Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained ...Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.展开更多
Plant phenotypic plasticity is controlled by diverse hormone pathways, which integrate and convey infor- mation from multiple developmental and environmental signals. Moreover, in plants many processes such as growth,...Plant phenotypic plasticity is controlled by diverse hormone pathways, which integrate and convey infor- mation from multiple developmental and environmental signals. Moreover, in plants many processes such as growth, development, and defense are regulated in similar ways by multiple hormones. Among them, gibberellins （GAs） are phytohormones with pleiotropic actions, regulating various growth processes throughout the plant life cycle. Previous work has revealed extensive interplay between GAs and other hor- mones, but the molecular mechanism became apparent only recently. Molecular and physiological studies have demonstrated that DELLA proteins, considered as master negative regulators of GA signaling, inte- grate multiple hormone signaling pathways through physical interactions with transcription factors or reg- ulatory proteins from different families. In this review, we summarize the latest progress in GA signaling and its direct crosstalk with the main phytohormone signaling, emphasizing the multifaceted role of DELLA proteins with key components of major hormone signaling pathways.展开更多
With the growing population and the reducing arable land, breeding has been considered as an effective way to solve the food crisis.As an important part in breeding, high-throughput phenotyping can accelerate the bree...With the growing population and the reducing arable land, breeding has been considered as an effective way to solve the food crisis.As an important part in breeding, high-throughput phenotyping can accelerate the breeding process effectively. Light detection and ranging(LiDAR) is an active remote sensing technology that is capable of acquiring three-dimensional(3 D) data accurately,and has a great potential in crop phenotyping. Given that crop phenotyping based on LiDAR technology is not common in China,we developed a high-throughput crop phenotyping platform, named Crop 3 D, which integrated LiDAR sensor, high-resolution camera, thermal camera and hyperspectral imager. Compared with traditional crop phenotyping techniques, Crop 3 D can acquire multi-source phenotypic data in the whole crop growing period and extract plant height, plant width, leaf length, leaf width, leaf area, leaf inclination angle and other parameters for plant biology and genomics analysis. In this paper, we described the designs,functions and testing results of the Crop 3 D platform, and briefly discussed the potential applications and future development of the platform in phenotyping. We concluded that platforms integrating LiDAR and traditional remote sensing techniques might be the future trend of crop high-throughput phenotyping.展开更多
Phoebe bournei（Hemsl.） Yang is a rare and protected plant in China. This study was conducted to determine the phenotypic variation in this species and to document phenotypic variation within and among populations of...Phoebe bournei（Hemsl.） Yang is a rare and protected plant in China. This study was conducted to determine the phenotypic variation in this species and to document phenotypic variation within and among populations of P. bournei. Nested analysis of variance, coefficient of variation, multiple comparisons, principal component analysis（PCA） and correlation analysis were used to analyze ten phenotypic traits in ten natural populations of P.bournei from both the northeastern and the primary region of the range of this species. Significant differences among and within populations were observed in leaf and seed phenotypic traits. Variation among populations（34.92%）was greater than that within populations（26.19%）. The mean phenotypic differentiation coefficient was 53.77% among populations, indicating that variation among populations comprised the majority of the phenotypic variation of P. bournei. The coefficient of variance（CV） of ten traits varied from 6.44 to 18.45%, with an average of 12.03%.The CV of leaf traits among populations（15.64%） was higher than that of seed traits（8.60%）, indicating that seed traits were more stable. The results from CV and PCA indicated that leaf area, leaf length and thousand seed weight were the main factors accounting for the observed phenotypic variations. Significant or highly significant correlations were observed among most leaf and/or in seed phenotypic traits, whereas no significant correlations were observed between phenotypic traits and geographic factors.Based on cluster analysis, the ten populations can be divided into three clusters. These clusters were not a result of geographic distances.展开更多
