Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to ...Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to their ability to suppress the inflammatory cascades.In this study,extensive screening of an in-house library of 1200 Chinese medicinal plant extracts identified Platycladus orientalis(L.)Franco(P.orientalis)as a potent PDE4 inhibitor,exhibiting 42.7%inhibition at 0.2μg/m L.Subsequent bioassayguided isolation revealed flavonoids,particularly amentoflavone(AMF),as the principal component responsible for PDE4 inhibition.To enrich the effective ingredients,a purification protocol using microporous resin was developed,yielding a flavonoid-rich extract(FLDs)that efficiently increased AMF content from 6.2%to 72.3%and improved PDE4 inhibitory activity to 74.2%at 0.2μg/mL.Notably,P.orientalis with favorable safety profiles demonstrated superior in vitro and in vivo anti-psoriasis effects to both AMF and the approved PDE4 inhibitor apremilast.These findings highlight the potential of P.orientalis as a novel therapeutic agent for psoriasis and provide valuable insights for its development in psoriasis treatment.展开更多
The orbital angular momentum(OAM)of light has been implemented as an information carrier in OAM holography.Holographic information can be multiplexed in theoretical unbounded OAM channels,promoting the applications of...The orbital angular momentum(OAM)of light has been implemented as an information carrier in OAM holography.Holographic information can be multiplexed in theoretical unbounded OAM channels,promoting the applications of optically addressable dynamic display and high-security optical encryption.However,the frame-rate of the dynamic extraction of the information reconstruction process in OAM holography is physically determined by the switching speed of the incident OAM states,which is currently below 30 Hz limited by refreshing rate of the phase-modulation spatial light modulator(SLM).Here,based on a cross convolution with the spatial frequency of the OAM-multiplexing hologram,the spatial frequencies of an elaborately-designed amplitude distribution,namely amplitude decoding key,has been adopted for the extraction of three-dimensional holographic information encoded in a specific OAM information channel.We experimentally demonstrated a dynamic extraction frame rate of 100 Hz from an OAM multiplexing hologram with 10 information channels indicated by individual OAM values from-50 to 50.The new concept of cross convolution theorem can even provide the potential of parallel reproduction and distribution of information encoded in many OAM channels at various positions which boosts the capacity of information processing far beyond the traditional decoding methods.Thus,our results provide a holographic paradigm for high-speed 3D information processing,paving an unprecedented way to achieve the high-capacity short-range optical communication system.展开更多
Monoamine oxidase A(MAO-A) is a prominent myocardial source of reactive oxygen species(ROS), and its expression and activity are strongly increased in failing hearts. Therefore, accurate evaluation of MAOA activity in...Monoamine oxidase A(MAO-A) is a prominent myocardial source of reactive oxygen species(ROS), and its expression and activity are strongly increased in failing hearts. Therefore, accurate evaluation of MAOA activity in cardiomyocytes is of great importance for understanding its biological functions and early diagnosing the progression of heart failure. However, so far, there is no report on the fluorescent diagnosis of heart failure by a specific probe for MAO-A. In this work, two far-red emissive fluorescent turn-on probes(KXS-M1 and KXS-M2) for the highly selective and sensitive detection of MAO-A were fabricated.Both probes exhibit good response to MAO-A, one of which, KXS-M2, performs better than the other one in terms of a fluorescence increment and sensitivity. Using the pioneering probe KXS-M2, specific fluorescence imaging of MAO-A in glucose-deprived H9c2 cardiac cells, zebrafish and isoprenaline-induced failing heart tissues was achieved, proving that KXS-M2 can serve as a powerful tool for the diagnosis and treatment of heart failure.展开更多
Efficiently tracking and imaging interested moving targets is crucial across various applications,from autonomous systems to surveillance.However,persistent challenges remain in various fields,including environmental ...Efficiently tracking and imaging interested moving targets is crucial across various applications,from autonomous systems to surveillance.However,persistent challenges remain in various fields,including environmental intricacies,limitations in perceptual technologies,and privacy considerations.We present a teacher-student learning model,the generative adversarial network(GAN)-guided diffractive neural network(DNN),which performs visual tracking and imaging of the interested moving target.The GAN,as a teacher model,empowers efficient acquisition of the skill to differentiate the specific target of interest in the domains of visual tracking and imaging.The DNN-based student model learns to master the skill to differentiate the interested target from the GAN.The process of obtaining a GAN-guided DNN starts with capturing moving objects effectively using an event camera with high temporal resolution and low latency.Then,the generative power of GAN is utilized to generate data with position-tracking capability for the interested moving target,subsequently serving as labels to the training of the DNN.The DNN learns to image the target during training while retaining the target’s positional information.Our experimental demonstration highlights the efficacy of the GAN-guided DNN in visual tracking and imaging of the interested moving target.We expect the GAN-guided DNN can significantly enhance autonomous systems and surveillance.展开更多
