IFNet: An Interactive Frequency Convolutional Neural Network for Enhancing Motor Imagery Decoding From EEG.

OBJECTIVE: The key principle of motor imagery (MI) decoding for electroencephalogram (EEG)-based Brain-Computer Interface (BCI) is to extract task-discriminative features from spectral, spatial, and temporal domains jointly and efficiently, whereas limited, noisy, and non-stationary EEG samples challenge the advanced design of decoding algorithms. METHODS: Inspired by the concept of cross-frequency coupling and its correlation with different behavioral tasks, this paper proposes a lightweight Interactive Frequency Convolutional Neural Network (IFNet) to explore cross-frequency interactions for enhancing representation of MI characteristics. IFNet first extracts spectro-spatial features in low and high-frequency bands, respectively. Then the interplay between the two bands is learned using an element-wise addition operation followed by temporal average pooling. Combined with repeated trial augmentation as a regularizer, IFNet yields spectro-spatio-temporally robust features for the final MI classification. We conduct extensive experiments on two benchmark datasets: the BCI competition IV 2a (BCIC-IV-2a) dataset and the OpenBMI dataset. RESULTS: Compared with state-of-the-art MI decoding algorithms, IFNet achieves significantly superior classification performance on both datasets while improving the winner's result in BCIC-IV-2a by 11%. Moreover, by conducting sensitivity analysis on decision windows, we show IFNet attains the best trade-off between decoding speed and accuracy. Detailed analysis and visualization verify IFNet can capture the coupling across frequency bands along with the known MI signatures. CONCLUSION: We demonstrate the effectiveness and superiority of the proposed IFNet for MI decoding. SIGNIFICANCE: This study suggests IFNet holds promise for rapid response and accurate control in MI-BCI applications.

Tactile Sensation Assisted Motor Imagery Training for Enhanced BCI Performance: A Randomized Controlled Study.

OBJECTIVE: Independent of conventional neurofeedback training, in this study, we propose a tactile sensation assisted motor imagery training (SA-MI Training) approach to improve the performance of MI-based BCI. METHODS: Twenty-six subjects were recruited and randomly divided into a Training-Group and a Control-Group. All subjects were required to perform three blocks of MI tasks. In the Training-Group, during the second block (SA-MI Training block), tactile stimulation was applied to the left or right wrist while the subjects were performing the left or right-hand MI task, while during the first block (Pre-Training block) and the third block (Post-Training block), subjects performed pure MI tasks without the tactile sensation assistance. In contrast, in the Control-Group, subjects performed the left and right-hand MI tasks in all three blocks. RESULTS: The performance of the Post-Training block (83.2 ± 11.4%) was significantly (p = 0.0014) higher than that of the Pre-Training block (73.2 ± 16.3%). By contrast, in the Control-Group, no significant difference was found among the three blocks. Moreover, after the SA-MI Training, the motor-related cortex activation (i.e., ERD/ERS) and the R 2 coefficient in the alpha-beta band were enhanced, while no training effect was found in the Control-Group. CONCLUSION: The proposed SA-MI Training approach can significantly improve the performance of MI, which provides a novel training framework for MI-based BCI. SIGNIFICANCE: It may be especially beneficial to those who are with difficulty in convention neurofeedback training or performing pure MI mental tasks to gain BCI control.

Panaxydol Derived from Panax notoginseng Promotes Nerve Regeneration after Sciatic Nerve Transection in Rats.

BACKGROUND: Peripheral nerve regeneration is a coordinated process of Schwann cell (SC) reprogramming and intrinsic neuronal growth program activation. Panaxydol (PND) is a strong biologically active traditional Chinese medicine monomer extracted from Panax notoginseng rhizomes. In vitro, PND protects neurons and SCs from injury and stimulates the expression and secretion of neurotrophic factors (NTFs) by SCs. We hypothesized that PND may also promote peripheral nerve regeneration in adult animals. METHODS: PND (10 mg/kg body weight) was injected intraperitoneally into the Sprague-Dawley (SD) rats for two consecutive weeks after sciatic nerve transection. The morphology of the repaired sciatic nerve was evaluated after 16 weeks, and sensory and motor function recovery was evaluated using functional and behavioral techniques. RESULTS: PND was biologically safe at an injection dose of 10 mg/kg/day. After 14 days, it significantly increased the myelination of regenerated nerve fibers, and promoted sensory and motor function recovery. In the early stage of injury, PND significantly upregulated the mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptors in distal injured nerves, which may represent a possible mechanism by which PND promotes nerve regeneration in vivo. CONCLUSIONS: Our study demonstrated that PND leads to sensory and motor recovery in a sciatic nerve transection model rat. Furthermore, we showed that BDNF mRNA level was significantly increased in the injured distal nerve, potentially contributing to the functional recovery. Further research is warrantied to examine whether direct injection is a more efficient method to increase BDNF expression compared to an exogenous BDNF administration.

