Objective:Laparoscopic pelvic lymph node dissection(LPND),which is an effective therapy for endometrial cancer,is challenging because of the complexity of the procedure and the occurrence of postoperative complication...Objective:Laparoscopic pelvic lymph node dissection(LPND),which is an effective therapy for endometrial cancer,is challenging because of the complexity of the procedure and the occurrence of postoperative complications.This study aimed to explore whether indocyanine green(ICG)-enhanced nearinfrared(NIR)fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma.Methods:In this retrospective study,we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine between January 2019 and January 2021.Depending on whether ICG-enhanced NIR fluorescence guidance was used,the patients were assigned to the ICG group or non-ICG group.Patients were followed-up for one year after surgery.Data on demographic characteristics,pathological results,operative outcomes,and complications were collected and analyzed.Results:The baseline characteristics were comparable between the ICG group and non-ICG group,including age,BMI,pregnancy history,and preoperative hemoglobin.For surgical outcomes,the patients in ICG group had significantly lower intraoperative blood loss(50 mL vs.120 mL,p<0.001),less postoperative pelvic drainage time(4.14±1.44 d vs.5.70±1.89 d,p¼0.001),shorter duration of hospital stay(5.26±1.41 d vs.7.37±1.85 d,p¼0.003),higher number of positive pelvic lymph nodes(PLNs)(1 vs.0,p¼0.003),and more PLN-positive cases(16.0%vs.3.6%,p¼0.003)than the patients in non-ICG group.However,no significant differences were noted in blood transfusion requirement,operative time,hemoglobin level decreases,number of PLNs harvested,or the presence of lymphocysts between the two groups.Conclusion:Our study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND.展开更多
The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflamma...The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune diseases.Innate immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully understood.Here,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)feeding.Sting^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of macrophages.Mechanically,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in macrophages.Additionally,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory granules.Pharmacologically inhibiting STING activation enhances insulin secretion to control hyperglycemia.Together,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.展开更多
The endosomal sorting complex required for transport(ESCRT)is highly conserved in eukaryotic cells and plays an essential role in the biogenesis of multivesicular bodies and cargo degradation to the plant vacuole or l...The endosomal sorting complex required for transport(ESCRT)is highly conserved in eukaryotic cells and plays an essential role in the biogenesis of multivesicular bodies and cargo degradation to the plant vacuole or lysosomes.Although ESCRT components affect a variety of plant growth and development processes,their impact on leaf development is rarely reported.Here,we found that OsSNF7.2,an ESCRT-Ⅲ component,controls leaf rolling in rice(Oryza sativa).The Ossnf7.2 mutant rolled leaf 17(rl17)has adaxially rolled leaves due to the decreased number and size of the bulliform cells.OsSNF7.2is expressed ubiquitously in all tissues,and its protein is localized in the endosomal compartments.OsSNF7.2 homologs,including OsSNF7,OsSNF7.3,and OsSNF7.4,can physically interact with OsSNF7.2,but their single mutation did not result in leaf rolling.Other ESCRT complex subunits,namely OsVPS20,OsVPS24,and OsBRO1,also interact with OsSNF7.2.Further assays revealed that OsSNF7.2 interacts with OsYUC8 and aids its vacuolar degradation.Both Osyuc8and rl17 Osyuc8 showed rolled leaves,indicating that OsYUC8 and OsSNF7.2 function in the same pathway,conferring leaf development.This study reveals a new biological function for the ESCRT-Ⅲcomponents,and provides new insights into the molecular mechanisms underlying leaf rolling.展开更多
Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However...Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However,its antitumor application is limited to local treatment of melanoma,and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity.We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus.Methods We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1.Then,we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1.Furthermore,we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models.Results We identified eight IFN-stimulated genes(ISGs)controlling HSV-1 replication,among which BTB and CNC homology 1(BACH1)suppressed HSV-1 replication by inhibiting the transcription of ICP4,ICP27,and UL39.Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis,HMGB1 secretion,and calreticulin exposure in tumor cells.More importantly,hemin,an FDA-approved drug known to downregulate BACH1,significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site.Conclusions Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1.展开更多
In the version of this article initially published,a grant name and the acknowledgment information were missing.The grant name and acknowledgment information have been added at the end of Acknowledgments:J.L.is suppor...In the version of this article initially published,a grant name and the acknowledgment information were missing.The grant name and acknowledgment information have been added at the end of Acknowledgments:J.L.is supported by WU Jieping Medical Foundation(320.6750.2021-17-12).We thank Dr.Chunfu Zheng for providing the HSV-1 BAC plasmid.The results and conclusions were not affected.展开更多
基金supported by the Medical and Health Research Project of Zhejiang Province(2018RC008,2018KY113,and WKJ-ZJ-2125)Zhejiang Provincial Natural Science Foundation(LQ20H040011).
