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treatment of uveitis and scleritis patients in Malaysia

International Journal of Ophthalmology(English edition) 2024年第3期17卷 518-527页

作者： Sieng teng Seow Iqbal tajunisah Fei Yee Lee Pooi wah Lott Sagili Chandrasekhara Reddy Department of Ophthalmology University Malaya Eye Research Centre(UMERC)Faculty of MedicineUniversiti MalayaKuala Lumpur 59100Malaysia Clinical Research Centre Selayang HospitalMinistry of Health MalaysiaSelangor 68100Malaysia Department of Ophthalmology Faculty of Medicine and Defence HealthNational Defence University of MalaysiaKuala Lumpur 57000Malaysia

●AIM:to determine the common causes and visual outcome after treatment among uveitis and scleritis patients.●MEtHODS:this is a retrospective cohort observational *** consecutive clinical records of patients with newly diagnosed uveitis and scleritis over a 4-year period,from Jan.1,2017 to Dec.31,2020,were *** was collected at the presentation and included a follow-up period of one year.●RESULtS:A total of 288 patients were recruited during the study *** uveitis was the most common anatomical diagnosis(50.0%)followed by panuveitis(25.0%),scleritis(13.5%),posterior uveitis(6.9%),and intermediate uveitis(4.5%).Viral Herpes was the most common cause of infectious cases,while Vogt-Koyanagi-Harada(VKH)disease and human leucocyte antigen(HLA)b27 spondyloarthropathy were the leading causes of identifiable non-infectious *** of patients presented with unilateral,non-granulomatous uveitis with an absence of *** locations like posterior uveitis and panuveitis,and visual acuity worse than 3/60 at presentation were the factors associated with poor visual outcomes(Pbout 60%of patients had an identifiable cause for the uveitis and scleritis,with nearly equal distribution of infectious(n=85,29.5%)and noninfectious causes(n=84,29.2%).About 14.5%of patients were clinically blind at 1y of *** most common complication in our uveitis patients was glaucoma(47.5%),followed by cystoid macula oedema(18.9%)and cataract(13.9%).●CONCLUSION:Uveitis and scleritis are important causes of ocular *** are potentially blinding diseases which can have a good outcome if diagnosed and treated early.

关键词： uveitis scleritis ocular morbidity blindness aetiology

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Luteolin， a common flavone in vegetables， acts as a hormetin possessing neurotrophic function: signaling mediated by inducing mitochondrial stress

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Food Science and Human Wellness 2024年

作者： Alex Xiong Gao tracy Chenxi Xia Maggie Suisui Guo Gary Kawing Yuen Kevin Qiyun Wu tina tingxia Dong Karl wah-Keung tsim Shenzhen Key Laboratory of Edible and Medicinal bioresources HKUSt Shenzhen Research Institute Division of Life Science and Center for Chinese Medicine the Hong Kong University of Science and technology

this study aims to uncover the hormetic process of luteolin， a common dietary flavone， in neuronal cells through its role in inducing mitochondrial stress. In rat pheochromocytoma PC12 cells， luteolin at low concentrations caused a mild and reversible loss of mitochondrial membrane potential (MMP)， while high concentrations of luteolin triggered intense and sustained depolarization of MMP. the MMP disturbance was shown to have a close association with the trophic and/or toxic effects triggered by luteolin; because the common mitochondrial uncouplers shared similar bi-phase dose-response on cell viability， as that of luteolin. Along with the induced MMP pertubation， luteolin triggered the development of autophagy and mitophagy， as determined by mCherry-GFP-LC3b tandem protein， and by the co-localization of mitochondrial/lysosomal staining. Subsequent application of autophagy inhibitors in the cultures blocked the luteolin-induced neurotrophic activities and sensitized the cells to be less resistant to luteolin-mediated cytotoxicity. Other flavonoids also displayed similar properties in the cultures， indicating that these compounds act as hormetic pharmacological inducers that stimulate cells to become more resilient and adapt to threats. this study provides a unifying mechanistic explanation for the neuro-beneficial effects of luteolin and other flavonoids.

