Autophagy is an evolutionarily conserved catabolic process that eliminates harmful components through lysosomal degradation.In addition to its role in maintaining cellular homeostasis,autophagy is critical to patholog...Autophagy is an evolutionarily conserved catabolic process that eliminates harmful components through lysosomal degradation.In addition to its role in maintaining cellular homeostasis,autophagy is critical to pathological processes,such as inflammation and cancer.Colitis-associated colorectal cancer(CAC)is a specific type of colorectal cancer that develops from long-standing colitis in inflammatory bowel disease(IBD)patients.Accumulating evidence indicates that autophagy of microenvironmental cells plays different but vital roles during tumorigenesis and CAC development.Herein,after summarizing the recent advances in understanding the role of autophagy in regulating the tumor microenvironment during different CAC stages,we draw the following conclusions:autophagy in intestinal epithelial cells inhibits colitis and CAC initiation but promotes CAC progression;autophagy in macrophages inhibits colitis,but its function on CAC is currently unclear;autophagy in neutrophils and cancer-associated fibroblasts(CAFs)promotes both colitis and CAC;autophagy in dendritic cells(DCs)and T cells represses both colitis and CAC;autophagy in natural killer cells(NKs)inhibits colitis,but promotes CAC;and autophagy in endothelial cells plays a controversial role in colitis and CAC.Understanding the role of autophagy in specific compartments of the tumor microenvironment during different stages of CAC may provide insight into malignant transformation,tumor progression,and combination therapy strategies for CAC.展开更多
The current bumblebee decline leads to inbreeding in populations that fosters a loss of allelic diversity and diploid male production. As diploid males are viable and their offspring are sterile, bumblebee populations...The current bumblebee decline leads to inbreeding in populations that fosters a loss of allelic diversity and diploid male production. As diploid males are viable and their offspring are sterile, bumblebee populations can quickly fall in a vortex of extinction. In this article, we investigate for the first time a potential premating mechanism through a major chemical reproductive trait （male cephalic labial gland secretions） that could prevent monandrous virgin queens from mating with diploid males. We focus our study on the cephalic labial gland secretions of diploid and haploid males ofBombus terrestris （L.）. Contrary to initial expectations, our results do not show any significant differentiation of cephalic labial gland secretions between diploid and haploid specimens. Queens seem therefore to be unable to avoid mating with diploid males based on their compositions of cephalic labial gland secretions. This suggests that the vortex of extinction of diploid males could not be stopped through premating avoidance based on the cephalic labial gland secretions but other mechanisms could avoid mating between diploid males and queens.展开更多
Social parasitic Hymenopterans have evolved morphological, chemical, and behavioral adaptations to overcome the sophisticated recognition and defense systems of their social host to invade host nests and exploit their...Social parasitic Hymenopterans have evolved morphological, chemical, and behavioral adaptations to overcome the sophisticated recognition and defense systems of their social host to invade host nests and exploit their worker force. In bumblebees, so- cial parasitism appeared in at least 3 subgenera independently： in the subgenus Psithyrus consisting entirely of parasitic species, in the subgenus Alpinobombus with Bombus hy- perboreus, and in the subgenus Thoracobombus with B. inexspectatus. Cuckoo bumblebee males utilize species-specific cephalic labial gland secretions for mating purposes that can impact their inquiline strategy. We performed cephalic labial gland secretions in B. hyperboreus, B. inexspectatus and their hosts. Males of both parasitic species exhibited high species specific levels of cephalic gland secretions, including different main com- pounds. Our results showed no chemical mimicry in the cephalic gland secretions between inquilines and their host and we did not identify the repellent compounds already known in other cuckoo bumblebees.展开更多
The aphid-ant mutnalistic relationships are not necessarily obligate for neither partners but evidence is that such interactions provide them strong advantages in terms of global fitness. While it is largely assumed t...The aphid-ant mutnalistic relationships are not necessarily obligate for neither partners but evidence is that such interactions provide them strong advantages in terms of global fitness. While it is largely assumed that ants actively search for their mutualistic partners namely using volatile cues; whether winged aphids （i.e., aphids＇ most mobile form） are able to select ant-frequented areas had not been investigated so far. Ant-frequented sites would indeed offer several advantages for these aphids including a lower predation pressure through ant presence and enhanced chances of establishing mutuaslistic interactions with neighbor ant colonies. In the field, aphid colonies are often observed in higher densities around ant nests, which is probably linked to a better survival ensured by ants＇ services. Nevertheless, this could also result from a preferential establishment of winged aphids in ant-frequented areas. We tested this last hypothesis through different ethological assays and show that the facultative myrmecophilous black bean aphid, Aphisfabae L., does not orientate its search for a host plant preferentially toward ant-frequented plants. However, our results suggest that ants reduce the number of winged aphids leaving the newly colonized plant. Thus, ants involved in facultative myrmecophilous interactions with aphids appear to contribute to structure aphid populations in the field by ensuring a better establishment and survival of newly established colonies rather than by inducing a deliberate plant selection by aphid partners based on the proximity of ant colonies.展开更多
