Esketamine accelerates emergence from isoflurane general anaesthesia by activating the paraventricular thalamus glutamatergic neurones in mice.

BACKGROUND: Delayed emergence from general anaesthesia poses a significant perioperative safety hazard. Subanaesthetic doses of ketamine not only deepen anaesthesia but also accelerate recovery from isoflurane anaesthesia; however, the mechanisms underlying this phenomenon remain elusive. Esketamine exhibits a more potent receptor affinity and fewer adverse effects than ketamine and exhibits shorter recovery times after brief periods of anaesthesia. As the paraventricular thalamus (PVT) plays a pivotal role in regulating wakefulness, we studied its role in the emergence process during combined esketamine and isoflurane anaesthesia. METHODS: The righting reflex and cortical electroencephalography were used as measures of consciousness in mice during isoflurane anaesthesia with coadministration of esketamine. The expression of c-Fos was used to determine neuronal activity changes in PVT neurones after esketamine administration. The effect of esketamine combined with isoflurane anaesthesia on PVT glutamatergic (PVTGlu) neuronal activity was monitored by fibre photometry, and chemogenetic technology was used to manipulate PVTGlu neuronal activity. RESULTS: A low dose of esketamine (5 mg kg-1) accelerated emergence from isoflurane general anaesthesia (474 [30] s vs 544 [39] s, P=0.001). Esketamine (5 mg kg-1) increased PVT c-Fos expression (508 [198] vs 258 [87], P=0.009) and enhanced the population activity of PVTGlu neurones (0.03 [1.7]% vs 6.9 [3.4]%, P=0.002) during isoflurane anaesthesia (1.9 [5.7]% vs -5.1 [5.3]%, P=0.016) and emergence (6.1 [6.2]% vs -1.1 [5.0]%, P=0.022). Chemogenetic suppression of PVTGlu neurones abolished the arousal-promoting effects of esketamine (459 [33] s vs 596 [33] s, P<0.001). CONCLUSIONS: Our results suggest that esketamine promotes recovery from isoflurane anaesthesia by activating PVTGlu neurones. This mechanism could explain the rapid arousability exhibited upon treatment with a low dose of esketamine.

Liquid-crystal-based fiber laser sensor for non-invasive gas detection.

This Letter reports a new optical fiber gas sensor for measuring breath acetone. The sensor is based on photonic bandgap (PBG) mode laser emission sensing technology using liquid crystal (LC), which is combined with silica fiber and chiral nematic liquid crystal (CNLC), thus providing an ultra-compact, fast-response and simple-to-produce sensing system with a fast response that can accurately and quantitatively determine the concentration of respiratory acetone within the normal oral temperature range (35-38°C). Since LCs are affected by temperature, we propose a method that eliminates the influence of the temperature to solve the problem of the temperature influence when measuring gas. The detection of acetone leads to splitting of the dual laser peaks, with a linear correlation of 0.99. The sensor has a limit of detection of 65 ppm for acetone vapor and thus is suitable for breath acetone detection in diabetic patients.

Knocking down Trim47 ameliorated sevoflurane-induced neuronal cell injury and cognitive impairment in rats.

Sevoflurane (SEV), usually causing neuronal damage and cognitive dysfunction, is one of the most commonly used anesthetics in clinical practice. However, the function of Trim47 in SEV-induced neuronal impairment remains elusive. The aim of this study was to study the effect of knocking down Trim47 on the nerve injury induced by SEV. Nerve injury was induced in rats by 3% SEV, and H19-7 was used to establish a pathological model, and sh-Trim47 was transfected into H19-7 to study the function of Trim47. The effects of SEV on the expression of Trim47 in the hippocampus and cognitive function of rats were studied by neurological function score and Moris water maze (MWM). The mRNA and protein expression of TNF-α, IL-1ß and IL-6 in the cells, along with the neuronal apoptosis in the hippocampus of rats in each group were studied by TUNEL or WB. Flow cytometry was used to study the effect of knockdown of Trim47 on cell apoptosis. CCK-8 was used to detect cell viability of H19-7 cells. Finally, the potential signaling pathway affected by knockdown of Trim47 after abrogation of SEV induction was investigated by WB. The results showed that, knockdown of Trim47 ameliorated SEV-induced neurological damage and cognitive deficits, inflammation and neuronal cell apoptosis in rats, and promoted hippocampal neuronal activity. Knockdown of Trim47 can inhibit the NF-κB signaling pathway and improve neuronal cell damage and cognitive impairment induced by SEV in neonatal rats by regulating NF-κB signaling pathway, alleviating inflammatory response, and inhibiting neuronal apoptosis.

