Field emission electric propulsion(FEEP) thrusters possess excellent characteristics, such as high specific impulse, low power requirements, compact size and precise pointing capabilities,making them ideal propulsion ...Field emission electric propulsion(FEEP) thrusters possess excellent characteristics, such as high specific impulse, low power requirements, compact size and precise pointing capabilities,making them ideal propulsion devices for micro-nano satellites. However, the detection of certain aspects, such as the evolution process of the liquid cone and the physical quantities at the cone apex, proves challenging due to the minute size of the needle tip and the vacuum environment in which they operate. Consequently, this paper introduces a computational fluid dynamics(CFD) model to gain insight into the formation process of the liquid cone on the tip apex of indium FEEP. The CFD model is based on electrohydrodynamic(EHD) equations and the volume of fluid(VOF) method. The entire cone formation process can be divided into three stages, and the time-dependent characteristics of the physical quantities at the cone apex are investigated. The influences of film thickness, apex radius size and applied voltage are compared.The results indicate a gradual increase in the values of electrostatic stress and surface tension stress at the cone apex over an initial period, followed by a rapid escalation within a short duration.Apex configurations featuring a small radius, thick film and high voltage exhibit a propensity for liquid cone formation, and the cone growth time decreases as the film thickness increases.Moreover, some unstable behavior is observed during the cone formation process.展开更多
Porphyra polysaccharide is a special kind of nutrient showing multiple physiological functions including regulating cell proliferation,but the detailed mechanisms are not fully revealed,impairing its further developme...Porphyra polysaccharide is a special kind of nutrient showing multiple physiological functions including regulating cell proliferation,but the detailed mechanisms are not fully revealed,impairing its further development and applications.This work was to purify and characterize the Porphyra haitanensis polysaccharide(PH),investigate its physiological function,and demonstrate the underlying mechanisms.The purified PH was first characterized by Fourier-transform infrared spectroscopy.Then an intestinal epithelial cell model was established,in which PH significantly suppressed cell hyperplasia.Specifically,PH activated the Hippo/YAP pathway,which subsequently activated m TOR pathway,however m TOR activated Hippo in the absence of PH.Moreover,both the inhibition of Hippo by YAP1 knock-down and the suppression of m TOR by rapamycin impaired PH function.These results indicated that PH attenuated hyperplasia activity by remodeling the cross-talk between Hippo/YAP and m TOR pathways,which revealed potential targets and approaches for treating hyperplasia-related diseases and provided novel ways to utilize P.haitanensis as well as other related functional foods.展开更多
Organic electrochemical transistors(OECTs)have attracted attention due to their unique function of converting ionic and biological signals into electronic signals,high transconductance,low energy consumption(below 1 V...Organic electrochemical transistors(OECTs)have attracted attention due to their unique function of converting ionic and biological signals into electronic signals,high transconductance,low energy consumption(below 1 V),stable operation in aqueous media,good biocompatibility[1,2].However,most OECTs are usually built on brittle and stiff substrates,and inappropriate to be adhered to or contacted with delicate human skin,thus impeding their use in wearable electronics.It is desirable to exploit stretchable OECTs to reduce the mechanical mismatch with soft tissues.展开更多
High temperature is an abiotic stress factor that threatens plant growth and development.Autophagy in response to heat stress involves the selective removal of heat-induced protein complexes.Previously,we showed that ...High temperature is an abiotic stress factor that threatens plant growth and development.Autophagy in response to heat stress involves the selective removal of heat-induced protein complexes.Previously,we showed that a crucial autophagy protein from apple,MdATG18a,has a positive effect on drought tolerance.In the present study,we treated transgenic apple(Malus domestica)plants overexpressing MdATG18a with high temperature and found that autophagy protected them from heat stress.Overexpression of MdATG18a in apple enhanced antioxidase activity and contributed to the production of increased beneficial antioxidants under heat stress.Transgenic apple plants exhibited higher photosynthetic capacity,as shown by the rate of CO_(2) assimilation,the maximum photochemical efficiency of photosystem II(PSII),the effective quantum yield,and the electron transport rates in photosystems I and II(PSI and PSII,respectively).We also detected elevated autophagic activity and reduced damage to chloroplasts in transgenic plants compared to WT plants.In addition,the transcriptional activities of several HSP genes were increased in transgenic apple plants.In summary,we propose that autophagy plays a critical role in basal thermotolerance in apple,primarily through a combination of enhanced antioxidant activity and reduced chloroplast damage.展开更多
An ionic liquid ion source(ILIS)is a kind of high brightness ion source capable of providing high-speed positive or negative ion beams.This paper presents a miniaturized ILIS based on an array of porous metal strips.T...An ionic liquid ion source(ILIS)is a kind of high brightness ion source capable of providing high-speed positive or negative ion beams.This paper presents a miniaturized ILIS based on an array of porous metal strips.The porous emitter array,integrated with seven 10 mm long strips,is fabricated using wire electrical discharge machining(WEDM)combined with electrochemical etching.The assembled ILIS is 30 mm×30 mm×17.5 mm in size and weighs less than 25 g.A series of experiments,including anⅠ-Ⅴcharacteristic test,a retarding potential analyzer(RPA)test,and a spatial plume distribution test,have been conducted in vacuo to characterize the performance of the ILIS.Results show that the emitted current is up to about 800μA and ion transparency is as high as 94%.Besides,RPA curves reveal that the total fragmentation rate of the emitted particles accounts for 48.8%in positive mode and 59.8%in negative mode.Further,with the increase in applied acceleration voltage,the voltage loss rises while the energy efficiency decreases.It is also found that the plume perpendicular to the strips has a higher divergence than the one parallel to the strips.A numerical simulation by COMSOL reveals that the electric field distribution between the two electrodes results in such a spatial plume profile.展开更多
