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Background: Thiazoles are an important class of heterocyclic compounds with many biological effects, including anticholinesterase activity. Objective: The purpose of this work was to synthesize new thiazole derivatives and evaluate as acetylcholinesterase inhibitors (AChEIs) for Alzheimer’s disease. Methods: A series of new N-acyl-4-(4-aminoalkoxy-phenyl)-thiazole-2-amine derivatives was designed and synthesized. Ellman assay protocol was used for the AchE and BuChE inhibitory activity. To correlate better the drug-like property, the theoretical prediction was calculated using Mol inspiration software 2015 online. The potential binding mode of compounds with AChE and BuChE was investigated by the molecular docking simulation. Results: All synthesized compounds exhibited a certain inhibitory activity on AChE and 5p had the most effective selective inhibitory effect on AChE. The inhibitory form of 5p on AChE was shown to be a combination of competitive and noncompetitive inhibition, according to enzyme kinetic tests. Docking simulation studies revealed that the binding energy of 5p with AChE was lower than that of it with BuChE, which also explained the selective inhibitory activity of 5p on AChE. Conclusion: These results provided valuable information for the design of potent AChEIs, and it was believed that 5p could be a promising lead structure for its further development for the treatment of AD.

BACKGROUND: In recent years, the incidence of viral keratitis has been on the rise. OBJECTIVE: This study explored the application effect of continuous care for patients with viral keratitis. METHODS: A total of 148 patients with viral keratitis admitted to the ophthalmology department of the authors’ hospital from January 2019 to December 2020 were selected and divided into the observation group and the control group via the random number table method, with 74 cases in each group. Continuous care was conducted following routine discharge guidance for patients in the observation group, while routine discharge guidance only was provided for the control group. The patients in both groups were continuously observed for one year. The medication compliance, return visit rate, recurrence rate, nursing satisfaction, and quality of life between the two groups were compared and analyzed after one year. RESULTS: The medication compliance was higher in the observation than in the control group and the difference was statistically significant (P< 0.05). The rate of return visits at 1 week, 1 month, 3 months, 6 months, and 1 year in the observation group were higher than those in the control group and the differences were statistically significant (P< 0.05). The difference in the recurrence rate between the two groups at 1 week was not statistically significant (P> 0.05), while the recurrence rate at 1, 3, and 6 months, and 1 year in the observation group were higher than those in the control group, and the difference was statistically significant (P< 0.05). The total score of the quality of life in the observation group was higher than in the control group and the difference was statistically significant (P< 0.05). CONCLUSION: Continuous care had a good application effect on patients with viral keratitis, which could potentially effectively improve medication compliance and the rate of return visits, reduce recurrence rate, and improve patient satisfaction and their quality of life. Accordingly, the results of this study present high clinical value.

In order to clarify the distribution law of the radiation optical field of the gas insulated switchgear disconnector defect and determine the detection range of partial discharge optical sensor, the optical model of the gas insulated switchgear disconnector based on the uniform geometrical theory of diffraction theory is established based on ray tracing method, and the distribution of the radiation light field is calculated when partial discharge occurs at the key positions such as the basin insulator, shield, and support insulator barrel. Based on the maximum irradiance, average irradiance and attenuation characteristics on the shell interface, the distribution law is further analysed, and based on this, the optimal location of the ultraviolet detector is proposed.

Objectives The Sonic hedgehog (SHH) signaling is essential in animal development and tissue homeostasis. Aberrant activation of SHH pathway has been implicated in tumorigenesis and progression of several cancers, including ovarian cancer. Therefore, targeting SHH pathway may pave the way for successful ovarian cancer treatment. Methods To identify the potential SHH inhibitors from traditional Chinese medicines, we herein employed two in vitro cell models. In addition, western blotting and quantitative real-time PCR were performed to evaluate the inhibitory activity of Anemarrhenasaponin I (An-I) on SHH signaling in ovarian cancer cells. Cell proliferation assay and transwell assay were used to assess the effect of An-I on tumorigenicity. We also applied RNA-seq to examine the potential mechanism of An-I against ovarian cancer. Results Drug screening results showed that An-I drastically inhibited SHH signaling. More importantly, An-I effectively suppressed ovarian cancer cell proliferation and aggressiveness. RNA-seq-based transcriptome data showed that An-I affected ovarian cancer cells by suppressing SHH-WNT-Matrix metalloproteinases (MMPs) pathway. Conclusions An-I suppressed ovarian cancer progression by inhibiting SHH-WNT-MMP signaling transduction, providing a new treatment strategy for ovarian cancer.

