Cardiovascular diseases are the leading cause of death globally; fortunately, 90% of cardiovascular diseases are preventable by long-term monitoring of physiological signals. Stable, ultralow power consumption, and high-sensitivity sensors are significant for miniaturized wearable physiological signal monitoring systems. Here, this study proposes a flexible self-powered ultrasensitive pulse sensor (SUPS) based on triboelectric active sensor with excellent output performance (1.52 V), high peak signal-noise ratio (45 dB), long-term performance (10 cycles), and low cost price. Attributed to the crucial features of acquiring easy-processed pulse waveform, which is consistent with second derivative of signal from conventional pulse sensor, SUPS can be integrated with a bluetooth chip to provide accurate, wireless, and real-time monitoring of pulse signals of cardiovascular system on a smart phone/PC. Antidiastole of coronary heart disease, atrial septal defect, and atrial fibrillation are made, and the arrhythmia (atrial fibrillation) is indicative diagnosed from health, by characteristic exponent analysis of pulse signals accessed from volunteer patients. This SUPS is expected to be applied in self-powered, wearable intelligent mobile diagnosis of cardiovascular disease in the future.

Objective Sphingomyelin synthase (SMS) catalyzes the conversion of ceramide to sphingomyelin (SM), and sits at the crossroads of sphingolipid biosynthesis. SMS has two isoforms: SMS1 and SMS2. Although they have the same SMS activity, they are different enzymes with distinguishable subcellular localizations and cell expression patterns. It is conceivable that these differences could yield different consequences, in terms of sphingolipid metabolism and its related atherogenesis. Methods and Results we created Sms1 gene knockout (KO) mice and found that Sms1 deficiency significantly decreased plasma, liver, and macrophage SM (59%, 45%, and 54%, respectively), but had only a marginal effect on ceramide levels. Surprisingly, we found that Sms1 deficiency dramatically increased glucosylceramide and GM3 levels in plasma, liver, and macrophages (4 to 12 fold), while Sms2 deficiency had no such effect. We evaluated total SMS activity in tissues and found that Sms1 deficiency causes 77% reduction of SMS activity, indicating SMS1 is the major SMS in macrophages. Moreover, Sms1 deficient-macrophages have significantly higher glucosylceramide synthase activity. We also found that Sms1 deficiency significantly attenuated toll-like 4 receptor-mediated NF-κB and MAP kinase activation after LPS treatment. To evaluate atherogenicity, we transplanted Sms1 KO mouse bone marrow into LDL receptor KO mice (Sms1−/−→Ldlr−/−). After 3 months on a Western diet, these animals showed a significant decrease of atherosclerotic lesions in the root and the entire aorta (35% and 44%, P<0.01, respectively), and macrophage content in lesions (51%, P<0.05), compared with WT→Ldlr−/−) mice. Conclusions Sms1 deficiency decreases SM, but dramatically increases the levels of glycosphingolipids. Atherosclerosis in Sms1−/−→Ldlr−/− mice is significantly decreased.

