Dexmedetomidine alleviates ferroptosis following hepatic ischemia-reperfusion injury by upregulating Nrf2/GPx4-dependent antioxidant responses.

Hepatic ischemia-reperfusion injury (HIRI) adversely affects liver transplant and resection outcomes. Recently, ferroptosis has been associated with HIRI. Dexmedetomidine (Dex), a potent sedative with anti-inflammatory, antioxidant, and anti-apoptotic properties, protects organs from hypoxic or ischemia-reperfusion (I/R) injuries. However, the mechanisms underlying this protective effect against I/R-induced liver injury remain unclear. This study evaluated the effect of Dex on HIRI in mouse models and the oxygen-glucose deprivation/reperfusion (OGD/R) AML12 cell model. We examined ferroptosis-related markers, including Fe2+ levels, reactive oxygen species (ROS) content, mitochondrial morphology, GPX4 protein expression, 4-hydroxynonenal (4-HNE), and Nrf2. The Nrf2 inhibitor ML385 was used in combination with Dex to treat HIRI mice and OGD/R-induced cellular models to explore the pathways by which Dex counteracts ferroptosis. Our results showed that Dex treatment significantly ameliorated OGD/R-induced ferroptosis in AML12 cells, including reduced Fe2+, ROS, malondialdehyde (MDA), and 4-HNE levels. Dex also ameliorated liver tissue damage and reduced serum AST, ALT, and inflammatory factor levels in HIRI mice. Additionally, Dex increased the levels of GSH, an antioxidative stress marker, and GPX4 expression in HIRI mice. Mechanistically, Nrf2 expression and nuclear translocation were significantly inhibited in both HIRI mice and OGD/R-treated AML12 cells. Dex treatment also restored the I/R-induced inhibition of Nrf2 expression and nuclear translocation. ML385 significantly inhibited Dex-promoted Nrf2 nuclear aggregation with Gpx4 protein expression, hindering the efficacy of Dex. In conclusion, Dex ameliorates ferroptosis in HIRI by positively regulating the Nrf2/GPx4 axis, potentially presenting a therapeutic avenue for addressing HIRI.

The study of different dosages of remazolam combined with sufentanil and propofol on painless gastroscopy: A randomized controlled trial.

BACKGROUND: Gastroscopy is one of the most commonly used diagnostic modalities for upper gastrointestinal disorders. Remazolam besylate, a new type of ultrashort-acting benzodiazepine drug, has been less studied in gastroscopy. In this study, we studied the efficacy and safety of remazolam combined with propofol for painless gastroscopy. METHODS: This is a single-center, randomized controlled clinical trial. Hundred patients undergoing painless gastroscopy were included in this study and randomly divided into 2 groups (n = 50 per group): the remazolam 3 mg group (R3 group) and the remazolam 6 mg group (R6 group). Sufentanil, remazolam, and propofol are used to anesthetize the patients, and then, the effects of different dosages of remazolam on these patients are compared and analyzed. The patient's general condition, vital signs at different times, the dosage of propofol (mg) and additional times, complications, duration of gastroscopy (minute), awakening time (minute), residence time in the resuscitation room (minute), and adverse reactions were recorded. RESULTS: R3 group systolic blood pressure and diastolic blood pressure are more stable (P < .05); The number of additional propofol in R6 group was less (P < .05). The incidence of hypotension was lower in R3 group, as well as the time of awakening and staying in the resuscitation room were shorter (P < .05). CONCLUSION: Remazolam 3mg combined with sufentanil and propofol have less effect on hemodynamics in painless gastroscopy, and the patients have shorter awakening time.

Effect of ciprofol on swallowing function in patients undergoing painless gastrointestinal endoscopy.

BACKGROUND: Gastroscopy is one of the most commonly used diagnostic modalities for upper gastrointestinal disorders. This study compared the effect of ciprofol and propofol on swallowing function during painless gastroenteroscopy. METHODS: This was a single-center, placebo-controlled randomized trial. Three hundred sixty-eight patients undergoing painless gastroscopy were included in this study and randomly divided into 2 groups: the propofol group (PRO group, n = 183) and the ciprofol group (CIP group, n = 185). Sufentanil, ciprofol, and propofol are used to anesthetize the patients, and the effects of different solutions on these patients are compared and analyzed. The patient's general condition, vocal cord adduction reflex, dysphagia severity score, penetration and aspiration scale score, vital signs at different times, complications, recovery time (minutes), residence time in the resuscitation room (minutes), and adverse reactions were recorded. RESULTS: During the examination, the incidence of severe swallowing dysfunction in CIP group was lower than that in PRO group (P < .05). The BP in CIP group was higher than that in PRO Group (P < .05). The HR of CIP group was lower than that of PRO Group (P < .05). SpO2 in CIP group was higher than that in PRO Group (P < .05). The recovery time of CIP group was longer than that of PRO Group, and the postanesthesia care unit stay time of PRO group was longer than that of CIP group(P < .05). The incidence of respiratory depression, hypotension and cough in CIP group was lower than that in PRO Group (P < .05). The incidence of injection pain in CIP group was lower than that in PRO Group (P < .05). CONCLUSION: Compared with propofol, ciprofol has less inhibition on swallowing function, less impact on hemodynamics, less respiratory depression, and less injection pain, which is more suitable for painless gastroscopy.