Association and prediction of subjective sleep quality and postoperative delirium during major non-cardiac surgery: a prospective observational study.

BACKGROUND: Postoperative delirium (POD) is an acute form of brain dysfunction that can result in serious adverse consequences. There has been a link between cognitive dysfunction and poor sleep. The present study aimed to determine the association and prediction of subjective sleep quality and postoperative delirium during major non-cardiac surgery. METHODS: One hundred and thirty-four patients, aged 60 years or older, were scheduled for elective laparotomy or orthopaedic procedures. The Pittsburgh Sleep Quality Index (PSQI) and sleep log were used to assess perioperative subjective sleep quality in participants. Nursing Delirium Screening Checklist (NU-DESC) was used for screening, and the Confusion Assessment Method (CAM) was used to diagnose POD during the first seven days following surgery. The association between subjective sleep quality and POD was assessed using a multivariate logistic regression model. Thereafter, the prediction performance of subjective sleep quality was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: All assessments were completed on 119 patients who had an average PSQI score of 7.0 ± 2.4 before surgery. 23 patients (19.3%) suffered from POD. The multivariate logistic regression analysis showed that the occurrence of POD was closely related to age, BMI, PSQI and operation time. After adjusting for related factors, there was a statistically significant association between PSQI and POD occurrence (OR = 1.422, 95%CI 1.079-1.873, per 1-point increase in PSQI). The ROC curve analysis showed that the optimal PSQI cutoff value was 8.0 for predicting POD, and the area under the ROC (AUROC) value of PSQI was 0.741 (95%CI 0.635 to 0.817). The AUROC of the model developed by the multivariate logistic regression analysis was 0.870 (95%CI 0.797 to 0.925). CONCLUSIONS: The study found that preoperative subjective sleep quality was strongly associated with POD during major non-cardiac surgery. Additionally, PSQI combined with age, BMI, and operation time improved POD prediction.

Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state.

Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.

Spike Phase Shift Relative to Beta Oscillations Mediates Modality Selection.

How does the brain selectively process signals from stimuli of different modalities? Coherent oscillations may function in coordinating communication between neuronal populations simultaneously involved in such cognitive behavior. Beta power (12-30 Hz) is implicated in top-down cognitive processes. Here we test the hypothesis that the brain increases encoding and behavioral influence of a target modality by shifting the relationship of neuronal spike phases relative to beta oscillations between primary sensory cortices and higher cortices. We simultaneously recorded neuronal spike and local field potentials in the posterior parietal cortex (PPC) and the primary auditory cortex (A1) when male rats made choices to either auditory or visual stimuli. Neuronal spikes exhibited modality-related phase locking to beta oscillations during stimulus sampling, and the phase shift between neuronal subpopulations demonstrated faster top-down signaling from PPC to A1 neurons when animals attended to auditory rather than visual stimuli. Importantly, complementary to spike timing, spike phase predicted rats' attended-to target in single trials, which was related to the animals' performance. Our findings support a candidate mechanism that cortices encode targets from different modalities by shifting neuronal spike phase. This work may extend our understanding of the importance of spike phase as a coding and readout mechanism.

Risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population: a systematic review and meta-analysis.

