In order to develop biological control of aphids by a ＂push-pull＂ approach, intercropping using repellent emitting plants was developed in different crop and associated plant models. Garlic is one of the potential p...In order to develop biological control of aphids by a ＂push-pull＂ approach, intercropping using repellent emitting plants was developed in different crop and associated plant models. Garlic is one of the potential plant that could be inserted in crops to decrease the pest occurrence in neighboring crop plots. In this study, field works were conducted in wheat fields in Langfang Experimental Station, Hebei Province in China from October 2009 to July 2010 during wheat developmental season. The effect of wheat intercropping with garlic but also the volatiles emission on the incidence of the English grain aphid, Sitobion avenae Fabricius （Homoptera： Aphididae） was assessed. Natural beneficial occurrence and global yields in two winter wheat varieties that were susceptible or resistant to cereal aphid were also determined comparing to control plots without the use of garlic plant intercrop nor semiochemical releaser in the fields. S. avenae was found to be lower in garlic oil blend treatment （GOB）, diallyl disulfide treatment （DD） and wheat-garlic intercropping treatment （WGI） when compared to the control plots for both two varieties （P〈0.01）. Both intercropping and application of volatile chemicals emitted by garlic could improve the population densities of natural enemies of cereal aphid, including ladybeetles and mummified aphids. Ladybeetle population density in WGI, GOB and mummified aphids densities in WGI, DD were significantly higher than those in control fields for both two varieties （P〈0.05）. There were significant interactions between cultivars and treatments to the population densities of S. avenae. The 1 000-grain weight and yield of wheat were also increased compared to the control. Due to their potential alternatives as a biological control agent against cereal aphid, garlic intercropping and related emitted volatiles are expected to contribute to the further improvement of integrated pest management systems and to potentially reduce the amount of traditional synthetic pesticides applied in wheat fields.展开更多
Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availabilit...Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availability of numerous therapeutic agents,limitations exhibit,including poor aqueous solubility,suboptimal stability,inadequate permeability,short half-lives,and multi-organ toxicity during long-term or high-dose administration.Nanoparticle-based drug delivery offers a robust strategy to mitigate these deficiencies while maximizing therapeutic efficacy through controlled-release mechanisms and rational administration route design.This review systematically summarizes recent advancements in nanoparticle drug delivery strategies for RA treatment from the perspective of three distinct mechanisms.It details the design rationales,therapeutic principles,and effects of various delivery systems,with particular emphasis on their interactions with the disease microenvironment and the entire body.展开更多
The preparation of a novel nanoscale imazalil(IMZ)-based coordination polymer[Zn(HBTC)(IMZ)_(2)]_(n)(PDCP1)(H_(3)BTC=1,3,5-benzenetricarboxylic acid),and its antifungal application within a sustainable delivery system...The preparation of a novel nanoscale imazalil(IMZ)-based coordination polymer[Zn(HBTC)(IMZ)_(2)]_(n)(PDCP1)(H_(3)BTC=1,3,5-benzenetricarboxylic acid),and its antifungal application within a sustainable delivery system was reported.The intermolecular interactions presented in the structure,and their contributions to crystal packing were studied by Hirshfeld,Fingerprint plot and Mayer bond order.The obtained PDCP1 had a relativelyhigh loadingrate of IMZ(68.5%).PDCP1 exhibitednotable antifungal activities againstColletotrichum gloeosporioides,Magnaporthe Oryzae,and Alternaria Nees strains,with EC_(50) values of 0.72,0.92,and 0.56μg/mL,respectively.The key benefits of the application of PDCP1 as a control release pesticide include high fungicide loading and offer nearly complete release,pH-responsive release,enhanced UV stability,exhibits favorable biosafety profiles.The remarkable inhibition of C.gloeosporioides growth by PDCP1 underscores a promising strategy for agrochemical material development,high loading of active ingredients and readily delivery fosters more efficient pesticides utilization in agricultural processes.展开更多
Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized on...Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.展开更多
T-cell acute lymphoblastic leukemia(T-ALL)is a common yet severe pediatric cancer treated with Lasparaginase(ASP).To boost the treatment's effectiveness and lessen its toxicity,enzyme@MOF nanoparticles were engine...T-cell acute lymphoblastic leukemia(T-ALL)is a common yet severe pediatric cancer treated with Lasparaginase(ASP).To boost the treatment's effectiveness and lessen its toxicity,enzyme@MOF nanoparticles were engineered with a hyaluronic acid(HA)-targeted polyethylene glycol(PEG)surface.These nanoparticles,termed ASP@MOF/PEG-HA,showed efficient uptake by drug-resistant T-ALL cells.The p Hsensitive zeolitic imidazolate framework-8(ZIF-8)based metal-organic framework(MOF)nanoparticles allowed the encapsulated ASP to significantly increase cytotoxicity against T-ALL cells.Furthermore,HA's ability to bind to T-ALL cells with elevated CD44 expression further induced apoptosis in CD44^(+) T-ALL cells with poor prognosis.In animal models,the nanoparticles improved survival rates and reduced the burden of leukemia,demonstrating substantial anti-leukemia effects.Thus,these nanoparticles offer an effective treatment approach for drug-resistant T-ALL cells characterized by increased CD44 expression.展开更多
Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(...Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(CB[8])as the host and terpyridine lanthanum ions metal complex as the vip,constructed by layer-by-layer self-assembly through supramolecular interaction.Moreover,nanofibers with lanthanide luminescence properties exhibit surprising pH-responsive deformation properties and antibacterial behavior.In the tumor micro-environment,the dramatic reduction in the size of the nanofibers enables specific and hierarchical release of anticancer drugs in tumor cells to exert an advanced therapeutic effect.In addition,the synergistic therapeutic efficacy was achieved by reducing the excess of Gram-positive and Gram-negative bacteria surrounding tumor cells.The novel supramolecular nanofibers with sequential drug release and combined therapeutic mode provide new guidance for the synthesis of drug carrier materials and direction for the promotion of nanomaterial-mediated cancer therapy.展开更多
