The measurement of black carbon (BC) and organic carbon (OC), dust in total suspended particulates (TSP) was carried out at Yulong Snow Mountain (Mt. Yulong) and Ganhaizi Basin, in the Mt. Yulong region, south...The measurement of black carbon (BC) and organic carbon (OC), dust in total suspended particulates (TSP) was carried out at Yulong Snow Mountain (Mt. Yulong) and Ganhaizi Basin, in the Mt. Yulong region, southwestern China. TSP samples were analyzed using a thermal/optical reflectance carbon analyzer. Results show that average BC and OC concentrations in TSP in the Mt. Yulong region were 1.61±1.15 μg/m3 and 2.96±1.59 μg/m3, respectively. Statistical results demonstrated that there were significant differences in mean BC and OC contents between Ganhaizi Basin and Mt. Yulong at the 0.05 level. Strong correlations between BC and OC indicate their common dominant emission sources and transport processes. Temporal variations ofBC, OC, and optical attenuation (ATN) values were consistent with each other in carbonaceous aerosols. The ratios of OC/BC in monsoon season were significantly higher than in non-monsoon in aerosols from Ganhaizi, which is closely related to the formation of secondary organic carbon (SOC) and extensive motor vehicle emissions from tourism activities. The temporal variations of BC, OC and ATN in carbonaceous aerosols in Ganhaizi and Mt. Yulong were totally different, probably due to elevation difference and diverse tourism activity intensity between the two sites. Time-averaged aerosol optical depth (AOD) at the wavelength of 550 nm in Mt. Yulong was higher than that of the inland of the Tibetan Plateau (TP). Source apportionment indicated that intensive exhaust emissions from tourism vehicles were the main local sources of atmospheric pollutant in the Mt. Yulong region. Biomass-burning emissions released from South Asia could penetrate into the inland of the TP under the transport of summer monsoon. Further study is needed to assess light absorption and radiative forcing of carbonaceous aerosols, and modeling research in combination with long-term in-situ observations of light-absorbing particulates (LAPs) in the TP is also urgently needed in future work.展开更多
To stop the decline of swimming crab(Portunus trituberculatus)stocks in the East China Sea,escape vents on crab pots are urgently required to improve pot selectivity and enable release of sublegal-sized crabs.This stu...To stop the decline of swimming crab(Portunus trituberculatus)stocks in the East China Sea,escape vents on crab pots are urgently required to improve pot selectivity and enable release of sublegal-sized crabs.This study presents field comparative fishing experiments,which examined the effectiveness of different shapes and sizes of escape vents in crab pots for the release of swimming crabs.Two sizes each of rectangular,elliptic,and circular escape vents were tested.The results of comparative fishing experiments indicated that experimental pots with escape vents,regardless of their configuration,caught significantly fewer sublegal-sized crabs(<49 mm carapace length,or<116 mm carapace width)than unmodified control pots.Although legal-sized swimming crabs were also less caught,analysis of size selectivity showed that rectangular vents produced steeper selectivity curves than elliptic and circular escape vents.This indicates that rectangular vents may be more suitable and controllable when escape vents will become a requirement and their use will be enforced in fisheries.Underwater observations were conducted using GoPro cameras and LED lights during the first 2.5 h of the deployments(which usually lasted between 5 and 12 h).Video recordings of experimental pots equipped with rectangular or elliptic escape vents showed that swimming crabs trapped in the pots could detect the vents,and readily approached and passed through these.However,no significant difference was detected in the response behavior of swimming crabs between rectangular and elliptic vent pots when quantitative indicators,derived from video recordings,were compared.The effect of different vent shapes on the escape behavior of swimming crab gradually manifested as an increased soak time and by the onset of the escape of larger crabs.Future underwater observations should thus last the entire duration of pot soaking to study how crabs escape from the pots.展开更多
Sjögren’s syndrome(SS)is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands.Our previous studies showed that myeloid-derived suppress...Sjögren’s syndrome(SS)is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands.Our previous studies showed that myeloid-derived suppressor cells(MDSCs)exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren’s syndrome(ESS),but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS.In this study,we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes(OE-MSC-Exos)significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels.Moreover,treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice.Mechanistically,OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs.In addition,the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling,indicating an autocrine pathway of MDSC functional modulation by IL-6.Taken together,our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs,possibly constituting a new strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases.展开更多
