Astaxanthin protects against MPP+-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis

BACKGROUND: Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. NOX2, a cytochrome subunit of NOX, transports electrons across the plasma membrane to generate ROS, leading to physiological and pathological processes. Heme oxygenase-1 (HO-1) can be rapidly induced by oxidative stress and other noxious stimuli in the brain or other tissues. Astaxanthin (ATX), a carotenoid with antioxidant properties, is 100–1000 times more effective than vitamin E. The present study investigated the neuroprotective effects of ATX on MPP(+)-induced oxidative stress in PC12 cells. RESULTS: MPP(+) significantly decreased MTT levels in a concentration-dependent manner. Hemin, SnPPIX and ATX didn’t exhibit any cytotoxic effects on PC12 cells. Pretreatment with ATX (5, 10, 20 μM), caused intracellular ROS production in the MPP(+) group to decrease by 13.06%, 22.13%, and 27.86%, respectively. MPP(+) increased NOX2, NRF2 and HO-1 protein expression compared with control (p < 0.05). Co-treatment with hemin or ATX suppressed NOX2 expression (p < 0.01), and greatly increased NRF2 and HO-1 expression (p < 0.01). MPP(+) treatment up-regulated both NOX2 (p < 0.01) and HO-1 (p < 0.01) mRNA levels. Co-treatment with hemin or ATX significantly increased HO-1 mRNA levels (p < 0.01), and decreased NOX2 mRNA levels (p < 0.01). MPP(+) increased NOX2 and HO-1 expression with considerable fluorescence extending out from the perinuclear region toward the periphery; this was attenuated by DPI. Co-treatment with hemin or ATX significantly up-regulated HO-1 expression and decreased NOX2 expression with considerable fluorescence intensity (stronger than the control and MPP(+) groups). CONCLUSIONS: ATX suppresses MPP(+)-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis. ATX should be strongly considered as a potential neuroprotectant and adjuvant therapy for patients with Parkinson’s disease

Filter-informed Spectral Graph Wavelet Networks for Multiscale Feature Extraction and Intelligent Fault Diagnosis

Intelligent fault diagnosis has been increasingly improved with the evolution of deep learning (DL) approaches. Recently, the emerging graph neural networks (GNNs) have also been introduced in the field of fault diagnosis with the goal to make better use of the inductive bias of the interdependencies between the different sensor measurements. However, there are some limitations with these GNN-based fault diagnosis methods. First, they lack the ability to realize multiscale feature extraction due to the fixed receptive field of GNNs. Secondly, they eventually encounter the over-smoothing problem with increase of model depth. Lastly, the extracted features of these GNNs are hard to understand owing to the black-box nature of GNNs. To address these issues, a filter-informed spectral graph wavelet network (SGWN) is proposed in this paper. In SGWN, the spectral graph wavelet convolutional (SGWConv) layer is established upon the spectral graph wavelet transform, which can decompose a graph signal into scaling function coefficients and spectral graph wavelet coefficients. With the help of SGWConv, SGWN is able to prevent the over-smoothing problem caused by long-range low-pass filtering, by simultaneously extracting low-pass and band-pass features. Furthermore, to speed up the computation of SGWN, the scaling kernel function and graph wavelet kernel function in SGWConv are approximated by the Chebyshev polynomials. The effectiveness of the proposed SGWN is evaluated on the collected solenoid valve dataset and aero-engine intershaft bearing dataset. The experimental results show that SGWN can outperform the comparative methods in both diagnostic accuracy and the ability to prevent over-smoothing. Moreover, its extracted features are also interpretable with domain knowledge

Ginsenoside Rg1 Attenuates Oligomeric Aβ1-42-Induced Mitochondrial Dysfunction

Mitochondrial dysfunction is one of the major pathological changes seen in Alzheimer's disease (AD). Amyloid beta-peptide (Aβ), a neurotoxic peptide, accumulates in the brain of AD subjects and mediates mitochondrial and neuronal stress. Therefore, protecting mitochondrion from Aβ-induced toxicity holds potential benefits for halting and treating and perhaps preventing AD. Here, we report that administration of ginsenoside Rg1, a known neuroprotective drug, to primary cultured cortical neurons, rescues Aβ-mediated mitochondrial dysfunction as shown by increases in mitochondrial membrane potential, ATP levels, activity of cytochrome c oxidase (a key enzyme associated with mitochondrial respiratory function), and decreases in cytochrome c release. The protective effects of Rg1 on mitochondrial dysfunction correlate to neuronal injury in the presence of Aβ. This finding suggests that ginsenoside Rg1 may attenuate Aβ-induced neuronal death through the suppression of intracellular mitochondrial oxidative stress and may rescue neurons in AD