Encapsulation of water-soluble cargoes in millimeter-sized capsules has enabled major advances in various fields,including pharmaceuticals,food,cosmetics,packaging,and materials.However,because of the lack of fabricat...Encapsulation of water-soluble cargoes in millimeter-sized capsules has enabled major advances in various fields,including pharmaceuticals,food,cosmetics,packaging,and materials.However,because of the lack of fabrication precision,low cargo retention,suboptimal mechanical properties,and difficulty in preventing water evaporation,this technique is more challenging than microencapsulation techniques.In this study,we developed a surfactant-free and organic solvent-free water-in-oil in-air emulsification approach for synthesizing double-layered“milli-capsules”for the precise encapsulation,enhanced retention,and force-triggered burst release of water-soluble bioactive cargoes.In particular,we synthesized milli-capsules with a first shell of poly(ethylene glycol dimethacrylate)for the efficient encapsulation of bioactive cargoes and a second shell of beeswax to prolong the retention of the entrapped bioactive compounds.Unlike traditional milli-capsules,which exhibit poor shape uniformity and mechanical stability,we introduced metallic ions to stabilize the interfacial tension and employed constant rotation to balance the gravity,buoyancy,inertial,and viscous forces imposed on the droplets,resulting in uniform and rigid milli-capsules with narrow rupture forces.Furthermore,additional hydrophobic beeswax coating prevented water volatilization and substantially prolonged the shelf life of the encapsulated compounds from a few days to a few months while maintaining their bioactivities.The proposed milli-capsule system addresses the challenge of precise fabrication of large carriers for water-soluble cargoes,representing a significant step toward the long-term storage and controlled release of bioactive cargoes for various industrial applications.展开更多
Dear Editor,The Cay2.1 channel,also known as the P/Q-type Ca^(2+) channel,is a particular type of voltage-gated Ca^(2+) channel primarily expressed on the presynaptic membrane in the brain[1].It serves as an essential...Dear Editor,The Cay2.1 channel,also known as the P/Q-type Ca^(2+) channel,is a particular type of voltage-gated Ca^(2+) channel primarily expressed on the presynaptic membrane in the brain[1].It serves as an essential part of the precisely orchestrated neurotransmitter release machinery.展开更多
The carbon cycle stands as a cornerstone among the Earth's material cycles,carrying profound implications for global climate dynamics and humanity's sustenance and advancement.Additionally,nitrogen,as a vital ...The carbon cycle stands as a cornerstone among the Earth's material cycles,carrying profound implications for global climate dynamics and humanity's sustenance and advancement.Additionally,nitrogen,as a vital nutrient element,plays a pivotal role in biogeochemical processes,exerting significant influence on the ecological environment within watersheds.In this study,an analysis of the carbon(C)and nitrogen(N)components in the river water of 12 alpine basins on the eastern margin of the Tibetan Plateau(TP)reveals that the average dissolved organic carbon(DOC)concentration in the river water is 0.76±0.67 mg/L,indicating a lower level compared to the global river average organic carbon content.Specifically,the average DOC concentrations were 0.42±0.22 and 1.56±0.68 mg/L in the glacial and non-glacial basins,respectively.The average dissolved inorganic carbon(DIC)concentration in the eastern TP is 27.04±20.19 mg/L,with the lowest DIC observed at Dagu Glacier and the highest at Daxia River.Furthermore,the average dissolved total carbon(DTC)concentration in glacier river water was 18.87±12.65 mg/L,contrasting with 48.23±21.07 mg/L in non-glacial basins.The mean concentration of total nitrogen(TN)in the eastern TP averaged 0.97±0.54 mg/L,with the glacial basin registering 1.01±0.47 mg/L and the non-glacial basin at 0.89±0.70 mg/L.Evaluating the release fluxes of carbon and nitrogen across 12 river basins revealed a range of DTC emission fluxes from 0.32×10^(9)to 31.02×10^(9)g·C/a,with inorganic carbon comprising 71.0%to 99.5%.Consequently,the carbon emission flux for seven glacier basins totaled 15.91×10^(9)g·C/a,while for the five non-glacial river basins,it reached 87.37×10^(9)g·C/a.The total TN release fluxes across 12 small river basins amounted to 2.46×10^(9)g·N/a,with 0.84×10^(9)g·N/a released in glacial basins and 1.62×10^(9)g·N/a in the nonglacial basin.This study elucidates the spatial distribution and transport mechanisms of carbon and nitrogen elements within the glacial and downstream non-glacial basins,offering valuable insights into the biogeochemical cycles of carbon and nitrogen in the eastern Tibetan Plateau.展开更多
Conventional locking/release mechanisms often face challenges in aircraft wing separation processes,such as excessive impact loads and insufficient synchronization.These may cause structural damage to the airframe or ...Conventional locking/release mechanisms often face challenges in aircraft wing separation processes,such as excessive impact loads and insufficient synchronization.These may cause structural damage to the airframe or attitude instability,seriously compromising mission reliability.To address this engineering challenge,this paper proposes a multi-point low-impact locking/release mechanism based on the mobility model and energy conversion strategy.Through establishing a DOF constraint framework system,this paper systematically analyzes the energy transfer and conversion characteristics during the wing separation process,reveals the generation mechanism of impact loads,and conducts research on low-impact design based on energy conversion strategy.Building on this foundation,a single-point locking/release mechanism employing parallel trapezoidal key shaft structure was designed,which increases frictional contact time and reduces the energy release rate,thereby achieving low-impact characteristics.The mechanism's performance was validated through physical prototype development and systematic functional testing(including unlocking force,synchronization,and impact tests).Experimental results demonstrate:(1)Under 14 kN preload condition,the maximum unlocking force was only 92.54 N,showing a linear relationship with preload that satisfies the"strong-connection/weak-unlock"design requirement;(2)Wing separation was completed within 46 ms,with synchronization time difference among three separation mechanisms stably controlled within 12-14 ms,proving rapid and reliable operation;(3)The unlocking impact acceleration ranged between 26 and 73 g,below the 100 g design limit,confirming the effectiveness of the energy conversion strategy.The proposed low-impact locking/release mechanism design method based on energy conversion strategy resolves the traditional challenges of high impact and synchronization deficiencies.The synergistic optimization mechanism of"structural load reduction and performance improvement"provides a highly reliable technical solution for wing separable mechanisms while offering novel design insights for wing connection/separation systems engineering.展开更多
