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A promising approach for quantifying focal stroke modeling and assessing stroke progression:optical resolution photoacoustic microscopy photothrombosis

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Neural Regeneration Research 2025年第7期20卷 2029-2037页

作者： Xiao Liang Xingping Quan Xiaorui Geng Yujing Huang Yonghua Zhao Lei Xi Zhen Yuan Ping Wang Bin Liu Faculty of Health Sciences University of MacaoMacao Special Administrative RegionChina Center for Cognitive and Brain Sciences University of MacaoMacao Special Administrative RegionChina Department of Biomedical Engineering Southern University of Science and TechnologyShenzhenGuangdong ProvinceChina State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina Department of Emergency Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

To investigate the mechanisms underlying the onset and progression of ischemic stroke,some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral ***,these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied,although ischemic stroke is strongly *** this study,we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed *** observed the molding process in mice of different ages and presented age-dependent vascular embolism ***,we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a *** imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages,thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes.

关键词： age-dependent cerebral cortex ischemic stroke mouse model optical coherence tomography angiography photoacoustic microscopy photothrombosis vascular imaging

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Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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Neural Regeneration Research 2025年第8期20卷 2181-2198页

作者： Jiali Chen Yiyang Li Xingping Quan Jinfen Chen Yan Han Li Yang Manfei Zhou Greta Seng Peng Mok Ruibing Wang Yonghua Zhao Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmacy Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan ProvinceChina Department of Electrical and Computer Engineering University of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on *** vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic ***,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery *** utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly ***,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic *** extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke *** this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification *** the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment ***,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

关键词： delivery engineering extracellular vesicles identification ischemic stroke isolation mitochondria targeting strategy therapeutic effects

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On equidistribution theorems for multi-sequences of holomorphic line bundles

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Science china Mathematics 2025年第2期68卷 285-298页

作者： Manli Liu Weixiong Mai Guokuan Shao Department of Mathematics South China Agricultural UniversityGuangzhou 510642China macao Center for Mathematical Sciences Macao University of Science and TechnologyMacao 999078China School of Mathematics(Zhuhai) Sun Yat-sen UniversityZhuhai 519082China

Given several sequences of Hermitian holomorphic line bundles{(L_(kp),h_(kp))}_(p=1)^(∞),we establish the distribution of common zeros of random holomorphic sections of Lkp with respect to singular *** also study the... 详细信息

关键词： equidistribution random holomorphic section pseudo-effective line bundle current

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Achievable Rate Analysis and Optimization of Double-RIS Assisted Spatially Correlated MIMO with Statistical CSI

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china Communications 2025年第1期22卷 139-157页

作者： Xu Kaizhe Guo Jiajia Zhang Jun Jin Shi Ma Shaodan Department of Communications and Networking Xi’an Jiaotong-Liverpool UniversitySuzhou 215123China State Key Laboratory of Internet of Things for Smart City University of MacaoMacao SARChina Jiangsu Key Laboratory of Wireless Communications Nanjing University of Posts and TelecommunicationsNanjing 210003China National Mobile Communications Research Laboratory Southeast UniversityNanjing 210096China State Key Laboratory of Internet of Things for Smart City and the Department of Electrical and Computer Engineering University of MacaoMacao SARChina

Reconfigurable intelligent surface(RIS)is a novel meta-material which can form a smart radio environment by dynamically altering reflection directions of the impinging electromagnetic *** the prior literature,the inter-RIS links which also contribute to the performance of the whole system are usually neglected when multiple RISs are *** this paper we investigate a general double-RIS assisted multiple-input multiple-output(MIMO)wireless communication system under spatially correlated non line-of-sight propagation channels,where the cooperation of the double RISs is also *** design objective is to maximize the achievable ergodic rate based on full statistical channel state information(CSI).Specifically,we firstly present a closedform asymptotic expression for the achievable ergodic rate by utilizing replica method from statistical *** a full statistical CSI-enabled optimal design is proposed which avoids high pilot training overhead compared to instantaneous CSI-enabled *** further reduce the signal processing overhead and lower the complexity for practical realization,a common-phase scheme is proposed to design the double *** results show that the derived asymptotic ergodic rate is quite accurate even for small-sized antenna *** the proposed optimization algorithm can achieve substantial gain at the expense of a low overhead and ***,the cooperative double-RIS assisted MIMO framework is proven to achieve superior ergodic rate performance and high communication reliability under harsh propagation environment.