Document Frequency(DF)is reported to be a simple yet quite effective measure for feature selection in text classification,which is a key step in processing big textual data collections.The calculation is based on how ...Document Frequency(DF)is reported to be a simple yet quite effective measure for feature selection in text classification,which is a key step in processing big textual data collections.The calculation is based on how many documents in a collection contain a feature,which can be a word,a phrase,a n-gram,or a specially derived attribute.It is an unsupervised and class independent metric.Features of the same DF value may have quite different distribution over different categories,and thus have different discriminative power over categories.For example,in a binary classification problem,if feature A only appears in one category,but feature B,which has the same DF value as feature A,is evenly distributed in both categories.Then,feature A is obviously more effective than feature B for classification.To overcome this weakness of the original document frequency feature selection metric,we,therefore,propose a class based document frequency strategy to further refine the original DF to some extent.Extensive experiments on three text classification datasets demonstrate the effectiveness of the proposed measures.Using Class Based Document Frequency to Select展开更多
Mitochondrial metabolism-regulated epigenetic modification is a driving force of aging and a promising target for therapeutic intervention.Mitochondrial malate dehydrogenase(MDH2),an enzyme in the TCA cycle,was identi...Mitochondrial metabolism-regulated epigenetic modification is a driving force of aging and a promising target for therapeutic intervention.Mitochondrial malate dehydrogenase(MDH2),an enzyme in the TCA cycle,was identified as an anti-aging target through activity-based protein profiling in present study.The expression level of MDH2 was positively correlated with the cellular senescence in Mdh2 knockdown or overexpression fibroblasts.Glibenclamide(Gli),a classic anti-glycemic drug,was found to inhibit the activity of MDH2 and relieve fibroblast senescence in an MDH2-dependent manner.The anti-aging effects of Gli were also further validated in vivo,as it extended the lifespan and reduced the frailty index of naturally aged mice.Liver specific Mdh2 knockdown eliminated Gli’s beneficial effects in naturally aged mice,reducing p^(16INK4a) expression and hepatic fibrosis.Mechanistically,MDH2 inhibition or knockdown disrupted central carbon metabolism,then enhanced the methionine cycle flux,and subsequently promoted histone methylation.Notably,the tri-methylation of H3K27,identified as a crucial methylation site in reversing cellular senescence,was significantly elevated in hepatic tissues of naturally aged mice with Mdh2 knockdown.Taken together,these findings reveal that MDH2 inhibition or knockdown delays the aging process through metabolic-epigenetic regulation.Our research not only identified MDH2 as a potential therapeutic target and Gli as a lead compound for anti-aging drug development,but also shed light on the intricate interplay of metabolism and epigenetic modifications in aging.展开更多
Secret sharing is a promising technology for information encryption by splitting the secret information into different shares.However,the traditional scheme suffers from information leakage in decryption process since...Secret sharing is a promising technology for information encryption by splitting the secret information into different shares.However,the traditional scheme suffers from information leakage in decryption process since the amount of available information channels is limited.Herein,we propose and demonstrate an optical secret sharing framework based on the multi-dimensional multiplexing liquid crystal(LC)holograms.The LC holograms are used as spatially separated shares to carry secret images.The polarization of the incident light and the distance between different shares are served as secret keys,which can significantly improve the information security and capacity.Besides,the decryption condition is also restricted by the applied external voltage due to the variant diffraction efficiency,which further increases the information security.In implementation,an artificial neural network(ANN)model is developed to carefully design the phase distribution of each LC hologram.With the advantage of high security,high capacity and simple configuration,our optical secret sharing framework has great potentials in optical encryption and dynamic holographic display.展开更多
Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity,expanding antibacterial spectra,and reducing required dosages.Previously,compound 15 was identified as a potential adjuvant for Poly...Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity,expanding antibacterial spectra,and reducing required dosages.Previously,compound 15 was identified as a potential adjuvant for Polymyxin B(PB)against multidrug-resistant(MDR)Pseudomonas aeruginosa DK2;however,its clinical utility was hindered by high cytotoxicity,uncertain in vivo efficacy,and an unclear synergetic mechanism.To address these challenges,we synthesized and evaluated a series of novel benzamide derivatives,with A22 emerging as a particularly promising candidate.A22 demonstrated potent synergistic activity to PB,minimal cytotoxicity,improved water solubility,and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains.In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22.Moreover,A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2.Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production,reducing ATP levels,increasing NOX activity,and inhibiting biofilm formation,leading to bacterial death.These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants,offering a robust approach to combating MDR Gram-negative bacterial infections.展开更多
Atmospheric turbulence(AT)severely degrades free-space communications,imaging,and sensing systems,driving critical demand for diagnostics of turbulence strength(C_(n)^(2)).However,existing approaches face limited adap...Atmospheric turbulence(AT)severely degrades free-space communications,imaging,and sensing systems,driving critical demand for diagnostics of turbulence strength(C_(n)^(2)).However,existing approaches face limited adaptability,high latency,and excessive power consumption for deployment.Here,we propose an orbital angular momentum(OAM)-mediated optoelectronic neural network(OOENN)that integrates a diffractive optical module for OAM spectrum feature extraction with a shallow electronic module for turbulence diagnostics,leveraging OAM spectrum data transformation.The optical module extracts turbulence-encoded features from distorted Laguerre–Gaussian(LG)beams and decomposes its output field into OAM spectrum data.These data are then fed into an electronic module that diagnoses turbulence strength using a minimal fully connected network with 9 input neurons and nonlinear activation.The OOENN performs feature extraction at light speed while enabling ultra-efficient electronic processing,thereby alleviating the latency and power constraints.Experimental results demonstrate diagnostics of five turbulence strengths within C_(n)^(2)=10-16 to 10-12 m^(-2∕3),achieving 82.4%accuracy at 80 ms latency per diagnosis.This fusion of structured light fields with optoelectronic intelligence establishes a technological foundation for next-generation adaptive systems in turbulence-resilient optical communications,remote sensing,and quantum information transfer.展开更多
Machine learning with optical neural networks has featured unique advantages of the information processing including high speed,ultrawide bandwidths and low energy consumption because the optical dimensions(time,space...Machine learning with optical neural networks has featured unique advantages of the information processing including high speed,ultrawide bandwidths and low energy consumption because the optical dimensions(time,space,wavelength,and polarization)could be utilized to increase the degree of freedom.However,due to the lack of the capability to extract the information features in the orbital angular momentum(OAM)domain,the theoretically unlimited OAM states have never been exploited to represent the signal of the input/output nodes in the neural network model.Here,we demonstrate OAM-mediated machine learning with an all-optical convolutional neural network(CNN)based on Laguerre-Gaussian(LG)beam modes with diverse diffraction losses.The proposed CNN architecture is composed of a trainable OAM mode-dispersion impulse as a convolutional kernel for feature extraction,and deep-learning diffractive layers as a classifier.The resultant OAM mode-dispersion selectivity can be applied in information mode-feature encoding,leading to an accuracy as high as 97.2%for MNIST database through detecting the energy weighting coefficients of the encoded OAM modes,as well as a resistance to eavesdropping in point-to-point free-space transmission.Moreover,through extending the target encoded modes into multiplexed OAM states,we realize all-optical dimension reduction for anomaly detection with an accuracy of 85%.Our work provides a deep insight to the mechanism of machine learning with spatial modes basis,which can be further utilized to improve the performances of various machine-vision tasks by constructing the unsupervised learning-based auto-encoder.展开更多
