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Background: Atherosclerosis (AS) is one of the leading causes of cardiovascular diseases. The traditional China herb pairs such as Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian showed therapeutic effects on AS by clearing heat and resolving phlegm, invigorating blood and removing blood stasis, as well as aromatic resuscitation, respectively. However, the common and specific mechanisms of these pairs against the same disease are elusive.Objective: This study aimed to explore the molecular mechanisms of 3 herb pairs treating AS by network pharmacology, molecular modeling and mechanism experiments.Methods: The components and their corresponding targets of 3 herb pairs, as well as AS-related targets, were collected from multiple databases and literature. Then the protein-protein interaction network was built to identify the key components and targets associated with AS. The pathway enrichment analysis using KEGG was carried out for analyzing the common mechanisms of 3 herb pairs against AS. Finally, the binding modes of the key components and targets were analyzed by molecular docking and molecular dynamic simulation.Results: The PPI network indicated that the common targets of 3 herb pairs focused on four pathways, including regulated vascular shear stress, TNF, ARE-RAGE, and IL-17 pathways. The molecular docking analysis indicated that the key component quercetin showed highest docking score with PTGS2 in comparison to other targets. Molecular dynamics simulations revealed that quercetin stably anchored to the active pocket of PTGS2 by forming hydrogen bonds with Thr175, Asn351, and Trp356.Conclusion: The molecular mechanism of Huanglian-Gualou, Honghua-Taoren, and Suhexiang-Bingpian against AS was preliminarily expounded, and we wish to provide a theoretical instruction for clinical treatment of AS.

Traditional enterprise-level food supply chain traceability systems are notoriously expensive and complex to set up, but there is a solution that can successfully address both of these problems: the food supply chain traceability system. This study, on the other hand, suggests a blockchain-based food supply chain traceability system business system. The paper is concerned with the food supply chain traceability system. The authentication and authorization procedures, traffic scheduling, and settlement monitoring are examples of some of the operations that make use of the blockchain infrastructure. In the meanwhile, the throughput of the system is increased by making improvements to the consensus method. Users of this system can provide customized service needs for food supply chain traceability systems by using this system. The issue of locking up the system in the food supply chain traceability system is successfully solved by the system, which embodies a great deal of application potential inside the food supply chain traceability system.

Insulin is produced and secreted by pancreatic β cells in the pancreas, which plays a key role in maintaining euglycemia. Insufficient secretion or deficient usage of insulin is the main cause of diabetes mellitus (DM). Drug therapy and islets transplantation are classical treatments for DM. Pancreatic β cell replacement therapy could help patients to get rid of drugs and alleviate the problem of lacking in transplantable donors. Pancreatic β-like cells can be acquired by cell reprogramming techniques or directed induction of stem cell differentiation. These cells are proved to be functional both

Lithium-rich layered oxides (LLOs) that can support both cationic and anionic redox chemistry are promising cathode materials, but they often suffer from significant oxygen evolution when first charged to a high voltage, resulting in a large capacity loss and deteriorated durability in subsequent charge-discharge cycles. We reported a simple method to eliminate the irreversible anionic redox in Li1.2Mn0.54Co0.13Ni0.13O2 via low-potential charge-discharge activation (LOWPA), achieving an ultra-high reversible capacity of 322 mAh g-1 (corresponding to 1141 Wh kg-1) as well as improved cycling durability and rate capability. Combined experimental and theoretical investigations reveal that LOWPA enables a delicate control of the order-to-disorder transformation of the transition metal layers of LLOs, leading to a cation-disordered structure that can support reversible oxygen redox up to 4.8 V by forming a stable ozonic ion (O3-). This LOWPA approach is simple and effective, boosting the development of high-energy-density batteries based on the oxygen-redox chemistry.

Pedestrian detection is a classic problem in computer vision, which has an essential impact on the safety of urban autonomous driving. Although significant improvement has been made in pedestrian detection recently, small‐scale pedestrian detection is still challenging. To effectively tackle this issue, a multi‐scale pedestrian detector based on self‐attention mechanism and adaptive spatial feature fusion is proposed in this paper. In order to better extract global information, the spatial attention mechanism asymmetric pyramid non‐local block (APNB) module is applied. To achieve scale‐invariance detection, multiple detection branches are designed, which include a high‐resolution detection branch and a low‐resolution detection branch. In integrating multi‐scale features, the adaptively spatial feature fusion (ASFF) method is employed, which can solve the problem of feature inconsistency across different scales. Experimental results show that the proposed method obtains competitive performance on Caltech and CityPersons datasets.

