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Simultaneously targeting extracellular vesicle trafficking and TGF-β receptor kinase activity blocks signaling hyperactivation and metastasis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 308-325页

作者： Adilson Fonseca Teixeira Yanhong Wang Josephine Iaria Peter ten Dijke Hong-Jian Zhu Department of Surgery(The Royal Melbourne Hospital) The University of MelbourneParkvilleVICAustralia Huagene institute Kecheng Science and Technology ParkPukou DistrictNanjingJiangsuChina Department of Cell and Chemical Biology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands

Metastasis is the leading cause of cancer-related deaths.Transforming growth factor beta(TGF-β)signaling drives metastasis and is strongly enhanced during cancer progression.Yet,the use of on-target TGF-βsignaling inhibitors in the treatment of cancer patients remains unsuccessful,highlighting a gap in the understanding of TGF-βbiology that limits the establishment of efficient anti-metastatic therapies.Here,we show that TGF-βsignaling hyperactivation in breast cancer cells is required for metastasis and relies on increased small extracellular vesicle(sEV)secretion.Demonstrating sEV’s unique role,TGF-βsignaling levels induced by sEVs exceed the activity of matching concentrations of soluble ligand TGF-β.Further,genetic disruption of sEV secretion in highlymetastatic breast cancer cells impairs cancer cell aggressiveness by reducing TGF-βsignaling to nearly-normal levels.Otherwise,TGF-βsignaling activity in non-invasive breast cancer cells is inherently low,but can be amplified by sEVs,enabling invasion and metastasis of poorly-metastatic breast cancer cells.Underscoring the translational potential of inhibiting sEV trafficking in advanced breast cancers,treatment with dimethyl amiloride(DMA)decreases sEV secretion,TGF-βsignaling activity,and breast cancer progression in vivo.Targeting both the sEV trafficking and TGF-βsignaling by combining DMA and SB431542 at suboptimal doses potentiated this effect,normalizing the TGF-βsignaling in primary tumors to potently reduce circulating tumor cells,metastasis,and tumor self-seeding.Collectively,this study establishes sEVs as critical elements in TGF-βbiology,demonstrating the feasibility of inhibiting sEV trafficking as a new therapeutic approach to impair metastasis by normalizing TGF-βsignaling levels in breast cancer cells.

关键词： metastasis doses invasion

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CD4^(+)T cells produce IFN-I to license cDC1s for induction of cytotoxic T-cell activity in human tumors

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Cellular & Molecular Immunology 2024年第4期21卷 374-392页

作者： Xin Lei Daniël C.de Groot Marij J.P.Welters Tom de Wit Ellen Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris L.Vos Charlotte L.Zuur Noel F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanling Xiao Department of Immunology Leiden University Medical CenterLeidenThe Netherlands oncode institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biology and Immunology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Medical Oncology Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of Medical Oncology The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinolaryngology Leiden University Medical Center LeidenThe Netherlands Department of Pathology Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cells can"help"or"license" conventional type 1 dendritic cells(cDC1s)to induce CD8^(+)cytotoxic T lymphocyte(CTL)anticancer responses,as proven in mouse models.We recently identified cDC1s with a transcriptomic imprint of CD4^(+)T-cell help,specifically in T-cell-infiltrated human cancers,and these cells were associated with a good prognosis and response to PD-1-targeting immunotherapy.Here,we delineate the mechanism of cDC1 licensing by CD4^(+)T cells in humans.Activated CD4^(+)T cells produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their ability to induce CTL anticancer responses.In cooperation with CD40 ligand(L),IFNβalso optimizes the costimulatory and other functions of cDC1s required for CTL response induction.IFN-I-producing CD4^(+)T cells are present in diverse T-cell-infiltrated cancers and likely deliver“help”signals to CTLs locally,according to their transcriptomic profile and colocalization with“helped/licensed”cDCs and tumor-reactive CD8^(+)T cells.In agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cells in the TME is associated with overall survival and the response to PD-1 checkpoint blockade in cancer patients.

