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Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill lam.lau Ying lo law Chi Seng leung Chun Yin Tong Kai Kap Wong Wing lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong maria V.Babak Yudai matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEm Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina moscow Clinical Research Center Named After A.S.loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with hom.logous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in anim.ls and demonstrates the utility of synthetic biology for creating m.lecules with improved biological activities.

关键词： Anim.l studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intraderm.l versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel m.S.Cheng Carolyn A.Cohen Daniel leung Xiwei Wang Xiaofeng mu Yuet Chung Tsun ming lau manni Wang Wenyue Zhang Yanmei Zhang Howard H.W.Wong leo C.H.Tsang Sara Chaothai Tsz Chun kwan John K.C.li Karl C.K.chan leo l.H.luk Jenson C.H.Ho Wing Yan li Amos m.T.lee Jennifer H.Y.lam Sau man chan Wilfred H.S.Wong Issan Y.S.Tam masashi mori Sophie A.Valkenburg m.lik Peiris Wenwei Tu Yu lung lau Department of Paediatrics and Adolescent medicine The University of Hong KongHong KongChina School of Public Health The University of Hong KongHong KongChina HKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is *** dosing by intraderm.l(ID)administration has been shown to be equally immunogenic as intramuscular(Im)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is *** study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over Im administration in *** Participants aged 11–17 years received two doses of Im or ID vaccine,followed by the 3rd dose 13–42 days *** and cellular immunogenicity outcomes were measured post-dose 2(Im-CC versus ID-CC)and post-dose 3(ImCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,*** Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNm[sum of individual(S),nucleocapsid protein(N),and membrane protein(m)peptide pool]-specific interleukin-2(Il-2)+CD4^(+),SNm-specific Il-2^(+)CD8^(+),S-specific Il-2^(+)CD8^(+),N-specific Il-2^(+)CD4^(+),N-specific Il-2^(+)CD8^(+)and m-specific Il-2^(+)CD4^(+)responses fulfilled the superior and non-inferior criteria for ID-CC compared to Im-CC,whereas IgG avidity was *** ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,m-specific Il-2^(+)CD4^(+),interferon-γ+CD8^(+)and Il-2^(+)CD8^(+)responses were superior and non-inferior to *** estimated vaccine efficacies were 49%,52%,66%and 79%for Im-CC,ID-CC,Im-CCC and ID-CCC,*** ID groups reported more local,m.ld adverse *** This is the first study to demonstrate superior antibody and m-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the

关键词： CoronaVac Coronavirus disease 2019 Immunity Intraderm.l Vaccine

Unknown DDoS Attack Detection with Fuzzy C-means Clustering and Spatial location Constraint Prototype loss

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Computers, materials & Continua 2024年第2期78卷 2181-2205页

作者： Thanh-lam Nguyen HaoKao Thanh-Tuan Nguyen mong-Fong Horng Chin-Shiuh Shieh Department of Electronic Engineering National Kaohsiung University of Science and TechnologyKaohsiung807618Taiwan Department of Electronic and Automation Engineering Nha Trang UniversityNha Trang650000Vietnam

Since its inception,the Internet has been rapidly *** the advancement of science and technology and the explosive growth of the population,the demand for the Internet has been on the *** applications in education,healthcare,entertainment,science,and more are being increasingly deployed based on the ***,m.licious threats on the internet are on the rise as *** Denial of Service(DDoS)attacks are among the most common and dangerous threats on the internet *** scale and com.lexity of DDoS attacks are constantly *** Detection Systems(IDS)have been deployed and have demonstrated their effectiveness in defense against those *** addition,the research of machine learning(ml)and Deep learning(Dl)in IDS has gained effective results and significant ***,one of the challenges when applying ml and Dl techniques in intrusion detection is the identification of unknown *** attacks,which are not encountered during the system’s training,can lead to misclassification with significant *** this research,we focused on addressing the issue of Unknown Attack Detection,combining two methods:Spatial location Constraint Prototype loss(SlCPl)and Fuzzy C-means(FCm).With the proposed method,we achieved promising results compared to traditional *** proposed method demonstrates a very high accuracy of up to 99.8%with a low false positive rate for known attacks on the Intrusion Detection Evaluation Dataset(CICIDS2017)***,the accuracy is also very high,reaching 99.7%,and the precision goes up to 99.9%for unknown DDoS attacks on the DDoS Evaluation Dataset(CICDDoS2019)*** success of the proposed method is due to the combination of SlCPl,an advanced Open-Set Recognition(OSR)technique,and FCm,a traditional yet highly applicable clustering *** has yielded a novel method in the field of unknown attack *** further expands the trend of applying Dl and m

