The question of whether leaders make events or events make leaders in history seemed to never come to a concrete answer.The reflexivity of this question highlights that perspectives matter,thus a definite conclusion t...The question of whether leaders make events or events make leaders in history seemed to never come to a concrete answer.The reflexivity of this question highlights that perspectives matter,thus a definite conclusion that meet the expectation of all historical research cannot be made.The Vietnam War was one of the critical historical events in American history,and it has largely altered the future of USA at an international level in terms of foreign policies and also at a domestic level since it influenced the US presidency by setting up a commitment trap[1].The relationship between leaders and events in the history will be discussed in this essay by talking about the succession of presidency in USA[1]during the Vietnam War.Moreover,making an attempt to show the possibility of leaders can portrait future development of events based on their unique personalities and thinking.展开更多
Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective...Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still lacking.Here,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR injury.Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in mice.Moreover,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways.Consistently,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this.Interestingly,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR injury.Furthermore,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in vivo.Collectively,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.展开更多
Inflammatory bowel disease(IBD)is a chronic,immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier.Due to the poor remission effect and...Inflammatory bowel disease(IBD)is a chronic,immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier.Due to the poor remission effect and severe adverse events associated with current clinical medications,IBD remains an incurable disease.Here,we demonstrated a novel treatment strategy with high safety and effective inflammation remission via tissue-adhesive molecular coating.The molecular coating is composed of o-nitrobenzaldehyde(NB)-modified Gelatin(GelNB),which can strongly bond with-NH_(2)on the intestinal surface of tissue to form a thin biophysical barrier.We found that this molecular coating was able to stay on the surface of the intestine for long periods of time,effectively protecting the damaged intestinal epithelium from irritations of external intestinal metabolites and harmful flora.In addition,our results showed that this coating not only provided a beneficial environment for cell migration and proliferation to promote intestinal repair and regeneration,but also achieved a better outcome of IBD by reducing intestinal inflammation.Moreover,the in vivo experiments showed that the GelNB was better than the classic clinical medication-mesalazine.Therefore,our molecular coating showed potential as a promising strategy for the prevention and treatment of IBD.展开更多
Aggregation-induced emission(AIE)is a photophysical phenomenon that a certain group of luminescent materials that become highly luminous when aggregated in a bad solvent or solid state.This year is the 20th anniversar...Aggregation-induced emission(AIE)is a photophysical phenomenon that a certain group of luminescent materials that become highly luminous when aggregated in a bad solvent or solid state.This year is the 20th anniversary since the AIE concept firstly proposed in 2001.Many advanced applications were gradually being explored,covering optics,electronics,energy,and bioscience and so on.At present,bibliometrics can enlighten the researchers with comprehensive sights of the achievements and trends of a specific field,which is critical for academic investigations.Herein,we presented a general bibliometric overview of AIE covering 20 years of evolution.With the assistance of Web of Science Core Collection database and several bibliometric software tools,the annual publication and citation,most influential countries/regions,most contributing authors,journals and institutions,second near-infrared(NIR-Ⅱ)related hotspots,as well as the forecast of frontiers were demonstrated and systematically analyzed.This study summarizes the current research status in AIE research field and provides a reference for future research directions.展开更多
Immune-mediated hepatitis(IMH)induced by immune checkpoint inhibitors(ICIs)is an immune-related adverse event(irAE).IMH usually occurs 8-12 weeks after the first dose of ICI therapy.We report an unusual case of a lung...Immune-mediated hepatitis(IMH)induced by immune checkpoint inhibitors(ICIs)is an immune-related adverse event(irAE).IMH usually occurs 8-12 weeks after the first dose of ICI therapy.We report an unusual case of a lung cancer patient who developed IMH 2 years after initial ICI treatment and relapsed during corticosteroid therapy.A 55-year-old male with stageⅣB lung cancer received ICIs(for over 2 years)and chemotherapy as a second-line therapy.Grade 4 IMH occurred 2 years after initial immunotherapy and was diagnosed as hepatitis via laboratory and imaging tests with the simultaneous exclusion of other causes.The patient responded well to the corticosteroids;however,he decided to discontinue treatment prematurely,meaning that the total treatment period was less than 4 weeks.This led to IMH reoccurrence and the need to readminister corticosteroids at a higher dose than before.Ultimately,the patient's IMH was controlled and did not reoccur.This case illustrates that immune-related toxicity needs to be monitored in patients undergoing long-term ICI therapy.Improving patient education is also essential for the management and treatment of irAEs.展开更多
