Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events in humans with type 2 diabetes (T2D); however, the underlying mechanism remains unclear. Activation of the NLR family, ...pyrin domain-containing 3 (NLRP3) inflammasome and subsequent interleukin (IL)-1β release induces atherosclerosis and heart failure. Here we show the effect of SGLT2 inhibitor empagliflozin on NLRP3 inflammasome activity. Patients with T2D and high cardiovascular risk receive SGLT2 inhibitor or sulfonylurea for 30 days, with NLRP3 inflammasome activation analyzed in macrophages. While the SGLT2 inhibitor's glucose-lowering capacity is similar to sulfonylurea, it shows a greater reduction in IL-1β secretion compared to sulfonylurea accompanied by increased serum β-hydroxybutyrate (BHB) and decreased serum insulin. Ex vivo experiments with macrophages verify the inhibitory effects of high BHB and low insulin levels on NLRP3 inflammasome activation. In conclusion, SGLT2 inhibitor attenuates NLRP3 inflammasome activation, which might help to explain its cardioprotective effects.
Dopamine is a key molecule in neurotransmission and has been known to be responsible for several neurological diseases. Hence, its sensitive and selective detection is important for the early ...diagnosis of diseases related to abnormal levels of dopamine. In this study, we reported a new cylindrical gold nanoelectrode (CAuNE) platform fabricated via sequential laser interference lithography and electrochemical deposition. Among the fabricated electrodes, CAuNEs with a diameter of 700 nm, 150 s deposited, was found to be the best for electrochemical dopamine detection. According to cyclic voltammetry results, the linear range of the CAuNE-700 nm was 1-100 µM of dopamine with a limit of detection (LOD) of 5.83 µM. Moreover, owing to the homogeneous periodic features of CAuNEs, human neural cells were successfully cultured and maintained for more than 5 days in vitro without the use of any extracellular matrix proteins and dopamine was detectable in the presence of these cells on the electrode. Therefore, we concluded that the developed dopamine sensing platform CAuNE can be used for many applications including early diagnosis of neurological diseases; function tests of dopaminergic neurons derived from various stem cell sources; and toxicity assessments of drugs, chemicals, and nanomaterials on human neuronal cells.
A high‐performance, transparent, and extremely thin (<15 nm) hydrogen (H2) gas sensor is developed using 2D electron gas (2DEG) at the interface of an Al2O3/TiO2 thin film heterostructure grown by ...atomic layer deposition (ALD), without using an epitaxial layer or a single crystalline substrate. Palladium nanoparticles (≈2 nm in thickness) are used on the surface of the Al2O3/TiO2 thin film heterostructure to detect H2. This extremely thin gas sensor can be fabricated on general substrates such as a quartz, enabling its practical application. Interestingly, the electron density of the Al2O3/TiO2 thin film heterostructure can be tailored using ALD process temperature in contrast to 2DEG at the epitaxial interfaces of the oxide heterostructures such as LaAlO3/SrTiO3. This tunability provides the optimal electron density for H2 detection. The Pd/Al2O3/TiO2 sensor detects H2 gas quickly with a short response time of <30 s at 300 K which outperforms conventional H2 gas sensors, indicating that heating modules are not required for the rapid detection of H2. A wide bandgap (>3.2 eV) with the extremely thin film thickness allows for a transparent sensor (transmittance of 83% in the visible spectrum) and this fabrication scheme enables the development of flexible gas sensors.
A high‐performance, transparent, and extremely thin (≈15 nm) hydrogen (H2) gas sensor is developed using 2D electron gas at the interface of an Al2O3/TiO2 thin film heterostructure. This extremely thin gas sensor can be fabricated on general substrates such as a glass using atomic layer deposition, and this fabrication scheme enables the development of flexible gas sensors.