Patients with rheumatic diseases are often more susceptible to different bacteria and viruses because of immune impairment, but it is not clear whether there is a higher risk of infection and a more serious course of disease for novel coronavirus (SARS-CoV-2). We performed this systematic review and meta analysis to assess the risk and clinical outcomes of COVID-19 in patients with rheumatic diseases compared with the general population. We searched PubMed, EMBASE, Scopus and Web of Science databases from January 1, 2020 to October 20, 2020 to determine epidemiological information related to patients with rheumatic diseases and COVID-19, including clear risk estimate or data that could be converted and extracted. We included 26 observational studies, totaling about 2000 patients with rheumatic diseases of whom were infected with COVID-19. Meta-analysis showed that the risk of COVID-19 infection in rheumatic patients was significantly higher than that in the general population (OR = 1.53, 95% CI 1.24-1.88, P = 0.000). In terms of hospitalization and severe clinical outcomes associated with COVID-19, we found that rheumatic patients showed similar results to the reference population (hospitalization OR = 1.36, 95% CI 0.81-2.29, P = 0.247; admitted to ICU OR = 1.94, 95% CI 0.88-4.27, P = 0.098; death OR = 1.29, 95% CI 0.84-1.97, P = 0.248). The presence of comorbidities, hypertension, lung diseases were significantly associated with the increased risk of COVID-19-related hospitalization in rheumatic patients and anti-TNF drugs were associated with lower hospitalization risk. Older age was related to severe COVID-19. Our meta-analysis indicated that rheumatic patients were at a higher risk of COVID-19 infection but might not lead to a more serious disease process.

Transmembrane channel-like (tmc) gene regulates Drosophila larval locomotion.

Drosophila larval locomotion, which entails rhythmic body contractions, is controlled by sensory feedback from proprioceptors. The molecular mechanisms mediating this feedback are little understood. By using genetic knock-in and immunostaining, we found that the Drosophila melanogaster transmembrane channel-like (tmc) gene is expressed in the larval class I and class II dendritic arborization (da) neurons and bipolar dendrite (bd) neurons, both of which are known to provide sensory feedback for larval locomotion. Larvae with knockdown or loss of tmc function displayed reduced crawling speeds, increased head cast frequencies, and enhanced backward locomotion. Expressing Drosophila TMC or mammalian TMC1 and/or TMC2 in the tmc-positive neurons rescued these mutant phenotypes. Bending of the larval body activated the tmc-positive neurons, and in tmc mutants this bending response was impaired. This implicates TMC's roles in Drosophila proprioception and the sensory control of larval locomotion. It also provides evidence for a functional conservation between Drosophila and mammalian TMCs.

Parallel pathways convey olfactory information with opposite polarities in Drosophila.

In insects, olfactory information received by peripheral olfactory receptor neurons (ORNs) is conveyed from the antennal lobes (ALs) to higher brain regions by olfactory projection neurons (PNs). Despite the knowledge that multiple types of PNs exist, little is known about how these different neuronal pathways work cooperatively. Here we studied the Drosophila GABAergic mediolateral antennocerebral tract PNs (mlPNs), which link ipsilateral AL and lateral horn (LH), in comparison with the cholinergic medial tract PNs (mPNs). We examined the connectivity of mlPNs in ALs and found that most mlPNs received inputs from both ORNs and mPNs and participated in AL network function by forming gap junctions with other AL neurons. Meanwhile, mlPNs might innervate LH neurons downstream of mPNs, exerting a feedforward inhibition. Using dual-color calcium imaging, which enables a simultaneous monitoring of neural activities in two groups of PNs, we found that mlPNs exhibited robust odor responses overlapping with, but broader than, those of mPNs. Moreover, preferentially down-regulation of GABA in most mlPNs caused abnormal courtship and aggressive behaviors in male flies. These findings demonstrate that in Drosophila, olfactory information in opposite polarities are carried coordinately by two parallel and interacted pathways, which could be essential for appropriate behaviors.

Sevoflurane inhibits embryonic stem cell self-renewal and subsequent neural differentiation by modulating the let-7a-Lin28 signaling pathway.

The commonly used inhalational anesthetic, sevoflurane, can cause toxicity to the central nervous system of the developing fetus. Lin28 has been reported to regulate let-7a, thereby modulating embryo development, neurodegeneration, and even neuron-related tumorigenesis. We demonstrate that pregnant mice receiving sevoflurane treatment during the early stage of pregnancy give birth to fewer offspring presenting a lower birth weight. We have also treated mouse embryonic stem cells (mESCs) with sevoflurane for 6 h and determined that mESCs self-renewal is repressed, and that differentiation is initiated earlier than in controls. We have induced neural differentiation in the treated mESCs and determined that their neurogenesis is weakened. Furthermore, sevoflurane upregulates the level of let-7a, which might repress mESC self-renewal by directly targeting the Lin28 3'-untranslated region. Lin28 overexpression attenuates the influence of sevoflurane or of let-7a on the self-renewal of mESCs and their subsequent neural differentiation. The let-7a inhibitor also abolishes the influence of sevoflurane. Thus, the let-7a-Lin28 pathway is involved in the sevoflurane-induced inhibition of ESC self-renewal and subsequent neurogenesis. Our study demonstrates the molecular mechanism underlying the side effects of sevoflurane during early development, laying the foundation for studies on the safe and reasonable usage of other inhalational anesthetics.