The northwestward subduction of the Izanagi Plate beneath the eastern Eurasian Plate during the Late Mesozoic caused a series of compressional deformation events in the Yanshan fold and thrust belt(YFTB), but the tect...The northwestward subduction of the Izanagi Plate beneath the eastern Eurasian Plate during the Late Mesozoic caused a series of compressional deformation events in the Yanshan fold and thrust belt(YFTB), but the tectonic deformation timing, tectonic properties and relationship between tectonic uplift and sediment accumulation in the intermontane basins continue to be debated. For this reason, the sedimentology, sediment provenance, and basin structure of the Qianjiadian Basin(QJB) in the northern Beijing region during the Late Jurassic and Early Cretaceous were studied in detail. The results suggest that a fault-propagation fold-type(FPFT) growth structure and growth strata developed on the western edge of the QJB and that the top part of Member 2 and Member 3 of the Tuchengzi Formation are growth strata controlled by the limb rotation mechanism. In two small thrust faults in the QJB, the Mesoproterozoic Xiamaling Formation is thrust over the Tuchengzi Formation, and these faults may have controlled the development of the fault-bend fold-type growth strata. An analysis of the "source-to-sink" process suggests that the hanging wall succession of the Shangyi-Pingquan fault(SPF) was the main source area of the Late Jurassic to early Early Cretaceous strata in the QJB. A zircon206 Pb/238 U age of 140.8±2.4 Ma for the volcanic rocks at the bottom of the FPFT growth strata represents the timing of the initiation of FPFT growth structure development. The discovery of the FPFT growth structure and growth strata in the QJB indicate that the QJB was an intermontane flexural basin controlled by fold and thrust structures during the early Early Cretaceous. Near the E-W-trending SPF, the NE-SW-trending Qianjiadian thrust fault(QJTF) and two small intrabasinal thrust faults may constitute a unified right-lateral strike-slip system that formed in response to the northwestward flat subduction of the Izanagi Plate beneath the East Asian continent during the Jurassic-Early Cretaceous.展开更多
Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoi...Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear.Here,we first found negative correlations between IL-10^(+)regulatory B(Breg)cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome(ESS).Moreover,we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice.In culture,IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation.By using an adoptive transfer approach and two-photon live imaging,we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/−mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/−mice transferred with wild-type B cells.In ESS mice,CD19^(+)CD1d^(hi)CD5^(+)Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation.Consistently,CD19^(+)CD24^(+)CD38^(hi) Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion.Furthermore,the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice.Together,these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.展开更多
The generation and function of plasma cells have been well recognized as the central events in humoral immunity.In particular,long-lived plasma cells,characterized by a long lifespan and the lack of cell division,pers...The generation and function of plasma cells have been well recognized as the central events in humoral immunity.In particular,long-lived plasma cells,characterized by a long lifespan and the lack of cell division,persistently secrete high-affinity antibodies to maintain serum antibody titers in the immune response and autoimmune inflammation.Although the significant expansion of plasma cells is observed during the aging process,autoimmune diseases and chronic infections,the expanding functional diversity and underlying mechanisms of plasma cells remain incompletely understood.Here,we describe recent advances in revealing new functional subsets and phenotypic features of plasma cells in aging and autoimmunity.展开更多
B cells play a pivotal role in the pathogenesis of autoimmune diseases.Although previous studies have shown many genetic polymorphisms associated with B-cell activation in patients with various autoimmune disorders,pr...B cells play a pivotal role in the pathogenesis of autoimmune diseases.Although previous studies have shown many genetic polymorphisms associated with B-cell activation in patients with various autoimmune disorders,progress in epigenetic research has revealed new mechanisms leading to B-cell hyperactivation.Epigenetic mechanisms,including those involving histone modifications,DNA methylation,and noncoding RNAs,regulate B-cell responses,and their dysregulation can contribute to the pathogenesis of autoimmune diseases.Patients with autoimmune diseases show epigenetic alterations that lead to the initiation and perpetuation of autoimmune inflammation.Moreover,many clinical and animal model studies have shown the promising potential of epigenetic therapies for patients.In this review,we present an up-to-date overview of epigenetic mechanisms with a focus on their roles in regulating functional B-cell subsets.Furthermore,we discuss epigenetic dysregulation in B cells and highlight its contribution to the development of autoimmune diseases.Based on clinical and preclinical evidence,we discuss novel epigenetic biomarkers and therapies for patients with autoimmune disorders.展开更多