Designing molecules with specific scaffolds can facilitate the discovery and optimization of lead compounds. Some scaffold-based molecular generation models have been developed using deep-learning methods based on specific scaffolds, although incorporating scaffold generalization is expected to achieve scaffold hopping. Moreover, most of the existing models focus on the 2D shape of the scaffold and overlook the stereochemical properties of the compound, especially for natural products. In this study, we optimized the scaffold-based molecular generation model designed by Lim et al. (Chemical Science 2020, 11, 1153-1164). Real-time ultrafast shape recognition with pharmacophore constraints (USRCAT) was introduced into the model to search for molecules similar to the 3D conformation and pharmacophore of the input scaffold sourced from the training set; the searched molecules were then used as new scaffolds to execute scaffold hopping. The optimized model could generate new molecules with the same chirality as the input scaffold. Furthermore, the probability distribution of the molecular structure and various physicochemical properties were analyzed to evaluate the model's generation capability. We thus believe that the optimized model can provide a basis for medicinal chemists to explore a wider chemical space toward optimization of the lead compounds and to screen the virtual compound library.

Atherosclerosis (AS) is a chronic disease that is associated with high morbidity. However, therapeutic approaches are limited. Wu-Zhu-Yu decoction (WZYD) is a well-known traditional Chinese medicine prescription that is traditionally used to treat headaches and vomiting. Modern studies have demonstrated the cardiotonic effects of WZYD. However, whether WZYD can alleviate AS and its underlying mechanisms remain unclear.This study aims to investigate the antiatherosclerotic efficacy of WZYD and illustrate its potential mechanisms using an integrated approach combining in vivo and in vitro assessments, including metabolomics, network pharmacology, cell experiments, and molecular docking analyses.In this work, an atherosclerotic mouse model was established by administering a high-fat diet to apolipoprotein-E deficient (ApoEWZYD decreased the lipid levels in serum, reduced the areas of aortic lesions, and attenuated intimal thickening, which had antiatherosclerotic effects in ApoEThis study revealed that WZYD exerted therapeutic effects on atherosclerosis, and the potential mechanisms were elucidated. Furthermore, it offered a powerful integrated strategy for studying the efficacy of traditional Chinese medicine and exploring its active components and possible mechanisms.

Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin: flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). Flavoproteins are involved in a wide array of biological processes, such as photosynthesis, DNA repair and natural product biosynthesis. It should be noted that 5%-10% of flavoproteins have a covalently linked flavin prosthetic group. Such covalent linkages benefit the holoenzyme in several ways including improving the stability and catalytic potency. During the past decade, significant progress has been made in covalent flavoproteins, especially with respect to enzyme-dependent biogenesis and discovery of novel linkage types. The present review gives a condensed overview of investigations published from March 2009 to December 2021, with emphasis on the discovery, biogenesis and their catalytic role in natural product biosynthesis.

Uniform distribution of Li2MnO3 and LiMO2 components in a Co-free Li-rich layered oxide is achieved by treating precursors with NH3·H2O, which expands the lattice parameter and promotes the activation of Li2MnO3, resulting in excellent electrochemical performance. What's more, it also contributes to the storage stability of Li-rich layered oxides.

The 3D convolutional neural network (CNN) is able to make full use of the spatial 3D context information of lung nodules. In this paper, a novel 3D CNN is proposed to classify lung nodule. To make the feature map towards the most informative components of an input, spatial attention and channel attention are integrated with the 3D CNN backbone. To combine global and local information, a multiple granularity architecture is designed. We conduct a binary classification (benign and malignant) on two computed tomography (CT) datasets (public Lung Image Database Consortium and Image Database Resource Initiative database (LIDC-IDRI) and private LIDC-TX dataset). It achieves a sensitivity of 0.962, specificity of 0.942 and error rate of 0.048 on LIDC-IDRI database. For the private LIDC-TX dataset, sensitivity, specificity and error rate are 0.718, 0.627 and 0.327, respectively. Experimental results demonstrate that the proposed method get a promising result compared with existing lung nodule classification methods.