关键词： Cybersecurity DDoS unknown attack detection machine learning deep learning incremental learning convolutional neural networks(CNN) open-set recognition(OSR) spatial location constraint prototype loss fuzzy c-means CICIDS2017 CICDDoS2019

Physics-informed deep learning for fringe pattern analysis

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Opto-Electronic Advances 2024年第1期7卷 4-15页

作者： Wei Yin Yuxuan Che Xinsheng li mingyu li Yan Hu Shijie Feng Edmund Y.lam Qian Chen Chao Zuo Smart Computational Imaging laboratory(SCIlab) School of Electronic and Optical EngineeringNanjing University of Science and TechnologyNanjing 210094China Smart Computational Imaging Research Institute(SCIRI)of Nanjing University of Science and Technology Nanjing 210019China Jiangsu Key laboratory of Spectral Imaging&Intelligent Sense Nanjing 210094China Department of Electrical and Electronic Engineering The University of Hong KongPokfulamHong Kong SAR 999077China

Recently,deep learning has yielded transformative success across optics and photonics,especially in optical *** neural networks (DNNs) with a fully convolutional architecture (e.g.,U-Net and its derivatives) have been widely im.lemented in an end-to-end manner to accom.lish various optical metrology tasks,such as fringe denoising,phase unwrapping,and fringe ***,the task of training a DNN to accurately identify an image-to-image transform from massive input and output data pairs seems at best naive,as the physical laws governing the image formation or other domain expertise pertaining to the measurement have not yet been fully exploited in current deep learning *** this end,we introduce a physics-informed deep learning method for fringe pattern analysis (PI-FPA) to overcome this limit by integrating a lightweight DNN with a learning-enhanced Fourier transform profilometry (le FTP) *** parameterizing conventional phase retrieval methods,the le FTP module embeds the prior knowledge in the network structure and the loss function to directly provide reliable phase results for new types of sam.les,while circumventing the requirement of collecting a large amount of high-quality data in supervised learning *** by the initial phase from.le FTP,the phase recovery ability of the lightweight DNN is enhanced to further improve the phase accuracy at a low computational cost compared with existing end-to-end *** results demonstrate that PI-FPA enables more accurate and computationally efficient single-shot phase retrieval,exhibiting its excellent generalization to various unseen objects during *** proposed PI-FPA presents that challenging issues in optical metrology can be potentially overcome through the synergy of physics-priors-based traditional tools and data-driven learning approaches,opening new avenues to achieve fast and accurate single-shot 3D imaging.

关键词： optical metrology deep learning physics-informed neural networks fringe analysis phase retrieval

Recent advances in functional utilisation of environmentally friendly and recyclable high-performance green biocomposites: A review

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Chinese Chemical letters 2024年第4期35卷 73-85页

作者： Guiyang Zheng Xuelian Kang Haoran Ye Wei Fan Christian Sonne Su Shiung lam Rock Keey liew changlei Xia Yang Shi Shengbo Ge Co-Innovation Center of Efficient Processing and Utilization of Forest Resources College of Materials Science and EngineeringNanjing Forestry UniversityNanjing 210037China School of Textile Science and Engineering&Key laboratory of Functional Textile material and Product of ministry of Education Xi'an Polytechnic UniversityXi'an 710048China Department of Bioscience Arctic Research Centre(ARC)Aarhus UniversityFrederiksborgvej 399PO Box 358DK-4000 RoskildeDenmark Sustainability Cluster School of EngineeringUniversity of Petroleum&Energy StudiesDehradunUttarakhand 248007India Higher Institution Centre of Excellence(HICoE) Institute of Tropical Aquaculture and Fisheries(AKUATROP)Universiti Malaysia Terengganu21030 Kuala NerusTerengganuMalaysia Center for Transdisciplinary Research Saveetha Institute of Medical and Technical SciencesSaveetha UniversityChennai 600072India NV Western PlT Georgetown 10400PenangMalaysia Aerospace Kaitian Environmental Technology Co. Ltd.Changsha 410000China Hunan Hongsen Novel material Technology Co. Ltd.Yiyang 413407China

Humans have relied on biomass for survival and development since the Stone Age. All aspects of human needs for materials are covered by tools, fuel, and buildings. Nowadays, metals and petroleum-based materials are widely used in highly developed industries. Unfortunately, environmental contamination and the loss of natural resources have led to the reemergence of biomass resources as efficient and sustainable energy sources. Notably, sim.le and direct applications can no longer meet the demand for functionalization, high performance of materials and construction materials. Therefore, it is imperative to modify biomass and combine its utilisation to produce functionalization and high performance materials. For exam.le, construction materials with superior mechanical properties and water resistance can be produced by reinforcing fibres to facilitate crosslinking. Water-oil separation or adsorption effects of hydrogels and aerogels are determined by the porosity and lightness of biomass, biocomposite conductor is prepared by chimaeric conductive material. Here, we review the approaches that have been taken to devise an environmentally friendly yet fully recyclable and sustainable functionalised biocomposites from biomass and its potential directions for future research.

