Combination of paeoniflorin and calycosin-7-glucoside alleviates ischaemic stroke injury via the PI3K/AKT signalling pathway.

CONTEXT: Paeoniflorin (PF) and calycosin-7-glucoside (CG, Paeonia lactiflora Pall. extract) have demonstrated protective effects in ischaemic stroke. OBJECTIVE: To investigate the synergistic effects of PF + CG on ischaemia/reperfusion injury in vivo and in vitro. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to the middle cerebral artery occlusion/reperfusion (MCAO/R). After MCAO/R for 24 h, rats were randomly subdivided into 5 groups: sham, model (MCAO/R), study treatment (PF + CG, 40 + 20 mg/kg), LY294002 (20 mg/kg), and study treatment + LY294002. Males were given via intragastric administration; the duration of the in vivo experiment was 8 days. Neurologic deficits, cerebral infarction, brain edoema, and protein levels were assessed in vivo. Hippocampal neurons (HT22) were refreshed with glucose-free DMEM and placed in an anaerobic chamber for 8 h. Subsequently, HT22 cells were reoxygenated in a 37 °C incubator with 5% CO2 for 6 h. SOD, MDA, ROS, LDH and protein levels were measured in vitro. RESULTS: PF + CG significantly reduced neurobehavioral outcomes (21%), cerebral infarct volume (44%), brain edoema (1.6%) compared with the MCAO/R group. Moreover, PF + CG increased p-PI3K/PI3K (4.69%, 7.4%), p-AKT/AKT (6.25%, 60.6%) and Bcl-2/BAX (33%, 49%) expression in vivo and in vitro, and reduced GSK-3ß (10.5%, 9.6%) expression. In vitro, PF + CG suppressed apoptosis in HT22 cells and decreased ROS and MDA levels (20%, 50%, respectively). CONCLUSIONS: PF + CG showed a synergistic protective effect against ischaemic brain injury, potentially being a future treatment for ischaemic stroke.

Calycosin-7-O-ß-D-glucoside Attenuates OGD/R-Induced Damage by Preventing Oxidative Stress and Neuronal Apoptosis via the SIRT1/FOXO1/PGC-1α Pathway in HT22 Cells.

Neuronal apoptosis induced by oxidative stress is a major pathological process that occurs after cerebral ischemia-reperfusion. Calycosin-7-O-ß-D-glucoside (CG) is a representative component of isoflavones in Radix Astragali (RA). Previous studies have shown that CG has potential neuroprotective effects. However, whether CG alleviates neuronal apoptosis through antioxidant stress after ischemia-reperfusion remains unknown. To investigate the positive effects of CG on oxidative stress and apoptosis of neurons, we simulated the ischemia-reperfusion process in vitro using an immortalized hippocampal neuron cell line (HT22) and oxygen-glucose deprivation/reperfusion (OGD/R) model. CG significantly improved cell viability and reduced oxidative stress and neuronal apoptosis. In addition, CG treatment upregulated the expression of SIRT1, FOXO1, PGC-1α, and Bcl-2 and downregulated the expression of Bax. In summary, our findings indicate that CG alleviates OGD/R-induced damage via the SIRT1/FOXO1/PGC-1α signaling pathway. Thus, CG maybe a promising therapeutic candidate for brain injury associated with ischemic stroke.

Advanced treatment and reuse of dye wastewater using thermo-irreversible on/off switch starch with disruption of dissolution/precipitation dynamic equilibrium.

The development of irreversible on/off switching materials is a potential strategy for unidirectional capture and encapsulation of pollutants, preventing the pollutant leakage problem resulting from the reversible dissolution of flocculants. Herein, a thermo-irreversible on/off switch starch (TISS) is prepared through modifying starch by etherification grafting glycidyl phenyl ether and 2,4-bis(dimethylamino)-6-chloro-[1,3,5]-triazine. It breaks the dissolution/precipitation dynamic equilibrium across heating-cooling cycles by thermal-induced irreversible coil-to-globule self-assembly of polymer chains, resulting in a 50-fold decrease in polymer solubility. Particularly, TISS shows a superior double-locking effect on pollutants and flocculants through its unique irreversible conformation memory capability, leading to a high-quality reuse water. 99.9 % of reactive brilliant red dye and 97.9 % of TISS remain fixed within sludge flocs even after prolonged immersion in cold water at 24 °C for 60 days. Furthermore, direct recycling and reuse of dye-bath energy can be realized through the isothermal flocculation and dyeing method, showing a 75 % decrease in energy consumption after three cycles compared to traditional dyeing techniques. This work presents a novel approach to constructing an irreversible pollutant delivery system using thermo-irreversible on/off switch starch, addressing the problems of high energy dissipation and water quality fluctuations during wastewater treatment.