Drug repurposing is an efficient strategy for new drug discovery.Our latest study found that nitazoxanide(NTZ),an approved anti-parasite drug,was an autophagy activator and could alleviate the symptom of Alzheimer’s ...Drug repurposing is an efficient strategy for new drug discovery.Our latest study found that nitazoxanide(NTZ),an approved anti-parasite drug,was an autophagy activator and could alleviate the symptom of Alzheimer’s disease(AD).In order to further improve the efficacy and discover new chemical entities,a series of NTZ-based derivatives were designed,synthesized,and evaluated as autophagy activator against AD.All compounds were screened by the inhibition of phosphorylation of p70S6K,which was the direct substrate of mammalian target of rapamycin(mTOR)and its phosphorylation level could reflect the mTOR-dependent autophagy level.Among these analogs,compound 22 exhibited excellent potency in promotingβ-amyloid(Aβ)clearance,inhibiting tau phosphorylation,as well as stimulating autophagy both in vitro and in vivo.What’s more,22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice.These results demonstrated that 22 was a potential candidate for the treatment of AD.展开更多
基金supported by the National Key R&D Program of China(No.2023YFF1205102)National Natural Science Foundation of China(Nos.22277019,22307031,22377023 and 22077143)+2 种基金the Fundamental Research Funds for Hainan University(Nos.RZ2200001094,KYQD(ZR)-21031,and KYQD(ZR)-21108)Collaborative Innovation Center Funds for Hainan University(No.XTCX2022JKA01)the Science Foundation of Hainan Province(Nos.KJRC2023B10 and 824YXQN420)。
文摘Psoriasis is a common and chronic immune-mediated disorder that severely impacts the life quality of patients.Phosphodiesterase-4(PDE4)inhibitors have attracted significant interests in the psoriasis treatment due to their ability to suppress the inflammatory cascades.In this study,extensive screening of an in-house library of 1200 Chinese medicinal plant extracts identified Platycladus orientalis(L.)Franco(P.orientalis)as a potent PDE4 inhibitor,exhibiting 42.7%inhibition at 0.2μg/m L.Subsequent bioassayguided isolation revealed flavonoids,particularly amentoflavone(AMF),as the principal component responsible for PDE4 inhibition.To enrich the effective ingredients,a purification protocol using microporous resin was developed,yielding a flavonoid-rich extract(FLDs)that efficiently increased AMF content from 6.2%to 72.3%and improved PDE4 inhibitory activity to 74.2%at 0.2μg/mL.Notably,P.orientalis with favorable safety profiles demonstrated superior in vitro and in vivo anti-psoriasis effects to both AMF and the approved PDE4 inhibitor apremilast.These findings highlight the potential of P.orientalis as a novel therapeutic agent for psoriasis and provide valuable insights for its development in psoriasis treatment.
文摘The orbital angular momentum(OAM)of light has been implemented as an information carrier in OAM holography.Holographic information can be multiplexed in theoretical unbounded OAM channels,promoting the applications of optically addressable dynamic display and high-security optical encryption.However,the frame-rate of the dynamic extraction of the information reconstruction process in OAM holography is physically determined by the switching speed of the incident OAM states,which is currently below 30 Hz limited by refreshing rate of the phase-modulation spatial light modulator(SLM).Here,based on a cross convolution with the spatial frequency of the OAM-multiplexing hologram,the spatial frequencies of an elaborately-designed amplitude distribution,namely amplitude decoding key,has been adopted for the extraction of three-dimensional holographic information encoded in a specific OAM information channel.We experimentally demonstrated a dynamic extraction frame rate of 100 Hz from an OAM multiplexing hologram with 10 information channels indicated by individual OAM values from-50 to 50.The new concept of cross convolution theorem can even provide the potential of parallel reproduction and distribution of information encoded in many OAM channels at various positions which boosts the capacity of information processing far beyond the traditional decoding methods.Thus,our results provide a holographic paradigm for high-speed 3D information processing,paving an unprecedented way to achieve the high-capacity short-range optical communication system.
基金supported by the National Natural Science Foundation of China (Nos. 22037002, 22007032 and 21977082)the National Mega-project for Innovative Drugs of China (No.2019ZX09721001-004-003)+1 种基金the Chinese Postdoctoral Science Foundation,China (No. 2019M660083)the Shanghai Sailing Program,China (No. 20YF1411200)。
文摘Monoamine oxidase A(MAO-A) is a prominent myocardial source of reactive oxygen species(ROS), and its expression and activity are strongly increased in failing hearts. Therefore, accurate evaluation of MAOA activity in cardiomyocytes is of great importance for understanding its biological functions and early diagnosing the progression of heart failure. However, so far, there is no report on the fluorescent diagnosis of heart failure by a specific probe for MAO-A. In this work, two far-red emissive fluorescent turn-on probes(KXS-M1 and KXS-M2) for the highly selective and sensitive detection of MAO-A were fabricated.Both probes exhibit good response to MAO-A, one of which, KXS-M2, performs better than the other one in terms of a fluorescence increment and sensitivity. Using the pioneering probe KXS-M2, specific fluorescence imaging of MAO-A in glucose-deprived H9c2 cardiac cells, zebrafish and isoprenaline-induced failing heart tissues was achieved, proving that KXS-M2 can serve as a powerful tool for the diagnosis and treatment of heart failure.
