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Development of biomedical hydrogels for rheumatoid arthritis treatment

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 35-48页

作者： Mirza Muhammad Faran Ashraf Baig Lee KiWong Abdul Wasy Zia hongkai Wu Department of Chemistry Hong Kong University of Science and TechnologyHong Kong 999077China Institute of Mechanical Process and Energy Engineering(IMPEE)School of Engineering and Physical SciencesHeriot-Watt UniversityEdinburghUnited Kingdom

Rheumatoid Arthritis(RA)is an autoimmune disorder that hinders the normal functioning of bones and joints and reduces the quality of human life.Every year,millions of people are diagnosed with RA worldwide,particularly among elderly individuals and women.Therefore,there is a global need to develop new biomaterials,medicines and therapeutic methods for treating RA.This will improve the Healthcare Access and Quality Index and also relieve administrative and financial burdens on healthcare service providers at a global scale.Hydrogels are soft and cross-linked polymeric materials that can store a chunk of fluids,drugs and biomolecules for hydration and therapeutic applications.Hydrogels are biocompatible and exhibit excellent mechanical properties,such as providing elastic cushions to articulating joints by mimicking the natural synovial fluid.Hence,hydrogels create a natural biological environment within the synovial cavity to reduce autoimmune reactions and friction.Hydrogels also lubricate the articulating joint surfaces to prevent degradation of synovial surfaces of bones and cartilage,thus exhibiting high potential for treating RA.This work reviews the progress in injectable and implantable hydrogels,synthesis methods,types of drugs,advantages and challenges.Additionally,it discusses the role of hydrogels in targeted drug delivery,mechanistic behaviour and tribological performance for RA treatment.

关键词： Rheumatoid arthritis Orthopeadic joints Hydrogel Therapeutics Mechanical properties Medicine

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of hong kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

Net effect of air pollution controls on health risk in the Beijing-Tianjin-Hebei region during the 2022 winter Olympics and Paralympics

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Journal of Environmental Sciences 2024年第1期135卷 560-569页

作者： Changqing Lin Peter K.K.Louie Alexis K.H.Lau Jimmy C.H.Fung Zibing Yuan Minghui Tao Xuguo Zhang Md.Shakhaoat Hossain Chengcai Li Xiang Qian Lao Division of Environment and Sustainability The Hong Kong University of Science and TechnologyHong KongChina Environmental Protection Department Hong Kong Government SARHong KongChina Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyHong KongChina Guangdong-hongkong-Macao Joint Laboratory of Collaborative Innovation for Environmental Quality The Hong Kong University of Science and TechnologyHong KongChina Department of Mathematics The Hong Kong University of Science and TechnologyHong KongChina School of Environment and Energy South China University of TechnologyGuangzhou 510006China Hubei Key Laboratory of Critical Zone Evolution School of Geography and Information EngineeringChina University of GeosciencesWuhan 430074China Department of Public Health and Informatics Jahangirnagar UniversityDhaka 1342Bangladesh Department of Atmospheric and Oceanic Sciences School of PhysicsPeking UniversityBeijing 100871China Jockey Club School of Public Health and Primary Care The Chinese University of Hong KongHong KongChina

Due to the non-linearity in ozone(O_(3))formation,reducing the emission of nitrogen oxides(NO_(x))may increase O_(3) concentration.Given the counteractive O_(3) response to NO_(x) reduction,overall impact of air pollution controls can be ambiguous when the assessments focus on the changes in pollutant concentrations.In this study,a risk-based method was used to gauge the net effect of air pollution controls on mortality risk in the Beijing–Tianjin–Hebei(BTH)region during the 2022 Winter Olympics and Paralympics(WOP).This mega-event presents a unique opportunity to investigate the efficacy of deep cuts in pollutant emissions.Results show that O_(3) concentrations greatly increased as nitrogen dioxide(NO_(2))concentrations decreased in the BTH.Due to the active photochemical formations,O_(3) became the dominant pollutant that affected human health during the WOP.Despite the substantial O_(3) increases,the health benefits of NO_(2) reductions overwhelmed the adverse health effects of O_(3) increases in most regions of the BTH(at 81 out of 112 stations).After considering the impacts of particulate matter,the integrated health risk of air pollution mixtures declined almost everywhere in the BTH.Our results underscore the great necessity of changing the assessment paradigm of pollution control from using concentration-based methods to using risk-based methods.Together with the carbon neutrality policy,stringent control of NO_(x)emission from combustion sources is a promising way to achieve synergistic control solutions for air pollution and climate change.

关键词： Ozone Nitrogen dioxide Health risk Carbon neutrality Mega-events

Does astrocytic L-lactate enhance cognition through myelination?