In the published Figure 11,errors appeared in Figure 1B on page 69.In Figure 1B,bands for p-Akt S473,Akt,and Actin in H1355 cells were mistakenly placed.Here,we have updated Figure 1B to correct the mistake above.The ...In the published Figure 11,errors appeared in Figure 1B on page 69.In Figure 1B,bands for p-Akt S473,Akt,and Actin in H1355 cells were mistakenly placed.Here,we have updated Figure 1B to correct the mistake above.The errors do not impact the conclusions of this article.We apologize for the errors and for any confusion it may have caused.展开更多
Though tremendous efforts have been made to investigate electrospray,some aspects,such as the evolution of the menisci on the micropores of porous emitter tips and the transient response of the meniscus during the pol...Though tremendous efforts have been made to investigate electrospray,some aspects,such as the evolution of the menisci on the micropores of porous emitter tips and the transient response of the meniscus during the polarity alternation,need to be further understood.This paper presents a computation fluid dynamics(CFD)model to describe the meniscus formation in the ionic liquid electrospray process.The CFD model,based on the Taylor–Melcher leaky dielectric fluid theory and the volume of fluid(VOF)method,is validated by experiments.The evolution of the meniscus on the basis of a micropore is presented using two typical ionic liquids,EMI-BF_(4) and EMI-Im.The influences of the pore size,flow rate and applied voltage on the formation of the meniscus have been studied.Results show that a larger pore is more likely to start emission,and the time consumed for liquid meniscus formation decreases with increasing applied voltage and flow rate.Further,it is found that alternation of polarity does not destroy the structure of the meniscus but retards the formation process,and a faster polarity alteration leads to a shorter delay in meniscus formation time.展开更多
Objective: Activating KRAS mutations are the most common drivers in the development of non-small cell lung cancer(NSCLC).However, unsuccess of treatment by direct inhibition of KRAS has been proven. Deregulation of PI...Objective: Activating KRAS mutations are the most common drivers in the development of non-small cell lung cancer(NSCLC).However, unsuccess of treatment by direct inhibition of KRAS has been proven. Deregulation of PI3K signaling plays an important role in tumorigenesis and drug resistance in NSCLC. The activity of PI3Kα-selective inhibition against KRAS-mutated NSCLC remains largely unknown.Methods: Cell proliferation was detected by sulforhodamine B assay. Cell cycle distribution and apoptosis were measured by flow cytometry. Cell signaling was assessed by Western blot and immunohistochemistry. RNA interference was used to down-regulate the expression of cyclin D1. Human NSCLC xenografts were employed to detect therapeutic efficacy in vivo.Results: CYH33 possessed variable activity against a panel of KRAS-mutated NSCLC cell lines. Although CYH33 blocked AKT phosphorylation in all tested cells, Rb phosphorylation decreased in CYH33-sensitive, but not in CYH33-resistant cells, which was consistent with G1 phase arrest in sensitive cells. Combined treatment with the CDK4/6 inhibitor, PD0332991, and CYH33 displayed synergistic activity against the proliferation of both CYH33-sensitive and CYH33-resistant cells, which was accompanied by enhanced G1-phase arrest. Moreover, down-regulation of cyclin D1 sensitized NSCLC cells to CYH33. Reciprocally, CYH33 abrogated the PD0332991-induced up-regulation of cyclin D1 and phosphorylation of AKT in A549 cells. Co-treatment with these two drugs demonstrated synergistic activity against A549 and H23 xenografts, with enhanced inhibition of Rb phosphorylation.Conclusions: Simultaneous inhibition of PI3Kα and CDK4/6 displayed synergistic activity against KRAS-mutated NSCLC. These data provide a mechanistic rationale for the combination of a PI3Kα inhibitor and a CDK4/6 inhibitor for the treatment of KRASmutated NSCLC.展开更多
Two-dimensional(2D)magnets provide an ideal platform to explore new physical phenomena in fundamental magnetism and to realize the miniaturization of magnetic devices.The study on its domain structure evolution with t...Two-dimensional(2D)magnets provide an ideal platform to explore new physical phenomena in fundamental magnetism and to realize the miniaturization of magnetic devices.The study on its domain structure evolution with thickness is of great significance for better understanding the 2D magnetism.Here,we investigate the magnetization reversal and domain structure evolution in 2D ferromagnet Fe_(3)GeTe_(2)(FGT)with a thickness range of 11.2-112 nm.Three types of domain structures and their corresponding hysteresis loops can be obtained.The magnetic domain varies from a circular domain via a dendritic domain to a labyrinthian domain with increasing FGT thickness,which is accompanied by a transition from squared to slanted hysteresis loops with reduced coercive fields.These features can be ascribed to the total energy changes from exchange interaction-dominated to dipolar interaction-dominated with increasing FGT thickness.Our finding not only enriches the fundamental magnetism,but also paves a way towards spintronics based on 2D magnet.展开更多
The superconducting ground state of kagome metals AV_(3)Sb_(5)(where A stands for K,Rb,or Cs)emerges from an exotic charge density wave(CDW)state that potentially breaks both rotational and time reversal symmetries.Ho...The superconducting ground state of kagome metals AV_(3)Sb_(5)(where A stands for K,Rb,or Cs)emerges from an exotic charge density wave(CDW)state that potentially breaks both rotational and time reversal symmetries.However,the specifics of the Cooper pairing mechanism,and the nature of the interplay between these two states remain elusive,largely due to the lack of momentum-space(k-space)superconducting energy gap structure.By implementing Bogoliubov quasiparticle interference(B QPI)imaging,we obtain k-space information on the multiband superconducting gap structureΔ_(SC)^(i)(k)in pristine CsV_(3)Sb_(5).We show that the estimated energy gap on the vanadium d_(xy/x^(2)-y^(2))orbital is anisotropic but nodeless,with a minimal value located near the M point.Interestingly,a comparison ofΔ_(SC)^(i)(k)with the CDW gapΔ_(CDW)^(i)(k)obtained by angle-re solved photoemission spectro scopy(ARPES)reveals direct k-space competition between the se two order parameters,i.e.,the opening of a large(small)CDW gap at a given momentum corresponds to a small(large)superconducting gap.When the long-range CDW order is suppressed by replacing vanadium with titanium,we find a nearly isotropic energy gap on both the V and Sb bands.This information will be critical for identifying the microscopic pairing mechanism and its interplay with intertwined electro nic orders in this kagome superconductor family.展开更多
