Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the applicati...Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer 'omics', including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.展开更多
A computer-aided ionic liquid design(CAILD) study is presented for the frequently encountered alkane/cycloalkane separations in petrochemical industry. Exhaustive experimental data are first collected to extend the UN...A computer-aided ionic liquid design(CAILD) study is presented for the frequently encountered alkane/cycloalkane separations in petrochemical industry. Exhaustive experimental data are first collected to extend the UNIFAC-IL model for this system, where the proximity effect in alkanes and cycloalkanes is considered specifically by defining distinct groups. The thermodynamic performances of a large number of ILs for 4 different alkane/cycloalkane systems are then compared to select a representative example of such separations. By applying n-heptane/methylcyclohexane extractive distillation as a case study, the CAILD task is cast as a mixed-integer nonlinear programming(MINLP) problem based on the obtained task-specific UNIFAC-IL model and two semi-empirical models for IL physical properties. The top 5 IL candidates determined by solving the MINLP problem are subsequently introduced into Aspen Plus for process simulation and economic analysis, which finally identify 1-hexadecyl-methylpiperidinium tricyanomethane([C_(16)MPip][C(CN)_3]) as the best entrainer for this separation.展开更多
Threatened animals respond with appropriate defensive behaviors to survive.It has been accepted that midbrain periaqueductal gray(PAG)plays an essential role in the circuitry system and organizes defensive behavioral ...Threatened animals respond with appropriate defensive behaviors to survive.It has been accepted that midbrain periaqueductal gray(PAG)plays an essential role in the circuitry system and organizes defensive behavioral responses.However,the role and correlation of different PAG subregions in the expression of different defensive behaviors remain largely unexplored.Here,we designed and manufactured a microelectrode array(MEA)to simultaneously detect the activities of dPAG and vPAG neurons in freely behaving rats.To improve the detection performance of the MEAs,PtNP/PEDOT:PSS nanocomposites were modified onto the MEAs.Subsequently,the predator odor was used to induce the rat’s innate fear,and the changes and information transmission in neuronal activities were detected in the dPAG and vPAG.Our results showed that the dPAG and vPAG participated in innate fear,but the activation degree was distinct in different defense behaviors.During flight,neuronal responses were stronger and earlier in the dPAG than the vPAG,while vPAG neurons responded more strongly during freezing.By applying high-performance MEA,it was revealed that neural information spread from the activated dPAG to the weakly activated vPAG.Our research also revealed that dPAG and vPAG neurons exhibited different defensive discharge characteristics,and dPAG neurons participated in the regulation of defense responses with burst-firing patterns.The slow activation and continuous firing of vPAG neurons cooresponded with the regulation of long-term freezing responses.The results demonstrated the important role of PAG neuronal activities in controlling different aspects of defensive behaviors and provided novel insights for investigating defense from the electrophysiological perspective.展开更多
Rapid building damage assessment following an earthquake is important for humanitarian relief and disaster emergency responses.In February 2023,two magnitude-7.8 earthquakes struck Turkey in quick succession,impacting...Rapid building damage assessment following an earthquake is important for humanitarian relief and disaster emergency responses.In February 2023,two magnitude-7.8 earthquakes struck Turkey in quick succession,impacting over 30 major cities across nearly 300 km.A quick and comprehensive understanding of the distribution of building damage is essential for e fficiently deploying rescue forces during critical rescue periods.This article presents the training of a two-stage convolutional neural network called BDANet that integrated image features captured before and after the disaster to evaluate the extent of building damage in Islahiye.Based on high-resolution remote sensing data from WorldView2,BDANet used predisaster imagery to extract building outlines;the image features before and after the disaster were then combined to conduct building damage assessment.We optimized these results to improve the accuracy of building edges and analyzed the damage to each building,and used population distribution information to estimate the population count and urgency of rescue at different disaster levels.The results indicate that the building area in the Islahiye region was 156.92 ha,with an affected area of 26.60 ha.Severely damaged buildings accounted for 15.67%of the total building area in the affected areas.WorldPop population distribution data indicated approximately 253,297,and 1,246 people in the collapsed,severely damaged,and lightly damaged areas,respectively.Accuracy verification showed that the BDANet model exhibited good performance in handling high-resolution images and can be used to directly assess building damage and provide rapid information for rescue operations in future disasters using model weights.展开更多
