Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients' poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.

Electrostimulation triggers an increase in cross-niche microbial associations toward enhancing organic nitrogen wastewater treatment.

As an efficient wastewater pretreatment biotechnology, electrostimulated hydrolysis acidification (eHA) has been used to accelerate the removal of refractory pollutants, which is closely related to the effects of electrostimulation on microbial interspecies associations. However, the ecological processes underpinning such linkages remain unresolved, especially for the microbial communities derived from different niches, such as the electrode surface and plankton. Herein, the principles of cross-niche microbial associations and community assembly were investigated using molecular ecological network and phylogenetic bin-based null model analysis (iCAMP) based on 16S rRNA gene sequences. The electrostimulated planktonic sludge and electrode biofilm displayed significantly (P < 0.05) 1.67 and 1.53 times higher organic nitrogen pollutant (azo dye Alizarin Yellow R) degradation efficiency than non-electrostimulation group, and the corresponding microbial community composition and structure were significantly (P < 0.05) changed. Electroactive bacteria and functional degraders were enriched in the electrode biofilm and planktonic sludge, respectively. Notably, electrostimulation strengthened the synergistic microbial associations (1.8 times more links) between sludge and biofilm members. Additionally, both electrostimulation and cross-niche microbial associations induced greater importance of deterministic assembly. Overall, this study highlights the specificity of cross-electrode surface microbial associations and ecological processes with electrostimulation and advances our understanding of the manipulation of sludge microbiomes in engineered wastewater treatment systems.

Plasma extracellular vesicle microRNA profiling and the identification of a diagnostic signature for stage I lung adenocarcinoma.

At present, there is no effective noninvasive method for the accurate diagnosis of early-stage lung adenocarcinoma (LUAD). This study examined the profile of plasma extracellular vesicle (EV)-delivered microRNAs (miRNAs) in patients with invasive stage I LUAD. In this study, a total of 460 participants were enrolled, including 254 patients with LUAD, 76 patients with benign pulmonary nodules (BPNs), and 130 healthy control patients (HCs). miRNA sequencing was used to analyze the EV miRNA profile of the patient plasma samples (n = 150). A diagnostic signature (d-signature) was identified by applying a stepwise logistic regression algorithm, and a single-center training cohort (n = 150) was tested, followed by a multicenter validation cohort (n = 100). A d-signature comprising four EV-derived miRNAs (hsa-miR-106b-3p, hsa-miR-125a-5p, hsa-miR-3615, and hsa-miR-450b-5p) was developed for the early detection of LUAD. The d-signature had high precision with area under the curve (AUC) values of 0.917 and 0.902 in the training and test cohorts, respectively. Moreover, the d-signature could recognize patients with adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) with AUC values of 0.846 and 0.92, respectively. To sum up, our study detailed the plasma EV-derived miRNA profile in early LUAD patients and developed an EV-derived miRNA d-signature to detect early LUAD.

MRI-based radiomics signature for identification of invisible basal cisterns changes in tuberculous meningitis: a preliminary multicenter study.

OBJECTIVE: To develop and evaluate a radiomics signature based on magnetic resonance imaging (MRI) from multicenter datasets for identification of invisible basal cisterns changes in tuberculous meningitis (TBM) patients. METHODS: Our retrospective study enrolled 184 TBM patients and 187 non-TBM controls from 3 Chinese hospitals (training dataset, 158 TBM patients and 159 non-TBM controls; testing dataset, 26 TBM patients and 28 non-TBM controls). nnU-Net was used to segment basal cisterns in fluid-attenuated inversion recovery (FLAIR) images. Subsequently, radiomics features were extracted from segmented basal cisterns in FLAIR and T2-weighted (T2W) images. Feature selection was carried out in three steps. Support vector machine (SVM) and logistic regression (LR) classifiers were applied to construct the radiomics signature to directly identify basal cisterns changes in TBM patients. Finally, the diagnostic performance was evaluated by the receiver operating characteristic (ROC) curve analysis, calibration curve, and decision curve analysis (DCA). RESULTS: The segmentation model achieved the mean Dice coefficients of 0.920 and 0.727 in the training and testing datasets, respectively. The SVM model with 7 T2WI-based radiomics features achieved best discrimination capability for basal cisterns changes with an AUC of 0.796 (95% CI, 0.744-0.847) in the training dataset, and an AUC of 0.751 (95% CI, 0.617-0.886) with good calibration in the testing dataset. DCA confirmed its clinical usefulness. CONCLUSION: The T2WI-based radiomics signature combined with deep learning segmentation could provide a fully automatic, non-invasive tool to identify invisible changes of basal cisterns, which has the potential to assist in the diagnosis of TBM. KEY POINTS: • The T2WI-based radiomics signature was useful for identifying invisible basal cistern changes in TBM. • The nnU-Net model achieved acceptable results for the auto-segmentation of basal cisterns. • Combining radiomics and deep learning segmentation provided an automatic, non-invasive approach to assist in the diagnosis of TBM.

