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Metal nanoparticles for cancer therapy:Precision targeting of DNA damage

Acta Pharmaceutica Sinica B 2024年第3期14卷 1132-1149页

作者： Qian Chen Chunyan fang fan Xia Qiyue Wang fangyuan Li Daishun ling Institute of Pharmaceutics Hangzhou Institute of Innovative MedicineCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Frontiers Science Center for Transformative Molecules School of Chemistry and Chemical EngineeringNational Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China World Laureates Association(WLA)Laboratories Shanghai 201203China Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province Hangzhou 310009China

Cancer,a complex and heterogeneous disease,arises from genomic instability.Currently,DNA damage-based cancer treatments,including radiotherapy and chemotherapy,are employed in clinical practice.However,the efficacy and safety of these therapies are constrained by various factors,limiting their ability to meet current clinical demands.Metal nanoparticles present promising avenues for enhancing each critical aspect of DNA damage-based cancer therapy.Their customizable physicochemical properties enable the development of targeted and personalized treatment platforms.In this review,we delve into the design principles and optimization strategies of metal nanoparticles.We shed light on the limitations of DNA damage-based therapy while highlighting the diverse strategies made possible by metal nanoparticles.These encompass targeted drug delivery,inhibition of DNA repair mechanisms,induction of cell death,and the cascading immune response.Moreover,we explore the pivotal role of physicochemical factors such as nanoparticle size,stimuli-responsiveness,and surface modification in shaping metal nanoparticle platforms.Finally,we present insights into the challenges and future directions of metal nanoparticles in advancing DNA damage-based cancer therapy,paving the way for novel treatment paradigms.

关键词： DNA damage Metal nanoparticles Nucleus-targeting DNA repair inhibition Immune response Size optimization Stimuli-responsiveness Surface modification

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Improving photochemical indicators for attributing ozone sensitivities in source apportionment analysis

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Journal of Environmental Sciences 2024年第9期143卷 235-246页

作者： Xiaohui Du Wei Tang Zhongzhi Zhang Yang Yu Yang Li ling Huang Greg Yarwood fan Meng Atmospheric Environment Institute Chinese Research Academy of Environmental SciencesBeijing 100012China College of Water Sciences Beijing Normal UniversityBeijing 100857China Asia Center for Air Pollution Research United Nations Environment Programme Asia and the Pacific OfficeNishi-kuNiigata-shi 9502144Japan School of Environmental and Chemical Engineering Shanghai UniversityShanghai 200444China Ramboll NovatoCalifornia 94945USA

Comprehensive Air Quality Model with extensions(CAMx)-Decoupled Direct Method(DDM)simulations of first-order ozone(O_(3))sensitivity to nitrogen oxides(NO_(x))and volatile organic compounds(VOCs)emissions were performed and combined with modelled P_(H_(2)O_(2))/P_(HNO_(3))ratios to obtain a range of thresholds for determining O_(3)-sensitivity regimes for different areas of China.Utilising the new threshold ranges for photochemical indicators,the method for determining O_(3)formation in the Ozone Source Apportionment Technology(OSAT)module within CAMx was improved by a dynamically varied threshold of P_(H_(2)O_(2))/P_(HNO_(3))ratio.The O_(3)concentration contributions in the newly added transition regime were apportioned to NO_(x)and VOCs emissions in proportion to the relationship between the P_(H_(2)O_(2))/P_(HNO_(3))ratio and first-order O_(3)sensitivity.The source contributions of O_(3)concentrations from different emission sectors from June to September 2019 were compared using the original and improved CAMx-OSAT.The results showed that the O_(3)concentration contributions changed significantly in the NO_(x)-limited regime,with a maximum decrease of 21.89%,while the contributions increased by up to 7.57%in the VOC-limited regime,and were within 15μg/m^(3)in the transition regime.The modified OSAT module enabled a more sophisticated attribution of O_(3)to precursor emissions and may have far-reaching implications for informing O_(3)pollution control policy.