Developing accurate and sensitive DNA methyltransferase(MTase) analysis methods is essential for early clinical diagnosis and development of antimicrobial drug targets. In this work, by coupling WO_(3-x) dotsencapsula...Developing accurate and sensitive DNA methyltransferase(MTase) analysis methods is essential for early clinical diagnosis and development of antimicrobial drug targets. In this work, by coupling WO_(3-x) dotsencapsulated metal-organic frameworks(MOFs) as co-reactants and terminal deoxynucleotidyl transferase(Td T)-mediated template-free branched polymerization, a dual signal-amplified electrochemiluminescent(ECL) biosensor was constructed to detect DNA adenine methylation(Dam) MTase. The employment of WO_(3-x) dots-encapsulated MOFs(i.e., NH_(2)-UIO66@WO_(3-x) ) was not only beneficial for biomolecule conjugation because of the abundant amino groups but also led to a 7-fold enhanced ECL response due to the increased loading of WO_(3-x). Moreover, Td T-mediated template-free branched polymerization promoted the capture of ECL emitters on the electrode surface, achieving 20-fold enhanced signal amplification. The presented ECL biosensor demonstrated a low detection limit of 2.4 × 10^(-4)U/m L, and displayed high reliability for the detection of Dam MTase in both spiked human serum and E. coli cell samples, and for the screening of potential inhibitors. This study opens a new avenue for designing a dual signal amplificationbased ECL bioassay for Dam MTase and screening inhibitors in the fields of clinical diagnosis and drug development.展开更多
After being launched into orbit,the geometric calibration of a satellite laser altimeter will reduce errors in laser pointing and ranging caused by satellite vibrations during launch,environmental changes,and thermal ...After being launched into orbit,the geometric calibration of a satellite laser altimeter will reduce errors in laser pointing and ranging caused by satellite vibrations during launch,environmental changes,and thermal effects during long-term operation,which guarantees the accuracy of measurement data.In this study,a satellite laser geometric calibration method combining infrared detectors and corner-cube retroreflectors(CCRs)is proposed.First,a CCR-based laser ranging error calibration method was established,and then a laser pointing error calibration model was derived based on a single infrared detector array.Taking GaoFen-7(GF-7)satellite laser beam 2 as the experimental object,laser geometric calibration was realized using an infrared detector and CCR-measured data.Then,the accuracy of the proposed method was compared with that of other calibration methods,the CMLID and the CMSPR.The results show that the accuracy of the proposed calibration method is equivalent to that of the CMLID and higher than that of the CMSPR.Among them,the accuracy of the laser pointing after calibration using the proposed method is better than 0.8 arcsec,and the elevation accuracy of the laser on flat,sloping,and mountainous terrains is better than 0.11 m,0.30 m,and 1.80 m,respectively.展开更多
Photocatalysis technology has been proved to be a potential strategy for removal of organic dyes,however high-power light sources are generally necessary to initiate photocatalytic reaction.In this work,we employed an...Photocatalysis technology has been proved to be a potential strategy for removal of organic dyes,however high-power light sources are generally necessary to initiate photocatalytic reaction.In this work,we employed an excellent photocatalyst of Bi_(2)WO_(6) with visible light harvest and meanwhile an intrinsic ferroelectricity,which realized the efficient degradation of organic dye via the synergetic photopiezocatalysis.Through coupling the illumination by a low-power(9 W)LED and the ultrasonic vibration(120 W)by an ultrasonic cleaner,the nano flower-like Bi_(2)WO_(6) composed of ultrathin nanosheets showed a much more enhanced photopiezocatalysis performance for purification of organic dye than the individual photocatalysis and piezocatalysis.Furthermore,the high mineralization efficiency and the good durability of the Bi_(2)WO_(6) catalyst were demonstrated.The possible mechanism of photopiezocatalysis was finally proposed,where the ultrasound-induced piezoelectric field in Bi_(2)WO_(6) drove photo-generated electrons and holes to diffuse along opposite directions,consequently promoting the separation efficiency of charge carriers.This work indicates that the synergetic photopiezocatalysis by coupling irradiation and ultrasonic vibration is a promising strategy to purify organic pollutants in wastewater.展开更多