Calcium ion(Ca^(2+))is a ubiquitous second messenger in eukaryotic cells.In response to electrical,hormonal,or mechanical stimulation,cytosolic Ca^(2+)levels increase due to Ca^(2+) influxes through ion channels embed...Calcium ion(Ca^(2+))is a ubiquitous second messenger in eukaryotic cells.In response to electrical,hormonal,or mechanical stimulation,cytosolic Ca^(2+)levels increase due to Ca^(2+) influxes through ion channels embedded in the plasma membrane or Ca^(2+) releases from intracellular Ca^(2+) stores,such as the endoplasmic展开更多
Cellular immunotherapy harnesses the body’’s own immune system to fight cancer by using engineered T cells,macrophages,or natural killer(NK)cells.Compared to chimeric antigen receptor T(CAR-T)cells that are commonly...Cellular immunotherapy harnesses the body’’s own immune system to fight cancer by using engineered T cells,macrophages,or natural killer(NK)cells.Compared to chimeric antigen receptor T(CAR-T)cells that are commonly used to treat hematological malignancies,CAR-NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety,reduced risk of graft-versus-host disease,fewer side effects,and amplified antitumor efficacy.Preclinical trials have unveiled the high potential of adoptive CAR-NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models.We brought forth herein the design principle of CAR-NK cells,highlighted the latest progress in the preclinical testing and clinical trials of CAR-NK cells,briefly delved into discussed major roadblocks in CAR-NK therapy,and discussed potential solutions to surmount these challenges.Given the accelerated progress in both basic and translational studies on immune cell engineering,CAR-NK cell therapy promises to become a serious contender and important addition to the next-generation cell-based immunotherapy.展开更多
基金This work was supported by the National Natural Science Foundation of China(81572361,81772543,and 81572592)the Zhejiang Province Preeminence Youth Fund(LR16H160001)the Zhejiang Medical Innovative Discipline Construction Project-2016.
文摘Autophagy is an evolutionarily conserved catabolic process that eliminates harmful components through lysosomal degradation.In addition to its role in maintaining cellular homeostasis,autophagy is critical to pathological processes,such as inflammation and cancer.Colitis-associated colorectal cancer(CAC)is a specific type of colorectal cancer that develops from long-standing colitis in inflammatory bowel disease(IBD)patients.Accumulating evidence indicates that autophagy of microenvironmental cells plays different but vital roles during tumorigenesis and CAC development.Herein,after summarizing the recent advances in understanding the role of autophagy in regulating the tumor microenvironment during different CAC stages,we draw the following conclusions:autophagy in intestinal epithelial cells inhibits colitis and CAC initiation but promotes CAC progression;autophagy in macrophages inhibits colitis,but its function on CAC is currently unclear;autophagy in neutrophils and cancer-associated fibroblasts(CAFs)promotes both colitis and CAC;autophagy in dendritic cells(DCs)and T cells represses both colitis and CAC;autophagy in natural killer cells(NKs)inhibits colitis,but promotes CAC;and autophagy in endothelial cells plays a controversial role in colitis and CAC.Understanding the role of autophagy in specific compartments of the tumor microenvironment during different stages of CAC may provide insight into malignant transformation,tumor progression,and combination therapy strategies for CAC.
文摘The current bumblebee decline leads to inbreeding in populations that fosters a loss of allelic diversity and diploid male production. As diploid males are viable and their offspring are sterile, bumblebee populations can quickly fall in a vortex of extinction. In this article, we investigate for the first time a potential premating mechanism through a major chemical reproductive trait （male cephalic labial gland secretions） that could prevent monandrous virgin queens from mating with diploid males. We focus our study on the cephalic labial gland secretions of diploid and haploid males ofBombus terrestris （L.）. Contrary to initial expectations, our results do not show any significant differentiation of cephalic labial gland secretions between diploid and haploid specimens. Queens seem therefore to be unable to avoid mating with diploid males based on their compositions of cephalic labial gland secretions. This suggests that the vortex of extinction of diploid males could not be stopped through premating avoidance based on the cephalic labial gland secretions but other mechanisms could avoid mating between diploid males and queens.
