Transcranial alternating current stimulation improves quality of life in Parkinson's disease: study protocol for a randomized, double-blind, controlled trial.

BACKGROUND: The neural cells in the brains of patients with Parkinson's disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson's disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson's disease based on the central-peripheral-central theory. METHODS: The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson's disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. DISCUSSION: The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

Mechanism-Based Inactivation of CYP2D6 by Phellopterin and Related Drug-Drug Interaction with Metoprolol.

Phellopterin (PLP) is a linear furanocoumarin widely found in citrus fruits and herbal medicines. The study aims to comprehensively investigate the mechanism of inhibition of CYP2D6 enzyme activity by PLP and its alteration of metoprolol pharmacokinetics. PLP was found to irreversibly inhibit CYP2D6 in time-, concentration-, and nicotinamide adenine dinucleotide phosphate-dependent manners. Coincubation with quinidine, which is a competitive inhibitor of CYP2D6, attenuated this time-dependent inhibition. Glutathione (GSH) and catalase/superoxide dismutase failed to reverse the PLP-induced CYP2D6 inactivation. GSH trapping experiments provided strong evidence that PLP metabolic activation produces epoxide or γ-ketoaldehyde intermediates. In addition, pretreatment with PLP resulted in significant increases in Cmax and area under curve of plasma metoprolol in rats.

Applications, prospects and challenges of metal borides in lithium sulfur batteries.

Although the lithium-sulfur (Li-S) battery has a theoretical capacity of up to 1675 mA h g-1, its practical application is limited owing to some problems, such as the shuttle effect of soluble lithium polysulfides (LiPSs) and the growth of Li dendrites. It has been verified that some transition metal compounds exhibit strong polarity, good chemical adsorption and high electrocatalytic activities, which are beneficial for the rapid conversion of intermediate product in order to effectively inhibit the "shuttle effect". Remarkably, being different from other metal compounds, it is a significant characteristic that both metal and boron atoms of transition metal borides (TMBs) can bind to LiPSs, which have shown great potential in recent years. Here, for the first time, almost all existing studies on TMBs employed in Li-S cells are comprehensively summarized. We firstly clarify special structures and electronic features of metal borides to show their great potential, and then existing strategies to improve the electrochemical properties of TMBs are summarized and discussed in the focus sections, such as carbon-matrix construction, morphology control, heteroatomic doping, heterostructure formation, phase engineering, preparation techniques. Finally, the remaining challenges and perspectives are proposed to point out a direction for realizing high-energy and long-life Li-S batteries.

Dihydrotanshinone I-Induced CYP1 Enzyme Inhibition and Alteration of Estradiol Metabolism.

Dihydrotanshinone I (DHTI) is a pharmacologically active component occurring in the roots of the herbal medicine Salvia miltiorrhiza Bunge. This study investigated DHTI-induced inhibition of CYP1A1, CYP1A2, and CYP1B1 with the aim to determine the potential effects of DHTI on the bioactivation of estradiol (E2), possibly related to preventive/therapeutic strategy for E2-associated breast cancer. Ethoxyresorufin as a specific substrate for CYP1s was incubated with human recombinant CYP1A1, CYP1A2, or CYP1B1 in the presence of DHTI at various concentrations. Enzymatic inhibition and kinetic behaviors were examined by monitoring the formation of the corresponding product. Molecular docking was further conducted to define the interactions between DHTI and the three CYP1s. The same method and procedure were employed to examine the DHTI-induced alteration of E2 metabolism. DHTI showed significant inhibition of ethoxyresorufin O-deethylation activity catalyzed by CYP1A1, CYP1A2 and CYP1B1 in a concentration-dependent manner (IC50 = 0.56, 0.44, and 0.11 µM, respectively). Kinetic analysis showed that DHTI acted as a competitive type of inhibitor of CYP1A1 and CYP1B1, whereas it noncompetitively inhibited CYP1A2. The observed enzyme inhibition was independent of NADPH and time. Molecular docking analysis revealed hydrogen bonding interactions between DHTI and Asp-326 of CYP1B1. Moreover, DHTI displayed preferential activity to inhibit 4-hydroxylation of E2 (a genotoxic pathway) mediated by CYP1B1. Exposure to DHTI could reduce the risk of genotoxicity induced by E2. SIGNIFICANCE STATEMENT: CYP1A1, CYP1A2, and CYP1B1 enzymes are involved in the conversion of estradiol (E2) into 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2) through oxidation. 2-OHE2 is negatively correlated with breast cancer risk, and 4-OHE2 may be a significant initiator and promoter of breast cancer. The present study revealed that dihydrotanshinone I (DHTI) competitively inhibits CYP1A1/CYP1B1 and noncompetitively inhibits CYP1A2. DHTI exhibits a preference for inhibiting the genotoxicity associated with E2 4-hydroxylation pathway mediated by CYP1B1, potentially reducing the risk of 4-OHE2-induced genotoxicity.