The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD...The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.展开更多
Explosive cyclones(ECs) are rapidly intensifying subtropical cyclones that can develop within a short time and pose considerable threats to coastal areas in middle and high latitudes.Gaining a comprehensive understand...Explosive cyclones(ECs) are rapidly intensifying subtropical cyclones that can develop within a short time and pose considerable threats to coastal areas in middle and high latitudes.Gaining a comprehensive understanding of their formation,evolution,and mechanisms of explosive development is essential for improving forecasts of extreme weather events and mitigating associated impacts.Potential vorticity(PV),which is closely related to cyclone dynamics,serves as a valuable diagnostic tool in the study of ECs.In this study,two wintertime ECs of differing intensity over the Northwestern Pacific Ocean are analyzed to examine how different atmospheric processes influence PV generation and the rapid development of ECs.The maximum deepening rates of the two ECs are 2.81 Bergeron(called EC1) and 1.52 Bergeron(referred to as EC2).Results indicate that different stages of EC evolution are closely associated with PV tendency changes at different atmospheric levels.Using the PV tendency equation,during the explosive development of EC1,latent heat release may trigger the downward propagation of upper-level PV.For EC2,latent heat release notably enhances low-level PV,directly contributing to its rapid intensification.To validate these findings,sensitivity tests are conducted using the Weather Research and Forecasting model,with latent heat release turned off in the microphysical scheme for both cases.The results confirm the crucial role of latent heat release in generating low-level PV,further revealing that latent heat release contributes more to the explosive development of EC2 than that of EC1.展开更多
Hypersonic morphing vehicle(HMV)can reconfigure aerodynamic geometries in real time,adapting to diverse needs like multi-mission profiles and wide-speed-range flight,spanwise morphing and sweep angle variation are rep...Hypersonic morphing vehicle(HMV)can reconfigure aerodynamic geometries in real time,adapting to diverse needs like multi-mission profiles and wide-speed-range flight,spanwise morphing and sweep angle variation are representative large-scale wing reconfiguration modes.To meet the HMV's need for an increased lift and a lift to drag ratio during hypersonic maneuverability and cruise or reentry equilibrium glide,this paper proposes an innovative single-DOF coupled morphing-wing system.We then systematically analyze its open-loop kinematics and closed-loop connectivity constraints,and the proposed system integrates three functional modules:the preset locking/release mechanism,the coupled morphing-wing mechanism,and the integrated wing locking with active stiffness control mechanism.Experimental validation confirms stable,continuous morphing under simulated aerodynamic loads.The experimental results indicate:(i)SMA actuators exhibit response times ranging from 18 s to 160 s,providing sufficient force output for wing unlocking;(ii)The integrated wing locking with active stiffness control mechanism effectively secures wing positions while eliminating airframe clearance via SMA actuation,improving the first-order natural frequency by more than 17%;(iii)The distributed aerodynamic loading system enables precise multi-stage follow-up loading during morphing,with the coupled morphing wing maintaining stable,continuous operation under 0-3500 N normal loads and 110-140 N axial force.The proposed single-DOF coupled morphing mechanism not only simplifies and improves structural efficiency but also demonstrates superior performance in locking control,stiffness enhancement,and aerodynamic responsiveness.This establishes a foundational framework for the design of future intelligent morphing configurations and the implementation of flight control systems.展开更多
Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achie...Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.展开更多
This study is dedicated to numerically investigate the dynamic behavior of a missile released from a helicopter under the influence of downwash from the rotating rotors using AGM-114 Hellfire and UH-60 as the testcase...This study is dedicated to numerically investigate the dynamic behavior of a missile released from a helicopter under the influence of downwash from the rotating rotors using AGM-114 Hellfire and UH-60 as the testcase.Simulations are conducted using unsteady Reynolds-averaged Navier-Stokes(URANS)with shear stress transport(SST)k-ωturbulence model,incorporating six-degree-of-freedom(6-DOF)motion and overset grid.Two releasing scenarios,viz.,hover and forward flight,are analyzed under varying missile launch thrust and helicopter forward flight speed.Results reveal that the rotor downwash significantly affects the stability of the missile,particularly during hovering case,where low thrust prolongs wake interaction.In forward flight,the increased airspeed can in principle reduce wake influence but introduces asymmetrical aerodynamic effects on the trajectory of the missile.The findings offer guidance for missile release and launch planning in rotorcraft operations.展开更多
During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their el...During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.展开更多
The electrochemical corrosion of ductile pipes(DPs)in drinking water distribution systems(DWDS)has a crucial impact on cement-mortar lining(CML)failure and metal release,potentially leading to drinking water quality d...The electrochemical corrosion of ductile pipes(DPs)in drinking water distribution systems(DWDS)has a crucial impact on cement-mortar lining(CML)failure and metal release,potentially leading to drinking water quality deterioration and posing a risk to public health.An in-situ scanning vibrating electrode technique(SVET)with micron-scale resolution,microscopic scale detection and water quality analysis were used to investigate the corrosion behavior and metal release from DPs throughout the whole CML failure process.Metal pollutants release occurred at three different stages of CML failure process,and there are potential risks of water quality deterioration exceeding the maximum allowable levels set by national standards in the partial failure stage and lining peeling stage.Furthermore,the effects of water chemistry(Cl^(−),SO_(4)^(2−),NO_(3)−,and Ca^(2+))on corrosion scale growth and iron release activity,were investigated during the CML partial failure stage.Results showed that the CML failure process in DPs was accelerated by the autocatalysis of localized corrosion.Cl^(−)was found to damage the uncorroded metal surface,while SO_(4)^(2−)mainly dissolved the corrosion scale surface,increasing iron release.Both the oxidation of NO_(3)−and selective sedimentation of Ca2+were found to enhance the stability of corrosion scales and inhibit iron release.展开更多
Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.I...Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.展开更多
Cascading thermal runaway(TR)propagation poses a critical safety concern for large-format sodium-ion battery(SIB)systems because of the heightened risks of fires or explosions.However,effectively suppressing TR propag...Cascading thermal runaway(TR)propagation poses a critical safety concern for large-format sodium-ion battery(SIB)systems because of the heightened risks of fires or explosions.However,effectively suppressing TR propagation without introducing unintended side effects remains a significant challenge.Herein,we demonstrate a localized energy release method to mitigate TR,by reducing the state of charge(SOC)of cells adjacent to the thermally runaway unit.We discover that as the SOCs decreased from 100%to 25%,the TR trigger temperature decreased significantly,and the maximum temperature decrease from 367 to 229℃.Meanwhile,the volume of gas decreased to one-third of its original value,while the range of explosion limits significantly narrowed.The analysis of the morphology of the debris further confirms that the structural damage is greater at higher SOC levels.Moreover,an Entropy Weight and Technique for Order Preference by Similarity to an Ideal Solution(EW-TOPSIS)method has been established to assess the safety status of SIBs,showing that the TR possibility is nearly linear with the SOCs,and the TR hazard is exponentially related to the SOCs.Finally,when the SOC of cells adjacent to the TR cell is reduced to 25%,TR can be directly blocked without the need for additional cooling or thermal insulation methods.This study not only advances the understanding of TR behavior in SIBs but also offers a straightforward approach to mitigating the TR risk in SIB systems.展开更多
基金supported by grants from the Cooperation Project between Belgium and China (CUD\PIC Shandong, 2010DFA32810)
文摘In order to develop biological control of aphids by a ＂push-pull＂ approach, intercropping using repellent emitting plants was developed in different crop and associated plant models. Garlic is one of the potential plant that could be inserted in crops to decrease the pest occurrence in neighboring crop plots. In this study, field works were conducted in wheat fields in Langfang Experimental Station, Hebei Province in China from October 2009 to July 2010 during wheat developmental season. The effect of wheat intercropping with garlic but also the volatiles emission on the incidence of the English grain aphid, Sitobion avenae Fabricius （Homoptera： Aphididae） was assessed. Natural beneficial occurrence and global yields in two winter wheat varieties that were susceptible or resistant to cereal aphid were also determined comparing to control plots without the use of garlic plant intercrop nor semiochemical releaser in the fields. S. avenae was found to be lower in garlic oil blend treatment （GOB）, diallyl disulfide treatment （DD） and wheat-garlic intercropping treatment （WGI） when compared to the control plots for both two varieties （P〈0.01）. Both intercropping and application of volatile chemicals emitted by garlic could improve the population densities of natural enemies of cereal aphid, including ladybeetles and mummified aphids. Ladybeetle population density in WGI, GOB and mummified aphids densities in WGI, DD were significantly higher than those in control fields for both two varieties （P〈0.05）. There were significant interactions between cultivars and treatments to the population densities of S. avenae. The 1 000-grain weight and yield of wheat were also increased compared to the control. Due to their potential alternatives as a biological control agent against cereal aphid, garlic intercropping and related emitted volatiles are expected to contribute to the further improvement of integrated pest management systems and to potentially reduce the amount of traditional synthetic pesticides applied in wheat fields.
文摘Rheumatoid arthritis(RA)is one of the most prevalent systemic autoimmune inflammatory diseases worldwide,causing chronic,progressively worsening arthritis that may ultimately lead to disability.Despite the availability of numerous therapeutic agents,limitations exhibit,including poor aqueous solubility,suboptimal stability,inadequate permeability,short half-lives,and multi-organ toxicity during long-term or high-dose administration.Nanoparticle-based drug delivery offers a robust strategy to mitigate these deficiencies while maximizing therapeutic efficacy through controlled-release mechanisms and rational administration route design.This review systematically summarizes recent advancements in nanoparticle drug delivery strategies for RA treatment from the perspective of three distinct mechanisms.It details the design rationales,therapeutic principles,and effects of various delivery systems,with particular emphasis on their interactions with the disease microenvironment and the entire body.
基金supported by Beijing Innovation Consortium of Agriculture Research System(No.BAIC01).
文摘The preparation of a novel nanoscale imazalil(IMZ)-based coordination polymer[Zn(HBTC)(IMZ)_(2)]_(n)(PDCP1)(H_(3)BTC=1,3,5-benzenetricarboxylic acid),and its antifungal application within a sustainable delivery system was reported.The intermolecular interactions presented in the structure,and their contributions to crystal packing were studied by Hirshfeld,Fingerprint plot and Mayer bond order.The obtained PDCP1 had a relativelyhigh loadingrate of IMZ(68.5%).PDCP1 exhibitednotable antifungal activities againstColletotrichum gloeosporioides,Magnaporthe Oryzae,and Alternaria Nees strains,with EC_(50) values of 0.72,0.92,and 0.56μg/mL,respectively.The key benefits of the application of PDCP1 as a control release pesticide include high fungicide loading and offer nearly complete release,pH-responsive release,enhanced UV stability,exhibits favorable biosafety profiles.The remarkable inhibition of C.gloeosporioides growth by PDCP1 underscores a promising strategy for agrochemical material development,high loading of active ingredients and readily delivery fosters more efficient pesticides utilization in agricultural processes.
