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Human cerebral organoids:Complex,versatile,and human-relevant models of neural development and brain diseases
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作者 Raquel Coronel Rosa González-Sastre +8 位作者 Patricia Mateos-Martínez Laura Maeso Elena Llorente-Beneyto Sabela Martín-Benito Viviana S.Costa Gagosian Leonardo Foti Ma Carmen González-Caballero Victoria López-Alonso Isabel Liste 《Neural Regeneration Research》 2026年第3期837-854,共18页
The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cereb... The brain is the most complex human organ,and commonly used models,such as two-dimensional-cell cultures and animal brains,often lack the sophistication needed to accurately use in research.In this context,human cerebral organoids have emerged as valuable tools offering a more complex,versatile,and human-relevant system than traditional animal models,which are often unable to replicate the intricate architecture and functionality of the human brain.Since human cerebral organoids are a state-of-the-art model for the study of neurodevelopment and different pathologies affecting the brain,this field is currently under constant development,and work in this area is abundant.In this review,we give a complete overview of human cerebral organoids technology,starting from the different types of protocols that exist to generate different human cerebral organoids.We continue with the use of brain organoids for the study of brain pathologies,highlighting neurodevelopmental,psychiatric,neurodegenerative,brain tumor,and infectious diseases.Because of the potential value of human cerebral organoids,we describe their use in transplantation,drug screening,and toxicology assays.We also discuss the technologies available to study cell diversity and physiological characteristics of organoids.Finally,we summarize the limitations that currently exist in the field,such as the development of vasculature and microglia,and highlight some of the novel approaches being pursued through bioengineering. 展开更多
关键词 assembloids BIOENGINEERING challenges disease modeling drug screening and toxicology human brain organoids human pluripotent stem cells neurodegenerative diseases NEURODEVELOPMENT VASCULARIZATION
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MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate Burn-Induced Acute Lung Injury in Rats 被引量:3
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作者 Zhigang Jia Lin Li +5 位作者 Peng Zhao Guo Fei Shuangru Li Qinqin Song Guangpeng Liu Jisong Liu 《Biomedical and Environmental Sciences》 SCIE CAS CSCD 2024年第9期1030-1043,共14页
Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechan... Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI. 展开更多
关键词 Acute lung injury human umbilical cord mesenchymal stem cell-derived exosomes MicroRNA-451 Tuberous sclerosis complex 1 Mammalian target of rapamycin pathway AUTOPHAGY
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Expression rates of p16,p53 in head and neck cutaneous squamous cell carcinoma based on human-papillomavirus positivity 被引量:2
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作者 Ha-Jong Nam Heongrae Ryu +5 位作者 Da-Woon Lee Je Yeon Byeon Jun Hyuk Kim Ji Hye Lee Soomin Lim Hwan Jun Choi 《World Journal of Clinical Cases》 SCIE 2025年第9期13-23,共11页
BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanis... BACKGROUND The high prevalence of human papillomavirus(HPV)infection in oropharyngeal squamous cell carcinoma(SCC)is well established,and p16 expression is a strong predictor.HPV-related tumors exhibit unique mechanisms that target p16 and p53 proteins.However,research on HPV prevalence and the combined predictive value of p16 and p53 expression in head and neck cutaneous SCC(HNCSCC),particularly in Asian populations,remains limited.This retrospective study surveyed 62 patients with HNSCC(2011-2020),excluding those with facial warts or other skin cancer.AIM To explore the prevalence of HPV and the predictive value of p16 and p53 expression in HNCSCC in Asian populations.METHODS All patients underwent wide excision and biopsy.Immunohistochemical staining for HPV,p16,and p53 yielded positive and negative results.The relevance of each marker was investigated by categorizing the tumor locations into high-risk and middle-risk zones based on recurrence frequency.RESULTS Of the 62 patients,20(32.26%)were male,with an average age of 82.27 years(range 26-103 years).High-risk included 19 cases(30.65%),with the eyelid and lip being the most common sites(five cases,8.06%).Middle-risk included 43 cases(69.35%),with the cheek being the most common(29 cases,46.77%).The p16 expression was detected in 24 patients(38.71%),p53 expression in 42 patients(72.58%),and HPV in five patients(8.06%).No significant association was found between p16 expression and the presence of HPV(P>0.99),with a positive predictive value of 8.33%.CONCLUSION This study revealed that p16,a surrogate HPV marker in oropharyngeal SCC,is not reliable in HNCSCC,providing valuable insights for further research in Asian populations. 展开更多