Artificial neural network-genetic algorithm-based optimization of aerobic composting process parameters of Ganoderma lucidum residue.

The rapid development of traditional Chinese medicine enterprises has put forward higher requirements for the resource utilization of traditional Chinese medicine residues (TCMR). Aerobic composting of TCMR to prepare bio-organic fertilizer is an effective resource utilization method. In this study, a back-propagation artificial neural network (BPNN) model using composting factors as inputs (C/N, initial moisture content, type of inoculant, composting days) and the humic acid content as the output was constructed based on the orthogonal test data. BPNN-GA (a genetic algorithm) was used for extreme value optimization, and the optimal composting process parameter combination was obtained and verified. The results show that the combination of orthogonal testing and BPNN can effectively establish the relationship between the composting process parameters and humic acid content. The R2 value was 0. 9064. The optimized parameter combination is as follows: C/N,37.42; moisture content,69.76%; bacteria,no; and composting time,50 d.

Supercritical CO2 fluid extraction of croton crassifolius Geisel root: Chemical composition and anti-proliferative, autophagic, apoptosis-inducing, and related molecular effects on A549 tumour cells.

BACKGROUND: The use of plant essential oils as pharmaceuticals is a fast-growing market especially in China. Throughout the 20th century, a rapid increase took place in the use of many essential oil-derived products in the medicinal industry as nutraceuticals, medicinal supplements, and pharmaceuticals. PURPOSE: The objective of this study was to explore the chemical composition of Croton crassifolius essential oil as well as its potential anti-tumour properties and related anti-proliferative, autophagic, and apoptosis-inducing effects. METHODS: Supercritical CO2 fluid extraction technology was used to extract CCEO and the chemical constituents of the essential oil were identified by comparing the retention indices and mass spectra data taken from the NIST library with those calculated based on the C7-C40 n-alkanes standard. The cytotoxic activity and anti-proliferative effects of CCEO were evaluated against five cancer cell lines and one normal human cell line via CCK-8 assays. In addition, flow cytometry was used to detect cell cycle arrest. The efficacy of CCEO treatments in controlling cancer cell proliferation was assessed by cell cycle analysis, clonal formation assays, RT-qPCR, and western blot analysis. Autophagic and apoptosis-inducing effects of oils and the associated molecular mechanisms were assessed by flow cytometry, cell staining, reactive oxygen species assays, RT-qPCR, and western blot analysis. CONCLUSION: Forty compounds representing 92.90% of the total oil were identified in CCEO. The results showed that CCEO exerted a measurable selectivity for cancer cell lines, especially for A549 with the lowest IC50 value of 25.00 ± 1.62 µg/mL. Assessment of the anti-proliferative effects of CCEO on A549 cells showed that the oil inhibited cell proliferation and colony formation in a dose- and time-dependent manner. Investigation of the molecular mechanisms of cell cycle regulation confirmed that the oil arrested A549 cells in G2/M phase by decreasing the expression of cyclin B1-CDK1 and cyclin A-CDK1 and increasing the expression of cyclin-dependent kinase inhibitor (CKI) P21 at both the transcriptional and translational levels. Autophagy staining assays and western blot analysis revealed that CCEO promoted the formation of autophagic vacuoles in A549 cells and increased the expression of autophagy-related proteins beclin-1 and LC3-II in a dose-dependent manner. A series of apoptosis analyses indicated that CCEO induces apoptosis through a mitochondria-mediated intrinsic pathway. This study revealed that CCEO is a promising candidate for development into an anti-tumour drug of the future.

Inhibition of Glutathione Synthesis via Decreased Glucose Metabolism in Stored RBCs.

BACKGROUND/AIMS: Although red blood cells (RBCs) transfusions can be lifesaving, they are not without risk. RBCs storage is associated with the abnormal metabolism of glutathione (GSH), which may increase the risk of the oxidative damage of RBCs after transfusion. The responsible mechanisms remain unknown. METHODS: We determined the L-cysteine efflux and influx by evaluating the changes of free -SH concentrations in stored RBCs. The glutamate cysteine ligase (GCL) activities and protein content in stored RBCs was determined by fluorescence assay and western blotting. In addition, the glucose metabolism enzyme activity of RBCs was measured by spectrophotometric assay under in vitro incubation conditions. RESULTS: We found that both L-cysteine transport and GCL activity significantly declined, thereby inducing the dysfunction of GSH synthesis during blood storage, which could be attenuated by ATP supplement and DTT treatment. In addition, the glycometabolic enzyme (G6PDH, HK, PK and LDH) activity significantly decreased after 6 weeks storage. Oxidant stress-induced dysfunction in glucose metabolism was the driving force for decreased GSH synthesis during storage. CONCLUSION: These experimental findings reflect an underlying molecular mechanism that oxidant stress induced glucose metabolism dysfunction contribute to decreased GSH synthesis in stored RBCs.

