N6-methyladenosine-modified circPLPP4 sustains cisplatin resistance in ovarian cancer cells via PIK3R1 upregulation.

BACKGROUND: Cisplatin (CDDP) is the first-line chemotherapeutic strategy to treat patients with ovarian cancer (OC). The development of CDDP resistance remains an unsurmountable obstacle in OC treatment and frequently induces tumor recurrence. Circular RNAs (circRNAs) are noncoding RNAs with important functions in cancer progression. Whether circRNAs function in CDDP resistance of OC is unclear. METHODS: Platinum-resistant circRNAs were screened via circRNA deep sequencing and examined using in situ hybridization (ISH) in OC. The role of circPLPP4 in CDDP resistance was assessed by clone formation and Annexin V assays in vitro, and by OC patient-derived xenografts and intraperitoneal tumor models in vivo. The mechanism underlying circPLPP4-mediated activation of miR-136/PIK3R1 signaling was examined by luciferase reporter assay, RNA pull-down, RIP, MeRIP and ISH. RESULTS: circPLPP4 was remarkably upregulated in platinum resistant OC. circPLPP4 overexpression significantly enhanced, whereas circPLPP4 silencing reduced, OC cell chemoresistance. Mechanistically, circPLPP4 acts as a microRNA sponge to sequester miR-136, thus competitively upregulating PIK3R1 expression and conferring CDDP resistance. The increased circPLPP4 level in CDDP-resistant cells was caused by increased RNA stability, mediated by increased N6-methyladenosine (m6A) modification of circPLPP4. In vivo delivery of an antisense oligonucleotide targeting circPLPP4 significantly enhanced CDDP efficacy in a tumor model. CONCLUSIONS: Our study reveals a plausible mechanism by which the m6A -induced circPLPP4/ miR-136/ PIK3R1 axis mediated CDDP resistance in OC, suggesting that circPLPP4 may serve as a promising therapeutic target against CDDP resistant OC. A circPLPP4-targeted drug in combination with CDDP might represent a rational regimen in OC.

The c-MYC-WDR43 signalling axis promotes chemoresistance and tumour growth in colorectal cancer by inhibiting p53 activity.

Oxaliplatin chemoresistance is a major challenge in the clinical treatment of colorectal cancer (CRC), which is one of the most common malignancies worldwide. In this study, we identified the tryptophan-aspartate repeat domain 43 (WDR43) as a potentially critical oncogenic factor in CRC pathogenesis through bioinformatics analysis. It was found that WDR43 is highly expressed in CRC tissues, and WDR43 overexpression is associated with poor prognosis of CRC patients. WDR43 knockdown significantly inhibits cell growth by arresting cell cycle and enhancing the effect of oxaliplatin chemotherapy both in vitro and in vivo. Mechanistically, upon oxaliplatin stimulation, c-MYC promotes the transcriptional regulation and expression of WDR43. WDR43 enhances the ubiquitination of p53 by MDM2 through binding to RPL11, thereby reducing the stability of the p53 protein, which induces proliferation and chemoresistance of CRC cells. Thus, the overexpression of WDR43 promotes CRC progression, and could be a potential therapeutic target of chemoresistance in CRC.

Oblique lumbar interbody fusion combined with anterolateral screw fixation and stress endplate augmentation for treating degenerative lumbar spondylolisthesis with osteoporosis.

PURPOSE: To evaluate the outcomes of Oblique lumbar interbody fusion (OLIF)combined with anterolateral screw fixation (AF) and Stress Endplate Augmentation(SEA) versus OLIF-AF in the treatment of degenerative lumbar spondylolisthesis (DLS)with osteoporosis (OP). METHODS: 30 patients underwent OLIF-AF-SEA (SEA group) were matched with 30 patients received OLIF-AF (control group), in terms of sex, age, body mass index (BMI) and bone mineral density (BMD). Clinical outcomes including visual analog scale (VAS) score of the lower back pain (VAS-LBP), leg pain (VAS-LP), and Oswestry Disability Index (ODI) were evaluated at different postoperative intervals and comparedwith their preoperative counterparts. Radiographic outcomes such as disk height (DH), slip distance (SD), lumbar lordosis (LL), segmental lordosis (SL), cage subsidence (CS) rate and fusion rate were evaluated at different postoperative intervals and compared with their preoperative counterparts. RESULTS: SEA group presented to be better at 3-month and 12-month follow-up, the VAS-LBP, VAS-LP and ODI scores of the SEA group were significantly lower than the control group (3-month SEA vs control: 2.30±0.70 vs 3.30±0.75, 2.03±0.72 vs 2.90±0.76,15.60±2.36 vs 23.23±3.07, respectively, all p<0.05. VAS-LBP and ODI 12-month SEA vs control: 1.27±0.74 vs 1.93±0.58, 12.20±1.88 vs 14.43±1.89,respectively, all p<0.05). At 24-month follow-up, both groups showed no difference in fusion rate (83.33% vs 90.00%, p=0.45), while SEA group showed a lower CS rate (13.33% vs 53.33%, p<0.05). CONCLUSION: OLIF-AF-SEA was safe with no adverse effects and resulted in lower CS rate and better sagittal balance. OLIF-AF-SEA is a promising surgical method for treating patients with DLS-OP.