Evaluating the residual life of exposed components in power industry is a very important procedure inroutine examination. The microstructures of a series of X20CrMoV12.1 martensitic superheater tube samples in a boile...Evaluating the residual life of exposed components in power industry is a very important procedure inroutine examination. The microstructures of a series of X20CrMoV12.1 martensitic superheater tube samples in a boiler in different service periods were investigated extensively to extract a quantitative relationship. During long-term service from start to rupture, hardness decreased monotonically with life depletion, and the decrease of hardness in prior austenite grain boundary was steeper than that in the matrix. Microstructure observation showed obvious damage characteristics, including carbide coarsening and martensite decomposing, and the martensite structure decomposed completely in rupture state. The morphology, distribution and composition of the main precipitates M23 C6 varied distinctly. The aspect ratio of coarsened carbides along grain boundary increased several fold with respect to their original size. The composition of coarsened M23 C6 carbide shows the most regular trend of Cr enrichment and the statistical result of Cr enrichment in M23 C6 shows a linear correlation between the ratio of Cr to Fe and service time to the power of 3/2, which may be considered as an index of material degradation due to long-term service exposure.展开更多
Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial inform...Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial information or involves nonspatial information remains elusive.Here,we fabricated an MEC-shaped microelectrode array(MEA)to detect the variation in neural spikes and local field potentials of the MEC when rats forage in a square enclosure with a planar,three-dimensional object and social landmarks in sequence.The results showed that grid cells exhibited rate remapping under social conditions in which spike firing fields closer to the social landmark had a higher firing rate.Furthermore,global remapping showed that hexagonal firing patterns were rotated and scaled when the planar landmark was replaced with object and social landmarks.In addition,when grid cells were activated,the local field potentials were dominated by the theta band(5–8 Hz),and spike phase locking was observed at troughs of theta oscillations.Our results suggest the pattern separation mechanism of grid cells in which the spatial firing structure and firing rate respond to spatial and social information,respectively,which may provide new insights into how the brain creates a cognitive map.展开更多
文摘Prostate cancer is a leading cause of global cancer-related death but attempts to improve diagnoses and develop novel therapies have been confounded by significant patient heterogeneity. In recent years, the application of next-generation sequencing to hundreds of prostate tumours has defined novel molecular subtypes and characterized extensive genomic aberration underlying disease initiation and progression. It is now clear that the heterogeneity observed in the clinic is underpinned by a molecular landscape rife with complexity, where genomic rearrangements and rare mutations combine to amplify transcriptomic diversity. This review dissects our current understanding of prostate cancer 'omics', including the sentinel role of copy number variation, the growing spectrum of oncogenic fusion genes, the potential influence of chromothripsis, and breakthroughs in defining mutation-associated subtypes. Increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways, yet recurrent gene aberration appears rare. Therefore, it is critical that we continue to define individual tumour genomes, especially in the context of their expressed transcriptome. Only through improved characterisation of tumour to tumour variability can we advance to an age of precision therapy and personalized oncology.
基金financial support from National Natural Science Foundation of China(21776074,21576081,and21861132019)
文摘A computer-aided ionic liquid design(CAILD) study is presented for the frequently encountered alkane/cycloalkane separations in petrochemical industry. Exhaustive experimental data are first collected to extend the UNIFAC-IL model for this system, where the proximity effect in alkanes and cycloalkanes is considered specifically by defining distinct groups. The thermodynamic performances of a large number of ILs for 4 different alkane/cycloalkane systems are then compared to select a representative example of such separations. By applying n-heptane/methylcyclohexane extractive distillation as a case study, the CAILD task is cast as a mixed-integer nonlinear programming(MINLP) problem based on the obtained task-specific UNIFAC-IL model and two semi-empirical models for IL physical properties. The top 5 IL candidates determined by solving the MINLP problem are subsequently introduced into Aspen Plus for process simulation and economic analysis, which finally identify 1-hexadecyl-methylpiperidinium tricyanomethane([C_(16)MPip][C(CN)_3]) as the best entrainer for this separation.
基金This work was sponsored by the National Natural Science Foundation of China(T2293731,L2224042,61988102,62121003,61960206012,62171434,61971400,61975206,and 61973292)the Frontier Interdisciplinary Project of the Chinese Academy of Sciences(XK2022XXC003)+2 种基金STI 2030-Major Projects 2021ZD0201600the National Key R&D Program of China(2022YFC2402501)the Scientific Instrument Developing Project of the Chinese Academy of Sciences(GJJSTD20210004).
