This paper proposes a method to predict nonlinear Pilot-Induced Oscillation(PIO)using an intelligent human pilot model.This method is based on a scalogram-based PIO metric,which uses wavelet transforms to analyze the ...This paper proposes a method to predict nonlinear Pilot-Induced Oscillation(PIO)using an intelligent human pilot model.This method is based on a scalogram-based PIO metric,which uses wavelet transforms to analyze the nonlinear characteristics of a time-varying system.The intelligent human pilot model includes three modules:perception module,decision and adaptive module,and execution module.Intelligent and adaptive features,including a neural network receptor,fuzzy decision and adaptation,are also introduced into the human pilot model to describe the behavior of the human pilot accommodating the nonlinear events.Furthermore,an algorithm is proposed to describe the procedure of the PIO prediction method with nonlinear evaluation cases.The prediction results obtained by numerical simulation are compared with the assessments of flight test data to validate the utility of the method.The flight test data were generated in the evaluation of the Smart-Cue/Smart-Gain,which is capable of reducing the PIO tendencies considerably.The results show that the method can be applied to predict the nonlinear PIO events by human pilot model simulation.展开更多
In modern chemical engineering processes, the involvement of solid/fluid interface is the most important component of process intensification techniques, such as confined membrane separation and catalysis. In the revi...In modern chemical engineering processes, the involvement of solid/fluid interface is the most important component of process intensification techniques, such as confined membrane separation and catalysis. In the review, we summarized the research progress of the latest theoretical and experimental works to elucidate the contribution of interface to the fluid properties and structures at nano-and micro-scale. We mainly focused on water, alcohol aqueous solution, and ionic liquids, because they are classical systems in interfacial science and/or widely involved in the industrialization process. Surface-induced fluids were observed in all reviewed systems and played a critical role in physicochemical properties and structures of outside fluid. It can even be regarded as a new interface, when the adsorption layer has a strong interaction with the solid surface. Finally, we proposed a perspective on scientific challenges in the modern chemical engineering processes and outlined future prospects.展开更多
Alzheimer’s disease is a neurodegenerative disease induced by multiple interconnected mechanisms.Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-face...Alzheimer’s disease is a neurodegenerative disease induced by multiple interconnected mechanisms.Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet pathology.However,clinical translation of peptide drugs is greatly hampered by their low permeability into brain.Herein,a hybrid peptide HNSS is generated by merging two therapeutic peptides(SS31 and S-14 G Humanin(HNG)),using a different approach from the classical shuttle-therapeutic peptide conjugate design.HNSS demonstrated increased bio-permeability,with a 2-fold improvement in brain distribution over HNG,thanks to its structure mimicking the design of signal peptide-derived cell-penetrating peptides.HNSS efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting,ROS scavenging and p-STAT3 activation.Meanwhile,HNSS with increased Aβaffinity greatly inhibited Aβoligomerization/fibrillation,and interrupted Aβinteraction with neuron/microglia by reducing neuronal mitochondrial Aβdeposition and promoting microglial phagocytosis of Aβ.In3×Tg-AD transgenic mice,HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive performance.This work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification,providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.展开更多
Human immunodeficiency virus(HIV) attacks human immune system and causes life-threatening acquired immune deficiency syndrome(AIDS). Treatment with combination antiretroviral therapy(cART) could inhibit virus growth a...Human immunodeficiency virus(HIV) attacks human immune system and causes life-threatening acquired immune deficiency syndrome(AIDS). Treatment with combination antiretroviral therapy(cART) could inhibit virus growth and slow progression of the disease, however, at the same time posing various adverse effects. Host ubiquitin-proteasome pathway(UPP) plays important roles in host immunity against pathogens including viruses by inducing degradation of viral proteins. Previously a series of methods for retargeting substrates for ubiquitin-proteasome degradation have been successfully established. In this study, we attempted to design and construct artificial chimeric ubiquitin ligases(E3 s) based on known human E3 s in order to manually target HIV-1 integrase for ubiquitin proteasome pathway-mediated degradation.Herein, a series of prototypical chimeric E3 s have been designed and constructed, and original substrate-binding domains of these E3 s were replaced with host protein domains which interacted with viral proteins. After functional assessment screening, 146 LI was identified as a functional chimeric E3 for HIV-1 NL4-3 integrase. 