关键词： common reflection pattern double RISs large system analysis MIMO replica method

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Pinelliae Rhizoma:a systematic review on botany,ethnopharmacology,phytochemistry,preclinical and clinical evidence

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Chinese Journal of Natural Medicines 2025年第1期23卷 1-20页

作者： Zuanji Liang Jinchao Wei Sioi Chan Siyuan Zhang Li Xu Chenxiao Shen Zhangfeng Zhong Yitao Wang macao Centre for Research and Development in Chinese Medicine State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau

Pinelliae Rhizoma(PR), known as Banxia in Chinese, Hange in Japanese, and Banha in Korean,is a renowned herbal medicine in East Asia derived from the dry tuber of Pinellia ternata(Thunb.) Breit.(PT). It is extensively utilized in dispensing granules, classical prescriptions,and herbal formulas to treat various conditions, including cough, infection, phlegm, nausea,asthma, and inflammation. Despite numerous studies on PR and its classical prescriptions over recent decades, a comprehensive synthesis of available evidence regarding its multifunctional roles and therapeutic potential is lacking. This review aims to address this gap by examining emerging evidence from metabonomics, preclinical studies, and clinical trials, while exploring potential trends and prospects for future research. A systematic literature search was conducted across six electronic databases, including Pub Med, Web of Science, Scopus,Science Direct, Wanfang, and china National Knowledge Infrastructure, to identify relevant articles on PR published until March 2023. PR contains 107 compounds with diverse pharmacological activities, including anti-inflammatory, immune regulatory, anti-viral, anti-cancer,anti-asthma, antitussive and expectorant, antioxidant, anti-obesity, anti-atherosclerosis, antimicrobial, emetic and anti-emetic, anti-convulsant and anti-epileptic, sedative and hypnotic,learning and memory enhancement, and anti-depressant effects. Metabonomic studies suggest that raw PR may exhibit cardiotoxicity and pregnancy toxicity while showing no apparent hepatorenal toxicity. However, limited pharmacokinetic investigations on PR constrain its clinical translation. Furthermore, clinical safety data on PR is scarce, with only four clinical trials assessing its positive effects in pediatric epilepsy, nausea and vomiting, soft tissue injury, and chronic sinus tract. This review aims to enhance understanding of PR and provide valuable information and recommendations for further research and devel

关键词： Classical prescription Dispensing granule Herbal medicine Pinellia ternata Pinelliae Rhizoma

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he BCM1-EGY1 module balances chlorophyll biosynthesis and breakdown to confer chlorophyll homeostasis in land plants

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Molecular Plant 2025年第1期18卷 76-94页

作者： Dali Fu Hanlin Zhou Bernhard Grimm Peng Wang School of Biological Sciences The University of Hong KongHong Kong SAR 999077China Institute of Biology/Plant Physiology Humboldt-Universität zu BerlinPhilippstrasse13Building 1210115 BerlinGermany State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongHong Kong SAR 999077China

Chlorophyll metabolism has evolved during plant *** strictly light-dependent nature of chlorophyll biosynthesis found in angiosperms requires tight coordination of chlorophyll biosynthesis and breakdown to achieve chlorophyll ***,the specific control mechanisms remain largely ***,we demonstrate that the scaffold protein BALANCE OF CHLOROPHYLL METABOLISM1(BCM1)has co-evolved with the carboxy-terminal domains of specific enzymes involved in chlorophyll biosynthesis and breakdown,including GENOMES UNCOUPLED 4(GUN4)and Mg-dechelatase 1(SGR1).We found that the land plant-specific interaction of BCM1 with the carboxy-terminal domains of GUN4 and SGR1 is indispensable for concurrent stimulation of chlorophyll biosynthesis and suppression of chlorophyll *** land plant-specific carboxy-terminal domain is essential for the membrane docking and turnover of GUN4,whereas it is key for proteolysis of *** importantly,we identified the metallopeptidase Gravitropism-deficient and Yellow-green 1(EGY1)as the proteolytic machinery responsible for BCM1-mediated proteolysis of *** summary,this study reveals the BCM1-EGY1 module has evolved to maintain chlorophyll homeostasis by the post-translational control of the balance between chlorophyll biosynthesis and *** mechanism thus represents an evolutionary response to the metabolic demands imposed on plants in terrestrial environments.

关键词： chlorophyll homeostasis scaffold protein BCM1 proteolytic machinery EGY1 post-translational control

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Integrated in silico formulation design of selfemulsifying drug delivery systems

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3585-3594页

作者： Haoshi Gao Haoyue Jia Jie Dong Xinggang Yang Haifeng Li Defang Ouyang State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Institute of Applied Physics and Materials Engineering University of MacaoMacao 999078China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China

The drug formulation design of self-emulsifying drug delivery systems(SEDDS)often requires numerous experiments,which are time-and *** research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches.4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning *** forest(RF)showed the best prediction performance with 91.3% for accuracy,92.0% for sensitivity and 90.7% for specificity in 5-fold *** pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy(89.51%).The central composite design(CCD)was used to screen the best ratio of ***,molecular dynamic(MD)simulation was used to investigate the molecular interaction between excipients and drugs,which revealed the diffusion behavior in water and the role of *** conclusion,this research combined machine learning,central composite design,molecular modeling and experimental approaches for rational SEDDS formulation *** integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