文摘Objective:Laparoscopic pelvic lymph node dissection(LPND),which is an effective therapy for endometrial cancer,is challenging because of the complexity of the procedure and the occurrence of postoperative complications.This study aimed to explore whether indocyanine green(ICG)-enhanced nearinfrared(NIR)fluorescence-guided LPND is superior to LPND in the context of early-stage endometrial carcinoma.Methods:In this retrospective study,we included the medical records of 190 patients with early-stage endometrioid adenocarcinoma who underwent LPND at the Department of Obstetrics and Gynecology,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine between January 2019 and January 2021.Depending on whether ICG-enhanced NIR fluorescence guidance was used,the patients were assigned to the ICG group or non-ICG group.Patients were followed-up for one year after surgery.Data on demographic characteristics,pathological results,operative outcomes,and complications were collected and analyzed.Results:The baseline characteristics were comparable between the ICG group and non-ICG group,including age,BMI,pregnancy history,and preoperative hemoglobin.For surgical outcomes,the patients in ICG group had significantly lower intraoperative blood loss(50 mL vs.120 mL,p<0.001),less postoperative pelvic drainage time(4.14±1.44 d vs.5.70±1.89 d,p¼0.001),shorter duration of hospital stay(5.26±1.41 d vs.7.37±1.85 d,p¼0.003),higher number of positive pelvic lymph nodes(PLNs)(1 vs.0,p¼0.003),and more PLN-positive cases(16.0%vs.3.6%,p¼0.003)than the patients in non-ICG group.However,no significant differences were noted in blood transfusion requirement,operative time,hemoglobin level decreases,number of PLNs harvested,or the presence of lymphocysts between the two groups.Conclusion:Our study showed that ICG-enhanced NIR fluorescence-guided operation may improve the accuracy and safety of LPND.
基金supported by the National Key Research and Development Program of China(2022YFC2303200,2021YFF0702003)China Postdoctoral Research Program(2019TQ0356)+3 种基金the“Double First-Class”Project of China Pharmaceutical University(CPU2022QZ01)the National Natural Science Foundation of China(31730018,82171751,82204408)the Natural Science Foundation of Chongqing(CSTB2022NSCQ-MSX1114)Key R&D Project of Jiangsu Province(BE2020725)。
文摘The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune diseases.Innate immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully understood.Here,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)feeding.Sting^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of macrophages.Mechanically,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in macrophages.Additionally,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory granules.Pharmacologically inhibiting STING activation enhances insulin secretion to control hyperglycemia.Together,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.