Epigenetic therapies that cause genome-wide epigenetic alterations,could trigger local interplay between different histone marks,leading to a switch of transcriptional outcome and therapeutic responses of epigenetic t...Epigenetic therapies that cause genome-wide epigenetic alterations,could trigger local interplay between different histone marks,leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment.However,in human cancers with diverse oncogenic activation,how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood.We herein discover that the hedgehog(Hh)pathway reprograms the histone methylation landscape in breast cancer,especially in triple-negative breast cancer(TNBC).This facilitates the histone acetylation caused by histone deacetylase(HDAC)inhibitors and gives rise to new therapeutic vulnerability of combination therapies.Specifically,overexpression of zinc finger protein of the cerebellum 1(ZIC1)in breast cancer promotes Hh activation,facilitating the switch of H3K27 methylation(H3K27me)to acetylation(H3K27ac).The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes.Using multiple in vivo breast cancer models including patient-derived TNBC xenograft,we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer.Together,this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.展开更多
Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,...Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment.Therefore,this study developed a novel and selective inhibitor of CSFIR and VEGFR,SYHA1813,possessing potent antitumor activity against GBM.SYHA1813 inhibited VEGFR and CSFIR kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo.SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models,including temozolomide(TMZ)insensitive tumors.Notably,SYHA1813 could penetrate the blood-brain barrier(BBB)and prolong the survival time of mice bearing intracranial GBM xenografts.Moreover,SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody.As a clinical proof of concept,SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial.The data of this study support the rationale for an ongoing phase I clinical study(ChiCTR2100045380).展开更多
Polarization control is at the heart of high-capacity data optical communication systems,such as polarizationdivision multiplexers and Stokes vector modulation transmitters.Despite passive polarization control being m...Polarization control is at the heart of high-capacity data optical communication systems,such as polarizationdivision multiplexers and Stokes vector modulation transmitters.Despite passive polarization control being mature,the realization of monolithically integrated polarization controllers and single longitudinal mode light sources,such as distributed-feedback(DFB)lasers,is of importance.In this research,we report an AlGaInAs multiple-quantum-well photonic integrated circuit device which can control the state of polarization of the output light source,consisting of a polarization mode converter(PMC),a differential phase shifter(DPS),and a sidewall grating DFB laser.We demonstrate an asymmetrical stepped-height ridge waveguide PMC to realize TE to TM polarization conversion and a symmetrical straight waveguide DPS to enable polarization rotation from approximately counterclockwise circular polarization to linear polarization.Based on the identical epitaxial layer scheme,all the PMC,DPS,and DFB lasers can be integrated monolithically using only a single step of metalorganic vapor-phase epitaxy and two steps of III-V material dry etching.For the DFB-PMC device,a high TE to TM polarization conversion efficiency(98.4%)over a wide range of DFB injection currents is reported at 1555 nm wavelength.For the DFB-PMC-DPS device,a nearly 60°rotation of the Stokes vector on the Poincarésphere was obtained with a range of bias voltage from 0 to-3.0 V at a laser drive current of 170 mA.展开更多
Leveraging the unique physical properties,two-dimensional(2D)materials have circumvented the disadvantages of conventional epitaxial semiconductors and held great promise for potential optoelectronic applications.So f...Leveraging the unique physical properties,two-dimensional(2D)materials have circumvented the disadvantages of conventional epitaxial semiconductors and held great promise for potential optoelectronic applications.So far,two main detector architectures including photodiode based on a van der Waals P-N junction or Schottky junction and phototransistor based on individual 2D materials or hybrids have been well developed.However,a trade-off between responsivity and speed always exists in those technologies thus hindering the overall performance improvement.Here,we propose a new device concept by sandwiching the 2D anisotropic semimetal between p-type and n-type semiconductors in the out-of-plane direction,called PSN architecture,realizing the improvement of each parameter including broad spectral coverage,fast speed,high sensitivity,power-free and polarization-sensitive.We stack the p-type 2H-MoTe_(2),Weyl semimetal 1T-MoTe_(2)and n-type SnSe_(2)layer-by-layer constructing vertical sandwich structure where the top and bottom layers contribute to the internal built-in electric field,the intermediate layer can facilitate the exciton dissociation and act as infrared polarized light sensitizers.As a result,this PSN device exhibits broadband photo-response from 405 to 1,550 nm without external bias supply.At optical communication band(1,310 nm),operating at self-driven mode and room temperature,the responsivity and detectivity can reach up to 64.2 mA·W^(–1)and 2.2×10^(11)Jones,respectively,along with fast speed on the order of millisecond.Moreover,the device simultaneously exhibits exceptional detection capability for infrared polarized light,demonstrating the anisotropic photocurrent ratio of 1.55 at 1,310 nm and 2.02 at 1,550 nm,which is attributed to the strong in-plane optical anisotropy of middle 1T-MoTe_(2)layer.This work develops a new photodetector scheme with novel PSN architecture toward broadband,self-power,polarized light sensing and imaging modules.展开更多
All memristor neuromorphic networks have great potential and advantage in both technology and computational protocols for artificial intelligence.It is crucial to find suitable elementary units for both performing fea...All memristor neuromorphic networks have great potential and advantage in both technology and computational protocols for artificial intelligence.It is crucial to find suitable elementary units for both performing featured neuromorphic functions and fabrication in large scale.Here a simple memristive structure,Nb/HfOx/Pd,is proposed for this goal.Its two resistive switching mechanisms,Mott transition of NbO2 and oxygen vacancy(Vo)migration,can be controlled by modulating external bias directions.Negative bias activates reversible phase transition and restrains Vo filament formation to allow the memristor to mimic the firing action potential.Positive bias activates Vo filament formation and restrains the other to allow the memristor to mimic synaptic plasticity and learning protocols.The system can respond adaptively to naturally generated action potentials and modified synaptic signals from the same memristive structure.In addition,some special features related to signal encoding and recognition are discovered when the system is settled according to chaos circuit theory.Our study provides a novel approach for designing elementary units for neuromorphic computations.展开更多