基金supported by the National Natural Science Foundation of China(Grant Nos.62422509 and 62405188)the Shanghai Natural Science Foundation(Grant No.23ZR1443700)+3 种基金the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(Grant No.23SG41)the Young Elite Scientist Sponsorship Program by CAST(Grant No.20220042)the Science and Technology Commission of Shanghai Municipality(Grant No.21DZ1100500)the Shanghai Municipal Science and Technology Major Project,and the Shanghai Frontiers Science Center Program(2021-2025 No.20).
文摘Efficiently tracking and imaging interested moving targets is crucial across various applications,from autonomous systems to surveillance.However,persistent challenges remain in various fields,including environmental intricacies,limitations in perceptual technologies,and privacy considerations.We present a teacher-student learning model,the generative adversarial network(GAN)-guided diffractive neural network(DNN),which performs visual tracking and imaging of the interested moving target.The GAN,as a teacher model,empowers efficient acquisition of the skill to differentiate the specific target of interest in the domains of visual tracking and imaging.The DNN-based student model learns to master the skill to differentiate the interested target from the GAN.The process of obtaining a GAN-guided DNN starts with capturing moving objects effectively using an event camera with high temporal resolution and low latency.Then,the generative power of GAN is utilized to generate data with position-tracking capability for the interested moving target,subsequently serving as labels to the training of the DNN.The DNN learns to image the target during training while retaining the target’s positional information.Our experimental demonstration highlights the efficacy of the GAN-guided DNN in visual tracking and imaging of the interested moving target.We expect the GAN-guided DNN can significantly enhance autonomous systems and surveillance.
文摘Document Frequency(DF)is reported to be a simple yet quite effective measure for feature selection in text classification,which is a key step in processing big textual data collections.The calculation is based on how many documents in a collection contain a feature,which can be a word,a phrase,a n-gram,or a specially derived attribute.It is an unsupervised and class independent metric.Features of the same DF value may have quite different distribution over different categories,and thus have different discriminative power over categories.For example,in a binary classification problem,if feature A only appears in one category,but feature B,which has the same DF value as feature A,is evenly distributed in both categories.Then,feature A is obviously more effective than feature B for classification.To overcome this weakness of the original document frequency feature selection metric,we,therefore,propose a class based document frequency strategy to further refine the original DF to some extent.Extensive experiments on three text classification datasets demonstrate the effectiveness of the proposed measures.Using Class Based Document Frequency to Select
基金the National Natural Science Foundation of China(grants 32121005 to J.L.,22277028 to Z.L.H.,22437002 to J.L,22467010 to B.L.L.,and 22207026 to W.W.L.)the Innovation Program of Shanghai Municipal Education Commission(grant 2021-01-07-00-02-E00104 to J.L.)+3 种基金the Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism(grant 2021 Sci&Tech 03-28 to J.L.)the Innovative Research Team of High-level Local Universities in Shanghai(grant SHSMU-ZDCX20212702 to J.L.)the Chinese Special Fund for State Key Laboratory of Bioreactor Engineering(2060204 to J.L.)the innovative research project of graduate students in Hainan Province(SA2400003375 to L.S.)。
文摘Mitochondrial metabolism-regulated epigenetic modification is a driving force of aging and a promising target for therapeutic intervention.Mitochondrial malate dehydrogenase(MDH2),an enzyme in the TCA cycle,was identified as an anti-aging target through activity-based protein profiling in present study.The expression level of MDH2 was positively correlated with the cellular senescence in Mdh2 knockdown or overexpression fibroblasts.Glibenclamide(Gli),a classic anti-glycemic drug,was found to inhibit the activity of MDH2 and relieve fibroblast senescence in an MDH2-dependent manner.The anti-aging effects of Gli were also further validated in vivo,as it extended the lifespan and reduced the frailty index of naturally aged mice.Liver specific Mdh2 knockdown eliminated Gli’s beneficial effects in naturally aged mice,reducing p^(16INK4a) expression and hepatic fibrosis.Mechanistically,MDH2 inhibition or knockdown disrupted central carbon metabolism,then enhanced the methionine cycle flux,and subsequently promoted histone methylation.Notably,the tri-methylation of H3K27,identified as a crucial methylation site in reversing cellular senescence,was significantly elevated in hepatic tissues of naturally aged mice with Mdh2 knockdown.Taken together,these findings reveal that MDH2 inhibition or knockdown delays the aging process through metabolic-epigenetic regulation.Our research not only identified MDH2 as a potential therapeutic target and Gli as a lead compound for anti-aging drug development,but also shed light on the intricate interplay of metabolism and epigenetic modifications in aging.