Sarcopenia is associated with nonalcoholic fatty liver disease (NAFLD). This study investigated whether sarcopenia is associated with significant liver fibrosis in subjects with NAFLD. Data from the ...Korean National Health and Nutrition Examination Surveys 2008‐2011 database were analyzed. NALFD was defined by NAFLD liver fat score, comprehensive NAFLD score, or hepatic steatosis index. Degree of liver fibrosis was assessed by NAFLD fibrosis score (NFS), FIB‐4, and Forns index. Significant liver fibrosis was defined as FIB‐4 ≥2.67 and the highest quartile values of NFS and Forns index. Sarcopenia index (= total appendicular skeletal muscle mass kg/body mass index (kg/m2) was calculated using dual‐energy X‐ray absorptiometry. Using the NAFLD liver fat score, NAFLD was identified in 2761 (28.5%) of 9676 subjects. Of subjects with NAFLD, sarcopenia was identified in 337 (12.2%). Sarcopenia was significantly associated with significant liver fibrosis assessed in fibrosis prediction models (all P < 0.05). In subgroups stratified according to body mass index and homeostasis model assessment of insulin resistance, a significant association between sarcopenia and significant liver fibrosis by NFS was consistently present (odds ratio = 1.76‐2.68 depending on the subgroup, all P < 0.05). Multivariate logistic regression analysis demonstrated an independent association between SI and significant liver fibrosis by NFS after adjusting for other confounders (odds ratio = 0.52‐0.67, all P < 0.01). Other NAFLD (comprehensive NAFLD score, hepatic steatosis index) and fibrosis prediction models (FIB‐4 and Forns index) produced similar results. Conclusion: Sarcopenia is associated with significant liver fibrosis in subjects with NAFLD, and the association is independent of obesity and insulin resistance. (Hepatology 2016;63:776–786)
Abstract
Recent advances in nanomaterials and nano-microfabrication have enabled the development of flexible wearable electronics. However, existing manufacturing methods still rely on a multi-step, ...error-prone complex process that requires a costly cleanroom facility. Here, we report a new class of additive nanomanufacturing of functional materials that enables a wireless, multilayered, seamlessly interconnected, and flexible hybrid electronic system. All-printed electronics, incorporating machine learning, offers multi-class and versatile human-machine interfaces. One of the key technological advancements is the use of a functionalized conductive graphene with enhanced biocompatibility, anti-oxidation, and solderability, which allows a wireless flexible circuit. The high-aspect ratio graphene offers gel-free, high-fidelity recording of muscle activities. The performance of the printed electronics is demonstrated by using real-time control of external systems via electromyograms. Anatomical study with deep learning-embedded electrophysiology mapping allows for an optimal selection of three channels to capture all finger motions with an accuracy of about 99% for seven classes.
Additional surgeries for implantable biomedical devices are inevitable to replace discharged batteries, but repeated surgeries can be a risk to patients, causing bleeding, inflammation, and ...infection. Therefore, developing self‐powered implantable devices is essential to reduce the patient's physical/psychological pain and financial burden. Although wireless communication plays a critical role in implantable biomedical devices that contain the function of data transmitting, it has never been integrated with in vivo piezoelectric self‐powered system due to its high‐level power consumption (microwatt‐scale). Here, wireless communication, which is essential for a ubiquitous healthcare system, is successfully driven with in vivo energy harvesting enabled by high‐performance single‐crystalline (1 − x)Pb(Mg1/3Nb2/3)O3−(x)Pb(Zr,Ti)O3 (PMN‐PZT). The PMN‐PZT energy harvester generates an open‐circuit voltage of 17.8 V and a short‐circuit current of 1.74 µA from porcine heartbeats, which are greater by a factor of 4.45 and 17.5 than those of previously reported in vivo piezoelectric energy harvesting. The energy harvester exhibits excellent biocompatibility, which implies the possibility for applying the device to biomedical applications.
In vivo self‐powered wireless transmission using a flexible single‐crystalline piezoelectric energy harvester is demonstrated. The high‐performance energy harvester generates an output voltage of 17.8 V and a current of 1.75 µA from the contraction and relaxation motion of porcine heart. The energy from in vivo physiological motion enables self‐powered wireless transmission, thus realizing practical application in the ubiquitous healthcare system.
Abstract The antimicrobial effects of silver (Ag) ion or salts are well known, but the effects of Ag nanoparticles on microorganisms and antimicrobial mechanism have not been revealed clearly. Stable ...Ag nanoparticles were prepared and their shape and size distribution characterized by particle characterizer and transmission electron microscopic study. The antimicrobial activity of Ag nanoparticles was investigated against yeast, Escherichia coli , and Staphylococcus aureus . In these tests, Muller Hinton agar plates were used and Ag nanoparticles of various concentrations were supplemented in liquid systems. As results, yeast and E. coli were inhibited at the low concentration of Ag nanoparticles, whereas the growth-inhibitory effects on S. aureus were mild. The free-radical generation effect of Ag nanoparticles on microbial growth inhibition was investigated by electron spin resonance spectroscopy. These results suggest that Ag nanoparticles can be used as effective growth inhibitors in various microorganisms, making them applicable to diverse medical devices and antimicrobial control systems.
