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Design of an automated robotic microinjection system for batch injection of zebrafish embryos and larvae

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Microsystems & Nanoengineering 2024年第1期10卷 89-103页

作者： Zhongyi Guo Nana Ai Wei Ge Qingsong Xu Department of Electromechanical Engineering Faculty of Science and TechnologyUniversity of MacaoMacaoChina Department of Biomedical Sciences and Centre of Reproduction Development and Aging(CRDA)Faculty of Health SciencesUniversity of MacaoMacaoChina

This paper presents the design of a vision-based automated robotic microinjection system for batch injection of both zebrafish embryos and larvae.A novel visual recognition algorithm based on an automatic threshold and excessive dilatation is introduced to accurately identify the center of zebrafish embryos and larval yolks.A corresponding software system is developed using the producer-consumer model as the framework structure,and a friendly user interface is designed to allow operators to choose from a range of desired functions according to their different needs.In addition,a novel microstructural agarose device is designed and fabricated to simultaneously immobilize mixed batches of embryos and larvae.Moreover,a prototype microinjection system is fabricated by integrating hardware devices with visual algorithms.An experimental study is conducted to verify the performance of the robotic microinjection system.The results show that the reported system can accurately identify zebrafish embryos and larvae and efficiently complete batch microinjection tasks of the mixtures with an injection success rate of 92.05%in 13.88 s per sample.Compared with manual and existing microinjection systems,the proposed system demonstrates the merits of versatility,excellent efficiency,high success rate,high survival rate,and sufficient stability.

关键词： zebra automated hardware

Attention Markets of Blockchain-Based Decentralized Autonomous Organizations

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IEEE/CAA Journal of Automatica Sinica 2024年第6期11卷 1370-1380页

作者： Juanjuan Li Rui Qin Sangtian Guan Wenwen Ding Fei Lin Fei-Yue Wang State Key Laboratory of Multimodal Artificial Intelligence Systems Institute of AutomationChinese Academy of SciencesBeijing 100190China Faculty of Innovation Engineering Macao University of Science and TechnologyMacao 999078China State Key Laboratory for Management and Control of Complex Systems Chinese Academy of SciencesBeijing 100190 Faculty of Innovation Engineering Macao University of Science and TechnologyMacao 999078China IEEE

The attention is a scarce resource in decentralized autonomous organizations(DAOs),as their self-governance relies heavily on the attention-intensive decision-making process of“proposal and voting”.To prevent the negative effects of pro-posers’attention-capturing strategies that contribute to the“tragedy of the commons”and ensure an efficient distribution of attention among multiple proposals,it is necessary to establish a market-driven allocation scheme for DAOs’attention.First,the Harberger tax-based attention markets are designed to facilitate its allocation via continuous and automated trading,where the individualized Harberger tax rate(HTR)determined by the pro-posers’reputation is adopted.Then,the Stackelberg game model is formulated in these markets,casting attention to owners in the role of leaders and other competitive proposers as followers.Its equilibrium trading strategies are also discussed to unravel the intricate dynamics of attention pricing.Moreover,utilizing the single-round Stackelberg game as an illustrative example,the existence of Nash equilibrium trading strategies is demonstrated.Finally,the impact of individualized HTR on trading strategies is investigated,and results suggest that it has a negative correlation with leaders’self-accessed prices and ownership duration,but its effect on their revenues varies under different conditions.This study is expected to provide valuable insights into leveraging attention resources to improve DAOs’governance and decision-making process.

关键词： Attention decentralized autonomous organizations Harberger tax Stackelberg game.

Small molecule deoxynyboquinone triggers alkylation and ubiquitination of Keap1 at Cys489 on Kelch domain for Nrf2 activation and inflammatory therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 401-415页

作者： Ke-Gang Linghu Tian Zhang Guang-Tao Zhang Peng Lv Wen-Jun Zhang Guan-Ding Zhao Shi-Hang Xiong Qiu-Shuo Ma Ming-Ming Zhao Meiwan Chen Yuan-Jia Hu Chang-Sheng Zhang Hua Yu State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina macao Centre for Research and Development in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Key Laboratory of Tropical Marine Bio-resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaRNAM Center for Marine MicrobiologySouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou510301China State Key Laboratory of Functions and Applications of Medicinal Plants&School of Pharmaceutical Sciences Guizhou Medical UniversityGuiyang550025China

