robots with desirable motion and function can be (re)configured. Finally, we demonstrated (re)configurable soft magnetic robots shifting into different modes to adapt and respond to varying scenarios. The customizable physical realization of complex soft robots with desirable actuation and diverse functions can pave a new way for constructing more sophisticated insect-scale soft machines that can be applied to practical applications soon.

Systematic review of leadless pacemaker.

Conventional pacing systems consist of a pacemaker and one or more leads threaded from the device pocket through veins into the heart conducting the pacing therapy to the desired pacing site. Although these devices are effective, approximately one in eight patients treated with these traditional pacing systems experiences a complication attributed to the pacemaker pocket or leads. With the technological advances in electronics, leadless pacemakers that small enough to implant within the heart were introduced. Leadless pacemakers have been developed to overcome many of the challenges of transvenous pacing including complications related to leads or pacemaker pockets. This review aims to provide an overview of advantages of leadless pacemaker, complications and limitations of leadless pacemaker, leadless pacemaker candidate, and future directions of this promising technology.

Knockdown of Herp alleviates hyperhomocysteinemia mediated atherosclerosis through the inhibition of vascular smooth muscle cell phenotype switching.

BACKGROUND: Phenotypic switching of vascular smooth muscle cells (VSMCs) plays a key role in atherosclerosis. We aimed to investigate whether Homocysteine-responsive endoplasmic reticulum protein (Herp) was involved in VSMC phenotypic switching and affected atheroprogression. METHODS: To assess the role of Herp in homocysteine (Hcy)-associated atherosclerosis, Herp-/- and LDLR-/- double knockout mice were generated and fed with a high methionine diet (HMD) to induce Hyperhomocysteinemia (HHcy). Atherosclerotic lesions, cholesterol homeostasis, endoplasmic reticulum (ER) stress activation, and the phenotype of VSMCs were assessed in vivo. We used siRNAs to knockdown Herp in cultured VSMCs to further validate our findings in vitro. RESULTS: HMD significantly activated the activating transcription factor 6 (ATF6)/Herp arm of ER stress in LDLR-/- mice, and induced the phenotypic switch of VSMCs, with the loss of contractile proteins (SMA and calponin) and an increase of OPN protein. Herp-/-/LDLR-/- mice developed reduced atherosclerotic lesions in the aortic sinus and the whole aorta when compared with LDLR-/- mice. However, Herp deficiency had no effect on diet-induced HHcy and hyperlipidemia. Inhibition of VSMC phenotypic switching, decreased proliferation and collagen accumulation were observed in Herp-/-/LDLR-/- mice when compared with LDLR-/- mice. In vitro experiments demonstrated that Hcy caused VSMC phenotypic switching, promoted cell proliferation and migration; this was reversed by Herp depletion. We achieved similar results via inhibition of ER stress using 4-phenylbutyric-acid (4-PBA) in Hcy-treated VSMCs. CONCLUSION: Herp deficiency inhibits the phenotypic switch of VSMCs and the development of atherosclerosis, thus providing novel insights into the role of Herp in atherogenesis.

Hyperhomocysteinemia independently causes and promotes atherosclerosis in LDL receptor-deficient mice.

BACKGROUND: Hyperhomocysteine is an independent risk factor of coronary heart disease (CHD). However, whether hyperhomocysteine affects the progression of atherosclerosis is unclear. In the present study, we examined the effect of hyperhomocysteine on the formation of atherosclerosis in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice. METHODS: Forty-eight 7-week-old LDLr(-/-) mice were assigned to the following groups: mice fed a standard rodent diet (control group), mice fed a high-methionine diet (high-methionine group), mice fed a high-fat diet (high-fat group), and mice fed a diet high in both methionine and fat (high-methionine and high-fat group). At the age of 19, 23, and 27 weeks, four mice at each interval in every group were sacrificed. RESULTS: At the end of the study, mice did not show atherosclerotic lesions in the aortic sinus and aortic surface until 27 weeks old in the control group. However, atherosclerotic lesions developed in the other three groups at 19 weeks. The amount of atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions on the aortic surface in the high-methionine and high-fat group were the most severe. The mean area of atherosclerotic lesions in the aortic sinus compared with atherosclerotic lesions on the aortic surface was lower in the high-methionine group than in the high-fat group (P < 0.001). Atherosclerotic lesions in the aortic sinus in the high-methionine and high-fat group were the most severe. CONCLUSIONS: Homocysteinemia accelerates atherosclerotic lesions and induces early atherosclerosis independently in LDLr(-/-) mice. Reducing the level of homocysteinemia may be beneficial for prevention and treatment of CHD.

Effects of rosuvastatin on the production and activation of matrix metalloproteinase-2 and migration of cultured rat vascular smooth muscle cells induced by homocysteine.