文摘Threatened animals respond with appropriate defensive behaviors to survive.It has been accepted that midbrain periaqueductal gray(PAG)plays an essential role in the circuitry system and organizes defensive behavioral responses.However,the role and correlation of different PAG subregions in the expression of different defensive behaviors remain largely unexplored.Here,we designed and manufactured a microelectrode array(MEA)to simultaneously detect the activities of dPAG and vPAG neurons in freely behaving rats.To improve the detection performance of the MEAs,PtNP/PEDOT:PSS nanocomposites were modified onto the MEAs.Subsequently,the predator odor was used to induce the rat’s innate fear,and the changes and information transmission in neuronal activities were detected in the dPAG and vPAG.Our results showed that the dPAG and vPAG participated in innate fear,but the activation degree was distinct in different defense behaviors.During flight,neuronal responses were stronger and earlier in the dPAG than the vPAG,while vPAG neurons responded more strongly during freezing.By applying high-performance MEA,it was revealed that neural information spread from the activated dPAG to the weakly activated vPAG.Our research also revealed that dPAG and vPAG neurons exhibited different defensive discharge characteristics,and dPAG neurons participated in the regulation of defense responses with burst-firing patterns.The slow activation and continuous firing of vPAG neurons cooresponded with the regulation of long-term freezing responses.The results demonstrated the important role of PAG neuronal activities in controlling different aspects of defensive behaviors and provided novel insights for investigating defense from the electrophysiological perspective.
基金supported by the Third Xinjiang Scientific Expedition Program(Grant 2022xjkk0600)。
文摘Rapid building damage assessment following an earthquake is important for humanitarian relief and disaster emergency responses.In February 2023,two magnitude-7.8 earthquakes struck Turkey in quick succession,impacting over 30 major cities across nearly 300 km.A quick and comprehensive understanding of the distribution of building damage is essential for e fficiently deploying rescue forces during critical rescue periods.This article presents the training of a two-stage convolutional neural network called BDANet that integrated image features captured before and after the disaster to evaluate the extent of building damage in Islahiye.Based on high-resolution remote sensing data from WorldView2,BDANet used predisaster imagery to extract building outlines;the image features before and after the disaster were then combined to conduct building damage assessment.We optimized these results to improve the accuracy of building edges and analyzed the damage to each building,and used population distribution information to estimate the population count and urgency of rescue at different disaster levels.The results indicate that the building area in the Islahiye region was 156.92 ha,with an affected area of 26.60 ha.Severely damaged buildings accounted for 15.67%of the total building area in the affected areas.WorldPop population distribution data indicated approximately 253,297,and 1,246 people in the collapsed,severely damaged,and lightly damaged areas,respectively.Accuracy verification showed that the BDANet model exhibited good performance in handling high-resolution images and can be used to directly assess building damage and provide rapid information for rescue operations in future disasters using model weights.
基金supported by the National Natural Science Foundation of China (Nos.22074015 and 22174014)。
文摘Developing accurate and sensitive DNA methyltransferase(MTase) analysis methods is essential for early clinical diagnosis and development of antimicrobial drug targets. In this work, by coupling WO_(3-x) dotsencapsulated metal-organic frameworks(MOFs) as co-reactants and terminal deoxynucleotidyl transferase(Td T)-mediated template-free branched polymerization, a dual signal-amplified electrochemiluminescent(ECL) biosensor was constructed to detect DNA adenine methylation(Dam) MTase. The employment of WO_(3-x) dots-encapsulated MOFs(i.e., NH_(2)-UIO66@WO_(3-x) ) was not only beneficial for biomolecule conjugation because of the abundant amino groups but also led to a 7-fold enhanced ECL response due to the increased loading of WO_(3-x). Moreover, Td T-mediated template-free branched polymerization promoted the capture of ECL emitters on the electrode surface, achieving 20-fold enhanced signal amplification. The presented ECL biosensor demonstrated a low detection limit of 2.4 × 10^(-4)U/m L, and displayed high reliability for the detection of Dam MTase in both spiked human serum and E. coli cell samples, and for the screening of potential inhibitors. This study opens a new avenue for designing a dual signal amplificationbased ECL bioassay for Dam MTase and screening inhibitors in the fields of clinical diagnosis and drug development.
基金supported by National Key Research and Development Program of China:[Grant Number 2020YFE0200800]National Natural Science Foundation of China:[Grant Number 41971426]+1 种基金Special Funds for Creative Research:[Grant Number 2022C61540]Innovative Youth Talents Program,Ministry of Natural Resources of the People’s Republic of China:[Grant Number 12110600000018003930].