Liquid nitric oxide donor for adjuvant therapy of acute ischemic stroke via nasal administration.

OBJECTIVES: The aim of this study was to synthesize and characterize a novel NO donor, PEI-PO-NONOate, using propylene oxide and to investigate its biosafety and therapeutic efficacy via nasal administration in vitro and vivo. EXPERIMENTAL PROCEDURES: The PEI-PO-NONOate was synthesized based on polyethylenimine (PEI) with different molecular weights and characterized using Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR), and ultraviolet (UV) spectroscopy. Cytotoxicity assays were performed on mouse fibroblast cells L929 and human nasal mucosa epithelial cells (HNEpC), and a rat middle cerebral artery occlusion (MCAO) model was established to evaluate the therapeutic efficacy of PEI-PO-NONOate via nasal administration. RESULTS: The PEI-PO-NONOate was found to be stable under dark, dry, and airproof conditions, and its release was accelerated in an aqueous phase or acidic environment, while it was slowed down in a polyethylene glycol (PEG) mixture system. The NO donor released approximately 0.4, 0.5, and 0.6 µmol of gaseous NO from 1.0 mg of the polymer based on PEI600, PEI1800, and PEI10K, respectively. Cytotoxicity assays showed that the PEI-PO-NONOates had a cryoprotective effect as compared with PEI and PEI-PO. Furthermore, nasal administration of PEI-PO-NONOates resulted in a significant reduction in overall necrotic ratio as compared with the control group (16.4% versus 24.6%, p < 0.05). CONCLUSION: The findings of this study suggest that PEI-PO-NONOates may have potential as an adjuvant therapy for acute ischemic stroke when administered via the nasal route.

Comparison of predictive performance for cage subsidence between CT-based Hounsfield units and MRI-based vertebral bone quality score following oblique lumbar interbody fusion.

OBJECTIVE: To compare the predictive performance between CT-based Hounsfield units (HU) and MRI-based vertebral bone quality (VBQ) for cage subsidence (CS) following oblique lumbar interbody fusion combined with anterolateral single-rod screw fixation (OLIF-AF). METHODS: A retrospective study was performed on consecutive patients who underwent OLIF-AF at our institution from 2018 to 2020. CS was determined by CT according to the change in the midpoint intervertebral space height. The VBQ score and HU value were measured from preoperative MRI and CT, respectively. Then, we evaluated the predictive performance of those two parameters by comparing the receiver operating characteristic (ROC) curves. RESULTS: The mean global and segmental VBQ scores were significantly higher in the CS group, and the mean global and segmental HU values were significantly lower in the CS group. The area under the curve (AUC) of CS prediction was higher in the operative segments' VBQ score and HU value than the measurement in the global lumbar spine. Finally, the combined segmental VBQ score and segmental HU value demonstrated the highest AUC. CONCLUSION: Both MRI-based VBQ score and CT-based HU value can achieve accurate CS prediction. Moreover, the combination of those two measurements indicated the best predictive performance. CLINICAL RELEVANCE STATEMENT: Both MRI-based VBQ score and CT-based HU value can be used for cage subsidence prediction, in order to take preventive measures early enough. KEY POINTS: • Osteoporosis is a risk factor for CS, both MRI-based VBQ score and CT-based HU value are important predictors during vertebral bone quality evaluation. • The VBQ score and HU value measured in the operative segments are better predictors of CS than the measurement in the global lumbar spine. • Combined segmental VBQ score and segmental HU value achieved the best predictive performance for CS.

