Phaeocystis is an important bloom-forming species and over 100 blooms have occurred since 1997 along the Chinese coasts,while only the species P.globosa was described.In this project,a total of 246 phytoplankton sampl...Phaeocystis is an important bloom-forming species and over 100 blooms have occurred since 1997 along the Chinese coasts,while only the species P.globosa was described.In this project,a total of 246 phytoplankton samples collected from the Bohai Sea,the Yellow Sea,and the East China Sea in April 2021 were analyzed to evaluate the species diversity and geographical distribution of the genus Phaeocystis based on metabarcoding 18S r DNA sequence.Four described Phaeocystis species were recognized,including P.globosa,P.pouchetii,P.jahnii,and P.cordata,and each has distinguished geographical distribution characteristics.P.globosa was the most widespread and abundant species,and P.pouchetii was found in the Bohai Sea and the northern Yellow Sea with substantially elevated abundance.P.cordata was also a widespread species,but its abundance was relatively low,while P.jahnii gathered only in the southeastern East China Sea.Water temperature,phosphate as well as ammonium contents were found to be associated with the abundance of P.globosa,P.pouchetii,and P.jahnii significantly.Moreover,two uncharacterized Phaeocystis species were detected in the Chinese seas,indicating the diversity of the genus remains underestimated worldwide.展开更多
The microalga Phaeocystis globosa is recognized as a harmful alga and also one of the few keystone phytoplankton genera that shape the structure and function of marine ecosystems.P.globosa possess a complex polymorphi...The microalga Phaeocystis globosa is recognized as a harmful alga and also one of the few keystone phytoplankton genera that shape the structure and function of marine ecosystems.P.globosa possess a complex polymorphic life cycle,exhibiting phase alternation between free-living cells of approximately 3-6μm in diameter and gelatinous colonies(palmelloid stage)reaching several millimeters.The knowledge on the factors that induced the morphological transition of P.globosa in the last two decades was reviewed.Emphasis is given to infochemicals,an additional biological factor induced by predator,with the attempt to reveal a relevant mechanism of induced morphological defense.展开更多
Bioavailability of nitrogen (N) and phosphorus (P) is known to affect marine phytoplankton physiology, thus influencing their primary productivity;and it’s of general interest to see how the N or/and P additions affe...Bioavailability of nitrogen (N) and phosphorus (P) is known to affect marine phytoplankton physiology, thus influencing their primary productivity;and it’s of general interest to see how the N or/and P additions affect the differently cell-sized phytoplankton assemblages. Data from the northern South China Sea showed that P addition increased up to 6 times of total chl a content within 24 h in the estuarine water;and N+P addition increased more than 20 times of chl a within 144 h in the pelagic water. The P addition powered 18.0% and 149% increase in the carbon fixation of larger (>3 μm) and smaller (展开更多
Currently the main treatment of acute myeloid leukemia(AML)is chemotherapy combining hematopoietic stem cell transplantation.However,the unbearable side effect of chemotherapy and the high risk of life-threatening inf...Currently the main treatment of acute myeloid leukemia(AML)is chemotherapy combining hematopoietic stem cell transplantation.However,the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice.Thus,there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects.Here,we revealed that umbilical cord-derived mesenchymal stem cells(UC-MSC)efficiently induced AML cell differentiation by shuttling the neutrophil elastase(NE)-packaged extracellular vesicles(EVs)into AML cells.Interestingly,the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor(VDR)activation in UC-MSC.Chemical activation of VDR by using its agonist 1a,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model.Based on these discoveries,to evade the risk of hypercalcemia,we synthetized and identified sw-22,a novel non-steroidal VDR agonist,which exerted a synergistic prodifferentiation function with UC-MSC on mitigating the progress of AML.Collectively,our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.展开更多
