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Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： Hui Yu Aliya Tiemuer Xufeng Yao Mingyuan Zuo hai-Yan Wang Yi Liu Xiaoyuan Chen Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical Engineering Southeast UniversityNanjing 211189China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine Translational Research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer treatment.However,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas therapy.In this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine scaffold.Under the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation energy.We also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target mitochondria.Under an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL imaging.Collectively,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo

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Transverse mode-coupling instability with longitudinal impedance

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Nuclear Science and Techniques 2024年第6期35卷 40-53页

作者： hai-Sheng Xu Chun-Tao Lin Na Wang Jing-Ye Xu Yuan Zhang Key Laboratory of Particle Acceleration Physics and Technology Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of Chinese Academy of Sciences Beijing 100049China Institute of Advanced Science Facilities Shenzhen 518107GuangdongChina

Transverse mode-coupling instability(TMCI)is a dangerous transverse single-bunch instability that can lead to severe par-ticle loss.The mechanism of TMCI can be explained by the coupling of transverse coherent oscillation modes owing to the transverse short-range wakefield(i.e.,the transverse broadband impedance).Recent studies on future circular colliders,e.g.,FCC-ee,showed that the threshold of TMCI decreased significantly when both longitudinal and transverse impedances were included.We performed computations for the circular electron-positron collider(CEPC)and observed a similar phenom-enon.Systematic studies on the influence of longitudinal impedance on the TMCI threshold were conducted.We concluded that the imaginary part of the longitudinal impedance,which caused a reduction in the incoherent synchrotron tune,was the primary reason for the reduction in the TMCI threshold.Additionally,the real part of the longitudinal impedance assists in increasing the TMCI threshold.

关键词： Transverse mode-coupling instability Longitudinal impedance

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Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2079-2085页

作者： hai-Yan Huang Kun-Peng Bu Jin-Wei Liu Jing Wei Department of Comprehensive Internal Medicine The Affiliated Cancer Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Doppler Ultrasound The Second Nanning People's HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Infections by non-tuberculous mycobacteria(NTM)have become more common in recent years.Mycobacterium canariasense(M.canariasense)was first reported as an opportunistic pathogen in 2004,but there have been very few case reports since then.Nocardia is a genus of aerobic and Gram-positive bacilli,and these species are also opportunistic pathogens and in the Mycobacteriales order.Conventional methods for diagnosis of NTM are inefficient.Metagenomic next-generation sequencing(mNGS)can rapidly detect many pathogenic microorganisms,even rare species.Most NTM and Nocardia infections occur in immunocompromised patients with atypical clinical symptoms.There are no previous reports of infection by M.canariasense and Nocardia farcinica(N.farcinica),especially in immunocompetent patients.This case report describes an immunocompetent 52-year-old woman who had overlapping infections of M.canariasense,N.farcinica,and Candida parapsilosis(C.parapsilosis)based on mNGS.CASE SUMMARY A 52-year-old woman presented with a productive cough and chest pain for 2 wk,and recurrent episodes of moderate-grade fever for 1 wk.She received antibiotics for 1 wk at a local hospital,and experienced defervescence,but the productive cough and chest pain persisted.We collected samples of a lung lesion and alveolar lavage fluid for mNGS.The lung tissue was positive for M.canariasense,N.farcinica,and C.parapsilosis,and the alveolar lavage fluid was positive for M.canariasense.The diagnosis was pneumonia,and application of appropriate antibiotic therapy cured the patient.CONCLUSION Etiological diagnosis is critical for patients with infectious diseases.mNGS can identify rare and novel pathogens,and does not require a priori knowledge.

关键词： Overlapping infection Mycobacterium canariasense Nocardia farcinica Metagenomic next-generation sequencing technology Case report

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Distributed Matching Theory-Based Task Re-Allocating for Heterogeneous Multi-UAV Edge Computing

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China Communications 2024年第1期21卷 260-278页

作者： Yangang Wang Xianglin Wei hai Wang Yongyang Hu Kuang Zhao Jianhua Fan College of Communications Engineering Army Engineering University of PLANanjing 210007China The Sixty-Third Research Institute National University of Defense TechnologyNanjing 210007China

Many efforts have been devoted to efficient task scheduling in Multi-Unmanned Aerial Vehicle(UAV)edge computing.However,the heterogeneity of UAV computation resource,and the task re-allocating between UAVs have not been fully considered yet.Moreover,most existing works neglect the fact that a task can only be executed on the UAV equipped with its desired service function(SF).In this backdrop,this paper formulates the task scheduling problem as a multi-objective task scheduling problem,which aims at maximizing the task execution success ratio while minimizing the average weighted sum of all tasks’completion time and energy consumption.Optimizing three coupled goals in a realtime manner with the dynamic arrival of tasks hinders us from adopting existing methods,like machine learning-based solutions that require a long training time and tremendous pre-knowledge about the task arrival process,or heuristic-based ones that usually incur a long decision-making time.To tackle this problem in a distributed manner,we establish a matching theory framework,in which three conflicting goals are treated as the preferences of tasks,SFs and UAVs.Then,a Distributed Matching Theory-based Re-allocating(DiMaToRe)algorithm is put forward.We formally proved that a stable matching can be achieved by our proposal.Extensive simulation results show that Di Ma To Re algorithm outperforms benchmark algorithms under diverse parameter settings and has good robustness.