In complex industrial processes, the technique of fault diagnosis has been playing an increasingly considerable role in ensuring the safety of life and property. Unfortunately, the process data of complex industrial processes have the features of high dimension. Feature extraction from high-dimensional data is promising to coping with the fault data with high dimension. Recently, one of manifold learning methods named discriminant locality preserving projection achieves excellent performance in feature extraction. However, the performance of discriminant locality preserving projection (DLPP) is subject to the problem of matrix decomposition in the denominator of the objection function caused by the small sample size (SSS) issue. To overcome this limitation, novel DLPP integrated with Monte Carlo sampling is proposed to enhance the performance of feature extraction through dimensionality reduction. In the proposed MC-DLPP, Monte Carlo sampling is first utilized to generate fault samples for each fault type. With the aid of the virtually generated fault samples, the rank of the matrix in the denominator of the objection function of DLPP increases, thus well addressing the SSS problem. The Softmax classifier is used for fault diagnosis. To test the performance of the improved DLPP-based fault diagnosis, case studies using the Tennessee Eastman process are carried out. Simulation results confirm the presented MC-DLPP achieves superior accuracy in fault diagnosis.

In 1928, neuroscientist Yushi Uchimura (1897–1980) published a landmark study detailing the hippocampal vasculature. Working in Walther Spielmeyer’s Munich laboratory (1925–1927), Uchimura sought evidence for a vascular theory of Ammon’s horn sclerosis (AHS). He described an artery supplying the vulnerable sector of the hippocampus, where pathognomonic changes of AHS were noted, and characterized the artery as particularly susceptible to circulatory disturbances. Discovery of this artery led to new concepts and new terminology pertaining to the hippocampus. In addition to having a distinguished career in psychiatry and academia (including a position as University of Tokyo dean), Uchimura was, before attending medical school, one of Japan’s best baseball pitchers; he was eventually named Nippon Professional Baseball Organization commissioner and inducted into the Japan Baseball Hall of Fame. Uchimura’s description of hippocampal vasculature, which is still subject to debate after nearly a century, brought international attention to AHS and epilepsy and showed the hippocampal vasculature to be variable and vulnerable; important considerations for later neurosurgeons in the development of selective mesial temporal surgery. Prominent figures in neurosurgery have since developed classification systems for the hippocampal vasculature in which the artery of Uchimura remains central. Perhaps no other brain artery has been the nexus for such intense investigation and debate about its association to structure, function, disease, and treatment methodology.

Structural variations (SVs) are a major contributor to genetic diversity and phenotypic variations, but their prevalence and functions in domestic animals are largely unexplored. Here we generated high-quality genome assemblies for 15 individuals from genetically diverse sheep breeds using Pacific Biosciences (PacBio) high-fidelity sequencing, discovering 130.3 Mb nonreference sequences, from which 588 genes were annotated. A total of 149,158 biallelic insertions/deletions, 6531 divergent alleles, and 14,707 multiallelic variations with precise breakpoints were discovered. The SV spectrum is characterized by an excess of derived insertions compared to deletions (94,422 vs. 33,571), suggesting recent active LINE expansions in sheep. Nearly half of the SVs display low to moderate linkage disequilibrium with surrounding single-nucleotide polymorphisms (SNPs) and most SVs cannot be tagged by SNP probes from the widely used ovine 50K SNP chip. We identified 865 population-stratified SVs including 122 SVs possibly derived in the domestication process among 690 individuals from sheep breeds worldwide. A novel 168-bp insertion in the 5′ untranslated region (5′ UTR) ofHOXB13is found at high frequency in long-tailed sheep. Further genome-wide association study and gene expression analyses suggest that this mutation is causative for the long-tail trait. In summary, we have developed a panel of high-quality de novo assemblies and present a catalog of structural variations in sheep. Our data capture abundant candidate functional variations that were previously unexplored and provide a fundamental resource for understanding trait biology in sheep.