146 LI was then further optimized to generate 146 LIS(146 LI short) which has been shown to induce Lys48-specific polyubiquitination and reduce protein level of HIV-1 NL4-3 integrase more effectively in cells. Lymphocyte cells with 146 LIS knock-in generated by CRISPR/Cas-mediated homology-directed repair(HDR) showed remarkably decreased integration of HIV-1 NL4-3 viral DNAs and reduced viral replication without obvious cell cytotoxicity. Our study successfully obtained an artificial chimeric E3 which can induce Lys48-specific polyubiquitination and proteasome-mediated degradation of HIV-1 NL4-3 integrase, thus effectively inhibiting viral DNA integration and viral replication upon virus infection.展开更多
This paper presents a Shared Control Architecture(SCA)between a human pilot and a smart inceptor for nonlinear Pilot Induced Oscillations(PIOs),e.g.,category II or III PIOs.One innovation of this paper is that an inte...This paper presents a Shared Control Architecture(SCA)between a human pilot and a smart inceptor for nonlinear Pilot Induced Oscillations(PIOs),e.g.,category II or III PIOs.One innovation of this paper is that an intelligent shared control architecture is developed based on the intelligent active inceptor technique,i.e.,Smart Adaptive Flight Effective Cue(SAFE-Cue).A deep reinforcement learning approach namely Deep Deterministic Policy Gradient(DDPG)method is chosen to design a gain adaptation mechanism for the SAFE-Cue module.By doing this,the gains of the SAFE-Cue will be intelligently tuned once nonlinear PIOs triggered;meanwhile,the human pilot will receive a force cue from the SAFE-Cue,and will consequently adapting his/her control policy.The second innovation of this paper is that the reward function of the DDPG based gain adaptation approach is constructed according to flying qualities.Under the premise of considering failure situation,task completion qualities and pilot workload are also taken into account.Finally,the proposed approach is validated using numerical simulation experiments with two types of scenarios:lower actuator rate limits and airframe damages.The Inceptor Peak Power-Phase(IPPP)metric is adopted to analyze the human-vehicle system simulation results.Results and analysis show that the DDPG based sharing control approach can well address nonlinear PIO problems consisting of Categories Ⅱ and Ⅲ PIO events.展开更多
The solution of large sparse linear systems is one of the most important problems in large scale scientific computing. Among the many methods developed, the preconditioned Krylov subspace methods [1] are considered th...The solution of large sparse linear systems is one of the most important problems in large scale scientific computing. Among the many methods developed, the preconditioned Krylov subspace methods [1] are considered the preferred methods. Selecting an effective preconditioner with appropriate parameters for a specific sparse linear system presents a challenging task for many application scientists and engineers who have little knowledge of preconditioned iterative methods. The purpose of this paper is to predict the parameter solvability space of the preconditioners with two or more parameters. The parameter solvability space is usually irregular, however, in many situations it shows spatial locality, i.e. the parameter locations that are closer in parameter space are more likely to have similar solvability. We propose three spatial data mining methods to predict the solvability of ILUT which make usage of spatial locality in different ways. The three methods are MSC （multi-points SVM classifier）, OSC （overall SVM classifier）, and OSAC （overall spatial autoregressive classifier）. The experimental results show that both MSC and OSAC can obtain 90% accuracy in prediction, but OSAC is much simpler to implement. We focus our work on ILUT preconditioner [2], but the proposed strategies should be applicable to other preconditioners with two or more parameters.展开更多
The facile synthesis of single-crystal hydrogen-bonded organic frameworks(HOFs)on a gram scale remains a significant challenge but is crucial for practical applications.Herein,we report a novel strategy to prepare two...The facile synthesis of single-crystal hydrogen-bonded organic frameworks(HOFs)on a gram scale remains a significant challenge but is crucial for practical applications.Herein,we report a novel strategy to prepare two three-dimensional(3D)single-crystal HOFs at ambient temperature and pressure with gram-scale products.The imine-linked oligomers were synthesized using ionic liquids as catalysts,which self-assembled in situ to form large single crystals.The optimal material,H1,exhibited iodine uptake capacities of 6.02 and 4.44 g g^(-1)from vapor and aqueous solutions,respectively,ranking among the highest reported HOFs.For the first time,the iodine-adsorbed H1 was used as an iodine source for synthesizingβ-iodoethers,achieving excellent yields comparable to those obtained using iodine as the reactant.This study not only presents a simple method for the scalable synthesis of single-crystal HOFs but also explores a potential application of iodine-adsorbed materials in organic synthesis.展开更多