Characterization of true triaxial rock bursts in sandstones with different water contents

The rockburst phenomenon occurs in dry red sandstone under high in situ stress, and the rockburst effect is weaker for a water-bearing rock. The rockburst effect on red sandstone with different water contents is analyzed in this paper. A true triaxial testing machine is used to conduct the loading, and acoustic emission recording equipment and a high-speed camera are used to monitor the acoustic signal inside the rock and the rock-caving situation throughout the entire process in order to analyze the characteristics of the acoustic emissions and the ejection form of the rockburst. The results show that rockburst occurs in dry red sandstone and 50% saturated red sandstone but not in saturated red sandstone. The phrase characteristics of the stress–strain curve of the dry rock vary more significantly than those of the water-bearing rock, and the elastic strain energy inside the rock decreases gradually as the water content increases. The double peak of the acoustic emissions curve occurs during the failure process of the dry rock and gradually transitions to a stepped pattern as the water content increases. The ejected fragments of dry red sandstone during the rockburst are abundant and large. The true triaxial test results illustrate the characteristic effect of the rockburst on red sandstone with different water contents, reveal the failure mode and ejection characteristics of red sandstone with different water contents, and demonstrate the influence of the water content on the rockburst characteristics of red sandstone. The results of this study provide a theoretical reference for the study of the rockburst mechanisms of similar hard rocks

Long Noncoding RNA FAM201A Mediates the Radiosensitivity of Esophageal Squamous Cell Cancer by Regulating ATM and mTOR Expression via miR-101

Background: The aim of the present study was to identify the potential long non-coding (lnc.)-RNA and its associated molecular mechanisms involved in the regulation of the radiosensitivity of esophageal squamous cell cancer (ESCC) in order to assess whether it could be a biomarker for the prediction of the response to radiotherapy and prognosis in patients with ESCC.Methods: Microarrays and bioinformatics analysis were utilized to screen the potential lncRNAs associated with radiosensitivity in radiosensitive (n = 3) and radioresistant (n = 3) ESCC tumor tissues. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed in 35 ESCC tumor tissues (20 radiosensitive and 15 radioresistant tissues, respectively) to validate the lncRNA that contributed the most to the radiosensitivity of ESCC (named the candidate lncRNA). MTT, flow cytometry, and western blot assays were conducted to assess the effect of the candidate lncRNA on radiosensitivity in vitro in ECA109/ECA109R ESCC cells. A mouse xenograft model was established to confirm the function of the candidate lncRNA in the radiosensitivity of ESCC in vivo. The putative downstream target genes regulated by the candidate lncRNA were predicted using Starbase 2.0 software and the TargetScan database. The interactions between the candidate lncRNA and the putative downstream target genes were examined by Luciferase reporter assay, and were confirmed by PCR.Results: A total of 113 aberrantly expressed lncRNAs were identified by microarray analysis, of which family with sequence similarity 201-member A (FAM201A) was identified as the lncRNA that contributed the most to the radiosensitivity of ESCC. FAM201A was upregulated in radioresistant ESCC tumor tissues and had a poorer short-term response to radiotherapy resulting in inferior overall survival. FAM201A knockdown enhanced the radiosensitivity of ECA109/ECA109R cells by upregulating ataxia telangiectasia mutated (ATM) and mammalian target of rapamycin (mTOR) expression via the negative regulation of miR-101 expression. The mouse xenograft model demonstrated that FAM201A knockdown improved the radiosensitivity of ESCC.Conclusion: The lncRNA FAM201A, which mediated the radiosensitivity of ESCC by regulating ATM and mTOR expression via miR-101 in the present study, may be a potential biomarker for predicting radiosensitivity and patient prognosis, and may be a therapeutic target for enhancing cancer radiosensitivity in ESCC