关键词： CD4^(+)T-cell help cDC1 licensing IFN-I signaling CD40 costimulation (cross-)presentation CTL priming Tumor control

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Uncovering the dominant contribution of intermediate volatility compounds in secondary organic aerosol formation from biomass-burning emissions

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National Science Review 2024年第3期11卷 150-158页

作者： Kun Li Jun Zhang David M.Bell Tiantian Wang Houssni Lamkaddam Tianqu Cui Lu Qi Mihnea Surdu Dongyu Wang Lin Du Imad El Haddad Jay G.Slowik Andre S.H.Prevot Environment Research institute Shandong University Laboratory of Atmospheric Chemistry Paul Scherrer Institute

Organic vapors from biomass burning are a major source of secondary organic aerosols(SOAs). Previous smog chamber studies found that the SOA contributors in biomass-burning emissions are mainly volatile organic compounds(VOCs). While intermediate volatility organic compounds(IVOCs) are efficient SOA precursors and contribute a considerable fraction of biomass-burning emissions, their contribution to SOA formation has not been directly observed. Here, by deploying a newly-developed oxidation flow reactor to study SOA formation from wood burning, we find that IVOCs can contribute ～70% of the formed SOA, i.e.>2 times more than VOCs. This previously missing SOA fraction is interpreted to be due to the high wall losses of semi-volatile oxidation products of IVOCs in smog chambers. The finding in this study reveals that SOA production from biomass burning is much higher than previously thought, and highlights the urgent need for more research on the IVOCs from biomass burning and potentially other emission sources.

关键词： atmospheric chemistry biomass burning secondary organic aerosol intermediate volatility organic compounds

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Motion of charged particles in bright squeezed vacuum

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Light(Science & Applications) 2024年第2期13卷 347-353页

作者： Matan Even Tzur Oren Cohen Solid State institute and Physics Department Technion-Israel Institute of TechnologyHaifa3200003Israel

The motion of laser-driven electrons quivers with an average energy termed pondermotive energy.We explore electron dynamics driven by bright squeezed vacuum(BSV),finding that BSV induces width oscillations,akin to electron quivering in laser light,with an equivalent ponderomotive energy.We identify closed and open trajectories of the electronic width that are associated with high harmonic generation and above-threshold ionization,respectively,similarly to trajectories of the electron position when its motion is driven by coherent light.In the case of bound electrons,the width oscillations may lead to ionization with noisy sub-cycle structure.Our results are foundational for strong-field and free-electron quantum optics,as they shed light on ionization,high harmonic generation,and nonlinear Compton scattering in BSV.

关键词： structure vacuum ionization

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On-Chip Micro Temperature Controllers Based on Freestanding Thermoelectric Nano Films for Low-Power Electronics

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Nano-Micro Letters 2024年第7期16卷 98-108页

作者： Qun Jin Tianxiao Guo Nicolas Perez Nianjun Yang Xin Jiang Kornelius Nielsch Heiko Reith institute for Metallic Materials Leibniz Institute for Solid State and Materials Research01069 DresdenGermany institute of Materials Engineering University of Siegen57076 SiegenGermany institute of Applied Physics Technical University of Dresden01069 DresdenGermany institute of Materials Science Technical University of Dresden01069 DresdenGermany

Multidimensional integration and multifunctional com-ponent assembly have been greatly explored in recent years to extend Moore’s Law of modern microelectronics.However,this inevitably exac-erbates the inhomogeneity of temperature distribution in microsystems,making precise temperature control for electronic components extremely challenging.Herein,we report an on-chip micro temperature controller including a pair of thermoelectric legs with a total area of 50×50μm^(2),which are fabricated from dense and flat freestanding Bi2Te3-based ther-moelectric nano films deposited on a newly developed nano graphene oxide membrane substrate.Its tunable equivalent thermal resistance is controlled by electrical currents to achieve energy-efficient temperature control for low-power electronics.A large cooling temperature difference of 44.5 K at 380 K is achieved with a power consumption of only 445μW,resulting in an ultrahigh temperature control capability over 100 K mW^(-1).Moreover,an ultra-fast cooling rate exceeding 2000 K s^(-1) and excellent reliability of up to 1 million cycles are observed.Our proposed on-chip temperature controller is expected to enable further miniaturization and multifunctional integration on a single chip for microelectronics.