Dear Editor,Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related death worldwide with a 5-year survival rate-50-80% after curative treatment,like surgery,targeted therapy plus TACE or RFA or loca...Dear Editor,Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related death worldwide with a 5-year survival rate-50-80% after curative treatment,like surgery,targeted therapy plus TACE or RFA or local treatments,immunotherapy,and so on.1 The approval of several angiogenesis inhibitors,such as sorafenib,regorafenib,lenvatinib,and cabozantinib,have shown therapeutic potential for HCC treatment.However,the improvement of overall survival or progression-free survival is still limited based on angiogenesis inhibitor monotherapy at present.展开更多
Rapid urbanisation in China has resulted in an increased demand for land in towns and cities.To upgrade and modernise,China has also moved many major industries from urban centres to less populated areas.With the high...Rapid urbanisation in China has resulted in an increased demand for land in towns and cities.To upgrade and modernise,China has also moved many major industries from urban centres to less populated areas.With the high economic value of urban land,the transformation and utilisation of brownfield areas have become important economically and socially.The Chinese government has recognised the need for strong frameworks to safeguard soil and groundwater quality,with brownfield sites a key category for management.Strong scientific,regulatory and decision-making frameworks are needed and being adopted to ensure practical,careful and wise use of central and localised government resources,to manage the reuse and regeneration of these brownfield sites.This paper reviews the context,policies and management procedures of developing brownfield sites in countries with a history of brownfield management and discusses China’s current situation and priorities for brownfield governance and redevelopment.These include(1)clarification of brownfield site soil contamination risk control standards and risk assessment procedures,(2)the responsibilities of different national and local agencies,(3)the establishment of a national expert committee to advise on best practices,policy and process,(4)the use of registered brownfield databases at national,provincial,municipal and county levels,and(5)the set up of soil pollution prevention fund at the provincial level.展开更多
Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells(NSCs/NPCs).It involves the proliferation and neuronal fate specification/differentiation of NSCs,as well as migration,maturat...Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells(NSCs/NPCs).It involves the proliferation and neuronal fate specification/differentiation of NSCs,as well as migration,maturation and functional integration of the neuronal progeny into neuronal network.NSCs exhibit the two essential properties of stem cells:self-renewal and multi-potency.Contrary to previous dogma that neurogenesis happens only during development,it is generally accepted now that neurogenesis can take place throughout life in mammalian brains.This raises a new therapeutic potential of applying stem cell therapy for stroke,neurodegenerative diseases and other diseases.However,the maintenance and differentiation of NSCs/NPCs are tightly controlled by the extremely intricate molecular networks.Uncovering the underlying mechanisms that drive the differentiation,migration and maturation of specific neuronal lineages for use in regenerative medicine is,therefore,crucial for the application of stem cell for clinical therapy as well as for providing insight into the mechanisms of human neurogenesis.Here,we focus on the role of bone morphogenetic protein(BMP)signaling in NSCs during mammalian brain development.展开更多
Wound management is an important issue that places enormous pressure on the physical and mental health of patients,especially in cases of infection,where the increased inflammatory response could lead to severe hypert...Wound management is an important issue that places enormous pressure on the physical and mental health of patients,especially in cases of infection,where the increased inflammatory response could lead to severe hypertrophic scars(HSs).In this study,a hydrogel dressing was developed by combining the high strength and toughness,swelling resistance,antibacterial and antioxidant capabilities.The hydrogel matrix was composed of a double network of polyvinyl alcohol(PVA)and agarose with excellent mechanical properties.Hyperbranched polylysine(HBPL),a highly effective antibacterial cationic polymer,and tannic acid(TA),a strong antioxidant molecule,were added to the hydrogel as functional components.Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA.In the in vivo studies of methicillin-resistant Staphylococcus aureus(MRSA)infection,the hydrogel had shown obvious promotion of wound healing,and more profoundly,significant suppression of scar formation.Due to the common raw materials and simple preparation methods,this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.展开更多
基金supported by National Natural Science Foundation of China(No.52075334)。
文摘Field emission electric propulsion(FEEP) thrusters possess excellent characteristics, such as high specific impulse, low power requirements, compact size and precise pointing capabilities,making them ideal propulsion devices for micro-nano satellites. However, the detection of certain aspects, such as the evolution process of the liquid cone and the physical quantities at the cone apex, proves challenging due to the minute size of the needle tip and the vacuum environment in which they operate. Consequently, this paper introduces a computational fluid dynamics(CFD) model to gain insight into the formation process of the liquid cone on the tip apex of indium FEEP. The CFD model is based on electrohydrodynamic(EHD) equations and the volume of fluid(VOF) method. The entire cone formation process can be divided into three stages, and the time-dependent characteristics of the physical quantities at the cone apex are investigated. The influences of film thickness, apex radius size and applied voltage are compared.The results indicate a gradual increase in the values of electrostatic stress and surface tension stress at the cone apex over an initial period, followed by a rapid escalation within a short duration.Apex configurations featuring a small radius, thick film and high voltage exhibit a propensity for liquid cone formation, and the cone growth time decreases as the film thickness increases.Moreover, some unstable behavior is observed during the cone formation process.
