Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identify...Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identifying macrophages as the primary immune responders to acoustic trauma,with a notable increase in their proportion in the cochlea.Immunofluorescence confirmed significant recruitment and activation of cochlear macrophages following noise exposure,while in vivo macrophage depletion resulted in the recovery of hearing.Furthermore,analyses of differentially-expressed genes and pathways revealed pronounced activation of NLRP3 inflammasome signaling in macrophages during night-time noise exposure.Measurements of elevated IL-1βand IL-18 expression in cochlear macrophages by multiplex immunohistochemistry correlated with heightened inflammation in the night-time exposure group.These findings were further confirmed by the administration of the selective NLRP3 inhibitor CY-09,which mitigated inflammasome activation,preserved synaptic integrity,and protect against hearing loss.In conclusion,our findings underscore the role of macrophage-driven NLRP3 inflammasome activation in mediating circadian variations in cochlear damage,offering a potential therapeutic target for mitigating NIHL.展开更多
Albinism in shoots of tea plants is a common phenotypic expression which gives the tea infusion a pleasant umami taste.A novel natural albino mutant tea germplasm containing high amino acids content was found and name...Albinism in shoots of tea plants is a common phenotypic expression which gives the tea infusion a pleasant umami taste.A novel natural albino mutant tea germplasm containing high amino acids content was found and named as‘Huabai 1’.‘Huabai 1’has white jade tender shoots under low temperature and turns green with increased temperature.In order to understand the molecular mechanism of color change in leaf of‘Huabai 1’,transcriptome analysis was performed to identify albino-associated differentially expressed genes(DEGs).A total of 483 DEGs were identified from white shoots of‘Huabai 1’compared to its green shoots.There were 15 DEGs identified to be involved in phenylpropanoid biosynthesis,which account for the majority of characterized DEGs.The metabolites related to phenylpropanoid biosynthesis revealed similar expression pattern of DEGs.Furthermore,metabolic pathways such as ubiquonone,tyrosine,and flavonoid biosynthesis associated with phenylpropanoid biosynthesis could also contribute to the color change in‘Huabai 1’tender shoots.Protein–protein interaction analysis revealed a hub protein NEDD8(CSA009575)which interacted with many regulated genes in spliceosome,nitrogen metabolism,phenylpropanoid biosynthesis,and other pathways.In conclusion,the findings in this study indicate that the color change of‘Huabai 1’tender shoots is a combined effect of phenylpropanoid biosynthesis pathway and other metabolic pathways including flavonoid biosynthesis in tea plants.Chlorophyll biosynthesis-related genes LHCII and SGR may also play some roles in color change of‘Huabai 1’.展开更多
Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LN...Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LNs),etc.The unique structure of LNs provides the microenvironment suitable for the survival,activation,and proliferation of multiple types of immune cells.LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses.Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein.Meanwhile,the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly.Therefore,LNs have become a key target for tumor immunotherapy.Unfortunately,the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells,which leads to unsatisfactory anti-tumor effects.The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs.Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues,exhibiting powerful and promising prospects for achieving effective delivery to LNs.Herein,the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly.Moreover,developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.展开更多
Micro/nanomotors(MNMs)are small-scale devices that can effectively convert various forms of energy into mechanical motion.Their controllable motility and good permeability have attracted the interest of researchers as...Micro/nanomotors(MNMs)are small-scale devices that can effectively convert various forms of energy into mechanical motion.Their controllable motility and good permeability have attracted the interest of researchers as promising drug carriers in cancer therapy.Compared with traditional formulations,micro/nanomotor drug delivery systems can greatly improve therapeutic efficiency and reduce the side effects of antitumor drugs.This review mainly discusses the advantages of micro/nanomotor drug delivery systems and the applications of MNMs propelled by exogenous,endogenous,and biohybrid power in cancer therapy.Finally,the main challenges of the applications of micro/nanomotor drug delivery systems,as well as future development trends and opportunities are discussed.展开更多
基金supported by the Scientific and Innovative Action Plan of Shanghai(CN)(22Y11902000)the National Natural Science Foundation of China(82371144 and 82201273)+2 种基金the Cross-Disciplinary Research Fund of Shanghai Ninth People's Hospital,Shanghai Jiao Tong University School of Medicine(JYJC202231)the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300)We extend our gratitude to Prof.Hao Wu and the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases for providing essential resources and laboratory facilities,and to Prof.Lei Song and Prof.Zhiyong Liu for valuable insights and guidance.