文摘After being launched into orbit,the geometric calibration of a satellite laser altimeter will reduce errors in laser pointing and ranging caused by satellite vibrations during launch,environmental changes,and thermal effects during long-term operation,which guarantees the accuracy of measurement data.In this study,a satellite laser geometric calibration method combining infrared detectors and corner-cube retroreflectors(CCRs)is proposed.First,a CCR-based laser ranging error calibration method was established,and then a laser pointing error calibration model was derived based on a single infrared detector array.Taking GaoFen-7(GF-7)satellite laser beam 2 as the experimental object,laser geometric calibration was realized using an infrared detector and CCR-measured data.Then,the accuracy of the proposed method was compared with that of other calibration methods,the CMLID and the CMSPR.The results show that the accuracy of the proposed calibration method is equivalent to that of the CMLID and higher than that of the CMSPR.Among them,the accuracy of the laser pointing after calibration using the proposed method is better than 0.8 arcsec,and the elevation accuracy of the laser on flat,sloping,and mountainous terrains is better than 0.11 m,0.30 m,and 1.80 m,respectively.
基金financially supported from the National Key Research and Development Program of China(No.2017YFE0127400)the Zhejiang Provincial Natural Science Foundation of China(No.LY17B010004)。
文摘Photocatalysis technology has been proved to be a potential strategy for removal of organic dyes,however high-power light sources are generally necessary to initiate photocatalytic reaction.In this work,we employed an excellent photocatalyst of Bi_(2)WO_(6) with visible light harvest and meanwhile an intrinsic ferroelectricity,which realized the efficient degradation of organic dye via the synergetic photopiezocatalysis.Through coupling the illumination by a low-power(9 W)LED and the ultrasonic vibration(120 W)by an ultrasonic cleaner,the nano flower-like Bi_(2)WO_(6) composed of ultrathin nanosheets showed a much more enhanced photopiezocatalysis performance for purification of organic dye than the individual photocatalysis and piezocatalysis.Furthermore,the high mineralization efficiency and the good durability of the Bi_(2)WO_(6) catalyst were demonstrated.The possible mechanism of photopiezocatalysis was finally proposed,where the ultrasound-induced piezoelectric field in Bi_(2)WO_(6) drove photo-generated electrons and holes to diffuse along opposite directions,consequently promoting the separation efficiency of charge carriers.This work indicates that the synergetic photopiezocatalysis by coupling irradiation and ultrasonic vibration is a promising strategy to purify organic pollutants in wastewater.
基金Item Sponsored by National Natural Science Foundation of China(50871076)
文摘Evaluating the residual life of exposed components in power industry is a very important procedure inroutine examination. The microstructures of a series of X20CrMoV12.1 martensitic superheater tube samples in a boiler in different service periods were investigated extensively to extract a quantitative relationship. During long-term service from start to rupture, hardness decreased monotonically with life depletion, and the decrease of hardness in prior austenite grain boundary was steeper than that in the matrix. Microstructure observation showed obvious damage characteristics, including carbide coarsening and martensite decomposing, and the martensite structure decomposed completely in rupture state. The morphology, distribution and composition of the main precipitates M23 C6 varied distinctly. The aspect ratio of coarsened carbides along grain boundary increased several fold with respect to their original size. The composition of coarsened M23 C6 carbide shows the most regular trend of Cr enrichment and the statistical result of Cr enrichment in M23 C6 shows a linear correlation between the ratio of Cr to Fe and service time to the power of 3/2, which may be considered as an index of material degradation due to long-term service exposure.
基金sponsored by the National Key R&D Program(Grant No.2017YFA0205902)the National Natural Science Foundation of China(Grant No.62121003,61960206012,61973292,61975206,61971400,and 62171434)+1 种基金the Scientific Instrument Developing Project of the Chinese Academy of Sciences(Grant No.GJJSTD20210004)the Major Program of Scientific and Technical Innovation 2030(No.2021ZD0201603).
文摘Grid cells with stable hexagonal firing patterns in the medial entorhinal cortex(MEC)carry the vital function of serving as a metric for the surrounding environment.Whether this mechanism processes only spatial information or involves nonspatial information remains elusive.Here,we fabricated an MEC-shaped microelectrode array(MEA)to detect the variation in neural spikes and local field potentials of the MEC when rats forage in a square enclosure with a planar,three-dimensional object and social landmarks in sequence.The results showed that grid cells exhibited rate remapping under social conditions in which spike firing fields closer to the social landmark had a higher firing rate.Furthermore,global remapping showed that hexagonal firing patterns were rotated and scaled when the planar landmark was replaced with object and social landmarks.In addition,when grid cells were activated,the local field potentials were dominated by the theta band(5–8 Hz),and spike phase locking was observed at troughs of theta oscillations.Our results suggest the pattern separation mechanism of grid cells in which the spatial firing structure and firing rate respond to spatial and social information,respectively,which may provide new insights into how the brain creates a cognitive map.