Background:Interleukin-15(IL-15)is a promising immunotherapeutic agent owing to its powerful immune-activating effects.However,the clinical benefits of these treatments are limited.Crosstalk between tumor cells and im...Background:Interleukin-15(IL-15)is a promising immunotherapeutic agent owing to its powerful immune-activating effects.However,the clinical benefits of these treatments are limited.Crosstalk between tumor cells and immune cells plays an important role in immune escape and immunotherapy drug resistance.Herein,this study aimed to obtain in-depth understanding of crosstalk in the tumor microenvironment for providing potential therapeutic strategies to prevent tumor progression.Methods:T-cell killing assays and co-culture models were developed to determine the role of crosstalk between macrophages and tumor cells in breast cancer resistant to IL-15.Western blotting,histological analysis,CRISPR-Cas9 knockout,multi-parameter flow cytometry,and tumor cell-macrophage co-injection mouse models were developed to examine the mechanism by which IL-15Rα^(+)tumor-associated macrophages(TAMs)regulate breast cancer cell resistance to IL-15.Results:We found thatmacrophages contributed to the resistance of tumor cells to IL-15,and tumor cells induced macrophages to express high levels of theαsubunit of the IL-15 receptor(IL-15Rα).Further investigation showed that IL-15Rα^(+)TAMs reduced the protein levels of chemokine CX3C chemokine ligand 1(CX3CL1)in tumor cells to inhibit the recruitment of CD8^(+)T cells by releasing the IL-15/IL-15Rαcomplex(IL-15Rc).Administration of an IL-15Rc blocking peptide markedly suppressed breast tumor growth and overcame the resistance of cancer cells to anti-programmed cell death protein 1(PD-1)antibody immunotherapy.Interestingly,Granulocyte-macrophage colony-stimulating factor(GMCSF)inducedγchain(γc)expression to promote tumor cell-macrophage crosstalk,which facilitated tumor resistance to IL-15.Additionally,we observed that the non-transcriptional regulatory function of hypoxia inducible factor-1alpha(HIF-1α)was essential for IL-15Rc to regulateCX3CL1 expression in tumor cells.Conclusions:The IL-15Rc-HIF-1α-CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the tumormicroenvironment of breast cancer.Targeting this pathway may provide a potential therapeutic strategy for enhancing the efficacy of cancer immunotherapy.展开更多
Dear Editor,Tumor-associated macrophages(TAMs)are critical pro-tumor immunocytes and depletion of TAMs has been exploited for cancer therapy.1 However,the phenotypes and functions of TAMs are plastic,TAMs can also be ...Dear Editor,Tumor-associated macrophages(TAMs)are critical pro-tumor immunocytes and depletion of TAMs has been exploited for cancer therapy.1 However,the phenotypes and functions of TAMs are plastic,TAMs can also be effector cells by engulfing tumor cells and recruiting cytotoxic T cells,thus shaping the actions of TAMs is more scientific rational than depleting them indiscriminately.2 To promote the entry of reorienting TAMs into the clinical treatments of tumors,it is essential to explore the underline mechanisms controlling the anti-and pro-tumor activities of TAMs.展开更多
基金Supported by the National Natural Science Foundation of China(No.41976114)the Open Fund of Laboratory for Marine Ecology and Environmental ScienceQingdao National Laboratory for Marine Science and Technology(No.LMEES201803)。
文摘Phaeocystis is an important bloom-forming species and over 100 blooms have occurred since 1997 along the Chinese coasts,while only the species P.globosa was described.In this project,a total of 246 phytoplankton samples collected from the Bohai Sea,the Yellow Sea,and the East China Sea in April 2021 were analyzed to evaluate the species diversity and geographical distribution of the genus Phaeocystis based on metabarcoding 18S r DNA sequence.Four described Phaeocystis species were recognized,including P.globosa,P.pouchetii,P.jahnii,and P.cordata,and each has distinguished geographical distribution characteristics.P.globosa was the most widespread and abundant species,and P.pouchetii was found in the Bohai Sea and the northern Yellow Sea with substantially elevated abundance.P.cordata was also a widespread species,but its abundance was relatively low,while P.jahnii gathered only in the southeastern East China Sea.Water temperature,phosphate as well as ammonium contents were found to be associated with the abundance of P.globosa,P.pouchetii,and P.jahnii significantly.Moreover,two uncharacterized Phaeocystis species were detected in the Chinese seas,indicating the diversity of the genus remains underestimated worldwide.
基金Supported by the Key Deployment Project of Center for Ocean Mega-Science,Chinese Academy of Sciences(No.COMS2019R04)the National Overseas High-level Talent Project,Taishan Scholar Program from Shandong Province of China(No.tsqn20190403)the Shuangbai Plan from Yantai City(No.2018020)。
文摘The microalga Phaeocystis globosa is recognized as a harmful alga and also one of the few keystone phytoplankton genera that shape the structure and function of marine ecosystems.P.globosa possess a complex polymorphic life cycle,exhibiting phase alternation between free-living cells of approximately 3-6μm in diameter and gelatinous colonies(palmelloid stage)reaching several millimeters.The knowledge on the factors that induced the morphological transition of P.globosa in the last two decades was reviewed.Emphasis is given to infochemicals,an additional biological factor induced by predator,with the attempt to reveal a relevant mechanism of induced morphological defense.