关键词： Biocomposite Renewable Sustainability Advanced functional material Pollution mitigation

Early anticoagulation in patients with stroke and atrial fibrillation is associated with fewer ischaemic lesions at 1 month: the ATTUNE study

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Stroke & Vascular Neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos Sharobeam.longting lin Christina lam Carlos Garcia-Esperon Yash Gawarikar Ronak Patel matthew lee-Archer Andrew Wong michael Roizman Amanda Gilligan Andrew lee Kee meng Tan Susan Day Christopher levi Stephen m Davis mark Parsons Bernard Yan m.lbourne Brain Centre at Royal m.lbourne Hospital ParkvilleVictoriaAustralia University of New South Wales South Western Sydney Clinical School LiverpoolNew South WalesAustralia Department of Neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of Neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of Neurology Northern Hospital EppingEppingVictoriaAustralia Department of Neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The University of Queensland School of medicine HerstonQueenslandAustralia Neurosciences Clinical Institute Epworth HealthcareRichmondVirginiaAustralia Department of Neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders University College of medicine and Public Health AdelaideSouth AustraliaAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia The University of Sydney Northern Clinical School St LeonardsNew South WalesAustralia Department of Neurology and Neurophysiology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optim.l time to commence anticoagulation in patients with atrial fibrillation(AF)after ischaemic stroke or transient ischaemic attack(TIA)is unclear,with guidelines differing in recommendations.A limitation of previous studies is the focus on clinically overt stroke,rather than radiologically obvious diffusion-weighted imaging ischaemic *** aimed to quantify silent ischaemic lesions and haemorrhages on mRI at 1month in patients commenced on early(late(≥4days)*** hypothesised that there would be fewer ischaemic lesions and more haemorrhages in the early anticoagulant group at 1-month *** A prospective m.lticentre,observational cohort study was performed at 11 Australian stroke *** and mRI data were collected at baseline and follow-up,with blinded imaging assessment performed by two *** of commencement of anticoagulation was at the discretion of the treating stroke *** We recruited 276 patients of whom 208 met the eligibility *** average age was 74.2 years(SD±10.63),and 79(38%)patients were *** National Institute of Health Stroke Scale score was 5(IQR 1–12).median baseline ischaemic lesion volume was 5ml(IQR 2–17).There were a greater number of new ischaemic lesions on follow-up mRI in patients commenced on anticoagulation≥4days after index event(17%vs 8%,p=0.04),but no difference in haemorrhage rates(22%vs 32%,p=0.10).Baseline ischaemic lesion volume of≤5ml was less likely to have a new haemorrhage at 1month(p=0.02).There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of>5ml,regardless of anticoagulation *** Commencing anticoagulationmic lesions at 1month in AF *** is no increased rate of haemorrhage with early *** results suggest that early anticoagulation after m.ld-to-moderate acute ischaemic stroke associated w

关键词： patients lesions ischaemic

Crystallographically vacancy‐induced mOF nanosheet as rational single‐atom support for accelerating CO_(2)electroreduction to CO

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Carbon Energy 2024年第8期6卷 49-62页

作者： Jin Hyuk Cho Joonhee ma Chaehyeon lee Jin Wook lim Youngho Kim Ho Yeon Jang Jaehyun Kim myung‐gi Seo Youngheon Choi Youn Jeong Jang Sang Hyun Ahn Ho Won Jang Seoin Back Jong‐lam.lee Soo Young Kim Department of materials Science and Engineering Korea UniversitySeoulRepublic of Korea Department of Chemical and Biom.lecular Engineering Sogang UniversitySeoulRepublic of Korea Department of materials Science and Engineering Pohang University of Science and Technology(POSTECH)PohangRepublic of Korea Department of materials Science and Engineering Research Institute of Advanced MaterialsSeoul National UniversitySeoulRepublic of Korea lotte Chemical R&D Center DaejeonRepublic of Korea Department of Chemical Engineering Hanyang UniversitySeoulRepublic of Korea School of Chemical Engineering and material Science Chung‐Ang UniversitySeoulRepublic of Korea