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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 *** is a major pathophysiology in *** 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 *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,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,*** simulation and bioLayer interferometry were used to confirm their binding *** 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)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,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

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Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica b 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin wah to Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell biology&Institute of biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor t-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity tumor immune microenvironment

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Radiative capture of proton through the ^(14)N(p,γ)^(15)O reaction at low energy

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Chinese Physics C 2024年第4期48卷 183-192页

作者： b.F.Irgaziev abdul Kabir Jameel-Un Nabi National University of Uzbekistan Tashkent 100174Uzbekistan Space and Astrophysics Research lab National Centre of GIS and Space ApplicationsDepartment of Space ScienceInstitute of Space TechnologyIslamabad 44000Pakistan University of wah Quaid AvenueWah Cantt 47040PunjabPakistan

the CNO cycle is the main source of energy in stars more massive than our *** process defines the energy production,the duration of which can be used to determine the lifetime of massive *** cycle is an important tool for determining the age of globular *** proton capture via p+^(14)N→^(15)O+γ,at energies of astrophysical interest,is an important process in the CNO *** this project,we apply a potential model to describe both non-resonant and resonant reactions in the channels where radiative capture occurs through electric E1 *** employed the R-matrix method to describe the ongoing reactions via M1 resonant transitions,when it was not possible to correctly reproduce the experimental data using the potential *** partial components of the astrophysical S-factor are calculated for all possible electric and magnetic dipole transitions in ^(15)*** linear extrapolated S-factor at zero energy(S(0))agrees well with earlier reported values for all transition types considered in this *** on the value of the total astrophysical S-factor,depending on the collision energy,we calculate the nuclear reaction rates for p+^(14)N→^(15)O+γ.the computed rates agree well with the results reported in the NACRE II Collaboration and most recent existing measurements.

关键词： CNO cycle potential model R-matrix method cross-section astrophysical S-factor nuclear rates.

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基于电子鼻和气质联用技术分析德庄火锅底料在煮制过程中挥发性物质变化

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食品工业科技 2024年

作者：何莲易宇文徐向波乔明锋裴红燕贾洪锋王钵 Chan Sook wah 杨翠邓静 School of biosciences Faculty of Health and Medical Sciences taylor’s University(Malaysia) 四川旅游学院食品学院西南大学食品科学学院四川旅游学院烹饪学院四川旅游学院烹饪科学四川省高等学校重点实验室

为探究0min（A），30min（b）、60min（C）和90min（D）不同煮制时间的德庄火锅底料挥发性物质的变化，试验以德庄火锅底料在煮制过程中挥发性物质为研究对象，采用电子鼻、捕集阱顶空-气质联用仪（trap head space -gas chromatography... 详细信息

为探究0min（A），30min（b）、60min（C）和90min（D）不同煮制时间的德庄火锅底料挥发性物质的变化，试验以德庄火锅底料在煮制过程中挥发性物质为研究对象，采用电子鼻、捕集阱顶空-气质联用仪（trap head space -gas chromatography-mass spectrometry，HS- trap-GC-MS）结合雷达图、主成分分析、气味活度值（odor activity value，OAV）和正交偏最小二乘法判别分析（orthogonal partial least squares discriminant analysis，OPLS-DA）探究不同煮制时间的德庄火锅底料气味变化规律。电子鼻检测结果表明，不同煮制时间的火锅底料的整体气味轮廓差异明显；GC-MS分析显示4个样品共检测到87种挥发性物质，烯烃、醇类和醚类物质是不同煮制时间的火锅底料的主要挥发性物质；OAV分析显示芳樟醇和茴香脑是不同煮制时间的共有关键挥发性物质。2-茨醇、二氢香芹醇、丙酮、二烯丙基二硫、丙酸异戊酯、α-松油醇、 (1S)-(+)-3-蒈烯、(E)- β-罗勒烯、P-伞花烃、丙酸乙酯、正戊烯、对二甲苯是导致样品差异的特征物质。煮制时间对德庄火锅底料的挥发性物质组成和气味特性有显著影响。研究结果可为火锅底料的研发、品控及指导消费提供参考。