基金supported by the Key Laboratory of Biology,Genetics and Breeding of Japonica Rice in the Mid-Lower Yangtze Riverthe Ministry of Agriculture,P.R.China+3 种基金the Southern Japonica Rice Research and Development Co.,Ltd(Nanjing,Jiangsu,China)provided by the Jiangsu Science and Technology Development Program(BE2021360)the Natural Science Foundation of Jiangsu Province,Major Project(BK20212010)the Agricultural Science and Technology Innovation Program of CAAS(CAAS-ZDXT20201,CAAS-ZDXT201903)。
文摘The endosomal sorting complex required for transport(ESCRT)is highly conserved in eukaryotic cells and plays an essential role in the biogenesis of multivesicular bodies and cargo degradation to the plant vacuole or lysosomes.Although ESCRT components affect a variety of plant growth and development processes,their impact on leaf development is rarely reported.Here,we found that OsSNF7.2,an ESCRT-Ⅲ component,controls leaf rolling in rice(Oryza sativa).The Ossnf7.2 mutant rolled leaf 17(rl17)has adaxially rolled leaves due to the decreased number and size of the bulliform cells.OsSNF7.2is expressed ubiquitously in all tissues,and its protein is localized in the endosomal compartments.OsSNF7.2 homologs,including OsSNF7,OsSNF7.3,and OsSNF7.4,can physically interact with OsSNF7.2,but their single mutation did not result in leaf rolling.Other ESCRT complex subunits,namely OsVPS20,OsVPS24,and OsBRO1,also interact with OsSNF7.2.Further assays revealed that OsSNF7.2 interacts with OsYUC8 and aids its vacuolar degradation.Both Osyuc8and rl17 Osyuc8 showed rolled leaves,indicating that OsYUC8 and OsSNF7.2 function in the same pathway,conferring leaf development.This study reveals a new biological function for the ESCRT-Ⅲcomponents,and provides new insights into the molecular mechanisms underlying leaf rolling.
基金This project was financially supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-1-047 and 2019-I2M-5-049)National Science Funds of China(82073181,81802870 and 82102371)+5 种基金Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-PT310-006,2019XK310002 and 2018TX31001)as well as NIH R01AI069120,AI158154,and AI140718 grants,the UCLA AIDS InstituteUCLA David Geffen School of Medicine-Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award ProgramH.Y.is supported by science funds from Jiangsu Province(BK20211554,BK20170407)the Innovative and Entrepreneurial Team grant(2018-2021)from Jiangsu ProvinceL.L.is supported by Innovative and Entrepreneurial Doctor grant(2020-2022)from Jiangsu Province.
文摘Background In 2015,herpes simplex virus 1(HSV-1)-derived talimogene laherparepvec(T-VEC)was the first oncolytic virus approved by the US Food and Drug Administration as a therapeutic agent for cancer treatment.However,its antitumor application is limited to local treatment of melanoma,and there is a lack of understanding of the mechanisms underlying the regulation of HSV-1 replication in cancer cells and the associated antitumor immunity.We hypothesized that increasing the replication capacity of HSV-1 in tumor cells would enhance the antitumor effect of this virus.Methods We systematically identified IFN-stimulated genes induced by HSV-1 by performing functional screens and clarified the mechanism by which BACH1 acts against HSV-1.Then,we tested the effect of BACH1 deficiency on immunogenic cell death induced by HSV-1.Furthermore,we investigated the antitumor effect of BACH1 deficiency on HSV-1 in MCA205 and B16 murine tumor models.Results We identified eight IFN-stimulated genes(ISGs)controlling HSV-1 replication,among which BTB and CNC homology 1(BACH1)suppressed HSV-1 replication by inhibiting the transcription of ICP4,ICP27,and UL39.Loss of Bach1 function not only increased HSV-1 proliferation but also promoted HSV-1-induced cell apoptosis,HMGB1 secretion,and calreticulin exposure in tumor cells.More importantly,hemin,an FDA-approved drug known to downregulate BACH1,significantly enhanced HSV-1-mediated antitumor activity with increased T lymphocyte infiltration at the tumor site.Conclusions Our studies uncovered a novel antiviral activity of BACH1 and provided a new strategy for improving the clinical efficiency of the oncolytic virus HSV-1.
文摘In the version of this article initially published,a grant name and the acknowledgment information were missing.The grant name and acknowledgment information have been added at the end of Acknowledgments:J.L.is supported by WU Jieping Medical Foundation(320.6750.2021-17-12).We thank Dr.Chunfu Zheng for providing the HSV-1 BAC plasmid.The results and conclusions were not affected.