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Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

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Analysis of the Clinical Effect of Chinese Medicine Combined with Acupuncture and Moxibustion on Insomnia

Research and Inheritance of Traditional Chinese Medicine

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Research and Inheritance of Traditional Chinese Medicine 2024年第1期2卷 1-6页

作者： Lizhou He Yanan jiang Ziqi lian College of Pharmacy Shandong University of Traditional Chinese Medicine

Objective:To explore and analyze the clinical efficacy of Chinese medicine combined with acupuncture and moxibustion in the treatment of ***:80 patients with primary insomnia were selected as the study sample,with 20 cases randomly selected as the control group and the rest as the observation *** control group was treated with ordinary western medicine,while the observation group patients were treated with traditional Chinese medicine combined with acupuncture and moxibustion based on this syndrome *** comparison items were treatment effect,sleep quality,mental health,quality of life,specific sleep indicators,cerebral blood flow and ***:The treatment effectiveness showed that the observation group had a higher treatment effectiveness rate than the control group(P<0.05);The results of sleep quality showed that after treatment,the scores of the observation group were lower than those of the control group in seven dimensions:sleep quality,sleep time,sleep onset time,sleep efficiency,sleep disorders,hypnotic drugs,and daytime dysfunc‐tion score(P<0.05);The quality of life results showed that after treatment,the observa‐tion group had higher scores than the control group in eight dimensions:physiological function,physiological function,physical pain,health status,energy,social function,emotional function,and mental health(P<0.05);The results of slow wave sleep time and fast eye movement sleep time showed that after treatment,the HAMA and HAMD scores of the physiological mechanism in the observation group were lower than those in the control group(P<0.05);The results of cerebral blood flow and neurotransmitter indica‐tors show that after treatment,glutamateγ-The peak systolic blood flow velocity of ami‐nobutyric acid,vertebral artery,and basilar artery in the observation group was higher than that in the control group(P<0.05).Conclusion:The clinical treatment of Chinese medicine combined with acupuncture and moxibusti

关键词： primary insomnia acupuncture and moxibustion traditional Chinese medicine sleep quality quality of life

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Development and Evaluation of a Promising Biomarker for Diagnosis of Latent and Active Tuberculosis Infection

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Infectious Diseases & Immunity 2024年第1期4卷 10-24页

作者： Cong Peng Fan jiang Yinping Liu Yong xue Peng Cheng Jie Wang liang Wang Wenping Gong Hebei North University Zhangjiakou 075000Hebei ProvinceChina Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment Senior Department of TuberculosisEighth Medical Center of PLA General HospitalBeijing 100091China Department of Geriatrics Eighth Medical Center of PLA General HospitalBeijing 100091China Section of Health No.94804 Unit of the Chinese People's Liberation ArmyShanghai 200434China

Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and ***,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection ***,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic ***:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and *** responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead *** study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,*** samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic ***:A novel MEBDB,designated as CP19128P,was ***19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell *** silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune ***19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and *** IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from

关键词： Tuberculosis Latent tuberculosis infection Active tuberculosis Multiepitope-based diagnostic biomarker Bioinformatics:Immunoinformatics

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Underestimated benefits of NO_(x) control in reducing SNA and O_(3) based on missing heterogeneous HONO sources

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Frontiers of Environmental Science & Engineering 2024年第3期18卷 57-67页

作者： Shuping Zhang Haotian Zheng Jun Liu Yao Shi Tianzeng Chen Chaoyang xue Fenfen Zhang Yueqi jiang Xiangping Zhang Shovan Kumar Sahu Biwu Chu Jia Xing State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing 100084China China Academy of Civil Aviation Science and Technology Beijing 100028China State Key Joint Laboratory of Environment Simulation and Pollution Control Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Yellow River Institute of Hydraulic Research Zhengzhou 450003China Centre for Climate Research Singapore Meteorological Service SingaporeSingapore 537054Singapore

Substantial NO_(x) emission mitigation is crucial for the synergistic reduction of particulate matter and ozone(O_(3))pollution in *** traditional air quality model does not consider heterogeneous HONO chemistry,leading to uncertainties in estimating the benefits of NO_(x) *** studies have shown that the parameterization of heterogeneous HONO formation increases both the simulated value of sulfate–nitrate–ammonium(SNA)and that of O_(3),thus adding the heterogeneous reactions of HONO into air quality models inevitably leads to changes in the estimated benefits of NO_(x) *** we investigated the changes in SNA and O_(3)concentrations from NO_(x) emission reduction before and after adding heterogeneous HONO reactions in the Community Multi-Scale Air Quality(CMAQ)*** heterogeneous HONO reactions in the simulation improved the benefits of NO_(x) reduction in terms of SNA control in *** 80%NO_(x) reduction,the reduction in SNA increased from 36.9%without considering heterogeneous HONO reactions to 42.8%with heterogeneous HONO *** reduction in the maximum daily 8h average(MDA8)O_(3)in summer caused by NO_(x) reduction increased slightly from 4.7%to 5.2%after adding heterogeneous HONO *** results in this study highlight the enhanced effectiveness of NO_(x) controls for the reduction of SNA and O_(3)after considering heterogeneous HONO formation in a complex chemical ambient,demonstrating the importance of NO_(x) controls in reducing PM2.5 and O_(3)pollution in China.