基金supported by the Vall d’Hebron Research Institute(PI23/01345)the Networking Research Centre on Bioengineering,Biomaterials,and Nanomedicine(CIBER-BBN),which is financed by the Instituto de Salud Carlos III(ISCIII)with assistance from the European Regional Development Fund(ERDF)+4 种基金supported by ANID FONDECYT REGULAR(Chile)through project No.1250634,and FOVI230019 granted to Esteban Duran-LaraDiana Rafael was supported by Marie Skłodowska-Curie Actions(MSCA-PF ID 101107735),“La Caixa Foundation”(LCF/BQ/PR24/12050008),and ISCIII(PI24/00745)Fernanda Andrade was granted by the Fundación Científica de la Asociación Española Contra el Cáncer(FCAECC Refs.INVES211530DASI and SNRGS247164DASI)“La Caixa Foundation”(HR24-00927).Júlia German-Cortés was granted by the 791 FAECC(PRDBA258393GERM)The authors also thank the denomination of Consolidated group from Generalitat de Catalunya(2021 SGR 01173)granted to the CB-DDT group。
文摘Despite remarkable advances in nanomedicine,localized delivery of advanced cancer therapeutics remains underexploited.Advanced therapies based on biopharmaceuticals,immunotherapy,or gene therapy have revolutionized oncology.Yet,their systemic administration is often associated with limitations such as poor sitespecific accumulation,instability,and systemic toxicity.Hydrogels/macrogels offer the ability to encapsulate,protect,and release biomolecules in situ with sustained and stimulus-responsive profiles,addressing key translational gaps.This review provides a focused synthesis of the last five years of hydrogel-based research for cancer therapy,with emphasis on peptides,antibodies,immunotherapeutic agents,and gene delivery systems.We discuss design principles,release mechanisms,and clinical translation challenges,highlighting structure-function relationships and comparative performance across therapeutic classes.By integrating mechanistic insights with recent breakthroughs,we outline how next-generation hydrogels can synergize with personalized medicine and combination therapies to redefine localized cancer treatment.This work explores the fundamental aspects and provides examples of hydrogel-based delivery for the advanced treatment of cancer.The review summarizes the dynamic landscape of hydrogel research of the last 5 years,showcasing their potential systems for the precise delivery of biomolecules.Specifically,we explore the multidimensional role of hydrogels in the sustained and localized release of antibodies,immunotherapeutic agents,and genes as next-generation platforms for localized cancer treatment.This review aims to critically evaluate the mechanisms and applications of these systems in order to assess their potential to transform medical interventions and advance patient care.
基金supported by the National Natural Science Foundation of China(Nos.52203206,52173150,81902004)Guangdong Basic and Applied Basic Research Foundation(Nos.2023A1515012193,2023A1515110025,2023A1515012575,2023A1515011962)+6 种基金Shenzhen Fundamental Research Program(Nos.JCYJ20220530144605012,JCYJ20240813150438050)China Postdoctoral Science Foundation(Nos.2023M744090,GZC20233296)Research Start-up Fund of Post-doctoral of SAHSYSU(No.ZSQYRSFPD0071)Distinguished Young Scientists projects by Guangdong Second Provincial General Hospital(No.2024E005)Guangdong International Science and Technology Cooperation Project(No.2023A0505050120)Shenzhen International Cooperative Research Project(No.GJHZ20220913142401003)Open Fund Key Project of the Guangdong Provincial Key Laboratory of Digestive Cancer Research(No.GPKLDCR202201Z)。
文摘T-cell acute lymphoblastic leukemia(T-ALL)is a common yet severe pediatric cancer treated with Lasparaginase(ASP).To boost the treatment's effectiveness and lessen its toxicity,enzyme@MOF nanoparticles were engineered with a hyaluronic acid(HA)-targeted polyethylene glycol(PEG)surface.These nanoparticles,termed ASP@MOF/PEG-HA,showed efficient uptake by drug-resistant T-ALL cells.The p Hsensitive zeolitic imidazolate framework-8(ZIF-8)based metal-organic framework(MOF)nanoparticles allowed the encapsulated ASP to significantly increase cytotoxicity against T-ALL cells.Furthermore,HA's ability to bind to T-ALL cells with elevated CD44 expression further induced apoptosis in CD44^(+) T-ALL cells with poor prognosis.In animal models,the nanoparticles improved survival rates and reduced the burden of leukemia,demonstrating substantial anti-leukemia effects.Thus,these nanoparticles offer an effective treatment approach for drug-resistant T-ALL cells characterized by increased CD44 expression.
基金supported by the National Natural Science Foundation of China(No.82273919)Natural Science Foundation of Heilongjiang Province(No.LH2024H013)China Postdoctoral Science Foundation(No.2022MD723781).
文摘Constructing nanofibers with specific therapeutic effects against cancer is a challenge.Here,we present the synthesis approach and application prospects of supramolecular nanofibers,which are based on cucurbit[8]uril(CB[8])as the host and terpyridine lanthanum ions metal complex as the vip,constructed by layer-by-layer self-assembly through supramolecular interaction.Moreover,nanofibers with lanthanide luminescence properties exhibit surprising pH-responsive deformation properties and antibacterial behavior.In the tumor micro-environment,the dramatic reduction in the size of the nanofibers enables specific and hierarchical release of anticancer drugs in tumor cells to exert an advanced therapeutic effect.In addition,the synergistic therapeutic efficacy was achieved by reducing the excess of Gram-positive and Gram-negative bacteria surrounding tumor cells.The novel supramolecular nanofibers with sequential drug release and combined therapeutic mode provide new guidance for the synthesis of drug carrier materials and direction for the promotion of nanomaterial-mediated cancer therapy.