Substrate Positioning Dynamics Involves a Non-Electrostatic Component to Mediate Catalysis.

Substrate positioning dynamics (SPD) orients the substrate in the active site, thereby influencing catalytic efficiency. However, it remains unknown whether SPD effects originate primarily from electrostatic perturbation inside the enzyme or can independently mediate catalysis with a significant non-electrostatic component. In this work, we investigated how the non-electrostatic component of SPD affects transition state (TS) stabilization. Using high-throughput enzyme modeling, we selected Kemp eliminase variants with similar electrostatics inside the enzyme but significantly different SPD. The kinetic parameters of these mutants were experimentally characterized. We observed a valley-shaped, two-segment linear correlation between the TS stabilization free energy (converted from kinetic parameters) and substrate positioning index (a metric to quantify SPD). The energy varies by approximately 2 kcal/mol. Favorable SPD was observed for the distal mutant R154W, increasing the proportion of reactive conformations and leading to the lowest activation free energy. These results indicate the substantial contribution of the non-electrostatic component of SPD to enzyme catalytic efficiency.

SDS-Net: A lightweight 3D convolutional neural network with multi-branch attention for multimodal brain tumor accurate segmentation.

The accurate and fast segmentation method of tumor regions in brain Magnetic Resonance Imaging (MRI) is significant for clinical diagnosis, treatment and monitoring, given the aggressive and high mortality rate of brain tumors. However, due to the limitation of computational complexity, convolutional neural networks (CNNs) face challenges in being efficiently deployed on resource-limited devices, which restricts their popularity in practical medical applications. To address this issue, we propose a lightweight and efficient 3D convolutional neural network SDS-Net for multimodal brain tumor MRI image segmentation. SDS-Net combines depthwise separable convolution and traditional convolution to construct the 3D lightweight backbone blocks, lightweight feature extraction (LFE) and lightweight feature fusion (LFF) modules, which effectively utilizes the rich local features in multimodal images and enhances the segmentation performance of sub-tumor regions. In addition, 3D shuffle attention (SA) and 3D self-ensemble (SE) modules are incorporated into the encoder and decoder of the network. The SA helps to capture high-quality spatial and channel features from the modalities, and the SE acquires more refined edge features by gathering information from each layer. The proposed SDS-Net was validated on the BRATS datasets. The Dice coefficients were achieved 92.7, 80.0 and 88.9% for whole tumor (WT), enhancing tumor (ET) and tumor core (TC), respectively, on the BRTAS 2020 dataset. On the BRTAS 2021 dataset, the Dice coefficients were 91.8, 82.5 and 86.8% for WT, ET and TC, respectively. Compared with other state-of-the-art methods, SDS-Net achieved superior segmentation performance with fewer parameters and less computational cost, under the condition of 2.52 M counts and 68.18 G FLOPs.

Progressive Classifier Mechanism for Bridge Expansion Joint Health Status Monitoring System Based on Acoustic Sensors.