Present study introduced a controlled freezing-point storage(CFPS)technique for the postharvest storage of satsuma mandarin(Citrus unshiu Marc.cv.Miyagawa Wase),with the environment temperature of−2℃ during the whole...Present study introduced a controlled freezing-point storage(CFPS)technique for the postharvest storage of satsuma mandarin(Citrus unshiu Marc.cv.Miyagawa Wase),with the environment temperature of−2℃ during the whole storage period.The postharvest loss and quality changes of satsuma mandarin were investigated.according to the results,CFPS completely prevented fruit decay in the 90 days storage and the following shelf period without causing fruit chilling injury.in comparison,the decay rate of fruit stored at 10℃ increased with the elongation of storage time,and reach to 6.67%after 90 days storage,then further increased to 33.33%after transferring to the shelf.CFPS significantly reduced the incidences of calyx browning,completely prevented fruit puffing,alleviated the decreases of citric acid,fructose and glucose in the long-term storage and the following shelf life of satsuma mandarin,compared with the 10℃ storage.but CFPS alleviated the postharvest rind color development of satsuma mandarin,leading to paler rind color compared to the 10℃ storage group.both 10℃ storage and CFPS group showed significant decrease of total aroma volatiles contents in the pulp after more than two months’storage.but most of the volatiles,including all of the monoterpenes and aliphatic alcohols,as well as part of the monoterpenes derivatives and aliphatic aldehydes,rebound after being transferred to the 20℃ shelf,with the extent much higher in 10℃ storage group than that in CFPS group.in the shelf-life,the total volatile content of the 10℃ storage group was about 2 fold that of the newly-harvested fruit,but the volatiles of the CFPS group were more similar to the newly-harvested fruit in content and composition.Correspondingly,the consumer’s sensory evaluation results showed that the fruit of CFPS group was slightly sourer and with better typical mandarin flavor than those stored at 10℃.Comprehensively,CFPS was applicable in reducing the postharvest loss and alleviating quality deterioration in the long-term storage of satsuma mandarin.展开更多
Various ions and antibiotics,widely used in industry and clinical medicine,respectively,are massively discharged to atmosphere and water,resulting in severe pollutions on environment and potential threats to human hea...Various ions and antibiotics,widely used in industry and clinical medicine,respectively,are massively discharged to atmosphere and water,resulting in severe pollutions on environment and potential threats to human health.Besides,amino acids,the primary substances for the establishment of proteins,cells and tissues,are crucial to human health.Therefore,seeking effective and practicable materials to detect aforesaid analytes is vitally meaningful.Metal-organic frameworks centered with lanthanide ions(Ln-MOFs),also known as lanthanide coordination polymers,are considered as a charming category of multi-functional hybrid crystalline materials with fascinating structures and incomparable luminescent characteristics.Benefited from their unique merits,Ln-MOFs have been largely developed as excellent luminescent sensors for fast and efficient sensing various analytes.In this review,we aim to introduce some of the recent researches between 2018 to 2022 on Ln-MOFs applied as chemical sensors for ions,antibiotics and amino acids based on luminescent quenching and enhancing effects,and provide an update and summary for the latest progresses in this field.展开更多
Gene therapy represents a promising treatment for the Alzheimer’s disease(AD). However,gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have deve...Gene therapy represents a promising treatment for the Alzheimer’s disease(AD). However,gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood–brain barrier(BBB)penetration and QSH peptide for β-amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against β-site amyloid precursor protein-cleaving enzyme 1(BACE1), the rate-limiting enzyme of Aβ production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the Aβ deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels,as well as Aβ and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.展开更多
Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obst...Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.展开更多