Activation of nuclear factor erythroid 2-related factor 2(Nrf2)by Kelch-like ECH-associated protein 1(Keap1)alkylation plays a central role in anti-inflammatory therapy.However,activators of Nrf2 through alkylation of Keap1-Kelch domain have not been identified.Deoxynyboquinone(DNQ)is a natural small molecule discovered from marine actinomycetes.The current study was designed to investigate the anti-inflammatory effects and molecular mechanisms of DNQ via alkylation of Keap1.DNQ exhibited significant anti-inflammatory properties both in vitro and in vivo.The pharmacophore responsible for the anti-inflammatory properties of DNQ was determined to be theα,β-unsaturated amides moieties by a chemical reaction between DNQ and N-acetylcysteine.DNQ exerted anti-inflammatory effects through activation of Nrf2/ARE pathway.Keap1 was demonstrated to be the direct target of DNQ and bound with DNQ through conjugate addition reaction involving alkylation.The specific alkylation site of DNQ on Keap1 for Nrf2 activation was elucidated with a synthesized probe in conjunction with liquid chromatography-tandem mass spectrometry.DNQ triggered the ubiquitination and subsequent degradation of Keap1 by alkylation of the cysteine residue 489(Cys489)on Keap1-Kelch domain,ultimately enabling the activation of Nrf2.Our findings revealed that DNQ exhibited potent anti-inflammatory capacity throughα,β-unsaturated amides moieties active group which specifically activated Nrf2 signal pathway via alkylation/ubiquitination of Keap1-Kelch domain,suggesting the potential values of targeting Cys489 on Keap1-Kelch domain by DNQ-like small molecules in inflammatory therapies.

关键词： Deoxynyboquinone Anti-inflammation Target Keap1/Nrf2 Alkylation Ubiquitination

Chemical derivatization strategies for enhancing the HPLC analytical performance of natural active triterpenoids

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Journal of Pharmaceutical Analysis 2024年第3期14卷 295-307页

作者： Xiao-Feng Huang Ying Xue Li Yong Tian-Tian Wang Pei Luo Lin-Sen Qing Chengdu Institute of Biology Chinese Academy of SciencesChengdu610041China State Key Laboratory for Quality Research in Chinese medicines Macao University of Science and TechnologyMacaoChina Sichuan Center for Disease Control and Prevention Chengdu610041China University of Chinese academy of Sciences Beijing100049China

riterpenoids widely exist in nature,displaying a variety of pharmacological activities.Determining triterpenoids in different matrices,especially in biological samples holds great significance.High-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical performance.However,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical methods.Additionally,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass spectrometry.Consequently,routine HPLC analysis suffers from poor sensitivity.Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance.Considering the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rhodamines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of triterpenoids.This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids.Moreover,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.

关键词： Triterpenoid HPLC Derivatization Quantification

Combination strategies for first-line treatment of patients with unresectable hepatocellular carcinoma:prospect of natural products

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Chinese Journal of Natural medicines 2024年第1期22卷 1-3页

作者： ZHANG Lele LU Jinjian School of Basic Medical Sciences Chengdu UniversityChengdu 610106China State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical practice.Traditionally,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.

关键词： Unresectable hepatocellular carcinoma Combination strategies Immunotherapy PD-1/PD-L1 Natural products

Supramolecular Manipulation of Intracellular Acidic Vesicles to Improve Cellular Self-Repair and Self-Defense

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CCS Chemistry 2024年第6期6卷 1487-1498页

作者： Ziyi Wang Chen Sun Yu Dong Yuan-Fu Ding Chen Zhao Ian Wa Ho Jiahong Lu Ruibing Wang State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao 999078