关键词： Heterogeneous HONO NO_(x) reduction PM_(2.5) O_(3)

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Alzheimer’s disease early diagnostic and staging biomarkers revealed by large-scale cerebrospinal fluid and serum proteomic profiling

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The Innovation 2024年第1期5卷 118-126页

作者： Qing-Qing Tao xue Cai Yan-Yan xue Weigang Ge liang Yue Xiao-Yan Li Rong-Rong Lin Guo-Ping Peng Wenhao jiang Sainan Li Kun-Mu Zheng Bin jiang Jian-Ping Jia Tiannan Guo Zhi-Ying Wu Department of Neurology and Research Center of Neurology in the Second Affiliated Hospital and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of MedicineHangzhou 310009China liangzhu Laboratory Zhejiang UniversityHangzhou 311100China Westlake Laboratory of Life Sciences and Biomedicine Key Laboratory of Structural Biology of Zhejiang ProvinceSchool of Life SciencesWestlake UniversityHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzho 310024China Department of Neurology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Department of Neurology First Affiliated HospitalSchool of MedicineXiamen UniversityXiamen 361009China Innovation Center for Neurological Disorders and Department of Neurology Xuanwu HospitalCapital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijing 100053China MOE Frontier Science Center for Brain Science and Brain-machine Integration School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China CAS Center for Excellence in Brain Science and Intelligence Technology Shanghai 200031China

Amyloid-b,tau pathology,and biomarkers of neurodegeneration make up the core diagnostic biomarkers of Alzheimer disease(AD).However,these proteins represent only a fraction of the complex biological processes underlying AD,and individuals with other brain diseases in which AD pathology is a comorbidity also test positive for these diagnostic *** ADspecific early diagnostic and disease staging biomarkers are *** this study,we performed tandem mass tag proteomic analysis of paired cerebrospinal fluid(CSF)and serum samples in a discovery cohort comprising 98 *** biomarkers were validated by parallel reaction monitoring–based targeted proteomic assays in an independent multicenter cohort comprising 288 *** quantified 3,238 CSF and 1,702 serum proteins in the discovery cohort,identifying 171 and 860 CSF proteins and 37 and 323 serum proteins as potential early diagnostic and staging biomarkers,*** the validation cohort,58 and 21 CSF proteins,as well as 12 and 18 serum proteins,were verified as early diagnostic and staging biomarkers,*** 19-protein CSF and an 8-protein serum biomarker panels were built by machine learning to accurately classify mild cognitive impairment(MCI)due to AD from normal cognition with areas under the curve of 0.984 and 0.881,*** 19-protein CSF biomarker panel also effectively discriminated patients with MCI due to AD from patients with other neurodegenerative ***,we identified 21 CSF and 18 serum stage-associated proteins re-flecting AD *** findings provide a foundation for developing bloodbased tests for AD screening and staging in clinical practice.

关键词： cerebrospinal Alzheimer fluid

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Al-doped ZnO/WO_(3) heterostructure films prepared by magnetron sputtering for isopropanol sensors

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Rare Metals 2024年第1期43卷 247-256页

作者： Wei-Xiang Gao xue-Ting Chang Xiao-Jie Zhu Jun-Feng Li Ying-Chang jiang Dong-Sheng Wang Chuan-Xiao Yang Shi-Bin Sun College of Logistics Engineering Shanghai Maritime UniversityShanghai 201306China College of Ocean Science and Engineering Shanghai Maritime UniversityShanghai 201306China Institute of Logistics Science and Engineering Shanghai Maritime UniversityShanghai 201306China

Metal oxide semiconductors(MOSs) are ideal sensing materials for detecting volatile organic compounds due to their low cost, diversity, high stability, and ease of production. However, it remains a grand challenge to develop the MOSs-based gas sensors for sensing isopropanol with desired performance via a simple, effective,and controllable method. Herein, we reported the preparation of the Al-doped Zn O(AZO)/WO_(3) heterostructure films by directly depositing the AZO coating onto the WO_(3) coating using a strategy of magnetron sputtering. The AZO/WO_(3) heterostructure films were constructed by numbers of irregular nanoparticles that were interconnected with each other. The AZO/WO_(3) heterostructure films-based gas sensors exhibited excellent isopropanolsensing performance with high response, promising selectivity, low detection limit, fast response rate, wide detection range, and ideal reproducibility. The promising isopropanol-sensing performance of the AZO/WO_(3) heterostructure films arises mainly from their high uniformity, unique microstructures with high surface roughness,and the construction of the heterostructure between the AZO and WO_(3) coatings. This work provides a versatile approach to prepare the MOSs-based heterostructure films for assembling the gas sensors.