Aims In perennial species,the allocation of resources to reproduction results in a reduction of allocation to vegetative growth and,therefore,impacts future reproductive success.As a consequence,variation in this trad...Aims In perennial species,the allocation of resources to reproduction results in a reduction of allocation to vegetative growth and,therefore,impacts future reproductive success.As a consequence,variation in this trade-off is among the most important driving forces in the life-history evolution of perennial plants and can lead to locally adapted genotypes.In addition to genetic variation,phenotypic plasticity might also contribute to local adaptation of plants to local conditions by mediating changes in reproductive allocation.Knowledge on the importance of genetic and environmental effects on the tradeoff between reproduction and vegetative growth is therefore essential to understand how plants may respond to environmental changes.Methods We conducted a transplant experiment along an altitudinal gradient from 425to1921 min the frontrange of the Western Alps of Switzerland to assess the influence of both altitudinal origin of populations and altitude of growing site on growth,reproductive investment and local adaptation in Poa alpina.Important findings In our study,the investment in reproduction increased with plant size.Plant growth and the relative importance of reproductive investment decreased in populations originating from higher altitudes compared to populations originating from lower altitudes.The changes in reproductive investment were mainly explained by differences in plant size.In contrast to genetic effects,phenotypic plasticity of all traits measured was low and not related to altitude.As a result,the population from the lowest altitude of origin performed best at all sites.Our results indicate that in P.alpina genetic differences in growth and reproductive investment are related to local conditions affecting growth,i.e.interspecific competition and soil moisture content.展开更多
AIM： To isolate putative pancreatic stem cells （PSCs） from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cyto...AIM： To isolate putative pancreatic stem cells （PSCs） from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well. METHODS： By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The MatrigelTM was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting （FACS） was used to detect the phenotypic markers of putative PSCs. RESULTS： A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin. They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29, CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 （SH2）, CD81, CD105（SH3）. CONCLUSION： In this study, we successfully isolated PSCs from adult human pancreatic duct by using serumfree medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.展开更多
In order to evaluate the performance of a molecular Hain line probe assay （Hain LPA） for rapid detection of rifampicin and isoniazid resistance of Mycobocterium tuberculosis in China, 1612 smear positive patients we...In order to evaluate the performance of a molecular Hain line probe assay （Hain LPA） for rapid detection of rifampicin and isoniazid resistance of Mycobocterium tuberculosis in China, 1612 smear positive patients were consecutively enrolled in this study. Smear positive sputum specimens were collected for Hain LPA and conventional drug susceptibility testing （DST）. The sensitivity and specificity of Hain LPA were analyzed by using conventional DST as golden reference. The sensitivity, specificity, positive predictive value {PPV） and negative predictive value （NPV） for rifampicin resistance detection were 88.33%, 97.66%, 81.54%, and 98.62%, respectively. The sensitivity, specificity, PPV and NPV for isoniazid resistance detection were 80.25%, 98.07%, 87.25%, and 96.78%, respectively. These findings suggested that Hain LPA can be an effective method worthy of broader use in China.展开更多
Transposable elements(TEs), originally discovered in maize as controlling elements, are the main components of most eukaryotic genomes. TEs have been regarded as deleterious genomic parasites due to their ability to u...Transposable elements(TEs), originally discovered in maize as controlling elements, are the main components of most eukaryotic genomes. TEs have been regarded as deleterious genomic parasites due to their ability to undergo massive amplification. However, TEs can regulate gene expression and alter phenotypes. Also, emerging findings demonstrate that TEs can establish and rewire gene regulatory networks by genetic and epigenetic mechanisms. In this review, we summarize the key roles of TEs in fine-tuning the regulation of gene expression leading to phenotypic plasticity in plants and humans, and the implications for adaption and natural selection.展开更多
Manifestations of diseases are determined by the .combined effect of genetic and environmentalfactors. Different physical, behavioral and social variations affect the prevalence and presentation of common diseases. Po...Manifestations of diseases are determined by the .combined effect of genetic and environmentalfactors. Different physical, behavioral and social variations affect the prevalence and presentation of common diseases. Polycystic ovary syndrome （PCOS）, with a heterogeneous presentation, is the most common endocrine disorder that affects about 5%-10% women of reproductive age. It is characterized by clinical and/or biochemical hyperandrogenism, ovulatory dysfunction and polycystic ovaries.展开更多
基金This work was supported by grants from the Beijing Advanced Innovation Center for Genomics at Peking University,Key Technologies R&D Program(2016YFC0900100 and 2016YFC0902300)the National Natural Science Foundation of China(31530036 and 91742203).