LETTER Simplify Support Vector Machines by Iterative Learning

Abstract—Support vector machines (SVM) are well known to give good results on a wide variety of pattern recognition problems, but for large scale problems, the number of support vectors usually is large, which results in substantially slow classification speed. Existing study has proposed to speed the SVM classification by decreasing the number of support vectors. In this paper it is found that SVM trained with most important training points have less support vectors and equivalent accuracy to those of SVM trained with the full training set. An iterative procedure is proposed to train the simplified SVM with most important training points, and the careful preprocessing on outliers also is used to speed the iterative learning. Computational results indicate that, compared with SVM trained with full training set, proposed method can obtain simplified SVMs with much less support vectors and equivalent classification accuracy, which supports proposed method as an effective method to obtain a simplified SVM for large problems. Keywords—Simplified SVM, Support Vector Machine, Iterative Learning 1

Astaxanthin protects against MPP⁺-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis

Abstract Background Although the etiology of PD remains unclear, increasing evidence has shown that oxidative stress plays an important role in its pathogenesis and that of other neurodegenerative disorders. NOX2, a cytochrome subunit of NOX, transports electrons across the plasma membrane to generate ROS, leading to physiological and pathological processes. Heme oxygenase-1 (HO-1) can be rapidly induced by oxidative stress and other noxious stimuli in the brain or other tissues. Astaxanthin (ATX), a carotenoid with antioxidant properties, is 100–1000 times more effective than vitamin E. The present study investigated the neuroprotective effects of ATX on MPP+-induced oxidative stress in PC12 cells. Results MPP+ significantly decreased MTT levels in a concentration-dependent manner. Hemin, SnPPIX and ATX didn’t exhibit any cytotoxic effects on PC12 cells. Pretreatment with ATX (5, 10, 20 μM), caused intracellular ROS production in the MPP+ group to decrease by 13.06%, 22.13%, and 27.86%, respectively. MPP+ increased NOX2, NRF2 and HO-1 protein expression compared with control (p + treatment up-regulated both NOX2 (p + increased NOX2 and HO-1 expression with considerable fluorescence extending out from the perinuclear region toward the periphery; this was attenuated by DPI. Co-treatment with hemin or ATX significantly up-regulated HO-1 expression and decreased NOX2 expression with considerable fluorescence intensity (stronger than the control and MPP+ groups). Conclusions ATX suppresses MPP+-induced oxidative stress in PC12 cells via the HO-1/NOX2 axis. ATX should be strongly considered as a potential neuroprotectant and adjuvant therapy for patients with Parkinson’s disease.</p

Evaluation of the safety and efficiency of color Doppler ultrasound-guided percutaneous nephrolithotomy in clinical practice: results from a retrospective study

AbstractThis study evaluated the clinical value of color Doppler ultrasound-guided percutaneous nephrolithotomy (PCNL) in avoiding bleeding caused by punctured blood vessels. Herein, we retrospectively included patients who underwent color Doppler ultrasound-guided PCNL or PCNL using the conventional channel technique from August 2018 to August 2022. The clinical characteristics of patients during surgery, complications, and hospital stay were recorded and compared. Overall, 228 patients were enrolled, with 126 patients (age, 47.6 ± 13.2 years; men: 57.14%) in the color Doppler ultrasound-guided PCNL group and 102 patients (age, 46.6 ± 12.3 years) in the B-mode ultrasound-guided puncture group. The total operation time (63.5 ± 15.5 vs. 61.3 ± 16.3 min, p = .5236) and stone clearance rate (86.50% vs. 83.33%, p = .7139) were similar between the two groups. However, the puncture time for the color Doppler ultrasound-guided PCNL group was longer than that for the B-mode ultrasound-guided puncture group (5.1 ± 2.3 vs. 2.6 ± 1.6 min, p = .0019). Moreover, the length of postoperative hospital stay in the color Doppler ultrasound-guided PCNL group reduced significantly by ∼1 day compared with that in the B-mode ultrasound-guided puncture group (4.5 ± 1.6 vs. 5.6 ± 2.1 days, p = .0087). The blood transfusion rate (1.58% vs. 4.9%, p = .0399), sedation-related adverse event rate (0.79% vs. 2.9%, p = .0332), perineal hematoma incidence (0% vs. 2.94%, p < .0001), and serum decreased hemoglobin levels (12.2 ± 9.7 vs. 23.5 ± 10.1 g/L, p < .001) after color Doppler ultrasound-guided PCNL were significantly lower than those after B-mode ultrasound-guided puncture. The stone clearance rate was similar between the two groups, with a similar operation time. Moreover, color Doppler ultrasound-guided PCNL shortened the postoperative hospital stay and decreased Hb levels, blood transfusion rate, and perineal hematoma incidence