OBJECTIVE: To test the influence of homocysteine on the production and activation of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of matrix metalloproteinase-2 (TIMP-2) and on cell migration of cultured rat vascular smooth muscle cells (VSMCs). Also, to explore whether rosuvastatin can alter the abnormal secretion and activation of MMP-2 and TIMP-2 and migration of VSMCs induced by homocysteine. METHODS: Rat VSMCs were incubated with different concentrations of homocysteine (50-5000 µmol/L). Western blotting and gelatin zymography were used to investigate the expressions and activities of MMP-2 and TIMP-2 in VSMCs in culture medium when induced with homocysteine for 24, 48, and 72 h. Transwell chambers were employed to test the migratory ability of VSMCs when incubated with homocysteine for 48 h. Different concentrations of rosuvastatin (10(-9)-10(-5) mol/L) were added when VSMCs were induced with 1000 µmol/L homocysteine. The expressions and activities of MMP-2 and TIMP-2 were examined after incubating for 24, 48, and 72 h, and the migration of VSMCs was also examined after incubating for 48 h. RESULTS: Homocysteine (50-1000 µmol/L) increased the production and activation of MMP-2 and expression of TIMP-2 in a dose-dependent manner. However, when incubated with 5000 µmol/L homocysteine, the expression of MMP-2 was up-regulated, but its activity was down-regulated. Increased homocysteine-induced production and activation of MMP-2 were reduced by rosuvastatin in a dose-dependent manner whereas secretion of TIMP-2 was not significantly altered by rosuvastatin. Homocysteine (50-5000 µmol/L) stimulated the migration of VSMCs in a dose-dependent manner, but this effect was eliminated by rosuvastatin. CONCLUSIONS: Homocysteine (50-1000 µmol/L) significantly increased the production and activation of MMP-2, the expression of TIMP-2, and the migration of VSMCs in a dose-dependent manner. Additional extracellular rosuvastatin can decrease the excessive expression and activation of MMP-2 and abnormal migration of VSMCs induced by homocysteine.

Rosuvastatin may modulate insulin signaling and inhibit atherogenesis beyond its plasma cholesterol-lowering effect in insulin-resistant mice.

OBJECTIVES: To provide evidence that rosuvastatin may improve insulin-resistance and inhibit atherogenesis by modulating insulin signaling, and whether this effect occurs beyond its plasma cholesterol-lowering effect. METHODS: Thirty-two 6-week-old low-density lipoprotein receptor deficient mice were randomized into 4 groups (n = 8 in each group): Normal control group (NC); High fat and high fructose diet group (HFF); HFF plus rosuvastatin group (HFFR); HFFR plus mevalonic acid group (HFFRMA). After 12 weeks, we measured fasting blood sugar, fasting insulin and cholesterol levels; the morphological concentrations of the aorta and aortic sinus; the expression of insulin receptor substrate 2, phosphorylated insulin receptor substrate 2, protein kinase B, phosphorylated protein kinase B and the glucose transporter 4 in the liver. RESULTS: Compared with other groups, fasting blood sugar and fasting insulin increased significantly in HFF group. Furthermore, HFF group had an increase in the morphological concentrations of the aorta and aortic sinus, but there was a significant decrease in the HFFRMA group and the HFFR group. Moreover, there was a high expression of insulin receptor substrate 2, phosphorylated insulin receptor substrate 2, protein kinase B, phosphorylated protein kinase B and the glucose transporter 4 in the HFFRMA and HFFR groups, but a low expression in the HFF group. No significant differences regarding each afore-mentioned index was observed in the HFFR and HFFRMA groups. CONCLUSIONS: Our data show that rosuvastatin may improve insulin-resistance and inhibit atherogenesis in HFF-fed mice by partially reversing the decrease in the insulin stimulated insulin receptor substrate 2/Phosphatidylinositol 3-kinase/protein kinase B/glucose transporter 4 pathway in the liver, and that this effect is independent of its cholesterol-lowering effect.

A case of delayed cardiac perforation of active ventricular lead.

A 65-year-old man was admitted as for one month of repetitive dizziness and one episode of syncope. Electrocardiogram showed sinus bradycardia and his Holter monitoring also showed sinus bradycardia with sinus arrest, sino-atrial block and a longest pause of 4.3 s. Then sick sinus syndrome and Adam-Stokes syndrome were diagnosed. Then a dual chamber pacemaker (Medtronic SDR303) was implanted and the parameters were normal by detection. The patient was discharged 1 week later with suture removed. Then 1.5 month late the patient was presented to hospital once again for sudden onset of chest pain with exacerbation after taking deep breath. Pacemaker programming showed both pacing and sensing abnormality with threshold of > 5.0V and resistance of 1200Ω. Lead perforation was revealed by chest X-ray and confirmed by echocardiogram. Considering the fact that there was high risk to remove ventricular lead, spiral tip of previous ventricular lead was withdrew followed by implantation of a new ventricular active lead to the septum. Previous ventricular lead was maintained. As we know that the complications of lead perforation in the clinic was rare. Here we discuss the clinical management and the possible reasons for cardiac perforation of active ventricular lead.

Chinese yellow wine and red wine inhibit matrix metalloproteinase-2 and improve atherosclerotic plaque in LDL receptor knockout mice.

