Dear Editor,Wheat(Triticum aestivum)is a major staple crop in the world and provides~20%of the food calories for human consumption(Appels et al.,2018).During the 1960s and 1970s,the introduction of two semi-dwarfing g...Dear Editor,Wheat(Triticum aestivum)is a major staple crop in the world and provides~20%of the food calories for human consumption(Appels et al.,2018).During the 1960s and 1970s,the introduction of two semi-dwarfing genes Rht-B1b and Rht-D1b in wheat varieties strikingly improved lodging resistance and harvest index,and therefore substantially increased grain yield,resulting in the well-known"Green Revolution"(Peng et al.,1999).However,plants carrying Rht-B1b and Rht-D1b suffer from several drawbacks.展开更多
The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to...The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system,exosomes efficiently transport functional components to recipient cells.Accumulating evidence has recently shown that exosomes derived from tumor cells,host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules,modulating the innate immune responses of the host.In this review,we describe the current understanding of EVs(mainly focusing on exosomes)and summarize and discuss their crucial roles in determining innate immune responses.Additionally,we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications.展开更多
A bicyclic depsipeptide, chromopeptide A(1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a relat...A bicyclic depsipeptide, chromopeptide A(1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a related known compound. The absolute configuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo K_α radiation(λ ? 0.71073 ?) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC_(50) values of 7.7, 7.0, and 16.5 nmol/L, respectively.展开更多
Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer(NSCLC)patients according to the predicted response to c-Met inhibitor...Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer(NSCLC)patients according to the predicted response to c-Met inhibitors(c-Metis),yet the overall clinical benefit of this strategy is quite limited.Notably,c-Met protein overexpression,which occurs in approximately 20–25%of NSCLC patients,has not yet been clearly defined as a clinically useful biomarker.An optimized strategy for accurately classifying patients with c-Met overexpression for decision-making regarding c-Meti treatment is lacking.Herein,we found that SYK regulates the plasticity of cells in an epithelial state and is associated with their sensitivity to c-Metis both in vitro and in vivo in PDX models with c-Met overexpression regardless of MET gene status.Furthermore,TGF-β1 treatment resulted in SYK transcriptional downregulation,increased Sp1-mediated transcription of FRA1,and restored the mesenchymal state,which conferred resistance to c-Metis.Clinically,a subpopulation of NSCLC patients with c-Met overexpression coupled with SYK overexpression exhibited a high response rate of 73.3%and longer progression-free survival with c-Meti treatment than other patients.SYK negativity coupled with TGF-β1 positivity conferred de novo and acquired resistance.In summary,SYK regulates cell plasticity toward a therapy-sensitive epithelial cell state.Furthermore,our findings showed that SYK overexpression can aid in precisely stratifying NSCLC patients with c-Met overexpression regardless of MET alterations and expand the population predicted to benefit from c-Met-targeted therapy.展开更多
Metropolitan cities in China are commonly confronted with unresolved traffic congestion issues, primarily due to rapidly increasing traffic demand. Group disparity between commuting mode choice and its spatial distrib...Metropolitan cities in China are commonly confronted with unresolved traffic congestion issues, primarily due to rapidly increasing traffic demand. Group disparity between commuting mode choice and its spatial distribution on road networks has enabled us to examine the factors that give rise to the discrepancies and the fundamental spatial causes of traffic congestion. In recent years, mi- cro-perspective, individual, and behavior-based spatial analysis have mushroomed and been facilitated with effective tools such as tem- poral geographic information systems （T-GIS）. It is difficult to study the interrelations between transport and space on the basis of commuting mode choice since the mode choice data are invisible in a specific space such as a particular road network. Therefore, in the field of transport, the classical origin destination （OD） four-stage model （FSM） is usually employed to calculate data when studying commuting mode choice. Based on the relative principles of T-GIS and the platform of ArcGIS, this paper considers Guangzhou as a case study and develops a spatio-temporal tool to examine the daily activities of residents. Meanwhile, the traffic volume distribution in rush hours, which was analyzed according to commuting modes and how they were reflected in the road network, was scrutinized with data extracted from travel diaries. Moreover, efforts were made to explain the relationship between traffic demand and urban spatial structure. Based on the investigation, this research indicates that traffic volumes in divergent groups and on the road networks is driven by： l） the socio-economie characteristics of travelers; 2） a jobs-housing imbalance under suburbanization; 3） differences in the spatial supply of transport modes; 4） the remains of the Danwei （work unit） system and market development in China; and 5） the transition of urban spatial structure and other factors.展开更多
基金This work was financially supported by the National Key Research and Development Program of China(grant no.2020YFE0202300)the National Natural Science Foundation of China(grant no.31801346 and 32172040)+1 种基金the China Agriculture Research System of MOF and MARA(grant no.CARS-03)the Agricultural Science and Technology Innovation Program(grant no.CAAS-ZDRW202109).
文摘Dear Editor,Wheat(Triticum aestivum)is a major staple crop in the world and provides~20%of the food calories for human consumption(Appels et al.,2018).During the 1960s and 1970s,the introduction of two semi-dwarfing genes Rht-B1b and Rht-D1b in wheat varieties strikingly improved lodging resistance and harvest index,and therefore substantially increased grain yield,resulting in the well-known"Green Revolution"(Peng et al.,1999).However,plants carrying Rht-B1b and Rht-D1b suffer from several drawbacks.