关键词： edge computing heterogeneity matching theory service function unmanned aerial vehicle

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Human influence on the duration of extreme temperature events in Asia's hotspot regions

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Advances in Climate Change Research 2024年第2期15卷 312-326页

作者： Zi-Meng WANG Hong-Yun MA Wei LI hai-Shan CHEN Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters(CIC-FEMD)/Key Laboratory of Meteorological Disaster Ministry of Education(KLME)Nanjing University of Information Science and TechnologyNanjing 210044China

Observations and models indicate that human activities exert a considerable impact on the frequency and intensity of extreme temperature events,which are associated with global warming.However,changes in the duration of extreme temperature events and their association with human influence have not been considered in most studies.Thus,the possible relationship between the observed changes in the warm and cold spell duration(WSDI and CSDI)in hotspot regions during 1960-2014 and human influence was investigated based on the NCEP/NCAR reanalysis version 1 and Coupled Model Inter-comparison Project Phase 6(CMIP6)data.Constraint projection based on these attribution results was also performed.The optimal fingerprinting technique was used to compare observed changes in WSDI and CSDI to simulated changes averaged across eight CMIP6 models.Results show that anthropogenic(ANT)forcing contributed to the observed increase in WSDI in the three hotspot regions(West Asia,South Asia and Southeast Asia),with the majority of the changes being attributed to greenhouse gas forcing.However,a generally weak ANT signal can be observed in the decreasing trend of CSDI and can be detected in South and Southeast Asia.The influence of aerosol forcing remains undetected in either WSDI or CSDI,which differs from the results for frequency and intensity of extreme temperatures.The attribution results revealed that the constrained projection of WSDI is lower than the raw projection for 2015-2100 in West Asia and Southeast Asia.However,no differences in future CSDI changes are found in Southeast Asia between the constrained and raw projections.

关键词： Extreme temperature events Duration Detection attribution Constraint projection Hotspot regions

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Effect of the extrahepatic bile duct anatomy on choledocholithiasis and its clinical significance

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1363-1370页

作者： Zheng Cao Jia Zhou Li Wei hai-Yu He Jun Li Department of Gastroenterology The Second Affiliated Hospital of Kunming Medical UniversityKunming 650000Yunnan ProvinceChina

BACKGROUND A comprehensive understanding of the extrahepatic bile duct anatomy is vital to guide surgical procedures and perform endoscopic retrograde cholangiography.Anatomical irregularities within the extrahepatic bile duct may increase susceptibility to bile duct stones.AIM To investigate the anatomical risk factors associated with extrahepatic bile ducts in patients diagnosed with choledocholithiasis,with a specific focus on preventing stone recurrence after surgical intervention and endoscopic lithotomy.METHODS We retrospectively analyzed the medical records of 124 patients without choledocholithiasis and 108 with confirmed choledocholithiasis who underwent magnetic resonance cholangiopancreatography examinations at our center between January 2022 and October 2022.Logistic regression analyses were conducted to identify the anatomical risk factors influencing the incidence of common bile duct stones.RESULTS Multivariate logistic regression analysis revealed that several factors independently contributed to choledocholithiasis risk.Significant independent risk factors for choledocholithiasis were diameter of the common hepatic[adjusted odds ratio(aOR)=1.43,95%confidence interval(CI):1.07-1.92,adjusted P value=0.016]and common bile(aOR=1.68,95%CI:1.27-2.23,adjusted P value<0.001)ducts,length of the common hepatic duct(aOR=0.92,95%CI:0.84-0.99,adjusted P value=0.034),and angle of the common bile duct(aOR=0.92,95%CI:0.89–0.95,adjusted P value<0.001).The anatomical features of the extrahepatic bile duct were directly associated with choledocholithiasis risk.Key risk factors include an enlarged diameter of the common hepatic and bile ducts,a shorter length of the common hepatic duct,and a reduced angle of the common bile duct.

关键词： Bile ducts Extrahepatic Choledocholithiasis Cholangiopancreatography Magnetic resonance Cholangiopancreatography Endoscopic retrograde

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Current and Potential Roles of Ferroptosis in Bladder Cancer

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Current Medical Science 2024年第1期44卷 51-63页

作者： Wen-xin AN Radheshyam Gupta Kun Zhai Ya-ru WANG Wan-hai XU Yan CUI Department of Urology Harbin Medical University Cancer HospitalHarbin 150081China Department of Internal Medical Oncology Harbin Medical University Cancer HospitalHarbin 150081China