Nervous and muscular adverse events after covid‐19 vaccination: A systematic review and meta‐analysis of clinical trials

Background: Nervous and muscular adverse events (NMAEs) have garnered considerable attention after the vaccination against coronavirus disease (COVID‐19). However, the incidences of NMAEs remain unclear. We aimed to calculate the pooled event rate of NMAEs after COVID‐19 vaccination. Methods: A systematic review and meta‐analysis of clinical trials on the incidences of NMAEs after COVID‐19 vaccination was conducted. The PubMed, Medline, Embase, Cochrane Li-brary, and Chinese National Knowledge Infrastructure databases were searched from inception to 2 June 2021. Two independent reviewers selected the study and extracted the data. Categorical var-iables were analyzed using Pearson’s chi‐square test. The pooled odds ratio (OR) with the corre-sponding 95% confidence intervals (CIs) were estimated and generated with random or fixed effects models. The protocol of the present study was registered on PROSPERO (CRD42021240450). Re-sults: In 15 phase 1/2 trials, NMAEs occurred in 29.2% vs. 21.6% (p &lt; 0.001) vaccinated participants and controls. Headache and myalgia accounted for 98.2% and 97.7%, and their incidences were 16.4% vs. 13.9% (OR = 1.97, 95% CI = 1.28–3.06, p = 0.002) and 16.0% vs. 7.9% (OR = 3.31, 95% CI = 2.05–5.35, p &lt; 0.001) in the vaccine and control groups, respectively. Headache and myalgia were more frequent in the newly licensed vaccines (OR = 1.97, 95% CI = 1.28–3.06, p = 0.02 and OR = 3.31, 95% CI = 2.05–5.35, p &lt; 0.001) and younger adults (OR = 1.40, 95% CI = 1.12–1.75, p = 0.003 and OR = 1.54, 95% CI = 1.20–1.96, p &lt; 0.001). In four open‐label trials, the incidences of headache, myalgia, and unsolicited NMAEs were 38.7%, 27.4%, and 1.5%. Following vaccination in phase 3 trials, headache and myalgia were still common with a rate of 29.5% and 19.2%, although the unsolicited NMAEs with incidence rates of ≤ 0.7% were not different from the control group in each study. Conclusions: Following the vaccination, NMAEs are common of which headache and myalgia com-prised a considerable measure, although life‐threatening unsolicited events are rare. NMAEs should be continuously monitored during the ongoing global COVID‐19 vaccination program.</p

Astaxanthin Suppresses MPP+-Induced Oxidative Damage in PC12 Cells through a Sp1/NR1 Signaling Pathway

Objective: To investigate astaxanthin (ATX) neuroprotection, and its mechanism, on a 1-methyl-4-phenyl-pyridine ion (MPP+)-induced cell model of Parkinson’s disease. Methods: Mature, differentiated PC12 cells treated with MPP+ were used as an in vitro cell model. The MTT assay was used to investigate cell viability after ATX treatment, and western blot analysis was used to observe Sp1 (activated transcription factor 1) and NR1 (NMDA receptor subunit 1) protein expression, real-time PCR was used to monitor Sp1 and NR1 mRNA, and cell immunofluorescence was used to determine the location of Sp1 and NR1 protein and the nuclear translocation of Sp1. Results: PC12 cell viability was significantly reduced by MPP+ treatment. The expression of Sp1 and NR1 mRNA and protein were increased compared with the control (p &lt; 0.01). Following co-treatment with ATX and MPP+, cell viability was significantly increased, and Sp1 and NR1 mRNA and protein were decreased, compared with the MPP+ groups (p &lt; 0.01). In addition, mithracycin A protected PC12 cells from oxidative stress caused by MPP+ by specifically inhibiting the expression of Sp1. Moreover, cell immunofluorescence revealed that ATX could suppress Sp1 nuclear transfer. Conclusion: ATX inhibited oxidative stress induced by MPP+ in PC12 cells, via the SP1/NR1 signaling pathway