文摘Immunotherapy has revolutionized cancer treatment and rejuvenated the field of tumor immunology.Several types of immunotherapy,including adoptive cell transfer(ACT)and immune checkpoint inhibitors(ICIs),have obtained durable clinical responses,but their efficacies vary,and only subsets of cancer patients can benefit from them.Immune infiltrates in the tumor microenvironment(TME)have been shown to play a key role in tumor development and will affect the clinical outcomes of cancer patients.Comprehensive profiling of tumor-infiltrating immune cells would shed light on the mechanisms of cancer–immune evasion,thus providing opportunities for the development of novel therapeutic strategies.However,the highly heterogeneous and dynamic nature of the TME impedes the precise dissection of intratumoral immune cells.With recent advances in single-cell technologies such as single-cell RNA sequencing(scRNA-seq)and mass cytometry,systematic interrogation of the TME is feasible and will provide insights into the functional diversities of tumor-infiltrating immune cells.In this review,we outline the recent progress in cancer immunotherapy,particularly by focusing on landmark studies and the recent single-cell characterization of tumor-associated immune cells,and we summarize the phenotypic diversities of intratumoral immune cells and their connections with cancer immunotherapy.We believe such a review could strengthen our understanding of the progress in cancer immunotherapy,facilitate the elucidation of immune cell modulation in tumor progression,and thus guide the development of novel immunotherapies for cancer treatment.
文摘Plant phenotypic plasticity is controlled by diverse hormone pathways, which integrate and convey infor- mation from multiple developmental and environmental signals. Moreover, in plants many processes such as growth, development, and defense are regulated in similar ways by multiple hormones. Among them, gibberellins （GAs） are phytohormones with pleiotropic actions, regulating various growth processes throughout the plant life cycle. Previous work has revealed extensive interplay between GAs and other hor- mones, but the molecular mechanism became apparent only recently. Molecular and physiological studies have demonstrated that DELLA proteins, considered as master negative regulators of GA signaling, inte- grate multiple hormone signaling pathways through physical interactions with transcription factors or reg- ulatory proteins from different families. In this review, we summarize the latest progress in GA signaling and its direct crosstalk with the main phytohormone signaling, emphasizing the multifaceted role of DELLA proteins with key components of major hormone signaling pathways.
基金supported by the Strategic Program of Molecular Module-Based Designer Breeding Systems(XDA08040107)the Instrument Developing Project of the Chinese Academy of Sciences(2014129)
文摘With the growing population and the reducing arable land, breeding has been considered as an effective way to solve the food crisis.As an important part in breeding, high-throughput phenotyping can accelerate the breeding process effectively. Light detection and ranging(LiDAR) is an active remote sensing technology that is capable of acquiring three-dimensional(3 D) data accurately,and has a great potential in crop phenotyping. Given that crop phenotyping based on LiDAR technology is not common in China,we developed a high-throughput crop phenotyping platform, named Crop 3 D, which integrated LiDAR sensor, high-resolution camera, thermal camera and hyperspectral imager. Compared with traditional crop phenotyping techniques, Crop 3 D can acquire multi-source phenotypic data in the whole crop growing period and extract plant height, plant width, leaf length, leaf width, leaf area, leaf inclination angle and other parameters for plant biology and genomics analysis. In this paper, we described the designs,functions and testing results of the Crop 3 D platform, and briefly discussed the potential applications and future development of the platform in phenotyping. We concluded that platforms integrating LiDAR and traditional remote sensing techniques might be the future trend of crop high-throughput phenotyping.
基金financially supported by the Major Science and Technology Project(No.2010C12009)Agricultural New Varieties Breeding Project(No.2012C12908-4)Key Research and Development Plan(No.2017C02028)of Zhejiang Province,China
文摘Phoebe bournei（Hemsl.） Yang is a rare and protected plant in China. This study was conducted to determine the phenotypic variation in this species and to document phenotypic variation within and among populations of P. bournei. Nested analysis of variance, coefficient of variation, multiple comparisons, principal component analysis（PCA） and correlation analysis were used to analyze ten phenotypic traits in ten natural populations of P.bournei from both the northeastern and the primary region of the range of this species. Significant differences among and within populations were observed in leaf and seed phenotypic traits. Variation among populations（34.92%）was greater than that within populations（26.19%）. The mean phenotypic differentiation coefficient was 53.77% among populations, indicating that variation among populations comprised the majority of the phenotypic variation of P. bournei. The coefficient of variance（CV） of ten traits varied from 6.44 to 18.45%, with an average of 12.03%.The CV of leaf traits among populations（15.64%） was higher than that of seed traits（8.60%）, indicating that seed traits were more stable. The results from CV and PCA indicated that leaf area, leaf length and thousand seed weight were the main factors accounting for the observed phenotypic variations. Significant or highly significant correlations were observed among most leaf and/or in seed phenotypic traits, whereas no significant correlations were observed between phenotypic traits and geographic factors.Based on cluster analysis, the ten populations can be divided into three clusters. These clusters were not a result of geographic distances.