Compromised autophagy and defective lysosomal clearance significantly contribute to impaired neuronal proteostasis,which represents a hallmark of Alzheimer’s disease(AD)and other age-related neurodegenerative disorde...Compromised autophagy and defective lysosomal clearance significantly contribute to impaired neuronal proteostasis,which represents a hallmark of Alzheimer’s disease(AD)and other age-related neurodegenerative disorders.Growing evidence has implicated that modulating autophagic flux,instead of inducing autophagosome formation alone,would be more reliable to rescue neuronal proteostasis.Concurrently,selectively enhancing drug concentrations in the leision areas,instead of the whole brain,will maximize therapeutic efficacy while reduing non-selective autophagy induction.Herein,we design a ROS-responsive targeted micelle system(TT-NM/Rapa)to enhance the delivery efficiency of rapamycin to neurons in AD lesions guided by the fusion peptide TPL,and facilitate its intracellular release via ROS-mediated disassembly of micelles,thereby maximizing autophagic flux modulating efficacy of rapamycin in neurons.Consequently,it promotes the efficient clearance of intracellular neurotoxic proteins,β-amyloid and hyperphosphorylated tau proteins,and ameliorates memory defects and neuronal damage in 3×Tg-AD transgenic mice.Our studies demonstrate a promising strategy to restore autophagic flux and improve neuronal proteostasis by rationally-engineered nano-systems for delaying the progression of AD.展开更多
The inferior electrical contact to two-dimensional(2D)materials is a critical challenge for their application in post-silicon very large-scale integrated circuits.Electrical contacts were generally related to their re...The inferior electrical contact to two-dimensional(2D)materials is a critical challenge for their application in post-silicon very large-scale integrated circuits.Electrical contacts were generally related to their resistive effect,quantified as contact resistance.With a systematic investigation,this work demonstrates a capacitive metal-insulator-semiconductor(MIS)field-effect at the electrical contacts to 2D materials:The field-effect depletes or accumulates charge carriers,redistributes the voltage potential,and gives rise to abnormal current saturation and nonlinearity.On one hand,the current saturation hinders the devices’driving ability,which can be eliminated with carefully engineered contact configurations.On the other hand,by introducing the nonlinearity to monolithic analog artificial neural network circuits,the circuits’perception ability can be significantly enhanced,as evidenced using a coronavirus disease 2019(COVID-19)critical illness prediction model.This work provides a comprehension of the field-effect at the electrical contacts to 2D materials,which is fundamental to the design,simulation,and fabrication of electronics based on 2D materials.展开更多
Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing ...Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.展开更多
The dynamic variation issues of variable-load unmanned aerial vehicle(UAV)used in agricultural plant protection activities was addressed by a disturbanceresistant control system based on PD(proportional-derivative)sli...The dynamic variation issues of variable-load unmanned aerial vehicle(UAV)used in agricultural plant protection activities was addressed by a disturbanceresistant control system based on PD(proportional-derivative)sliding mode control.First,a time-varying dynamic model was developed by analyzing the variations in mass,center of gravity and moment of inertia across time.Then a trajectory tracking control approach based on PD sliding mode control was designed to develop an inner-loop attitude controller and an outer-loop trajectory controller to accomplish precise and closely coupled trajectory tracking.Numerical simulations were conducted to verify the trajectory tracking performance,demonstrating accurate tracking of the desired trajectory with standard deviations of 0.0507,0.1613 and 0.0002 m in the horizontal,lateral and vertical directions,respectively.In terms of attitude control,the system exhibited favorable performance on the roll,pitch and yaw axes,with small transient errors and rapid convergence.Flight experiments further demonstrated that the UAV accurately followed the specified path,and errors in both straight and twisting segments satisfied control criteria.This control system ensured efficient and steady trajectory tracking,offering theoretical and application references for intelligent and precise agricultural plant protection activities.展开更多
基金co-supported by the National Natural Science Foundation of China (No. 11502008)the Aeronautical Science Foundation of China (No. 2017ZA51002)
文摘This paper proposes a method to predict nonlinear Pilot-Induced Oscillation(PIO)using an intelligent human pilot model.This method is based on a scalogram-based PIO metric,which uses wavelet transforms to analyze the nonlinear characteristics of a time-varying system.The intelligent human pilot model includes three modules:perception module,decision and adaptive module,and execution module.Intelligent and adaptive features,including a neural network receptor,fuzzy decision and adaptation,are also introduced into the human pilot model to describe the behavior of the human pilot accommodating the nonlinear events.Furthermore,an algorithm is proposed to describe the procedure of the PIO prediction method with nonlinear evaluation cases.The prediction results obtained by numerical simulation are compared with the assessments of flight test data to validate the utility of the method.The flight test data were generated in the evaluation of the Smart-Cue/Smart-Gain,which is capable of reducing the PIO tendencies considerably.The results show that the method can be applied to predict the nonlinear PIO events by human pilot model simulation.
