The growing attention on urban tourism was very widespread. There are two angles to study urban tourism: supply-side and demand-side. And the supply-side of the tourism remains very important. The RBD (Recreation Busi...The growing attention on urban tourism was very widespread. There are two angles to study urban tourism: supply-side and demand-side. And the supply-side of the tourism remains very important. The RBD (Recreation Business District) is a useful framework to understand the components of urban tourism and how they fit together. The paper begins with a review on the RBD and the spatial structure of tourism in urban areas and then attempts to develop a more general understanding of the spatial structure evolution of RBDs in a tourist-historic city-Suzhou. The spatial structures and functions of the RBDs in Suzhou are examined, based on field observations, interviews with city officials and industry leaders, and a review of available documents. The urban tourism of Suzhou has developed in a range of contexts, that various types of RBDs have emerged as a result of different urban development strategies. The spatial structure has evolved from the past "Single-cored Structure" to "Double-cored Structure" at present, and then to "Chain Structure" in the future. The spatial form and evolution of RBD in Suzhou are closely relative with its urban spatial expansion. Urban area dispersal is the prerequisite of the emergence of the RBD. Planning and constructing the RBD becomes a new impetus to urban growth or renewal. Finally, a number of strategies for planning and developing the RBD in Suzhou are suggested. The different RBDs should adopt different strategies. Intensification can be the possible strategy for the RBDs in the ancient city. Accreting with the urban theme park or engrafting on the Jinji Lake is suggested respectively for the RBD in the Suzhou New District and the Suzhou Industrial Park.展开更多
Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat CRPC.Treatments that t...Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat CRPC.Treatments that target programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for human cancers with clinical benefit.However,many patients,especially prostate cancer,fail to respond to anti-PD-1/PD-L1 treatment,so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy.In the present study,analyzing the data from our prostate cancer tissue microarray,we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L(Hn RNP L).Hence,we further investigated the potential role of Hn RNP L on the PD-L1 expression,the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC.Indeed,Hn RNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo,on the contrary,Hn RNP L overexpression led to the opposite effect in CRPC cells.In addition,consistent with the previous study,we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death,and Hn RNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells.Furthermore,Hn RNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8^(+)T cells and synergized with anti-PD-1 therapy in CRPC tumors.This study provided biological evidence that Hn RNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.展开更多
As the emergence of various highbandwidth services and the requirements to support 5G/Wi-Fi 6 wireless networks,the next generation fixed networks,i.e.F5G,are expected to be realized in the 5G era.F5G is endowed with ...As the emergence of various highbandwidth services and the requirements to support 5G/Wi-Fi 6 wireless networks,the next generation fixed networks,i.e.F5G,are expected to be realized in the 5G era.F5G is endowed with new characteristics,including ultra-high bandwidth,all-optical connections and optimal service experience.With the prospect of optical-to-everywhere,optical technologies are used for mobile front-haul,mid-haul,and back-haul.Optical access networks would play an important role in F5G to support radio access network and fixed access network.Low-latency PON is a key for cost effective-haul traffic aggregation.In terms of signal transmission,intensity modulation directdetection(IM-DD)is a promising scheme due to its simple architecture.The fundamental challenge associated with direct-detection is the disappearance of the transmitted signal’s phase.In access network,the flexibility and low latency are the two key factors affecting service experience.In this article,we review the evolution of PONs and the challenges of current PONs in detail.We analyze key enabling digital signal processing(DSP)techniques,including detection linearization for direct-detection and simplified coherent detection,adaptive equalizers,digital filer enabled flexible access network and low-latency inter-ONU communications.Finally,we discuss the developing trends of future optical access networks.展开更多