基金Swiss National Science Foundation(grant 110000 to A.G.)the European Commission(FP6 projects MACIS and ECOCHANGE).
文摘Aims In perennial species,the allocation of resources to reproduction results in a reduction of allocation to vegetative growth and,therefore,impacts future reproductive success.As a consequence,variation in this trade-off is among the most important driving forces in the life-history evolution of perennial plants and can lead to locally adapted genotypes.In addition to genetic variation,phenotypic plasticity might also contribute to local adaptation of plants to local conditions by mediating changes in reproductive allocation.Knowledge on the importance of genetic and environmental effects on the tradeoff between reproduction and vegetative growth is therefore essential to understand how plants may respond to environmental changes.Methods We conducted a transplant experiment along an altitudinal gradient from 425to1921 min the frontrange of the Western Alps of Switzerland to assess the influence of both altitudinal origin of populations and altitude of growing site on growth,reproductive investment and local adaptation in Poa alpina.Important findings In our study,the investment in reproduction increased with plant size.Plant growth and the relative importance of reproductive investment decreased in populations originating from higher altitudes compared to populations originating from lower altitudes.The changes in reproductive investment were mainly explained by differences in plant size.In contrast to genetic effects,phenotypic plasticity of all traits measured was low and not related to altitude.As a result,the population from the lowest altitude of origin performed best at all sites.Our results indicate that in P.alpina genetic differences in growth and reproductive investment are related to local conditions affecting growth,i.e.interspecific competition and soil moisture content.
基金Supported by National Science Council, Yen-Tj ing-Ling Medical Foundation and Taipei Veterans General Hospital
文摘AIM： To isolate putative pancreatic stem cells （PSCs） from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well. METHODS： By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The MatrigelTM was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting （FACS） was used to detect the phenotypic markers of putative PSCs. RESULTS： A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin. They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29, CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 （SH2）, CD81, CD105（SH3）. CONCLUSION： In this study, we successfully isolated PSCs from adult human pancreatic duct by using serumfree medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.
基金supported by Bill&Melinda Gates Foundation Tuberculosis Prevention and Control Project(2009-04-01)
文摘In order to evaluate the performance of a molecular Hain line probe assay （Hain LPA） for rapid detection of rifampicin and isoniazid resistance of Mycobocterium tuberculosis in China, 1612 smear positive patients were consecutively enrolled in this study. Smear positive sputum specimens were collected for Hain LPA and conventional drug susceptibility testing （DST）. The sensitivity and specificity of Hain LPA were analyzed by using conventional DST as golden reference. The sensitivity, specificity, positive predictive value {PPV） and negative predictive value （NPV） for rifampicin resistance detection were 88.33%, 97.66%, 81.54%, and 98.62%, respectively. The sensitivity, specificity, PPV and NPV for isoniazid resistance detection were 80.25%, 98.07%, 87.25%, and 96.78%, respectively. These findings suggested that Hain LPA can be an effective method worthy of broader use in China.
基金supported by the National Natural Science Foundation of China(3121010390131123007)+2 种基金the National Basic Research Program of China(2013CB835200)the State Key Laboratory of Plant Genomics(2015B0129-01)Liya Wei was supported by the China Postdoctoral Science Foundation(2015M570170)
文摘Transposable elements(TEs), originally discovered in maize as controlling elements, are the main components of most eukaryotic genomes. TEs have been regarded as deleterious genomic parasites due to their ability to undergo massive amplification. However, TEs can regulate gene expression and alter phenotypes. Also, emerging findings demonstrate that TEs can establish and rewire gene regulatory networks by genetic and epigenetic mechanisms. In this review, we summarize the key roles of TEs in fine-tuning the regulation of gene expression leading to phenotypic plasticity in plants and humans, and the implications for adaption and natural selection.
文摘Manifestations of diseases are determined by the .combined effect of genetic and environmentalfactors. Different physical, behavioral and social variations affect the prevalence and presentation of common diseases. Polycystic ovary syndrome （PCOS）, with a heterogeneous presentation, is the most common endocrine disorder that affects about 5%-10% women of reproductive age. It is characterized by clinical and/or biochemical hyperandrogenism, ovulatory dysfunction and polycystic ovaries.