文摘Circadian sensitivity significantly influences the severity of noise-induced hearing loss(NIHL),but the underlying mechanisms remain unclear.Here,we applied single-cell RNA sequencing to 97,043 cochlear cells,identifying macrophages as the primary immune responders to acoustic trauma,with a notable increase in their proportion in the cochlea.Immunofluorescence confirmed significant recruitment and activation of cochlear macrophages following noise exposure,while in vivo macrophage depletion resulted in the recovery of hearing.Furthermore,analyses of differentially-expressed genes and pathways revealed pronounced activation of NLRP3 inflammasome signaling in macrophages during night-time noise exposure.Measurements of elevated IL-1βand IL-18 expression in cochlear macrophages by multiplex immunohistochemistry correlated with heightened inflammation in the night-time exposure group.These findings were further confirmed by the administration of the selective NLRP3 inhibitor CY-09,which mitigated inflammasome activation,preserved synaptic integrity,and protect against hearing loss.In conclusion,our findings underscore the role of macrophage-driven NLRP3 inflammasome activation in mediating circadian variations in cochlear damage,offering a potential therapeutic target for mitigating NIHL.
基金This study was supported by the key R&D Plan of Liyang city for development of a novel albino tea germplasm‘Huabai 1’,National Natural Science Foundation of China(31470690,31570689)the China Earmarked Fund for Modern Agro-industry Technology Research System(CARS-19).
文摘Albinism in shoots of tea plants is a common phenotypic expression which gives the tea infusion a pleasant umami taste.A novel natural albino mutant tea germplasm containing high amino acids content was found and named as‘Huabai 1’.‘Huabai 1’has white jade tender shoots under low temperature and turns green with increased temperature.In order to understand the molecular mechanism of color change in leaf of‘Huabai 1’,transcriptome analysis was performed to identify albino-associated differentially expressed genes(DEGs).A total of 483 DEGs were identified from white shoots of‘Huabai 1’compared to its green shoots.There were 15 DEGs identified to be involved in phenylpropanoid biosynthesis,which account for the majority of characterized DEGs.The metabolites related to phenylpropanoid biosynthesis revealed similar expression pattern of DEGs.Furthermore,metabolic pathways such as ubiquonone,tyrosine,and flavonoid biosynthesis associated with phenylpropanoid biosynthesis could also contribute to the color change in‘Huabai 1’tender shoots.Protein–protein interaction analysis revealed a hub protein NEDD8(CSA009575)which interacted with many regulated genes in spliceosome,nitrogen metabolism,phenylpropanoid biosynthesis,and other pathways.In conclusion,the findings in this study indicate that the color change of‘Huabai 1’tender shoots is a combined effect of phenylpropanoid biosynthesis pathway and other metabolic pathways including flavonoid biosynthesis in tea plants.Chlorophyll biosynthesis-related genes LHCII and SGR may also play some roles in color change of‘Huabai 1’.
基金supported by National Natural Science Foundation of China(No.82173757,No.82173756)Scientists Fund of National Natural Science Foundation of China(82003682)+1 种基金Medical Science and Technolpgy Program of Henan Province(Joint construction project,LHGJ20200026)Shandong Excellent Youth Fund(ZR2022YQ76).
文摘Immunotherapy has become a promising research“hotspot”in cancer treatment.“Soldier”immune cells are not uniform throughout the body;they accumulate mostly in the immune organs such as the spleen and lymph nodes(LNs),etc.The unique structure of LNs provides the microenvironment suitable for the survival,activation,and proliferation of multiple types of immune cells.LNs play an important role in both the initiation of adaptive immunity and the generation of durable anti-tumor responses.Antigens taken up by antigen-presenting cells in peripheral tissues need to migrate with lymphatic fluid to LNs to activate the lymphocytes therein.Meanwhile,the accumulation and retaining of many immune functional compounds in LNs enhance their efficacy significantly.Therefore,LNs have become a key target for tumor immunotherapy.Unfortunately,the nonspecific distribution of the immune drugs in vivo greatly limits the activation and proliferation of immune cells,which leads to unsatisfactory anti-tumor effects.The efficient nano-delivery system to LNs is an effective strategy to maximize the efficacy of immune drugs.Nano-delivery systems have shown beneficial in improving biodistribution and enhancing accumulation in lymphoid tissues,exhibiting powerful and promising prospects for achieving effective delivery to LNs.Herein,the physiological structure and the delivery barriers of LNs were summarized and the factors affecting LNs accumulation were discussed thoroughly.Moreover,developments in nano-delivery systems were reviewed and the transformation prospects of LNs targeting nanocarriers were summarized and discussed.
基金supported by the National Natural Science Founda-tion of China(82173757)the Young Scholar Program of Shandong University(YSPSDU,2017WLJH40)。
文摘Micro/nanomotors(MNMs)are small-scale devices that can effectively convert various forms of energy into mechanical motion.Their controllable motility and good permeability have attracted the interest of researchers as promising drug carriers in cancer therapy.Compared with traditional formulations,micro/nanomotor drug delivery systems can greatly improve therapeutic efficiency and reduce the side effects of antitumor drugs.This review mainly discusses the advantages of micro/nanomotor drug delivery systems and the applications of MNMs propelled by exogenous,endogenous,and biohybrid power in cancer therapy.Finally,the main challenges of the applications of micro/nanomotor drug delivery systems,as well as future development trends and opportunities are discussed.