关键词 Squamous cell carcinoma OROPHARYNGEAL Non-oropharyngeal human papillomavirus The p16 The p53
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Copper complexes of anthrahydrazone bearing pyridyl side chain:Synthesis,crystal structure,anticancer activity,and DNA binding 被引量:1
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作者 HUANG Yao WU Yingshu +5 位作者 BAO Zhichun HUANG Yue TANG Shangfeng LIU Ruixue LIU Yancheng LIANG Hong 《无机化学学报》 北大核心 2025年第1期213-224,共12页
To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bisp... To expand the study on the structures and biological activities of the anthracyclines anticancer drugs and reduce their toxic side effects,the new anthraquinone derivatives,9‑pyridylanthrahydrazone(9‑PAH)and 9,10‑bispyridylanthrahydrazone(9,10‑PAH)were designed and synthesized.Utilizing 9‑PAH and 9,10‑PAH as promising anticancer ligands,their respective copper complexes,namely[Cu(L1)Cl_(2)]Cl(1)and{[Cu_(4)(μ_(2)‑Cl)_(3)Cl_(4)(9,10‑PAH)_(2)(DMSO)_(2)]Cl_(2)}_(n)(2),were subsequently synthesized,where the new ligand L1 is formed by coupling two 9‑PAH ligands in the coordination reaction.The chemical and crystal structures of 1 and 2 were elucidated by IR,MS,elemental analysis,and single‑crystal X‑ray diffraction.Complex 1 forms a mononuclear structure.L1 coordinates with Cu through its three N atoms,together with two Cl atoms,to form a five‑coordinated square pyramidal geometry.Complex 2 constitutes a polymeric structure,wherein each structural unit centrosymmetrically encompasses two five‑coordinated binuclear copper complexes(Cu1,Cu2)of 9,10‑PAH,with similar square pyramidal geometry.A chlorine atom(Cl_(2)),located at the symmetry center,bridges Cu1 and Cu1A to connect the two binuclear copper structures.Meanwhile,the two five‑coordinated Cu2 atoms symmetrically bridge the adjacent structural units via one coordinated Cl atom,respectively,thus forming a 1D chain‑like polymeric structure.In vitro anticancer activity assessments revealed that 1 and 2 showed significant cytotoxicity even higher than cisplatin.Specifically,the IC_(50)values of 2 against HeLa‑229 and SK‑OV‑3 cancer cell lines were determined to be(5.92±0.32)μmol·L^(-1)and(6.48±0.39)μmol·L^(-1),respectively.2 could also block the proliferation of HeLa‑229 cells in S phase and significantly induce cell apoptosis.In addition,fluorescence quenching competition experiments suggested that 2 might interact with DNA by an intercalative binding mode,offering insights into its underlying anticancer mechanism.CCDC:2388918,1;2388919,2. 展开更多
关键词 anthrahydrazone metal complex crystal structure anticancer activity cell apoptosis
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Preliminary study on the preparation of lyophilized acellular nerve scaffold complexes from rabbit sciatic nerves with human umbilical cord mesenchymal stem cells
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作者 Chuang Qian Shang-Yu Guo +4 位作者 Zheng Xu Zhi-Qiang Zhang Hao-Dong Li Hao Li Xiong-Sheng Chen 《World Journal of Stem Cells》 SCIE 2024年第12期1047-1061,共15页
BACKGROUND The gold standard of care for patients with severe peripheral nerve injury is autologous nerve grafting;however,autologous nerve grafts are usually limited for patients because of the limited number of auto... BACKGROUND The gold standard of care for patients with severe peripheral nerve injury is autologous nerve grafting;however,autologous nerve grafts are usually limited for patients because of the limited number of autologous nerve sources and the loss of neurosensory sensation in the donor area,whereas allogeneic or xenografts are even more limited by immune rejection.Tissue-engineered peripheral nerve scaffolds,with the morphology and structure of natural nerves and complex biological signals,hold the most promise as ideal peripheral nerve“replacements”.AIM To prepare allogenic peripheral nerve scaffolds using a low-toxicity decellularization method,and use human umbilical cord mesenchymal stem cells(hUCMSCs)as seed cells to cultivate scaffold-cell complexes for the repair of injured peripheral nerves.METHODS After obtaining sciatic nerves from New Zealand rabbits,an optimal acellular scaffold preparation scheme was established by mechanical separation,varying lyophilization cycles,and trypsin and DNase digestion at different times.The scaffolds were evaluated by hematoxylin and eosin(HE)and