Identification of microRNAs as novel biomarkers for detecting esophageal squamous cell carcinoma in Asians: a meta-analysis.

Accumulating evidence has suggested that microRNAs (miRNAs) may play potential role as ideal diagnostic indicators of esophageal squamous cell carcinoma (ESCC). However, previous studies have met discrepant results. Thus, we conducted this meta-analysis to assess the potential diagnostic value of miRNAs for ESCC. A systematic literature search was conducted in PubMed and other databases. The pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated to evaluate the overall test performance. The Q statistic and the I(2) test were used to assess between-study heterogeneity. The potential sources of heterogeneity were further analyzed by subgroup analyses and meta-regression. Seventeen studies from eight articles, including 995 ESCC patients and 733 healthy controls, were included in this meta-analysis. The pooled SEN and SPE were 0.81 (95% confidence interval (CI) 0.76-0.85) and 0.83 (95 % CI 0.76-0.88), respectively. The pooled PLR was 4.6 (95% CI 3.3-6.5), NLR was 0.23 (95% CI 0.19-0.29), and DOR was 20 (95% CI 13-31). The pooled AUC was 0.91 (95% CI 0.88-0.93). Subgroup analyses indicated that blood-based miRNA assay displays better diagnostic accuracy than saliva-based miRNA assay. In summary, miRNA analysis may serve as novel noninvasive biomarkers for ESCC with excellent diagnostic characteristic. In addition, subgroup analysis suggested that blood-based assay yields better diagnostic characteristics than saliva-based assay. However, many issues should be managed before these findings can be translated into a clinically useful detection method for ESCC.

Graphene-SnO2 nanocomposites decorated with quantum tunneling junctions: preparation strategies, microstructures and formation mechanism.

Tin dioxide (SnO2) and graphene are versatile materials that are vitally important for creating new functional and smart materials. A facile, simple and efficient ultrasonic-assisted hydrothermal synthesis approach has been developed to prepare graphene-SnO2 nanocomposites (GSNCs), including three samples with graphene/Sn weight ratios = 1 : 2 (GSNC-2), 1 : 1 (GSNC-1), and graphene oxide/Sn weight ratio = 1 : 1 (GOSNC-1). Low-magnification electron microscopy analysis indicated that graphene was exfoliated and adorned with SnO2 nanoparticles, which were dispersed uniformly on both the sides of the graphene nanosheets. High-magnification electron microscopy analysis confirmed that the graphene-SnO2 nanocomposites presented network tunneling frameworks, which were decorated with the SnO2 quantum tunneling junctions. The size distribution of SnO2 nanoparticles was estimated to range from 3 to 5.5 nm. Comparing GSNC-2, GSNC-1, and GOSNC-1, GOSNC-1 was found to exhibit a significantly better the homogeneous distribution and a considerably smaller size distribution of SnO2 nanoparticles, which indicated that it was better to use graphene oxide as a supporting material and SnCl4·5H2O as a precursor to synthesize hybrid graphene-SnO2 nanocomposites. Experimental results suggest that the graphene-SnO2 nanocomposites with interesting SnO2 quantum tunneling junctions may be a promising material to facilitate the improvement of the future design of micro/nanodevices.

Excellent ultraviolet-blocking properties of chiral nematic liquid crystals.