基金supported by a special program from the Chinese National Natural Science Funds(31701232 to F.X.,31671457 and 91753139 to L.Z.,and 31871405 and 31571460 to F.Z.)the National Postdoctoral Program for Innovative Talents(BX201700165 to F.X.)+4 种基金the National Science Foundation for Postdoctoral Scientists of China(BX201700165 to F.X.)Distinguished Young Scholars of Jiangsu Province(BK20180043 to F.Z.)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003 to F.Z.)the Shenzhen Basic Research Program(JCYJ20180507182203049 to S.Z.)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘The innate immune system plays a crucial role in the host defense against viral and microbial infection.Exosomes constitute a subset of extracellular vesicles(EVs)that can be released by almost all cell types.Owing to their capacity to shield the payload from degradation and to evade recognition and subsequent removal by the immune system,exosomes efficiently transport functional components to recipient cells.Accumulating evidence has recently shown that exosomes derived from tumor cells,host cells and even bacteria and parasites mediate the communication between the invader and innate immune cells and thus play an irreplaceable function in the dissemination of pathogens and donor cell-derived molecules,modulating the innate immune responses of the host.In this review,we describe the current understanding of EVs(mainly focusing on exosomes)and summarize and discuss their crucial roles in determining innate immune responses.Additionally,we discuss the potential of using exosomes as biomarkers and cancer vaccines in diagnostic and therapeutic applications.
基金financially supported by the National Marine ‘863’ Project (Nos. 2012AA092105 and 2013AA092902)the National Natural Science Foundation of China (No. 81273430)
文摘A bicyclic depsipeptide, chromopeptide A(1), was isolated from a deep-sea-derived bacterium Chromobacterium sp. HS-13-94. Its structure was determined by extensive spectroscopic analysis and by comparison with a related known compound. The absolute configuration of chromopeptide A was established by X-ray diffraction analysis employing graphite monochromated Mo K_α radiation(λ ? 0.71073 ?) with small Flack parameter 0.03. Chromopeptide A suppressed the proliferation of HL-60, K-562, and Ramos cells with average IC_(50) values of 7.7, 7.0, and 16.5 nmol/L, respectively.
基金supported by the Natural Science Foundation of China for Innovation Research Group(No.81821005 to M.G.)the National Natural Science Foundation of China(No.81874314 to H.J,No.82173834 to J.A,No.82173202 to X.Z.)+4 种基金the Lingang Laboratory Grant(No.LG202103-02-01 to J.A)the Collaborative Innovation Cluster Project of Shanghai Municipal Commission of Health and Family Planning(No.2020CXJQ02 to M.G.)Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer(No.2017B030314120 to Y.W.)Guangdong Provincial Natural Science Program(No.2019A1515010900 to X.Z.)GDPH Dengfeng Program(No.DFJH201903&KJ012019444&8197103306 to X.Z.).
文摘Genomic MET amplification and exon 14 skipping are currently clinically recognized biomarkers for stratifying subsets of non-small cell lung cancer(NSCLC)patients according to the predicted response to c-Met inhibitors(c-Metis),yet the overall clinical benefit of this strategy is quite limited.Notably,c-Met protein overexpression,which occurs in approximately 20–25%of NSCLC patients,has not yet been clearly defined as a clinically useful biomarker.An optimized strategy for accurately classifying patients with c-Met overexpression for decision-making regarding c-Meti treatment is lacking.Herein,we found that SYK regulates the plasticity of cells in an epithelial state and is associated with their sensitivity to c-Metis both in vitro and in vivo in PDX models with c-Met overexpression regardless of MET gene status.Furthermore,TGF-β1 treatment resulted in SYK transcriptional downregulation,increased Sp1-mediated transcription of FRA1,and restored the mesenchymal state,which conferred resistance to c-Metis.Clinically,a subpopulation of NSCLC patients with c-Met overexpression coupled with SYK overexpression exhibited a high response rate of 73.3%and longer progression-free survival with c-Meti treatment than other patients.SYK negativity coupled with TGF-β1 positivity conferred de novo and acquired resistance.In summary,SYK regulates cell plasticity toward a therapy-sensitive epithelial cell state.Furthermore,our findings showed that SYK overexpression can aid in precisely stratifying NSCLC patients with c-Met overexpression regardless of MET alterations and expand the population predicted to benefit from c-Met-targeted therapy.
基金Under the auspices of National Natural Science Foundation of China(No.40971098)National High Technology Research and Development Program of China(No.2012AA121402)
文摘Metropolitan cities in China are commonly confronted with unresolved traffic congestion issues, primarily due to rapidly increasing traffic demand. Group disparity between commuting mode choice and its spatial distribution on road networks has enabled us to examine the factors that give rise to the discrepancies and the fundamental spatial causes of traffic congestion. In recent years, mi- cro-perspective, individual, and behavior-based spatial analysis have mushroomed and been facilitated with effective tools such as tem- poral geographic information systems （T-GIS）. It is difficult to study the interrelations between transport and space on the basis of commuting mode choice since the mode choice data are invisible in a specific space such as a particular road network. Therefore, in the field of transport, the classical origin destination （OD） four-stage model （FSM） is usually employed to calculate data when studying commuting mode choice. Based on the relative principles of T-GIS and the platform of ArcGIS, this paper considers Guangzhou as a case study and develops a spatio-temporal tool to examine the daily activities of residents. Meanwhile, the traffic volume distribution in rush hours, which was analyzed according to commuting modes and how they were reflected in the road network, was scrutinized with data extracted from travel diaries. Moreover, efforts were made to explain the relationship between traffic demand and urban spatial structure. Based on the investigation, this research indicates that traffic volumes in divergent groups and on the road networks is driven by： l） the socio-economie characteristics of travelers; 2） a jobs-housing imbalance under suburbanization; 3） differences in the spatial supply of transport modes; 4） the remains of the Danwei （work unit） system and market development in China; and 5） the transition of urban spatial structure and other factors.
