SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD
)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell ...proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.
Hypoxic training improves the microcirculation function of human skeletal muscle, but its mechanism is still unclear. Silent information regulator 2 homolog 3 (Sirt3) can improve mitochondrial ...function and oxidative status. We aimed to examine the role of Sirt3 in the process of hypoxic training, which affects skeletal muscle microcirculation. C57BL/6 mice were assigned to control (C), hypoxic training (HT), Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine (3-TYP), and 3-TYP + hypoxic training (3-TYP + HT) groups (
n
= 6/group). Sirt3 inhibition was induced by intraperitoneal injection of Sirt3 inhibitor 3-TYP. After 6 weeks of intervention, microcirculatory capillary formation and vasomotor capacity were evaluated using immunofluorescence, Western blot, biochemical tests, and transmission electron microscopy (TEM). Laser Doppler flowmetry was used to evaluate skeletal muscle microcirculation blood flow characteristics. Six weeks of hypoxic training enhanced skeletal muscle microcirculation function and increased microcirculatory vasodilation capacity and capillary formation. After the pharmacological inhibition of Sirt3, the reserve capacity of skeletal muscle microcirculation was reduced to varying degrees. After the inhibition of Sirt3, mice completed the same hypoxic training, and we failed to observe the microcirculation function adaptation like that observed in hypoxic training alone. The microcirculation vasodilation and the capillaries number did not improve. Hypoxic training improved skeletal muscle microcirculation vasodilation capacity and increased skeletal muscle microcirculation capillary density. Sirt3 is involved in the adaptation of skeletal muscle microcirculation induced by hypoxic training.
In this paper, in order to reduce the time cost of prediction experiments in industry, a new narrow gap oscillation calculation method is developed in ABAQUS thermomechanical coupling analysis to ...study the distribution trend of residual weld stresses in comparison with conventional multi-layer welding processes. The blind hole detection technique and thermocouple measurement method verify the reliability of the prediction experiment. The results show that the experimental and simulation results have a high degree of agreement. In the prediction experiments, the calculation time of the high-energy single-layer welding experiments is 1/4 of the traditional multi-layer welding. Two welding processes of longitudinal residual stress and transverse residual stress distribution trends are the same. The high-energy single-layer welding experiment stress distribution range and transverse residual stress peak are smaller, but the longitudinal residual stress peak is slightly higher, which can be effectively reduced by increasing the preheating temperature of the welded parts. This implies that in the specific case of increasing the initial temperature of the workpiece, the use of high-energy single-layer welding instead of multi-layer welding to study the residual stress distribution trend not only optimizes the weld quality but also reduces the time cost to a large extent.
Thick section steel plates are widely used in many industries, and the main technique for welding steel plates is still the electric arc welding process. In this study, a numerical model of 5-pass ...weld joint with plate of 20 mm thickness was established, combining finite element transient heat flow analysis with thermodynamic coupling analysis to predict the residual stress distribution on the specimen, comparing the simulation results of swing and non-swing arc as a means of discussing the impact of the calculation time and the distribution of residual stress. The residual stresses of the welded specimen were measured using the blind drill method and the data obtained were compared with the residual stresses predicted by the numerical simulation, two results are in good agreement. The simulation results of the swing and non-swing arcs show that the distribution of residual stress in the three-dimensional direction is basically the same, but the calculation time for the linear motion is much less than swing, which means that in specific cases, the linear heat source can be used instead of the swing heat source to study the distribution of residual stress in thick plate welding, which can save the calculation cost to a great extent.
We present a case of 80 years woman chronic smoker (10 cigarettes)/ per day for 50 years diagnosed with adenocarcinoma in the upper left lobe of her lungs in a geriatric clinic. She has no history of ...diabetes but taking medicine for hypertension and dyslipidemia. She was admitted and operated on for partial pneumonectomy and discharged after 11 days of care with all essential drugs, and instructions. After 4 weeks of treatment, she complained of unusual polyuria, diagnosed in the department of Geriatrics, Zhongnan Hospital of Wuhan University, China.