文摘Social parasitic Hymenopterans have evolved morphological, chemical, and behavioral adaptations to overcome the sophisticated recognition and defense systems of their social host to invade host nests and exploit their worker force. In bumblebees, so- cial parasitism appeared in at least 3 subgenera independently： in the subgenus Psithyrus consisting entirely of parasitic species, in the subgenus Alpinobombus with Bombus hy- perboreus, and in the subgenus Thoracobombus with B. inexspectatus. Cuckoo bumblebee males utilize species-specific cephalic labial gland secretions for mating purposes that can impact their inquiline strategy. We performed cephalic labial gland secretions in B. hyperboreus, B. inexspectatus and their hosts. Males of both parasitic species exhibited high species specific levels of cephalic gland secretions, including different main com- pounds. Our results showed no chemical mimicry in the cephalic gland secretions between inquilines and their host and we did not identify the repellent compounds already known in other cuckoo bumblebees.
文摘The aphid-ant mutnalistic relationships are not necessarily obligate for neither partners but evidence is that such interactions provide them strong advantages in terms of global fitness. While it is largely assumed that ants actively search for their mutualistic partners namely using volatile cues; whether winged aphids （i.e., aphids＇ most mobile form） are able to select ant-frequented areas had not been investigated so far. Ant-frequented sites would indeed offer several advantages for these aphids including a lower predation pressure through ant presence and enhanced chances of establishing mutuaslistic interactions with neighbor ant colonies. In the field, aphid colonies are often observed in higher densities around ant nests, which is probably linked to a better survival ensured by ants＇ services. Nevertheless, this could also result from a preferential establishment of winged aphids in ant-frequented areas. We tested this last hypothesis through different ethological assays and show that the facultative myrmecophilous black bean aphid, Aphisfabae L., does not orientate its search for a host plant preferentially toward ant-frequented plants. However, our results suggest that ants reduce the number of winged aphids leaving the newly colonized plant. Thus, ants involved in facultative myrmecophilous interactions with aphids appear to contribute to structure aphid populations in the field by ensuring a better establishment and survival of newly established colonies rather than by inducing a deliberate plant selection by aphid partners based on the proximity of ant colonies.
基金supported by the National Natural Science Foundation of China (NSFC-31671492 and NSFC-31471279 to Y.W.)the American Cancer Society (RSG-16-215-01-TBE to Y.Z.)+1 种基金the Welch Foundation (BE-1913 to Y.Z.)the National Institutes of Health (R01GM112003 and R21GM126532 to Y.Z.)
文摘Calcium ion(Ca^(2+))is a ubiquitous second messenger in eukaryotic cells.In response to electrical,hormonal,or mechanical stimulation,cytosolic Ca^(2+)levels increase due to Ca^(2+) influxes through ion channels embedded in the plasma membrane or Ca^(2+) releases from intracellular Ca^(2+) stores,such as the endoplasmic
基金Cancer Prevention and Research Institute of Texas(Grant/Award Number:RP210070)National Cancer Institute(Grant/Award Number:R01CA232017)Welch Foundation(Grant/Award Number:BE-1913-20220331)。
文摘Cellular immunotherapy harnesses the body’’s own immune system to fight cancer by using engineered T cells,macrophages,or natural killer(NK)cells.Compared to chimeric antigen receptor T(CAR-T)cells that are commonly used to treat hematological malignancies,CAR-NK cells have shown remarkable therapeutic effectiveness while exhibiting enhanced safety,reduced risk of graft-versus-host disease,fewer side effects,and amplified antitumor efficacy.Preclinical trials have unveiled the high potential of adoptive CAR-NK cell therapy to curtail or even eliminate both hematological malignancies and solid tumors in animal models.We brought forth herein the design principle of CAR-NK cells,highlighted the latest progress in the preclinical testing and clinical trials of CAR-NK cells,briefly delved into discussed major roadblocks in CAR-NK therapy,and discussed potential solutions to surmount these challenges.Given the accelerated progress in both basic and translational studies on immune cell engineering,CAR-NK cell therapy promises to become a serious contender and important addition to the next-generation cell-based immunotherapy.