<>The sparrow search algorithm (SSA) is a novel intelligent optimization algorithm that simulates the foraging and anti-predation behavior of sparrows. The sparrow search algorithm (SSA) can optimize continuous problems, but in reality many problems are binary problems. In this paper, the binary sparrow search algorithm (BSSA) is proposed to solve binary optimization problems, such as feature selection. The transfer function is crucial to BSSA and it directly affects the performance of BSSA. This paper proposes three new transfer functions to improve the performance of BSSA. Mathematical analysis revealed that the original SSA scroungers position update equation is no longer adapted to BSSA. This paper improves the position update equation. We compared BSSA with BPSO, BGWO, and BBA algorithms, and tested on 23 benchmark functions. In addition, statistical analysis of the experimental results, Friedman test and Wilcoxon rank-sum test were performed to verify the effectiveness of BSSA. Finally, the algorithm was used to successfully implement feature selection and obtain satisfactory results in the UCI data set.<>

To understand pyroptosis induced by ionizing radiation and its implications for radiation therapy, we explored the involved factors, possible mechanisms of radiation-induced pyroptosis and consequent antitumor immunity.The occurrence of pyroptosis was assessed by cell morphology, lactate dehydrogenase release, Annexin V/PI staining and the cleavage of Gasdermin E (GSDME). Cell radiosensitivity was tested with MTT and colony survival assays. Xenograft tumor volume, Ki-67, CD8Irradiation induced pyroptosis in GSDME high-expressing tumor cell lines covering lung, liver, breast, and glioma cancers. Cleavage of GSDME occurred in a dose- and time-dependent manner after irradiation, and pyroptosis could be induced by various kinds of irradiation. The combination of chemotherapy drugs for DNA damage (cisplatin or etoposide) or demethylation (decitabine or azacytidine) and irradiation significantly enhanced the occurrence of pyroptosis. Moreover, we revealed that the Caspase 9/Caspase 3/GSDME pathway was involved in irradiation-induced pyroptosis. Notably, enhanced tumor suppression was observed in Balb/c mice bearing GSDME-overexpressing 4T1 tumors compared with those bearing vector tumors for the promotion of antitumor immunity, which was manifested as distinctly elevated levels of cytotoxic T lymphocytes and release of the related cytokines rather than the direct effect of pyroptosis on tumor cell radiosensitivity.As an immunogenic cell death caused by radiation, pyroptosis promotes antitumor immunity after irradiation. Our findings may provide new insights to improve the efficacy of tumor radiation therapy.

By aiming at addressing the left-turning problem of an autonomous vehicle considering the oncoming vehicles at an urban unsignallized intersection, a hierarchical reinforcement learning is proposed and a two-layer model is established to study behaviors of left-turning driving. Compared with the conventional decision-making models with a fixed path, the proposed multi-paths decision-making algorithm with horizontal and vertical strategies can improve the efficiency of autonomous vehicles crossing intersections while ensuring safety.

Hypoxic stress, caused by the low cellular oxygen in the events of flooding or waterlogging, limits crop productivity in many regions of the world. Hypoxic stress in plants is often dynamic and followed by a reoxygenation process that returns the oxygen level to normal. Although metabolic responses to hypoxia have been studied in many plants, less is known about the recovery processes following stress removal. To better understand the dynamic metabolic shift from a low-oxygen environment to a reoxygenated environment, we performed time-course measurements of metabolites in Arabidopsis seedlings at 0, 6, 12, and 24 h of reoxygenation recovery after 24 h of hypoxia stress (100% N2 environment). Among the 80 metabolic features characterized using GC-MS, 60% of them were significantly changed under hypoxia. The reoxygenation phase was accompanied by progressively fewer metabolic changes. Only 26% significantly changed metabolic features by the 24 h reoxygenation. Hypoxia-induced metabolic changes returned to normal levels at different speeds. For example, hypoxia-induced accumulation of lactate decreased to a basal level after 6 h of reoxygenation, whereas hypoxia-induced accumulation of alanine and GABA showed partial recovery after 24 h of reoxygenation. Some metabolites, such as gluconate, xylose, guanine, and adenosine, constantly increased during hypoxia reoxygenation. These dynamic metabolic changes demonstrate the flexibility and complexity of plant metabolism during hypoxia stress and subsequent reoxygenation recovery.

The thioether-directed regioselective cycloaddition of internal alkynes with azides was enabled by the in situ generated cationic Ir species, providing modular access to complex S-containing triazoles.

Fe/Co–N/Sx–C catalysts with a sulfur dopant are designed and successfully synthesized, and they show excellent ORR and OER bifunctional electrocatalytic performance both theoretically and experimentally.