This article explores crossover literature, that is, literature transcending age boundaries and, in particular, the boundaries between adult and child readership. This article suggests that texts transcending age boun...This article explores crossover literature, that is, literature transcending age boundaries and, in particular, the boundaries between adult and child readership. This article suggests that texts transcending age boundaries are not a recent phenomenon—adults have almost always existed in children’s literature as a background authority or a hidden and even active addressee. But it is the changes in a social, historical, and cultural context that call for a new term, crossover, to designate this phenomenon. Central to the discussion of crossover literature is how to conceptualise the different readings that a text can elicit from child and adult readers. Drawing on developments in cognitive literary studies, this article argues that crossover literature is characterised by its potential to accommodate both child and adult readers’ different levels of cognitive-affective development, subject to the factor of age. The argument is exemplified with a close analysis of Anthony Browne’s picturebook The Big Baby(1995). It is particularly productive and illuminating to discuss how crossover picturebooks can attract both children and adults, contrary to the traditional assumption that picturebooks are merely 'kids’ stuff.' The close analysis of The Big Baby reveals that cognitive literary studies can tease out the implications of the age difference, which are crucial to crossover research, and shed new light on how crossover literature may attract readers of different ages.展开更多
This article investigates the picturebook as the aesthetic object that integrates the verbal narrative and the visual narrative, and hinges on interactions between the two levels of narratives. Often drawing on the th...This article investigates the picturebook as the aesthetic object that integrates the verbal narrative and the visual narrative, and hinges on interactions between the two levels of narratives. Often drawing on the theory of semiotics, picturebook scholars have revealed the complex interactions between the verbal and the visual, the demands that a picturebook may put on the reader, and the hermeneutic nature of picturebook reading. Two signifi cant issues, however, still need to be further explored: why the reader can possibly relate and integrate the verbal and the visual, and why some readers may turn to pictures more than to words, or vice versa. I propose to explore the two issues primarily through the model of double-scope stories within the theoretical framework of cognitive criticism. I argue that the universality of the intellectual and imaginative activity of conceptual blending makes it possible for the reader to relate pictures to words, or vice versa, and to integrate them. Though to make meaning from the picturebook as a double-scope story requires the reader to integrate the two levels of narratives, the verbal and the visual can sometimes constitute two relatively independent input stories. Readers may be more oriented towards either one of them, partially due to the difference in their innate cognitive structures. The arguments will be illustrated with a close analysis of Lane Smith's picturebook Grandpa Green.展开更多
Crossover picturebooks attract readers of different ages.The trend of refocusing on the body in children’s literature criticism,especially under the influence of literary cognitive studies as Maria Nikolajeva points ...Crossover picturebooks attract readers of different ages.The trend of refocusing on the body in children’s literature criticism,especially under the influence of literary cognitive studies as Maria Nikolajeva points out(2016),provides a context to reconfigure our understanding of crossover picturebooks.Informed by literary cognitive studies,particularly the theory of brain laterality,the project selects the picturebook that may have crossover potential to start with,then investigates the actual readers’engagement with the potentially crossover picturebook,and finally feeds the insights gleaned from the empirical study back into the understanding of the selected text,and possibly crossover picturebooks generally.The project aims to learn about the crossover picturebook through exploring how it impacts readers.It was a small-scale case study,conducted in the east of England,UK.Colin Thompson’s How to Live Forever was used with two adults and two children.Observation and interviewing were used to collect data.Text-related creative activities served to support or clarify the oral response.The project reveals:the multileveled nature of crossover picturebooks that many scholars emphasize may correspond to the multileveled engagement that texts can elicit from readers,which is partially the outcome of cognitive-affective skills and mechanisms engaged differently across children and adults.This study also shows the crossover potential particular to picturebooks:picturebooks may use the visual to flesh out the embodied experience,which can springboard further thinking about abstract,complicated notions.This mode of representation corresponds to the way the human mind works,thus engaging children and adults alike.展开更多
