By analyzing GPS, leveling and gravity observation data from the Minle, Huazangsi and Shagouhe profiles across the Qilian Mountain-Haiyuan fault during 2005 - 2009, the changes of these data and activity characteristi...By analyzing GPS, leveling and gravity observation data from the Minle, Huazangsi and Shagouhe profiles across the Qilian Mountain-Haiyuan fault during 2005 - 2009, the changes of these data and activity characteristics of the main faults in different time are obtained. The results show that the Changma-Erbo, Maomaoshan, Zhunglanghe and Haiyuan faults have been active in recent years. The relationship between the vertical displacement and mobile gravity data is analyzed, and the results reveal the gravity changes are mainly due to mass transfer. The results of GPS observation show that the direction of the horizontal movement velocity was almost along the fault strike in 2006 - 2007, while the horizontal velocity deviated from the fault direction in 2007 - 2008, characterized by increased eastward displacement. Further analysis upon removal of the linear trend on the time series of the N and E coordinate values of the continuous observation stations of the Crustal Movement Observation Network of China near the three profiles reveals that the Wenchuan earthquake had an effect on the observations in 2007 - 2008. Comparing the gravitational changes in 2008 - 2009 with the Bouguer gravity anomaly background, we find that the area near Minle profile is in the stage of adjustment and recovery, while the anomaly is not completely recovered around Huazangsi and Shagouhe profiles.展开更多
Glycosylation is one of the most complex and important post-translational modifications in proteins,playing essential roles in cellular signaling,protein folding,and immune responses[1].Despite its biological sig-nifi...Glycosylation is one of the most complex and important post-translational modifications in proteins,playing essential roles in cellular signaling,protein folding,and immune responses[1].Despite its biological sig-nificance,low abundance and high heterogeneity of glycoproteins pose significant analytical challenges.In a recent study published in National Science Review,a team of scientists led by Prof.Haojie Lu from Fudan University developed a groundbreaking strategy to address these challenges,offering a robust and scalable method for the comprehensive profiling of protein glycosylation[2].展开更多
Osimertinib,the first approved third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI),exhibits notable efficacy in EGFR-mutant non-small cell lung cancer(NSCLC).This is a prospective,mu...Osimertinib,the first approved third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI),exhibits notable efficacy in EGFR-mutant non-small cell lung cancer(NSCLC).This is a prospective,multicenter,comprehensive genomic profile signature(GPS)study in paired tissue and plasma samples from 149 patients with advanced NSCLC harboring EGFR exon 19 deletion(Ex19del)or L858R mutation at the first-line treatment failure of osimertinib(NCT05219162).Next-generation sequencing(NGS)was used for comprehensive GPS analysis of paired tissue and plasma samples.Fluorescence in situ hybridization(FISH)and next-generation sequencing(NGS)were used for tissue samples,while droplet digital polymerase chain reaction(ddPCR)and NGS were used for plasma samples to perform a concordance analysis of MET amplification.At the first-line treatment failure of osimertinib(study entry),EGFR alterations in tissue samples included EGFR Ex19del(49.0%,73/149),EGFR L858R mutation(43.0%,64/149),EGFR amplification(32.9%,49/149),EGFR L718Q/V mutation(4.7%,7/149),and EGFR C797S mutation(3.4%,5/149);bypass signaling activation and downstream pathway activation alterations included TP53 mutation(69.8%,104/149)and MET amplification(30.9%,46/149).Among the 136 patients with EGFR Ex19del/L858R mutation in tissue samples,72.1%(98/136),35.3%(48/136),and 32.4%(44/136)had TP53 mutations,EGFR amplification,and MET amplification,respectively.Taking tissue samples as references,the GPS in plasma samples showed high specificity(90.7–100%)for almost all genomic alterations.Compared with FISH(gene copy number[GCN]≥10),the overall percent agreement of tissue NGS,optimized tissue NGS(GCN≥8.63),plasma NGS,and plasma ddPCR for MET amplification were 75.0%(27/36),100%(36/36),88.9%(32/36),and 94.4%(34/36),respectively.This study represents the largest-scale,prospective study with paired tissue and plasma samples to enable comprehensive analysis of GPS,providing a novel perspective into coalterations at the first-line treatment failure of osimertinib.A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable.Moreover,the integration of FISH,NGS,and ddPCR provided a comprehensive assessment of MET amplification.展开更多