luxol fast blue(LFB)staining.The maximum load,durability,and elastic modulus of the acellular scaffolds were assessed using a universal material testing machine.The acellular scaffolds were implanted into the dorsal erector spinae muscle of SD rats and the scaffold degradation and systemic inflammatory reactions were observed at 3 days,1 week,3 weeks,and 6 weeks following surgery to determine the histocompatibility between xenografts.The effect of acellular scaffold extracts on fibroblast proliferation was assessed using an MTT assay to measure the cytotoxicity of the scaffold residual reagents.In addition,the umbilical cord from cesarean section fetuses was collected,and the Wharton’s jelly(WJ)was separated into culture cells and confirm the osteogenic and adipogenic differentiation of mesenchymal stem cells(MSCs)and hUC-MSCs.The cultured cells were induced to differentiate into Schwann cells by the antioxidant-growth factor induction method,and the differentiated cells and the myelinogenic properties were identified.RESULTS The experiments effectively decellularized the sciatic nerve of the New Zealand rabbits.After comparing the completed acellular scaffolds among the groups,the optimal decellularization preparation steps were established as follows:Mechanical separation of the epineurium,two cycles of lyophilization-rewarming,trypsin digestion for 5 hours,and DNase digestion for 10 hours.After HE staining,no residual nuclear components were evident on the scaffold,whereas the extracellular matrix remained intact.LFB staining showed a significant decrease in myelin sheath composition of the scaffold compared with that before preparation.Biomechanical testing revealed that the maximum tensile strength,elastic modulus,and durability of the acellular scaffold were reduced compared with normal peripheral nerves.Based on the histocompatibility test,the immune response of the recipient SD rats to the scaffold New Zealand rabbits began to decline3 weeks following surgery,and there was no significant rejection after 6 weeks.The MTT assay revealed that the acellular reagent extract had no obvious effects on cell proliferation.The cells were successfully isolated,cultured,and passaged from human umbilical cord WJ by MSC medium,and their ability to differentiate into Schwann-like cells was demonstrated by morphological and immunohistochemical identification.The differentiated cells could also myelinate in vitro.CONCLUSION The acellular peripheral nerve scaffold with complete cell removal and intact matrix may be prepared by combining lyophilization and enzyme digestion.The resulting scaffold exhibited good histocompatibility and low cytotoxicity.In addition,hUC-MSCs have the potential to differentiate into Schwann-like cells with myelinogenic ability following in vitro induction. 展开更多
关键词 human umbilical cord mesenchymal stem cells Peripheral nerve injury Schwann cells Acellular nerve scaffolds
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The Effect of a Novel Complex, Composed of Ceramide, Energizing Peptide and Camu Camu Extract, on Epidermal Barrier Function and Dermal Antiaging Properties in Ex Vivo Human Skin Small Live Cohort
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作者 Landau Marina Landau-Blum Shir +6 位作者 Samuel Kassirer Audrey Le Mestr Armelle Perrin Julien Verdon Laurine Bergeron Corinne Morel Isabelle Imbert 《Journal of Cosmetics, Dermatological Sciences and Applications》 2024年第1期1-11,共11页
The skin’s primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary s... The skin’s primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary structures and components responsible for the skin’s barrier function are susceptible to environmental variables, dermatological conditions, and the aging process. The ensuing alterations to structure, composition, and organizational attributes of the epidermal barrier can impact its integrity and functionality. The aim of this study was to assess the effect of a novel complex composed of a ceramide, energizing peptide, and Camu Camu extract (SUPCERAT<sup>TM</sup> complex) on specific markers of epidermal barrier integrity, as well as epidermal and dermal function. All the experiments were conducted on fresh human abdominal skin explants. Intradermal production of hyaluronic acid, epidermal claudin-1, and ceramide synthase 3 expressions, as well as epidermal lipids content were assessed using specific fluorescent stainings on ex vivo skin after the application of the complex or placebo. Additionally, dermal elastase and collagenase activities were assessed using in tubo enzymatic assays. Lastly, the effect of a cosmetic cream containing SUPCERAT<sup>TM</sup> complex was assessed using subjective Global Aesthetic Improvement Scale (GAIS) in a small cohort of patients after 60 days of use. The application of the SUPCERAT<sup>TM</sup> complex on ex vivo skin led to significant increase in dermal hyaluronic acid content and epidermal activity of claudin-1, ceramide synthase 3 and epidermal ceramide content. Furthermore, in tubo enzymatic assays demonstrated inhibition of both dermal elastase and collagenase activities. In addition, the patient-reported results indicated significant improvements in skin quality and appearance. . 展开更多