IgG1 Is the Optimal Subtype for Treating Atherosclerosis by Inducing M2 Macrophage Differentiation, and Is Independent of the FcγRIIA Gene Polymorphism.

In recent years, it has been established that atherosclerosis is an autoimmune disease. However, little is currently known about the role of FcγRIIA in atherosclerosis. Herein, we sought to investigate the relationship between FcγRIIA genotypes and the effectiveness of different IgG subclasses in treating atherosclerosis. We constructed and produced different subtypes of IgG and Fc-engineered antibodies. In vitro, we observed the effect of different subtypes of IgG and Fc-engineered antibodies on the differentiation of CD14+ monocytes from patients or healthy individuals. In vivo, Apoe-/- mice were fed a high-fat diet (HFD) for 20 weeks and administered injections of different CVI-IgG subclasses or Fc-engineered antibodies. Flow cytometry was used to assess the polarization of monocytes and macrophages. Although CVI-IgG4 reduced the release of MCP-1 compared to the other subtypes, IgG4 did not yield an anti-inflammatory effect by induction of human monocyte and macrophage differentiation in vitro. Furthermore, genetic polymorphisms of FcγRIIA were not associated with different CVI-IgG subclasses during the treatment of atherosclerosis. In vivo, CVI-IgG1 decreased Ly6Chigh monocyte differentiation and promoted M2 macrophage polarization. We also found that the secretion of IL-10 was upregulated in the CVI-IgG1-treated group, whereas V11 and GAALIE exerted no significant effect. These findings highlight that IgG1 is the optimal subtype for treating atherosclerosis, and CVI-IgG1 can induce monocyte/macrophage polarization. Overall, these results have important implications for the development of therapeutic antibodies.

High AKAP8L expression predicts poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a severe disease with high mortality, and is associated with poor prognosis and frequent lymphatic metastasis. Therefore, prognostic indicators for ESCC are urgently needed. A-kinase anchor-protein 8-like (AKAP8L) is a member of the A kinase anchor-protein (AKAPs) family and is overexpressed in many cancers. However, the role of AKAP8L in ESCC remains unclear. The aim of this study is to investigate the expression patterns and prognostic value of AKAP8L in ESCC. METHODS: The mRNA expression of AKAP8L was analyzed from the dataset of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Immunohistochemistry was applied to detect the AKAP8L expression in tissue microarray. Pearson's chi-square test was carried out for the correlation analysis of clinicopathological features and AKAP8L expression. The prognostic significance of clinicopathological features and AKAP8L expression was determined by univariate and multivariate Cox hazard models. Kaplan-Meier survival curve was used for survival analysis. RESULTS: We found that the mRNA level of AKAP8L was higher in tumor tissues than in adjacent tissues in TCGA and GEO dataset. High AKAP8L expression was associated with poor overall survival (OS) in ESCC patients (p = 0.0039). Besides, AKAP8L expression was highly expressed in patients with lymph node metastasis detected by ESCC tissue microarray (p = 0.0014). The comparison of the different clinicopathological features of ESCC between high and low AKAP8L expression groups revealed that high AKAP8L expression was related to lymph node stage (p = 0.041). Kaplan-Meier survival analysis revealed that high AKAP8L expression indicates an unfavorable progression-free survival (PFS) and OS in ESCC patients (p < 0.0001). Univariate and multivariate analyses confirmed that AKAP8L was an independent prognostic factor for PFS and OS in ESCC (p = 0.003 and p < 0.0001). CONCLUSIONS: In conclusion, this study demonstrated that high expression of AKAP8L is associated with poor prognosis of ESCC and can be considered an independent risk factor for ESCC.

Computational fluid dynamics simulation of hemodynamic changes in a hemodialysis patient with central venous stenosis treated with stent.