基金supported by the National Natural Science Foundation of China(Nos.52273102,31870957,and 52302344)the Fundamental Research Funds for the Central Universities(Nos.DUT24YG155,DUT20YG103,and DUT22LAB601)Liaoning Provincial Science and Technology Plan Joint Plan(No.2023JH2/101700341)。
文摘Encapsulation of water-soluble cargoes in millimeter-sized capsules has enabled major advances in various fields,including pharmaceuticals,food,cosmetics,packaging,and materials.However,because of the lack of fabrication precision,low cargo retention,suboptimal mechanical properties,and difficulty in preventing water evaporation,this technique is more challenging than microencapsulation techniques.In this study,we developed a surfactant-free and organic solvent-free water-in-oil in-air emulsification approach for synthesizing double-layered“milli-capsules”for the precise encapsulation,enhanced retention,and force-triggered burst release of water-soluble bioactive cargoes.In particular,we synthesized milli-capsules with a first shell of poly(ethylene glycol dimethacrylate)for the efficient encapsulation of bioactive cargoes and a second shell of beeswax to prolong the retention of the entrapped bioactive compounds.Unlike traditional milli-capsules,which exhibit poor shape uniformity and mechanical stability,we introduced metallic ions to stabilize the interfacial tension and employed constant rotation to balance the gravity,buoyancy,inertial,and viscous forces imposed on the droplets,resulting in uniform and rigid milli-capsules with narrow rupture forces.Furthermore,additional hydrophobic beeswax coating prevented water volatilization and substantially prolonged the shelf life of the encapsulated compounds from a few days to a few months while maintaining their bioactivities.The proposed milli-capsule system addresses the challenge of precise fabrication of large carriers for water-soluble cargoes,representing a significant step toward the long-term storage and controlled release of bioactive cargoes for various industrial applications.
基金supported by the National Natural Science Foundation of China(32100773 and U20A6005)the National Science and Technology Innovation 2030-Major Project of China(2021ZD0202500)+4 种基金Shenzhen Medical Research Fund(B2402024)China Postdoctoral Science Foundation(2021M693296)Shenzhen Science and Technology Program(JCYJ20230807093815032)Guangdong High-level Hospital Construction Fund(ynkt2021-zz33 and LCYJ2022093)the Natural Science Foundation of Guangdong Province,China(2022A1515010297).
文摘Dear Editor,The Cay2.1 channel,also known as the P/Q-type Ca^(2+) channel,is a particular type of voltage-gated Ca^(2+) channel primarily expressed on the presynaptic membrane in the brain[1].It serves as an essential part of the precisely orchestrated neurotransmitter release machinery.
基金supported by the National Natural Science Foundation of China(Nos.42371139,42201152)the Fundamental Research Funds for the Central Universities,China University of Geosciences(Wuhan)(No.CUG240629)+2 种基金the“CUG Scholar”Scientific Research Funds at China University of Geosciences(Wuhan)(No.2023092)the Gansu Province Natural Science Foundation Key Project(No.23JRRA858)CAS President's International Fellowship for Visiting Scientists(No.2024PVC003)。
文摘The carbon cycle stands as a cornerstone among the Earth's material cycles,carrying profound implications for global climate dynamics and humanity's sustenance and advancement.Additionally,nitrogen,as a vital nutrient element,plays a pivotal role in biogeochemical processes,exerting significant influence on the ecological environment within watersheds.In this study,an analysis of the carbon(C)and nitrogen(N)components in the river water of 12 alpine basins on the eastern margin of the Tibetan Plateau(TP)reveals that the average dissolved organic carbon(DOC)concentration in the river water is 0.76±0.67 mg/L,indicating a lower level compared to the global river average organic carbon content.Specifically,the average DOC concentrations were 0.42±0.22 and 1.56±0.68 mg/L in the glacial and non-glacial basins,respectively.The average dissolved inorganic carbon(DIC)concentration in the eastern TP is 27.04±20.19 mg/L,with the lowest DIC observed at Dagu Glacier and the highest at Daxia River.Furthermore,the average dissolved total carbon(DTC)concentration in glacier river water was 18.87±12.65 mg/L,contrasting with 48.23±21.07 mg/L in non-glacial basins.The mean concentration of total nitrogen(TN)in the eastern TP averaged 0.97±0.54 mg/L,with the glacial basin registering 1.01±0.47 mg/L and the non-glacial basin at 0.89±0.70 mg/L.Evaluating the release fluxes of carbon and nitrogen across 12 river basins revealed a range of DTC emission fluxes from 0.32×10^(9)to 31.02×10^(9)g·C/a,with inorganic carbon comprising 71.0%to 99.5%.Consequently,the carbon emission flux for seven glacier basins totaled 15.91×10^(9)g·C/a,while for the five non-glacial river basins,it reached 87.37×10^(9)g·C/a.The total TN release fluxes across 12 small river basins amounted to 2.46×10^(9)g·N/a,with 0.84×10^(9)g·N/a released in glacial basins and 1.62×10^(9)g·N/a in the nonglacial basin.This study elucidates the spatial distribution and transport mechanisms of carbon and nitrogen elements within the glacial and downstream non-glacial basins,offering valuable insights into the biogeochemical cycles of carbon and nitrogen in the eastern Tibetan Plateau.
文摘Conventional locking/release mechanisms often face challenges in aircraft wing separation processes,such as excessive impact loads and insufficient synchronization.These may cause structural damage to the airframe or attitude instability,seriously compromising mission reliability.To address this engineering challenge,this paper proposes a multi-point low-impact locking/release mechanism based on the mobility model and energy conversion strategy.Through establishing a DOF constraint framework system,this paper systematically analyzes the energy transfer and conversion characteristics during the wing separation process,reveals the generation mechanism of impact loads,and conducts research on low-impact design based on energy conversion strategy.Building on this foundation,a single-point locking/release mechanism employing parallel trapezoidal key shaft structure was designed,which increases frictional contact time and reduces the energy release rate,thereby achieving low-impact characteristics.The mechanism's performance was validated through physical prototype development and systematic functional testing(including unlocking force,synchronization,and impact tests).Experimental results demonstrate:(1)Under 14 kN preload condition,the maximum unlocking force was only 92.54 N,showing a linear relationship with preload that satisfies the"strong-connection/weak-unlock"design requirement;(2)Wing separation was completed within 46 ms,with synchronization time difference among three separation mechanisms stably controlled within 12-14 ms,proving rapid and reliable operation;(3)The unlocking impact acceleration ranged between 26 and 73 g,below the 100 g design limit,confirming the effectiveness of the energy conversion strategy.The proposed low-impact locking/release mechanism design method based on energy conversion strategy resolves the traditional challenges of high impact and synchronization deficiencies.The synergistic optimization mechanism of"structural load reduction and performance improvement"provides a highly reliable technical solution for wing separable mechanisms while offering novel design insights for wing connection/separation systems engineering.