关键词： O_(3) modeling O_(3)-sensitivity regimes Ozone source apportionment technology Photochemical indicators

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Small tracking error correction for moving targets of intelligent electro-optical detection systems

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Frontiers of Mechanical Engineering 2024年第2期19卷 29-44页

作者： Cheng SHEN Zhijie WEN Wenliang ZHU Dapeng fan Mingyuan ling College of Intelligence Science and Technology National University of Defense TechnologyChangsha 410073China

Small tracking error correction for electro-optical systems is essential to improve the tracking precision of future mechanical and defense technology.Aerial threats,such as“low,slow,and small(LSS)”moving targets,pose increasing challenges to society.The core goal of this work is to address the issues,such as small tracking error correction and aiming control,of electro-optical detection systems by using mechatronics drive modeling,composite velocity–image stability control,and improved interpolation filter design.A tracking controller delay prediction method for moving targets is proposed based on the Euler transformation model of a two-axis,two-gimbal cantilever beam coaxial configuration.Small tracking error formation is analyzed in detail to reveal the scientific mechanism of composite control between the tracking controller’s feedback and the motor’s velocity–stability loop.An improved segmental interpolation filtering algorithm is established by combining line of sight(LOS)position correction and multivariable typical tracking fault diagnosis.Then,a platform with 2 degrees of freedom is used to test the system.An LSS moving target shooting object with a tracking distance of S=100 m,target board area of A=1 m^(2),and target linear velocity of v=5 m/s is simulated.Results show that the optimal method’s distribution probability of the tracking error in a circle with a radius of 1 mrad is 66.7%,and that of the traditional method is 41.6%.Compared with the LOS shooting accuracy of the traditional method,the LOS shooting accuracy of the optimized method is improved by 37.6%.

关键词： electro-optical detection system small tracking error moving target visual servo aiming contro

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Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 257-264页

作者： Min-Shu Wang Xue-Chuan Dong Mi-Yun Zheng Xiang fan Ge-Ge Xiao Jing Hong ling-ling Wu Department of Ophthalmology Peking University Third HospitalBeijing 100191China Key Laboratory of Restoration of Damaged Ocular Nerve Beijing 100191China NIMO Ophthalmology Research Institute Beijing 100176China Department of Ophthalmology the First Hospital of PutianTeaching HospitalFujian Medical UniversityPutian 351100Fujian ProvinceChina

AIM:To compare the surgical outcomes of glaucoma drainage device implantation(GDI)and trans-scleral neodymium:YAG cyclophotocoagulation(CPC)in the management of refractory glaucoma after Descemetstripping automated endothelial keratoplasty(DSAEK).METHODS:This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery(15 with GDI and 14 with CPC).The main outcome measures were intraocular pressure(IOP),glaucoma surgery success rate(defined as IOP of 6–21 mm Hg without additional anti-glaucoma operation),number of glaucoma medications,endothelial graft status,and best-corrected visual acuity(BCVA).RESULTS:The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries,both for the GDI and CPC groups.Both groups showed significant IOP reduction after glaucoma surgery.The GDI group presented a significantly higher success rate in IOP control than the CPC group(60%vs 21.4%,P=0.03).Both procedures significantly decreased the number of glaucoma medications(P=0.03).Forty percent and 57%of cases in the GDI and the CPC group,respectively,experienced endothelial graft failure during follow-up(P=0.36).Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group.CONCLUSION:Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK.GDI is preferable to CPC in refractory glaucoma cases after DSAEK,as it manifests a significantly higher success rate for IOP control,similar endothelial graft failure rate,and relatively preserves BCVA than CPC.

关键词： glaucoma drainage device implantation cyclophotocoagulation refractory glaucoma Descemetstripping automated endothelial keratoplasty

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METTL5 promotes cell proliferation,invasion,and migration by up-regulating Toll-like receptor 8 expression in colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2006-2017页

作者： ling-Shang Kong Ran Tao Yi-fan Li Wen-Bin Wang Xue Zhao Department of General Surgery The Second Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Vascular Surgery The Second Affiliated Hospital of Anhui Medical UniversityHefei 230002Anhui ProvinceChina Department of General Surgery The First Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina Anhui Public Health Clinical Center Hefei 230012Anhui ProvinceChina Department of Scientific Research Anhui Public Health Clinical CenterHefei 230012Anhui ProvinceChina Department of Scientific Research The First Affiliated Hospital of Anhui Medical UniversityHefei 230001Anhui ProvinceChina

BACKGROUND N6-methyladenosine(m6A)modification represents the predominant alteration found in eukaryotic messenger RNA and plays a crucial role in the progression of various tumors.However,despite its significance,the comprehensive investigation of METTL5,a key m6A methyltransferase,in colorectal cancer(CRC)remains limited.AIM To investigate the role of METTL5 in CRC.METHODS We assessed METTL5 expression levels in clinical samples obtained from CRC patients as well as in CRC cell lines.To elucidate the downstream targets of METTL5,we performed RNA-sequencing analysis coupled with correlation analysis,leading us to identify Toll-like receptor 8(TLR8)as a potential downstream target.In vitro functional assessments of METTL5 and TLR8 were conducted using CCK-8 assays,scratch assays,as well as assays measuring cell migration and invasion.RESULTS Our findings reveal a pronounced upregulation of METTL5 expression in both CRC cells and tissues,which correlated significantly with an unfavorable prognosis.In vitro experiments unequivocally demonstrated the oncogenic role of METTL5,as evidenced by its promotion of CRC cell proliferation,invasion,and migration.Notably,we identified TLR8 as a downstream target of METTL5,and subsequent down-regulation of TLR8 led to a significant inhibition of CRC cell proliferation,invasion,and tumor growth.CONCLUSION The heightened expression of METTL5 in CRC is strongly associated with clinicopathological features and a poor prognosis,thereby underscoring its potential utility as a critical marker for facilitating early diagnosis and prognostication in CRC.