关键词 SUPCERATTM complex Epidermal Skin Barrier Moisturization ANTIAGING CERAMIDE Camu Camu Extract
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Call for Paper from Food Science and Human Wellness
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《食品科学》 EI CAS 北大核心 2025年第1期I0006-I0006,共1页
Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics ... Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,biochemistry,microbiology,immunology and toxicology. 展开更多
关键词 human SHE advancement
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Call for Paper from Food Science and Human Wellness
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《食品科学》 EI CAS 北大核心 2025年第2期I0014-I0014,共1页
Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics ... Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology. 展开更多
关键词 human SHE advancement
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Commentary on:“Human neural stem cell-derived artificial organelles to improve oxidative phosphorylation”
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作者 Kwok-Fai So 《Neural Regeneration Research》 SCIE CAS 2025年第10期3040-3040,共1页
Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata... Mitochondrial function is fundamental to neuroregeneration,particularly in neurons,where high energy demands are essential for repair and recovery(Patrón and Zinsmaier,2016;Beckervordersandforth et al.,2017;Iwata et al.,2023).Mitochondrial dysfunction,characterized by an imbalance in ATP levels and excessive production of mitochondrial reactive oxygen species,is a key factor that impedes neural regeneration in neurodegenerative diseases and after neuronal injury(Han et al.,2016,2020;Zheng et al.,2016;Zong et al.,2024). 展开更多
关键词 NEURAL Becker human
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NUP62 alleviates senescence and promotes the stemness of human dental pulp stem cells via NSD2-dependent epigenetic reprogramming 被引量:1
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作者 Xiping Wang Li Wang +11 位作者 Linxi Zhou Lu Chen Jiayi Shi Jing Ge Sha Tian Zihan Yang Yuqiong Zhou Qihao Yu Jiacheng Jin Chen Ding Yihuai Pan Duohong Zou 《International Journal of Oral Science》 2025年第4期584-595,共12页
Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a... Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming. 展开更多
关键词 SENESCENCE stem cells human dental pulp stem cells stem cell STEMNESS NSD human dental pulp stem cells hdpscs obtained NUP
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Data-Driven Prediction in Complex Systems of Virus Evolution and Global Warming 被引量:1
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作者 LUO Liaofu LÜJun 《内蒙古大学学报(自然科学版)》 2025年第1期1-7,共7页
A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(da... A complex system is inherently high-dimensional.Recent studies indicate that,even without complete knowledge of its evolutionary dynamics,the future behavior of such a system can be predicted using time-series data(data-driven prediction).This suggests that the essential dynamics of a complex system can be captured through a low-dimensional representation.Virus evolution and climate change are two examples of complex,time-varying systems.In this article,we show that mutations in the spike protein provide valuable data for predicting SARS-CoV-2 variants,forecasting the possible emergence of the new macro-lineage Q in the near future.Our analysis also demonstrates that carbon dioxide concentration is a reliable indicator for predicting the evolution of the climate system,extending global surface air temperature(GSAT)forecasts through 2500. 展开更多
关键词 data-drivenprediction complex system virus evolution global warming
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Human endogenous retrovirus type-W and multiple sclerosis–related smoldering neuroinflammation
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作者 Joel Gruchot Laura Reiche +2 位作者 Andrew Chan Robert Hoepner Patrick Küry 《Neural Regeneration Research》 SCIE CAS 2025年第3期813-814,共2页
Introduction to human endogenous retrovirus type-W(HERV-W): Genomic inheritance from the past includes retroviral sequences that have been stably incorporated into our genomes and account for up to 8% of human DNA.