Noncooperative computer systems and network confrontation present a core challenge in cyberspace security.Traditional cybersecurity technologies predominantly rely on passive response mechanisms,which exhibit signific...Noncooperative computer systems and network confrontation present a core challenge in cyberspace security.Traditional cybersecurity technologies predominantly rely on passive response mechanisms,which exhibit significant limitations when addressing real-world complex and unknown threats.This paper introduces the concept of“active cybersecurity,”aiming to enhance network security not only through technical measures but also by leveraging strategy-level defenses.The core assumption of this concept is that attackers and defenders,in the context of network confrontations,act as rational decision-makers seeking to maximize their respective objectives.Building on this observation,this paper integrates game theory to analyze the interdependent relationships between attackers and defenders,thereby optimizing their strategies.Guided by this foundational idea,we propose an active cybersecurity model involving intelligent threat sensing,in-depth behavior analysis,comprehensive path profiling,and dynamic countermeasures,termed SAPC,designed to foster an integrated defense capability encompassing threat perception,analysis,tracing,and response.At its core,SAPC incorporates theoretical analyses of adversarial behavior and the optimization of corresponding strategies informed by game theory.By profiling adversaries and modeling confrontation as a“game,”the model establishes a comprehensive framework that provides both theoretical insights into and practical guidance for cybersecurity.The proposed active cybersecurity model marks a transformative shift from passive defense to proactive perception and confrontation.It facilitates the evolution of cybersecurity technologies toward a new paradigm characterized by active prediction,prevention,and strategic guidance.展开更多
Vehicle evaporation is an essential source of VOCs in cities but is not well understood in China.Reported emission factors from previous studies are not enough for understanding the atmospheric chemical process of veh...Vehicle evaporation is an essential source of VOCs in cities but is not well understood in China.Reported emission factors from previous studies are not enough for understanding the atmospheric chemical process of vehicular evaporative VOCs.In this work,a serious of detailed VOCs speciation profiles are developed based on test processes and emission processes.A mass balance method was used to divide different emission processes during diurnal tests.The results show that headspace vapor of gasoline cannot represent the real-world vehicle evaporation because of the significant differences in VOCs speciation profiles,especially for aromatics.To further distinguish emissions from evaporation and exhaust,only the ratios of MTBE/benzene and MTBE/toluene can serve as indicators when considering species from all evaporative processes.Besides,emissions from different sources change significantly with the seasons.To solve these problems,we developed a monthly comprehensive evaporation speciation profile.The individual profiles at the emission processes are weighted by the emission of the in-use vehicle fleet in Beijing to derive the comprehensive speciation profile of evaporative VOCs.Ozone formation potential(OFP)and secondary organic aerosol potential(SOAP)were used to evaluate the environmental impact.For SOAP,100 g evaporative emissions are equal to 6.05-12.71 g toluene in different months,much higher than that given using headspace vapors,especially in winter(7.2 times higher in December).These findings would improve our understanding of the evaporative VOCs emissions in China and their environmental impacts(e.g.,O3 and SOA formation).展开更多
Gastric cancer(GC)is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide,with China bearing nearly half of the global burden[1,2].Most patients are diagnosed at stage Ⅲ–Ⅳ...Gastric cancer(GC)is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide,with China bearing nearly half of the global burden[1,2].Most patients are diagnosed at stage Ⅲ–Ⅳ,and despite perioperative therapy plus D2 gastrectomy being the standard of care,long-term survival remains poor[3,4].展开更多
基金sponsored by Special Scientific Research Project,China Earthquake Administration(200908029)National Natural Science Foundation of China(40674057)
文摘By analyzing GPS, leveling and gravity observation data from the Minle, Huazangsi and Shagouhe profiles across the Qilian Mountain-Haiyuan fault during 2005 - 2009, the changes of these data and activity characteristics of the main faults in different time are obtained. The results show that the Changma-Erbo, Maomaoshan, Zhunglanghe and Haiyuan faults have been active in recent years. The relationship between the vertical displacement and mobile gravity data is analyzed, and the results reveal the gravity changes are mainly due to mass transfer. The results of GPS observation show that the direction of the horizontal movement velocity was almost along the fault strike in 2006 - 2007, while the horizontal velocity deviated from the fault direction in 2007 - 2008, characterized by increased eastward displacement. Further analysis upon removal of the linear trend on the time series of the N and E coordinate values of the continuous observation stations of the Crustal Movement Observation Network of China near the three profiles reveals that the Wenchuan earthquake had an effect on the observations in 2007 - 2008. Comparing the gravitational changes in 2008 - 2009 with the Bouguer gravity anomaly background, we find that the area near Minle profile is in the stage of adjustment and recovery, while the anomaly is not completely recovered around Huazangsi and Shagouhe profiles.
