CD11b-NOX2 mutual regulation-mediated microglial exosome release contributes to rotenone-induced inflammation and neurotoxicity in BV2 microglia and primary cultures.

Epidemiological studies have revealed a potent association between chronic exposure to rotenone, a commonly used pesticide, in individuals and the incidence of Parkinson's disease (PD). We previously identified the contribution of the activation of microglial NADPH oxidase (NOX2) in rotenone-induced neurotoxicity. However, the regulation of NOX2 activation remains unexplored. Integrins are known to be bidirectionally regulated in the plasma membrane through the inside-out and outside-in signaling. CD11b is the α-chain of integrin macrophage antigen complex-1. This study aimed to investigate whether CD11b mediates rotenone-induced NOX2 activation. We observed that rotenone exposure increased NOX2 activation in BV2 microglia, which was associated with elevated CD11b expression. Silencing CD11b significantly reduced rotenone-induced ROS production and p47phox phosphorylation, a key step for NOX2 activation. Furthermore, the Src-FAK-PKB and Syk-Vav1-Rac1 signaling pathways downstream of CD11b were found to be essential for CD11b-mediated NOX2 activation in rotenone-intoxicated microglia. Interestingly, we also found that inhibition of NOX2 decreased rotenone-induced CD11b expression, indicating a crosstalk between CD11b and NOX2. Subsequently, the inhibition of the CD11b-NOX2 axis suppressed rotenone-induced microglial activation and exosome release. Furthermore, inhibiting exosome synthesis in microglia blocked rotenone-induced gene expression of proinflammatory factors and related neurotoxicity. Finally, blocking the CD11b-NOX2 axis and exosome synthesis or endocytosis mitigated microglial activation and dopaminergic neurodegeneration in rotenone-intoxicated midbrain primary cultures. Our findings highlight the crucial involvement of the CD11b-NOX2 axis in rotenone-induced inflammation and neurotoxicity, offering fresh perspectives on the underlying mechanisms of pesticide-induced neuronal damage.

Evaluating the efficacy and safety of perianal injection of liposomal ropivacaine HR18034 for postoperative analgesia following hemorrhoidectomy: A multicenter, randomized, double-blind, controlled phase II clinical trial.

STUDY OBJECTIVE: HR18034, composed of the ropivacaine encapsulated in multi-lamellar, concentric circular structure liposomes as the major component and a small amount of free ropivacaine, has performed well in animal experiments and phase I clinical trials. This trial was to investigate the efficacy, safety, pharmacokinetic profile and the minimum effective dose of HR18034 for postoperative analgesia after hemorrhoidectomy compared with ropivacaine. DESIGN: A multicenter, randomized, double-blind trial. SETTING: 19 medical centers in China. PATIENTS: 85 patients undergoing hemorrhoidectomy between October 2022 to November 2022. INTERVENTIONS: Patients were randomly divided into HR 18034 190 mg group, 285 mg group, 380 mg group and ropivacaine 75 mg group, receiving single local anesthetic perianal injection for postoperative analgesia. MEASUREMENTS: The primary outcome was the area under the resting state NRS score -time curve within 72 h after injection. The second outcomes included the proportion of patients without pain, the proportion of patients not requiring rescue analgesia, cumulative morphine consumption for rescue analgesia, etc. Safety was evaluated by adverse events incidence and plasma ropivacaine concentrations were measured to explore the pharmacokinetic characteristics of HR18034. MAIN RESULTS: The areas under the NRS score (at rest and moving states)-time curve were significantly lower in HR 18034 380 mg group than ropivacaine 75 mg at 24 h, 48 h, and 72 h after administration. However, this superiority was not observed in HR18034 190 mg group and 285 mg group. There was no difference in cumulative morphine consumption for rescue analgesia between HR 18034 groups and ropivacaine group. CONCLUSIONS: HR 18034 380 mg showed superior analgesic efficacy and equivalent safety compared to ropivacaine 75 mg after hemorrhoidectomy, thus preliminarily determined as minimum effective dose.

Optimizing Epoxy Interfacial Bonding Properties and Failure Mechanism between Carbon Textile-Reinforced Mortar Composites and Concrete Substrates.

Textile-reinforced mortar (TRM) composites have been extensively utilized in building reinforcement due to their exceptional mechanical properties. The weakest link in the entire structure is the interface between the TRM composites and the concrete; however, it plays a crucial role in effectively transferring stress. Researchers have taken measures to improve the strength of the interface, but the results are relatively scattered. In this paper, the surface treatment of the substrate, the thickness of the surfactant, and the physical doping of the surfactant on the interfacial bonding strength of the concrete were comparatively studied. The results demonstrate that the sandblasting treatment on the surface of the concrete enhances the bonding area between the mortar and the concrete of the reinforcement layer, leading to a 50% increase in the bending resistance of the structure. When the surfactant thickness increases to 0.5 kg/m2, more surfactants penetrate the mortar and concrete. This significantly inhibits the occurrence of cracks in the structure. The addition of 2.5% Al2O3 nanomaterials to the surfactant diminishes the shrinkage rate of the curing process, enhances the impact toughness, and improves the flexural and compressive properties of the bonding layer. The ultimate load of the structure increases by 65%. Physical doping of the surfactant is the most effective measure with the most apparent improvement result. It significantly enhances the bonding strength of the interface and can be widely used in construction.