Probing the Functional and Structural Connectivity Underlying EEG Traveling Waves.

Neural oscillations play an important role in the maintenance of brain function by regulating multi-scale neural activity. Characterizing the traveling properties of EEG is helpful for understanding the spatiotemporal dynamics of neural oscillations. However, traveling EEG based on non-invasive approach has little been investigated, and the relationship with brain intrinsic connectivity is not well known. In this study, traveling EEG of different frequency bands on the scalp in terms of the center of mass (EEG-CM) was examined. Then, two quantitative indexes describing the spatiotemporal features of EEG-CM were proposed, i.e., the traveling lateralization and velocity of EEG-CM. Further, based on simultaneous EEG-MRI approach, the relationship between traveling EEG-CM and the resting-state functional networks, as well as the microstructural connectivity of white matter was investigated. The results showed that there was similar spatial distribution of EEG-CM under different frequency bands, while the velocity of rhythmic EEG-CM increased in higher frequency bands. The lateralization of EEG-CM in low frequency bands (< 30 Hz) demonstrated negative relationship with the basal ganglia network (BGN). In addition, the velocity of the traveling EEG-CM was associated with the fractional anisotropy (FA) in corpus callosum and corona radiate. These results provided valid quantitative EEG index for understanding the spatiotemporal characteristics of the scalp EEG, and implied that the EEG dynamics were representations of functional and structural organization of cortical and subcortical structures.

WeBrain: A web-based brainformatics platform of computational ecosystem for EEG big data analysis.

The current evolution of 'cloud neuroscience' leads to more efforts with the large-scale EEG applications, by using EEG pipelines to handle the rapidly accumulating EEG data. However, there are a few specific cloud platforms that seek to address the cloud computational challenges of EEG big data analysis to benefit the EEG community. In response to the challenges, a WeBrain cloud platform (https://webrain.uestc.edu.cn/) is designed as a web-based brainformatics platform and computational ecosystem to enable large-scale EEG data storage, exploration and analysis using cloud high-performance computing (HPC) facilities. WeBrain connects researchers from different fields to EEG and multimodal tools that have become the norm in the field and the cloud processing power required to handle those large EEG datasets. This platform provides an easy-to-use system for novice users (even no computer programming skills) and provides satisfactory maintainability, sustainability and flexibility for IT administrators and tool developers. A range of resources are also available on https://webrain.uestc.edu.cn/, including documents, manuals, example datasets related to WeBrain, and collected links to open EEG datasets and tools. It is not necessary for users or administrators to install any software or system, and all that is needed is a modern web browser, which reduces the technical expertise required to use or manage WeBrain. The WeBrain platform is sponsored and driven by the China-Canada-Cuba international brain cooperation project (CCC-Axis, http://ccc-axis.org/), and we hope that WeBrain will be a promising cloud brainformatics platform for exploring brain information in large-scale EEG applications in the EEG community.

Identification and validation of cellular senescence patterns to predict clinical outcomes and immunotherapeutic responses in lung adenocarcinoma.