基金supported by the National Key R&D Program of China(2017YFD0400203)the National Natural Science Foundation of China(31801452)+3 种基金the Zhejiang Provincial Science and Technology Foundation of China(2018C02025 and 2019C02069)the Zhejiang Provincial Natural Science Foundation of China(LGN21C200013)the China Postdoctoral Science Foundation(2019M662108)the Scientific Research Fund of Zhejiang Provincial Education Department(Y201942404)。
文摘Porphyra polysaccharide is a special kind of nutrient showing multiple physiological functions including regulating cell proliferation,but the detailed mechanisms are not fully revealed,impairing its further development and applications.This work was to purify and characterize the Porphyra haitanensis polysaccharide(PH),investigate its physiological function,and demonstrate the underlying mechanisms.The purified PH was first characterized by Fourier-transform infrared spectroscopy.Then an intestinal epithelial cell model was established,in which PH significantly suppressed cell hyperplasia.Specifically,PH activated the Hippo/YAP pathway,which subsequently activated m TOR pathway,however m TOR activated Hippo in the absence of PH.Moreover,both the inhibition of Hippo by YAP1 knock-down and the suppression of m TOR by rapamycin impaired PH function.These results indicated that PH attenuated hyperplasia activity by remodeling the cross-talk between Hippo/YAP and m TOR pathways,which revealed potential targets and approaches for treating hyperplasia-related diseases and provided novel ways to utilize P.haitanensis as well as other related functional foods.
基金supported by the National Natural Science Foundation of China (52263019)the National Natural Science Foundation of China (21961160720)+3 种基金the Yunnan Fundamental Research Project (202301AT070313)the Yunnan Provincial Department of Education Science Research Fund (2023Y0236)the National Key Research and Development Program of China (2022YFB3803300)the open research fund of Songshan Lake Materials Laboratory (2021SLABFK02)。
文摘Organic electrochemical transistors(OECTs)have attracted attention due to their unique function of converting ionic and biological signals into electronic signals,high transconductance,low energy consumption(below 1 V),stable operation in aqueous media,good biocompatibility[1,2].However,most OECTs are usually built on brittle and stiff substrates,and inappropriate to be adhered to or contacted with delicate human skin,thus impeding their use in wearable electronics.It is desirable to exploit stretchable OECTs to reduce the mechanical mismatch with soft tissues.
基金supported by the National Key Research and Development Program of China(2018YFD1000300)the Earmarked Fund for China Agriculture Research System(CARS-27).
文摘High temperature is an abiotic stress factor that threatens plant growth and development.Autophagy in response to heat stress involves the selective removal of heat-induced protein complexes.Previously,we showed that a crucial autophagy protein from apple,MdATG18a,has a positive effect on drought tolerance.In the present study,we treated transgenic apple(Malus domestica)plants overexpressing MdATG18a with high temperature and found that autophagy protected them from heat stress.Overexpression of MdATG18a in apple enhanced antioxidase activity and contributed to the production of increased beneficial antioxidants under heat stress.Transgenic apple plants exhibited higher photosynthetic capacity,as shown by the rate of CO_(2) assimilation,the maximum photochemical efficiency of photosystem II(PSII),the effective quantum yield,and the electron transport rates in photosystems I and II(PSI and PSII,respectively).We also detected elevated autophagic activity and reduced damage to chloroplasts in transgenic plants compared to WT plants.In addition,the transcriptional activities of several HSP genes were increased in transgenic apple plants.In summary,we propose that autophagy plays a critical role in basal thermotolerance in apple,primarily through a combination of enhanced antioxidant activity and reduced chloroplast damage.
基金supported by National Natural Science Foundation of China(No.52075334)。
文摘An ionic liquid ion source(ILIS)is a kind of high brightness ion source capable of providing high-speed positive or negative ion beams.This paper presents a miniaturized ILIS based on an array of porous metal strips.The porous emitter array,integrated with seven 10 mm long strips,is fabricated using wire electrical discharge machining(WEDM)combined with electrochemical etching.The assembled ILIS is 30 mm×30 mm×17.5 mm in size and weighs less than 25 g.A series of experiments,including anⅠ-Ⅴcharacteristic test,a retarding potential analyzer(RPA)test,and a spatial plume distribution test,have been conducted in vacuo to characterize the performance of the ILIS.Results show that the emitted current is up to about 800μA and ion transparency is as high as 94%.Besides,RPA curves reveal that the total fragmentation rate of the emitted particles accounts for 48.8%in positive mode and 59.8%in negative mode.Further,with the increase in applied acceleration voltage,the voltage loss rises while the energy efficiency decreases.It is also found that the plume perpendicular to the strips has a higher divergence than the one parallel to the strips.A numerical simulation by COMSOL reveals that the electric field distribution between the two electrodes results in such a spatial plume profile.
文摘In the published Figure 11,errors appeared in Figure 1B on page 69.In Figure 1B,bands for p-Akt S473,Akt,and Actin in H1355 cells were mistakenly placed.Here,we have updated Figure 1B to correct the mistake above.The errors do not impact the conclusions of this article.We apologize for the errors and for any confusion it may have caused.
基金supported by National Natural Science Foundation of China(No.52075334)。
文摘Though tremendous efforts have been made to investigate electrospray,some aspects,such as the evolution of the menisci on the micropores of porous emitter tips and the transient response of the meniscus during the polarity alternation,need to be further understood.This paper presents a computation fluid dynamics(CFD)model to describe the meniscus formation in the ionic liquid electrospray process.The CFD model,based on the Taylor–Melcher leaky dielectric fluid theory and the volume of fluid(VOF)method,is validated by experiments.The evolution of the meniscus on the basis of a micropore is presented using two typical ionic liquids,EMI-BF_(4) and EMI-Im.The influences of the pore size,flow rate and applied voltage on the formation of the meniscus have been studied.Results show that a larger pore is more likely to start emission,and the time consumed for liquid meniscus formation decreases with increasing applied voltage and flow rate.Further,it is found that alternation of polarity does not destroy the structure of the meniscus but retards the formation process,and a faster polarity alteration leads to a shorter delay in meniscus formation time.