Efficacy and safety of ciprofol versus propofol for anesthesia induction in adult patients received elective surgeries: a meta­analysis.

BACKGROUND: Propofol is use widely used in anesthesia, known for its effectiveness, may lead to cardiopulmonary issues in some patients. Ciprofol has emerged as a possible alternative to propofol because it can achieve comparable effects to propofol while causing fewer adverse events at lower doses. However, no definitive conclusion has been reached yet. This meta-analysis aimed to evaluate the efficacy and safety of ciprofol versus propofol in adult patients undergoing elective surgeries under general anesthesia. METHODS: We searched PubMed, EMBASE, the Cochrane library, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) to identify potentially eligible randomized controlled trials (RCT) comparing ciprofol with propofol in general anesthesia until September 30, 2023. The efficacy outcomes encompassed induction success rate, time to onset of successful induction, time to disappearance of eyelash reflex, and overall estimate means in Bispectral Index (BIS). Safety outcomes were assessed through time to full alertness, incidence of hypotension, incidence of arrhythmia, and incidence of injection-site pain. Continuous variables were expressed as mean difference (MD) with 95% confidence interval (CI), and dichotomous variables were expressed as risk ratio (RR) with 95% CI. Statistical analyses were performed using RevMan 5.4 and STATA 14.0. The quality of the evidence was rated through the grading of recommendations, assessment, development and evaluation (GRADE) system. RESULTS: A total of 712 patients from 6 RCTs were analyzed. Meta-analysis suggested that ciprofol was equivalent to propofol in terms of successful induction rate, time to onset of successful induction, time to disappearance of eyelash reflex, time to full alertness, and incidence of arrhythmia, while ciprofol was better than propofol in overall estimated mean in BIS (MD: -3.79, 95% CI: -4.57 to -3.01, p < 0.001), incidence of hypotension (RR: 0.63, 95% CI: 0.42 to 0.94, p = 0.02), and incidence of injection-site pain (RR: 0.26, 95% CI: 0.14 to 0.47, p < 0.001). All results were supported by moderate to high evidence. CONCLUSIONS: Ciprofol may be a promising alternative to propofol because it facilitates achieving a satisfactory anesthesia depth and results in fewer hypotension and injection-site pain. However, we still recommend conducting more studies with large-scale studies to validate our findings because only limited data were accumulated in this study. TRIAL REGISTRATION: PROSPERO 2023 CRD42023479767.

Targeted Elimination of Surface Defects in Carbon Fibers: Formation of a Hybrid Structure Combining Rigidity with Flexibility from Sonochemical-Induced Directional Growth of Nano-ZIF-8 and Subsequent Annealing.

Currently, the mechanical performance of carbon fibers (CFs) has yet to fully realize its theoretical potential. This is predominantly attributed to the significant constraints posed by surface defects, greatly impeding the widespread application of carbon fibers. In order to address this issue, we employed a sonochemical-induced approach in this study to achieve in situ growth of nanoscale zeolitic imidazolate framework-8 (ZIF-8) at the surface defects of carbon fibers. After high-temperature treatment, the structure of ZIF-8 decomposed into ZnO and inorganic carbon, reinforcing the carbon fiber structure from both flexible and rigid aspects. Our research indicates that when the temperature reaches 500 °C, a substantial portion of ZIF-8 undergoes thermal decomposition, giving rise to zinc oxide and inorganic carbon. The flexible inorganic carbon and rigid ZnO form a meshlike structure, which welds to the surface defects of carbon fibers, resulting in strong interactions and contributing to the delay of fiber fracture. Compared to unmodified carbon fibers, the mechanical performance increased by approximately 15.86%. Based on the aforementioned analysis, this method can be considered a direct and effective approach for reinforcing carbon fiber structures, presenting a novel approach for the precise elimination of surface defects on carbon fibers.

Homogeneous regulation of arranged polymorphic manganese dioxide nanocrystals as cathode materials for high-performance zinc-ion batteries.