Prodigiosin is a secondary metabolite mainly produced at 30°C in Serratia marcescens,but it can hardly be synthetized at 37°C or higher.In this study,we provide insight into the metabolic regulation of prodi...Prodigiosin is a secondary metabolite mainly produced at 30°C in Serratia marcescens,but it can hardly be synthetized at 37°C or higher.In this study,we provide insight into the metabolic regulation of prodigiosin synthesis in response to temperature through transcriptome sequencing.The analysis of the function of differentially expressed genes suggested that temperature resulted in significant alteration of the metabolic pathways between 30 and 37°C.Specifically,30°C favored transcriptional expression of the pig gene cluster.At the same time,the carbon flux was redistributed to pathways of pyruvate,proline,serine,especially homoserine,cystathionine,homocysteine,methionine,and s-adenosylmethionine metabolism,all involved in prodigiosin biosynthesis,and was finally increased towards the prodigiosin synthesis pathway in S.marcescens at 30°C.Interestingly,results further confirmed increased transcriptional level of five regulators(LuxS,RpoS,Hfq,EepR,CRP),and decreased content of hexS through qPCR.Finally,successful co-overexpression of mmuM and metK,related to homocysteine,methionine,and s-adenosylmethionine metabolism,in the chromosome of JNB5-1(JNB5-1/MK)resulted in increased prodigiosin titer up to 7.57 g/L in JNB5-1/MK at 30°C,which was 41.2%higher than that in JNB5-1.Our transcriptome analysis provides further insight into the strain’s response to temperature changes at the transcription level,which is of great significance for improving the production of prodigiosin.展开更多
Racemize 2-hydroxybutyric acid is usually synthesized by organic methods and needs additional deracemization to obtain optically pure enantiomers for industrial application.Here we present a cascade biocatalysis syste...Racemize 2-hydroxybutyric acid is usually synthesized by organic methods and needs additional deracemization to obtain optically pure enantiomers for industrial application.Here we present a cascade biocatalysis system in Escherichia coli BL21 which employed L-threonine deaminase(TD),NAD-dependent L-lactate dehydrogenase(LDH)and alcohol dehydrogenase(ADH)for producing optically pure(S)-2-hydroxybutyric acid((S)-2-HBA)from bulk chemical L-threonine.To solve the mismatch in the conversion rate and the consumption rate of intermediate 2-oxobutyric acid(2-OBA)formed in the multi-enzyme catalysis reaction,ribosome binding site regulation strategy was explored to control TD expression levels,achieving an eightfold alteration in the conversion rate of 2-OBA.With the optimized activity ratio of the three enzymes and using ADH for NADH regeneration,the recombinant strain ADH-r53 showed increased production of(S)-2-HBA with the highest titer of 129 g/L and molar yield of 93%within 24 h,which is approximately 1.65 times that of the highest yield reported so far.Moreover,(S)-2-HBA could easily be purified by distillation,making it have great potential for industrial application.Additionally,our results indicated that constructing a tunable multi-enzyme-coordinate expression system in single cell had great significance in biocatalysis of hydroxyl acids.展开更多
This paper tries to apply a new and more comprehensive method to urban tourism research in an expanded field instead of only partially, unilaterally and separately focusing on the city itself. Taking the urban tourism...This paper tries to apply a new and more comprehensive method to urban tourism research in an expanded field instead of only partially, unilaterally and separately focusing on the city itself. Taking the urban tourism of Guangdong, Hong Kong and Macao as an example, it aims at presenting a new spatial system of urban tourism research and pointing out the new orientation of urban tourism research in combination of macro level and micro level, from description to explanation. The meanings of the spatial framework construction for urban tourism study are to make clear how urban tourism studies vary with the changes of dimensions of time and space. This is a meaningful discussion because it will bring great changes to the using of literatures, the opening of research perspectives on urban tourism and the upgrading of theories, so as to create a new stage for urban tourism study.展开更多
文摘The growing attention on urban tourism was very widespread. There are two angles to study urban tourism: supply-side and demand-side. And the supply-side of the tourism remains very important. The RBD (Recreation Business District) is a useful framework to understand the components of urban tourism and how they fit together. The paper begins with a review on the RBD and the spatial structure of tourism in urban areas and then attempts to develop a more general understanding of the spatial structure evolution of RBDs in a tourist-historic city-Suzhou. The spatial structures and functions of the RBDs in Suzhou are examined, based on field observations, interviews with city officials and industry leaders, and a review of available documents. The urban tourism of Suzhou has developed in a range of contexts, that various types of RBDs have emerged as a result of different urban development strategies. The spatial structure has evolved from the past "Single-cored Structure" to "Double-cored Structure" at present, and then to "Chain Structure" in the future. The spatial form and evolution of RBD in Suzhou are closely relative with its urban spatial expansion. Urban area dispersal is the prerequisite of the emergence of the RBD. Planning and constructing the RBD becomes a new impetus to urban growth or renewal. Finally, a number of strategies for planning and developing the RBD in Suzhou are suggested. The different RBDs should adopt different strategies. Intensification can be the possible strategy for the RBDs in the ancient city. Accreting with the urban theme park or engrafting on the Jinji Lake is suggested respectively for the RBD in the Suzhou New District and the Suzhou Industrial Park.