文摘Glycosylation is one of the most complex and important post-translational modifications in proteins,playing essential roles in cellular signaling,protein folding,and immune responses[1].Despite its biological sig-nificance,low abundance and high heterogeneity of glycoproteins pose significant analytical challenges.In a recent study published in National Science Review,a team of scientists led by Prof.Haojie Lu from Fudan University developed a groundbreaking strategy to address these challenges,offering a robust and scalable method for the comprehensive profiling of protein glycosylation[2].
文摘Osimertinib,the first approved third-generation epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitor(TKI),exhibits notable efficacy in EGFR-mutant non-small cell lung cancer(NSCLC).This is a prospective,multicenter,comprehensive genomic profile signature(GPS)study in paired tissue and plasma samples from 149 patients with advanced NSCLC harboring EGFR exon 19 deletion(Ex19del)or L858R mutation at the first-line treatment failure of osimertinib(NCT05219162).Next-generation sequencing(NGS)was used for comprehensive GPS analysis of paired tissue and plasma samples.Fluorescence in situ hybridization(FISH)and next-generation sequencing(NGS)were used for tissue samples,while droplet digital polymerase chain reaction(ddPCR)and NGS were used for plasma samples to perform a concordance analysis of MET amplification.At the first-line treatment failure of osimertinib(study entry),EGFR alterations in tissue samples included EGFR Ex19del(49.0%,73/149),EGFR L858R mutation(43.0%,64/149),EGFR amplification(32.9%,49/149),EGFR L718Q/V mutation(4.7%,7/149),and EGFR C797S mutation(3.4%,5/149);bypass signaling activation and downstream pathway activation alterations included TP53 mutation(69.8%,104/149)and MET amplification(30.9%,46/149).Among the 136 patients with EGFR Ex19del/L858R mutation in tissue samples,72.1%(98/136),35.3%(48/136),and 32.4%(44/136)had TP53 mutations,EGFR amplification,and MET amplification,respectively.Taking tissue samples as references,the GPS in plasma samples showed high specificity(90.7–100%)for almost all genomic alterations.Compared with FISH(gene copy number[GCN]≥10),the overall percent agreement of tissue NGS,optimized tissue NGS(GCN≥8.63),plasma NGS,and plasma ddPCR for MET amplification were 75.0%(27/36),100%(36/36),88.9%(32/36),and 94.4%(34/36),respectively.This study represents the largest-scale,prospective study with paired tissue and plasma samples to enable comprehensive analysis of GPS,providing a novel perspective into coalterations at the first-line treatment failure of osimertinib.A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable.Moreover,the integration of FISH,NGS,and ddPCR provided a comprehensive assessment of MET amplification.