Rechargeable aqueous zinc-ion batteries have emerged as attractive energy storage devices by virtue of their low cost, high safety and eco-friendliness. However, zinc-ion cathodes are bottlenecked by their vulnerable crystal structures in the process of zinc embedding and significant capacity fading during long-term cycling. Herein, we report the rational and homogeneous regulation of polycrystalline manganese dioxide (MnO2) nanocrystals as zinc cathodes via a surfactant template-assisted strategy. Benefiting from the homogeneous regulation, MnO2 nanocrystals with an ordered crystal arrangement, including nanorod-like polyvinylpyrrolidone-manganese dioxide (PVP-MnO2), nanowire-like sodium dodecyl benzene sulfonate-manganese dioxide and nanodot-like cetyltrimethylammonium bromide-manganese dioxide, are obtained. Among these, the nanorod-like PVP-MnO2 nanocrystals exhibit stable long-life cycling of 210 mAh g-1 over 180 cycles at a high rate of 0.3 A g-1 and with a high capacity retention of 84% over 850 cycles at a high rate of 1 A g-1. The good performance of this cathode significantly results from the facile charge and mass transfer at the interface between the electrode and electrolyte, featuring the crystal stability and uniform morphology of the arranged MnO2 nanocrystals. This work provides crucial insights into the development of advanced MnO2 cathodes for low-cost and high-performance rechargeable aqueous zinc-ion batteries.

The effect of sevoflurane on the spatial recall ability and expression of apolipoprotein E and ß amyloid in the hippocampus in rats.

This study aimed to observe the recent spatial recall ability and the changes of expression of hippocampal apolipoprotein E (ApoE) and amyloid ß protein (Aß) in adult rats after inhaling sevoflurane anesthetic drugs, and to analyze the mechanism of action. For this purpose, a total of 54 adult SD clean-grade rats were selected in this study and were randomly divided into the sevoflurane anesthesia group, carrier gas group and control group, 18 rats in each group. The rats in the carrier gas group were inhaled with 1 L/min of oxygen O2+1 L/min air mixed carrier gas for 2 h, and the rats in the sevoflurane anesthesia group were given 3.2%sevoflurane for 2 hours based on the carrier gas group, the control rats were naturally reared. Before the model was copied, the Morris water maze experiment was performed before the material was taken. Some rat brain tissues were extracted on the first day (T1), the third day (T3), and the seventh day (T7) after model replication. The immunohistochemistry was used to measure the mean optical density (MOD) value of APOE and Aß in hippocampal CA1, CA3 and DG regions. The indicators above at different time points of each group were compared and analyzed. Results showed that the number of crossing the original platform at each time point, the residence time of the original platform quadrant, the number of entering the original platform quadrant, and the percentage of the original platform quadrant residence time in the sevoflurane anesthesia group and the carrier gas group were compared, and there were no significant differences between two groups (P>0.05). Compared with the carrier gas group, the MOD values of APOE in the hippocampus at T1 and T3 time points in the sevoflurane anesthesia group were decreased (P<0.05), the MOD values of Aß in the hippocampus at the T7 time point were increased (P<0.05). It concluded that Inhalation of 3.2%sevoflurane has no obvious damage to the recent spatial recall ability of adult rats. Within 7 days after inhalation of 3.2% sevoflurane, it can inhibit hippocampus Aß deposition through down-regulating APOE expression level. The critical time point for hippocampal Aß increasing was 7 days after anesthesia.

MicroRNA-217 relieved neuropathic pain through targeting toll-like receptor 5 expression.

Neuropathic pain is the most common chronic pain that is caused by nerve injury or disease that influences the nervous system. Increasing evidence suggested that microRNAs (miRNAs) play a crucial role in neuropathic pain and neuroinflammation development. However, the functional role of miR-217 in the development of neuropathic pain remains unknown. In this study, we used rats to establish a neuropathic pain model and showed that the miR-217 expression level was upregulated in the spinal dorsal horn of bilateral sciatic nerve chronic constriction injury (bCCI). However, the expression of miR-217 was not changed in the anterior cingulated cortex (ACC), hippocampus, and dorsal root ganglion (DRG) of bCCI rats. Ectopic expression of miR-217 attenuated neuropathic pain and suppressed neuroinflammation expression in vivo. We identified toll-like receptor 5 (TLR5) as a direct target gene of miR-217 in the PC12 cell. In addition, we demonstrated that the expression level of TLR5 was upregulated in bCCI rats. Moreover, restoration of TLR5 rescued the inhibitory roles induced by miR-217 overexpression on neuropathic pain and neuroinflammation development. These data suggested that miR-217 played a pivotal role in the development of neuropathic pain partly through regulating TLR5 expression.

Effects of dexmedetomidine on TNF-α and interleukin-2 in serum of rats with severe craniocerebral injury.