基金financially supported by the Natural Science Foundation of Jiangsu Province (No.BK20200709)the Natural Science Foundation of China (Nos.62288102,32201127 and 82270113)+2 种基金the Natural Science Foundation of Guangdong Province (No.2023A1515011386)the Natural Science Foundation of the Jiangsu Higher Education Institutes (No.20KJB430031)the startup fund from Nanjing Tech University,and Disciplinary Fund of School of Pharmaceutical Sciences (2024)。
文摘The field of nanomedicine has been revolutionized by the concept of immunogenic cell death(ICD)-enhanced cancer therapy,which holds immense promise for the efficient treatment of cancer.However,precise delivery of ICD inducer is severely hindered by complex biological barriers.How to design and build intelligent nanoplatform for adaptive and dynamic cancer therapy remains a big challenge.Herein,this article presents the design and preparation of CD44-targeting and ZIF-8 gated gold nanocage(Au@ZH) for programmed delivery of the 1,2-diaminocyclohexane-Pt(Ⅱ)(DACHPt) as ICD inducer.After actively targeting the CD44 on the surface of 4T1 tumor cell,this Pt-Au@ZH can be effectively endocytosed by the 4T1 cell and release the DACHPt in tumor acidic environment,resulting in ICD effect and superior antitumor efficacy both in vitro and in vivo in the presence of mild 808 nm laser irradiation.By integration of internal and external stimuli intelligently,this programmed nanoplatform is poised to become a cornerstone in the pursuit of effective and targeted cancer therapy in the foreseeable future.
基金financially supported by the National Key R&D Program of China (No. 2022YFC3004204)the National Natural Science Foundation of China (No. 42275001)the Natural Science Foundation of Shandong Province (No. ZR2022MD038)。
文摘Explosive cyclones(ECs) are rapidly intensifying subtropical cyclones that can develop within a short time and pose considerable threats to coastal areas in middle and high latitudes.Gaining a comprehensive understanding of their formation,evolution,and mechanisms of explosive development is essential for improving forecasts of extreme weather events and mitigating associated impacts.Potential vorticity(PV),which is closely related to cyclone dynamics,serves as a valuable diagnostic tool in the study of ECs.In this study,two wintertime ECs of differing intensity over the Northwestern Pacific Ocean are analyzed to examine how different atmospheric processes influence PV generation and the rapid development of ECs.The maximum deepening rates of the two ECs are 2.81 Bergeron(called EC1) and 1.52 Bergeron(referred to as EC2).Results indicate that different stages of EC evolution are closely associated with PV tendency changes at different atmospheric levels.Using the PV tendency equation,during the explosive development of EC1,latent heat release may trigger the downward propagation of upper-level PV.For EC2,latent heat release notably enhances low-level PV,directly contributing to its rapid intensification.To validate these findings,sensitivity tests are conducted using the Weather Research and Forecasting model,with latent heat release turned off in the microphysical scheme for both cases.The results confirm the crucial role of latent heat release in generating low-level PV,further revealing that latent heat release contributes more to the explosive development of EC2 than that of EC1.
基金supported by the National Natural Science Foundation of China(Grant No.52405257)the China Postdoctoral Science Foundation(Grant No.2024M764201).
文摘Hypersonic morphing vehicle(HMV)can reconfigure aerodynamic geometries in real time,adapting to diverse needs like multi-mission profiles and wide-speed-range flight,spanwise morphing and sweep angle variation are representative large-scale wing reconfiguration modes.To meet the HMV's need for an increased lift and a lift to drag ratio during hypersonic maneuverability and cruise or reentry equilibrium glide,this paper proposes an innovative single-DOF coupled morphing-wing system.We then systematically analyze its open-loop kinematics and closed-loop connectivity constraints,and the proposed system integrates three functional modules:the preset locking/release mechanism,the coupled morphing-wing mechanism,and the integrated wing locking with active stiffness control mechanism.Experimental validation confirms stable,continuous morphing under simulated aerodynamic loads.The experimental results indicate:(i)SMA actuators exhibit response times ranging from 18 s to 160 s,providing sufficient force output for wing unlocking;(ii)The integrated wing locking with active stiffness control mechanism effectively secures wing positions while eliminating airframe clearance via SMA actuation,improving the first-order natural frequency by more than 17%;(iii)The distributed aerodynamic loading system enables precise multi-stage follow-up loading during morphing,with the coupled morphing wing maintaining stable,continuous operation under 0-3500 N normal loads and 110-140 N axial force.The proposed single-DOF coupled morphing mechanism not only simplifies and improves structural efficiency but also demonstrates superior performance in locking control,stiffness enhancement,and aerodynamic responsiveness.This establishes a foundational framework for the design of future intelligent morphing configurations and the implementation of flight control systems.
基金supported by the financial assistance from Natural Science Fund Project of Science and Technology Department of Jilin Province (Nos.YDZJ202301ZYTS141,YDZJ202501ZYTS793)。
文摘Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.
基金supported by the National Natural Science Foundation of China(No.11602200)。
文摘This study is dedicated to numerically investigate the dynamic behavior of a missile released from a helicopter under the influence of downwash from the rotating rotors using AGM-114 Hellfire and UH-60 as the testcase.Simulations are conducted using unsteady Reynolds-averaged Navier-Stokes(URANS)with shear stress transport(SST)k-ωturbulence model,incorporating six-degree-of-freedom(6-DOF)motion and overset grid.Two releasing scenarios,viz.,hover and forward flight,are analyzed under varying missile launch thrust and helicopter forward flight speed.Results reveal that the rotor downwash significantly affects the stability of the missile,particularly during hovering case,where low thrust prolongs wake interaction.In forward flight,the increased airspeed can in principle reduce wake influence but introduces asymmetrical aerodynamic effects on the trajectory of the missile.The findings offer guidance for missile release and launch planning in rotorcraft operations.