关键词： Temperature control Low-power electronics On-chip micro temperature controller Freestanding thermoelectric nano films Temperature-sensitive components

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Deep Guided Attention Network for Joint Denoising and Demosaicing in Real Image

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Chinese Journal of Electronics 2024年第1期33卷 303-312页

作者： Tao ZHANG Ying FU Jun ZHANG School of Computer Science and Technology Beijing Institute of Technology Advanced Reasearch institute of Multidisciplinary Science Beijing Institute of Technology

Denoising(DN) and demosaicing(DM) are the first crucial stages in the image signal processing pipeline. Recently, researches pay more attention to solve DN and DM in a joint manner, which is an extremely undetermined inverse problem. Existing deep learning methods learn the desired prior on synthetic dataset, which limits the generalization of learned network to the real world data. Moreover, existing methods mainly focus on the raw data property of high green information sampling rate for DM, but occasionally exploit the high intensity and signalto-noise(SNR) of green channel. In this work, a deep guided attention network(DGAN) is presented for real image joint DN and DM(JDD), which considers both high SNR and high sampling rate of green information for DN and DM, respectively. To ease the training and fully exploit the data property of green channel, we first train DN and DM sub-networks sequentially and then learn them jointly, which can alleviate the error accumulation. Besides, in order to support the real image JDD, we collect paired raw clean RGB and noisy mosaic images to conduct a realistic dataset. The experimental results on real JDD dataset show the presented approach performs better than the state-of-the-art methods, in terms of both quantitative metrics and qualitative visualization.

关键词： Image denoising Image demosaicing Joint processing Guided attention Paired real dataset

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Advances in Wireless,Batteryless,Implantable Electronics for Real‑Time,Continuous Physiological Monitoring

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Nano-Micro Letters 2024年第3期16卷 254-302页

作者： Hyeonseok Kim Bruno Rigo Gabriella Wong Yoon Jae Lee Woon‑Hong Yeo IEN Center for Wearable Intelligent Systems and Healthcare Georgia Institute of TechnologyAtlantaGA 30332USA George W.Woodruff School of Mechanical Engineering Georgia Institute of TechnologyAtlantaGA 30332USA School of Electrical and Computer Engineering Georgia Institute of TechnologyAtlantaGA 30332USA Wallace H.Coulter Department of Biomedical Engineering Georgia Tech and Emory University School of MedicineAtlantaGA 30332USA Parker H.Petit institute for Bioengineering and Biosciences Institute for MaterialsInstitute for Robotics and Intelligent MachinesGeorgia Institute of TechnologyAtlantaGA 30332USA

This review summarizes recent progress in developing wireless,batteryless,fully implantable biomedical devices for real-time continuous physiological signal monitoring,focusing on advancing human health care.Design considerations,such as biological constraints,energy sourcing,and wireless communication,are discussed in achieving the desired performance of the devices and enhanced interface with human tissues.In addition,we review the recent achievements in materials used for developing implantable systems,emphasizing their importance in achieving multi-functionalities,biocompatibility,and hemocompatibility.The wireless,batteryless devices offer minimally invasive device insertion to the body,enabling portable health monitoring and advanced disease diagnosis.Lastly,we summarize the most recent practical applications of advanced implantable devices for human health care,highlighting their potential for immediate commercialization and clinical uses.

关键词： Implantable electronics Biomedical systems Batteryless devices Wireless electronics Physiological signal monitoring

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The safety aspect of sodium ion batteries for practical applications

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Journal of Energy Chemistry 2024年第8期95卷 407-427页

作者： Yingshuai Wang Runqing Ou Jingjing Yang Yuhang Xin Preetam Singh Feng Wu Yumin Qian Hongcai Gao School of Materials Science & Engineering Beijing Institute of Technology Department of Ceramic Engineering Indian Institute of Technology(Banaras Hindu University) Varanasi School of Physics Beijing Institute of Technology Yangtze Delta Region Academy of Beijing institute of Technology Beijing institute of Technology Chongqing Innovation Center

Sodium-ion batteries(SIBs) with advantages of abundant resource and low cost have emerged as promising candidates for the next-generation energy storage systems. However, safety issues existing in electrolytes, anodes, and cathodes bring about frequent accidents regarding battery fires and explosions and impede the development of high-performance SIBs. Therefore, safety analysis and high-safety battery design have become prerequisites for the development of advanced energy storage systems. The reported reviews that only focus on a specific issue are difficult to provide overall guidance for building high-safety SIBs. To overcome the limitation, this review summarizes the recent research progress from the perspective of key components of SIBs for the first time and evaluates the characteristics of various improvement strategies. By orderly analyzing the root causes of safety problems associated with different components in SIBs(including electrolytes, anodes, and cathodes), corresponding improvement strategies for each component were discussed systematically. In addition, some noteworthy points and perspectives including the chain reaction between security issues and the selection of improvement strategies tailored to different needs have also been proposed. In brief, this review is designed to deepen our understanding of the SIBs safety issues and provide guidance and assistance for designing high-safety SIBs.