BACKGROUND: It has not been demonstrated that computational fluid dynamics (CFD) can be used to model central venous stenosis (CVS), nor that hemodynamic changes in CVS treated with stent placement can be anticipated. The purpose of this study was to demonstrate the hemodynamic performance of CVS patients treated with stent placement. METHODS: Patient-specific geometric models were constructed using computed tomography images of veins from hemodialysis patients treated with stent placement. CFD simulation based on geometry was performed using ANSYS-15 to compare pressure quantitatively, wall shear stress (WSS), and flow velocity in the brachial vein before and after stent placement. RESULTS: Following a covered stent placement, the swelling of the left upper extremity was relieved. Prior to stent implantation, the maximum and mean brachial vein wall pressures were 465.2 Pa and 224.609 Pa, respectively. It was determined that the maximum WSS value was 8.449 Pa and that the mean WSS value was 0.743 Pa. The maximum and mean flow velocities were 1.16 and 0.173 m/s, respectively. After stent placement, the maximum wall pressure, maximum WSS, and maximum flow velocity dropped by 59.4%, 71.2%, and 57.8%, respectively. The mean wall pressure, mean WSS, and mean flow rate decreased by 43.5%, 52.7%, and 17.6%, respectively. CONCLUSION: Hemodynamics of CVS in hemodialysis patients exhibited turbulent, imbalances and disorders, which can be improved by stent placement.

Spontaneous facet joint fusion in patients following oblique lateral lumbar interbody fusion combined with lateral single screw-rod fixation: prevalence, characteristics and significance.

PURPOSE: To explore the characteristics of spontaneous facet joint fusion (SFJF) in patients after oblique lateral lumbar interbody fusion combined with lateral single screw-rod fixation (OLIF-LSRF). METHODS: We randomly selected 300 patients from 723 patients treated with OLIF-LSRF into a cross-sectional study based on the pilot study results. A novel fusion classification system was designed to evaluate the fusion status of the facet joints at three time points. Ultimately, the prevalence, characteristics, and significance of SFJF were analyzed. RESULTS: A total of 265 (333 levels) qualified cases were included in our study. The novel classification for SFJF has excellent reliability (kappa > 0.75). The rate of SFJF was 15.20% (45/296 levels) at 3 months postoperatively, 31.34% (89/284 levels) at 6 months postoperatively, and 33.63% (112/333 levels) at the last follow-up. The circumferential fusion rate was 31.53% (105/333 levels) at the last follow-up. The location of SFJF was mostly on the right facet joint (P < 0.001), and the rate of SFJF increased significantly from 3 to 6 months after the operation (P < 0.001). The average age of patients with SFJF was older than that of patients without SFJF (P < 0.001). There was no significant difference in Visual Analog Scale or Oswestry Disability Index scores between patients with and without SFJF. CONCLUSION: In the OLIF-LSRF procedure, SFJF occurs mostly at 3-6 months postoperatively, especially in elderly patients and at the right facet joint. OLIF-LSRF has the potential for circumferential fusion.

Stepwise reduction of bone mineral density increases the risk of cage subsidence in oblique lumbar interbody fusion patients biomechanically: an in-silico study.

BACKGROUND: Cage subsidence causes poor prognoses in patients treated by oblique lumbar interbody fusion (OLIF). Deterioration of the biomechanical environment initially triggers cage subsidence, and patients with low bone mineral density (BMD) suffer a higher risk of cage subsidence. However, whether low BMD increases the risk of cage subsidence by deteriorating the local biomechanical environment has not been clearly identified. METHODS: OLIF without additional fixation (stand-alone, S-A) and with different additional fixation devices (AFDs), including anterolateral single rod screws (ALSRs) and bilateral pedicle screws (BPSs) fixation, was simulated in the L4-L5 segment of a well-validated finite element model. The biomechanical effects of different BMDs were investigated by adjusting the material properties of bony structures. Biomechanical indicators related to cage subsidence were computed and recorded under different directional moments. RESULTS: Overall, low BMD triggers stress concentration in surgical segment, the highest equivalent stress can be observed in osteoporosis models under most loading conditions. Compared with the flexion-extension loading condition, this variation tendency was more pronounced under bending and rotation loading conditions. In addition, AFDs obviously reduced the stress concentration on both bony endplates and the OLIF cage, and the maximum stress on ALSRs was evidently higher than that on BPSs under almost all loading conditions. CONCLUSIONS: Stepwise reduction of BMD increases the risk of a poor local biomechanical environment in OLIF patients, and regular anti-osteoporosis therapy should be considered an effective method to biomechanically optimize the prognosis of OLIF patients.

The potential of microRNA-126 in predicting disease risk, mortality of sepsis, and its correlation with inflammation and sepsis severity.