基金supported by Catalan Government,Nos.2014SGR344(to JT),2017SGR704(to JT),2021SGR01214(to MAL)MCIN/AEI/10.13039/501100011033/by“ERDF A way of making Europe,”Nos.SAF2015-67143(to JT),PID2019-106332GB-I00(to JT and MAL)and PID2022-141252NB-I00(to MAL).
文摘During the development of the nervous system,there is an overproduction of neurons and synapses.Hebbian competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or strengthening.We have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse consolidation.The purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this process.In particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(PKA and PKC)and voltage-gated calcium channels,at different nerve endings in developmental competition.The dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific endings.We describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75NTR pathways that can influence the timing and fate of the competitive interactions between the different axon terminals.The downstream displacement of the PKA/PKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary synapses.Finally,calcium entry through L-and P/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the N-type channel in developing nerve terminals)contributes to reduce transmitter release and promote withdrawal of the most unfavorable nerve terminals during elimination(the weakest in acetylcholine release and those that have already become silent).The main findings contribute to a better understanding of punishment-rewarding interactions between nerve endings during development.Identifying the molecular targets and signaling pathways that allow synapse consolidation or withdrawal of synapses in different situations is important for potential therapies in neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China(Nos.51808158,52170101,and 52200116)Tianjin Natural Science Foundation(No.23JCYBJC00640).
文摘The electrochemical corrosion of ductile pipes(DPs)in drinking water distribution systems(DWDS)has a crucial impact on cement-mortar lining(CML)failure and metal release,potentially leading to drinking water quality deterioration and posing a risk to public health.An in-situ scanning vibrating electrode technique(SVET)with micron-scale resolution,microscopic scale detection and water quality analysis were used to investigate the corrosion behavior and metal release from DPs throughout the whole CML failure process.Metal pollutants release occurred at three different stages of CML failure process,and there are potential risks of water quality deterioration exceeding the maximum allowable levels set by national standards in the partial failure stage and lining peeling stage.Furthermore,the effects of water chemistry(Cl^(−),SO_(4)^(2−),NO_(3)−,and Ca^(2+))on corrosion scale growth and iron release activity,were investigated during the CML partial failure stage.Results showed that the CML failure process in DPs was accelerated by the autocatalysis of localized corrosion.Cl^(−)was found to damage the uncorroded metal surface,while SO_(4)^(2−)mainly dissolved the corrosion scale surface,increasing iron release.Both the oxidation of NO_(3)−and selective sedimentation of Ca2+were found to enhance the stability of corrosion scales and inhibit iron release.
基金supported by the Natural Science Foundation of Liaoning Province(2023-MSBA-020)the Fundamental Research Funds for Central Universities(DUT24MS020)Science and Technology Innovation Fund of Dalian(2022JJ13SN073).
文摘Ferroptosis is a novel form of cell death driven by oxidative damage,and is implicated in various pathological conditions,including neurodegenerative diseases,retinal damage,and ischemia-reperfusion injury of organs.Inhibiting ferroptosis has shown great promise as a therapeutic strategy for these diseases,underscoring the urgent need to develop effective ferroptosis inhibitors.Although Ferrostatin-1(Fer-1)is a potent ferroptosis inhibitor,its susceptibility to oxidation and metabolic inactivation limits its clinical utility.In this study,the accumulation of peroxides and the resulting oxidative damage in the cellular microenvironment during ferroptosis were utilized to design Ferrostatin-1 prodrugs with reactive oxygen species-responsive features.This approach led to the development of a series of ferroptosis inhibitors that were capable of recognizing oxidative damage in diseased areas,allowing for targeted release and improved stability.The novel compounds demonstrated significant inhibitory effects and selectivity against RSL-3-induced ferroptosis in HK-2 cells,with compound a1 exhibiting an EC50 of 15.4�0.7μM,outperforming Fer-1.These compounds effectively identify the oxidative microenvironment associated with ferroptosis,enabling the targeted release of Fer-1,which prevents lipid peroxide accumulation and inhibits ferroptosis.This strategy holds promise for treating diseases related to ferroptosis,offering a targeted and intelligent therapeutic approach.
基金supported by the National Key R&D Program of China(2023YFB2407900)the National Natural Science Foundation of China(52302512)+1 种基金State Key Laboratory of New Ceramic and Fine Processing Tsinghua University(KFZD202305)Zhejiang Province Science and Technology Program Grant(2024C0127(SD2))。
文摘Cascading thermal runaway(TR)propagation poses a critical safety concern for large-format sodium-ion battery(SIB)systems because of the heightened risks of fires or explosions.However,effectively suppressing TR propagation without introducing unintended side effects remains a significant challenge.Herein,we demonstrate a localized energy release method to mitigate TR,by reducing the state of charge(SOC)of cells adjacent to the thermally runaway unit.We discover that as the SOCs decreased from 100%to 25%,the TR trigger temperature decreased significantly,and the maximum temperature decrease from 367 to 229℃.Meanwhile,the volume of gas decreased to one-third of its original value,while the range of explosion limits significantly narrowed.The analysis of the morphology of the debris further confirms that the structural damage is greater at higher SOC levels.Moreover,an Entropy Weight and Technique for Order Preference by Similarity to an Ideal Solution(EW-TOPSIS)method has been established to assess the safety status of SIBs,showing that the TR possibility is nearly linear with the SOCs,and the TR hazard is exponentially related to the SOCs.Finally,when the SOC of cells adjacent to the TR cell is reduced to 25%,TR can be directly blocked without the need for additional cooling or thermal insulation methods.This study not only advances the understanding of TR behavior in SIBs but also offers a straightforward approach to mitigating the TR risk in SIB systems.