关键词 ENDOGENOUS INFLAMMATION human
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Exploring the Effects of Background Image Complexity and Map Symbol Load on the Usability of Image-maps 被引量:1
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作者 PENG Qian XIA Yuxin QIU Zeren 《Journal of Geodesy and Geoinformation Science》 2025年第2期5-20,共16页
Image-maps,a hybrid design with satellite images as background and map symbols uploaded,aim to combine the advantages of maps’high interpretation efficiency and satellite images’realism.The usability of image-maps i... Image-maps,a hybrid design with satellite images as background and map symbols uploaded,aim to combine the advantages of maps’high interpretation efficiency and satellite images’realism.The usability of image-maps is influenced by the representations of background images and map symbols.Many researchers explored the optimizations for background images and symbolization techniques for symbols to reduce the complexity of image-maps and improve the usability.However,little literature was found for the optimum amount of symbol loading.This study focuses on the effects of background image complexity and map symbol load on the usability(i.e.,effectiveness and efficiency)of image-maps.Experiments were conducted by user studies via eye-tracking equipment and an online questionnaire survey.Experimental data sets included image-maps with ten levels of map symbol load in ten areas.Forty volunteers took part in the target searching experiments.It has been found that the usability,i.e.,average time viewed(efficiency)and average revisits(effectiveness)of targets recorded,is influenced by the complexity of background images,a peak exists for optimum symbol load for an image-map.The optimum levels for symbol load for different image-maps also have a peak when the complexity of the background image/image map increases.The complexity of background images serves as a guideline for optimum map symbol load in image-map design.This study enhanced user experience by optimizing visual clarity and managing cognitive load.Understanding how these factors interact can help create adaptive maps that maintain clarity and usability,guiding AI algorithms to adjust symbol density based on user context.This research establishes the practices for map design,making cartographic tools more innovative and more user-centric. 展开更多
关键词 remote sensing image map point label complexity
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A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms
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作者 Nazar Mashtalir 《四川生理科学杂志》 2024年第1期214-214,共1页
Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate genomic architecture.Here,we present a structural model of the endogenously purified human canonical BAF complex bound to the ... Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate genomic architecture.Here,we present a structural model of the endogenously purified human canonical BAF complex bound to the nucleosome,generated using cryoelectron microscopy(cryo-EM),cross-linking mass spectrometry,and homology modeling. 展开更多
关键词 LINKING human architecture.
