Water-fueled autocatalytic bactericidal pathway based on e-Fenton-like reactions triggered by galvanic corrosion and extracellular electron transfer.

Water is generally considered to be an undesirable substance in fuel system, which may lead to microbial contamination. The antibacterial strategies that can turn water into things of value with high disinfection efficacy have been urgently needed for fuel system. Here, we reveal a water-fueled autocatalytic bactericidal pathway comprised by bi-metal micro-electrode system, which can spontaneously produce reactive oxygen species (mainly H2O2 and O2•-) by the electron Fenton-like reaction in water medium without external energy., The respiratory chain component of bacteria and the galvanic corrosion on the coated metals were two electron sources in the system. The specific model of Ag-Ru water-fueled autocatalytic (WFA) microelectrode particles presents extremely high disinfection efficiency (>99.9999%) in less than one hour for three aerobic bacteria (Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis) in LB media and high disinfection efficiency for the anaerobic bacteria (Desulfovibrio alaskensis) in Postgate E media without natural light irradiation. Overall, the novel WFA Ag-Ru antibacterial material explored in this study has a high potential for sterilizing applications in fuel system and this work provides the potential for the development of non-chemical and water-based antibacterial materials, such as WFA Ag-Ru antibacterial coating on stainless steel.

Control Meets Inference: Using Network Control to Uncover the Behaviour of Opponents.

Using observational data to infer the coupling structure or parameters in dynamical systems is important in many real-world applications. In this paper, we propose a framework of strategically influencing a dynamical process that generates observations with the aim of making hidden parameters more easily inferable. More specifically, we consider a model of networked agents who exchange opinions subject to voting dynamics. Agent dynamics are subject to peer influence and to the influence of two controllers. One of these controllers is treated as passive and we presume its influence is unknown. We then consider a scenario in which the other active controller attempts to infer the passive controller's influence from observations. Moreover, we explore how the active controller can strategically deploy its own influence to manipulate the dynamics with the aim of accelerating the convergence of its estimates of the opponent. Along with benchmark cases we propose two heuristic algorithms for designing optimal influence allocations. We establish that the proposed algorithms accelerate the inference process by strategically interacting with the network dynamics. Investigating configurations in which optimal control is deployed. We first find that agents with higher degrees and larger opponent allocations are harder to predict. Second, even factoring in strategical allocations, opponent's influence is typically the harder to predict the more degree-heterogeneous the social network.

OCT-Based Periodontal Inspection Framework.

Periodontal diagnosis requires discovery of the relations among teeth, gingiva (i.e., gums), and alveolar bones, but alveolar bones are inside gingiva and not visible for inspection. Traditional probe examination causes pain, and X-ray based examination is not suited for frequent inspection. This work develops an automatic non-invasive periodontal inspection framework based on gum penetrative Optical Coherence Tomography (OCT), which can be frequently applied without high radiation. We sum up interference responses of all penetration depths for all shooting directions respectively to form the shooting amplitude projection. Because the reaching interference strength decays exponentially with tissues' penetration depth, this projection mainly reveals the responses of the top most gingiva or teeth. Since gingiva and teeth have different air-tissue responses, the gumline, revealing itself as an obvious boundary between teeth and gingiva, is the basis line for periodontal inspection. Our system can also automatically identify regions of gingiva, teeth, and alveolar bones from slices of the cross-sectional volume. Although deep networks can successfully and possibly segment noisy maps, reducing the number of manually labeled maps for training is critical for our framework. In order to enhance the effectiveness and efficiency of training and classification, we adjust Snake segmentation to consider neighboring slices in order to locate those regions possibly containing gingiva-teeth and gingiva-alveolar boundaries. Additionally, we also adapt a truncated direct logarithm based on the Snake-segmented region for intensity quantization to emphasize these boundaries for easier identification. Later, the alveolar-gingiva boundary point directly under the gumline is the desired alveolar sample, and we can measure the distance between the gumline and alveolar line for visualization and direct periodontal inspection. At the end, we experimentally verify our choice in intensity quantization and boundary identification against several other algorithms while applying the framework to locate gumline and alveolar line in vivo data successfully.

Key Role of the Membrane Trafficking of Nav1.5 Channel Protein in Antidepressant-Induced Brugada Syndrome.