关键词： METTL5 Toll-like receptor 8 Colorectal cancer

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Effect of cytochrome P4502C19(CYP2C19)gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI

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Journal of Geriatric Cardiology 2024年第1期21卷 90-103页

作者： Cheng-Yan HU Yan-ling WANG Zhen-Xing fan Xi-Peng SUN Shuai WANG Zhi LIU Department of Geriatrics Fu Xing HospitalCapital Medical UniversityBeijingChina Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Emergency Department of Xuanwu Hospital Capital Medical UniversityBeijingChina

Objective To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with longterm clinical outcome in patients with coronary heart disease(CHD)undergoing percutaneous coronary intervention(PCI).Methods In total,675 patients were enrolled.Based on the platelet inhibition rate,patients were categorized into two groups:clopidogrel low responsiveness(CLR)and normal clopidogrel responsiveness(NCR).The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment.Patients were classified into three groups(normal metabolizer,intermediate metabolizer,and poor metabolizer)based on the CYP2C19 genotype.We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity.The cumulative rates of 12-month all-cause deaths,major adverse cardiovascular events(MACCEs),and bleeding events were calculated.Results CLR was observed in 44.4%of the overall population.Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes(P0.05).Conclusions Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism.CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI,which is better than either test alone.

关键词： CYP2C19 drugs PCI

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Ferroptosis mechanism and Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1741-1750页

作者： Lina Feng Jingyi Sun ling Xia Qiang Shi Yajun Hou Lili Zhang Mingquan Li Cundong fan Baoliang Sun Shandong Key Laboratory of TCM Multi-Target Intervention and Disease Control the Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina Department of Internal Medicine Taian Traffic HospitalTaianShandong ProvinceChina Department of Neurology the Third Affiliated Clinical Hospital of Changchun University of Chinese MedicineChangchunJilin ProvinceChina

Regulated cell death is a genetically determined form of programmed cell death that commonly occurs during the development of living organisms.This process plays a crucial role in modulating homeostasis and is evolutionarily conserved across a diverse range of living organisms.Ferroptosis is a classic regulatory mode of cell death.Extensive studies of regulatory cell death in Alzheimer’s disease have yielded increasing evidence that fe rroptosis is closely related to the occurrence,development,and prognosis of Alzheimer’s disease.This review summarizes the molecular mechanisms of ferroptosis and recent research advances in the role of ferro ptosis in Alzheimer’s disease.Our findings are expected to serve as a theoretical and experimental foundation for clinical research and targeted therapy for Alzheimer’s disease.

关键词： Alzheimer’s disease apolipoprotein E Fe^(2+) ferroptosis glial cell glutathione peroxidase 4 imbalance in iron homeostasis lipid peroxidation regulated cell death system Xc^(-)

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Ghrelin inhibits autophagy mediated by AKT/mTOR pathway to ameliorate retinal angiogenesis induced by high glucose stress

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 785-793页

作者： Jiang-Li fan Rong Li Min Zhang Chao Chen Guo-Min Yao ling-Xiao Zhou Department of Ophthalmology Gongshu District People’s Hospital of Integrated Traditional Chinese and Western MedicineHangzhou 310004Zhejiang ProvinceChina Department of Ophthalmology the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina Department of Endocrinology the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina Department of General Surgery the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina

AIM:To observe the effect of ghrelin,a growth hormonereleasing peptide,on retinal angiogenesis in vitro under high glucose(HG)stress and to explore the possible mechanism of autophagy.METHODS:Human retinal microvascular endothelial cells(HRMECs)were treated with high concentration of glucose alone or in combination with ghrelin.The cell migration,tube formation and the expression of the autophagy-related proteins LC3-II/I,Beclin-1,p62,phosphorylated AKT(p-AKT)/AKT and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR were detected.Then,to clarify the correlation between ghrelin effect and autophagy,AKT inhibitor VIII was adopted to treat HRMECs,and cell migration,tube formation as well as the protein expressions of LC3-II/I,Beclin-1 and p62 were observed.RESULTS:Under HG stress,ghrelin inhibited migration and tube formation of HRMECs.Ghrelin inhibited the increases in the protein levels of LC3-II/I,Beclin-1 and the decreases in the protein levels of p62,p-AKT/AKT and p-mTOR/mTOR induced by HG stress.Moreover,under the action of AKT/mTOR pathway inhibitors,the effects of ghrelin on migration and tube formation were both reduced.In addition,the expression of LC3-II/I and Beclin-1 were significantly up-regulated and the expression of p62 was down-regulated.CONCLUSION:Retinal angiogenesis under in vitro HG stress can be inhibited by ghrelin through activating AKT/mTOR pathway to inhibit autophagy.

关键词： ghrelin retinal endothelial cell angiogenesis autophagy stress

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Computational and dark-field ghost imaging with ultraviolet light

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Photonics Research 2024年第2期12卷 226-234页

作者： JIAQI SONG BAOLEI LIU YAO WANG CHAOHAO CHEN XUCHEN SHAN XIAOLAN ZHONG ling-AN WU fan WANG School of Physics Beihang UniversityBeijing 102206China Australian Research Council Centre of Excellence for Transformative Meta-Optical Systems Department of Electronic Materials EngineeringResearch School of PhysicsThe Australian National UniversityCanberraACT 2600Australia Institute of Physics Chinese Academy of SciencesBeijing 100190China

Ultraviolet(UV)imaging enables a diverse array of applications,such as material composition analysis,biological fluorescence imaging,and detecting defects in semiconductor manufacturing.However,scientific-grade UV cameras with high quantum efficiency are expensive and include complex thermoelectric cooling systems.Here,we demonstrate a UV computational ghost imaging(UV-CGI)method to provide a cost-effective UV imaging and detection strategy.By applying spatial–temporal illumination patterns and using a 325 nm laser source,a singlepixel detector is enough to reconstruct the images of objects.We use UV-CGI to distinguish four UV-sensitive sunscreen areas with different densities on a sample.Furthermore,we demonstrate dark-field UV-CGI in both transmission and reflection schemes.By only collecting the scattered light from objects,we can detect the edges of pure phase objects and small scratches on a compact disc.Our results showcase a feasible low-cost solution for nondestructive UV imaging and detection.By combining it with other imaging techniques,such as hyperspectral imaging or time-resolved imaging,a compact and versatile UV computational imaging platform may be realized for future applications.

关键词： ghost illumination versatile

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HvMPK4 phosphorylates HvWRKY1 to enhance its suppression of barley immunity to powdery mildew fungus

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Journal of Genetics and Genomics 2024年第3期51卷 313-325页

作者： Pengya Xue ling Zhang Renchun fan Yanan Li Xinyun Han Ting Qi Lifang Zhao Deshui Yu Qian-Hua Shen State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions College of Advanced Agricultural SciencesUniversity of Chinese Academy of SciencesBeijing 100049China Department of Nutritional Sciences&Toxicology University of CaliforniaBerkeleyCA 94720USA Lushan Botanical Garden Chinese Academy of ScienceJiujiangJiangxi 332900China

Mitogen-activated protein kinase(MAPK)cascades play important roles in disease resistance in model plant species.However,the functions of MAPK signaling pathways in crop disease resistance are largely unknown.Here we report the function of HvMKK1-HvMPK4-HvWRKY1 module in barley immune system.HvMPK4 is identified to play a negative role in barley immune response against Bgh,as virus-induced gene silencing of HvMPK4 results in enhanced disease resistance whilst stably overexpressing HvMPK4 leads to super-susceptibility to Bgh infection.Furthermore,the barley MAPK kinase HvMKK1 is found to specifically interact with HvMPK4,and the activated HvMKK1^(DD) variant specifically phosphorylates HvMPK4 in vitro.Moreover,the transcription factor HvWRKY1 is identified to be a downstream target of HvMPK4 and phosphorylated by HvMPK4 in vitro in the presence of HvMKK1^(DD).Phosphorylation assay coupled with mutagenesis analyses identifies S122,T284,and S347 in HvWRKY1 as the major residues phosphorylated by HvMPK4.HvWRKY1 is phosphorylated in barley at the early stages of Bgh infection,which enhances its suppression on barley immunity likely due to enhanced DNA-binding and transcriptional repression activity.Our data suggest that the HvMKK1-HvMPK4 kinase pair acts upstream of HvWRKY1 to negatively regulate barley immunity against powdery mildew.

关键词： Barley MPK4 WRKY1 Phosphorylation Disease resistance Powdery mildew

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