基金supported by the National Natural Science Foundation of China(41601071,41721091)the Key Research Program for Frontier Science of Chinese Academy of Sciences(QYZDJ-SSWDQC039)+2 种基金the independent program of SKLCS(SKLCS-ZZ-2018)the CAS"Light of West China"Program(Y62992)Postdoctoral Science Foundation(2015M582725,2016T90963)
文摘The measurement of black carbon (BC) and organic carbon (OC), dust in total suspended particulates (TSP) was carried out at Yulong Snow Mountain (Mt. Yulong) and Ganhaizi Basin, in the Mt. Yulong region, southwestern China. TSP samples were analyzed using a thermal/optical reflectance carbon analyzer. Results show that average BC and OC concentrations in TSP in the Mt. Yulong region were 1.61±1.15 μg/m3 and 2.96±1.59 μg/m3, respectively. Statistical results demonstrated that there were significant differences in mean BC and OC contents between Ganhaizi Basin and Mt. Yulong at the 0.05 level. Strong correlations between BC and OC indicate their common dominant emission sources and transport processes. Temporal variations ofBC, OC, and optical attenuation (ATN) values were consistent with each other in carbonaceous aerosols. The ratios of OC/BC in monsoon season were significantly higher than in non-monsoon in aerosols from Ganhaizi, which is closely related to the formation of secondary organic carbon (SOC) and extensive motor vehicle emissions from tourism activities. The temporal variations of BC, OC and ATN in carbonaceous aerosols in Ganhaizi and Mt. Yulong were totally different, probably due to elevation difference and diverse tourism activity intensity between the two sites. Time-averaged aerosol optical depth (AOD) at the wavelength of 550 nm in Mt. Yulong was higher than that of the inland of the Tibetan Plateau (TP). Source apportionment indicated that intensive exhaust emissions from tourism vehicles were the main local sources of atmospheric pollutant in the Mt. Yulong region. Biomass-burning emissions released from South Asia could penetrate into the inland of the TP under the transport of summer monsoon. Further study is needed to assess light absorption and radiative forcing of carbonaceous aerosols, and modeling research in combination with long-term in-situ observations of light-absorbing particulates (LAPs) in the TP is also urgently needed in future work.
基金study was jointly funded by the National Natural Science Foundation of China(31001138)the National Key Research and Development Program of China(2020YFD0900803).
文摘To stop the decline of swimming crab(Portunus trituberculatus)stocks in the East China Sea,escape vents on crab pots are urgently required to improve pot selectivity and enable release of sublegal-sized crabs.This study presents field comparative fishing experiments,which examined the effectiveness of different shapes and sizes of escape vents in crab pots for the release of swimming crabs.Two sizes each of rectangular,elliptic,and circular escape vents were tested.The results of comparative fishing experiments indicated that experimental pots with escape vents,regardless of their configuration,caught significantly fewer sublegal-sized crabs(<49 mm carapace length,or<116 mm carapace width)than unmodified control pots.Although legal-sized swimming crabs were also less caught,analysis of size selectivity showed that rectangular vents produced steeper selectivity curves than elliptic and circular escape vents.This indicates that rectangular vents may be more suitable and controllable when escape vents will become a requirement and their use will be enforced in fisheries.Underwater observations were conducted using GoPro cameras and LED lights during the first 2.5 h of the deployments(which usually lasted between 5 and 12 h).Video recordings of experimental pots equipped with rectangular or elliptic escape vents showed that swimming crabs trapped in the pots could detect the vents,and readily approached and passed through these.However,no significant difference was detected in the response behavior of swimming crabs between rectangular and elliptic vent pots when quantitative indicators,derived from video recordings,were compared.The effect of different vent shapes on the escape behavior of swimming crab gradually manifested as an increased soak time and by the onset of the escape of larger crabs.Future underwater observations should thus last the entire duration of pot soaking to study how crabs escape from the pots.