BACKGROUND: MicroRNA-126 (miR-126) has been investigated in autoimmune diseases and organ failures, whereas its implication in sepsis is rarely reported. Our study initially explored the value of miR-126 in diagnosing sepsis and predicting disease severity, degree of inflammation, and mortality. METHODS: Totally, 208 sepsis patients and 210 healthy controls were enrolled; then, their plasma samples were collected for detecting circulating miR-126 by quantitative polymerase chain reaction. For sepsis patients, their cytokine levels in plasma samples were detected by enzyme-linked immunosorbent assay. RESULTS: miR-126 was upregulated in sepsis patients compared with healthy controls, and it was of certain value in distinguishing sepsis patients from healthy controls (AUC: 0.726 (95% CI: 0.678-0.774)). miR-126 expression was positively correlated with acute physiology and chronic health evaluation II score, serum creatinine, and C-reactive protein but not albumin or white blood cell count in sepsis patients. Regarding cytokines, miR-126 was positively correlated with tumor necrosis factor-α, interleukin (IL)-6, and IL-8, but negatively correlated with IL-10 in sepsis patients. As for mortality, miR-126 expression was higher in deaths compared with survivors, and ROC curve displayed that it could predict mortality of sepsis patients to some extent with AUC of 0.619 (95% CI: 0.533-0.705). CONCLUSION: miR-126 potentially serves as an assistant diagnostic and prognostic biomarker for sepsis.

Metal-free one-pot synthesis of 2-substituted and 2,3-disubstituted morpholines from aziridines.

The metal-free synthesis of 2-substituted and 2,3-disubstituted morpholines through a one-pot strategy is described. A simple and inexpensive ammonium persulfate salt enables the reaction of aziridines with halogenated alcohols to proceed via an SN2-type ring opening followed by cyclization of the resulting haloalkoxy amine.

Visible-light-induced bromoetherification of alkenols for the synthesis of ß-bromotetrahydrofurans and -tetrahydropyrans.

A visible-light-induced photoredox-catalyzed bromoetherification of alkenols is described. This approach, with CBr4 as the bromine source through generation of bromine in situ, provides a mild and operationally simple access to the synthesis of ß-bromotetrahydrofurans and -tetrahydropyrans with high efficiency and regioselectivity.

Ultrashort echo time (UTE) imaging of receptor targeted magnetic iron oxide nanoparticles in mouse tumor models.

PURPOSE: The purpose of this study was to investigate an ultrashort echo time (UTE) imaging approach for improving the detection of receptor targeted magnetic nanoparticles in cancer xenograft models using positive contrast. MATERIALS AND METHODS: Iron oxide nanoparticle (IONP) conjugated with tumor targeting ligands were prepared. A 3D UTE gradient echo sequence with the shortest TE of 0.07 msec was evaluated on a 3T magnetic resonance imaging (MRI) scanner using IONP solution, cancer cells bound with targeted IONPs and orthotopic human pancreatic, and breast cancer mouse models administered tumor targeting IONPs. A simulation was performed to analyze contrast-to-noise ratios (CNR) of UTE images and subtraction of the images obtained UTE and longer TE (SubUTE). T2-weighted imaging and T2 relaxometry mapping were applied for comparison and validation. RESULTS: UTE and SubUTE images showed positive contrast in pancreatic tumors accumulated with EGFR targeted ScFvEGFR-IONPs and mammary tumors accumulated with uPAR targeted ATF-IONPs. The positive contrast observed in UTE images was consistent with the negative contrast observed in the T2-weighted images. A flip angle of 10° and a maximal possible TE for the second echo are suitable for SubUTE imaging. CONCLUSION: UTE imaging is capable of detecting tumor targeted IONPs in vivo with positive contrast in molecular MRI applications.

Visible-light photoredox catalysis enabled bromination of phenols and alkenes.

A mild and efficient methodology for the bromination of phenols and alkenes has been developed utilizing visible light-induced photoredox catalysis. The bromine was generated in situ from the oxidation of Br(-) by Ru(bpy)3 (3+), both of which resulted from the oxidative quenching process.

A novel multitask learning algorithm for tasks with distinct chemical space: zebrafish toxicity prediction as an example.