Lysosomes are the“cell stomach”that digests various species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and phagosomes.Therefore,artificially manipulating intracellular vesicles could potentially promote lysosome-mediated intracellular digestion for disease prevention and treatment.Herein,a supramolecular strategy to efficiently tether and fuse acidic vesicles(i.e.,lysosomes,late endosomes,autolysosomes,and phagosomes)has been developed for the first time to enhance the digestion of cellular wastes and foreign matter,including pathogens.A linear polyethylene glycol(PEG)derivative dually tagged with morpholine(MOR)and adamantane(ADA)on the opposite side,namely,MOR-PEG-ADA,was designed to target intracellular acidic vesicles via MOR and to decorate their surfaces with ADA.Subsequently,the addition of cucurbit[7]uril(CB[7])grafted hyaluronic acid(HA)induced supramolecular tethering and fusion of acidic vesicles via strong host-guest interactions between CB[7]of CB[7]-HA and ADA residing on the surface of acidic vesicles.As a proof-ofconcept,the overall cellular metabolism,including endogenous autophagy and the exogenous endocytosis and phagocytosis,was effectively upregulated,demonstrating that supramolecular regulation of the dynamics of intracellular acidic vesicles may promote the lysosome’s digestion to significantly improve cellular self-repair and self-defense.

关键词： supramolecular chemistry organelle regulation intracellular acidic vesicles lysosomes selfdefense self-repair

Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

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Food Science and Human Wellness 2024年第2期13卷 568-596页

作者： Sijia Wu Siyuan Zhang Bo Peng Dechao Tan Mingyue Wu Jinchao Wei Yitao Wang Hua Luo macao Centre for Research and Development in Chinese medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China College of Pharmacy Guangxi Medical UniversityNanning 530021China Guangxi University of Chinese medicine Nanning 530001China

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that G.lucidum has various clinical therapeutic effects.And experimental studies have confirmed that G.lucidum has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so on.With the deepening of research,more than 300 compounds have been isolated from G.lucidum.There is an increasing population of G.lucidum-based products,and its international development is expanding.Currently,G.lucidum has drawn much attention to its chemical composition,therapeutic effect,clinical value,and safety.This paper provides a comprehensive review of these aspects to enhance the global promotion of G.lucidum.

关键词： Ganoderma lucidum Phytochemistry Efficacy Safety Clinical study

WavEnhancer: Unifying Wavelet and Transformer for Image Enhancement

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Journal of Computer Science & Technology 2024年第2期39卷 336-345页

作者：李梓诺陈绪行郭淑娜王书强潘治文 Department of Computer and Information Science University of MacaoMacao 999078China Research Center for Biomedical Information Technology Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Image enhancement is a widely used technique in digital image processing that aims to improve image aesthetics and visual quality. However, traditional methods of enhancement based on pixel-level or global-level modifications have limited effectiveness. Recently, as learning-based techniques gain popularity, various studies are now focusing on utilizing networks for image enhancement. However, these techniques often fail to optimize image frequency domains. This study addresses this gap by introducing a transformer-based model for improving images in the wavelet domain. The proposed model refines various frequency bands of an image and prioritizes local details and high-level features. Consequently, the proposed technique produces superior enhancement results. The proposed model’s performance was assessed through comprehensive benchmark evaluations, and the results suggest it outperforms the state-of-the-art techniques.

关键词： transformer wavelet transform image enhancement

State-Based Opacity Verification of Networked Discrete Event Systems Using Labeled Petri Nets

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IEEE/CAA Journal of Automatica Sinica 2024年第5期11卷 1274-1291页

作者： Yifan Dong Naiqi Wu Zhiwu Li The authors are with the Institute of Systems Engineering Macao University of Science and TechnologyTaipa 999078MacaoChina

The opaque property plays an important role in the operation of a security-critical system,implying that pre-defined secret information of the system is not able to be inferred through partially observing its behavior.This paper addresses the verification of current-state,initial-state,infinite-step,and K-step opacity of networked discrete event systems modeled by labeled Petri nets,where communication losses and delays are considered.Based on the symbolic technique for the representation of states in Petri nets,an observer and an estimator are designed for the verification of current-state and initial-state opacity,respectively.Then,we propose a structure called an I-observer that is combined with secret states to verify whether a networked discrete event system is infinite-step opaque or K-step opaque.Due to the utilization of symbolic approaches for the state-based opacity verification,the computation of the reachability graphs of labeled Petri nets is avoided,which dramatically reduces the computational overheads stemming from networked discrete event systems.

关键词： infinite system symbolic