Automatic data augmentation for medical image segmentation using Adaptive Sequence-length based Deep Reinforcement Learning.

Although existing deep reinforcement learning-based approaches have achieved some success in image augmentation tasks, their effectiveness and adequacy for data augmentation in intelligent medical image analysis are still unsatisfactory. Therefore, we propose a novel Adaptive Sequence-length based Deep Reinforcement Learning (ASDRL) model for Automatic Data Augmentation (AutoAug) in intelligent medical image analysis. The improvements of ASDRL-AutoAug are two-fold: (i) To remedy the problem of some augmented images being invalid, we construct a more accurate reward function based on different variations of the augmentation trajectories. This reward function assesses the validity of each augmentation transformation more accurately by introducing different information about the validity of the augmented images. (ii) Then, to alleviate the problem of insufficient augmentation, we further propose a more intelligent automatic stopping mechanism (ASM). ASM feeds a stop signal to the agent automatically by judging the adequacy of image augmentation. This ensures that each transformation before stopping the augmentation can smoothly improve the model performance. Extensive experimental results on three medical image segmentation datasets show that (i) ASDRL-AutoAug greatly outperforms the state-of-the-art data augmentation methods in medical image segmentation tasks, (ii) the proposed improvements are both effective and essential for ASDRL-AutoAug to achieve superior performance, and the new reward evaluates the transformations more accurately than existing reward functions, and (iii) we also demonstrate that ASDRL-AutoAug is adaptive for different images in terms of sequence length, as well as generalizable across different segmentation models.

Abnormal methylation of HOXA11 promoter promotes tumor progression in testicular germ cell tumor.

OBJECTIVE: To investigate the methylation of HOXA11 gene promoter in testicular germ cell tumor (GCT). METHOD: The clinicopathological data of 63 patients with primary testicular GCT who underwent surgery during Apr. 2019 to Mar. 2021, were retrospectively analyzed. Their GCT tissue and paraneoplastic testicular tissue were obtained, and genomic DNA was extracted from both. The methylation of HOXA11 gene promoter region was detected by methylation-specific PCR (MSP). The incidence of HOXA11 methylation in testicular GCT and adjacent tissues was compared, and the connection between methylation level in testicular GCT and clinicopathologic features of patients was statistically analyzed. Testicular GCT cells were treated with methylated transferase inhibitor 5-Aza-dC in vitro, and HOXA11 mRNA expression was detected by real-time PCR. RESULTS: The positive rate of HOXA11 promoter methylation in testicular GCT tissues was notably higher than that of paired adjacent tissues (P<0.05). The abnormal methylation of HOXA11 gene promoter was correlated with lymph node metastasis and TNM stage in patients (P<0.05). HOXA11 mRNA expression in testicular GCT cells treated with 5-Aza-dC was increased (P<0.05). CONCLUSION: Abnormal methylation of HOXA11 gene promoter in testicular germ cell tumor tissue inhibits transcription and expression of HOXA11 gene. The abnormal methylation of HOXA11 promoter region is tightly associated with lymph node metastasis and TNM staging in testicular germ cell tumors.

An energy harvesting shock absorber for powering on-board electrical equipment in freight trains.

To realize smart detection and safe operation of freight trains, a continuous and stable energy source is required for electrical equipment on the train. It is a feasible scheme to harvest the vibration energy of train suspension to supply power for on-board electrical equipment. This paper presents an energy-harvesting shock absorber (EHSA) based on the slider-crank mechanism and ratchet-pawl mechanism, which provide a vibration reduction effect and renewable electricity. To determine the damping performance and the power generation performance of EHSA, a dynamic model is established based on MATLAB. According to the tests on the mechanical testing and sensing (MTS) bench, the maximum power generation mechanical efficiency of the EHSA is 67.75%, and the maximum output power of the EHSA is 1.65W. In addition, the charging tests on the MTS bench show that the proposed device is applicable to power on-board electrical equipment on freight trains.