Anti-depressant treatment has been found to be associated with the development of Brugada syndrome (BrS) through poorly defined mechanisms. Herein, this study aimed to explore the molecular basis for amitriptyline-induced BrS. The effects of long-term treatments of amitriptyline on Nav1.5 were investigated using neonatal rat ventricular myocytes. The electrophysiological properties, expression and distribution of Nav1.5 were studied using the patch clamp, Western blot and confocal laser microscopy assays. Interactions between Nav1.5 and its interacting proteins, including ankyrin-G and dystrophin, were evaluated by co-immunoprecipitation. A larger decrease in the peak INa occurred after long-term treatments to amitriptyline (56.64%) than after acute exposure to amitriptyline (28%). Slow recovery from inactivation of Nav1.5 was observed after acute or long-term treatments to amitriptyline. The expression of Nav1.5 on the cell membrane showed a larger decrease by long-term treatments to amitriptyline than by acute exposure to amitriptyline. After long-term treatments to amitriptyline, we observed reduced Nav1.5 proteins on the cell membrane and the disrupted co-localization of Nav1.5 and ankyrin-G or dystrophin. Co-immunoprecipitation experiments further testified that the combination of Nav1.5 and ankyrin-G or dystrophin was severely weakened after long-term treatments to amitriptyline, implying the failed interaction between Nav1.5 and ankyrin-G or dystrophin. Our data suggest that the long-term effect of amitriptyline serves as an important contribution to BrS induced by amitriptyline. The mechanisms of BrS induced by amitriptyline were related to Nav1.5 trafficking and could be explained by the disrupted interaction of ankyrin-G, dystrophin and Nav1.5.

Effects of allitridum on the transient outward potassium current in rats with heart failure.

OBJECTIVE: To study the effect of allitridum on the transient outward potassium current (Ito) of ventricular myocytes in heart failure (HF). METHODS: The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. RESULTS: The Ito current had a significant decrease in the HF group, compared with the control group. The density of Ito in the HF group was increased after treatment of allitridum (30 µmol/L). The peak current densities of Ito were enhanced in the HF group from 6.01 ± 0.30 pA/pF to 8.41 ± 0.54 pA/pF (P < 0.01) at +50 mV after treatment with allitridum (30 µmol/L). We also determined the effect of allitridum on the gating mechanism of the Ito in the HF group. CONCLUSIONS: We found that allitridum increased the Ito by accelerating the activation of channels and shortened the time constants of inactivation, and allitridum decreased the remodeling of Ito in ventricular myocytes of rats with HF.

The mitochondrial calcium uniporter is involved in mitochondrial calcium cycle dysfunction: Underlying mechanism of hypertension associated with mitochondrial tRNA(Ile) A4263G mutation.

Recent studies have shown that the mitochondrial DNA mutations are involved in the pathogenesis of hypertension. Our previous study identified mitochondrial tRNA(Ile) A4263G mutation in a large Chinese Han family with maternally-inherited hypertension. This mutation may contribute to mitochondrial Ca(2+) cycling dysfuntion, but the mechanism is unclear. Lymphoblastoid cell lines were derived from hypertensive and normotensive individuals, either with or without tRNA(Ile) A4263G mutation. The mitochondrial calcium ([Ca(2+)]m) in cells from hypertensive subjects with the tRNA(Ile) A4263G mutation, was lower than in cells from normotension or hypertension without mutation, or normotension with mutation (P<0.05). Meanwhile, cytosolic calcium ([Ca(2+)]c) in hypertensive with mutation cells was higher than another three groups. After exposure to caffeine, which could increase the [Ca(2+)]c by activating ryanodine receptor on endoplasmic reticulum, [Ca(2+)]c/[Ca(2+)]m increased higher than in hypertensive with mutation cells from another three groups. Moreover, MCU expression was decreased in hypertensive with mutation cells compared with in another three groups (P<0.05). [Ca(2+)]c increased and [Ca(2+)]m decreased after treatment with Ru360 (an inhibitor of MCU) or an siRNA against MCU. In this study we found decreased MCU expression in hypertensive with mutation cells contributed to dysregulated Ca(2+) uptake into the mitochondria, and cytoplasmic Ca(2+) overload. This abnormality might be involved in the underlying mechanisms of maternally inherited hypertension in subjects carrying the mitochondrial tRNA(Ile) A4263G mutation.

Effects of allocryptopine on outward potassium current and slow delayed rectifier potassium current in rabbit myocardium.