基金support from the National Natural Science Foundation of China (No.62005164,62222507,62175101,and 62005166)the Shanghai Natural Science Foundation (23ZR1443700)+3 种基金Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission (23SG41)the Young Elite Scientist Sponsorship Program by CAST (No.20220042)Science and Technology Commission of Shanghai Municipality (Grant No.21DZ1100500)the Shanghai Municipal Science and Technology Major Project,and the Shanghai Frontiers Science Center Program (2021-2025 No.20).
文摘Secret sharing is a promising technology for information encryption by splitting the secret information into different shares.However,the traditional scheme suffers from information leakage in decryption process since the amount of available information channels is limited.Herein,we propose and demonstrate an optical secret sharing framework based on the multi-dimensional multiplexing liquid crystal(LC)holograms.The LC holograms are used as spatially separated shares to carry secret images.The polarization of the incident light and the distance between different shares are served as secret keys,which can significantly improve the information security and capacity.Besides,the decryption condition is also restricted by the applied external voltage due to the variant diffraction efficiency,which further increases the information security.In implementation,an artificial neural network(ANN)model is developed to carefully design the phase distribution of each LC hologram.With the advantage of high security,high capacity and simple configuration,our optical secret sharing framework has great potentials in optical encryption and dynamic holographic display.
基金supported by the National Natural Science Foundation of China(No.22107023 and 32300033)the Natural Science Foundation of Hainan(No.222QN220,China)the Scientific Research Foundation of Hainan University(No.KYQD(ZR)-22010 and KYQD(ZR)-23006,China).
文摘Antibiotic adjuvants offer a promising strategy for restoring antibiotic sensitivity,expanding antibacterial spectra,and reducing required dosages.Previously,compound 15 was identified as a potential adjuvant for Polymyxin B(PB)against multidrug-resistant(MDR)Pseudomonas aeruginosa DK2;however,its clinical utility was hindered by high cytotoxicity,uncertain in vivo efficacy,and an unclear synergetic mechanism.To address these challenges,we synthesized and evaluated a series of novel benzamide derivatives,with A22 emerging as a particularly promising candidate.A22 demonstrated potent synergistic activity to PB,minimal cytotoxicity,improved water solubility,and broad-spectrum synergism of polymyxins against various clinically isolated MDR Gram-negative strains.In vivo studies using Caenorhabditis elegans and mouse models further confirmed the efficacy of A22.Moreover,A22 effectively suppressed the development of PB resistance in Pseudomonas aeruginosa DK2.Mechanistic investigations revealed that A22 enhances polymyxins activity by inducing reactive oxygen species production,reducing ATP levels,increasing NOX activity,and inhibiting biofilm formation,leading to bacterial death.These findings position A22 as a highly promising candidate for the development of polymyxin adjuvants,offering a robust approach to combating MDR Gram-negative bacterial infections.