The application of IoT (Internet of Things) technology to the health monitoring of expansion joints is of great importance in enhancing the efficiency of bridge expansion joint maintenance. In this study, a low-power, high-efficiency, end-to-cloud coordinated monitoring system analyzes acoustic signals to identify faults in bridge expansion joints. To address the issue of scarce authentic data related to bridge expansion joint failures, an expansion joint damage simulation data collection platform is established for well-annotated datasets. Based on this, a progressive two-level classifier mechanism is proposed, combining template matching based on AMPD (Automatic Peak Detection) and deep learning algorithms based on VMD (Variational Mode Decomposition), denoising, and utilizing edge and cloud computing power efficiently. The simulation-based datasets were used to test the two-level algorithm, with the first-level edge-end template matching algorithm achieving fault detection rates of 93.3% and the second-level cloud-based deep learning algorithm achieving classification accuracy of 98.4%. The proposed system in this paper has demonstrated efficient performance in monitoring the health of expansion joints, according to the aforementioned results.

Two-birds with one stone: Improving both cathode and anode electrochemical performances via two-dimensional Te-CoTe2/rGO ultrathin nanosheets as sulfur hosts in lithium-sulfur batteries.

A Te-doped CoTe2 film could be grown in situ on reduced graphene oxide (rGO) to develop a Te-CoTe2/rGO composite with an ultrathin layered structure, which has multiple protective effects on both the sulfur positive electrode and lithium negative electrode in lithium sulfur (Li-S) batteries. The Te-CoTe2/rGO composite as a sulfur host not only shows a strong adsorbing ability for lithium polysulfides (LiPSs) but can also accelerate the conversion reaction of active material sulfur during the charging/discharging process. More importantly, this host can turn the shuttle effect from an unfavorable factor to a favorable factor, which could improve the electrochemical performance of the lithium anode with uniform lithium plating/stripping resulting from the intermediate polytellurosulfide species (Li2TexSy), which could be generated on the cathode surface via Te reacting with soluble Li2Sn (4 ≤ n ≤ 8). As a result, the S@Te-CoTe2/rGO cathode shows a discharge capacity of 970.0 mA h g-1 in the first cycle at 1 C and retains a high capacity of 545.5 mA h g-1 after 1000 cycles, corresponding to a low capacity decay rate of only 0.043% per cycle. In addition, in situ X-ray diffraction (XRD) and in situ Raman were used to explore the sulfur conversion process. This study not only demonstrates that a two-dimensional (2D) ultrathin Te-CoTe2/rGO composite is successfully developed with multiple effects on Li-S batteries but also opens a new pathway for designing unique sulfur hosts to promote the electrochemical performance of Li-S batteries.

Improving performances of Lithium-Sulfur cells via regulating of VSe2 functional mediator with Doping-Defect engineering and Electrode-Separator integration strategy.

The sluggish redox kinetics and the severe shuttle effect of soluble lithium polysulfides (LiPSs) are the main key issues which would hinder the development of lithium-sulfur (Li-S) batteries. In this work, a nickel-doped vanadium selenide in-situ grows on reduced graphene oxide(rGO) to form a two-dimensional (2D) composite Ni-VSe2/rGO by a simple solvothermal method. When it is used as a modified separator in Li-S batteries, the Ni-VSe2/rGO material with the doped defect and super-thin layered structure can greatly adsorb LiPSs and catalyze the conversion reaction of LiPSs, resulting in effectively reducing LiPSs diffusion and suppressing the shuttle effect. More importantly, the cathode-separator bonding body is first developed as a new strategy of electrode-separator integration in Li-S batteries, which not only could decrease the LiPSs dissolution and improve the catalysis performance of the functional separator as the upper current-collector, but also is good for the high sulfur loading and the low electrolyte/sulfur (E/S) ratio for high energy density Li-S batteries. When the Ni-VSe2/rGO-PP (polypropylene, Celgard 2400) modified separator is applied, the Li-S cell can retain 510.3 mA h g-1 capacity after 1190 cycles at 0.5C. In the electrode-separator integrated system, the Li-S cell can still maintain 552.9 mA h g-1 for 190 cycles at a sulfur loading 6.4 mg cm-2 and 4.9 mA h cm-2 for 100 cycles at a sulfur loading 7.0 mg cm-2. The experimental results indicate that both the doped defect engineering and the super-thin layered structure design might optimally be chosen to fabricate a new modified separator material, and especially, the electrode-separator integration strategy would open a practical way to promote the electrochemical behavior of Li-S batteries with high sulfur loading and low E/S ratio.