Aims: Endothelial dysfunction appears in early diabetes mellitus partially because of epidermal growth factor receptor (EGFR) abnormal activation and downstream oxidative stress. The aim of this study was to determine whether Y396, a synthesized analog of rhynchophylline, could protect against endothelial dysfunction in diabetes and the underlying molecular mechanism. Results: Y396 could directly target the EGFR and inhibit its phosphorylation induced by high glucose and EGF, downstream translocation to the nucleus of E2F1, and its transcriptional activity and expression of Nox4. Diabetes-induced endothelium malfunction was ameliorated by Y396 treatment through EGFR inhibition. Downstream oxidative stress was decreased by Y396 in the aortas of type 1 diabetes mellitus mice and primary rat aorta endothelial cells (RAECs). Y396 could also ameliorate tunicamycin-induced oxidative stress in the aorta and RAECs. In addition, we again determined the protective effects of Y396 on high-fat diet/streptozotocin-induced type 2 diabetes mellitus. Innovation: This is the first study to demonstrate that Y396, a novel rhynchophylline analog, suppressed high-glucose-induced endothelial malfunction both in vivo and in vitro by inhibiting abnormal phosphorylation of EGFR. Our work uncovered EGFR as a novel therapeutic target and Y396 as a potential therapy against diabetes-induced complication. Conclusion: Y396 could directly bind with EGFR, and inhibit its phosphorylation and downstream E2F1 transcriptional activity. It could also preserve tunicamycin-evoked endothelial dysfunction and oxidative stress. It could protect against diabetes-induced endothelium malfunction in vivo through EGFR inhibition and downstream oxidative stress. Antioxid. Redox Signal. 32, 743-765.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by learning and memory impairments. Recent studies have suggested that AD can be induced by multiple factors, such as cholinergic system dysfunction and β-amyloid (Aβ) neurotoxicity. It was reported that 6-bromo-N-propionyltryptamine could treat neurological diseases, including AD. In the present study, 6-bromotryptamine A, a derivative of 6-bromo-N-propionyltryptamine, was synthesized by the condensation of 2-(6-bromo-1H-indol-3-yl)ethan-1-amine and 2-(4-bromophenyl)acetic acid, and was used as a potential anti-AD molecule. Furthermore, scopolamine can induce impairments of learning and memory, and was widely used to establish AD animal models. The results demonstrated that 6-bromotryptamine A significantly prevented scopolamine-induced short-term cognitive impairments, as revealed by various behavioral tests in mice. Furthermore, an acetylcholinesterase (AChE) activity assay revealed that 6-bromotryptamine A directly inhibited AChE activity. Notably, it was observed that 6-bromotryptamine A blocked the formation of Aβ oligomer, as evaluated by the dot blot assay. All these results suggested that 6-bromotryptamine A may be used to prevent impairments in short-term learning and memory ability possibly via the inhibition of AChE and the blockade of Aβ oligomer formation.

Aims Ischemic stroke is one of the leading causes of death worldwide. MicroRNAs (miRNAs) have been reported to be implicated in cerebral hypoxia injury and could serve as a therapeutic target. As the third gasotransmitter, hydrogen sulfide (H2S) plays a critical role in hypoxia-induced injury in the central nervous system. Cystathionine β-synthase (CBS) is the main enzyme catalyzing the production of H2S in brain. The objective of this study was to investigate the effect of miR-125b-5p on protecting against oxygen and glucose deprivation (OGD) injury in PC-12 cells by regulating CBS and H2S generation. Results The level of miR-125b-5p was increased in the rat MCAO model as well as OGD model in PC-12 cells. Meanwhile, CBS expression was remarkably downregulated. Overexpression of miR-125b-5p reduced CBS expression, decreased the H2S generation, and deteriorated OGD injury in PC-12 cells. On the contrary, silencing miR-125b-5p protected PC-12 cells from OGD injury by upregulated CBS and H2S levels. We found the protective effect of miR-125b-5p inhibition was associated with anti-oxidative and anti-apoptotic cell signaling through decreasing ROS level and reducing mitochondrial membrane potential (ΔΨm). Furthermore, the protective effect was absent when CBS was knockdown in PC-12 cells. Innovation and conclusion Our research discovered the regulation of CBS by miR-125b-5p. Besides, we provide the evidence for the therapeutic potential of miR-125b-5p inhibition for cerebral ischemia via CBS/H2S pathway.