We report the evaluation of chiral nematic liquid crystal (CNLC) in blocking ultraviolet (UV). The CNLC was coated on a calcium fluoride substrate to measure the spectral transmittance, which was measured to detect the UV-blocking effect of CNLC. The results show that CNLC could reduce UVB (290-320 nm) by 99.9% and UVA (320-400 nm) by 95.6%. The barrier effect of cake-shaped semi-solidified CNLC microspheres was further investigated, and it was found that cake-shaped semi-solidified CNLC microspheres could reduce UVB by 58.2% and UVA by 34.1%. This is due to the chemical absorption property of CNLC, which has UV-absorbing functional groups such as the benzene rings. And the physical reflection properties of CNLC could periodically reflect a certain wavelength of light. Liquid crystal (LC) is a rich set of soft materials with rod-like structures widely existing in nature, which is harmless to the human body and environment. Therefore, using CNLC's function of blocking UV, a new sunscreen can be developed.

Epidemiological investigation and ß-lactam antibiotic resistance of Riemerella anatipestifer isolates with waterfowl origination in Anhui Province, China.

Riemerella anatipestifer (R. anatipestifer) is a highly pathogenic and complex serotypes waterfowl pathogen with inherent resistance to multiple antibiotics. This study was aimed to investigate the antibiotic resistance characteristics and genomic features of R. anatipestifer isolates in Anhui Province, China in 2023. A total of 287 cases were analysed from duck farms and goose farms, and the R. anatipestifer isolates were subjected to drug resistance tests for 30 antimicrobials. Whole genome sequencing (WGS) and bioinformatics analysis were performed on the bacterial genomes, targeting the ß-lactam resistance genes. The results showed that a total of 74 isolates of R. anatipestifer were isolated from 287 cases, with a prevalence of 25.8%. The antimicrobial susceptibility testing (AST) revealed that all the 74 isolates were resistant to multiple drugs, ranging from 13 to 26 kinds of drugs. Notably, these isolates showed significant resistance to aminoglycosides and macrolides, which are also commonly used in clinical practices. Data revealed the presence of several ß-lactamase-related genes among the isolates, including a novel blaRASA-1 variant (16.2%), the class A extended-spectrum ß-lactamase blaRAA-1 (12.2%), and a blaOXA-209 variant (98.6%). Functional analysis of the variants blaRASA-1 and blaOXA-209 showed that the blaRASA-1 variant exhibited activity against various ß-lactam antibiotics while their occurrence in R. anatipestifer were not common. The blaOXA-209 variant, on the other hand, did not perform any ß-lactam antibiotic resistance. Furthermore, we observed that blaRAA-1 could undergo horizontal transmission among different bacteria via the insertion sequence IS982. In conclusion, this study delves into the high prevalence of R. anatipestifer infection in waterfowl in Anhui, China. The isolated strains exhibit severe drug resistance issues, closely associated with the prevalence of antibiotic resistance genes (ARG). Additionally, our research investigates the ß-lactam antibiotic resistance mechanism in R. anatipestifer.

NOMPC is likely a key component of Drosophila mechanotransduction channels.

Mechanotransduction is the basis of several sensory modalities, including touch, hearing, proprioception and gravity sensation. Despite its importance to sensory processing and behavior, the molecular mechanisms underlying mechanotransduction remain to be fully understood. In particular, the identity of the ion channels serving mechanotransduction is still unknown in many species. Drosophila melanogaster nompC (no mechanoreceptor potential C) has been shown to be essential for mechanotransduction in flies, yet there is no direct evidence demonstrating that NOMPC is indeed a mechanotransducing ion channel in Drosophila. To dissect the functional roles of NOMPC in mechanotransduction, we found that NOMPC-dependent transient adapting mechanoreceptor current (MRC) in the external bristle sensory organ was also chloride dependent. However, this chloride-dependent current was not necessary for spike generation. Furthermore, ectopic expression of wild-type NOMPC conferred mechanosensitivity on the interneurons in the antennal lobe (AL) and cation-mediated inward mechanocurrent was recorded, while a point mutation in the putative selective filter region of NOMPC failed to produce the mechanocurrent in the AL interneurons. These functional studies imply that NOMPC is likely to be a crucial component of mechanotransducers that accounts for mechanotransductions in mechanosensory neurons of Drosophila.

Silencing circPalm2 inhibits sepsis-induced acute lung injury by sponging miR-376b-3p and targeting MAP3K1.