Effects of Prunus Tomentosa Thumb Total Flavones on adjuvant arthritis in rats and regulation of autophagy.

BACKGROUND: Rheumatoid arthritis (RA) is a slow in taking effect systemic autoimmune disease. Prunus Tomentosa Thumb Total Flavones (PTTTF) has anti-inflammatory and antioxidant properties. OBJECTIVE: The purpose of this study is to the PTTTF on adjuvant arthritis (AA) in rats and to explore the mechanism of autophagy. METHODS: Adjuvant arthritis model was established in rats. The cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-17 (IL-17), tumor necrosis factor (TNF-α) of rat synovial tissue were determined by RT-PCR. The histopathological varieties of knee joints in AA rats were observed by HE staining. The expressions of autophagy-related proteins ATG5, ATG7, ATG12, Beclin1, Lc3II and Bcl-2 in rat synovial tissue were determined by Western Blotting. RESULTS: PTTTF (50, 100, 200 mg/kg) significantly inhibited inflammation in rats (P< 0.01). PTTTF significantly inhibited inflammatory factor COX in rat synovial tissue. COX-2, IL-1ß, IL-6, IL-17, TNF-α expression (P< 0.05); PTTTF can significantly improve the pathological damage of rat knee joint PTTTF and can significantly inhibited the expression of autophagy-related proteins in rat synovium (P< 0.05 ). CONCLUSION: PTTTF can inhibit adjuvant arthritis in rats and can inhibit the expression of autophagy-related proteins ATG5, ATG7, ATG12, Beclin1, Lc3II and Bcl-2.

Mechanistic Study of Xanthotoxin-Mediated Inactivation of CYP1A2 and Related Drug-Drug Interaction with Tacrine.

Xanthotoxin (XTT) is a biologically active furanocoumarin widely present in foods and plants. The present study is designed to systematically investigate the enzymatic interaction of XTT with CYP1A2, along with pharmacokinetic alteration of tacrine resulting from the co-administration of XTT. The results showed that XTT induced a time-, concentration-, and NADPH-dependent inhibition of CYP1A2, and the inhibition was irreversible. Co-incubation of glutathione (GSH) and catalase/superoxide dismutase was unable to prevent enzyme inactivation. Nevertheless, competitive inhibitor fluvoxamine exhibited a concentration-dependent protective effect against the XTT-induced CYP1A2 inactivation. A GSH trapping experiment provided strong evidence for the production of epoxide or/and γ-ketoenal intermediates resulting from the metabolic activation of XTT. Furthermore, pretreatment of rats with XTT was found to significantly increase the Cmax and area under the curve of plasma tacrine relative to those of tacrine administration alone.

Kerr soliton frequency comb generation by tuning the coupling coefficient in coupled nonlinear microcavities.

Kerr soliton frequency comb generation in nonlinear microcavities with compact configurations are promising on-chip sources. Current Kerr comb generation by using a single microcavity with a tunable CW pump laser or high-power femtosecond pulse pump are difficult to be integrated on chip. In this paper, we propose an on-chip soliton comb generation scheme by tuning the coupling coefficient of two coupled microcavities instead of tuning the wavelength of the cw pump laser or using a pulsed pump laser in a single microcavity. The two microcavities are assumed to be identical. We showed by numerical simulation that Kerr comb generation is possible in both the blue and red detuned regions of the main microcavity in the coupled cavity system. We further found that the range and boundary of the soliton generation region of the couple microcavities depend on the coupling coefficient between the coupled cavities. To ensure that the modes being coupled have identical optical paths, we designed a Sagnac loop structure which couples the clockwise and counterclockwise modes in a single microcavity and demonstrated Kerr comb generation in both the blue and red detuned regions by tuning the coupling coefficient. The proposed Kerr comb generation scheme can be utilized for chip-scale integrated soliton comb sources, which will contribute to the development of on-chip applications.

Acid-degradable nanocomposite hydrogel and glucose oxidase combination for killing bacterial with photothermal augmented chemodynamic therapy.