Astrocytes are complex glial cells with numerous fine cellular processes that infiltrate the neuropil and interact with synapses. The mechanisms that control the establishment of astrocyte morphology ...are unknown, and it is unclear whether impairing astrocytic infiltration of the neuropil alters synaptic connectivity. Here we show that astrocyte morphogenesis in the mouse cortex depends on direct contact with neuronal processes and occurs in parallel with the growth and activity of synaptic circuits. The neuroligin family cell adhesion proteins NL1, NL2, and NL3, which are expressed by cortical astrocytes, control astrocyte morphogenesis through interactions with neuronal neurexins. Furthermore, in the absence of astrocytic NL2, the formation and function of cortical excitatory synapses are diminished, whereas inhibitory synaptic function is enhanced. Our findings highlight a previously undescribed mechanism of action for neuroligins and link astrocyte morphogenesis to synaptogenesis. Because neuroligin mutations have been implicated in various neurological disorders, these findings also point towards an astrocyte-based mechanism of neural pathology.
Background and Aims
Cardiovascular disease (CVD) is the main cause of mortality in subjects with non‐alcoholic fatty liver disease (NAFLD). We investigated the association between CVD risk and ...metabolic dysfunction‐associated fatty liver disease (MAFLD) or NAFLD and the influence of significant liver fibrosis on the CVD risk.
Methods
Subjects who underwent a comprehensive medical check‐up were recruited (2014–2019). Significant liver fibrosis was defined using NAFLD fibrosis score, fibrosis‐4 index, aspartate aminotransferase to platelet ratio index, or FibroScan‐aspartate aminotransferase score. High probability of atherosclerotic CVD (ASCVD) was defined as ASCVD risk score > 10%.
Results
Of the study population (n = 78 762), 27 047 (34.3%) and 24 036 (30.5%) subjects had MAFLD and NAFLD respectively. A total of 1084 (4.0%) or 921 (3.8%) subjects had previous CVD history in MAFLD or NAFLD subgroup respectively. The previous CVD history and high probability of ASCVD were significantly higher in MAFLD or NAFLD subgroup with significant liver fibrosis than in the other groups (all p < .001). In multivariable analysis, MAFLD was independently associated with previous CVD history after adjusting for confounders (adjusted odds ratio aOR = 1.10, p = .038), whereas NAFLD was not (all p > .05). MAFLD (aOR = 1.40) or NAFLD (aOR = 1.22) was independently associated with high probability of ASCVD after full adjustment respectively (all p < .001). Significant liver fibrosis was independently associated with previous CVD history and high probability of ASCVD after adjustment in MAFLD or NAFLD subgroup respectively (all p < .05).
Conclusion
MAFLD might better identify subjects with CVD risk than NAFLD. Fibrosis assessment might be helpful for detailed prognostication in subjects with MAFLD.
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•Highly porous SnO2-CuO nanocomposite hollow nanofibers were synthesized for use as a high-performance H2S gas sensor.•SnO2-CuO nanotubes were formed by electrospinning with mixed ...solutions by the Kirkendall effect.•CuO nanoparticles were homogeneously distributed within a SnO2 tubular shape.•A high response of 1395 (Ra/Rg) and a very fast response time of 5.27 s toward 5 ppm H2S gas at 200 °C.•These materials are highly promising candidates for gas sensing due to increased surface area and p-n junctions.
Highly porous SnO2-CuO hollow nanofiber mats were synthesized by electrospinning combined with thermal processing for high performance H2S gas sensing applications. The porous morphology generated in the one-dimensional (1-D) nanocomposite led to an improvement in surface-to-adsorbate molecule interactions. Our novel concept lies in fabrication of SnO2-CuO with a 1-D highly porous structure by electrospinning coupled with generation of hollow nanostructures drawing on nanofiber-to-nanotube transformation affected by Kirkendall effect during thermal processing. The fibrous structure was synthesized by electrospinning with mixed solution of Sn and Cu precursors, which then underwent heat treatment under various temperature conditions. The hollow structures were generated based on the different diffusion rates between SnO2-CuO and Sn/Cu. The SnO2-CuO nanotubes have low operating temperatures and high H2S sensing performance. The increased surface area for detecting H2S resulted in great enhancement of the response (Ra/Rg = 1395) and a very fast response time of 5.27 s with a stable recovery time to a low concentration of H2S to 5 ppm at 200 °C. The porous SnO2-CuO hollow nanofiber gas sensor proved to be a promising candidate for gas sensor systems due to increased surface area with metal oxide catalyst. The mechanisms involved in enhancement of gas response and extended applications are also discussed.
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