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Sphingomyelin (SM) is one of the major lipid components of plasma lipoproteins. Serine palmitoyltransferase (SPT) is the key enzyme in SM biosynthesis. Mice totally lacking in SPT are embryonic lethal. The liver is the major site for plasma lipoprotein biosynthesis, secretion, and degradation, and in this study we utilized a liver-specific knock-out approach for evaluating liver SPT activity and also its role in plasma SM and lipoprotein metabolism. We found that a deficiency of liver-specific Sptlc2 (a subunit of SPT) decreased liver SPT protein mass and activity by 95 and 92%, respectively, but had no effect on other tissues. Liver Sptlc2 deficiency decreased plasma SM levels (in both high density lipoprotein and non-high density lipoprotein fractions) by 36 and 35% (p < 0.01), respectively, and increased phosphatidylcholine levels by 19% (p < 0.05), thus increasing the phosphatidylcholine/SM ratio by 77% (p < 0.001), compared with controls. This deficiency also decreased SM levels in the liver by 38% (p < 0.01) and in the hepatocyte plasma membranes (based on a lysenin-mediated cell lysis assay). Liver-specific Sptlc2 deficiency significantly increased hepatocyte apoE secretion and thus increased plasma apoE levels 3.5-fold (p < 0.0001). Furthermore, plasma from Sptlc2 knock-out mice had a significantly stronger potential for promoting cholesterol efflux from macrophages than from wild-type mice (p < 0.01) because of a greater amount of apoE in the circulation. As a result of these findings, we believe that the ability to control liver SPT activity could result in regulation of lipoprotein metabolism and might have an impact on the development of atherosclerosis. Sphingomyelin (SM),2 an amphipathic phospholipid located in the surface monolayer of all classes of plasma lipoproteins (LDL/very low density lipoprotein, 70 -75%; HDL, 25-30%) (1), has significant effects on lipoprotein metabolism.A number of studies indicate that plasma SM levels influence the metabolism of apoB-containing lipoproteins. It has been reported that SM, but not cholesterol, significantly inhibits triglyceride lipolysis by lipoprotein lipase (2, 3). It has also been found that SM in lipoproteins delays remnant clearance by decreasing the binding of apoE to cell membrane receptors (4).Plasma SM levels also influence high density lipoprotein (HDL) metabolism. There have been reports that SM affects the structure of discoidal and spherical HDL (5). SM can inhibit lecithin-cholesterol acyltransferase by decreasing its binding to HDL (6). A negative correlation between the SM content of HDL and lecithin-cholesterol acyltransferase activity was observed in studies with proteoliposomes or reconstituted HDL (7). SM-rich recombinant HDL can inhibit scavenger receptor class B type I-mediated cholesterol ester-selective uptake in HepG2 cells (8).It is known that subendothelial retention and aggregation of atherogenic lipoproteins play an important role in atherogenesis (9). LDL extracted from human atherosclerotic lesions is highly enriched in SM ...

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Objective The sphingolipid de novo synthesis pathway is considered a promising target for pharmacological intervention in atherosclerosis. However, its potential is hampered by the fact that the substance’s atherogenic mechanism is not completely understood. To unravel the complex mechanisms, we utilized the sphingomyelin synthase 2 (Sms2) gene knockout approach to test our hypothesis that selectively decreasing plasma lipoprotein SM, can play an important role in preventing atherosclerosis. Methods and Results We prepared Sms2 and Apoe double knockout (KO) mice. They showed a significant decrease in plasma lipoprotein SM levels (35%, P<0.01) and a significant increase in ceramide and dihydroceramide levels (87.5 and 27%, P<0.01, respectively), but no significant changes in other tested sphingolipids, cholesterol, and triglyceride. Non-HDL lipoproteins from the double KO mice showed a reduction of SM but not cholesterol and displayed a less tendency toward aortic sphingomyelinase-mediated lipoprotein aggregation in vitro and retention in aortas in vivo, compared to controls. More important, at age 19 weeks, Sms2 KO/Apoe KO mice showed a significant reduction in atherosclerotic lesions of the aortic arch and root (52%, P<0.01), compared to controls. We also found that the Sms2 KO/Apoe KO brachiocephalic artery (BCA) contained significantly less SM, ceramide, free cholesterol, and cholesteryl ester (35, 32, 58, and 60%, P<0.01, respectively), than that of Apoe KO BCA. Conclusions Decreasing plasma SM levels through decreasing SMS2 activity could become a promising treatment for atherosclerosis.

In this review, we discuss the recent development of near-infrared photoacoustic probes based on small molecule dyes, which focus on their “always on” and “activatable” form in biomedicine.

Toluene and its derivatives are petroleum-derived raw materials produced from gasoline by catalytic reformation. These abundant chemical feedstocks are commonly used as solvents in organic synthesis. The C(sp 3 )−H functionalization of these unactivated substrates has been widely used to directly introduce benzylic motifs into diverse molecules to furnish important compounds. Despite these advances, progress in asymmetric catalysis remains underdeveloped. Here, we report photoinduced radical-based enantioselective C(sp 3 )−C(sp 3 ) coupling reactions of activated ketones with toluene and its derivatives by means of chiral acid catalysis. With a La(OTf) 3 /pybox complex catalyst, a variety of chiral 3-hydroxy-3-benzyl-substituted 2-oxindoles, including many conventionally difficult-to-access variants, are obtained directly from isatins in high yields with good to excellent enantioselectivities. Acenaphthoquinone is also compatible with the use of a chiral phosphoric acid (CPA) catalyst, leading to another series of important enantioenriched tertiary alcohols.