Bacterial infection often delays diabetic wound healing, and even causes serious life-threatening complications. Herein, we successfully developed a Cu2O/Pt nanocubes-dopping alginate (ALG)- hyaluronic acid (HA) hydrogel (Cu2O/Pt hydrogel) by simple assembly of the Cu2O/Pt nanocubes and the ALG-HA mixture. The Cu2O/Pt hydrogel combined with the glucose oxidase (GOx) can be used for photothermal- and starving-enhanced chemodynamic therapy (CDT) against Gram-negative and Gram-positive bacteria. The GOx can catalyze the glucose to produce gluconic acid and H2O2 for starvation therapy, following which the released Cu2O/Pt nanocubes react with H2O2 in the acidic microenvironment to generate highly cytotoxic hydroxyl radicals (·OH) for CDT. Additionally, the Cu2O/Pt hydrogel can release copper ions gradually with the decrease of pH induced by gluconic acid, which can increase the protein expression and secretion of vascular endothelial growth factor (VEGF) and promote endothelial cell proliferation, migration and angiogenesis, subsequently promoting diabetic wound healing in rats. Our results suggested that the Cu2O/Pt hydrogel combined with GOx may be a potential therapeutic approach for treating the infected diabetic wound.

The role of selenium vacancies functionalized mediator of bimetal (Co, Fe) selenide for high-energy-density lithium-sulfur batteries.

Lithium-sulfur (Li-S) batteries are currently only in the basic research stage and have not been commercialized, which is mainly affected by the poor conductivity of sulfur/lithium sulfide (S/Li2S), volume expansion effect of sulfur and the shuttle effect of lithium polysulfides (LiPSs). Herein, a three dimensional (3D) carbon nanotubes (CNTs) decorated cubic Co9Se8-x/FeSe2-y (0 ï¼œ x ï¼œ 8, 0 ï¼œ y ï¼œ 2) composite (Co9Se8-x/FeSe2-y@CNTs) is developed, and used as the functionalized mediator on polypropylene (PP) in Li-S batteries. Benefiting from the good electrical conductivity, large number of Se vacancies and the triple block/adsorption/catalytic effects of Co9Se8-x/FeSe2-y@CNTs, the cell with Co9Se8-x/FeSe2-y@CNTs//PP modified separator delivers a high reversible capacity (1103.5 mA h g-1) at 1C after three cycles activation at 0.5C and remains 446 mA g h-1 after 750 cycles with a 0.08% capacity decay rate each cycle. Moreover, at 0.2C, a high areal capacity of 3.63 mA h cm-2 after 100 cycles with a high sulfur loading of 4.1 mg cm-2 is obtained. The in-situ XRD tests revealing the transition path of α-S8 â†’ Li2S â†’ ß-S8 during the first charge-discharge process, then ß-S8 â†’ Li2S â†’ ß-S8 conversion reaction in the next cycles, and firstly determine the sulfur-selenide active intermediates (Se1.1S6.9) during cycles. The work provides a new insight into the development of bimetallic selenide composites by defect engineering with highly adsorptive and catalytic properties for Li-S batteries.

IntEnzyDB: an Integrated Structure-Kinetics Enzymology Database.

Data-driven modeling has emerged as a new paradigm for biocatalyst design and discovery. Biocatalytic databases that integrate enzyme structure and function data are in urgent need. Here we describe IntEnzyDB as an integrated structure-kinetics database for facile statistical modeling and machine learning. IntEnzyDB employs a relational database architecture with a flattened data structure, which allows rapid data operation. This architecture also makes it easy for IntEnzyDB to incorporate more types of enzyme function data. IntEnzyDB contains enzyme kinetics and structure data from six enzyme commission classes. Using 1050 enzyme structure-kinetics pairs, we investigated the efficiency-perturbing propensities of mutations that are close or distal to the active site. The statistical results show that efficiency-enhancing mutations are globally encoded and that deleterious mutations are much more likely to occur in close mutations than in distal mutations. Finally, we describe a web interface that allows public users to access enzymology data stored in IntEnzyDB. IntEnzyDB will provide a computational facility for data-driven modeling in biocatalysis and molecular evolution.

Extraordinary electrochemical performance of lithium-sulfur battery with 2D ultrathin BiOBr/rGO sheet as an efficient sulfur host.