Our previous study found that Chinese yellow wine could inhibit the production of homocysteine (HCY) induced extracellular matrix metalloproteinase-2 (MMP-2) in the cultured rat vascular smooth muscle cells. Little is known about the relationship between Chinese yellow wine and atherosclerosis or MMP-2 in vivo. Thirty-two LDL Receptor knockout mice on a high-fat and L-methionine diet developed plasma hyperhomocysteinemia and atherosclerosis. They were randomly divided into yellow wine group (n = 8), red wine group (n = 8), ethanol group (n = 8), and control group (n = 8), they were sacrificed after 14 weeks. There were no significant differences with plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in the four groups. Plasma HCY was significantly decreased in the yellow wine group compared to the other three groups (P < 0.01). Yellow wine and red wine groups significantly reduced the atherosclerosis lesion area compared to ethanol and control groups (P < 0.001). However, there was no significant discrepancy between the yellow wine group and red wine group. Compared to the control group and ethanol group, the production of MMP-2 reduced 26.8% and 23.6% in the aortic sinus and the activation of MMP-2 reduced 32.6% and 27.3% in the aortic arch in the yellow wine group; the production of MMP-2 reduced 25.7% and 22.4% in the aortic sinus and the activation of MMP-2 reduced 30.2% and 26.6% in the aortic arch in the red wine group. These results suggest that Chinese yellow wine and red wine can inhibit MMP-2 and improve atherosclerosis, and maybe both Chinese yellow wine and red wine have beneficial effects on cardiovascular disease by inhibiting MMP-2.

Heparin inhibits the production of matrix metalloproteinase-2 and improves atherosclerosis in LDL receptor-deficient mice.

OBJECTIVE: This study aimed to find the effects of heparin on atherosclerosis and the production of matrix metalloproteinase (MMP)-2 in low-density lipoprotein receptor-deficient (LDLr(-/-)) mice. METHODS: Sixteen 7-week-old LDLr(-/-) mice were randomized to receive sterile water or heparin. The levels of total cholesterol, high-density lipoprotein cholesterol, triglyceride and homocysteine were measured. Mean lesions area was calculated as the total atherosclerotic lesions area and expressed as a percentage of total luminal surface area. The lesions area was measured blindly by the same person using computer-assisted image analysis. The expression and localization of the MMP-2 was examined by immunohistochemistry. RESULTS: All mice exhibited atherosclerotic lesions in the aortic sinus and aortic surface. Total cholesterol was decreased, while high-density lipoprotein cholesterol was increased in heparin compared with that in control group (P=0.001 and 0.002). Triglyceride was not significantly different between the two groups (P=0.92). The amount of atherosclerotic lesions in the aortic surface was 40.5% lower in heparin group than that in the control group (P<0.001). The mean area of atherosclerotic lesions in the aortic sinus was also less in the heparin group than that in the control group. Coincidently, the expression of MMP-2 in the atherosclerotic lesions in the heparin group was 49.3% lower than that in the control group (P<0.001). CONCLUSION: Heparin can inhibit the production of MMP-2 in the atherosclerotic lesions and improve the atherosclerotic lesions in LDLr(-/-) mice.

Rosuvastatin inhibits MMP-2 expression and limits the progression of atherosclerosis in LDLR-deficient mice.

BACKGROUND AND AIMS: Statins have been shown to reduce morbidity and mortality of coronary heart disease (CHD). Matrix metalloproteinases (MMPs) have been found to be involved in atherosclerotic plaque growth and instability. Rosuvastatin may inhibit the secretion of MMP-2 and MMP-9 from vascular smooth muscle cells and macrophages in vitro. The present study investigated the effects of rosuvastatin on the progression of atherosclerosis and the expression of MMP-2/-9 in LDLR-deficient mice. METHODS: LDLR-deficient mice were included in rosuvastatin group and control group on a high-fat and high-cholesterol diet. After 12 weeks, we randomly sacrificed and examined the atherosclerotic lesion area in aortic artery and aortic sinus and levels of plasma lipid, glucose and insulin and expression of MMP-2 and MMP-9 in the atherosclerotic plaques. RESULTS: Atherosclerotic lesion area was significantly decreased in rosuvastatin group vs. control group. Meanwhile, levels of plasma total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and oxidized (ox)LDL in the rosuvastatin group were decreased as well as MMP-2 and MMP-9 expression in aortic arch with gelatin zymography and the production of MMP-2 in the aortic sinus through immunohistochemical methods. Levels of plasma high-density lipoprotein cholesterol (HDL-C), glucose and insulin were also decreased in rosuvastatin group but failed to achieve statistical significance compared with control group. Interestingly, we found that the value of HDL-C/TC ratio was increased in rosuvastatin group. CONCLUSIONS: Rosuvastatin inhibits the expression of MMP-2/-9 and limits the progression of atherosclerosis in LDLR-deficient mice. This may be one of the pathways of rosuvastatin on atherosclerosis through which rosuvastatin induced its benefit to the therapy of coronary heart disease (CHD).