Data scarcity is one of the most critical issues impeding the development of prediction models for chemical effects. Multitask learning algorithms leveraging knowledge from relevant tasks showed potential for dealing with tasks with limited data. However, current multitask methods mainly focus on learning from datasets whose task labels are available for most of the training samples. Since datasets were generated for different purposes with distinct chemical spaces, the conventional multitask learning methods may not be suitable. This study presents a novel multitask learning method MTForestNet that can deal with data scarcity problems and learn from tasks with distinct chemical space. The MTForestNet consists of nodes of random forest classifiers organized in the form of a progressive network, where each node represents a random forest model learned from a specific task. To demonstrate the effectiveness of the MTForestNet, 48 zebrafish toxicity datasets were collected and utilized as an example. Among them, two tasks are very different from other tasks with only 1.3% common chemicals shared with other tasks. In an independent test, MTForestNet with a high area under the receiver operating characteristic curve (AUC) value of 0.911 provided superior performance over compared single-task and multitask methods. The overall toxicity derived from the developed models of zebrafish toxicity is well correlated with the experimentally determined overall toxicity. In addition, the outputs from the developed models of zebrafish toxicity can be utilized as features to boost the prediction of developmental toxicity. The developed models are effective for predicting zebrafish toxicity and the proposed MTForestNet is expected to be useful for tasks with distinct chemical space that can be applied in other tasks.Scieific contributionA novel multitask learning algorithm MTForestNet was proposed to address the challenges of developing models using datasets with distinct chemical space that is a common issue of cheminformatics tasks. As an example, zebrafish toxicity prediction models were developed using the proposed MTForestNet which provide superior performance over conventional single-task and multitask learning methods. In addition, the developed zebrafish toxicity prediction models can reduce animal testing.

COL6A6 Peptide Vaccine Alleviates Atherosclerosis through Inducing Immune Response and Regulating Lipid Metabolism in Apoe-/- Mice.

Atherosclerosis is an autoimmune disease characterized by lipid imbalances and chronic inflammation within blood vessels, with limited preventive and treatment options currently available. In this study, a vaccine prepared with COL6A6 peptide (named the Pep_A6 vaccine) was administered to immunize Apoe-/- mice, and the immune mechanism of the Pep_A6 vaccine against atherosclerosis was first investigated. The results of arterial oil red O staining demonstrated that the Pep_A6 vaccine significantly reduced the atherosclerotic plaque area in Apoe-/- mice fed with a high-fat diet for 20 weeks. A flow cytometry analysis revealed that the Pep_A6 vaccine inhibited Th1 cell differentiation and increased the proportion of Treg cells. Furthermore, there was a significant increase in Ly6Clow monocytes observed in the vaccinated group. The ELISA results showed that the Pep_A6 vaccine induced a significant expression of Pep_A6-specific antibody IgG and IgG1 in mouse serum. Additionally, we found that the Pep_A6 vaccine significantly decreased serum LDL-C content and regulated the expression of genes related to liver lipid metabolism. Together, our findings suggest that the Pep_A6 vaccine alleviates atherosclerosis by inducing a positive immune response and regulating lipid metabolism, providing new insights into potential prevention strategies for atherosclerosis as an innovative vaccine.

Convolutional Dynamically Convergent Differential Neural Network for Brain Signal Classification.

The brain signal classification is the basis for the implementation of brain-computer interfaces (BCIs). However, most existing brain signal classification methods are based on signal processing technology, which require a significant amount of manual intervention, such as channel selection and dimensionality reduction, and often struggle to achieve satisfactory classification accuracy. To achieve high classification accuracy and as little manual intervention as possible, a convolutional dynamically convergent differential neural network (ConvDCDNN) is proposed for solving the electroencephalography (EEG) signal classification problem. First, a single-layer convolutional neural network is used to replace the preprocessing steps in previous work. Then, focal loss is used to overcome the imbalance in the dataset. After that, a novel automatic dynamic convergence learning (ADCL) algorithm is proposed and proved for training neural networks. Experimental results on the BCI Competition 2003, BCI Competition III A, and BCI Competition III B datasets demonstrate that the proposed ConvDCDNN framework achieved state-of-the-art performance with accuracies of 100%, 99%, and 98%, respectively. In addition, the proposed algorithm exhibits a higher information transfer rate (ITR) compared with current algorithms.

Acupressure: a possible therapeutic strategy for anxiety related to COVID-19: a meta-analysis of randomized controlled trials.