Neutrophils constitute a significant portion of the immune cells present within the tumor microenvironment.Evidence generated by our group has confirmed neutrophils to be an adverse independent prognostic factor affec...Neutrophils constitute a significant portion of the immune cells present within the tumor microenvironment.Evidence generated by our group has confirmed neutrophils to be an adverse independent prognostic factor affecting the disease-free survival of gastric carcinoma(GC)patients.1 Neutrophil extracellular traps(NETs),protein-covered DNA webs that interact with tumor cells in the tumor microenvironment,were detected in GC tissues and found to clinically associated with disease progression in our previous study.2 NETosis could be mediated by a series of agonists,such as interleukin 8(IL-8).3 However,the mechanism of IL-8 in the progression of GC occurs via NETs remains unclear.In this study,we identified that IL-8-mediated NETosis can promote the proliferation,migration,and invasion of GC cells in vitro,which can be abrogated by NET degradation through deoxyribonucleaseI(DNase I)or IL-8 suppression through neutralizing antibodies.Disruption of NETs by DNase I or blockade of the IL-8-CXC chemokine receptor 2(CXCR2)axis could result in growth retardation in mouse models.We also confirmed that NETs may influence the biological behavior of GC cells by up-regulating the expression of transcription factor IB-related factor 1(BRF1)and cyclin p21/p27.展开更多
文摘The question of whether leaders make events or events make leaders in history seemed to never come to a concrete answer.The reflexivity of this question highlights that perspectives matter,thus a definite conclusion that meet the expectation of all historical research cannot be made.The Vietnam War was one of the critical historical events in American history,and it has largely altered the future of USA at an international level in terms of foreign policies and also at a domestic level since it influenced the US presidency by setting up a commitment trap[1].The relationship between leaders and events in the history will be discussed in this essay by talking about the succession of presidency in USA[1]during the Vietnam War.Moreover,making an attempt to show the possibility of leaders can portrait future development of events based on their unique personalities and thinking.
基金the National Key Research and Development Project[2017YFC0110802]the Zhejiang Province Key Research and Development Project[2020C01059,2020]+4 种基金the Natural Science Foundation of China[82030108,31872796,81874059,32071102,and 82102105]the Natural Science Foundation of Zhejiang Province[LQ22H160017]the Zhejiang Engineering Research Center of Cognitive Healthcare[2017E10011]the National Key Scientific Instrument and Equipment Development Project[81827804]the China Postdoctoral Science Foundation[2021M702825].
文摘Hepatic ischemia–reperfusion(IR)injury is a serious clinical problem that complicates liver resection and transplantation.Despite recent advances in understanding of the pathophysiology of hepatic IR injury,effective interventions and therapeutics are still lacking.Here,we examined the role of transient receptor potential melastatin 2(TRPM2),a Ca^(2+)-permeable,non-selective cation channel,in mediating hepatic IR injury.Our data showed that TRPM2 deficiency attenuated IR-induced liver dysfunction,inflammation,and cell death in mice.Moreover,RNA sequencing analysis indicated that TRPM2-induced IR injury occurs via ferroptosis-related pathways.Consistently,as a ferroptosis inducer,(1S,3R)-RSL3 treatment induced mitochondrial dysfunction in hepatocytes and a TRPM2 inhibitor suppressed this.Interestingly,TRPM2-mediated calcium influx caused mitochondrial calcium accumulation via the mitochondrial Ca^(2+)-selective uniporter and increased the expression level of arachidonate 12-lipoxygenase(ALOX12),which results in mitochondrial lipid peroxidation during hepatic IR injury.Furthermore,hepatic IR injury-induced ferroptosis was obviously relieved by a TRPM2 inhibitor or calcium depletion,both in vitro and in vivo.Collectively,these findings demonstrate a crucial role for TRPM2-mediated ferroptosis in hepatic IR injury via increased Ca^(2+)-induced ALOX12 expression,indicating that pharmacological inhibition of TRPM2 may provide an effective therapeutic strategy for hepatic IR injury-related diseases,such as during liver resection and transplantation.
文摘Inflammatory bowel disease(IBD)is a chronic,immune-mediated inflammatory disease characterized by the destruction of the structure and function of the intestinal epithelial barrier.Due to the poor remission effect and severe adverse events associated with current clinical medications,IBD remains an incurable disease.Here,we demonstrated a novel treatment strategy with high safety and effective inflammation remission via tissue-adhesive molecular coating.The molecular coating is composed of o-nitrobenzaldehyde(NB)-modified Gelatin(GelNB),which can strongly bond with-NH_(2)on the intestinal surface of tissue to form a thin biophysical barrier.We found that this molecular coating was able to stay on the surface of the intestine for long periods of time,effectively protecting the damaged intestinal epithelium from irritations of external intestinal metabolites and harmful flora.In addition,our results showed that this coating not only provided a beneficial environment for cell migration and proliferation to promote intestinal repair and regeneration,but also achieved a better outcome of IBD by reducing intestinal inflammation.Moreover,the in vivo experiments showed that the GelNB was better than the classic clinical medication-mesalazine.Therefore,our molecular coating showed potential as a promising strategy for the prevention and treatment of IBD.