BACKGROUND: Aging and senescence can alter immune cell fitness and influence the efficacy of lung cancer treatments, especially immunotherapy. However, the correlations between cellular senescence and tumor microenvironment are still not clearly clarified and the value of cellular senescence-related genes in evaluating the immune infiltration and clinical outcomes of lung adenocarcinoma (LUAD) need further investigated. METHODS: We identified three cellular senescence clusters by NMF algorithm and correlated the cellular senescence clusters with the immune landscape in LUAD patients. A prognostic scoring system was established using random survival forest algorithm and validated in 4 external cohorts. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the scoring system. Expression of LYPD3 was evaluated by immunohistochemistry in LUAD samples. RESULTS: Based on the mRNA expression profiles of 278 cellular senescence-related genes, three cellular senescence clusters with distinct prognosis were identified. We characterized three cellular senescence clusters by differences in biological processes, EMT score, expression of immunomodulatory genes, extent of intratumor heterogeneity and response to immunotherapy. Meanwhile, a cellular senescence-related scoring system (CSS) was established and validated as an independent prognostic factor and immunotherapy predictor of LUAD. Patients with low CSS was characterized by prolonged survival time. In response to anti-cancer drugs, patients with low CSS exhibited higher sensitivities to molecular drugs, such as Roscovitine (CDKs inhibitor), Lenaidornide (TNF-α inhibitor), MK2206 (Akt 1/2/3 inhibitor), and especially increased response to anti-PD-1/L1 immunotherapy. CONCLUSIONS: This study demonstrated the correlations between cellular senescence patterns and tumor immune landscape in LUAD, which enhanced our understanding of the tumor immune microenvironment and provided new insights for improving the outcome of immunotherapy for LUAD patients.

The size effect in adhesive contact on a gradient nanostructured coating.

The adhesive contact problem between a rigid cylindrical punch and a gradient nanostructured (GNS) coating is investigated by considering the size effect. The laminated plate model is applied to characterize the material properties of a GNS coating in plane strain couple stress elasticity. By using the Fourier integral transform and transfer matrix method, the governing integral equation(s) for the two-dimensional adhesive contact problem are obtained. Numerically calculated results are presented to analyse the effect of characteristic material length, the adhesion parameter and nonhomogeneous parameters on the mechanical response of the GNS coating for the adhesive contact problem. We explore the nanoscale contact of a GNS coating with shear modulus varying as a function of depth according to an exponential function or the power-law function. The present results provide a way to improve the contact deformation and damage to nanoelectromechanical systems by adjusting the gradient index of the GNS coating.

Reference Electrode Standardization Interpolation Technique (RESIT): A Novel Interpolation Method for Scalp EEG.

"Bad channels" are common phenomena during scalp electroencephalography (EEG) recording that arise due to various technique-related reasons, and reconstructing signals from bad channels is an inevitable choice in EEG processing. However, current interpolation methods are all based on purely mathematical interpolation theory, ignoring the neurophysiological basis of the EEG signals, and their performance needs to be further improved, especially when there are many scattered or adjacent bad channels. Therefore, a new interpolation method, named the reference electrode standardization interpolation technique (RESIT), was developed for interpolating scalp EEG channels. Resting-state and event-related EEG datasets were used to investigate the performance of the RESIT. The main results showed that (1) assuming 10% bad channels, RESIT can reconstruct the bad channels well; (2) as the percentage of bad channels increased (from 2% to 85%), the absolute and relative errors between the true and RESIT-reconstructed signals generally increased, and the correlations between the true and RESIT signals decreased; (3) for a range of bad channel percentages (2% ~ 85%), the RESIT had lower absolute error (approximately 2.39% ~ 33.5% reduction), lower relative errors (approximately 1.3% ~ 35.7% reduction) and higher correlations (approximately 2% ~ 690% increase) than traditional interpolation methods, including neighbor interpolation (NI) and spherical spline interpolation (SSI). In addition, the RESIT was integrated into the EEG preprocessing pipeline on the WeBrain cloud platform ( https://webrain.uestc.edu.cn/ ). These results suggest that the RESIT is a promising interpolation method for both separate and simultaneous EEG preprocessing that benefits further EEG analysis, including event-related potential (ERP) analysis, EEG network analysis, and strict group-level statistics.

[Yishen Huoxue Decoction for infertility in elderly men with kidney deficiency and blood stasis].