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A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms
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作者 Nazar Mashtalir 《四川生理科学杂志》 2024年第4期755-755,共1页
Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate genomic architecture.Here,we present a structural model of the endogenously purified human canonical BAF complex bound to the ... Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate genomic architecture.Here,we present a structural model of the endogenously purified human canonical BAF complex bound to the nucleosome,generated using cryoelectron microscopy(cryo-EM),cross-linking mass spectrometry,and homology modeling.BAF complexes bilaterally engage the nucleosome H2A/H2B acidic patch regions through the SMARCB1 C-terminalα-helix and the SMARCA4/2 C-terminal SnAc/postSnAc regions,with disease-associated mutations in either causing attenuated chromatin remodeling activities.Further,we define changes in BAF complex architecture upon nucleosome engagement and compare the structural model of endogenous BAF to those of related SWI/SNF-family complexes.Finally,we assign and experimentally interrogate cancer-associated hot-spot mutations localizing within the endogenous human BAF complex,identifying those that disrupt BAF subunit-subunit and subunit-nucleosome interfaces in the nucleosome-bound conformation.Taken together,this integrative structural approach provides important biophysical foundations for understanding the mechanisms of BAF complex function in normal and disease states. 展开更多
关键词 STRUCTURAL LINKING human
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Zircon U-Pb-Hf and Trace Element Signatures Reveal the Petrogenesis of the Jiuyishan Granitic Complex,South China:Implications for W-Sn and Rare Metal Mineralization 被引量:1
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作者 Wenzhou Xiao Chaoyun Liu +6 位作者 Kaixuan Tan Xianzhe Duan Qinglin Sui Kaituo Shi Peng Feng Mabrouk Sami Quan Ou 《Journal of Earth Science》 2025年第3期1069-1089,共21页
The Jiuyishan granitic complex,located in the Nanling Range,South China,is composed of five granitic plutons(Xuehuading,Jinjiling,Pangxiemu,Shaziling and Xishan).Zircon U-Pb dating of four plutons(Jinjiling,Pangxiemu,... The Jiuyishan granitic complex,located in the Nanling Range,South China,is composed of five granitic plutons(Xuehuading,Jinjiling,Pangxiemu,Shaziling and Xishan).Zircon U-Pb dating of four plutons(Jinjiling,Pangxiemu,Shaziling and Xishan)yielded similar ages of approximately 153 Ma,indicating indistinguishable ages within error.Three plutons except the Shaziling pluton,have consistentε_(Nd)(t)(-7.8 to-5.8)andε_(Hf)(t)(-9.1 to-2.2)values,which are similar to those of the lower crustal granulitic metasedimentary and meta-igneous rocks in South China.Compared to other three plutons,the Shaziling pluton has consistentε_(Nd)(t)(-7.4 to-6.8)andε_(Hf)(t)(-7.5 to-4.7)values and shows similar source,but the Shaziling mafic microgranular enclaves(MMEs)show variableε_(Hf)(t)(-14.2 to 4.8)values,indicating a remarkable mantle magma injection of the Shaziling pluton.Zircon Ce/Sm-Yb/Gd,whole-rock CaO-P_(2)O_(5)and CaO-TiO_(2)linear trends reveal that from the Xishan to the Shaziling and from the Jinjiling to the Pangxiemu granites,they experienced apatite and titanite fractionation,respectively.Zircon Th,U,Nb,Ta,Hf,Ti,Y,P and rare earth element(REE)contents and whole-rock Sr,Ba and Rb contents also show that the Shaziling,Xishan,Jinjiling and Pangxiemu granites followed a discontinuous evolutionary series,but the Pangxiemu granites exhibit highly evolved nature.Four main controlling factors of W-Sn and rare metal mineralization in granitic rocks were discussed,and we found that the mineralization in Jiuyishan granitic complex was mainly controlled by the fractionation degree and crystallization temperature,but were rarely affected by oxygen fugacity and mantle material input.The Pangxiemu granites show particularly higher Rb and Ta contents than the other three plutons,implying that the ore deposits developed in the Jiuyishan Complex were directly related to the most evolved Pangxiemu pluton,with the occurrence of Rb and Ta as the most likely rare metal mineralization in the Jiuyishan District.A crystal mush model is proposed to interpret the petrogenetic and mineralizing processes of the Jiuyishan granitic complex. 展开更多
关键词 Jiuyishan granitic complex ZIRCON fractionation geochemistry rare metal mineralization
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A phenylphenthiazide anchored Tb(Ⅲ)-cyclen complex for fluorescent turn-on sensing of ClO^(-) 被引量:1