关键词： Anode bulk modification Cathode bulk design Organic electrolytes modification Safety Sodium ion batteries Solid-state electrolyte

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Small mammal community composition impacts bank vole (Clethrionomys glareolus) population dynamics and associated seroprevalence of Puumala orthohantavirus

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Integrative Zoology 2024年第1期19卷 52-65页

作者： Felicitas Maria BUJNOCH Daniela REIL Stephan DREWES Ulrike MROSENFELD Rainer G.ULRICH Jens JACOB Christian IMHOLT Julius Kühn-institute Federal Research Centre for Cultivated PlantsInstitute for Epidemiology and Pathogen DiagnosticsRodent ResearchMünsterGermany University of Münster Institute for Evolution and BiodiversityMünsterGermany Friedrich-Loeffler-Institut Federal Research Institute for Animal HealthInstitute of Novel and Emerging Infectious DiseasesGreifswald-Insel RiemsGermany

Rodents are important reservoirs for zoonotic pathogens that cause diseases in humans.Biodiversity is hypoth-esized to be closely related to pathogen prevalence through multiple direct and indirect pathways.For example,the presence of non-host species can reduce contact rates of the main reservoir host and thus reduce the risk of transmission(“dilution effect”).In addition,an overlap in ecological niches between two species could lead to increased interspecific competition,potentially limiting host densities and reducing density-dependent pathogen transmission processes.In this study,we investigated the relative impact of population-level regulation of direct and indirect drivers of the prevalence of Puumala orthohantavirus(PUUV)in bank voles(Clethrionomys glareolus)during years with high abundance.We compiled data on small mammal community composition from four regions in Germany between 2010 and 2013.Structural equation modeling revealed a strong seasonality in PUUV control mechanisms in bank voles.The abundance of shrews tended to have a negative relationship with host abundance,and host abundance positively influenced PUUV seroprevalence,while at the same time increasing the abundance of competing non-hosts like the wood mouse(Apodemus sylvaticus)and the yellow-neckedfield mouse(Apodemusflavicollis)were associated with reduced PUUV seroprevalence in the host.These results indicate that for PUUV in bank voles,dilution is associated with increased interspecific competition.Anthropogenic pressures leading to the decline of Apodemus spp.in a specific habitat could lead to the amplification of mechanisms promoting PUUV transmission within the host populations.

关键词： bank vole biodiversity Puumala orthohantavirus small mammals

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Performance of the Multilayer Film for Infrared Stealth based on VO2 Thermochromism

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Journal of Thermal Science 2024年第4期33卷 1312-1324页

作者： LI Yaru WANG Fuqiang ZHANG Aoyu FU Zhichang SU Ronghua GAO Tengfei WANG Zhen GUO Jicheng ORDOS institute of Technology School of New Energy Harbin Institute of Technology at Weihai School of Energy Science and Engineering Harbin Institute of Technology Defense Engineering institute AMSPLA

With the development of detection and identification technology,infrared stealth is of great value to realize anti-reconnaissance detection of military targets.At present,infrared stealth materials generally have deficiency,such as complex structure,inconvenient radiation regulation and cumbersome preparation steps,which greatly limit the practical application of infrared stealth materials.In view of the above deficiency of infrared stealth materials,we proposed a kind of multilayer film for infrared stealth using VO2thermochromism based on the temperature response mechanism of tuna to adjust its color,and through the intelligent reversible radiation regulation mechanism to meet the infrared stealth requirements of tanks in different actual scenes.The results show that when the temperature increases from 300 K to 373 K,the peak emissivity of the film decreases from 94% to 20% in the 8-14 μm band after structural optimization,which can realize the infrared stealth of the high temperature target in the 8-14 μm band.The average emissivity of the multilayer film for infrared stealth at3-5μm and 8-14μm band can be reduced to 34% and 27% at 373 K,and the peak emissivity at 5-8 μm band can reach 65%,realizing dual-band infrared stealth in the 3-5 μm and 8-14 μm bands and heat dissipation in the 5-8μm band.The multilayer film for infrared stealth based on VO2thermochromism designed by the authors can meet the characteristics of simple film structure,convenient radiation regulation and simple preparation.

关键词： vanadium dioxide multilayer film infrared stealth thermal management

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