Penehyclidine hydrochloride alleviates lung ischemia-reperfusion injury by inhibiting pyroptosis.

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.

Fast Distributed Model Predictive Control Method for Active Suspension Systems.

In order to balance the performance index and computational efficiency of the active suspension control system, this paper offers a fast distributed model predictive control (DMPC) method based on multi-agents for the active suspension system. Firstly, a seven-degrees-of-freedom model of the vehicle is created. This study establishes a reduced-dimension vehicle model based on graph theory in accordance with its network topology and mutual coupling constraints. Then, for engineering applications, a multi-agent-based distributed model predictive control method of an active suspension system is presented. The partial differential equation of rolling optimization is solved by a radical basis function (RBF) neural network. It improves the computational efficiency of the algorithm on the premise of satisfying multi-objective optimization. Finally, the joint simulation of CarSim and Matlab/Simulink shows that the control system can greatly minimize the vertical acceleration, pitch acceleration, and roll acceleration of the vehicle body. In particular, under the steering condition, it can take into account the safety, comfort, and handling stability of the vehicle at the same time.

Long-term sevoflurane exposure resulted in temporary rather than lasting cognitive impairment in Drosophila.

Sevoflurane is the primary inhaled anesthetic used in pediatric surgery. It has been the focus of research since animal models studies found that it was neurotoxic to the developing brain two decades ago. However, whether pediatric general anesthesia can lead to permanent cognitive deficits remained a subject of heated debate. Therefore, our study aims to determine the lifetime neurotoxicity of early long-time sevoflurane exposure using a short-life-cycle animal model, Drosophila melanogaster. To investigate this question, we measured the lifetime changes of two-day-old flies' learning and memory abilities after anesthesia with 3 % sevoflurane for 6 h by the T-maze memory assay. We evaluated the apoptosis, levels of ATP and ROS, and related genes in the fly head. Our results suggest that 6 h 3 % sevoflurane exposure at a young age can only induce transient neuroapoptosis and cognitive deficits around the first week after anesthesia. But this brain damage recedes with time and vanishes in late life. We also found that the mRNA level of caspases and Bcl-2, ROS level, and ATP level increased during this temporary neuroapoptosis process. And mRNA levels of antioxidants, such as SOD2 and CAT, increased and decreased simultaneously with the rise and fall of the ROS level, indicating a possible contribution to the recovery from the sevoflurane impairment. In conclusion, our results suggest that one early prolonged sevoflurane-based general anesthesia can induce neuroapoptosis and learning and memory deficit transiently but not permanently in Drosophila.

Anesthetic propofol suppresses growth and metastasis of lung adenocarcinoma in vitro through downregulating circ-MEMO1-miR-485-3p-NEK4 ceRNA axis.

BACKGROUND: Recently, circular RNAs (circRNAs) have been emerging as new regulators in the propofol-induced tumor-suppressive role. Here, we intended to investigate the involvement of circRNA-Mediator of cell motility 1 (circ-MEMO1; hsa_circ_0007385) in propofol role in cancer hallmarks of lung adenocarcinoma (LUAD). METHODS: Real-time quantitative PCR and western blotting examined transcriptional and translational levels of circ-MEMO1, microRNA (miR)-485-3p, and NIMA-related kinase-4 (NEK4), and markers of growth and metastasis including E-cadherin, CyclinD1, and Vimentin. Cancer hallmarks were measured by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, 5-ethynyl-2-deoxyuridine assay, and transwell assay. The interaction among circ-MEMO1, miR-485-3p, NEK4 was determined by dual-luciferase reporter assay and Pearson's correlation analysis. RESULTS: Circ-MEMO1 and NEK4 were high-expressed, and miR-485-3p was low-expressed in LUAD patients and cells; moreover, circ-MEMO1 and NEK4 expression in LUAD cells could be suppressed, whereas miR-485-3p could be elevated with propofol anesthesia. Functionally, propofol restrained cell viability, cell cycle entrance, cell proliferation, migration, and invasion of LUAD cells, accompanied by promoted E-cadherin and depressed CyclinD1 and Vimentin. Coincidently, high circ-MEMO1 was associated with low overall survival of LUAD patients, and overexpressing circ-MEMO1 could overall attenuate propofol effects in LUAD cells. Of note, upregulating miR-485-3p and/or interfering NEK4 could partially countermand the adverse impacts of circ-MEMO1 on propofol's role in LUAD cells. Importantly, circ-MEMO1 acted as a sponge for miR-485-3p to modulate the expression of miR-485-3p-targeted oncogene NEK4. CONCLUSION: Promoting the circ-MEMO1-miR-485-3p-NEK4 axis might halt the tumor-inhibiting role of propofol in LUAD cells in vitro, suggesting a potential epigenetic pathway of propofol.

Phosphoinositide interacting regulator of TRP (Pirt) enhances TRPM8 channel activity in vitro via increasing channel conductance.

AIM: Pirt is a two-transmembrane domain protein that regulates the function of a variety of ion channels. Our previous study indicated that Pirt acts as a positive endogenous regulator of the TRPM8 channel. The aim of this study was to investigate the mechanism underlying the regulation of TRPM8 channel by Pirt. METHODS: HEK293 cells were transfected with TRPM8+Pirt or TRPM8 alone. Menthol (1 mmol/L) was applied through perfusion to induce TRPM8-mediated voltage-dependent currents, which were recorded using a whole-cell recording technique. PIP2 (10 µmol/L) was added into the electrode pipettes (PI was taken as a control). Additionally, cell-attached single-channel recordings were conducted in CHO cells transfected with TRPM8+Pirt or TRPM8 alone, and menthol (1 mmol/L) was added into the pipette solution. RESULTS: Either co-transfection with Pirt or intracellular application of PIP2 (but not PI) significantly enhanced menthol-induced TRPM8 currents. Furthermore, Pirt and PIP2 synergistically modulated menthol-induced TRPM8 currents. Single-channel recordings revealed that co-transfection with Pirt significantly increased the single channel conductance. CONCLUSION: Pirt and PIP2 synergistically enhance TRPM8 channel activity, and Pirt regulates TRPM8 channel activity by increasing the single channel conductance.