关键词： Self-emulsifying drug delivery system Random forest Central composite design Molecular dynamic simulation Meloxicam

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Predicting complexation performance between cyclodextrins and guest molecules by integrated machine learning and molecular modeling techniques

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Acta Pharmaceutica Sinica B 2019年第6期9卷 1241-1252页

作者： Qianqian Zhao Zhuyifan Ye Yan Su Defang Ouyang State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacaoChina

Most pharmaceutical formulation developments are complex and ideal formulations are generally obtained after extensive *** learning is increasingly advancing many aspects in modern society and has achieved significant success in multiple *** research demonstrated that machine learning can be adopted to build up high-accurate predictive models in drugs/cyclodextrins(CDs)*** descriptors of compounds and experimental conditions were employed as inputs,while complexation free energy as *** showed that the light gradient boosting machine provided significantly improved predictive performance over random forest and deep *** mean absolute error was 1.38 kJ/mol and squared correlation coefficient *** evaluation of relative importance of molecular descriptors further demonstrated the key factors affecting molecular interactions in drugs/CD *** the specific ketoprofen-CD systems,machine learning model showed better predictive performance than molecular modeling calculation,while molecular simulation could provide structural,dynamic and energetic *** integration of machine learning and molecular simulation could produce synergistic effect for interpreting and predicting pharmaceutical *** conclusion,the developed predictive models were able to quickly and accurately predict the solubilizing capacity of CD *** research has taken an important step toward the application of machine learning in pharmaceutical formulation design.

关键词： Machine learning Deep learning LightGBM Random forest Cyclodextrin Binding free energy Molecular modeling Ketoprofen

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Small molecules for fat combustion: targeting obesity

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Acta Pharmaceutica Sinica B 2019年第2期9卷 220-236页

作者： Jingxin Liu Yitao Wang Ligen Lin State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macao

Obesity is increasing in an alarming rate worldwide, which causes higher risks of some diseases, such as type 2 diabetes, cardiovascular diseases, and cancer. Current therapeutic approaches,either pancreatic lipase inhibitors or appetite suppressors, are generally of limited effectiveness. Brown adipose tissue(BAT) and beige cells dissipate fatty acids as heat to maintain body temperature, termed non-shivering thermogenesis; the activity and mass of BAT and beige cells are negatively correlated with overweight and obesity. The existence of BAT and beige cells in human adults provides an effective weight reduction therapy, a process likely to be amenable to pharmacological intervention. Herein, we combed through the physiology of thermogenesis and the role of BAT and beige cells in combating with obesity. We summarized the thermogenic regulators identified in the past decades, targeting G proteincoupled receptors, transient receptor potential channels, nuclear receptors and miscellaneous *** in clinical trials were also presented. The main purpose of this review is to provide a comprehensive and up-to-date knowledge from the biological importance of thermogenesis in energy homeostasis to the representative thermogenic regulators for treating obesity. Thermogenic regulatorsmight have a large potential for further investigations to be developed as lead compounds in fighting obesity.

关键词： Thermogenesis Brown adipose tissue Beige cells Obesity Uncoupling protein 1

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Click chemistry-based enrichment strategy for tracing cellular fatty acid metabolism by LC-MS/MS

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Journal of Pharmaceutical Analysis 2023年第10期13卷 1221-1231页

作者： Ru-Jie Yang Jian Zou Jia-Yue Liu Jiang-Kun Dai Jian-Bo Wan State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR999078China

Fatty acids(FAs),which were initially recognized as energy sources and essential building blocks of biomembranes,serve as the precursors of important signaling *** FA metabolism is essential to understanding the biochemical activity and role of FAs in physiological and pathological *** by the advances in click chemistry for protein enrichment,we herein established a click chemistry-based enrichment(CCBE)strategy for tracing the cellular metabolism of eicosapentaenoic acid(EPA,20:5 n-3)in neural *** alkyne-labeled EPA(EPAA)used as a surrogate was incubated with N2a,mouse neuroblastoma cells,and alkyne-labeled metabolites(ALMs)were selectively captured by an azide-modified resin via a Cu(I)-catalyzed azide-alkyne cycloaddition reaction for *** removing unlabeled metabolites,ALMs containing a triazole moiety were cleaved from solid-phase resins and subjected to liquid chromatography mass spectrometry(LC-MS)*** proposed CCBE strategy is highly selective for capturing and enriching alkyne-labeled metabolites from the complicated *** addition,this method can overcome current detection limits by enhancing MS sensitivity of targets,improving the chromatographic separation of sn-position glycerophospholipid regioisomers,facilitating structural characterization of ALMs by a specific MS/MS fragmentation signature,and providing versatile fluorescence detection of ALMs for cellular *** CCBE strategy might be expanded to trace the metabolism of other FAs,small molecules,or drugs.

关键词： Click chemistry-based enrichment EPA metabolism Terminal alkyne-labeled EPA Azide-modified resin LC-MS/MS

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