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Neural Regeneration Research 2024年第6期19卷 1167-1168页

作者： Mastura Akter Ying Li Department of Neuroscience City University of Hong Kong Department of Biomedical Sciences City Universit of Hong Kong Centre for Regenerative Medicine and Health Hong Kong Institute of Science & Innovation Chinese Academy of Sciences Centre for Biosystems Neuroscience and Nanotechnology City University of Hong Kong

Introduction: Astrocytes, the predominant glial cell in the brain, play a vital role in a plethora of central ner vous system functions. They are the major storage site of glycogen in the central nervous system. They produce L-lactate by glycogenolysis and glycolysis which is then transported to neurons(Magistreti and Allaman,

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Multiple Uplift and Exhumation of the Southeastern Tibetan Plateau:Evidence from Low-Temperature Thermochronology

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Acta Geologica Sinica(English Edition) 2024年第3期98卷 569-584页

作者： WU Limin PENG Touping FAN Weiming ZHAO Guochun GAO Jianfeng DONG Xiaohan PENG Shili MIN Kang Tin Aung MYINT State Key Laboratory of Isotope Geochemistry Guangzhou Institute of GeochemistryChinese Academy of SciencesGuangzhou 510640China Chinese Academy of Sciences Center for Excellence in Deep Earth Science Guangzhou 510640China University of Chinese Academy of Sciences Beijing 100049China Chinese Academy of Sciences Center for Excellence in Tibetan Plateau Earth Sciences Beijing 100101China Department of Earth Sciences The University of Hong KongHong Kong 999077China State Key Laboratory of Ore Deposit Geochemistry Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai) ZhuhaiGuangdong 519085China Department of Geology University of MandalayMandalay 05011Myanmar

Since the Cenozoic,the Tibetan Plateau has experienced large-scale uplift and outgrowth due to the India-Asia collision.However,the mechanism and timing of these tectonic processes still remain debated.Here,using apatite fission track dating and inverse thermal modeling,we explore the mechanism of different phases of rapid cooling for different batholiths and intrusions in the southeastern Tibetan Plateau.In contrast to previous views,we find that the coeval granitic batholith exposed in the same tectonic zone experienced differential fast uplift in different sites,indicating that the present Tibetan Plateau was the result of differential uplift rather than the entire lithosphere uplift related to lithospheric collapse during Cenozoic times.In addition,we also suggest that the 5-2 Ma mantle-related magmatism should be regarded as the critical trigger for the widely coeval cooling event in the southeastern Tibetan Plateau,because it led to the increase in atmospheric CO_(2)level and a hotter upper crust than before,which are efficient for suddenly fast rock weathering and erosion.Finally,we propose that the current landform of the southeastern Tibetan Plateau was the combined influences of tectonic and climate.

关键词： apatite fission track rapid cooling differential uplift magmatism southeastern Tibetan Plateau

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可压缩壁湍流物理与建模研究进展

Acta Mechanica Sinica 2024年第1期40卷 1-34页

作者：程诚陈贤亮朱文凯史维傅林 Department of Mechanical and Aerospace Engineering The Hong Kong University of Science and TechnologyHong KongChina Institute for Advanced Study The Hong Kong University of Science and TechnologyHong KongChina Department of Mathematics The Hong Kong University of Science and TechnologyHong KongChina Center for Ocean Research in hong kong and Macao(CORE) The Hong Kong University of Science and TechnologyHong KongChina HKUST Shenzhen-hong kong Collaborative Innovation Research Institute Shenzhen518045China

对高速边界层转捩与湍流的理解、建模与控制不但具有广泛的学术兴趣,而且对高速飞行器的设计与节能有至关重要的意义,因为转捩和湍流会急剧增加壁面摩阻和热流.根据Morkovin假设,高速流动具有一些与不可压缩流动本质上相似的特征,但另... 详细信息

对高速边界层转捩与湍流的理解、建模与控制不但具有广泛的学术兴趣,而且对高速飞行器的设计与节能有至关重要的意义,因为转捩和湍流会急剧增加壁面摩阻和热流.根据Morkovin假设,高速流动具有一些与不可压缩流动本质上相似的特征,但另一方面,由于存在热力学过程、激波、高焓效应等多物理场耦合,与不可压缩流动也有显著区别.本文综述了高速边界层转捩与湍流的物理和建模方面的最新研究进展,其中较大部分内容为湍流研究.为了物理过程描述的完整性,我们首先简要综述了高速流动转捩,主要关注气动加热原理和推迟转捩的被动控制策略.随后,我们总结了近期在湍流平均流向速度和温度的标度率方面的一些令人鼓舞的发现,这些标度率能够用于构建一系列新颖的壁面模型以提高模式精度.此外,作为湍流建模的基础之一,我们还总结了湍流结构方面的研究,尤其关注边界层对数区含能运动的标度率与建模.另外,我们综述了各种用于预测壁湍流的线性模型.尽管湍流通常被认为是高度非线性的,这些线性模型在过去二十年的研究中取得了较大的成功.最后,我们对综述进行总结,并简要展望未来研究.