基金supported by the National Natural Science Foundation of China [21878144, 21729601, 21838004]the Foundation for Innovative Research Groups of the National Natural Science Foundation of China [21921006]+3 种基金Project of Jiangsu Natural Science Foundation of China [BK20171464]Project of Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)the Kempe Foundation in Swedengrant of Ministry of Research and Innovation, CNCS-UEFISCDI, Romania, project number PN-III-P4-ID-PCCF-2016-0050, within PNCDI III and the Swedish Science Council (VR)。
文摘In modern chemical engineering processes, the involvement of solid/fluid interface is the most important component of process intensification techniques, such as confined membrane separation and catalysis. In the review, we summarized the research progress of the latest theoretical and experimental works to elucidate the contribution of interface to the fluid properties and structures at nano-and micro-scale. We mainly focused on water, alcohol aqueous solution, and ionic liquids, because they are classical systems in interfacial science and/or widely involved in the industrialization process. Surface-induced fluids were observed in all reviewed systems and played a critical role in physicochemical properties and structures of outside fluid. It can even be regarded as a new interface, when the adsorption layer has a strong interaction with the solid surface. Finally, we proposed a perspective on scientific challenges in the modern chemical engineering processes and outlined future prospects.
基金supported by National Natural Science Foundation of China(82273868 and 82073780)Shanghai Municipal Natural Science Foundation(19ZR1406200).
文摘Alzheimer’s disease is a neurodegenerative disease induced by multiple interconnected mechanisms.Peptide drug candidates with multi-modal efficacy generated from fusion strategy are suitable for addressing multi-facet pathology.However,clinical translation of peptide drugs is greatly hampered by their low permeability into brain.Herein,a hybrid peptide HNSS is generated by merging two therapeutic peptides(SS31 and S-14 G Humanin(HNG)),using a different approach from the classical shuttle-therapeutic peptide conjugate design.HNSS demonstrated increased bio-permeability,with a 2-fold improvement in brain distribution over HNG,thanks to its structure mimicking the design of signal peptide-derived cell-penetrating peptides.HNSS efficiently alleviated mitochondrial dysfunction through the combined effects of mitochondrial targeting,ROS scavenging and p-STAT3 activation.Meanwhile,HNSS with increased Aβaffinity greatly inhibited Aβoligomerization/fibrillation,and interrupted Aβinteraction with neuron/microglia by reducing neuronal mitochondrial Aβdeposition and promoting microglial phagocytosis of Aβ.In3×Tg-AD transgenic mice,HNSS treatment efficiently inhibited brain neuron loss and improved the cognitive performance.This work validates the rational fusion design-based strategy for bio-permeability improvement and efficacy amplification,providing a paradigm for developing therapeutic peptide candidates against neurodegenerative disease.
基金supported by Grants from the National Science and Technology Major Project of China (2014ZX10001003)National Natural Science Foundation of China (#81620108020 & #31400774)。
文摘Human immunodeficiency virus(HIV) attacks human immune system and causes life-threatening acquired immune deficiency syndrome(AIDS). Treatment with combination antiretroviral therapy(cART) could inhibit virus growth and slow progression of the disease, however, at the same time posing various adverse effects. Host ubiquitin-proteasome pathway(UPP) plays important roles in host immunity against pathogens including viruses by inducing degradation of viral proteins. Previously a series of methods for retargeting substrates for ubiquitin-proteasome degradation have been successfully established. In this study, we attempted to design and construct artificial chimeric ubiquitin ligases(E3 s) based on known human E3 s in order to manually target HIV-1 integrase for ubiquitin proteasome pathway-mediated degradation.Herein, a series of prototypical chimeric E3 s have been designed and constructed, and original substrate-binding domains of these E3 s were replaced with host protein domains which interacted with viral proteins. After functional assessment screening, 146 LI was identified as a functional chimeric E3 for HIV-1 NL4-3 integrase. 146 LI was then further optimized to generate 146 LIS(146 LI short) which has been shown to induce Lys48-specific polyubiquitination and reduce protein level of HIV-1 NL4-3 integrase more effectively in cells. Lymphocyte cells with 146 LIS knock-in generated by CRISPR/Cas-mediated homology-directed repair(HDR) showed remarkably decreased integration of HIV-1 NL4-3 viral DNAs and reduced viral replication without obvious cell cytotoxicity. Our study successfully obtained an artificial chimeric E3 which can induce Lys48-specific polyubiquitination and proteasome-mediated degradation of HIV-1 NL4-3 integrase, thus effectively inhibiting viral DNA integration and viral replication upon virus infection.