BACKGROUND: Dexmedetomidine is a highly selective adrenergic receptor agonist, which has a dose-dependent sedative hypnotic effect. Furthermore, it also has pharmacological properties, and the ability to inhibit sympathetic activity and improve cardiovascular stability during an operation. However, its protective effect on patients with severe craniocerebral injury in the perioperative period remains unclear. METHOD: Eighty adult male SD rats were used and divided into two groups (n = 40, each group): dexmedetomidine injury group (experimental group), and sodium chloride injury group (control group). Models of severe craniocerebral injury were established in these two groups using the modified Feeney's free-fall method. As soon as the establishment of models was succeed, rat in the experimental group received 1 µg of dexmedetomidine (0.1 ml), while each rat in the control group was given 0.1 ml of 0.9% sodium chloride. Blood was sampled from an incision at the femoral vein to detect TNF-α and IL-2 levels at 1, 12, 24,36,48 and 72 h after establishing the model in the two groups. RESULTS: After severe craniocerebral injury, TNF-α levels of rats were lower in every stage and at different degrees in the experimental group than in the control group (P < 0.05), while IL-2 levels were lower in the experimental group to different extents (P < 0.05). CONCLUSION: Dexmedetomidine protects the brain of rats with severe craniocerebral injury by reducing the release of inflammatory mediators.

Effects of oxycodone on immune function in patients undergoing radical resection of rectal cancer under general anesthesia.

This study aims to explore the effect of oxycodone hydrochloride injection on the immune function of patients who underwent radical resection of rectal cancer under general anesthesia.Eighty patients were enrolled and randomly divided into group A and B (n = 40, each). All patients underwent general intravenous anesthesia. At the end of surgery, each patient in group A was injected with 5 mg (5 mL) of oxycodone hydrochloride, while 5 mg (5 mL) of morphine hydrochloride in group B. Venous blood was withdrawn in both groups at different time points. Changes in the numbers of T lymphocyte subsets and natural killer (NK) cells were determined by flow cytometry.First the numbers of T lymphocyte subsets and NK cells at T1, T2, T3, and T4 decreased in both groups, compared with those at T0, and the differences were statistically significant. Furthermore, the numbers reduced to a minimum at T2 and began to recover at T3. Second the differences between group A and B at T1, T2, T3, and T4 were statistically significant; and the numbers of T lymphocytes and NK cells were higher in group A than in group B at corresponding time points.Oxycodone hydrochloride and morphine hydrochloride both have inhibitory effects on immune function in patients undergoing radical resection of rectal cancer after surgery. However, oxycodone hydrochloride has a smaller effect compared to morphine hydrochloride.

Assessment of different loading doses of dexmedetomidine hydrochloride in preventing adverse reaction after combined spinal-epidural anesthesia.

We conducted the present study to investigate the effects of the different loading doses of dexmedetomidine hydrochloride in the prevention of adverse reactions after combined spinal-epidural anesthesia. A total of 200 patients that were admitted to the Department of Obstetrics at the Second Affiliated Hospital of Xi'an Jiaotong University hospital and treated with cesarean section through the use of combined spinal-epidural anesthesia from December, 2014 to June, 2016, were randomly divided into 4 groups. The therapeutic regimens of patients were shown as follows: group A was administered an intravenous pump of 10 ml/l physiological saline in surgery until the end of the delivery. group B was administered 0.2 µg/kg dexmedetomidine. group C was administered 0.4 µg/kg dexmedetomidine. group D was administered 0.6 µg/kg dexmedetomidine. The anesthesia plane was adjusted to the level below the T10 plane. After the onset of anesthesia, participants of each group were treated with an intravenous pump of dexmedetomidine at loading dose. After intravenous pumping for 10 min in each group during the surgery, patients were administered with an intraoperative maintenance dose of 0.2 µg/kg/h until the end of the delivery. The heart rate (HR), mean arterial pressure (MAP), Narcotrend index (NI), Ramsay sedation score and the incidence of adverse reactions at each time-point of the start of drug administration (T0), 10 min (T2), 30 min (T3), 60 min (T4), 90 min (T5) and the end of surgery (T6) were recorded. Within 24 h post-delivery, the degree of amnesia from using dexmedetomidine until the end of the delivery were followed up. Compared to group A and T0, the HRs of participants at T3-6 in groups B and C were decreased. The MAP at T1 in group D was increased. In groups B and C, the NIs were significantly decreased at T2-6, the Ramsay scores were increased at T3-6, and the differences were statistically significant (P<0.05). The follow-up within 24 h after delivery showed that the degree of anterograde amnesia from groups B to D was significantly higher than group A, with statistically significant difference (P<0.05). A combined spinal-epidural anesthesia with 0.6 µg/kg loading dose of dexmedetomidine, by intravenous pumping within 10 min before cesarean section, can achieve a satisfied sedative effect at 30 min after administration. It maintains the characteristics of intraoperative hemodynamic stability and less adverse reactions. Therefore, it is of great significance to improve the quality of cesarean section delivery.