Dexmedetomidine improves DM-induced oxidative stress injury to protect liver function through Nrf2 pathway.

OBJECTIVE: Diabetes mellitus-induced oxidative stress (OS) causes liver injury. Intraoperative pumping of dexmedetomidine (DEX) effectively reduced the postoperative OS response in patients with type 2 diabetes mellitus (T2DM) and had a certain protective effect on liver function. However, the mechanisms of the protective effect on the liver remained unclear. In this study, we investigated the antagonistic effects and the possible mechanism of DEX on T2DM-induced liver injury in the mouse model and Palmitic acid (Pal)-induced injury in hepatocellular carcinoma cells (HepG2). METHODS: Seven wt/wt mice served as Control group, and 28 db/db mice were randomly divided into four groups using a random number table method: Model group (n=7), D25 group (n=7), D50 group (n=7) and D75 group (n=7). Different concentrations of DEX were injected intraperitoneally in the D25 group, D50 group and D75 group, while the Control group and the Model group were intraperitoneally injected with the same amount of normal saline for 3 weeks. In the cell intervention experiments, HepG2 cell line was used. The control group (Con group), the palmitic acid group (Pal group) and the DEX treatment group (Pal + Dex group) were set up. The test results were compared among mice groups and cell groups, respectively. RESULTS: DEX alleviated the increase of alanine aminotransferase, triglyceride, total cholesterol and aspartate aminotransferase contents induced by high fat or T2DM. DEX reversed the decrease of nuclear factor E2 related factor 2 (Nrf2) in the nuclear translocation and the lower transcriptional activity of Nrf2 to inhibit the expression of heme oxygenase-1, NADPH quinone oxidoreductase-1 and superoxide dismutase 2 and reduced the activity of superoxide dismutase to increase reactive oxygen species content induced by high fat or T2DM. CONCLUSION: By attenuating the high-fat or T2DM-induced Nrf2 pathway impairment, DEX can reduce OS injury and inhibit the disorder of lipid anabolism and protect liver function. This study provides a theoretical basis for the protection of liver function by DEX in clinical T2DM patients.

Study on the protective mechanism of dexmedetomidine on the liver of perioperative diabetic patients: A randomized controlled trial.

BACKGROUND: Although several studies have reported that dexmedetomidine is a highly selective α2-adrenergic receptor agonist that protects liver function in perioperative patients by inhibiting oxidative stress (OS) and inflammatory response, patients with type 2 diabetes mellitus (T2DM) have not been included in the previous studies. The purpose of this study was to investigate the effects of perioperative low-dose dexmedetomidine on perioperative liver function in T2DM patients. METHODS: This was a single-center, placebo-controlled randomized trial. Fifty-four T2DM patients scheduled for debridement of lower extremity ulcers were included in this study and randomly divided into 2 groups (n = 27 per group): the dexmedetomidine group (DEX group) and the control group (CON group). Continuous intravenous infusion of dexmedetomidine (DEX group) or normal saline (CON group) was administered from the completion of monitoring to the end of surgery. All participants received femoral and sciatic nerve block with 0.33% ropivacaine. The main result was the activity of liver enzymes (AST, ALT) reflecting liver function. The secondary results included variables reflecting blood glucose (Glu), blood lipids (TG, HDL, LDL, total cholesterol), biomarkers of OS (MDA, SOD), and systemic inflammatory response (TNF-α, IL-6). RESULTS: Compared with CON group, DEX group exhibited a reduction in hemodynamic parameters, Glu, systemic inflammatory response, and liver injury indicators. OS response MDA activity was lower in DEX group than in CON group, while SOD was higher than that in CON group. The variables reflecting lipid metabolism function showed no differences between the groups. CONCLUSION SUBSECTIONS: Dexmedetomidine administered perioperatively can reduce Glu levels and protect the liver by attenuating OS injury and inflammatory response in T2DM patients without any potential risk.