基金supported by the National Natural Science Foundation of China(Grant No.81773277)Science and Technology Program of Guangzhou,China(Grant No.201803010014)+3 种基金Guangdong Basic and Applied Basic Research Foundation(Grant Nos.2020A1515110922 and 2019A1515110033,China)China Postdoctoral Science Foundation funded project(Grant Nos.2018M643126 and 2019M662865)Distinguished Young Talents in Higher Education Foundation of Guangdong Province(Grant No.2019KQNCX115,China)Achievement Cultivation and Clinical Transformation Application Cultivation Projects of the First Affiliated Hospital of Guangzhou Medical University(Grant No.ZH201908,China)。
文摘Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat CRPC.Treatments that target programmed cell death protein 1(PD-1)and programmed death ligand-1(PD-L1)have been approved for human cancers with clinical benefit.However,many patients,especially prostate cancer,fail to respond to anti-PD-1/PD-L1 treatment,so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy.In the present study,analyzing the data from our prostate cancer tissue microarray,we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L(Hn RNP L).Hence,we further investigated the potential role of Hn RNP L on the PD-L1 expression,the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC.Indeed,Hn RNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo,on the contrary,Hn RNP L overexpression led to the opposite effect in CRPC cells.In addition,consistent with the previous study,we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death,and Hn RNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells.Furthermore,Hn RNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8^(+)T cells and synergized with anti-PD-1 therapy in CRPC tumors.This study provided biological evidence that Hn RNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.
基金National Science Foundation of China(NSFC)(61871082 and 62111530150)Fundamental Research Funds for the Central Universities(ZYGX2020ZB043 and ZYGX2019J008).
文摘As the emergence of various highbandwidth services and the requirements to support 5G/Wi-Fi 6 wireless networks,the next generation fixed networks,i.e.F5G,are expected to be realized in the 5G era.F5G is endowed with new characteristics,including ultra-high bandwidth,all-optical connections and optimal service experience.With the prospect of optical-to-everywhere,optical technologies are used for mobile front-haul,mid-haul,and back-haul.Optical access networks would play an important role in F5G to support radio access network and fixed access network.Low-latency PON is a key for cost effective-haul traffic aggregation.In terms of signal transmission,intensity modulation directdetection(IM-DD)is a promising scheme due to its simple architecture.The fundamental challenge associated with direct-detection is the disappearance of the transmitted signal’s phase.In access network,the flexibility and low latency are the two key factors affecting service experience.In this article,we review the evolution of PONs and the challenges of current PONs in detail.We analyze key enabling digital signal processing(DSP)techniques,including detection linearization for direct-detection and simplified coherent detection,adaptive equalizers,digital filer enabled flexible access network and low-latency inter-ONU communications.Finally,we discuss the developing trends of future optical access networks.
基金This work was supported by the National Key Research and Development Program of China(2018YFA0900300)the National Natural Science Foundation of China(31870066,21778024)+1 种基金National First-Class Discipline Program of Light Industry Technology and Engineering(LITE2018-06)the Program of Introducing Talents of Discipline to Universities(111-2-06).