Abstract
Blood-brain barrier penetrating peptides (BBBPs) are short peptide sequences that possess the ability to traverse the selective blood-brain interface, making them valuable drug candidates or ...carriers for various payloads. However, the in vivo or in vitro validation of BBBPs is resource-intensive and time-consuming, driving the need for accurate in silico prediction methods. Unfortunately, the scarcity of experimentally validated BBBPs hinders the efficacy of current machine-learning approaches in generating reliable predictions. In this paper, we present DeepB3P3, a novel framework for BBBPs prediction. Our contribution encompasses four key aspects. Firstly, we propose a novel deep learning model consisting of a transformer encoder layer, a convolutional network backbone, and a capsule network classification head. This integrated architecture effectively learns representative features from peptide sequences. Secondly, we introduce masked peptides as a powerful data augmentation technique to compensate for small training set sizes in BBBP prediction. Thirdly, we develop a novel threshold-tuning method to handle imbalanced data by approximating the optimal decision threshold using the training set. Lastly, DeepB3P3 provides an accurate estimation of the uncertainty level associated with each prediction. Through extensive experiments, we demonstrate that DeepB3P3 achieves state-of-the-art accuracy of up to 98.31% on a benchmarking dataset, solidifying its potential as a promising computational tool for the prediction and discovery of BBBPs.
The accuracy of peptide retention time (RT) prediction model in liquid chromatography (LC) is still not sufficient for wider implementation in proteomics practice. Herein, we propose deep learning as ...an ideal tool to considerably improve this prediction. A new peptide RT prediction tool, DeepRT, was designed using a capsule network model, and the public data sets containing peptides separated by reverse-phase liquid chromatography were used to evaluate the DeepRT performance. Compared with other prevailing RT predictors, DeepRT attained overall improvement in the prediction of peptide RTs with an R 2 of ∼0.994. Moreover, DeepRT was able to accommodate to the peptides that were separated by different types of LC, such as strong cation exchange (SCX) and hydrophilic interaction liquid chromatography (HILIC) and to reach the RT prediction with R 2 values of ∼0.996 for SCX and ∼0.993 for HILIC, respectively. If a large peptide data set is available for one type of LC, DeepRT can be promoted to DeepRT(+) using transfer learning. Based on a large peptide data set gained from SWATH, DeepRT(+) further elevated the accuracy of RT prediction for peptides in a small data set and enabled a satisfactory prediction upon limited peptides approximating hundreds. Further, DeepRT automatically learns retention-related properties of amino acids under different separation mechanisms, which are well consistent with retention coefficients (Rc) of the amino acids. DeepRT was thus proven to be an improved RT predictor with high flexibility and efficiency. DeepRT is available at https://github.com/horsepurve/DeepRTplus.
In this paper, the submicron-sized WC particles (~300nm) with the content of 3wt.% and 5wt.% are incorporated into high velocity oxy-fuel (HVOF) sprayed WC-Co coatings with the aim of improving ...properties of the coatings. XRD analyses suggest a small amount of decarburization of the incorporated WC phase after the composite coating deposition. The SEM microstructure showed even distribution of WC particles at the interfaces of WC-Co splats, indicating significantly enhanced wear resistance of the coatings with the wear rate as much as ~10−7mm3/N·m. The content of submicron-sized WC particles plays an important role in determining the wear performances of the coatings. The increment of submicron-sized WC particles causes a decrease in wear rate from 6.09×10−7mm3/N·m to 5.15×10−7mm3/N·m. Also, the Vickers microhardness of the coatings enhances as the increasing of WC particle ratio (reaches 1365HV with the content of the WC particles of 5wt.%). The wear failure analysis gives further insight into the mechanism of the property enhancement. The change of stress state and crack initiation at splats' interfaces act as the predominant mechanism, which is caused by the presence of submicron-sized WC particles at splats' interfaces.
•The submicron-sized WC particles are bound with WC-Co powders by ball mill method.•The even distribution of WC particles at the interfaces of WC-Co splats is achieved.•The presence of WC particles changes the stress state at the splats' interfaces.•The WC particles at the splats' interface inhibit the propagation of microcracks.•The addition of WC particles enhances the microhardness and sliding wear resistance.
Compared with the constant current (CC) charging mode, the constant power (CP) charging mode can speed up the battery charging rate and free the charger from excessive thermal design problems. ...However, the range of the battery's equivalent resistance in CP mode is wider than that in CC mode, which makes it difficult to track the optimal resistance of the inductive power transfer (IPT) system for efficiency enhancement. To solve this problem, this article proposes a single-stage active rectifier (SSAR) integrating an interleaved buck converter with a full-bridge active rectifier (FBAR). Compared with the traditional FBAR, the resistance conversion ratio range of the SSAR is extended from <inline-formula><tex-math notation="LaTeX">0, 8/\pi ^{2}</tex-math></inline-formula> to <inline-formula><tex-math notation="LaTeX">0, 8</tex-math></inline-formula>, and the output current ripple is reduced due to the interleaved operation. A novel optimal phase angle control strategy is correspondingly proposed for the IPT system with the SSAR, which features advantages of wide impedance conversion ratio range, zero voltage switching turn- on of all mosfet s, and no communication between the primary and the secondary sides. A 150-W experimental prototype is provided to verify the effectiveness of the proposed rectifier.
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