The apoptosis and inflammation of pulmonary epithelial cells are important pathogenic factors of sepsis-induced acute lung injury (ALI). Upregulation of circPalm2 (circ_0001212) expression levels has been previously detected in the lung tissue of ALI rats. Herein, the biological significance and detailed mechanism of circPalm2 in ALI pathogenesis were investigated. In vivo models of sepsis-induced ALI were established by treating C57BL/6 mice with cecal ligation and puncture (CLP) surgery. Murine pulmonary epithelial cells (MLE-12 cells) were stimulated with lipopolysaccharide (LPS) to establish in vitro septic ALI models. MLE-12 cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometry analysis, respectively. The pathological alterations of the lung tissue were analysed based on hematoxylin-eosin (H&E) staining. Cell apoptosis in the lung tissue samples was examined by TUNEL staining assay. LPS administration suppressed the viability and accelerated the inflammation and apoptotic behaviours of MLE-12 cells. CircPalm2 displayed high expression in LPS-stimulated MLE-12 cells and possessed circular characteristics. The silencing of circPalm2 impeded apoptosis and inflammation in LPS-stimulated MLE-12 cells. Mechanistically, circPalm2 bound with miR-376b-3p, which targeted MAP3K1. In rescue assays, MAP3K1 enhancement reversed the repressive effects of circPalm2 depletion on LPS-triggered inflammatory injury and MLE-12 cell apoptosis. Furthermore, the lung tissue collected from CLP model mice displayed low miR-376b-3p expression and high levels of circPalm2 and MAP3K1. CircPalm2 positively regulated MAP3K1 expression by downregulating miR-376b-3p in murine lung tissues. Importantly, circPalm2 knockdown attenuated CLP-induced inflammation, apoptosis, and pathological alterations in lung tissues collected from mice. Silenced circPalm2 inhibits LPS-induced pulmonary epithelial cell dysfunction and mitigates abnormalities in lung tissues collected from CLP-stimulated mice via the miR-376b-3p/MAP3K1 axis in septic ALI. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-022-00169-7.

Dorsal BNST DRD2+ neurons mediate sex-specific anxiety-like behavior induced by chronic social isolation.

The dorsal bed nucleus of stria terminalis (dBNST) is a pivotal hub for stress response modulation. Dysfunction of dopamine (DA) network is associated with chronic stress, but the roles of DA network of dBNST in chronic stress-induced emotional disorders remain unclear. We examine the role of dBNST Drd1+ and Drd2+ neurons in post-weaning social isolation (PWSI)-induced behavior deficits. We find that male, but not female, PWSI rats exhibit negative emotional phenotypes and the increase of excitability and E-I balance of dBNST Drd2+ neurons. More importantly, hypofunction of dBNST Drd2 receptor underlies PWSI-stress-induced male-specific neuronal plasticity change of dBNST Drd2+ neurons. Furthermore, chemogenetic activation of dBNST Drd2+ neurons is sufficient to induce anxiogenic effects, while Kir4.1-mediated chronic inhibition of dBNST Drd2+ neurons ameliorate PWSI-induced anxiety-like behaviors. Our findings reveal an important neural mechanism underlying PWSI-induced sex-specific behavioral abnormalities and potentially provide a target for the treatment of social stress-related emotional disorder.

Lin28A Reduced Sevoflurane-Induced Nerve Injury and Cognitive Dysfunction by Inhibiting Tau Acetylation and Phosphorylation via Activating SIRT1 in Elderly Rats.

Sevoflurane (Sev) might cause neurotoxicity in elderly rats. However, the role of Lin28A in Sev-induced neurotoxicity remains unclear in elderly rats. In this study, elderly rats were used to construct an Sev-induced nerve injury model. Learning and memory abilities were assessed by Morris water maze (MWM) trainings; pathological alterations in hippocampal region were assessed by HE staining; neuronal apoptosis was assessed by TUNEL; related protein expression was analyzed by immunofluorescence, immunohistochemistry, and Western blotting. Results of this study showed that Sev treatment caused nerve injury and cognitive dysfunction in elderly rats, with increased neuronal apoptosis and decreased Lin28A levels. Pathological impairment and learning and memory abilities of elderly rats were significantly improved after forced overexpression of Lin28A using AAV, accompanied by decreased expression of CD68, Iba-1, and GFAP. TUNEL analysis showed that Lin28A overexpression significantly reversed Sev-induced neuronal apoptosis. Further mechanistic analysis showed that Lin28A significantly promoted SIRT1 expression, which further reversed Sev-induced Tau acetylation at lysine 280 and 686 and Tau hyperphosphorylation, thereby alleviating nerve injury and cognitive dysfunction in elderly rats. The introduction of SIRT1 inhibitor EX527 further confirmed the involvement of SIRT1 in the regulation of Lin28A in elderly rats. In conclusion, our findings demonstrated that Lin28A reduced sevoflurane-induced nerve injury and cognitive dysfunction by inhibiting Tau acetylation and phosphorylation via activating SIRT1 in elderly rats.