基金co-supported by the Fundamental Research Funds for the Central Universities of China(No.YWF-23-SDHK-L-005)the 1912 Project,China and the Aeronautical Science Foundation of China(No.20220048051001).
文摘This paper presents a Shared Control Architecture(SCA)between a human pilot and a smart inceptor for nonlinear Pilot Induced Oscillations(PIOs),e.g.,category II or III PIOs.One innovation of this paper is that an intelligent shared control architecture is developed based on the intelligent active inceptor technique,i.e.,Smart Adaptive Flight Effective Cue(SAFE-Cue).A deep reinforcement learning approach namely Deep Deterministic Policy Gradient(DDPG)method is chosen to design a gain adaptation mechanism for the SAFE-Cue module.By doing this,the gains of the SAFE-Cue will be intelligently tuned once nonlinear PIOs triggered;meanwhile,the human pilot will receive a force cue from the SAFE-Cue,and will consequently adapting his/her control policy.The second innovation of this paper is that the reward function of the DDPG based gain adaptation approach is constructed according to flying qualities.Under the premise of considering failure situation,task completion qualities and pilot workload are also taken into account.Finally,the proposed approach is validated using numerical simulation experiments with two types of scenarios:lower actuator rate limits and airframe damages.The Inceptor Peak Power-Phase(IPPP)metric is adopted to analyze the human-vehicle system simulation results.Results and analysis show that the DDPG based sharing control approach can well address nonlinear PIO problems consisting of Categories Ⅱ and Ⅲ PIO events.
文摘The solution of large sparse linear systems is one of the most important problems in large scale scientific computing. Among the many methods developed, the preconditioned Krylov subspace methods [1] are considered the preferred methods. Selecting an effective preconditioner with appropriate parameters for a specific sparse linear system presents a challenging task for many application scientists and engineers who have little knowledge of preconditioned iterative methods. The purpose of this paper is to predict the parameter solvability space of the preconditioners with two or more parameters. The parameter solvability space is usually irregular, however, in many situations it shows spatial locality, i.e. the parameter locations that are closer in parameter space are more likely to have similar solvability. We propose three spatial data mining methods to predict the solvability of ILUT which make usage of spatial locality in different ways. The three methods are MSC （multi-points SVM classifier）, OSC （overall SVM classifier）, and OSAC （overall spatial autoregressive classifier）. The experimental results show that both MSC and OSAC can obtain 90% accuracy in prediction, but OSAC is much simpler to implement. We focus our work on ILUT preconditioner [2], but the proposed strategies should be applicable to other preconditioners with two or more parameters.
基金supported by the National Natural Science Foundation of China(21975153)。
文摘The facile synthesis of single-crystal hydrogen-bonded organic frameworks(HOFs)on a gram scale remains a significant challenge but is crucial for practical applications.Herein,we report a novel strategy to prepare two three-dimensional(3D)single-crystal HOFs at ambient temperature and pressure with gram-scale products.The imine-linked oligomers were synthesized using ionic liquids as catalysts,which self-assembled in situ to form large single crystals.The optimal material,H1,exhibited iodine uptake capacities of 6.02 and 4.44 g g^(-1)from vapor and aqueous solutions,respectively,ranking among the highest reported HOFs.For the first time,the iodine-adsorbed H1 was used as an iodine source for synthesizingβ-iodoethers,achieving excellent yields comparable to those obtained using iodine as the reactant.This study not only presents a simple method for the scalable synthesis of single-crystal HOFs but also explores a potential application of iodine-adsorbed materials in organic synthesis.