Yuan-yuan Wu,1 Wen-Hui Liao,1 Zong-ling Niu,1 Si-Han Zhou,1 Tian-Tian Wu,1 Zhe Li,2 Qi-Hua Zhao,1 Jing-Yuan Xu,2 Ming-jin Xie1 1School of Chemical Science and Technology, Yunnan University, Kunming, People’s Republic of China; 2Department of Chemical Biology and Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Ming-jin Xie, Email mjxie@ynu.edu.cnBackground: Gallium (III) metal-organic complexes have been shown to have the ability to inhibit tumor growth, but the poor water solubility of many of the complexes precludes further application. The use of materials with high biocompatibility as drug delivery carriers for metal-organic complexes to enhance the bioavailability of the drug is a feasible approach.Methods: Here, we modified the ligands of gallium 8-hydroxyquinolinate complex with good clinical anticancer activity by replacing the 8-hydroxyquinoline ligands with 5-bromo-8-hydroxyquinoline (HBrQ), and the resulting Ga(III) + HBrQ complex had poor water solubility. Two biocompatible materials, bovine serum albumin (BSA) and graphene oxide (GO), were used to synthesize the corresponding Ga(III) + HBrQ complex nanoparticles (NPs) BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs in different ways to enhance the drug delivery of the metal complex.Results: Both of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs can maintain stable existence in different solution states. In vitro cytotoxicity test showed that two nanomedicines had excellent anti-proliferation effect on HCT116 cells, which shown higher level of intracellular ROS and apoptosis ratio than that of cisplatin and oxaliplatin. In addition, the superior emissive properties of BSA/Ga/HBrQ NPs and GO/Ga/HBrQ NPs allow their use for in vivo imaging showing highly effective therapy in HCT116 tumor-bearing mouse models.Conclusion: The use of biocompatible materials for the preparation of NPs against poorly biocompatible metal-organic complexes to construct drug delivery systems is a promising strategy that can further improve drug delivery and therapeutic efficacy.Graphical Abstract: Keywords: gallium complex, nanomedicine, anticancer, colorectal cells, drug delivery, in vivo imaging

Recently, novel 2D InGeTe3 has been successfully synthesized and attracted attention due to its excellent properties.

The unmanned aerial vehicle (UAV), as a remote sensing platform, has attracted many researchers in precision agriculture because of its operational flexibility and capability of producing high spatial and temporal resolution images of agricultural fields. This study proposed machine learning (ML) models and their ensembles for peanut yield prediction using UAV multispectral data. We utilized five bands (red, green, blue, near-infra-red (NIR) and red-edge) multispectral images acquired at various growth stages of peanuts using UAV. The correlation between spectral bands and yield was analyzed for each growth stage, which showed that the maturity stages had a significant correlation between peanut yield and spectral bands: red, green, NIR and red edge (REDE). Using these four bands spectral data, we assessed the potential for peanut yield prediction using multiple linear regression and seven non-linear ML models whose hyperparameters were optimized using simulated annealing (SA). The best three ML models, random forest (RF), support vector machine (SVM) and XGBoost, were then selected to construct a cooperative yield prediction framework with both the best ML model and the ensemble scheme from the best three as comparable recommendations to the farmers.

An electrochemical mass spectrometry method was developed for speciation analysis of heavy metals in suspended particulate matter in lake water.

Intrinsic descriptor is unraveled based on coarse-fine two-stage activity regulation mechanism to design superior bimetallic 2D c-MOFs for CO2RR.

In vitro fertilization (IVF) embryo evaluation based on morphology is an effective method to improve the success rate of transplantation. Although convolutional neural networks (CNNs) have made great achievements in many image classifications, there are still great challenges in accurately classifying embryos due to the insufficient samples, interference of exfoliated cells, and inappropriate hyperparameter configuration in the classification network. In this paper, a residual neural network optimized by the adaptive genetic algorithm is proposed to evaluate embryos. Firstly, a novel algorithm for extracting the region of interest (ROI) is embedded in the preprocessing part of the model to eliminate exfoliated cells close to the embryo. Secondly, several kinds of specific transformation methods are established to expand the dataset based on the symmetry of embryos. In addition, an adaptive genetic algorithm is adopted to search for optimal hyperparameters. Experiments on the data set provided by Shanghai General Hospital show that the algorithm has an excellent performance in embryo evaluation. The accuracy of our model is 86.4%, the recall is 88.4%, and the AUC is 0.93. Our results indicated that the proposed model can effectively improve the classification performance of ResNet, and thus achieve the clinic requirements of embryo evaluation. &nbsp