OBJECTIVE: To observe the clinical effect of Yishen Huoxue Decoction on infertility in elderly men with kidney deficiency and blood stasis. METHODS: We randomly assigned 60 infertility male patients with kidney deficiency and blood stasis to two groups of an equal number to receive Yishen Huoxue Decoction, 1 dose a day, twice daily in the morning and evening (the observation group, aged ï¼»42.10 ± 3.82ï¼½ yr) or Shengjing Tablets (4 tablets once, tid) combined with L-carnitine oral solution at 10 ml, bid (the control group, aged ï¼»42.79 ± 3.56ï¼½ yr), both for 3 months. Before and after treatment, we obtained the semen parameters, levels of reproductive hormones and traditional Chinese medicine (TCM) clinical symptoms scores from the patients and compared them between the two groups. RESULTS: A total of 57 patients completed this clinical study, 29 in the observation group, with pregnancy achieved in 2 cases (6.90%), and 28 in the control group, with pregnancy achieved in 1 (3.57%). The patients in the observation group, compared with the controls, showed significantly higher total effectiveness (82.76% vs 71.43%, P < 0.05) and overall therapeutic efficacy on TCM syndromes (93.10% vs 85.71%, P < 0.05), as well as higher semen volume, sperm concentration, total sperm count, total sperm motility, percentages of progressively motile sperm (PMS) and morphologically normal sperm (MNS), and TCM clinical symptoms scores (all P < 0.05), but no statistically significant difference in the levels of reproductive hormones (E2, LH, PRL, T and FSH) (P > 0.05). Remarkable increases were observed in both the observation and control groups after medication in sperm concentration, total sperm count, total sperm motility, PMS, MNS, and TCM clinical symptom scores (all P < 0.05). CONCLUSIONS: Yishen Huoxue Decoction can significantly improve the semen quality and TCM clinical symptoms of elderly infertility males with kidney deficiency and blood stasis.

[Bacomics--a new discipline integrating brain and the outside].

Bacomics is a unified framework for the interactions of the brain and the outside world, integrating the subject, method, and application mode of brain-apparatus conversation. This article divides the brain-apparatus conversation modes from the perspective of biological and non-biological apparatus, including the brain-biological organ interaction (BAC-1), brain-external non-living equipment and environment interaction (BAC-2), and the fusion agents of these two interactions (BAC-3), and explains the ways and potential applications in different modes.

Disruption of microRNA-214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2.

Duration of surgical general anaesthesia is associated with severe brain injury and neurological deficits. The specific mechanisms underlying post-general anaesthesia brain injury, however, still remain to be elucidated. Herein, we explore the role of microRNA-214 (miR-214) in the occurrence of brain injury after general anaesthesia and its underlying mechanism. Hippocampal tissues and neurons were isolated from rats exposed to 2% sevoflurane. TUNEL stains reflect hippocampal neuron apoptosis. Cultured hippocampal neurons stained with JC-1 and MitoTracker dyes were imaged by fluorescence microscope to visualize changes of mitochondrial membrane potential and mitochondrial fusion. Mitochondrial function was evaluated. Mitofusin 2 (Mfn2) binding to miR-214 or pyruvate kinase M2 (Pkm2) was confirmed by co-immunoprecipitation, immunofluorescence, dual luciferase reporter gene and RNA immunoprecipitation assays. After exposure to 2% sevoflurane, up-regulated miR-214 expression and impaired interaction between Mfn2 and Pkm2 were found in rat hippocampal tissues. Rats exposed to 2% sevoflurane also experienced neuronal injury, mitochondrial defects and deficits in the brain-derived neurotrophic factor (Bdnf) signalling. miR-214 was shown to target Mfn2 by impairing its binding with Pkm2. Inhibiting miR-214 expression using its specific inhibitor improved mitochondrial membrane potential, enhanced mitochondrial fusion, maintained mitochondrial function, restored interaction between Mfn2 and Pkm2, and activated the Bdnf signalling in cultured hippocampal neurons. Adenovirus infection of miR-214 inhibitor reduced neuron apoptosis and maintained mitochondrial function in the hippocampus of rats exposed to 2% sevoflurane. Taken together, the study demonstrates inhibition of miR-214 is cerebral protective against brain injury following general anaesthesia.

Value of the Barthel scale in prognostic prediction for patients with cerebral infarction.