Ferroptosis,a type of regulated cell death driven by iron-dependent lipid peroxidation,is mainly initiated by extramitochondrial lipid peroxidation due to the accumulation of iron-dependent reactive oxygen species.Ferroptosis is a prevalent and primitive form of cell death.Numerous cellular metabolic processes regulate ferroptosis,including redox homeostasis,iron regulation,mitochondrial activity,amino acid metabolism,lipid metabolism,and various disease-related signaling pathways.Ferroptosis plays a pivotal role in cancer therapy,particularly in the eradication of aggressive malignancies resistant to conventional treatments.Multiple studies have explored the connection between ferroptosis and bladder cancer,focusing on its incidence and treatment outcomes.Several biomolecules and tumor-associated signaling pathways,such as p53,heat shock protein 1,nuclear receptor coactivator 4,RAS-RAF-MEK,phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin,and the Hippo-tafazzin signaling system,exert a moderating influence on ferroptosis in bladder cancer.Ferroptosis inducers,including erastin,artemisinin,conjugated polymer nanoparticles,and quinazolinyl-arylurea derivatives,hold promise for enhancing the effectiveness of conventional anticancer medications in bladder cancer treatment.Combining conventional therapeutic drugs and treatment methods related to ferroptosis offers a promising approach for the treatment of bladder cancer.In this review,we analyze the research on ferroptosis to augment the efficacy of bladder cancer treatment.

关键词： ferroptosis bladder cancer ferroptosis-associated tumor signaling pathway ferroptosis inducer

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Supermassive black holes triggered by QCD axion bubbles

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Communications in Theoretical Physics 2024年第5期76卷 134-139页

作者： hai-Jun Li Ying-Quan Peng Wei Chao Yu-Feng Zhou Key Laboratory of Theoretical Physics Institute of Theoretical PhysicsChinese Academy of SciencesBeijing 100190China Center for Advanced Quantum Studies Department of PhysicsBeijing Normal UniversityBeijing 100875China School of Physical Sciences University of Chinese Academy of SciencesBeijing 100049China School of Fundamental Physics and Mathematical Sciences Hangzhou Institute for Advanced StudyUCASHangzhou 310024China International Centre for Theoretical Physics Asia-Pacific Beijing/HangzhouChina

Supermassive black holes(SMBHs)are ubiquitous in the center of galaxies,although the origin of their massive seeds is still unknown.In this paper,we investigate the formation of SMBHs from the quantum chromodynamics(QCD)axion bubbles.In this case,primordial black holes(PBHs)are considered as the seeds of SMBHs,which are generated from the QCD axion bubbles due to an explicit Peccei–Quinn(PQ)symmetry breaking after inflation.The QCD axion bubbles are formed when the QCD axion starts to oscillate during the QCD phase transition.We consider a general case in which the axion bubbles are formed with the bubble effective angle θ_(eff)∈(0,π],leading to the minimum PBH mass∼■(10^(4)−10^(7))M⊙for the axion decay constant f_(a)∼■(10^(16))GeV.The PBHs at this mass region may account for the seeds of SMBHs.

关键词： supermassive black holes primordial black holes quantum chromodynamics axion

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Precise control of page cache for containers

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Frontiers of Computer Science 2024年第2期18卷 17-30页

作者： Kun WANG Song WU Shengbang LI Zhuo HUANG Hao FAN Chen YU hai JIN National Engineering Research Center for Big Data Technology and System Services Computing Technology and System LabCluster and Grid Computing Lab School of Computer Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China

Container-based virtualization isbecoming increasingly popular in cloud computing due to its efficiency and flexibility.Resource isolation is a fundamental property of containers.Existing works have indicated weak resource isolation could cause significant performance degradation for containerized applications and enhanced resource isolation.However,current studies have almost not discussed the isolation problems of page cache which is a key resource for containers.Containers leverage memory cgroup to control page cache usage.Unfortunately,existing policy introduces two major problems in a container-based environment.First,containers can utilize more memory than limited by their cgroup,effectively breaking memory isolation.Second,the Os kernel has to evict page cache to make space for newly-arrived memory requests,slowing down containerized applications.This paper performs an empirical study of these problems and demonstrates the performance impacts on containerized applications.Then we propose pCache(precise control of page cache)to address the problems by dividing page cache into private and shared and controlling both kinds of page cache separately and precisely.To do so,pCache leverages two new technologies:fair account(f-account)and evict on demand(EoD).F-account splits the shared page cache charging based on per-container share to prevent containers from using memory for free,enhancing memory isolation.And EoD reduces unnecessary page cache evictions to avoid the performance impacts.The evaluation results demonstrate that our system can effectively enhance memory isolation for containers and achieve substantial performance improvement over the original page cache management policy.

关键词： page cache memory cgroup container isolation cloud computing

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Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

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Current Medical Science 2024年第2期44卷 355-368页

作者： Shao-ze JING Shu-han YANG Yun-kun QU hai-hu HAO Hua WU Department of Orthopedics Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032China Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation.This study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata D.Don,in rats.Methods:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1βgroup,IL-1β+SCU 50µmol/L group,and IL-1β+SCU 100µmol/L group.Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining.CCK-8 method was used to detect the cytotoxicity of SCU.ELISA,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1βintervention.Additionally,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA model.Histological changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and immunohistochemistry.Results:SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms.Specifically,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation.In addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint cartilage.Furthermore,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA treatment.In vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in cartilage.Conclusion:SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.

关键词： scutellarein osteoarthritis apoptosis mitogen-activated protein kinase(MAPK) nuclear factor kappa-B(NF-κB)

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