To enable the accurate detection of grain moisture content and improve the efficiency of the drying process, a parallel-plate moisture content detection device (PPMCDD) was developed in this study. Firstly, the detection principle and influencing factors of this device are analyzed. Then the effects of three key factors as distance, thickness, relative area on the accuracy of the device were determined through simulation, and the optimal combination of parameters was obtained through analysis of variance of a regression model and response surface methodology. Finally, a simple test bench is built to verify the effectiveness of PPMCDD by comparative experiment. Through simulation and response surface analysis, the optimal combination parameters are as follows: thickness =1 mm, pacing =19.54 mm, relative area =4023.17 mm2, corresponding to the measured capacitance value of 37.676 pF. By comparative experimental analysis, it is found that the maximal relative error of the moisture content detection device evaluated in this study was 1.58%. The detection error is small, and the device exhibits high accuracy and stability and meets the design requirement.

Ulcerative colitis (UC) is a nonspecific intestinal inflammatory disease. Dexmedetomidine (DEX) is a selective alpha 2-adrenergic receptor agonist commonly used for analgesia and sedation in intensive care units. Herein, the role and mechanism of DEX in dextran sulfate sodium (DSS)-induced colitis was explored.A murine model of DSS-induced colitis was established by adding 3.5% (w/v) DSS in drinking water to C57BL/6J female mice. The severity of colitis was measured by the disease activity index (DAI) score, colon length and body weight of mice. The serum concentration and mRNA levels of inflammatory cytokines in colon tissues were assessed by ELISA and RT-qPCR, respectively. Protein levels of apoptotic markers, tight junction proteins and genes involved in the TLR4/MyD88/NF-κB signaling were quantified utilizing Western blotting. The pathological changes of colon tissues were evaluated by hematoxylin-eosin (HE) staining and histological score. Intestinal permeability in vivo was assessed by fluorescein isothiocyanate (FITC)-dextran (FITC-D) administration. TUNEL assay was used to determine cell apoptosis in the intestinal epithelium.DSS administration resulted in weight loss, shortening of the colon, increased DAI score, histological abnormalities, and increased serum FITC-D levels in mice, all of which were reversed by DEX injection. Moreover, DEX attenuated DSS-triggered inflammatory response, intestinal barrier injury and intestinal epithelial cell apoptosis. Mechanically, DEX inactivated the TLR4/MyD88/NF-κB signaling in the colon tissues.DEX exerts beneficial effects against the intestinal barrier dysfunction, inflammatory response, and apoptosis of intestinal epithelial cells via inactivation of the TLR4/MyD88/NF-κB signaling in mice with DSS-induced colitis.

[EN] Rabbit coccidiosis is a very serious disease caused by protozoan parasites of the genus Eimeria, which increases the production rate of free radicals, especially reactive oxygen species. When the generation of free radicals exceeds the scavenging capacity of the body s antioxidant system, the oxidant-antioxidant balance is broken, resulting in oxidative stress. This study was designed to investigate the effect on the oxidant-antioxidant status of rabbits infected with E. intestinalis and E. magna. To this end, eighteen 30-d-old weaned rabbits were randomly allocated into three groups as follows: the E. intestinalis infection group with 3×103 sporulated oocysts of E. intestinalis, the E. magna infection group with 20×103 sporulated oocysts of E. magna, and the uninfected control group. We measured the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) and the contents of malondialdehyde (MDA) in rabbits small intestinal tissues (duodenum, jejunum and ileum) of the three groupson day 8. The results showed that CAT activity and MDA levels significantly increased, while the activities of SOD, GSH-Px and T-AOC decreased after E. intestinalis and E. magna infection. Besides, the jejunum and ileum were particularly damaged in the rabbits. It is concluded that the pathological oxidative stress occurs during the E. intestinalis and E. magna infection process and the body s oxidant-antioxidant balance is disrupted., This experiment was supported by the National Natural Science Foundation Project of China (nos. 31960688 and 31360592) and the Natural Science Foundation Project of Jiangxi Province (no. 20181BAB204016).