1-Isoquinolin-1(2H)-one skeleton exists widely in natural products,pharmaceuticals and materials.We disclose here a fluorine effect and catalyst cooperatively induced regioselective or regiospecific 3,4-functionalizat...1-Isoquinolin-1(2H)-one skeleton exists widely in natural products,pharmaceuticals and materials.We disclose here a fluorine effect and catalyst cooperatively induced regioselective or regiospecific 3,4-functionalization of unsymmetric 2-CF_(3)-1,3-enynes.The presence of trifluoromethyl group is determinable for the regioselectivity.When the CF_(3) group was replaced with the methyl or amide group,the regioselectivity decreased to a ratio of 1.3:1 or 1:1.7,respectively.For alkyl substitutedβ-CF_(3)-1,3-enynes,a regiospecificity was obtained.This strategy features excellent regioselectivity,broad substrate scope and high functional group tolerance.Mechanistic studies showed that C–H bond activation is the rate-limiting step.展开更多
Friction stir processing(FSP)induces severe plastic deformation,generating intense strains and localized heating,which modifies the surface and enables the fabrication of magnesium(Mg)-based composites.This technique ...Friction stir processing(FSP)induces severe plastic deformation,generating intense strains and localized heating,which modifies the surface and enables the fabrication of magnesium(Mg)-based composites.This technique refines the microstructure of Mg alloys,enhancing mechanical properties—particularly ductility,a key limitation of these HCP alloys.This review addresses the underlying microstructural evolution during FSP of Mg alloys and Mg-matrix composites,including(i)grain refinement via continuous and discontinuous dynamic recrystallization(CDRX and DDRX),(ii)fragmentation and redistribution of secondary phases and intermetallics,(iii)transformation of low-and high-angle grain boundaries,and(iv)additional microstructural changes induced by external reinforcements.This review provides a comprehensive analysis of the strengthening mechanisms and their impact on the mechanical properties of FSP Mg alloys and Mgmatrix composites(MMCs).The paper examines the correlation between FSP processing parameters,microstructural evolution,and resulting mechanical properties.It critically highlights how the type of reinforcement and the dynamic recrystallization induced by friction stir processing influence grain boundary character and,consequently,the material’s strengthening response.It includes a comparative evaluation of yield stress,ultimate tensile strength,microhardness,elongation,and fractography for various FSP-treated Mg alloys and MMCs,including AZxx,WExx,ZExx,ZKxx,AMxx,AExx,and Mg-rare earth alloys.Additionally,the novelty of this review lies in its emphasis on connecting microstructural transformations to mechanical performance trends across different alloy systems and processing strategies,an aspect that has been underexplored in previous reviews.Recent advancements in FSP techniques and their implications for improving the performance of Mg-based materials are also discussed.展开更多
Ovarian cancer remains a leading cause of gynecological cancer mortality1,and patients with advanced stage ovarian cancer frequently develop malignant ascites that foster immunosuppressive microenvironments and therap...Ovarian cancer remains a leading cause of gynecological cancer mortality1,and patients with advanced stage ovarian cancer frequently develop malignant ascites that foster immunosuppressive microenvironments and therapeutic resistance2,3.Although ascites have traditionally been considered detrimental,we report a paradoxical role in which they enhance the cytotoxicity ofγδT cells—a unique T cell subset that can be allogenically transferred for cancer treatment4,5—toward ovarian cancer.展开更多
Macrophages(MΦ) differe ntiate from blood monocytes and participate in innate and adaptive immunity.Because of their abilities to recognize pathogens and activate bactericidal activities,MΦ are always discovered at ...Macrophages(MΦ) differe ntiate from blood monocytes and participate in innate and adaptive immunity.Because of their abilities to recognize pathogens and activate bactericidal activities,MΦ are always discovered at the site of immune defense.MΦ in the intestine are unique,such that in the healthy intestine,they possess complex mechanisms to protect the gut from inflammation.In these complex mechanisms,they produce anti-inflammatory cytokines,such as interleukin-10 and transforming growth factor-β,and inhibit the inflammatory pathways mediated by Toll-like receptors.It has been demonstrated that resident MΦ play a crucial role in maintaining intestinal homeostasis,and they can be recognized by their unique markers.Nonetheless,in the inflamed intestine,the function of MΦ will change because of environmental variation,which may be one of the mechanisms of inflammatory bowel disease(IBD).We provide further explanation about these mechanisms in our review.In addition,we review recent discoveries that MΦ may be involved in the development of gastrointestinal tumors.We will highlight the possible therapeutic targets for the management of IBD and gastrointestinal tumors,and we also discuss why more details are needed to fully understand all other effects of intestinal MΦ.展开更多