关键词：不可压缩流动线性模型热力学过程多物理场耦合展望未来湍流研究湍流结构高速流动

片仔癀通过调节小鼠的肠道菌群和代谢物抑制非酒精性脂肪性肝炎

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Engineering 2024年第4期35卷 257-269页

作者： Xianyi Zeng Xiang Zhang Hao Su hongyan Gou Harry Cheuk-Hay Lau Xiaoxu Hu Ziheng Huang Yan Li Jun Yu Shenzhen Research Institute The Chinese University of Hong KongShenzhen 518057China Department of Medicine and Therapeutics Institute of Digestive DiseaseState Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077China

Non-alcoholic steatohepatitis(NASH)is a severe form of non-alcoholic fatty liver disease without effective treatment.The traditional Chinese medicine formulation Pien Tze Huang(PTH)can suppress inflammatory diseases.Here,we evaluate the effects of PTH on the evolution of NASH and its underlying mechanisms.We found that PTH prevented the development of steatohepatitis induced by various dietary models,including a high-fat high-cholesterol(HFHC)diet,choline-deficient high-fat diet(CD-HFD),and methionine-and choline-deficient(MCD)diet,along with significant suppression of liver injury,hepatic triglyceride,and lipid peroxidation.Moreover,ten days of PTH treatment after the onset of NASH significantly ameliorated MCD diet-induced steatosis and liver injury in mice.Through the metagenomic sequencing of stool samples,we found that PTH administration restored the gut microbiota with enrichment of probiotics including Lactobacillus acidophilus(L.acidophilus),Lactobacillus plantarum,Lactococcus lactis,and Bacillus subtilis.The enriched L.acidophilus prevented MCD diet-induced steatohepatitis.In addition,PTH restored the gut barrier function in mice with steatohepatitis,as evidenced by reduced intestinal permeability,decreased serum lipopolysaccharides(LPS)level,and increased epithelial tightjunction protein E-cadherin expression.Our metabolomic analysis via liquid chromatography-mass spectrometry profiling identified the alteration in the metabolism of bile acids in the portal vein of PTHtreated mice.We further confirmed that an intact gut microbiota is necessary for PTH to exhibit antisteatohepatitis effects.In conclusion,PTH protects against steatohepatitis development by modulating the gut microbiota and metabolites.PTH is a potential promising prophylactic and therapeutic option for patients with NASH.

关键词： Pien Tze Huang Non-alcoholic steatohepatitis Gut barrier function Gut microbiota

Stability and Generalization of Hypergraph Collaborative Networks

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Machine Intelligence Research 2024年第1期21卷 184-196页

作者： Michael K.Ng Hanrui Wu Andy Yip Institute of Data Science The University of Hong KongHong KongChina Department of Mathematics The University of Hong KongHong KongChina College of Information Science and Technology Jinan UniversityGuangzhou 510006China

Graph neural networks have been shown to be very effective in utilizing pairwise relationships across samples.Recently,there have been several successful proposals to generalize graph neural networks to hypergraph neural networks to exploit more com-plex relationships.In particular,the hypergraph collaborative networks yield superior results compared to other hypergraph neural net-works for various semi-supervised learning tasks.The collaborative network can provide high quality vertex embeddings and hyperedge embeddings together by formulating them as a joint optimization problem and by using their consistency in reconstructing the given hy-pergraph.In this paper,we aim to establish the algorithmic stability of the core layer of the collaborative network and provide generaliz--ation guarantees.The analysis sheds light on the design of hypergraph filters in collaborative networks,for instance,how the data and hypergraph filters should be scaled to achieve uniform stability of the learning process.Some experimental results on real-world datasets are presented to illustrate the theory.

关键词： Hypergraphs vertices hyperedges collaborative networks graph convolutional neural networks(CNNs) stability generalization guarantees

Nuclear mass predictions based on a deep neural network and finite-range droplet model(2012)

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Chinese Physics C 2024年第2期48卷 112-123页

作者：姚道驄梁豪兆李曉菁 Department of Physics The University of Hong KongHong Kong 999077China Department of Physics Graduate School of ScienceThe University of TokyoTokyo 113-0033Japan Interdisciplinary Theoretical and Mathematical Sciences Program(iTHEMS) RIKENWako 351-0198Japan

A neural network with two hidden layers is developed for nuclear mass prediction,based on the finiterange droplet model(FRDM12).Different hyperparameters,including the number of hidden units,choice of activation functions,initializers,and learning rates,are adjusted explicitly and systematically.The resulting mass predictions are achieved by averaging the predictions given by several different sets of hyperparameters with different regularizers and seed numbers.This can provide not only the average values of mass predictions but also reliable estimations in the mass prediction uncertainties.The overall root-mean-square deviations of nuclear mass are reduced from 0.603 MeV for the FRDM12 model to 0.200 MeV and 0.232 MeV for the training and validation sets,respectively.

关键词： nuclear mass machine learning deep neural network