// Wenbo Tang 1, 2, * , Rujiao Liu 1, 2, * , Yan Yan 1, 2, * , Xiaoli Pan 3 , Minjun Wang 4 , Xiaotian Han 2, 5 , Hui Ren 6 and Zhe Zhang 1, 2 1 Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China 2 Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, P.R. China 3 Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, P.R. China 4 Shanghai Key Laboratory of Bioactive Small Molecules, Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai, P.R. China 5 Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, P.R. China 6 Department of Breast Surgery, Lanzhou General Hospital, Lanzhou, P.R. China * These authors have contributed equally to the work Correspondence to: Zhe Zhang, email: zhangzhe2010fduscc@gmail.com Keywords: gastric cancer, estrogen receptor, androgen receptor, epithelial-mesenchymal transition Received: April 04, 2016 Accepted: March 13, 2017 Published: March 28, 2017 ABSTRACT Despite the mounting studies exploring the role of estrogen receptor alpha (ERα), estrogen receptor beta (ERβ) and androgen receptor (AR) in gastric cancer (GC), there remain controversies in those findings. The present study investigated the expression of ERα, ERβ and AR in Chinese gastric cancer by immunohistochemistry, analyzed their clinical relevance in gastric cancer, and examined the potential mechanisms by which ERα and AR modulated GC progression. The positive rate of ERα, ERβ and AR in GC tissues was 6% (9/150), 93.5% (143/153), and 42.4% (59/139), respectively. The expression of ERα was an independent unfavorable risk factor for overall survival (OS) (hazard ratio [HR] = 3.639, 95% confidence interval [CI] = 1.432-9.246, p = 0.007) for GC patients. Moreover, AR was borderline significantly associated with poor progress free survival (PFS) after adjustment with other variables (HR = 1.573, 95% CI = 0.955-2.592, p = 0.075). Knockdown of ERα inhibited the proliferation, migration and invasion of GC cells possibly via modulating the expression of p53, p21, p27, cyclin D1 and E-cadherin. Downregulation of AR suppressed the migration and invasion of GC cells and inhibited the epithelial-mesenchymal transition (EMT) associated pathways. Conclusion: The present study showed that positive ERα was associated with poor prognosis of Chinese GC patients. ERα might modulate the proliferation, migration and invasion via regulating the expression of p53, p21, p27, cyclin D1 and E-cadherin. ERα could be a valuable prognostic biomarker and promising therapeutic target for Chinese GC patients.

The addition of inert support is important for the Cu-based oxygen carrier used in chemical looping combustion (CLC). The effects of the ZrO2 support on the stability and reactivity of Cu-based oxygen carrier were investigated using the density functional theory (DFT). First, the sintering inhibition mechanism of ZrO2 that support active CuO was investigated. The optimized Cu4O4/ZrO2 structure showed a strong interaction occurred between the Cu4O4 cluster and ZrO2(1 0 1) surface. The interaction prevented the migration and agglomeration of CuO. Next, the adsorption of CO on Cu4O4/ZrO2 and the mechanism of the CuO/ZrO2 reduction by CO were studied. CO mainly chemisorbed on the Cu site and ZrO2 acted as an electron donor in the adsorption system. The energy barrier of CuO/ZrO2 reduction by CO (0.79 eV) was much lower than that of the pure CuO cluster (1.44 eV), indicating that ZrO2 had a positive effect on CuO/ZrO2 reduction by CO. After CO was oxidized in the fuel reactor, the CuO was reduced into Cu. The adsorption of O2 on Cu2/ZrO2 and the most likely pathway of Cu2/ZrO2 oxidation by O2 were investigated. The adsorption of O2 was found a strong chemisorption behavior. The energy barriers were low enough for the Cu-based oxygen carrier oxidation reaction.

A method based on depth volume and network for facial expression recognition was proposed. This method takes the facial expression image as the input of the CNN and trains the CNN network, and then uses the trained network to perform facial expression recognition. This paper uses jaffe and ck+ two face expression libraries to verify the algorithm, proves the effectiveness of the algorithm, and shows that its performance is better than the traditional method.

As the hot and difficult issue in computer vision, binocular stereo vision is an important form of computer vision,which has a broad application prospects in many computer vision fields,such as aerial mapping,vision navigation,motion analysis and industrial inspection etc.In this paper, a research is done into binocular stereo camera calibration, image feature extraction and stereo matching. In the binocular stereo camera calibration module, the internal parameters of a single camera are obtained by using the checkerboard lattice of zhang zhengyou the field of image feature extraction and stereo matching, adopted the SURF operator in the local feature operator and the SGBM algorithm in the global matching algorithm are used respectively, and the performance are compared. After completed the feature points matching, we can build the corresponding between matching points and the 3D object points using the camera parameters which are calibrated, which means the 3D information.