BACKGROUND Patients with cirrhosis with hepatopulmonary syndrome(HPS)have a poorer prognosis.The disease has a subtle onset,symptoms are easily masked,clinical attention is insufficient,and misdiagnosis rates are high...BACKGROUND Patients with cirrhosis with hepatopulmonary syndrome(HPS)have a poorer prognosis.The disease has a subtle onset,symptoms are easily masked,clinical attention is insufficient,and misdiagnosis rates are high.AIM To compare the clinical characteristics of patients with cirrhosis,cirrhosis combined with intrapulmonary vascular dilatation(IPVD),and HPS,and to establish predictive models for IPVD and HPS.METHODS Patients with cirrhosis were prospectively screened at a liver-specialized university teaching hospital.Clinical information and blood samples were collected,and biomarker levels in blood samples were measured.Patients with cirrhosis were divided into three groups:Those with pure cirrhosis,those with combined IPVD,and those with HPS based on contrast-enhanced transthoracic echocardiography results and the pulmonary alveolar-arterial oxygen gradient values.Univariate logistic regression and Least Absolute Shrinkage and Selection Operator(LASSO)regression methods were utilized to identify risk factors for IPVD and HPS,and nomograms were constructed to predict IPVD and HPS.RESULTS A total of 320 patients were analyzed,with 101 diagnosed with IPVD,of whom 54 were diagnosed with HPS.There were statistically significant differences in clinical parameters among these three groups of patients.Among the tested biomarkers,sphingosine 1 phosphate,angiopoietin-2,and platelet-derived growth factor BB were significantly associated with IPVD and HPS in patients with cirrhosis.Following LASSO logistic regression screening,prediction models for IPVD and HPS were established.The area under the receiver operating characteristic curve for IPVD prediction was 0.792(95%confidence interval[CI]:0.737-0.847),and for HPS prediction was 0.891(95%CI:0.848-0.934).CONCLUSION This study systematically compared the clinical characteristics of patients with cirrhosis,IPVD,and HPS,and constructed predictive models for IPVD and HPS based on clinical parameters and laboratory indicators.These models showed good predictive value for IPVD and HPS in patients with cirrhosis.They can assist clinicians in the early prognosis assessment of patients with cirrhosis,ultimately benefiting the patients.展开更多
基金supported by National Natural Science Founda:tion of China(22461002,22308061,22305046)Natural Science Foundation(NSF)of Jiangxi Province(20224BAB213011,20242BAB20110,20224BAB213012)+1 种基金High-Level and Highly Demanded Overseas Talent Programs of Jiangxi Province(20232BCJ25050)Gannan Normal University Start-up Fund(BSJJ202109).
文摘1-Isoquinolin-1(2H)-one skeleton exists widely in natural products,pharmaceuticals and materials.We disclose here a fluorine effect and catalyst cooperatively induced regioselective or regiospecific 3,4-functionalization of unsymmetric 2-CF_(3)-1,3-enynes.The presence of trifluoromethyl group is determinable for the regioselectivity.When the CF_(3) group was replaced with the methyl or amide group,the regioselectivity decreased to a ratio of 1.3:1 or 1:1.7,respectively.For alkyl substitutedβ-CF_(3)-1,3-enynes,a regiospecificity was obtained.This strategy features excellent regioselectivity,broad substrate scope and high functional group tolerance.Mechanistic studies showed that C–H bond activation is the rate-limiting step.
基金the National Science Foundation under grant number CMMI-2339857.
文摘Friction stir processing(FSP)induces severe plastic deformation,generating intense strains and localized heating,which modifies the surface and enables the fabrication of magnesium(Mg)-based composites.This technique refines the microstructure of Mg alloys,enhancing mechanical properties—particularly ductility,a key limitation of these HCP alloys.This review addresses the underlying microstructural evolution during FSP of Mg alloys and Mg-matrix composites,including(i)grain refinement via continuous and discontinuous dynamic recrystallization(CDRX and DDRX),(ii)fragmentation and redistribution of secondary phases and intermetallics,(iii)transformation of low-and high-angle grain boundaries,and(iv)additional microstructural changes induced by external reinforcements.This review provides a comprehensive analysis of the strengthening mechanisms and their impact on the mechanical properties of FSP Mg alloys and Mgmatrix composites(MMCs).The paper examines the correlation between FSP processing parameters,microstructural evolution,and resulting mechanical properties.It critically highlights how the type of reinforcement and the dynamic recrystallization induced by friction stir processing influence grain boundary character and,consequently,the material’s strengthening response.It includes a comparative evaluation of yield stress,ultimate tensile strength,microhardness,elongation,and fractography for various FSP-treated Mg alloys and MMCs,including AZxx,WExx,ZExx,ZKxx,AMxx,AExx,and Mg-rare earth alloys.Additionally,the novelty of this review lies in its emphasis on connecting microstructural transformations to mechanical performance trends across different alloy systems and processing strategies,an aspect that has been underexplored in previous reviews.Recent advancements in FSP techniques and their implications for improving the performance of Mg-based materials are also discussed.