Enormous Berry-Curvature-Based Anomalous Hall Effect in Topological Insulator (Bi,Sb)2Te3 on Ferrimagnetic Europium Iron Garnet beyond 400 K.

To realize the quantum anomalous Hall effect (QAHE) at elevated temperatures, the approach of magnetic proximity effect (MPE) was adopted to break the time-reversal symmetry in the topological insulator (Bi0.3Sb0.7)2Te3 (BST) based heterostructures with a ferrimagnetic insulator europium iron garnet (EuIG) of perpendicular magnetic anisotropy. Here we demonstrate large anomalous Hall resistance (RAHE) exceeding 8 Ω (ρAHE of 3.2 µΩ·cm) at 300 K and sustaining to 400 K in 35 BST/EuIG samples, surpassing the past record of 0.28 Ω (ρAHE of 0.14 µΩ·cm) at 300 K. The large RAHE is attributed to an atomically abrupt, Fe-rich interface between BST and EuIG. Importantly, the gate dependence of the AHE loops shows no sign change with varying chemical potential. This observation is supported by our first-principles calculations via applying a gradient Zeeman field plus a contact potential on BST. Our calculations further demonstrate that the AHE in this heterostructure is attributed to the intrinsic Berry curvature. Furthermore, for gate-biased 4 nm BST on EuIG, a pronounced topological Hall effect-like (THE-like) feature coexisting with AHE is observed at the negative top-gate voltage up to 15 K. Interface tuning with theoretical calculations has realized topologically distinct phenomena in tailored magnetic TI-based heterostructures.

Implicit adaptation compensates for erratic explicit strategy in human motor learning.

Sports are replete with strategies, yet coaching lore often emphasizes 'quieting the mind', 'trusting the body' and 'avoiding overthinking' in referring to the importance of relying less on high-level explicit strategies in favor of low-level implicit motor learning. We investigated the interactions between explicit strategy and implicit motor adaptation by designing a sensorimotor learning paradigm that drives adaptive changes in some dimensions but not others. We find that strategy and implicit adaptation synergize in driven dimensions, but effectively cancel each other in undriven dimensions. Independent analyses-based on time lags, the correlational structure in the data and computational modeling-demonstrate that this cancellation occurs because implicit adaptation effectively compensates for noise in explicit strategy rather than the converse, acting to clean up the motor noise resulting from low-fidelity explicit strategy during motor learning. These results provide new insight into why implicit learning increasingly takes over from explicit strategy as skill learning proceeds.

Pharmacokinetic Analysis of Huangqi Guizhi Wuwu Decoction on Blood and Brain Tissue in Rats with Normal and Cerebral Ischemia-Reperfusion Injury by Microdialysis with HPLC-MS/MS.

OBJECTIVE: The aim of our research was to analyze and compare the pharmacokinetics of paeoniflorin, calycosin, calycosin-7-o-ß-d-6-glucoside, and 6-gingerol in the blood and brain tissue of normal and cerebral ischemia-reperfusion injury rats by HPLC-MS/MS method. METHODS: The blood and brain tissue samples of normal and middle cerebral artery occlusion (MCAO) rats were compared. The blood and brain tissue samples were collected by using microdialysis technique. The concentrations of paeoniflorin, calycosin, calycosin-7-o-ß-d-6-glucoside, and 6-gingerol in blood and brain tissues were determined by the HPLC-MS/MS internal standard method. RESULTS: Compared with the normal group, the model group after the administration of the Huangqi Guizhi Wuwu Decoction showed that Cmax blood, AUC0-t blood, and AUC0-inf blood of paeoniflorin were increased, CLblood, t1/2 brain, and Vbrain of paeoniflorin were decreased; Cmaxblood, AUC0-tblood, AUC0-infblood, and average residence time (MRTbrain) of calycosin-7-o-ß-d-6-glucoside were decreased and the CLblood and Cmax brain of calycosin-7-o-ß-d-6-glucoside were increased; Cmax blood of calycosin was decreased, Vblood and Vbrain of calycosin were increased; Cmax blood, AUC0-t blood, AUC0-inf blood, and MRTbrain of 6-gingerol were decreased, CLblood of 6-gingerol was increased. CONCLUSION: This method is simple, rapid, and sensitive. It is suitable for the pharmacokinetic study of Huangqi Guizhi Wuwu Decoction in the blood and brain tissue of rats. Cerebral ischemia-reperfusion injury increased the content of paeoniflorin, calycosin, calycosin-7-o-ß-d-6-glucoside, and 6-gingerol in the blood, affecting the clearance rate of paeoniflorin in the brain, the detention time of calycosin-7-o-ß-d-6-glucoside and the 6-gingerol in the brain. In normal and cerebral ischemia-reperfusion rats, the content of paeoniflorin and 6-gingerol in the blood was higher than that in brain tissue, while the content of calycosin, calycosin-7-o-ß-d-6-glucoside in the brain tissue was higher than that in blood, suggesting that calycosin and calycosin-7-o-ß-d-6-glucoside have brain targeting properties.