Synephrine Hydrochloride Suppresses Esophageal Cancer Tumor Growth and Metastatic Potential through Inhibition of Galectin-3-AKT/ERK Signaling.

A library consisting of 429 food-source compounds was used to screen the natural products with anticancer properties in esophageal squamous cell carcinoma (ESCC). We demonstrated for the first time that synephrine, an active compound isolated from leaves of citrus trees, markedly suppressed cell proliferation (inhibition rate with 20 µM synephrine at day 5:71.1 ± 5.8% and 75.7 ± 6.2% for KYSE30 and KYSE270, respectively) and colony formation (inhibition rate with 10 µM synephrine: 86.5 ± 5.9% and 82.3 ± 4.5% for KYSE30 and KYSE270, respectively), as well as migration (inhibition rate with 10 µM synephrine: 76.9 ± 4.4% and 62.2 ± 5.8% for KYSE30 and KYSE270, respectively) and invasion abilities (inhibition rate with 10 µM synephrine: 73.3 ± 7.5% and 75.3 ± 3.4% for KYSE30 and KYSE270, respectively) of ESCC cells in a dose-dependent manner, without significant toxic effect on normal esophageal epithelial cells. Mechanistically, quantitative proteomics and bioinformatics analyses were performed to explore the synephrine-regulated proteins. Western blot and qRT-PCR data indicated that synephrine may downregulate Galectin-3 to inactivate AKT and ERK pathways. In addition, we found that the sensitivity of ESCC to fluorouracil (5-FU) could be enhanced by synephrine. Furthermore, in vivo experiments showed that synephrine had significant antitumor effect on ESCC tumor xenografts in nude mice (inhibition rate with 20 mg/kg synephrine is 61.3 ± 20.5%) without observed side effects on the animals. Taken together, synephrine, a food-source natural product, may be a potential therapeutic strategy in ESCC.

Optogenetic control of thalamus as a tool for interrupting penicillin induced seizures.

Penicillin epilepsy model, whose discharge resembles that of human absence epilepsy, is one of the most useful acute experimental epilepsy models. Though closed-loop optogenetic strategy of interrupting seizures was proved sufficient to switch off epilepsy by controlling thalamus in the post-lesion partial chronic epilepsy model, doubts still exist in absence epilepsy attenuation through silencing thalamus. Here we directly arrested the thalamus to modulate penicillin-induced absence seizures through pseudorandom responsive stimulation on eNpHR-transfected rats. Our data suggested that the duration of epileptiform bursts under light conditions, compared with no light conditions, did not increase or decrease when modulated specific eNpHR-expressing neurons in thalamus.

Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression.

Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models. Here, we study the InsR-up-regulating and glucose-lowering activities of BBR in humans. Our results showed that BBR increased InsR messenger RNA and protein expression in a variety of human cell lines, including CEM, HCT-116, SW1990, HT1080, 293T, and hepatitis B virus-transfected human liver cells. Accordingly, insulin-stimulated phosphorylations of InsR beta-subunit and Akt were increased after BBR treatment in cultured cells. In the clinical study, BBR significantly lowered fasting blood glucose (FBG), hemoglobin A(1c), triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM). The FBG- and hemoglobin A(1c)-lowering efficacies of BBR were similar to those of metformin and rosiglitazone. In the BBR-treated patients, the percentages of peripheral blood lymphocytes that express InsR were significantly elevated after therapy. Berberine also lowered FBG effectively in chronic hepatitis B and hepatitis C patients with T2DM or impaired fasting glucose. Liver function was improved greatly in these patients by showing reduction of liver enzymes. Our results confirmed the activity of BBR on InsR in humans and its relationship with the glucose-lowering effect. Together with our previous report, we strongly suggest BBR as an ideal medicine for T2DM with a mechanism different from metformin and rosiglitazone.

Synthesis and activity evaluation of benzoylurea derivatives as potential antiproliferative agents.

3-Haloacylamino benzoylureas (3-HBUs) consist of a new family of tubulin ligands that kill cancer cells through mitotic arrest. In exploring the structure-activity relationship (SAR), 17 analogues defined through variations of formylurea at the 1-position of the aromatic ring were synthesized. SAR analysis revealed that (i) the p-pi conjugation between the aromatic ring and formylurea was essential; (ii) suitable aryl substitutions at the N'-end increased anticancer activity with a mechanism different from that of parent compounds; and (iii) introduction of pyridyl at the N'-end provided an opportunity of making soluble salts to improve bioavailability. Among the analogues, 16c bearing 3,4,5-trimethoxyphenyl and 16g bearing 2-pyridyl at the N'-end showed an enhanced activity and were active in hepatoma cells that were resistant to tubulin ligands including the parent compounds. Furthermore, 16c and 16g killed cancer cells with a mechanism independent of mitotic arrest, indicating a change of action mode.