基金supported by the National Natural Science Foundation of China(Grant No.82274034)the Peking University Medicine plus X Pilot Program-Platform Construction Project(Grant No.2024YXXLHPT004).
文摘Ovarian cancer remains a leading cause of gynecological cancer mortality1,and patients with advanced stage ovarian cancer frequently develop malignant ascites that foster immunosuppressive microenvironments and therapeutic resistance2,3.Although ascites have traditionally been considered detrimental,we report a paradoxical role in which they enhance the cytotoxicity ofγδT cells—a unique T cell subset that can be allogenically transferred for cancer treatment4,5—toward ovarian cancer.
基金Supported by National Natural Science Foundation of China,No.81274173,No.81673671 and No.81270443Beijing National Science Foundation,No.7122017
文摘Macrophages(MΦ) differe ntiate from blood monocytes and participate in innate and adaptive immunity.Because of their abilities to recognize pathogens and activate bactericidal activities,MΦ are always discovered at the site of immune defense.MΦ in the intestine are unique,such that in the healthy intestine,they possess complex mechanisms to protect the gut from inflammation.In these complex mechanisms,they produce anti-inflammatory cytokines,such as interleukin-10 and transforming growth factor-β,and inhibit the inflammatory pathways mediated by Toll-like receptors.It has been demonstrated that resident MΦ play a crucial role in maintaining intestinal homeostasis,and they can be recognized by their unique markers.Nonetheless,in the inflamed intestine,the function of MΦ will change because of environmental variation,which may be one of the mechanisms of inflammatory bowel disease(IBD).We provide further explanation about these mechanisms in our review.In addition,we review recent discoveries that MΦ may be involved in the development of gastrointestinal tumors.We will highlight the possible therapeutic targets for the management of IBD and gastrointestinal tumors,and we also discuss why more details are needed to fully understand all other effects of intestinal MΦ.
基金Supported by the National Key Research and Development Program of China,No.2022YFC2305002Beijing Natural Science Foundation,No.7232079+1 种基金Middle-aged and Young Talent Incubation Programs(Clinical Research)of Beijing Youan Hospital,No.BJYAYY-YN2022-12,No.BJYAYY-YN2022-13,and No.BJYAYY-YN2022-01the China Postdoctoral Science Foundation,No.2023M732410 and No.2024T170595.
文摘BACKGROUND Patients with cirrhosis with hepatopulmonary syndrome(HPS)have a poorer prognosis.The disease has a subtle onset,symptoms are easily masked,clinical attention is insufficient,and misdiagnosis rates are high.AIM To compare the clinical characteristics of patients with cirrhosis,cirrhosis combined with intrapulmonary vascular dilatation(IPVD),and HPS,and to establish predictive models for IPVD and HPS.METHODS Patients with cirrhosis were prospectively screened at a liver-specialized university teaching hospital.Clinical information and blood samples were collected,and biomarker levels in blood samples were measured.Patients with cirrhosis were divided into three groups:Those with pure cirrhosis,those with combined IPVD,and those with HPS based on contrast-enhanced transthoracic echocardiography results and the pulmonary alveolar-arterial oxygen gradient values.Univariate logistic regression and Least Absolute Shrinkage and Selection Operator(LASSO)regression methods were utilized to identify risk factors for IPVD and HPS,and nomograms were constructed to predict IPVD and HPS.RESULTS A total of 320 patients were analyzed,with 101 diagnosed with IPVD,of whom 54 were diagnosed with HPS.There were statistically significant differences in clinical parameters among these three groups of patients.Among the tested biomarkers,sphingosine 1 phosphate,angiopoietin-2,and platelet-derived growth factor BB were significantly associated with IPVD and HPS in patients with cirrhosis.Following LASSO logistic regression screening,prediction models for IPVD and HPS were established.The area under the receiver operating characteristic curve for IPVD prediction was 0.792(95%confidence interval[CI]:0.737-0.847),and for HPS prediction was 0.891(95%CI:0.848-0.934).CONCLUSION This study systematically compared the clinical characteristics of patients with cirrhosis,IPVD,and HPS,and constructed predictive models for IPVD and HPS based on clinical parameters and laboratory indicators.These models showed good predictive value for IPVD and HPS in patients with cirrhosis.They can assist clinicians in the early prognosis assessment of patients with cirrhosis,ultimately benefiting the patients.