文摘Prodigiosin is a secondary metabolite mainly produced at 30°C in Serratia marcescens,but it can hardly be synthetized at 37°C or higher.In this study,we provide insight into the metabolic regulation of prodigiosin synthesis in response to temperature through transcriptome sequencing.The analysis of the function of differentially expressed genes suggested that temperature resulted in significant alteration of the metabolic pathways between 30 and 37°C.Specifically,30°C favored transcriptional expression of the pig gene cluster.At the same time,the carbon flux was redistributed to pathways of pyruvate,proline,serine,especially homoserine,cystathionine,homocysteine,methionine,and s-adenosylmethionine metabolism,all involved in prodigiosin biosynthesis,and was finally increased towards the prodigiosin synthesis pathway in S.marcescens at 30°C.Interestingly,results further confirmed increased transcriptional level of five regulators(LuxS,RpoS,Hfq,EepR,CRP),and decreased content of hexS through qPCR.Finally,successful co-overexpression of mmuM and metK,related to homocysteine,methionine,and s-adenosylmethionine metabolism,in the chromosome of JNB5-1(JNB5-1/MK)resulted in increased prodigiosin titer up to 7.57 g/L in JNB5-1/MK at 30°C,which was 41.2%higher than that in JNB5-1.Our transcriptome analysis provides further insight into the strain’s response to temperature changes at the transcription level,which is of great significance for improving the production of prodigiosin.
基金This work was funded by the National Key Research and Development Program of China(2018YFA0900300)the National Natural Science Foundation of China(31770058,32070035)+3 种基金Natural Science Foundation of Jiangsu Province(BK20181205)the Key Research and Development Program of Ningxia Hui Autonomous Region(No.2019BCH01002)the national first-class discipline program of Light Industry Technology and Engineering(LITE2018-06)the 111 Project(111-2-06).
文摘Racemize 2-hydroxybutyric acid is usually synthesized by organic methods and needs additional deracemization to obtain optically pure enantiomers for industrial application.Here we present a cascade biocatalysis system in Escherichia coli BL21 which employed L-threonine deaminase(TD),NAD-dependent L-lactate dehydrogenase(LDH)and alcohol dehydrogenase(ADH)for producing optically pure(S)-2-hydroxybutyric acid((S)-2-HBA)from bulk chemical L-threonine.To solve the mismatch in the conversion rate and the consumption rate of intermediate 2-oxobutyric acid(2-OBA)formed in the multi-enzyme catalysis reaction,ribosome binding site regulation strategy was explored to control TD expression levels,achieving an eightfold alteration in the conversion rate of 2-OBA.With the optimized activity ratio of the three enzymes and using ADH for NADH regeneration,the recombinant strain ADH-r53 showed increased production of(S)-2-HBA with the highest titer of 129 g/L and molar yield of 93%within 24 h,which is approximately 1.65 times that of the highest yield reported so far.Moreover,(S)-2-HBA could easily be purified by distillation,making it have great potential for industrial application.Additionally,our results indicated that constructing a tunable multi-enzyme-coordinate expression system in single cell had great significance in biocatalysis of hydroxyl acids.
基金Under the auspices of the National Natural Science Foundation of China (No .40201017)
文摘This paper tries to apply a new and more comprehensive method to urban tourism research in an expanded field instead of only partially, unilaterally and separately focusing on the city itself. Taking the urban tourism of Guangdong, Hong Kong and Macao as an example, it aims at presenting a new spatial system of urban tourism research and pointing out the new orientation of urban tourism research in combination of macro level and micro level, from description to explanation. The meanings of the spatial framework construction for urban tourism study are to make clear how urban tourism studies vary with the changes of dimensions of time and space. This is a meaningful discussion because it will bring great changes to the using of literatures, the opening of research perspectives on urban tourism and the upgrading of theories, so as to create a new stage for urban tourism study.