基金This work was supported by the National Natural Science Foundation of China(Grant nos.81701612,81971542,81702080,and 82071817)Natural Science Foundation of Jiangsu(Grant no.BK20170563)+2 种基金Chongqing International Institute for Immunology(2020YJC10)Summit of the Six Top Talents Program of Jiangsu Province(Grant no.2017-YY-006)Youth Science and Technology Talent Promotion Project of Jiangsu and Hong Kong Croucher Foundation(Grant no.260960116).
文摘Sjögren’s syndrome(SS)is a systemic autoimmune disease characterized by progressive inflammation and tissue damage in salivary glands and lacrimal glands.Our previous studies showed that myeloid-derived suppressor cells(MDSCs)exhibited impaired immunosuppressive function during disease progression in patients with SS and mice with experimental Sjögren’s syndrome(ESS),but it remains unclear whether restoring the function of MDSCs can effectively ameliorate the development of ESS.In this study,we found that murine olfactory ecto-mesenchymal stem cell-derived exosomes(OE-MSC-Exos)significantly enhanced the suppressive function of MDSCs by upregulating arginase expression and increasing ROS and NO levels.Moreover,treatment with OE-MSC-Exos via intravenous injection markedly attenuated disease progression and restored MDSC function in ESS mice.Mechanistically,OE-MSC-Exo-secreted IL-6 activated the Jak2/Stat3 pathway in MDSCs.In addition,the abundant S100A4 in OE-MSC-Exos acted as a key factor in mediating the endogenous production of IL-6 by MDSCs via TLR4 signaling,indicating an autocrine pathway of MDSC functional modulation by IL-6.Taken together,our results demonstrated that OE-MSC-Exos possess therapeutic potential to attenuate ESS progression by enhancing the immunosuppressive function of MDSCs,possibly constituting a new strategy for the treatment of Sjögren’s syndrome and other autoimmune diseases.
基金supported by the National Key Research and Development Project (Grant No. 2017YFC0601405)the National Natural Science Foundation of China (Grant Nos. 41572189 & 41820104004)the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant No. XDB18030604)
文摘The northwestward subduction of the Izanagi Plate beneath the eastern Eurasian Plate during the Late Mesozoic caused a series of compressional deformation events in the Yanshan fold and thrust belt(YFTB), but the tectonic deformation timing, tectonic properties and relationship between tectonic uplift and sediment accumulation in the intermontane basins continue to be debated. For this reason, the sedimentology, sediment provenance, and basin structure of the Qianjiadian Basin(QJB) in the northern Beijing region during the Late Jurassic and Early Cretaceous were studied in detail. The results suggest that a fault-propagation fold-type(FPFT) growth structure and growth strata developed on the western edge of the QJB and that the top part of Member 2 and Member 3 of the Tuchengzi Formation are growth strata controlled by the limb rotation mechanism. In two small thrust faults in the QJB, the Mesoproterozoic Xiamaling Formation is thrust over the Tuchengzi Formation, and these faults may have controlled the development of the fault-bend fold-type growth strata. An analysis of the "source-to-sink" process suggests that the hanging wall succession of the Shangyi-Pingquan fault(SPF) was the main source area of the Late Jurassic to early Early Cretaceous strata in the QJB. A zircon206 Pb/238 U age of 140.8±2.4 Ma for the volcanic rocks at the bottom of the FPFT growth strata represents the timing of the initiation of FPFT growth structure development. The discovery of the FPFT growth structure and growth strata in the QJB indicate that the QJB was an intermontane flexural basin controlled by fold and thrust structures during the early Early Cretaceous. Near the E-W-trending SPF, the NE-SW-trending Qianjiadian thrust fault(QJTF) and two small intrabasinal thrust faults may constitute a unified right-lateral strike-slip system that formed in response to the northwestward flat subduction of the Izanagi Plate beneath the East Asian continent during the Jurassic-Early Cretaceous.
