SLC44A2 regulates vascular smooth muscle cell phenotypic switching and aortic aneurysm.

Aortic aneurysm is a life-threatening disease with limited interventions that is closely related to vascular smooth muscle cell (VSMC) phenotypic switching. SLC44A2, a member of the solute carrier series 44 (SLC44) family, remains undercharacterized in the context of cardiovascular diseases. Venn diagram analysis based on microarray and single-cell RNA sequencing identified SLC44A2 as a major regulator of VSMC phenotypic switching in aortic aneurysm. Screening for Slc44a2 among aortic cell lineages demonstrated its predominant location in VSMCs. Elevated levels of SLC44A2 were evident in the aorta of both patients with abdominal aortic aneurysm and angiotensin II-infused (Ang II-infused) Apoe-/- mice. In vitro, SLC44A2 silencing promoted VSMCs toward a synthetic phenotype, while SLC44A2 overexpression attenuated VSMC phenotypic switching. VSMC-specific SLC44A2-knockout mice were more susceptible to aortic aneurysm under Ang II infusion, while SLC44A2 overexpression showed protective effects. Mechanistically, SLC44A2's interaction with NRP1 and ITGB3 activates TGF-ß/SMAD signaling, thereby promoting contractile gene expression. Elevated SLC44A2 in aortic aneurysm is associated with upregulated runt-related transcription factor 1 (RUNX1). Furthermore, low-dose lenalidomide (LEN; 20 mg/kg/day) suppressed aortic aneurysm progression by enhancing SLC44A2 expression. These findings reveal that the SLC44A2-NRP1-ITGB3 complex is a major regulator of VSMC phenotypic switching and provide a potential therapeutic approach (LEN) for aortic aneurysm treatment.

Smart needle electrical bioimpedance to provide information on needle tip relationship to target nerve prior to local anesthetic deposition in peripheral nerve block (USgPNB) procedures.

Ultrasound guided peripheral nerve block (USgPNB) refers to anaesthetic techniques to deposit local anesthetic next to nerves, permitting painful surgery without necessitating general anesthesia. Needle tip position prior to local anesthetic deposition is a key determinant of block success and safety. Nerve puncture and intra-neural injection of local anesthetic can cause permanent nerve injury. Currently ultrasound guidance is not sufficiently sensitive to reliably detect needle to nerve proximity. Feedback with bioimpedance data from the smart needle tip might provide the anesthetist with information as to the relationship between the needle tip and the target nerve prior to local anesthetic deposition. Bioimpedance using a smart needle integrated with a two-electrode impedance sensor has been developed to determine needle to nerve proximity during USgPNB. Having obtained all necessary ethical and regulatory approvals, in vivo data on brachial plexus, vagus, femoral and sciatic nerves were obtained from seven pig models using the smart needle bioimpedance system. The excision and histological analysis of above peripheral nerves and observation of the architecture and structure of nerves by means of histology allow the calculation of the ratios of connective tissue to neural tissue to determine the influence of this variable on absolute impedance. The ratio results give extra clinical data and explain the hetrogeneity of impedance data in the pig models and the hypothesis that connective tissue with intra-neural fat has higher impedance than neural tissue.

Rapid determination of NSAIDs by capillary and microchip electrophoresis with capacitively coupled contactless conductivity detection in wastewater.

A simple, rapid method using CE and microchip electrophoresis with C4 D has been developed for the separation of four nonsteroidal anti-inflammatory drugs (NSAIDs) in the environmental sample. The investigated compounds were ibuprofen (IB), ketoprofen (KET), acetylsalicylic acid (ASA), and diclofenac sodium (DIC). In the present study, we applied for the first time microchip electrophoresis with C4 D detection to the separation and detection of ASA, IB, DIC, and KET in the wastewater matrix. Under optimum conditions, the four NSAIDs compounds could be well separated in less than 1 min in a BGE composed of 20 mM His/15 mM Tris, pH 8.6, 2 mM hydroxypropyl-beta-cyclodextrin, and 10% methanol (v/v) at a separation voltage of 1000-1200 V. The proposed method showed excellent repeatability, good sensitivity (LODs ranging between 0.156 and 0.6 mg/L), low cost, high sample throughputs, portable instrumentation for mobile deployment, and extremely lower reagent and sample consumption. The developed method was applied to the analysis of pharmaceuticals in wastewater samples with satisfactory recoveries ranging from 62.5% to 118%.

Fast determination of paracetamol and its hydrolytic degradation product p-aminophenol by capillary and microchip electrophoresis with contactless conductivity detection.

Paracetamol (PAC) is one of the most extensively used analgesics and antipyretic drugs to treat mild and moderate pain. P-aminophenol (PAP), the main hydrolytic degradation product of PAC, can be found in environmental water. Recently, CE has been developed for the detection of a wide variety of chemical substances. The purpose of this study is to develop a simple and fast method for the detection and separation of PAC and its main hydrolysis product PAP using CE and microchip electrophoresis with capacitively coupled contactless conductivity detection. The determination of these compounds using microchip electrophoresis with capacitively coupled contactless conductivity detection is being reported for the first time. The separation was run for all analytes using a BGE (20 mM ß-alanine, pH 11) containing 14% (v/v) methanol. The RSDs obtained for migration time were less than 4%, and RSDs obtained for peak area were less than 7%. The detection limits (S/N = 3) that were achieved ranged from 0.3 to 0.6 mg/L without sample preconcentration. The presented method showed rapid analysis time (less than 1 min), high efficiency and precision, low cost, and a significant decrease in the consumption of reagents. The microchip system has proved to be an excellent analytical technique for fast and reliable environmental applications.

Development of a Mobile Analytical Chemistry Workstation Using a Silicon Electrochromatography Microchip and Capacitively Coupled Contactless Conductivity Detector.

Capillary electrochromatography (CEC) is a separation technique that hybridizes liquid chromatography (LC) and capillary electrophoresis (CE). The selectivity offered by LC stationary phase results in rapid separations, high efficiency, high selectivity, minimal analyte and buffer consumption. Chip-based CE and CEC separation techniques are also gaining interest, as the microchip can provide precise on-chip control over the experiment. Capacitively coupled contactless conductivity detection (C4D) offers the contactless electrode configuration, and thus is not in contact with the solutions under investigation. This prevents contamination, so it can be easy to use as well as maintain. This study investigated a chip-based CE/CEC with C4D technique, including silicon-based microfluidic device fabrication processes with packaging, design and optimization. It also examined the compatibility of the silicon-based CEC microchip interfaced with C4D. In this paper, the authors demonstrated a nanofabrication technique for a novel microchip electrochromatography (MEC) device, whose capability is to be used as a mobile analytical equipment. This research investigated using samples of potassium ions, sodium ions and aspirin (acetylsalicylic acid).