关键词： Metal oxide semiconductors Gas sensors Aldoped ZnO/WO_(3) Heterostructure films Isopropanol Magnetron sputtering

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Evaluating the influence of sarcopenia and myosteatosis on clinical outcomes in gastric cancer patients undergoing immune checkpoint inhibitor

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World Journal of Gastroenterology 2024年第8期30卷 863-880页

作者： Gui-Ming Deng Hai-Bin Song Zhong-Ze Du Ying-Wei xue Hong-jiang Song Yuan-Zhou Li Department of Gastrointestinal Surgery Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina Department of Radiology Harbin Medical University Cancer HospitalHarbin 150081Heilongjiang ProvinceChina

BACKGROUND The development and progression of gastric cancer(GC)are closely linked to the nutritional status of *** immunotherapy has been demonstrated to be clinically effective,the relationships of sarcopenia and myosteatosis with the use of immune checkpoint inhibitors(ICIs)in patients with gastric cancer remain to be *** We performed a retrospective study of patients who were undergoing immuno-therapy for *** the evaluation of sarcopenia,the optimal cut-off value for the skeletal muscle index was established using receiver operating characteristic analysis of data obtained from pre-treatment computed tomography images at the L3 vertebral *** was defined using the mean skeletal muscle density(SMD),with a threshold value of<41 Hounsfield units(HU)for patients with a body mass index(BMI)<25 kg/m^(2)and<33 HU for those with a BMI≥25 kg/m^(2).The log-rank test was used to compare progression-free survival(PFS)and overall survival(OS),and a Cox proportional hazard model was used to identify prognostic *** were developed to predict the PFS and OS of patients on the basis of the results of multivariate *** We studied 115 patients who were undergoing ICI therapy for GC,of whom 27.4%had sarcopenia and 29.8%had *** with sarcopenia or myosteatosis had significantly shorter PFS and OS than those without these ***,both sarcopenia and myosteatosis were found to be independent predictors of PFS and OS in patients with GC administering an *** prediction models created for PFS and OS were associated with C-indexes of 0.758 and 0.781,*** The presence of sarcopenia or myosteatosis is a reliable predictor of the clinical outcomes of patients with GC who are undergoing treatment with an ICI.

关键词： Gastric cancer Sarcopenia Myosteatosis,Immune checkpoint inhibitor Prognostic factor Overall survival Progression-free survival

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Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations

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Asian Journal of Andrology 2024年第4期26卷 426-432页

作者： Yu-Fan Yang Hai-Lu Ma Xi Wang Min Nie jiang-Feng Mao xue-Yan Wu Department of Endocrinology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China.

Fibroblast growth factor receptor 1(FGFR1)mutations are associated with congenital hypogonadotropic hypogonadism(CHH)through inheritance or spontaneous *** detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital(Beijing,China)using next-generation and Sanger *** assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation *** 19 patients with FGFR1 mutations,three were recurrent,and 16 were novel *** of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics(ACMG)guidelines,with the prevalent P366L *** majority of FGFR1 mutations was inherited(57.9%),with frameshift mutations exclusive to the de novo mutation *** inherited mutation group had a lower incidence of cryptorchidism,short stature,and skeletal *** the inherited mutation group,luteinizing hormone(LH)levels were 0.5 IU l−1,follicle-stimulating hormone(FSH)levels were 1.0 IU l−1,and testosterone levels were 1.3 nmol l−*** contrast,the de novo group had LH levels of 0.2 IU l−1,FSH levels of 0.5 IU l−1,and testosterone levels of 0.9 nmol l−1,indicating milder hypothalamus–pituitary–gonadal axis(HPGA)functional deficiency in the inherited *** inherited mutation group showed a tendency toward higher spermatogenesis *** conclusion,this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations,contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

关键词： congenital hypogonadotropic hypogonadism de novo FGFR1 inherited

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Mechanisms of fracture propagation from multi-cluster using a phase field based HMD coupling model in fractured reservoir

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Petroleum Science 2024年第3期21卷 1829-1851页