Background: From the end of 2019 to December 2023, the world grappled with the COVID-19 pandemic. The scope and ultimate repercussions of the pandemic on global health and well-being remained uncertain, ushering in a wave of fear, anxiety, and worry. This resulted in many individuals succumbing to fear and despair. Acupoint massage emerged as a safe and effective alternative therapy for anxiety relief. However, its efficacy was yet to be extensively backed by evidence-based medicine. This study aimed to enhance the clinical effectiveness of acupoint massage and extend its benefits to a wider population. It undertakes a systematic review of the existing randomized controlled trials (RCTs) assessing the impact of acupoint massage on anxiety treatment, discussing its potential benefits and implications. This research aims to furnish robust evidence supporting anxiety treatment strategies for patients afflicted with COVID-19 disease and spark new approaches to anxiety management. Objectives: This study evaluates the evidence derived from randomised controlled trials (RCTs), quantifies the impact of acupressure on anxiety manifestations within the general population, and proposes viable supplementary intervention strategies for managing COVID-19 related anxiety. Materials and methods: This review included RCTs published between February 2014 and July 2023, that compared the effects of acupressure with sham control in alleviating anxiety symptomatology as the outcome measure. The studies were sourced from the multiple databases, including CINAHL, EBM Reviews, Embase, Medline, PsycINFO, Scopus and Web of Science. A meta-analysis was performed on the eligible studies, and an overall effect size was computed specifically for the anxiety outcome. The Cochrane Collaboration Bias Risk Assessment Tool (RevMan V5.4) was employed to assess bias risk, data integration, meta-analysis, and subgroup analysis. The mean difference, standard mean deviation, and binary data were used to represent continuous outcomes. Results: Of 1,110 studies of potential relevance, 39 met the criteria for inclusion in the meta-analysis. The majority of the studies reported a positive effect of acupressure in assuaging anticipatory anxiety about treatment. Eighteen studies were evaluated using the STAI scale. The acupressure procedures were thoroughly documented, and studies exhibited a low risk of bias. The cumulative results of the 18 trials showcased a more substantial reduction in anxiety in the acupressure group compared to controls (SMD = -5.39, 95% CI -5.61 to -5.17, p < 0.01). A subsequent subgroup analysis, based on different interventions in the control group, demonstrated improvement in anxiety levels with sham acupressure in improving changes in anxiety levels (SMD -1.61, 95% CI: -2.34 to -0.87, p < 0.0001), and blank controls (SMD -0.92, 95% CI: -2.37 to 0.53, p = 0.22). Conclusion: In the clinical research of traditional Chinese medicine treatment of anxiety, acupressure demonstrated effectiveness in providing instant relief from anxiety related to multiple diseases with a medium effect size. Considering the increasing incidence of anxiety caused by long COVID, the widespread application of acupressure appears feasible. However, the results were inconsistent regarding improvements on physiological indicators, calling for more stringent reporting procedures, including allocation concealment, to solidify the findings.

Simultaneous antioxidant and neuroprotective effects of two-dimensional (2D) MXene-loaded isoquercetin for ischemic stroke treatment.

Oxidative stress and reactive oxygen species drive ischemic stroke and its related complications. New antioxidant medications are therefore crucial for treating ischemic stroke. We developed Ti2C@BSA-ISO nanocomposites loaded with the hydrophobic drug isoquercetin (ISO) encapsulated in BSA on Ti2C nano-enzymes as a novel therapeutic nanomedicine for the treatment of ischemic stroke targeting reactive oxygen species (ROS). TEM visually proved the successful preparation of Ti2C@BSA-ISO, and the FTIR, XPS, zeta potential and DLS together demonstrated the acquisition of Ti2C@BSA-ISO. In addition, the enzyme-mimicking activity of Ti2C was evaluated and the antioxidant capacity of Ti2C@BSA-ISO was verified. Ti2C@BSA-ISO was able to reverse the decrease in cellular activity caused by ROS. Experiments in vivo showed that Ti2C@BSA-ISO could promote neuroprotection and scavenging of ROS in the hippocampal CA1 area and cerebral cortex of rats, thereby inhibiting cellular death and alleviating ischaemic stroke. Specifically, Ti2C@BSA-ISO alleviated ischemic stroke by inhibiting NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis. Our study demonstrates the effectiveness of nanomedicines that can be directly used as drugs for the treatment of ischemic stroke in synergy with other drugs, which greatly expands the application of nanomaterials in the treatment of ischemic stroke.