文摘Bioavailability of nitrogen (N) and phosphorus (P) is known to affect marine phytoplankton physiology, thus influencing their primary productivity;and it’s of general interest to see how the N or/and P additions affect the differently cell-sized phytoplankton assemblages. Data from the northern South China Sea showed that P addition increased up to 6 times of total chl a content within 24 h in the estuarine water;and N+P addition increased more than 20 times of chl a within 144 h in the pelagic water. The P addition powered 18.0% and 149% increase in the carbon fixation of larger (>3 μm) and smaller (
基金supported by grants from the Natural Science Foundation of Jiangsu Province(BK20222009,China)Guangdong Basic and Applied Basic Research Foundation(2021B1515120016,China)+2 种基金National Natural Science Foundation of China(81972261)China Postdoctoral Science Foundation(2022M712436)Zhejiang Provincial Natural Science Foundation of China under Grant No.LQ23H070001。
文摘Currently the main treatment of acute myeloid leukemia(AML)is chemotherapy combining hematopoietic stem cell transplantation.However,the unbearable side effect of chemotherapy and the high risk of life-threatening infections and disease relapse following hematopoietic stem cell transplantation restrict its application in clinical practice.Thus,there is an urgent need to develop alternative therapeutic tactics with significant efficacy and attenuated adverse effects.Here,we revealed that umbilical cord-derived mesenchymal stem cells(UC-MSC)efficiently induced AML cell differentiation by shuttling the neutrophil elastase(NE)-packaged extracellular vesicles(EVs)into AML cells.Interestingly,the generation and release of NE-packaged EVs could be dramatically increased by vitamin D receptor(VDR)activation in UC-MSC.Chemical activation of VDR by using its agonist 1a,25-dihydroxyvitamin D3 efficiently enhanced the pro-differentiation capacity of UC-MSC and then alleviated malignant burden in AML mouse model.Based on these discoveries,to evade the risk of hypercalcemia,we synthetized and identified sw-22,a novel non-steroidal VDR agonist,which exerted a synergistic prodifferentiation function with UC-MSC on mitigating the progress of AML.Collectively,our findings provided a non-gene editing MSC-based therapeutic regimen to overcome the differentiation blockade in AML.
基金National Key Research and Development Plan,Grant/Award Number:2017YFA0506000Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2021B1515120016+1 种基金National Natural Science Foundation of China,Grant/Award Number:82072822the Key Research and Development Program of Jiangsu Province,China-Social Development Projects,Grant/Award Number:BE2020687。
文摘Background:Interleukin-15(IL-15)is a promising immunotherapeutic agent owing to its powerful immune-activating effects.However,the clinical benefits of these treatments are limited.Crosstalk between tumor cells and immune cells plays an important role in immune escape and immunotherapy drug resistance.Herein,this study aimed to obtain in-depth understanding of crosstalk in the tumor microenvironment for providing potential therapeutic strategies to prevent tumor progression.Methods:T-cell killing assays and co-culture models were developed to determine the role of crosstalk between macrophages and tumor cells in breast cancer resistant to IL-15.Western blotting,histological analysis,CRISPR-Cas9 knockout,multi-parameter flow cytometry,and tumor cell-macrophage co-injection mouse models were developed to examine the mechanism by which IL-15Rα^(+)tumor-associated macrophages(TAMs)regulate breast cancer cell resistance to IL-15.Results:We found thatmacrophages contributed to the resistance of tumor cells to IL-15,and tumor cells induced macrophages to express high levels of theαsubunit of the IL-15 receptor(IL-15Rα).Further investigation showed that IL-15Rα^(+)TAMs reduced the protein levels of chemokine CX3C chemokine ligand 1(CX3CL1)in tumor cells to inhibit the recruitment of CD8^(+)T cells by releasing the IL-15/IL-15Rαcomplex(IL-15Rc).Administration of an IL-15Rc blocking peptide markedly suppressed breast tumor growth and overcame the resistance of cancer cells to anti-programmed cell death protein 1(PD-1)antibody immunotherapy.Interestingly,Granulocyte-macrophage colony-stimulating factor(GMCSF)inducedγchain(γc)expression to promote tumor cell-macrophage crosstalk,which facilitated tumor resistance to IL-15.Additionally,we observed that the non-transcriptional regulatory function of hypoxia inducible factor-1alpha(HIF-1α)was essential for IL-15Rc to regulateCX3CL1 expression in tumor cells.Conclusions:The IL-15Rc-HIF-1α-CX3CL1 signaling pathway serves as a crosstalk between macrophages and tumor cells in the tumormicroenvironment of breast cancer.Targeting this pathway may provide a potential therapeutic strategy for enhancing the efficacy of cancer immunotherapy.
文摘Dear Editor,Tumor-associated macrophages(TAMs)are critical pro-tumor immunocytes and depletion of TAMs has been exploited for cancer therapy.1 However,the phenotypes and functions of TAMs are plastic,TAMs can also be effector cells by engulfing tumor cells and recruiting cytotoxic T cells,thus shaping the actions of TAMs is more scientific rational than depleting them indiscriminately.2 To promote the entry of reorienting TAMs into the clinical treatments of tumors,it is essential to explore the underline mechanisms controlling the anti-and pro-tumor activities of TAMs.