基金supported by grants from the National Natural Science Foundation of China(81771761 and 91842304)Chinese National Key Technology R&D Program,Ministry of Science and Technology(2017YFC0907601 and 2017YFC0907605)+2 种基金General Research Fund,Hong Kong Research Grants Council(17114515 and 17149716)Hong Kong Croucher Foundation(260960116)Sanming Project of Medicine in Shenzhen(SZSM201512019).
文摘Increased numbers of T follicular helper(Tfh)cells have been implicated in the development of autoimmune diseases including primary Sjögren’s syndrome(pSS),but how the Tfh cell response is regulated during autoimmune pathogenesis remains largely unclear.Here,we first found negative correlations between IL-10^(+)regulatory B(Breg)cell numbers and Tfh cell responses and disease activity in patients with pSS and mice with experimental Sjögren’s syndrome(ESS).Moreover,we detected high expression of IL-10 receptor on Tfh cells and their precursors in both humans and mice.In culture,IL-10 suppressed human and murine Tfh cell differentiation by promoting STAT5 phosphorylation.By using an adoptive transfer approach and two-photon live imaging,we found significantly increased numbers of Tfh cells with enhanced T cell homing into B cell follicles in the draining cervical lymph nodes of RAG-2−/−mice transferred with IL-10-deficient B cells during ESS development compared with those of RAG-2−/−mice transferred with wild-type B cells.In ESS mice,CD19^(+)CD1d^(hi)CD5^(+)Breg cells with decreased IL-10 production exhibited severely impaired suppressive effects on T cell proliferation.Consistently,CD19^(+)CD24^(+)CD38^(hi) Breg cells from pSS patients showed significantly reduced IL-10 production with defective inhibitory function in the suppression of autologous Tfh cell expansion.Furthermore,the adoptive transfer of IL-10-producing Breg cells markedly suppressed the Tfh cell response and ameliorated ESS progression in ESS mice.Together,these findings demonstrate a critical role for IL-10-producing Breg cells in restraining the effector Tfh cell response during pSS development.
基金supported by grants from the National Natural Science Foundation of China(No.91842304,81771761,and 81901635)the Hong Kong SAR Government(No.17114515)HKU Seed Funding for Strategic Interdisciplinary Research Scheme and the Hong Kong Croucher Foundation(260960116).
文摘The generation and function of plasma cells have been well recognized as the central events in humoral immunity.In particular,long-lived plasma cells,characterized by a long lifespan and the lack of cell division,persistently secrete high-affinity antibodies to maintain serum antibody titers in the immune response and autoimmune inflammation.Although the significant expansion of plasma cells is observed during the aging process,autoimmune diseases and chronic infections,the expanding functional diversity and underlying mechanisms of plasma cells remain incompletely understood.Here,we describe recent advances in revealing new functional subsets and phenotypic features of plasma cells in aging and autoimmunity.
基金This work was supported by Chongqing International Institute for Immunology(2020YJC10)National Natural Science Foundation of China(82071817,91842304,82171771,and 82271854)+2 种基金Shenzhen Science and Technology Program(JCYJ20210324114602008)Hong Kong Research Grants Council(17113319 and 17103821),RGC Theme-based Research Scheme(TRS)(T12-703/19-R)the Centre for Oncology and Immunology under the Health@InnoHK Initiative funded by the Innovation and Technology Commission,Hong Kong,China.The figures were created with BioRender.com.
文摘B cells play a pivotal role in the pathogenesis of autoimmune diseases.Although previous studies have shown many genetic polymorphisms associated with B-cell activation in patients with various autoimmune disorders,progress in epigenetic research has revealed new mechanisms leading to B-cell hyperactivation.Epigenetic mechanisms,including those involving histone modifications,DNA methylation,and noncoding RNAs,regulate B-cell responses,and their dysregulation can contribute to the pathogenesis of autoimmune diseases.Patients with autoimmune diseases show epigenetic alterations that lead to the initiation and perpetuation of autoimmune inflammation.Moreover,many clinical and animal model studies have shown the promising potential of epigenetic therapies for patients.In this review,we present an up-to-date overview of epigenetic mechanisms with a focus on their roles in regulating functional B-cell subsets.Furthermore,we discuss epigenetic dysregulation in B cells and highlight its contribution to the development of autoimmune diseases.Based on clinical and preclinical evidence,we discuss novel epigenetic biomarkers and therapies for patients with autoimmune disorders.