Cell Chromatography-Based Screening of the Active Components in Buyang Huanwu Decoction Promoting Axonal Regeneration.

Buyang Huanwu decoction (BHD), a popular formulation prescribed in traditional Chinese medicine (TCM) for the treatment of ischemic stroke, has been reported to have a potential role in promoting axonal regeneration. The purpose of the study was to screen and identify bioactive compounds from BHD using live PC12 cells coupled with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Using this approach, we successfully identified six bioactive components from BHD. These components have protective effects on oxygen-glucose deprivation/reperfusion (OGD/R) injury to PC12 cells. Furthermore, calycosin-7-d-glucoside (CG) and formononetin-7-O-ß-d-glucoside (FG) could upregulate the protein expression of growth-associated protein 43 (GAP-43) and brain-derived neurotrophic factor (BDNF). This study suggests that living cells combined with HPLC-MS/MS can be used for the screening of active ingredients in TCMs.

Erythrocyte membrane affinity chromatography, solid-phase extraction and UPLC-QTOF-MS/MS to screen active ingredients of Buyang Huanwu decoction.

Buyang Huanwu decoction (BHD) is a well-known traditional Chinese medicine that has long been used to treat ischemic brain damage which is associated with hemorheology. To screen active ingredients in BHD responsible for reducing blood viscosity by reducing red blood cell (RBC) lesions to treat ischemic stroke, a method involving RBC membrane binding and solid-phase extraction (SPE) was developed in this study. The components of BHD interacting with RBC were analyzed by mass spectrometry and four compounds, calycosin, paeoniflorin, 6-hydroxy behenol-3,6-di-O-glucoside and calycosin-7-O-ß-d-glucoside, showed binding affinity to RBCs. An erythrocyte activity assay revealed that the identified ingredients promoted the activities of Na+-K+-ATPase, sialic acid and superoxide dismutase and reduced the content of cholesterol on the RBC membrane, suggesting a mechanism underlying their anti-erythrocyte aggregation activity. Based on these results, the RBC membrane binding assay combined with SPE and mass spectrometry is a novel and effective approach for screening potentially anti-erythrocyte lesion constituents in traditional Chinese medicines.

Research on musculoskeletal model of elbow joint for evaluating the feasibility of FES.

Tremor usually occurs in a patient's upper limb with a roughly sinusoidal profile. Understanding the inner mechanism of the involuntary movement is fundamental to improving tremor suppression treatments. Therefore, the musculoskeletal model of the elbow joint was developed in this study. Initially, healthy subjects were selected to simulate tremor and the tremulous data was collected with the purpose of sparing patients from fatigue. With the recorded joint angle and surface EMG (sEMG), the model was calibrated to subjects by optimization approach. The activation derived from the electric pulse was employed to drive the tuned model and the model's output was compared with the angle predicted by the EMG-driven musculoskeletal model. The results demonstrated that the performance of the calibrated model was improved by a smaller normalized root mean square error and a higher coefficient of determination compared with the no-tuned model. There was no significant difference between the angles estimated by the tuned model activated by the electric pulse and muscle excitation. It indicates that neural activation could be replaced by the electric pulse to excite the limbs for desired angle. Therefore, the study presents a good way to evaluate the feasibility of Functional Electric Stimulation to suppress tremor.