There are many challenges such as the shuttling effect of soluble lithium polysulfides species (LiPSs) and the slow solid-state conversion between Li2S4 and Li2S in the development process of lithium-sulfur battery (LSB), so it is vital how to design and fabricate sulfur hosts with strong adsorption and good electrocatalysis. In this work, BiOBr in-situ forms onto both sides of reduced graphene oxide (rGO) to obtain a novel ultrathin BiOBr/rGO sheet, then self-constructing a hydrogel cylinder in shape, via a one-step hydrothermal process. The BiOBr/rGO composite with sandwich structure not only shows the outstanding adsorption effect on LiPSs, resulting from a strong bonding interaction between BiOBr/rGO and Li2S6 demonstrated by XPS technique, but also exhibits the extraordinary electrocatalytic performance on both the LiPSs conversion reaction in cyclic voltammetry experiment of symmetric cell and the Li2S nucleation process in potentiostatic deposited experiment, which will significantly improve the electrochemical performance of LSB. The S@BiOBr/rGO electrodes deliver the superior capacity and long cyclic stability with 882.2 mA h g-1 at 0.5 C after 1000 cycles, as well as displays the excellent rate performance with 823.9, 692.6 and 554.2 mA h g-1 at 1 C, 3 C and 5 C, respectively, after 400 cycles. Even though the sulfur loading reaches 4.9 mg cm-1, the reversible specific capacity of 424.6 mA h g-1can be maintained at 0.5 C after 400 cycles. Based on the in-situ X-ray diffraction and in-situ Raman spectroscopy, it could be revealed that the initial discharge process of active sulfur on the BiOBr/rGO cathode is α-S8 â†’ Li2S8 â†’ Li2S6 â†’ Li2S3 â†’ Li2S2 â†’ Li2S, while the charging progress is the corresponding reverse reaction, but the final substance is ß-S8. This research not only shows that the two-dimensional ultrathin BiOBr/rGO hybrid is successfully developed in LSB with excellent electrochemical performances, but also provides a strategy for exploring the construction of sulfur host materials.

Anti-inflammatory effect of baicalin in rats with adjuvant arthritis and its autophagy- related mechanism.

BACKGROUND: It has been found that baicalin have anti-inflammatory effects since it reduces the elevated levels of pro-inflammatory cytokines. Meanwhile, it has also been shown that baicalin brings positive effects against rheumatoid arthritis (RA). However, little is observed on its beneficial effects on adjuvant arthritis. OBJECTIVE: To consider the anti-inflammatory influence of baicalin on adjuvant arthritis rats and its related autophagy mechanism. METHODS: In this research, there are six groups of rats, each has 10 rats in it. These groups are normal group (normal saline), model group (normal saline), dexamethasone group (0.125 mg/kg dexamethasone), low-dose baicalin group (50 mg/kg baicalin), medium-dose baicalin group (100 mg/kg baicalin) and high-dose baicalin group (200 mg/kg baicalin). The degrees of adjuvant-induced swelling in rats' feet were measured every 4 days and the arthritis scores were calculated every 7 days. The inflamed joint tissues were taken after rats were sacrificed. The rat' joints showed pathological changes, which were observed by HE staining. The relative expression levels of inflammatory factors IL-6, IL-1, IL-17, TNF-α, COX2, and COX1 in the rats' snovial tissues were detected by RT-PCR. As for the expression levels of autophagy markers Beclin1, Atg5, Atg7, Atg12, microtubule-associated protein-light chain3-II (LC3-II), Bcl-2, and Bax in the synovial tissue, they were discoverd by Western blot. RESULTS: Baicalin could significantly inhibit the inflammatory response of adjuvant arthritis rats. CONCLUSIONS: RT-PCR studies showed that the different doses of baicalin could inhibit the expression of TNF-a, IL-6, IL-1, IL-17, COX2 and COX1 in the synovial tissue (P< 0.05 or P< 0.01). Western blot studies showed that the different doses of baicalin could reduce the expression of Atg5, Atg7, Atg12, LC3-II, Beclin1 and Bcl-2 proteins, and increase the expression of Bax proteins in the synovial tissue.

Kv7.4 channel is a key regulator of vascular inflammation and remodeling in neointimal hyperplasia and abdominal aortic aneurysms.