基金part of the research project “Contemporary Western Picturebook Theory”(18WWC005) funded by Jiangsu Planning Office of Philosophy and Social Sciencethe project “Chinese Picturebooks and Their English Translations”(2017SJB1318) funded by Jiangsu Education Department
文摘This article explores crossover literature, that is, literature transcending age boundaries and, in particular, the boundaries between adult and child readership. This article suggests that texts transcending age boundaries are not a recent phenomenon—adults have almost always existed in children’s literature as a background authority or a hidden and even active addressee. But it is the changes in a social, historical, and cultural context that call for a new term, crossover, to designate this phenomenon. Central to the discussion of crossover literature is how to conceptualise the different readings that a text can elicit from child and adult readers. Drawing on developments in cognitive literary studies, this article argues that crossover literature is characterised by its potential to accommodate both child and adult readers’ different levels of cognitive-affective development, subject to the factor of age. The argument is exemplified with a close analysis of Anthony Browne’s picturebook The Big Baby(1995). It is particularly productive and illuminating to discuss how crossover picturebooks can attract both children and adults, contrary to the traditional assumption that picturebooks are merely 'kids’ stuff.' The close analysis of The Big Baby reveals that cognitive literary studies can tease out the implications of the age difference, which are crucial to crossover research, and shed new light on how crossover literature may attract readers of different ages.
文摘This article investigates the picturebook as the aesthetic object that integrates the verbal narrative and the visual narrative, and hinges on interactions between the two levels of narratives. Often drawing on the theory of semiotics, picturebook scholars have revealed the complex interactions between the verbal and the visual, the demands that a picturebook may put on the reader, and the hermeneutic nature of picturebook reading. Two signifi cant issues, however, still need to be further explored: why the reader can possibly relate and integrate the verbal and the visual, and why some readers may turn to pictures more than to words, or vice versa. I propose to explore the two issues primarily through the model of double-scope stories within the theoretical framework of cognitive criticism. I argue that the universality of the intellectual and imaginative activity of conceptual blending makes it possible for the reader to relate pictures to words, or vice versa, and to integrate them. Though to make meaning from the picturebook as a double-scope story requires the reader to integrate the two levels of narratives, the verbal and the visual can sometimes constitute two relatively independent input stories. Readers may be more oriented towards either one of them, partially due to the difference in their innate cognitive structures. The arguments will be illustrated with a close analysis of Lane Smith's picturebook Grandpa Green.
基金The writing up of this study is supported by the research project“Contemporary Western Picturebook Theory”(18WWC005)funded by Jiangsu Planning Office of Philosophy and Social Science and the project“Chinese Picturebooks and Their English Translations”(2017SJB1318)funded by Jiangsu Education Department。
文摘Crossover picturebooks attract readers of different ages.The trend of refocusing on the body in children’s literature criticism,especially under the influence of literary cognitive studies as Maria Nikolajeva points out(2016),provides a context to reconfigure our understanding of crossover picturebooks.Informed by literary cognitive studies,particularly the theory of brain laterality,the project selects the picturebook that may have crossover potential to start with,then investigates the actual readers’engagement with the potentially crossover picturebook,and finally feeds the insights gleaned from the empirical study back into the understanding of the selected text,and possibly crossover picturebooks generally.The project aims to learn about the crossover picturebook through exploring how it impacts readers.It was a small-scale case study,conducted in the east of England,UK.Colin Thompson’s How to Live Forever was used with two adults and two children.Observation and interviewing were used to collect data.Text-related creative activities served to support or clarify the oral response.The project reveals:the multileveled nature of crossover picturebooks that many scholars emphasize may correspond to the multileveled engagement that texts can elicit from readers,which is partially the outcome of cognitive-affective skills and mechanisms engaged differently across children and adults.This study also shows the crossover potential particular to picturebooks:picturebooks may use the visual to flesh out the embodied experience,which can springboard further thinking about abstract,complicated notions.This mode of representation corresponds to the way the human mind works,thus engaging children and adults alike.