基金National Natural Science Foundation of China(62422509,62575180)Natural Science Foundation of Shanghai Municipality(23ZR1443700,25ZR1402386)+3 种基金Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(23SG41)Young Elite Scientist Sponsorship Program by Cast(20220042)Shanghai Municipal Science and Technology Major ProjectShanghai Frontiers Science Center Program(2021±2025 No.20)。
文摘Atmospheric turbulence(AT)severely degrades free-space communications,imaging,and sensing systems,driving critical demand for diagnostics of turbulence strength(C_(n)^(2)).However,existing approaches face limited adaptability,high latency,and excessive power consumption for deployment.Here,we propose an orbital angular momentum(OAM)-mediated optoelectronic neural network(OOENN)that integrates a diffractive optical module for OAM spectrum feature extraction with a shallow electronic module for turbulence diagnostics,leveraging OAM spectrum data transformation.The optical module extracts turbulence-encoded features from distorted Laguerre–Gaussian(LG)beams and decomposes its output field into OAM spectrum data.These data are then fed into an electronic module that diagnoses turbulence strength using a minimal fully connected network with 9 input neurons and nonlinear activation.The OOENN performs feature extraction at light speed while enabling ultra-efficient electronic processing,thereby alleviating the latency and power constraints.Experimental results demonstrate diagnostics of five turbulence strengths within C_(n)^(2)=10-16 to 10-12 m^(-2∕3),achieving 82.4%accuracy at 80 ms latency per diagnosis.This fusion of structured light fields with optoelectronic intelligence establishes a technological foundation for next-generation adaptive systems in turbulence-resilient optical communications,remote sensing,and quantum information transfer.
基金the support from the National Natural Science Foundation of China(62005164,62005166)the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(23SG41)+5 种基金the Young Elite Scientist Sponsorship Program by Cast(No.20220042)the Shanghai Natural Science Foundation(23ZR1443700)the Shanghai Rising-Star Program(20QA1404100)the Science and Technology Commission of Shanghai Municipality(Grant No.21DZ1100500)the Shanghai Municipal Science and Technology Major Project,the Shanghai Frontiers Science Center Program(2021-2025 No.20)the National Key Research and Development program of China(Grant Nos.2022YFB2874271).
文摘Machine learning with optical neural networks has featured unique advantages of the information processing including high speed,ultrawide bandwidths and low energy consumption because the optical dimensions(time,space,wavelength,and polarization)could be utilized to increase the degree of freedom.However,due to the lack of the capability to extract the information features in the orbital angular momentum(OAM)domain,the theoretically unlimited OAM states have never been exploited to represent the signal of the input/output nodes in the neural network model.Here,we demonstrate OAM-mediated machine learning with an all-optical convolutional neural network(CNN)based on Laguerre-Gaussian(LG)beam modes with diverse diffraction losses.The proposed CNN architecture is composed of a trainable OAM mode-dispersion impulse as a convolutional kernel for feature extraction,and deep-learning diffractive layers as a classifier.The resultant OAM mode-dispersion selectivity can be applied in information mode-feature encoding,leading to an accuracy as high as 97.2%for MNIST database through detecting the energy weighting coefficients of the encoded OAM modes,as well as a resistance to eavesdropping in point-to-point free-space transmission.Moreover,through extending the target encoded modes into multiplexed OAM states,we realize all-optical dimension reduction for anomaly detection with an accuracy of 85%.Our work provides a deep insight to the mechanism of machine learning with spatial modes basis,which can be further utilized to improve the performances of various machine-vision tasks by constructing the unsupervised learning-based auto-encoder.
基金provided by the National Sciences and Technology Major Project of China,(2018ZX09711002-003-010)the National Natural Science Foundation of China,(81872747,21672064)+5 种基金the 111 Project(B07023,China)the Chinese Postdoctoral Science Foundation(2018M641946)the Shanghai Sailing Program(19YF1412600,China)the Shanghai Morning Light Program(18CG33,China)the National Special Fund for State Key Laboratory of Bioreactor Engineering(2060204,China)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX18_1600,China).
文摘Drug repurposing is an efficient strategy for new drug discovery.Our latest study found that nitazoxanide(NTZ),an approved anti-parasite drug,was an autophagy activator and could alleviate the symptom of Alzheimer’s disease(AD).In order to further improve the efficacy and discover new chemical entities,a series of NTZ-based derivatives were designed,synthesized,and evaluated as autophagy activator against AD.All compounds were screened by the inhibition of phosphorylation of p70S6K,which was the direct substrate of mammalian target of rapamycin(mTOR)and its phosphorylation level could reflect the mTOR-dependent autophagy level.Among these analogs,compound 22 exhibited excellent potency in promotingβ-amyloid(Aβ)clearance,inhibiting tau phosphorylation,as well as stimulating autophagy both in vitro and in vivo.What’s more,22 could effectively improve the memory and cognitive impairments in APP/PS1 transgenic AD model mice.These results demonstrated that 22 was a potential candidate for the treatment of AD.