Glucose regulated protein 78 kDa (GRP78) is a recently emerged target for cancer therapy and a biomarker for cancer prognosis. Overexpression of GRP78 is observed in many types of cancers, with the cell-surface GRP78 being preferentially present in cancer cells and cancer blood vessel endothelial cells. Isthmin (ISM) is a secreted high-affinity proapoptotic protein ligand of cell-surface GRP78 that suppresses angiogenesis and tumor growth in mice. The C-terminal AMOP (adhesion-associated domain in MUC4 and other proteins) domain of ISM is critical in mediating its interaction with human umbilical vein endothelial cells (HUVECs). In this work, we report novel cyclic peptides harboring the RKD motif in the ISM AMOP domain that function as proapoptotic ligands of cell-surface GRP78. The most potent peptide, BC71, binds to GRP78 and converge to tumor in mice. Intravenous administration of BC71 suppressed xenograft tumor growth in mice as a single agent, with significant reduction in tumor angiogenesis and upsurge in apoptosis. Fluorescent-labeled BC71 accumulates in tumor in mice by targeting cell-surface GRP78. We show that BC71 triggers apoptosis via cell-surface GRP78 and activates caspase-8 and p53 signaling pathways in HUVECs. Using amide hydrogen-deuterium exchange mass spectrometry (HDXMS), we identified that BC71 preferentially binds to ATP-bound GRP78 via amino acid residues 244–257 of GRP78. Hence, BC71 serves as a valuable prototype for further development of peptidomimetic anticancer drugs targeting cell-surface GRP78 as well as PET imaging agents for cancer prognosis., Graphical Abstract Unlabelled Image

Ischemic stroke is one of the leading causes of death worldwide. MicroRNAs (miRNAs) have been reported to be implicated in cerebral hypoxia injury and could serve as a therapeutic target. As the third gasotransmitter, hydrogen sulfide (HThe level of miR-125b-5p was increased in the rat MCAO model as well as OGD model in PC-12 cells. Meanwhile, CBS expression was remarkably downregulated. Overexpression of miR-125b-5p reduced CBS expression, decreased the HOur research discovered the regulation of CBS by miR-125b-5p. Besides, we provide the evidence for the therapeutic potential of miR-125b-5p inhibition for cerebral ischemia via CBS/H

Oxyfuel combustion using O2–CO2 mixed gas as the oxidant is a promising technology for effectively capturing high concentration CO2. Chemical looping air separation (CLAS) is a novel approach with a low energy footprint for O2–CO2 mixed gas production. In this work, a series of Zr-doped Cu-based oxygen carriers were prepared by the sol–gel combustion method and used to produce the O2–CO2 gas mixture. The effects of doping Zr on phase structure, surface topography, O2 absorption/desorption, and cyclic reaction of Cu-based oxygen carriers were studied by experiments. The influencing mechanism of Zr doping on O2 release of Cu-based oxygen carrier was investigated using density functional theory (DFT) calculations. The results indicate that the addition of Zr enlarges the specific surface area and refines the grains. The Zr-doped Cu-based oxygen carriers have high desorption reaction rates. The oxygen release capacity increases with the increasing Zr doping amount. The cyclic operation indicates that the Zr-d...

An electrochemical biosensor that used an aptamer as a biological element was constructed to detect endotoxin. Biolayer interferometry was used to obtain the affinity constant of an aptamer for lipopolysaccharide, which had an equilibrium dissociation constant of 22.9 nM. The amine-terminated aptamer was then assembled on a gold electrode surface using 3-mercaptopropionic acid as an intermediate linker. The modification of the gold electrode was confirmed by cyclic voltammetry and electrochemical impedance spectroscopy. In the range of 0.001-1 EU/mL, the increase in electron transfer resistance of the biosensor was linear with the logarithmic value of the endotoxin concentration. The constructed biosensor exhibits sensitivity and a low limit of detection.

Aims: Anemia of inflammation (AI), the second prevalent anemia, is associated with worse prognosis and increased mortality in numerous chronic diseases. We recently reported that the gasotransmitter hydrogen sulfide (H2S) suppressed the inflammatory activation of signal transducer and activator of transcription 3 (STAT3) and hepcidin, the critical mediators of AI. Adenosine 5′-monophosphate-activated protein kinase (AMPK) is a novel inflammatory regulator and might be activated by H2S. In this study, we determined whether AMPK played a role in H2S-mediated anti-inflammatory response in AI and evaluated the therapeutic potential of AMPK against AI by pharmacological and clinical approaches. Results: We showed that AMPK mediated the inhibition of STAT3, hepcidin, and AI by H2S during inflammation. Moreover, pharmacological and genetic activation of AMPK ameliorated hepcidin production, corrected iron dysregulation, and relieved hypoferremia and anemia in both acute and chronic inflammation models i...