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作者 Ya-Ping Liu Zhi-Rong Gui +4 位作者 Zhen-Wen Zhang Sai-Kang Wang Wei Lang Yanzhu Liu Qian-Yong Cao 《Chinese Chemical Letters》 2025年第2期269-273,共5页
A phenylphenothiazine anchored Tb(Ⅲ)-cyclen complex PTP-Cy-Tb for hypochlorite ion(ClO^(-))detection has been designed and prepared.PTP-Cy-Tb shows a weak Tb-based emission with AIE-characteristics in aqueous solutio... A phenylphenothiazine anchored Tb(Ⅲ)-cyclen complex PTP-Cy-Tb for hypochlorite ion(ClO^(-))detection has been designed and prepared.PTP-Cy-Tb shows a weak Tb-based emission with AIE-characteristics in aqueous solutions.After addition of ClO^(-),the fluorescence of PTP-Cy-Tb gives a large enhancement for oxidization the thioether to sulfoxide group.The detection limit of PTP-Cy-Tb toward ClO^(-)is as low as 8.85 nmol/L.The sensing mechanism was detailedly investigated by time of flight mass spectrometer(TOF-MS),Fourier transform infrared spectroscopy(FT-IR)and density functional theory(DFT)calculation.In addition,PTP-Cy-Tb has been successfully used for on-site and real-time detection of ClO^(-)in real water samples by using the smartphone-based visualization method and test strips. 展开更多
关键词 Phenylphenothiazine Tb(III)complex AIE Hypochlorite ion SENSING
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A mitochondria targeting Ir(Ⅲ)complex triggers ferroptosis and autophagy for cancer therapy:A case of aggregation enhanced PDT strategy for metal complexes 被引量:1
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作者 Panpan Wang Hongbao Fang +5 位作者 Mengmeng Wang Guandong Zhang Na Xu Yan Su Hongke Liu Zhi Su 《Chinese Chemical Letters》 2025年第1期374-380,共7页
Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxyge... Metal complexes hold significant promise in tumor diagnosis and treatment.However,their potential applications in photodynamic therapy(PDT)are hindered by issues such as poor photostability,low yield of reactive oxygen species(ROS),and aggregation-induced ROS quenching.To address these challenges,we present a molecular self-assembly strategy utilizing aggregation-induced emission(AIE)conjugates for metal complexes.As a proof of concept,we synthesized a mitochondrial-targeting cyclometalated Ir(Ⅲ)photosensitizer Ir-TPE.This approach significantly enhances the photodynamic effect while mitigating the dark toxicity associated with AIE groups.Ir-TPE readily self-assembles into nanoaggregates in aqueous solution,leading to a significant production of ROS upon light irradiation.Photoirradiated Ir-TPE triggers multiple modes of death by excessively accumulating ROS in the mitochondria,resulting in mitochondrial DNA damage.This damage can lead to ferroptosis and autophagy,two forms of cell death that are highly cytotoxic to cancer cells.The aggregation-enhanced photodynamic effect of Ir-TPE significantly enhances the production of ROS,leading to a more pronounced cytotoxic effect.In vitro and in vivo experiments demonstrate this aggregation-enhanced PDT approach achieves effective in situ tumor eradication.This study not only addresses the limitations of metal complexes in terms of low ROS production due to aggregation but also highlights the potential of this strategy for enhancing ROS production in PDT. 展开更多
关键词 Metal complex AIEgens Mitochondria targeting Enhanced photodynamic therapy Anticancer agent
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Call for Paper from Food Science and Human Wellness
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《食品科学》 北大核心 2025年第6期I0014-I0014,共1页
Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics ... Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology. 展开更多
关键词 human SHE advancement
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Call for Paper from Food Seience and Human Wellness
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《肉类研究》 北大核心 2025年第3期I0017-I0017,共1页
Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics ... Food Science and Human Wellness(FSHW ISSN:2213-4530,CN 10-1750/TS)publishes original research papers demonstrating the latest advancement of multidisci-plinary subjects related to food science and human health.Topics may include but not limited to:nutriology,bio-chemistry,microbiology,immunology and toxicology.Papers regarding components of fod especially nutrients and non-nutrient bioactive compounds(with putative health benefits)are welcomed.FSHW aims to unveil the correlations between food science and human health through the dissemination of both fundamental and applied research outcomes worldwide. 展开更多
关键词 human SHE advancement
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