Knockdown of UAF1 alleviates sevoflurane-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.

Evidence has shown that suppression of the activation of NLRP3 inflammasome could ameliorate surgery/sevoflurane (SEV)-induced post-operative cognitive dysfunction (POCD). However, the underlying mechanisms remain unclear. UAF1 acts as a binding partner of USP1, which inhibits the ubiquitination-mediated degradation of NLRP3, indicating that UAF1 may be implicated in POCD through regulating the NLRP3 inflammasome. Here, we studied the role of UAF1/NLRP3 in SEV-induced cognitive impairment and neurotoxicity in rats. Neonatal rats were randomly divided into control, SEV, SEV+AAV-shNC and SEV+AAV-shUAF1 (UAF1-downregulated) groups. Morris water maze (MWM) test was applied to assess cognitive impairment. TUNEL staining, qRT-PCR and ELISA were used to assess the apoptosis and inflammation markers, respectively. The levels of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were quantified to determine oxidative stress. The results showed that SEV treatment led to significant cognitive impairment, increased apoptosis in hippocampal tissues, upregulation of MDA and inflammatory factors (TNF-α, IL-1ß, IL-18), as well as a decrease in SOD and CAT levels. All of the above observations were reversed by UAF1 downregulation. Furthermore, depletion of UAF1 neutralized SEV-mediated increase in p-NLRP3, p-IκBα and p-p65 levels. Altogether, the current study demonstrated that knockdown of UAF1 could alleviate SEV-induced cognitive impairment and neurotoxicity in rats by inhibiting pro-inflammatory signaling and oxidative stress.

Probiotic Saccharomyces boulardii attenuates cardiopulmonary bypass-induced acute lung injury by inhibiting ferroptosis.

OBJECTIVE: Acute lung injury (ALI) is one of the most common and fatal complications of cardiopulmonary bypass (CPB). Probiotics treatment has been shown to reduce lung injury in different experimental models. However, the effect of probiotics on CPB-induced ALI is still poorly understood. This study aimed to investigate whether probiotic Saccharomyces boulardii CNCM I-745 treatment protects against lung injury in a rat model of CPB. METHODS: Rats were orally gavaged with Saccharomyces boulardii CNCM I-745 once a day for 5 days before being subjected to CPB. Rats were euthanized post-CPB, and samples of lung tissue were processed for later investigation. The levels of inflammatory cytokines were measured by ELISA. The expression levels of ferroptosis markers in lungs were assessed by western blot. The microbes in feces and proximal colon of rats were analyzed by using 16S rDNA amplicon sequencing method. The ratio and maturity of conventional dendritic cells (cDCs) were determined by flow-cytometry. RESULTS: Saccharomyces boulardii CNCM I-745 treatment improved lung function, attenuated pathologic lung changes and decelerated the exacerbation of inflammatory cytokine level after experimental CPB. Saccharomyces boulardii CNCM I-745 treatment also inhibited CPB-induced ferroptosis, as evidenced by the changes of main markers of ferroptosis, namely, the increase of Glutathione peroxidase 4 (GPX4) and the decrease of Acyl-CoA synthetase long chain family member 4 (ACSL4). In addition, after Saccharomyces boulardii CNCM I-745 treatment, the ratio and maturity of conventional dendritic cells (cDCs) in the guts of rats with CPB were significantly up-regulated. CONCLUSION: Our findings suggest that probiotic Saccharomyces boulardii CNCM I-745 reduces CPB-induced lung injury through suppression of the ferroptosis in lung and up-regulation of the ratio and maturity of cDCs in gut.