基金supported by grants from "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDA12020218 & XDA12020111)National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program" (Grant No. 2018ZX09711002-011-014)+1 种基金National Natural Science Foundation of China (Grant No. 81773760)partially supported by FudanSIMM Joint Research Program (Grant No. FUSIMM20172005)
文摘Objective: Activating KRAS mutations are the most common drivers in the development of non-small cell lung cancer(NSCLC).However, unsuccess of treatment by direct inhibition of KRAS has been proven. Deregulation of PI3K signaling plays an important role in tumorigenesis and drug resistance in NSCLC. The activity of PI3Kα-selective inhibition against KRAS-mutated NSCLC remains largely unknown.Methods: Cell proliferation was detected by sulforhodamine B assay. Cell cycle distribution and apoptosis were measured by flow cytometry. Cell signaling was assessed by Western blot and immunohistochemistry. RNA interference was used to down-regulate the expression of cyclin D1. Human NSCLC xenografts were employed to detect therapeutic efficacy in vivo.Results: CYH33 possessed variable activity against a panel of KRAS-mutated NSCLC cell lines. Although CYH33 blocked AKT phosphorylation in all tested cells, Rb phosphorylation decreased in CYH33-sensitive, but not in CYH33-resistant cells, which was consistent with G1 phase arrest in sensitive cells. Combined treatment with the CDK4/6 inhibitor, PD0332991, and CYH33 displayed synergistic activity against the proliferation of both CYH33-sensitive and CYH33-resistant cells, which was accompanied by enhanced G1-phase arrest. Moreover, down-regulation of cyclin D1 sensitized NSCLC cells to CYH33. Reciprocally, CYH33 abrogated the PD0332991-induced up-regulation of cyclin D1 and phosphorylation of AKT in A549 cells. Co-treatment with these two drugs demonstrated synergistic activity against A549 and H23 xenografts, with enhanced inhibition of Rb phosphorylation.Conclusions: Simultaneous inhibition of PI3Kα and CDK4/6 displayed synergistic activity against KRAS-mutated NSCLC. These data provide a mechanistic rationale for the combination of a PI3Kα inhibitor and a CDK4/6 inhibitor for the treatment of KRASmutated NSCLC.
基金Project supported by the National Key R&D Program of China(Grant Nos.2017YFA0206202 and 2019YFA0308000)the National Natural Science Foundation of China(Grant Nos.51871130,62022089,and 11874405)the Youth Innovation Promotion Association of Chinese Academy of Sciences(Grant No.2019007)。
文摘Two-dimensional(2D)magnets provide an ideal platform to explore new physical phenomena in fundamental magnetism and to realize the miniaturization of magnetic devices.The study on its domain structure evolution with thickness is of great significance for better understanding the 2D magnetism.Here,we investigate the magnetization reversal and domain structure evolution in 2D ferromagnet Fe_(3)GeTe_(2)(FGT)with a thickness range of 11.2-112 nm.Three types of domain structures and their corresponding hysteresis loops can be obtained.The magnetic domain varies from a circular domain via a dendritic domain to a labyrinthian domain with increasing FGT thickness,which is accompanied by a transition from squared to slanted hysteresis loops with reduced coercive fields.These features can be ascribed to the total energy changes from exchange interaction-dominated to dipolar interaction-dominated with increasing FGT thickness.Our finding not only enriches the fundamental magnetism,but also paves a way towards spintronics based on 2D magnet.
基金supported by the National Key R&D Program of China(Grant Nos.2022YFA1602600,and 2018YFA0305602)the National Natural Science Foundation of China(Grant Nos.11888101,12074364,52273309,and 52261135638)+5 种基金the Innovation Program for Quantum Science and Technology(Grant No.2021ZD0302802)the Basic Research Program of the Chinese Academy of Sciences Based on Major Scientific Infrastructures(Grant No.JZHKYPT-2021-08)the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB25000000)the Anhui Initiative in Quantum Information Technologies(Grant No.AHY160000)the Fundamental Research Funds for the Central Universities(Grant Nos.WK3510000012,and WK3510000015)the Major Basic Program of the Natural Science Foundation of Shandong Province(Grant No.ZR2021ZD01)。
文摘The superconducting ground state of kagome metals AV_(3)Sb_(5)(where A stands for K,Rb,or Cs)emerges from an exotic charge density wave(CDW)state that potentially breaks both rotational and time reversal symmetries.However,the specifics of the Cooper pairing mechanism,and the nature of the interplay between these two states remain elusive,largely due to the lack of momentum-space(k-space)superconducting energy gap structure.By implementing Bogoliubov quasiparticle interference(B QPI)imaging,we obtain k-space information on the multiband superconducting gap structureΔ_(SC)^(i)(k)in pristine CsV_(3)Sb_(5).We show that the estimated energy gap on the vanadium d_(xy/x^(2)-y^(2))orbital is anisotropic but nodeless,with a minimal value located near the M point.Interestingly,a comparison ofΔ_(SC)^(i)(k)with the CDW gapΔ_(CDW)^(i)(k)obtained by angle-re solved photoemission spectro scopy(ARPES)reveals direct k-space competition between the se two order parameters,i.e.,the opening of a large(small)CDW gap at a given momentum corresponds to a small(large)superconducting gap.When the long-range CDW order is suppressed by replacing vanadium with titanium,we find a nearly isotropic energy gap on both the V and Sb bands.This information will be critical for identifying the microscopic pairing mechanism and its interplay with intertwined electro nic orders in this kagome superconductor family.