OBJECTIVE: Allocryptopine (ALL) is an effective alkaloid of Corydalis decumbens (Thunb.) Pers. Papaveraceae and has proved to be anti-arrhythmic. The purpose of our study is to investigate the effects of ALL on transmural repolarizing ionic ingredients of outward potassium current (I to) and slow delayed rectifier potassium current (I Ks). METHODS: The monophasic action potential (MAP) technique was used to record the MAP duration of the epicardium (Epi), myocardium (M) and endocardium (Endo) of the rabbit heart and the whole cell patch clamp was used to record I to and I Ks in cardiomyocytes of Epi, M and Endo layers that were isolated from rabbit ventricles. RESULTS: The effects of ALL on MAP of Epi, M and Endo layers were disequilibrium. ALL could effectively reduce the transmural dispersion of repolarization (TDR) in rabbit transmural ventricular wall. ALL decreased the current densities of I to and I Ks in a voltage and concentration dependent way and narrowed the repolarizing differences among three layers. The analysis of gating kinetics showed ALL accelerated the channel activation of I to in M layers and partly inhibit the channel openings of I to in Epi, M and Endo cells. On the other hand, ALL mainly slowed channel deactivation of I Ks channel in Epi and Endo layers without affecting its activation. CONCLUSIONS: Our study gives partially explanation about the mechanisms of transmural inhibition of I to and I Ks channels by ALL in rabbit myocardium. These findings provide novel perspective regarding the anti-arrhythmogenesis application of ALL in clinical settings.

[The reverse effects of allitridum on sodium current decrease caused by SCN5A-F1473S mutation].

This study was designed to test the allitridum (All) activity in correction of sodium current decrease caused by SCN5A-F1473S mutation in HEK293 cells. The result may provide a theoretical basis for screening of new drugs in the treatment of Brugada syndrome. We transferred SCN5A-F1473S channel plasmids into HEK293 cells in a transient transfection. All was administrated acutely and chronically using extracellular irrigation flow and co-culture model. The concentration of All was 30 µmol·L(-1). We used whole cell patch clamp technique in voltage clamp mode to record current and gating kinetics. In order to explore the rescue function of All on decreased sodium peak current, we used confocal microscopy and Western blot to detect the expression of channel proteins in the cell membrane. We found a significant increase in sodium peak current of the 30 µmol·L(-1) All HEK293 cells (269.8 ± 16.6 pA/pF, P < 0.01), almost closed to the current density of the control group（298.2 ± 17.5 p A/p F, P < 0.01）. All allowed the steady-state inactivation of the channel to move toward a more positive direction (V(1/2, inact) returns to -79.5 ± 2.4 mV, P < 0.01). It also slowed the intermediate state inactivation of the channel (inactivation prolongated to 598.1 ± 22.6 ms, P < 0.01). Meanwhile, All increased distribution and expression of the channel protein in the cell membrane (compared to F1473S, P < 0.01). All caused an increase of current in SCN5A-F1473S mutation cells. We consider that the main mechanism may be related to the reduced channel inactivation by the drug with an improvement of the migration barrier of the mutational channel.

Effect of α-Allocryptopine on Delayed Afterdepolarizations and Triggered Activities in Mice Cardiomyocytes Treated with Isoproterenol.

Objective. To investigate the effect of α-allocryptopine (ALL) on delayed afterdepolarization (DAD) incidence and triggered activity (TA) in mice administered isoproterenol (ISO). Methods. Mouse ventricular myocytes were isolated. And the cellular electrophysiological properties of ventricular myocytes were investigated. Results. We found that the incidences of DADs and TA in mouse myocytes were increased by ISO treatment. In sharp contrast, triggered arrhythmia events were rarely observed in myocytes with 10 µM ALL treatment. Transient inward current (I ti) was reduced significantly with ALL treatment, which contributed to DAD-related triggered arrhythmia. Compared to Iso-treated group, the L-type calcium current (I Ca,L) densities were decreased after exposure to ALL, along with slower activation, quicker inactivation, and longer time constant of recovery from inactivation kinetics. Conclusion. There is less triggered arrhythmia events in ventricular myocytes treated with ALL. This effect may be associated with the inhibition of I ti and I Ca,L.

Identification of ALK5 inhibitor via structure-based virtual screening and ADMET prediction.

TGF-ß plays a critical role in the initiation and progression of fibrosis in various organ systems such as kidney, heart, lung and liver. TGF-ß and its receptors (ALK5 and TßR II) are able to control the cellular growth and promote several biological responses. To date, many pharmaceutical companies have employed virtual screening to identify potent inhibitors against ALK5. Nevertheless, none of these studies had involved the in silico ADMET evaluation and Raccoon filtering. In our experiment, all 57423 molecules were downloaded from TCM database and were filtered and converted to PDBQT formats by Raccoon software. Then 24 189 structures were run through AutoDock Vina in PyRx 0.8, 164 molecules were selected and further evaluated by ADMET Predictor 6.5, and 56 structures were selected and docked by Glide 6.2. Finally, the top 10 hits were identified as promising oral ALK5 inhibitors according to their Glide scores. The Glide scores of the best two compounds, 40686 and 33534, were -10.75 and -10.30 kcal/mol, respectively. This research provides a set of combined and detailed virtual screening protocol and is helpful for explaining the mechanism of receptor-ligand interactions.