To attain a circular carbon economy and resolve CO_(2)electroreduction technology obstacles,single‐atom catalysts(SACs)have emerged as a logical option for electrocatalysis because of their extraordinary catalytic *** SACs,metal–organic frameworks(mOFs)have been recognized as promising support materials because of their exceptional ability to prevent metal *** study shows that atomically dispersed Ni single atoms on a precisely engineered mOF nanosheet display a high Faradaic efficiency of approximately 100%for CO formation in H‐cell and three‐compartment microfluidic flow‐cell reactors and an excellent turnover frequency of 23,699 h−1,validating their intrinsic catalytic *** results suggest that crystallographic variations affect the abundant vacancy sites on the mOF nanosheets,which are linked to the evaporation of Zn‐containing organic linkers during ***,using X‐ray absorption spectroscopy and density functional theory calculations,a comprehensive investigation of the unsaturated atomic coordination environments and the underlying mechanism involving CO^(*)preadsorbed sites as initial states was possible and provided valuable insights.

关键词： 2‐dimensional material carbon dioxide reduction metal-organic frameworks single‐atom catalysts vacancy sites

Comparison between empirical prokinetics, Helicobacter test-and-treat and empirical endoscopy in primary-care patients presenting with dyspepsia: A one-year study

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World Journal of Gastroenterology 2006年第31期12卷 5010-5016页

作者： Wayne HC Hu SK lam Cindy lK lam Wm Wong KF lam KC lai YH Wong Benjamin CY Wong Annie OO chan CK chan Gabriel m.leung Wm Hui Department of medicine University of Hong Kong Hong Kong China Department of Statistics and Actuarial Science University of Hong Kong Hong Kong China Department of Community medicine University of Hong Kong Hong Kong China

AIm： To investigate the optim.l strategy to treat dyspeptic patients in primary care. mETHODS： Dyspeptic patients presenting to primary care outpatient clinics were randomly assigned to- （1） empirical endoscopy, （2） H pylori test-and-treat, and （3） empirical prokinetic treatment with cisapride. Early endoscopy was arranged if patients remained symptomatic after 2 wk. Symptom severity, quality-of-life （SF-36） as well as patient preference and satisfaction were assessed. All patients underwent endoscopy by wk 6. Patients were followed up for one year. RESUlTS： Two hundred and thirty four patients were recruited （163 fem.le, mean age 49）. 46% were H pylori positive. 26% of H pylori tested and 25% of empirical prokinetic patients showed no improvement at wk 2 follow-up and needed early endoscopy. 15% of patients receiving empirical cisapride responded well to treatment but peptic ulcer was the final diagnosis. Symptom resolution and quality-of-life were sim.lar among the groups. Costs for the three strategies were HK$4343, $1771 and $1750 per patient. 66% of the patients preferred to have early endoscopy. CONClUSION： The three strategies are equally effective. Empirical prokinetic treatment was the least expensive but peptic ulcers may be missed with this treatment. The H pylori test-and-treat was the most cost-effective option .

关键词： Empirical endoscopy Dyspeptic patients Hpylori test-and treat

Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

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m.litary medical Research 2024年第2期11卷 206-227页

作者： Guang-Hui Deng Chao-Feng Wu Yun-Jia li Hao Shi Wei-Chao Zhong mu-Keng Hong Jun-Jie li Jia-min Zhao chang liu meng-Chen Qin Zhi-Yun Zeng Wei-min Zhang Ken Kin lam Yung Zhi-Ping lv lei Gao Department of Gastroenterology Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China School of Traditional Chinese medicine Southern Medical UniversityGuangzhou 510515China Department of Hepatology Cancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China Shenzhen Traditional Chinese medicine Hospital Shenzhen 518033GuangdongChina Department of Biology Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SAR 999077China

Background:Nonalcoholic fatty liver disease(NAFlD)is associated with disordered lipid and iron *** previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the *** study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in ***:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this ***-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in ***,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFlD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload ***,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and *** related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and ***:Significant disorder of lipid and iron metabolism occurred in *** expression of Cav-1 was decreased in NAFlD hepatocytes(Pmpanied by iron metabolism ***-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFlD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the ***,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accum.lation in the liver,which was contrary to the effect of Cav-1 in *** correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFlD patients and healthy volunteers(Plusions:These findings confirm that Cav-1 is an essential target protein that reg

关键词： Caveolin-1 Nonalcoholic fatty liver disease Iron metabolism Ferritin Oxidative stress