基金supported by the National Natural Science Foundation of China(Nos.82225046,81821005,and 81903640)the Program of Shanghai Academic Research Leader(20XD1424800,China)。
文摘Epigenetic therapies that cause genome-wide epigenetic alterations,could trigger local interplay between different histone marks,leading to a switch of transcriptional outcome and therapeutic responses of epigenetic treatment.However,in human cancers with diverse oncogenic activation,how oncogenic pathways cooperate with epigenetic modifiers to regulate the histone mark interplay is poorly understood.We herein discover that the hedgehog(Hh)pathway reprograms the histone methylation landscape in breast cancer,especially in triple-negative breast cancer(TNBC).This facilitates the histone acetylation caused by histone deacetylase(HDAC)inhibitors and gives rise to new therapeutic vulnerability of combination therapies.Specifically,overexpression of zinc finger protein of the cerebellum 1(ZIC1)in breast cancer promotes Hh activation,facilitating the switch of H3K27 methylation(H3K27me)to acetylation(H3K27ac).The mutually exclusive relationship of H3K27me and H3K27ac allows their functional interplay at oncogenic gene locus and switches therapeutic outcomes.Using multiple in vivo breast cancer models including patient-derived TNBC xenograft,we show that Hh signaling-orchestrated H3K27me and H3K27ac interplay tailors combination epigenetic drugs in treating breast cancer.Together,this study reveals the new role of Hh signaling-regulated histone modifications interplay in responding to HDAC inhibitors and suggests new epigenetically-targeted therapeutic solutions for treating TNBC.
基金supported by grants from the Natural Science Foundation of China for Innovation Research Group(81821005)the National Natural Science Foundation of China(82273948 and 81573271)+2 种基金the"Personalized Medicines,Molecular Signaturebased Drug Discovery and Development",Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12020203 and XDA12020228,China)the National Science&Technology Major Project"Key New Drug Creation and Manufacturing Program",China(2018ZX09711002-011-016)the Youth Innovation Promotion Association of CAS(2018324,China).
文摘Glioblastoma(GBM)is the most common and aggressive malignant brain tumor in adults and is poorly controlled.Previous studies have shown that both macrophages and angiogenesis play significant roles in GBM progression,and co-targeting of CSF1R and VEGFR is likely to be an effective strategy for GBM treatment.Therefore,this study developed a novel and selective inhibitor of CSFIR and VEGFR,SYHA1813,possessing potent antitumor activity against GBM.SYHA1813 inhibited VEGFR and CSFIR kinase activities with high potency and selectivity and thus blocked the cell viability of HUVECs and macrophages and exhibited anti-angiogenetic effects both in vitro and in vivo.SYHA1813 also displayed potent in vivo antitumor activity against GBM in immune-competent and immune-deficient mouse models,including temozolomide(TMZ)insensitive tumors.Notably,SYHA1813 could penetrate the blood-brain barrier(BBB)and prolong the survival time of mice bearing intracranial GBM xenografts.Moreover,SYHA1813 treatment resulted in a synergistic antitumor efficacy in combination with the PD-1 antibody.As a clinical proof of concept,SYHA1813 achieved confirmed responses in patients with recurrent GBM in an ongoing first-in-human phase I trial.The data of this study support the rationale for an ongoing phase I clinical study(ChiCTR2100045380).
基金Engineering and Physical Sciences Research Council(EP/R042578/1)Chinese Ministry of Education Collaborative Project(B17023)。
文摘Polarization control is at the heart of high-capacity data optical communication systems,such as polarizationdivision multiplexers and Stokes vector modulation transmitters.Despite passive polarization control being mature,the realization of monolithically integrated polarization controllers and single longitudinal mode light sources,such as distributed-feedback(DFB)lasers,is of importance.In this research,we report an AlGaInAs multiple-quantum-well photonic integrated circuit device which can control the state of polarization of the output light source,consisting of a polarization mode converter(PMC),a differential phase shifter(DPS),and a sidewall grating DFB laser.We demonstrate an asymmetrical stepped-height ridge waveguide PMC to realize TE to TM polarization conversion and a symmetrical straight waveguide DPS to enable polarization rotation from approximately counterclockwise circular polarization to linear polarization.Based on the identical epitaxial layer scheme,all the PMC,DPS,and DFB lasers can be integrated monolithically using only a single step of metalorganic vapor-phase epitaxy and two steps of III-V material dry etching.For the DFB-PMC device,a high TE to TM polarization conversion efficiency(98.4%)over a wide range of DFB injection currents is reported at 1555 nm wavelength.For the DFB-PMC-DPS device,a nearly 60°rotation of the Stokes vector on the Poincarésphere was obtained with a range of bias voltage from 0 to-3.0 V at a laser drive current of 170 mA.
基金supported by the National Natural Science Foundation of China(Nos.11904108 and 62004071)the China Postdoctoral Science Foundation(No.2020M672680)+1 种基金the“The Pearl River Talent Recruitment Program”(No.2019ZT08X639)X.M.W.thanks the support of Natural Science Foundation of Guangdong Province in China(Nos.2019A1515011132 and 2017A030313022).
文摘Leveraging the unique physical properties,two-dimensional(2D)materials have circumvented the disadvantages of conventional epitaxial semiconductors and held great promise for potential optoelectronic applications.So far,two main detector architectures including photodiode based on a van der Waals P-N junction or Schottky junction and phototransistor based on individual 2D materials or hybrids have been well developed.However,a trade-off between responsivity and speed always exists in those technologies thus hindering the overall performance improvement.Here,we propose a new device concept by sandwiching the 2D anisotropic semimetal between p-type and n-type semiconductors in the out-of-plane direction,called PSN architecture,realizing the improvement of each parameter including broad spectral coverage,fast speed,high sensitivity,power-free and polarization-sensitive.We stack the p-type 2H-MoTe_(2),Weyl semimetal 1T-MoTe_(2)and n-type SnSe_(2)layer-by-layer constructing vertical sandwich structure where the top and bottom layers contribute to the internal built-in electric field,the intermediate layer can facilitate the exciton dissociation and act as infrared polarized light sensitizers.As a result,this PSN device exhibits broadband photo-response from 405 to 1,550 nm without external bias supply.At optical communication band(1,310 nm),operating at self-driven mode and room temperature,the responsivity and detectivity can reach up to 64.2 mA·W^(–1)and 2.2×10^(11)Jones,respectively,along with fast speed on the order of millisecond.Moreover,the device simultaneously exhibits exceptional detection capability for infrared polarized light,demonstrating the anisotropic photocurrent ratio of 1.55 at 1,310 nm and 2.02 at 1,550 nm,which is attributed to the strong in-plane optical anisotropy of middle 1T-MoTe_(2)layer.This work develops a new photodetector scheme with novel PSN architecture toward broadband,self-power,polarized light sensing and imaging modules.