BACKGROUND: This study aims to evaluate the ADL(activity of daily living) of patients with acute cerebral infarction through BI scoring, in order to observe its predictive value in the prognosis of these patients. METHODS: According to the inclusion and exclusion criteria, patients with acute anterior circulation cerebral infarction were included in the present study. Then, the BI scoring was analyzed through five grades, in order to further investigate the dose-response relationship between BI scoring and mortality risk in patients with cerebral infarction. The receiver operating characteristic (ROC) curves for BI-scored patients were drawn, and the predictive authenticity of the Barthel scale in prognostic prediction for patients with cerebral infarction was estimated. RESULTS: The difference in BI scores between the survival group and death group were statistically significant (t = 10.029, P < 0.05), in which the score was lower in the death group than in the survival group. According to the linear trend ×2-test, the decrease in BI score indicates an increase in mortality risk in patients with cerebral infarction. The area under the curve (AUC) of the ROC curve was 0.794 with a P-value of < 0.05. CONCLUSION: BI scoring is a highly valuable scoring system for the prognostic prediction of patients with acute cerebral infarction.

Temporal changes of CT findings between non-severe and severe cases of COVID-19 pneumonia: a multi-center, retrospective, longitudinal Study.

Background and aim: To perform a longitudinal analysis of serial CT findings over time in patients with COVID-19 pneumonia. Methods: From February 5 to March 8, 2020, 73 patients (male to female, ratio of 43:30; mean age, 51 years) with COVID-19 pneumonia were retrospectively enrolled and followed up until discharge from three institutions in China. The patients were divided into the severe and non-severe groups according to treatment option. The patterns and distribution of lung abnormalities, total CT scores, single ground-glass opacity (GGO) CT scores, single consolidation CT scores, single reticular CT scores and the amounts of zones involved were reviewed by 2 radiologists. These features were analyzed for temporal changes. Results: In non-severe group, total CT scores (median, 9.5) and the amounts of zones involved were slowly increased and peaked in disease week 2. In the severe group, the increase was faster, with scores also peaking at 2 weeks (median, 20). In both groups, the later parameters began to decrease in week 4 (median values of 9 and 19 in the non-severe and severe groups, respectively). In the severe group, the dominant residual lung lesions were reticular (median single reticular CT score, 10) and consolidation (median single consolidation CT score, 7). In the non-severe group, the dominant residual lung lesions were GGO (median single GGO CT score, 7) and reticular (median single reticular CT score, 4). In both non-severe and severe groups, the GGO pattern was dominant in week 1, with a higher proportion in the severe group compared with the non-severe group (72% vs. 65%). The consolidation pattern peaked in week 2, with 9 (32%) and 19 (73%) in the non-severe and severe groups, respectively; the reticular pattern became dominant from week 4 (both group >40%). Conclusion: The extent of CT abnormalities in the severe and non-severe groups peaked in disease week 2. The temporal changes of CT manifestations followed a specific pattern, which might indicate disease progression and recovery.

BOLD-fMRI reveals the association between renal oxygenation and functional connectivity in the aging brain.

Aging is accompanied by a decline in physical and cognitive function. Vascular aging may provide a major influence on these measures. The purpose of this study was to explore the relationship between renal oxygenation and functional connectivity of the aging brain because of the anatomic and hemodynamic similarities between cerebral and renal vessels. Fifty-two healthy older adults were recruited to undergo a BOLD-fMRI scan of the brain and kidneys, and forty-four healthy younger subjects were recruited as the control group. First, cerebral functional connectivity density (FCD) was used to evaluate functional connectivity. Renal medullary and cortical R2* values were extracted respectively, and the ratio of medullary and cortical R2* values (MCR) was calculated. Then, the association between brain FCD and renal MCR was analyzed. Compared with younger adults, the elderly group showed higher renal medullary R2* and MCR, which might reflect a slight abnormality of renal oxygenation with aging. The older subjects also showed enhanced FCD in bilateral motor-related regions and decreased FCD in regions of the default mode network (DMN). The findings indicated that the functional connectivity in the DMN and motor cortices was vulnerable to aging. Moreover, the altered brain FCD values in the watershed regions, DMN and motor cortices were significantly correlated with the renal MCR value in the elderly group. The association between renal oxygenation abnormalities and spontaneous activity in the brain might reflect vascular aging and its influence on the kidney and brain during aging to some extent. This study provided a new perspective for understanding the relationship between tissue oxygenation and brain functional connectivity.