基金supported by the Key Research and Development Projects of Zhejiang Province(2021C02015)Fundamental Research Funds for the Central Universities(226-2022-00215)Science and Technology Innovation Team of the Ministry of Agriculture and Rural Affairs.
文摘Present study introduced a controlled freezing-point storage(CFPS)technique for the postharvest storage of satsuma mandarin(Citrus unshiu Marc.cv.Miyagawa Wase),with the environment temperature of−2℃ during the whole storage period.The postharvest loss and quality changes of satsuma mandarin were investigated.according to the results,CFPS completely prevented fruit decay in the 90 days storage and the following shelf period without causing fruit chilling injury.in comparison,the decay rate of fruit stored at 10℃ increased with the elongation of storage time,and reach to 6.67%after 90 days storage,then further increased to 33.33%after transferring to the shelf.CFPS significantly reduced the incidences of calyx browning,completely prevented fruit puffing,alleviated the decreases of citric acid,fructose and glucose in the long-term storage and the following shelf life of satsuma mandarin,compared with the 10℃ storage.but CFPS alleviated the postharvest rind color development of satsuma mandarin,leading to paler rind color compared to the 10℃ storage group.both 10℃ storage and CFPS group showed significant decrease of total aroma volatiles contents in the pulp after more than two months’storage.but most of the volatiles,including all of the monoterpenes and aliphatic alcohols,as well as part of the monoterpenes derivatives and aliphatic aldehydes,rebound after being transferred to the 20℃ shelf,with the extent much higher in 10℃ storage group than that in CFPS group.in the shelf-life,the total volatile content of the 10℃ storage group was about 2 fold that of the newly-harvested fruit,but the volatiles of the CFPS group were more similar to the newly-harvested fruit in content and composition.Correspondingly,the consumer’s sensory evaluation results showed that the fruit of CFPS group was slightly sourer and with better typical mandarin flavor than those stored at 10℃.Comprehensively,CFPS was applicable in reducing the postharvest loss and alleviating quality deterioration in the long-term storage of satsuma mandarin.
基金financially supported by the National Natural Science Foundation of China(21801107)the Natural Science Foundation of Shandong Province(ZR2018BB005)the Youth Innovation Team of Shandong Colleges and Universities(2019KJC027)。
文摘Various ions and antibiotics,widely used in industry and clinical medicine,respectively,are massively discharged to atmosphere and water,resulting in severe pollutions on environment and potential threats to human health.Besides,amino acids,the primary substances for the establishment of proteins,cells and tissues,are crucial to human health.Therefore,seeking effective and practicable materials to detect aforesaid analytes is vitally meaningful.Metal-organic frameworks centered with lanthanide ions(Ln-MOFs),also known as lanthanide coordination polymers,are considered as a charming category of multi-functional hybrid crystalline materials with fascinating structures and incomparable luminescent characteristics.Benefited from their unique merits,Ln-MOFs have been largely developed as excellent luminescent sensors for fast and efficient sensing various analytes.In this review,we aim to introduce some of the recent researches between 2018 to 2022 on Ln-MOFs applied as chemical sensors for ions,antibiotics and amino acids based on luminescent quenching and enhancing effects,and provide an update and summary for the latest progresses in this field.
基金supported by the National Natural Science Foundation of China (Nos. 81473150 and 81273461)Major Program of National Natural Science Foundation of China (No. 81690263)the National Basic Research Program of China (No. 2013CB932500)
文摘Gene therapy represents a promising treatment for the Alzheimer’s disease(AD). However,gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood–brain barrier(BBB)penetration and QSH peptide for β-amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against β-site amyloid precursor protein-cleaving enzyme 1(BACE1), the rate-limiting enzyme of Aβ production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the Aβ deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels,as well as Aβ and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.
基金supported by National Natural Science Foundation of China(Nos.82073780 and 82273868,China)Shanghai Municipal Natural Science Foundation(No.19ZR1406200,China)。
文摘Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.
基金supported by National Natural Science Foundation of China(No.82073780 and 81690263)Shanghai Municipal Natural Science Foundation(No.19ZR140620).