基金National Key Research and Development Project,Grant/Award Number:2017YFC0110802Zhejiang province Key Research and Development Project,Grant/Award Number:2020C01059+3 种基金National Natural Science Foundation of China,Grant/Award Numbers:81874059,82102105,61975172,61735016Zhejiang Engineering Research Center of Cognitive Healthcare,Grant/Award Number:2017E10011National Key Scientific Instrument and Equipment Development Project,Grant/Award Number:81827804Fundamental Research Funds for the Central Universities,Grant/Award Number:2020-KYY-511108-0007。
文摘Aggregation-induced emission(AIE)is a photophysical phenomenon that a certain group of luminescent materials that become highly luminous when aggregated in a bad solvent or solid state.This year is the 20th anniversary since the AIE concept firstly proposed in 2001.Many advanced applications were gradually being explored,covering optics,electronics,energy,and bioscience and so on.At present,bibliometrics can enlighten the researchers with comprehensive sights of the achievements and trends of a specific field,which is critical for academic investigations.Herein,we presented a general bibliometric overview of AIE covering 20 years of evolution.With the assistance of Web of Science Core Collection database and several bibliometric software tools,the annual publication and citation,most influential countries/regions,most contributing authors,journals and institutions,second near-infrared(NIR-Ⅱ)related hotspots,as well as the forecast of frontiers were demonstrated and systematically analyzed.This study summarizes the current research status in AIE research field and provides a reference for future research directions.
文摘Immune-mediated hepatitis(IMH)induced by immune checkpoint inhibitors(ICIs)is an immune-related adverse event(irAE).IMH usually occurs 8-12 weeks after the first dose of ICI therapy.We report an unusual case of a lung cancer patient who developed IMH 2 years after initial ICI treatment and relapsed during corticosteroid therapy.A 55-year-old male with stageⅣB lung cancer received ICIs(for over 2 years)and chemotherapy as a second-line therapy.Grade 4 IMH occurred 2 years after initial immunotherapy and was diagnosed as hepatitis via laboratory and imaging tests with the simultaneous exclusion of other causes.The patient responded well to the corticosteroids;however,he decided to discontinue treatment prematurely,meaning that the total treatment period was less than 4 weeks.This led to IMH reoccurrence and the need to readminister corticosteroids at a higher dose than before.Ultimately,the patient's IMH was controlled and did not reoccur.This case illustrates that immune-related toxicity needs to be monitored in patients undergoing long-term ICI therapy.Improving patient education is also essential for the management and treatment of irAEs.
基金supported by grants from The Natural Science Foundation of Anhui Province,China(No.1908085QH333)the Key Research and Development Project of Anhui Province,China(No.202004j07020044)+1 种基金the Natural Science Research Project of Anhui Provincial University(China)(No.KJ2018ZD019)Foundation of Beijing Life Oasis Public Service Center(China)(No.cphcf-2022-021).
文摘Neutrophils constitute a significant portion of the immune cells present within the tumor microenvironment.Evidence generated by our group has confirmed neutrophils to be an adverse independent prognostic factor affecting the disease-free survival of gastric carcinoma(GC)patients.1 Neutrophil extracellular traps(NETs),protein-covered DNA webs that interact with tumor cells in the tumor microenvironment,were detected in GC tissues and found to clinically associated with disease progression in our previous study.2 NETosis could be mediated by a series of agonists,such as interleukin 8(IL-8).3 However,the mechanism of IL-8 in the progression of GC occurs via NETs remains unclear.In this study,we identified that IL-8-mediated NETosis can promote the proliferation,migration,and invasion of GC cells in vitro,which can be abrogated by NET degradation through deoxyribonucleaseI(DNase I)or IL-8 suppression through neutralizing antibodies.Disruption of NETs by DNase I or blockade of the IL-8-CXC chemokine receptor 2(CXCR2)axis could result in growth retardation in mouse models.We also confirmed that NETs may influence the biological behavior of GC cells by up-regulating the expression of transcription factor IB-related factor 1(BRF1)and cyclin p21/p27.