作者： Yun-Jin Wang Bo Wang Hang Su Tu Chang Ren-Cheng Dong Li-Zhe Li Wei-Yu Tang Ting-xue jiang Fu-Jian Zhou State Key Laboratory of Petroleum Resources and Engineering China University of Petroleum-BeijingBejing2249China China University of Petroleum-Beijing at Karamay Karamay834000XinjiangChina China National Oil and Gas Exploration and Development Corporation Ltd. Beijing100034China University of Texas at Austin United States SINOPEC Research Institute of Petroleum Engineering Beijing100101China

Natural fractures(NFs)are common in shale and tight reservoirs,where staged multi-cluster fracturing of horizontal wells is a prevalent technique for reservoir *** NFs and stress interference are recognized as significant factors affecting hydraulic fracture(HF)propagation,the combined influence of these factors remains poorly *** address this knowledge gap,a novel coupled hydromechanical-damage(HMD)model based on the phase field method is developed to investigate the propagation of multi-cluster HFs in fractured *** comprehensive energy functional and control functions are established,while incorporating dynamic fluid distribution between multiple perforation clusters and refined changes in rock mechanical parameters during hydraulic *** HMD coupled multi-cluster HF propagation model investigates various scenarios,including single HF and single NF,reservoir heterogeneity,single HF and NF clusters,and multi-cluster HFs with NF *** results show that the HMD coupling model can accurately capture the impact of approach angle(θ),stress difference and cementation strength on the interaction of HF and *** criterion of the open and cross zones is not *** NF angle(a)is not a decisive parameter to discriminate the *** to the relationship between approach angle(θ)and NF angle(a),the contact relationship of HF can be divided into three categories(θ=a,θa).The connected NF can increase the complexity of HF by inducing it to form branch fracture,resulting in a fractal dimension of HF as high as2.1280 at angles of±45°.Inter-fracture interference from the heel to the toe of HF shows the phenomenon of no,strong and weak ***,under the influence of NFs,distant HFs from the injection can become dominant ***,as a gradually increases,inter-fracture stress interference becomes the primary factor influencing HF propagation,gradually superseding the dominance of NF

关键词： HMD coupling Phase field Natural fracture Flow distribution Hydraulic fracturing Inter-fracture interference

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Sustainable development of unconventional resources: Analysis of the transient linear flow oriented straight-line analysis technique

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Energy Reviews 2024年第1期3卷 49-75页

作者： Dan xue liangliang jiang Zixiang Wei Maojie Chai jiang Liu Peng Deng Fuhe Lin Jian Li Jiansheng Zhang Zhangxing Chen Department of Chemical and Petroleum Engineering University of CalgaryCalgaryAlbertaCanada Guangdong University of Petrochemical and Technology MaomingChina School of Mathematics and Data Science Shaanxi University of Science and TechnologyXi'anChina Department of Energy and Power Engineering Tsinghua UniversityBeijingChina Eastern Institute for Advanced Study NingboChina China University of Petroleum(Beijing) BeijingChina

On the backdrop of dwindling conventional reserves,unconventional reservoirs have emerged as a pivotal chapter in resource *** their challenges,such as low permeability,complex fluid storage,and flow mechanisms,hydraulic fracturing technology has underpinned the development of unconventional ***,this has brought about a shift in the sequence of flow regimes,e.g.,the transient radial flow regime has been largely shortened by the lengthy transient linear flow regime due to the low permeability of unconventional ***,straight-line analysis(SLA),the simplest technique in rate transient analysis(RTA),is a fundamental and potent tool for swiftly extracting reservoir and hydraulic fracture information,estimating oil and gas reserves,and furnishing crucial initial data for subsequent historical matching ***,there is currently a dearth of review papers pertaining to a necessary guide of applying SLA in various transient linear flow(TLF)regimes and different unconventional ***,this paper commences by elucidating the classification of TLF regimes,commonly used methods for recognizing flow regimes,and the diverse SLA methods used for different TLF ***,it delves into a discussion of different modification techniques for variable rate/flowing pressure,gas phase,complex reservoir characteristics in unconventional reservoirs,and dynamic drainage area concepts ***,the application of SLA in specific domains,namely core analysis and the flowback period,is *** culminates by surveying the advancements through an integration of novel technologies to enhance estimation *** paper also highlights certain drawbacks of current SLA technology and proposes new research ***,this paper would serve as an indispensable resource,offering foundational knowledge for the application of SLA in TLF to promote the production of global unconventional resources in a c

关键词： Unconventional reservoirs Straight-line analysis(SLA) Transient linear flow(TLF) Oil/gas reserves Hydraulic fracture information

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