文摘Compromised autophagy and defective lysosomal clearance significantly contribute to impaired neuronal proteostasis,which represents a hallmark of Alzheimer’s disease(AD)and other age-related neurodegenerative disorders.Growing evidence has implicated that modulating autophagic flux,instead of inducing autophagosome formation alone,would be more reliable to rescue neuronal proteostasis.Concurrently,selectively enhancing drug concentrations in the leision areas,instead of the whole brain,will maximize therapeutic efficacy while reduing non-selective autophagy induction.Herein,we design a ROS-responsive targeted micelle system(TT-NM/Rapa)to enhance the delivery efficiency of rapamycin to neurons in AD lesions guided by the fusion peptide TPL,and facilitate its intracellular release via ROS-mediated disassembly of micelles,thereby maximizing autophagic flux modulating efficacy of rapamycin in neurons.Consequently,it promotes the efficient clearance of intracellular neurotoxic proteins,β-amyloid and hyperphosphorylated tau proteins,and ameliorates memory defects and neuronal damage in 3×Tg-AD transgenic mice.Our studies demonstrate a promising strategy to restore autophagic flux and improve neuronal proteostasis by rationally-engineered nano-systems for delaying the progression of AD.
基金This work was supported the National Natural Science Foundation of China(No.11804024).
文摘The inferior electrical contact to two-dimensional(2D)materials is a critical challenge for their application in post-silicon very large-scale integrated circuits.Electrical contacts were generally related to their resistive effect,quantified as contact resistance.With a systematic investigation,this work demonstrates a capacitive metal-insulator-semiconductor(MIS)field-effect at the electrical contacts to 2D materials:The field-effect depletes or accumulates charge carriers,redistributes the voltage potential,and gives rise to abnormal current saturation and nonlinearity.On one hand,the current saturation hinders the devices’driving ability,which can be eliminated with carefully engineered contact configurations.On the other hand,by introducing the nonlinearity to monolithic analog artificial neural network circuits,the circuits’perception ability can be significantly enhanced,as evidenced using a coronavirus disease 2019(COVID-19)critical illness prediction model.This work provides a comprehension of the field-effect at the electrical contacts to 2D materials,which is fundamental to the design,simulation,and fabrication of electronics based on 2D materials.
基金National Natural Science Foundation of China,Grant/Award Number:82222903Li Ka Shing Faculty of Medicine(Start-up Fund)of The University of Hong Kong.
文摘Nowadays,cancer has become the leading cause of death worldwide,driving the need for effective therapeutics to improve patient prognosis.Photodynamic therapy(PDT)has been widely applied as an antitumor modality,owing to its minimal invasiveness,localized tumor damage,and high safety profile.However,its efficacy is limited by poor stability of photosensitizers,inadequate tumor accumulation,and a complex tumor microenvironment.To overcome these challenges,extensive endeavors have been made to explore the co-assembly of the widely used photosensitizer chlorin e6(Ce6)with various functional small molecules to enhance pharmacodynamic activity.This review provides a comprehensive overview of current studies on Ce6-based nanoparticles for effective PDT and precise delivery of functional molecules.The self-assembly mechanism will be discussed in detail,with a focus on potential strategies for combinational therapy with PDT.
基金supported by National Natural Science Foundation of China(12402413).
文摘The dynamic variation issues of variable-load unmanned aerial vehicle(UAV)used in agricultural plant protection activities was addressed by a disturbanceresistant control system based on PD(proportional-derivative)sliding mode control.First,a time-varying dynamic model was developed by analyzing the variations in mass,center of gravity and moment of inertia across time.Then a trajectory tracking control approach based on PD sliding mode control was designed to develop an inner-loop attitude controller and an outer-loop trajectory controller to accomplish precise and closely coupled trajectory tracking.Numerical simulations were conducted to verify the trajectory tracking performance,demonstrating accurate tracking of the desired trajectory with standard deviations of 0.0507,0.1613 and 0.0002 m in the horizontal,lateral and vertical directions,respectively.In terms of attitude control,the system exhibited favorable performance on the roll,pitch and yaw axes,with small transient errors and rapid convergence.Flight experiments further demonstrated that the UAV accurately followed the specified path,and errors in both straight and twisting segments satisfied control criteria.This control system ensured efficient and steady trajectory tracking,offering theoretical and application references for intelligent and precise agricultural plant protection activities.