基金supported by the National Natural Science Foundation of China(Nos.U2336204 and 62372086)the Natural Science Foundation of Sichuan Province,China(Nos.2024NSFSC0004 and2025ZNSFSC0500)。
文摘Noncooperative computer systems and network confrontation present a core challenge in cyberspace security.Traditional cybersecurity technologies predominantly rely on passive response mechanisms,which exhibit significant limitations when addressing real-world complex and unknown threats.This paper introduces the concept of“active cybersecurity,”aiming to enhance network security not only through technical measures but also by leveraging strategy-level defenses.The core assumption of this concept is that attackers and defenders,in the context of network confrontations,act as rational decision-makers seeking to maximize their respective objectives.Building on this observation,this paper integrates game theory to analyze the interdependent relationships between attackers and defenders,thereby optimizing their strategies.Guided by this foundational idea,we propose an active cybersecurity model involving intelligent threat sensing,in-depth behavior analysis,comprehensive path profiling,and dynamic countermeasures,termed SAPC,designed to foster an integrated defense capability encompassing threat perception,analysis,tracing,and response.At its core,SAPC incorporates theoretical analyses of adversarial behavior and the optimization of corresponding strategies informed by game theory.By profiling adversaries and modeling confrontation as a“game,”the model establishes a comprehensive framework that provides both theoretical insights into and practical guidance for cybersecurity.The proposed active cybersecurity model marks a transformative shift from passive defense to proactive perception and confrontation.It facilitates the evolution of cybersecurity technologies toward a new paradigm characterized by active prediction,prevention,and strategic guidance.
基金supported by the National Key R&D Program(2016YFC0201504)the National Natural Science Foundation of China(Nos.41822505 and 41571447)+2 种基金National Research Program for Key Issues in Air Pollution Control(DQGG0201&0207)Beijing Nova Program(Z181100006218077)SEE Foundation.
文摘Vehicle evaporation is an essential source of VOCs in cities but is not well understood in China.Reported emission factors from previous studies are not enough for understanding the atmospheric chemical process of vehicular evaporative VOCs.In this work,a serious of detailed VOCs speciation profiles are developed based on test processes and emission processes.A mass balance method was used to divide different emission processes during diurnal tests.The results show that headspace vapor of gasoline cannot represent the real-world vehicle evaporation because of the significant differences in VOCs speciation profiles,especially for aromatics.To further distinguish emissions from evaporation and exhaust,only the ratios of MTBE/benzene and MTBE/toluene can serve as indicators when considering species from all evaporative processes.Besides,emissions from different sources change significantly with the seasons.To solve these problems,we developed a monthly comprehensive evaporation speciation profile.The individual profiles at the emission processes are weighted by the emission of the in-use vehicle fleet in Beijing to derive the comprehensive speciation profile of evaporative VOCs.Ozone formation potential(OFP)and secondary organic aerosol potential(SOAP)were used to evaluate the environmental impact.For SOAP,100 g evaporative emissions are equal to 6.05-12.71 g toluene in different months,much higher than that given using headspace vapors,especially in winter(7.2 times higher in December).These findings would improve our understanding of the evaporative VOCs emissions in China and their environmental impacts(e.g.,O3 and SOA formation).
基金supported by the National Key Research and Development Program of China(2021YFA0910100 and 2022YFC2504602)Healthy Zhejiang One Million People Cohort(K-20230085)+9 种基金National Natural Science Foundation of China(82304946,82241230,T2125002,82341007,82304946,82473489,and 82573745)Zhejiang gastrointestinal cancer Clinical Medical Research Center(2022E50006)Medical Science and Technology Project of Zhejiang Province(WKJ-ZJ-2323)Beijing Natural Science Foundation(Z220014)Natural Science Foundation of Zhejiang Province(LR21H280001,LBZ22H160002,LBD24H290001,and LMS25H160006)Science and Technology Projects of Zhejiang Province(2019C03049)Program of Zhejiang Provincial TCM Sci-tech Plan(2018ZY006 and 2020ZZ005)Science and Technology Projects of Zhejiang Province(2022KY684)Program of Zhejiang Provincial TCM Sci-tech Plan(2022ZQ020)the New Cornerstone Science Foundation through the XPLORER PRIZE.
文摘Gastric cancer(GC)is the fifth most common malignancy and the fourth leading cause of cancer-related death worldwide,with China bearing nearly half of the global burden[1,2].Most patients are diagnosed at stage Ⅲ–Ⅳ,and despite perioperative therapy plus D2 gastrectomy being the standard of care,long-term survival remains poor[3,4].