基金the National Natural Science Foundation of China(No.51972192).
文摘All memristor neuromorphic networks have great potential and advantage in both technology and computational protocols for artificial intelligence.It is crucial to find suitable elementary units for both performing featured neuromorphic functions and fabrication in large scale.Here a simple memristive structure,Nb/HfOx/Pd,is proposed for this goal.Its two resistive switching mechanisms,Mott transition of NbO2 and oxygen vacancy(Vo)migration,can be controlled by modulating external bias directions.Negative bias activates reversible phase transition and restrains Vo filament formation to allow the memristor to mimic the firing action potential.Positive bias activates Vo filament formation and restrains the other to allow the memristor to mimic synaptic plasticity and learning protocols.The system can respond adaptively to naturally generated action potentials and modified synaptic signals from the same memristive structure.In addition,some special features related to signal encoding and recognition are discovered when the system is settled according to chaos circuit theory.Our study provides a novel approach for designing elementary units for neuromorphic computations.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Science(Nos.XDA12020101 and XDA12050101)National Natural Science Foundation of China(81521005).
文摘Dear Editor,Hepatocellular carcinoma(HCC)is the second leading cause of cancer-related death worldwide with a 5-year survival rate-50-80% after curative treatment,like surgery,targeted therapy plus TACE or RFA or local treatments,immunotherapy,and so on.1 The approval of several angiogenesis inhibitors,such as sorafenib,regorafenib,lenvatinib,and cabozantinib,have shown therapeutic potential for HCC treatment.However,the improvement of overall survival or progression-free survival is still limited based on angiogenesis inhibitor monotherapy at present.
基金supported by the Budget Surplus of Central Financial Science and Technology Plan(2021-JY-36).
文摘Rapid urbanisation in China has resulted in an increased demand for land in towns and cities.To upgrade and modernise,China has also moved many major industries from urban centres to less populated areas.With the high economic value of urban land,the transformation and utilisation of brownfield areas have become important economically and socially.The Chinese government has recognised the need for strong frameworks to safeguard soil and groundwater quality,with brownfield sites a key category for management.Strong scientific,regulatory and decision-making frameworks are needed and being adopted to ensure practical,careful and wise use of central and localised government resources,to manage the reuse and regeneration of these brownfield sites.This paper reviews the context,policies and management procedures of developing brownfield sites in countries with a history of brownfield management and discusses China’s current situation and priorities for brownfield governance and redevelopment.These include(1)clarification of brownfield site soil contamination risk control standards and risk assessment procedures,(2)the responsibilities of different national and local agencies,(3)the establishment of a national expert committee to advise on best practices,policy and process,(4)the use of registered brownfield databases at national,provincial,municipal and county levels,and(5)the set up of soil pollution prevention fund at the provincial level.
文摘Neurogenesis is the process in which neurons are generated from neural stem/progenitor cells(NSCs/NPCs).It involves the proliferation and neuronal fate specification/differentiation of NSCs,as well as migration,maturation and functional integration of the neuronal progeny into neuronal network.NSCs exhibit the two essential properties of stem cells:self-renewal and multi-potency.Contrary to previous dogma that neurogenesis happens only during development,it is generally accepted now that neurogenesis can take place throughout life in mammalian brains.This raises a new therapeutic potential of applying stem cell therapy for stroke,neurodegenerative diseases and other diseases.However,the maintenance and differentiation of NSCs/NPCs are tightly controlled by the extremely intricate molecular networks.Uncovering the underlying mechanisms that drive the differentiation,migration and maturation of specific neuronal lineages for use in regenerative medicine is,therefore,crucial for the application of stem cell for clinical therapy as well as for providing insight into the mechanisms of human neurogenesis.Here,we focus on the role of bone morphogenetic protein(BMP)signaling in NSCs during mammalian brain development.
基金supported by the Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(2021SZ-TD004)the Natural Science Foundation of Zhejiang Province(LD21E030001)+1 种基金the Joint Fund of National Natural Science Foundation of China(U22A20155)the Lingyan Program of Zhejiang Province(2022C01106).
文摘Wound management is an important issue that places enormous pressure on the physical and mental health of patients,especially in cases of infection,where the increased inflammatory response could lead to severe hypertrophic scars(HSs).In this study,a hydrogel dressing was developed by combining the high strength and toughness,swelling resistance,antibacterial and antioxidant capabilities.The hydrogel matrix was composed of a double network of polyvinyl alcohol(PVA)and agarose with excellent mechanical properties.Hyperbranched polylysine(HBPL),a highly effective antibacterial cationic polymer,and tannic acid(TA),a strong antioxidant molecule,were added to the hydrogel as functional components.Examination of antibacterial and antioxidant properties of the hydrogel confirmed the full play of the efficacy of HBPL and TA.In the in vivo studies of methicillin-resistant Staphylococcus aureus(MRSA)infection,the hydrogel had shown obvious promotion of wound healing,and more profoundly,significant suppression of scar formation.Due to the common raw materials and simple preparation methods,this hydrogel can be mass produced and used for accelerating wound healing while preventing HSs in infected wounds.