Inflammation has recently emerged as an important contributor for cardiovascular disease development and participates pivotally in the development of neointimal hyperplasia and abdominal aortic aneurysms (AAA) formation. Kv7.4/KCNQ4, a K+ channel, is one of the important regulators of vascular function but its role in vascular inflammation is unexplored. Here, we showed that the expression of Kv7.4 channel was elevated in the neointima and AAA tissues from mice and humans. Genetic deletion or pharmacological inhibition of Kv7.4 channel in mice alleviated neointimal hyperplasia and AAA formation via downregulation of a set of vascular inflammation-related genes, matrix metalloproteinases (MMP) 2/9, and intercellular adhesion molecule (ICAM-1). Furthermore, genetic deletion or inhibition of Kv7.4 channel suppressed the activation of tumor necrosis factor receptor 1 (TNFR1)-nuclear factor (NF)-κB signaling pathway via blockade of interaction between TNFR1 and TNFR1-associated death domain protein (TRADD) in vascular smooth muscle cells (VSMCs). Knockdown of Kv7.4 in vivo identified VSMC-expressed Kv7.4 as a major factor in vascular inflammation. Collectively, our findings suggest that Kv7.4 channel aggravates vascular inflammatory response, which promotes the neointimal hyperplasia and AAA formation. Inhibition of Kv7.4 channel may be a novel therapeutic strategy for vascular inflammatory diseases.

Classification of ERP signal from amnestic mild cognitive impairment with type 2 diabetes mellitus using single-scale multi-input convolution neural network.

BACKGROUND: The application of deep learning models to electroencephalogram (EEG) signal classification has recently become a popular research topic. Several deep learning models have been proposed to classify EEG signals in patients with various neurological diseases. However, no effective deep learning model for event-related potential (ERP) signal classification is yet available for amnestic mild cognitive impairment (aMCI) with type 2 diabetes mellitus (T2DM). METHOD: This study proposed a single-scale multi-input convolutional neural network (SSMICNN) method to classify ERP signals between aMCI patients with T2DM and the control group. Firstly, the 18-electrode ERP signal on alpha, beta, and theta frequency bands was extracted by using the fast Fourier transform, and then the mean, sum of squares, and absolute value feature of each frequency band were calculated. Finally, these three features are converted into multispectral images respectively and used as the input of the SSMICNN network to realize the classification task. RESULTS: The results show that the SSMICNN can fuse MSI formed by different features, SSMICNN enriches the feature quantity of the neural network input layer and has excellent robustness, and the errors of SSMICNN can be simultaneously transmitted to the three convolution channels in the back-propagation phase. Comparison with Existing Method(s): SSMICNN could more effectively identify ERP signals from aMCI with T2DM from the control group compared to existing classification methods, including convolution neural network, support vector machine, and logistic regression. CONCLUSIONS: The combination of SSMICNN and MSI can be used as an effective biological marker to distinguish aMCI patients with T2DM from the control group.

Co-Design of Dynamic Event-Triggered Communication Scheme and Resilient Observer-Based Control Under Aperiodic DoS Attacks.

This article is concerned with the problem of observer-based dynamic event-triggered control for a networked control system (NCS) under a class of power-constrained denial-of-service (DoS) attacks that aim at impeding the network communication from time to time. First, by carefully modeling such DoS attacks as aperiodic pulse-width-modulated (PWM) jamming signals, a switching observer, adapting to the DoS attacks, is delicately constructed to deal with the unavailability of full-state information. Second, to economize the limited bandwidth resources, a dynamic event-triggered communication scheme is designed under the aperiodic DoS jamming attacks, whose duration and frequency are assumed to be restricted. Third, a switching system model with artificial state delay is formulated, which characterizes the effects of the aperiodic DoS attacks and event-triggered communication scheme in a unified framework. Then, the asymptotic stability analysis and controller/observer synthesis conditions of the resulting switching system are obtained by using a piecewise Lyapunov-Krasovskii functional approach. Furthermore, a co-design method of the dynamic triggering parameters, controller, and observer gains is presented. Finally, an example is employed to verify the effectiveness of the obtained results.