关键词：火锅底料煮制时间电子鼻气相色谱质谱联用仪香气活性值正交偏最小二乘判别分析

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A Hybrid Model for Improving Software Cost Estimation in Global Software Development

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Computers, Materials & Continua 2024年第1期78卷 1399-1422页

作者： Mehmood Ahmed Noraini b.Ibrahim Wasif Nisar Adeel Ahmed Muhammad Junaid Emmanuel Soriano Flores Divya Anand Faculty of Computer Science and Information technology Universiti Tun Hussein Onn Malaysia Parit RajaBatu Pahat86400Malaysia Department of Computer Science COMSATS University Wah Cantt CampusIslamabad47010Pakistan Department of Information technology The University of HaripurKhyber Pakhtunkhwa22620Pakistan Engineering Research Innovation Group Universidad Europea del AtlanticoSantander39011Spain

Accurate software cost estimation in Global Software Development(GSD)remains challenging due to reliance on historical data and expert *** models,such as the Constructive Cost Model(COCOMO II),rely heavily on historical and accurate *** addition,expert judgment is required to set many input parameters,which can introduce subjectivity and variability in the estimation ***,there is a need to improve the current GSD models to mitigate reliance on historical data,subjectivity in expert judgment,inadequate consideration of GSD-based cost drivers and limited integration of modern technologies with cost *** study introduces a novel hybrid model that synergizes the COCOMO II with Artificial Neural Networks(ANN)to address these *** proposed hybrid model integrates additional GSD-based cost drivers identified through a systematic literature review and further vetted by industry *** article compares the effectiveness of the proposedmodelwith state-of-the-artmachine learning-basedmodels for software cost *** the NASA 93 dataset by adopting twenty-six GSD-based cost drivers reveals that our hybrid model achieves superior accuracy,outperforming existing *** findings indicate the potential of combining COCOMO II,ANN,and additional GSD-based cost drivers to transform cost estimation in GSD.

关键词： Artificial neural networks COCOMO II cost drivers global software development linear regression software cost estimation

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Revealing effect of aluminum alloying on work hardening and impact behaviors of low-density Fe-18Mn-1.3C-2Cr-(4,11)Al casting steel

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China Foundry 2022年第4期19卷 359-368页

作者： Zhi-bin Zheng Hao-kun Yang A.P.Shatrava Wai-wah Lai Jun Long Kai-hong Zheng Institute of New Materials Guangdong Academy of SciencesGuangdong Provincial Key Laboratory of Metal Toughening Technology and ApplicationGuangzhou 510650China Smart Manufacturing Division Hong Kong Productivity CouncilHong Kong 999077China Physicotechnological Institute of Metals and Alloys National Academy of SciencesKiev 03142Ukraine National Engineering Research Center of Powder Metallurgy of titanium&Rare Metals Guangdong Provincial Iron Matrix Composite Engineering Research CenterGuangzhou 510650China

the present study designed two kinds of Fe-18Mn-1.3C-2Cr-(4,11)Al(wt.%)low-density *** and impact tests were carried out to evaluate the work hardening and impact toughness properties via aluminum(Al)alloying ***,microstructure evolution and fracture morphology were investigated by X-ray diffraction(XRD),a scanning electron microscope(SEM)equipped with electron backscatter diffraction(EbSD),a transmission electron microscope(tEM),and a stereo-optical microscope(OM).It is found that the Al addition obviously promotes the dislocation planar slipping,resulting in cleavage and brittle impact fracture in 11wt.%Al ***,the microband-induced plasticity(MbIP)mechanism is found in 4wt.%Al containing steel,introducing considerable work hardening capacity and impact toughness of 156.8±17.4 *** present study provides a direct illustration of the relationship between work hardening and impact toughness behaviors of these two low-density steels for potential application as impact-resistant components.