Electronic-Sports Experience Related to Functional Enhancement in Central Executive and Default Mode Areas.

Electronic-sports (e-sports) is a form of organized, online, multiplayer video game competition, which requires both action skills and the ability and process of forming and adapting a strategy (referred to as strategization hereafter) to achieve goals. Over the past few decades, research has shown that video gaming experience has an important impact on the plasticity of the sensorimotor, attentional, and executive brain areas. However, little research has examined the relationship between e-sports experience and the plasticity of brain networks that are related to strategization. Using resting-state fMRI data and the local functional connectivity density (lFCD) analysis, this study investigated the relationship between e-sports experience (League of Legends [LOL] in this study) and brain plasticity by comparing between top-ranking LOL players and lower-ranking (yet experienced) LOL players. Results showed that the top-ranking LOL players had superior local functional integration in the executive areas compared to lower-ranking players. Furthermore, the top-ranking players had higher lFCD in the default mode areas, which have been found related to various subprocesses (e.g., memory and planning) essential for strategization. Finally, the top-ranking players' lFCD was related to their LOL expertise rank level, as indicated by a comprehensive score assigned by the gaming software based on players' gaming experience and expertise. Thus, the result showed that the local functional connectivity in central executive and default mode brain areas was enhanced in the top-ranking e-sports players, suggesting that e-sports experience is related to the plasticity of the central executive and default mode areas.

Experimental Investigation on Interfacial Defect Criticality of FRP-Confined Concrete Columns.

Defects between fiber reinforced polymer (FRP) and repaired concrete components may easily come out due to misoperation during manufacturing, environmental deterioration, or impact from external load during service life. The defects may cause a degraded structure performance and even the unexpected structural failure. Different non-destructive techniques (NDTs) and sensors have been developed to assess the defects in FRP bonded system. The information of linking up the detected defects by NDTs and repair schemes is needed by assessing the criticality of detected defects. In this study, FRP confined concrete columns with interfacial defects were experimentally tested to determine the interfacial defect criticality on structural performance. It is found that interfacial defect can reduce the FRP confinement effectiveness, and ultimate strength and its corresponding strain of column deteriorate significantly if the interfacial defect area is larger than 50% of total confinement area. Meanwhile, proposed analytical model considering the defect ratio is validated for the prediction of stress⁻strain behavior of FRP confined columns. The evaluation of defect criticality could be made by comparing predicted stress⁻strain behavior with the original design to determine corresponding maintenance strategies.

Effects of microRNA-206 and its target gene IGF-1 on sevoflurane-induced activation of hippocampal astrocytes in aged rats through the PI3K/AKT/CREB signaling pathway.

The study aims to explore the effects of microRNA-206 (miR-206) targeting IGF-1 on the activation of hippocampal astrocytes in aged rats induced by sevoflurane through the PI3K/AKT/CREB signaling pathway. Wistar rats and astrocytes were divided into the normal/blank, sham/negative control (NC), sevoflurane (sevo), miR-206 mimics+sevo, miR-206 inhibitors+sevo, miR-206 NC+sevo, IGF-1 shRNA+sevo, and miR-206 inhibitors+IGF-1 shRNA+sevo groups. The Morris water maze test was exhibited to assess the cognitive functions. Glial fibrillary acidic protein (GFAP) expression was detected by immunofluorescence assay. Western blotting and RT-qPCR were used to detect the expression of miR-206, IGF-1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, cytochrome-c (Cyt-c), and caspase-3. Cell viability and apoptosis were detected by MTT assay and annexin V/PI double staining respectively. Mitochondrial transmembrane potential (MTP) were determined by flow cytometry. The IGF-1 shRNA+sevo group showed reduced miR-206 expression. Compared with the normal/blank group, the sevo, and miR-206 NC+sevo groups showed decreased miR-206 and GFAP expressions, cell viability and MTP but increased expressions of IGF-1, PI3K, AKT, CREB, pPI3K, pAKT, pCREB, Cyt-c and caspase-3, as well as cell apoptosis. Similar trends were observed in the miR-206 inhibitors+sevo group when compared with the sevo group. The study provides evidence that miR-206 alleviates the inhibition of activation of hippocampal astrocytes in aged rats induced by sevoflurane by targeting IGT-1 through suppressing the PI3K/AKT/CREB signaling pathway.

Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP/PKA Pathway in Mice.

BACKGROUND/AIMS: Long non-coding RNA (lncRNA) and glucagon-like peptide 1 receptor (GLP-1R) are crucial for heart development and for adult heart structural maintenance and function. Herein, we performed a study to explore the effect of lncRNA LINC00652 (LINC00652) on myocardial ischemia-reperfusion (I/R) injury by targeting GLP-1R through the cyclic adenosine monophosphate-protein kinase A (cAMP/PKA) pathway. METHODS: Bioinformatics software was used to screen the long-chain non-coding RNAs associated with myocardial ischemia-reperfusion and to predict target genes. The mRNA and protein levels of LINC00652, GLP-1R and CREB were detected by RT-qPCR and western blotting. In order to identify the interaction between LINC00652 and myocardial I/R injury, the cardiac function, the hemodynamic changes, the pathological changes of the myocardial tissues, the myocardial infarct size, and the apoptosis of myocardial cells of mice were measured. Meanwhile, the levels of serum IL-1ß and TNF-α were detected. RESULTS: LINC00652 was overexpressed in the myocardial cells of mice with myocardial I/R injury. GLP-1R is the target gene of LINC00652. We also determined higher levels of LINC00652 and GLP-1R in the I/R modeled mice. Additionally, si-LINC00652 decreased cardiac pathology, infarct size, apoptosis rates of myocardial cells, and levels of IL-1ß and TNF-α, and increased GLP-1R expression cardiac function, normal hemodynamic index, and the expression and phosphorylation of GLP-1R and CREB proteins. CONCLUSION: Taken together, our key findings of the present highlight LINC00652 inhibits the activation of the cAMP/PKA pathway by targeting GLP-1R to reduce the protective effect of sevoflurane on myocardial I/R injury in mice.

MicroRNA-374 Exerts Protective Effects by Inhibiting SP1 Through Activating the PI3K/Akt Pathway in Rat Models of Myocardial Ischemia-Reperfusion After Sevoflurane Preconditioning.

BACKGROUND/AIMS: Ischemic heart disease is a leading cause of death in cardiovascular diseases, and microRNAs (miRs) have been reported to be potential therapeutic targets in heart disease. Herein, this study aims to investigate the effects of microRNA (miR)-374 on myocardial ischemia-reperfusion (I/R) injury in rat models pretreated with sevoflurane by targeting SP1 through the PI3K/Akt pathway. METHODS: SD rats were grouped into sham, I/R and sevoflurane + I/R (sevoflurane preconditioning and I/R) groups. The biochemical indicators, pathological changes, positive expression of SP1 protein, and apoptosis rates were measured using biochemical detection, Evans blue-TTC staining, immunohistochemistry and TUNEL staining. RT-qPCR and Western blotting were used to investigate the expression of miR-374 mRNA and the protein expression of SP1, PI3K, HO-1, p53, iNOS, c-fos, Akt/p-Akt, and GSK-3ß/p-GSK-3ß. Cardiomyocytes were treated with miR-374 mimics, miR-374 inhibitors, or siRNA-SP1. Cardiomyocyte proliferation and cycle distribution and apoptosis were studied by MTT and flow cytometry. RESULTS: Compared with the I/R group, in the sevoflurane + I/R group, serum SOD and IL-10 increased, while MDA, LDH, CK, TNF-α, IL-6 and IL-10 decreased, as did the percentage of infarct area, the positive rate of SP1 and the apoptosis index. The expression of SP1, p53, iNOS and c-fos decreased, and the miR-374 expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. With the upregulation of miR-374 and the downregulation of SP1, the expression of SP1, p53, iNOS and c-fos decreased, as did the proportion of cells in G1 phase and the apoptosis rate; the expression of PI3K, HO-1, Akt/p-Akt, GSK-3ß/p-GSK-3ß increased. The results in the miR-374 inhibitor group contrasted with the above results. CONCLUSION: The results indicated that miR-374 could alleviate myocardial I/R damage in rat models pretreated with sevoflurane by targeting SP1 by activating the PI3K/Akt pathway.