Improvement of K-Means Algorithm and Its Application in Air Passenger Grouping.

The k-means is one of the most popular clustering analysis algorithm and widely used in various fields. Nevertheless, it continues to have some shortcomings, for example, extremely sensitive to the initial center points selection and the special points such as noise or outliers. Therefore, this paper proposed initial center points' selection optimization and phased assignment optimization to improve the k-means algorithm. The experimental results on 15 real-world and 10 synthetic datasets show that the improved k-means outperforms its main competitor k-means ++ and under the same setting conditions, namely, using the default parameters,its clustering performance is better than Affinity Propagation, Mean Shift, and DBSCAN. The proposed algorithm was applied to analyze the airline seat selection data to air passengers grouping. The clustering results, as well as absolute deviation rate analysis, realized customer grouping and found out suitable audience group for the recommendation of seat selection services.

Mechanical Properties, Melting and Crystallization Behaviors, and Morphology of Carbon Nanotubes/Continuous Carbon Fiber Reinforced Polyethylene Terephthalate Composites.

Carbon nanotube/continuous carbon fiber reinforced poly(ethylene terephthalate) (CNT/CCF/PET) composites are prepared by melt impregnating. The effects of CF and CNT content on the mechanical properties, melt and crystallization behaviors, and submicroscopic morphology of CNT/CCF/PET composites are studied. The tensile test results show that the increase of CF and the addition of appropriate amount of CNT improved the tensile strength and tensile modulus of the composites. When the content of CNT is 1.0 wt% and the content of CF is 56 wt%, the properties of the composites are the best, with tensile strength of 1728.7 MPa and tensile modulus of 25.1 GPa, which is much higher than that of traditional resin matrix composites. The results of dynamic mechanical analysis (DMA) show that the storage modulus of the composites increased with the increase of CF and CNT content. In particular, the addition of CNT greatly reduced the loss modulus of the composites. Morphological analysis show that the addition of CNT improved the fiber-matrix interface of the composite, which changes from fiber pull-out and fracture failure to fiber matrix fracture failure, and the fiber matrix interface is firmly bonded. In addition, there are polymer coated CNT protrusions on the surface of the fiber was observed. The results of differential scanning calorimetry (DSC) show that the melting temperature and crystallization temperature of the composites increased with the increase of CF content. The addition of CNT had little effect on the melting temperature of the composites, but it further improved the crystallization temperature of the composites. The effect of CNT content on the crystallization kinetics of the composites is studied. The non-isothermal crystallization kinetics of the composites is described by Jeziorny's improved Avrami equation. The results show that CNT has a great influence on the crystallization type of the composites. As a nucleating agent, CNT has obvious heterogeneous nucleation effect in the composites, which improves the crystallization rate of PET.

Effects of the Interlayer Toughening Agent Structure on the Flow Behavior during the z-RTM Process.

In this paper, interlayer toughening composites were prepared by the z-directional injection RTM process (z-RTM), which has the advantage of increasing the interlaminar toughness and shortening the filling time and completely impregnating the fibers. The nonwoven fabrics and dot matrix structure material were used as ex situ interlayer toughening agents. The effect of the interlayer toughening agent structure on the resin flow behavior during the z-RTM process was investigated. The macro-flowing and micro-infiltration behaviors of the resin inside the preforms were deduced. The permeability of the fabric preforms with different toughening agents was investigated. The results show that the introduction of the nonwoven structure toughening agent makes the macro flow slow, and the flow front more uniform. The toughening agent with a dot matrix structure promotes the resin macro flow in the preforms, and shortens the injection time. The z-directional permeability of the preform with a dot matrix structural toughening agent is one order of magnitude lower than that of the non-toughened preform, while being higher than the preform toughened by the nonwoven fabric preforms, which is helpful for the further applicability of the z-RTM process. Furthermore, the mode II interlaminar fracture toughness of composites was evaluated.

Production of cloned transgenic cow expressing omega-3 fatty acids.

n-3 Polyunsaturated fatty acids (n-3 PUFA) are important for human health. Alternative resources of n-3 PUAFs created by transgenic domestic animals would be an economic approach. In this study, we generated a mfat-1 transgenic cattle expressed a Caenorhabditis elegans gene, mfat-1, encoding an n-3 fatty acid desaturase. Fatty acids analysis of tissue and milk showed that all of the examined n-3 PUAFs were greatly increased and simultaneously the n-6 PUAFs decreased in the transgenic cow. A significantly reduction of n-6/n-3 ratios (P<0.05) in both tissue and milk were observed.