关键词： casting steel aluminum work hardening impact toughness tensile fractography impact fractography

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Rational design of platinum(Ⅱ)complexes with orthogonally oriented triazolyl ligand with emission enhancement characteristics for cancer chemotherapy in vivo

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Science China Chemistry 2023年第10期66卷 2878-2884页

作者： Yeye Ai Zherui Zhang Yuexuan Fei Ruirong Ye Angela Sin-Yee Law Zong-Wan Mao Junqiu Liu Yongguang Li Vivian Wing-wah Yam Key Laboratory of Organosilicon Chemistry and Material technology of Ministry of Education College of Material Chemistry and Chemical EngineeringHangzhou Normal UniversityHangzhou 311121China Institute of Molecular Functional Materials State Key Laboratory of Synthetic Chemistry and Department of ChemistryThe University of Hong KongHong KongChina School of Chemistry Sun Yat-Sen UniversityGuangzhou 510275China State Key Laboratory of Supramolecular Structure and Materials Jilin UniversityChangchun 130012China

the mitochondria are essential for tumorigenesis and have been regarded as important targets in cancer ***,the mitochondria-targeted platinum(Ⅱ)complexes have been *** introduction of the triazole group with larger steric hindrance through post-click reaction converts the hybridization of carbon from sp to sp^(2),endowing the complexes with an orthogonally oriented ligand with restricted rotation and emission enhancement *** of the triazolyl ligand has led to platinum(Ⅱ)complexes that can efficiently enter cancer cells and selectively accumulate in mitochondria,leading to significant enhancement in *** vivo anti-cancer investigations have demonstrated their distinct antitumor efficacy in substantial inhibition of tumor growth in breast cancer mice through dissipation of mitochondrial membrane potential,inducing apoptosis of tumor cell with negligibly systemic cytotoxicity.

关键词： platinum(Ⅱ)complexes post-click reaction emission enhancement mitochondria-targeting antitumor

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the host-targeting compound peruvoside has a broad-spectrum antiviral activity against positive-sense RNA viruses

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Acta Pharmaceutica Sinica b 2023年第5期13卷 2039-2055页

作者： Kan Xing Wu thinesshwary Yogarajah Marcus Wing Choy Loe Parveen Kaur Regina Ching Hua Lee Chee Keng Mok Yi Hao Wong Patchara Phuektes Li Sze Yeo Vincent t.K.Chow Yong wah tan Justin Jang Hann Chu Department of Microbiology and Immunology Yong Loo Lin School of MedicineNational University Health SystemNational University of SingaporeSingapore 117597Singapore Department of Pathobiology Faculty of Veterinary MedicineKhonkaen UniversityKhonkaen 40002Thailand Infectious Disease Programme Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell biology Agency for ScienceTechnology and Research(A∗STAR)Singapore 138648Singapore Lee Kong Chian School of Medicine Nanyang Technological UniversitySingapore 308232Singapore NUSMed biosafety Level 3 Core Facility Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore

Positive-sense RNA viruses modify intracellular calcium stores,endoplasmic reticulum and Golgi apparatus(Golgi)to generate membranous replication organelles known as viral *** factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in ***,we identified the vital role of a broadspectrum antiviral,peruvoside in limiting the formation of viral ***,we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1(GbF1)phosphorylation and Golgi vesiculation by peruvoside *** ramification of GbF1 phosphorylation fosters GbF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories *** investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GbF1 phosphorylation at threonine 1337(t1337).We also showed 100%of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in *** findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside,host-directed antivirals for positive-sense RNA virus-mediated disease,in the interim where no vaccine is available.

关键词： Positive-sense RNA viruses Peruvoside Antiviral CDKI signaling Viral factories Calcium efflux broad-spectrum Golgi apparatus

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