Recent studies have successfully demonstrated high-Tc superconductivity in bilayer nickelate La3Ni2O7.However,research on modulating the structural and transport characteristics of La3Ni2O7 films by applying“chemical...Recent studies have successfully demonstrated high-Tc superconductivity in bilayer nickelate La3Ni2O7.However,research on modulating the structural and transport characteristics of La3Ni2O7 films by applying“chemical”compressive pressure through cation substitution is still limited.Here,we address this issue in the La_(3−x)Nd_(x)Ni_(2)O_(7)(x=0,1.0,1.5,2.0,and 2.5)thin film samples.It was found that using Nd3+with a smaller radius instead of La3+can reduce the c-axis lattice constant and shift the metal-insulator transition(MIT)temperature TMIT.To probe the origin of the MIT at cryogenic temperatures,experimental measurements of magnetoresistance were conducted,and theoretical analysis was carried out using the Kondo model,Hikami-Larkin-Nagaoka equation,and other methods.The results indicate that as Nd doping rises,the contributions of the Kondo effect and two-dimensional weak localization(WL)first decrease and then increase.The total contribution of WL and the Kondo effect in the mid-doped La_(1.5)Nd_(1.5)Ni_(2)O_(7)sample was the smallest,which to some extent explains the changes in TMIT.The Kondo effect dominates in other La_(3−x)Nd_(x)Ni_(2)O_(7)(x=0,1.0,2.0,and 2.5)samples.This work demonstrates that cation doping has a significant impact on bilayer nickelates,providing experimental evidence for understanding the physical mechanism of the MIT in bilayer nickelates.展开更多
Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the an...Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.展开更多
The recent discovery of superconductivity in La_(3)Ni_(2)O_(7-δ)with a transition temperature Tc close to 80 K at high pressures has attracted significant attention,due particularly to a possible density wave(DW)tran...The recent discovery of superconductivity in La_(3)Ni_(2)O_(7-δ)with a transition temperature Tc close to 80 K at high pressures has attracted significant attention,due particularly to a possible density wave(DW)transition occurring near the superconducting dome.Identifying the type of DW order is crucial for understanding the origin of superconductivity in this system.However,owing to the presence of La4Ni3O10 and other intergrowth phases in La_(3)Ni_(2)O_(7-δ)samples,extracting the intrinsic information from the La_(3)Ni_(2)O_(7) phase is challenging.In this study,we employed ^(139)La nuclear quadrupole resonance(NQR)measurements to eliminate the influence of other structural phases in the sample and obtain microscopic insights into the DW transition in La_(3)Ni_(2)O_(7-δ).Below the DW transition temperature T_(DW)∼153 K,we observe a distinct splitting in the±5/2↔±7/2 transition of the NQR resonance peak at the La(2)site,while only a line broadening is seen in the±3/2↔±5/2 transition peak.Through further analysis of the spectra,we show that the line splitting is due to a unidirectional charge modulation.A magnetic line broadening is also observed below T_(DW),accompanied by a large enhancement of the spin-lattice relaxation rate,indicating the formation of magnetically ordered moments in the DW state.Our results suggest a simultaneous formation of charge-and spin-density wave orders in La_(3)Ni_(2)O_(7-δ),thereby offering critical insights into the electronic correlations in Ni-based superconductors.展开更多
In a high heat flux ablative environment,the surface temperature of aircraft rises rapidly,leading to traditional high thermal conductivity materials being ineffective at protecting internal metal components.In this s...In a high heat flux ablative environment,the surface temperature of aircraft rises rapidly,leading to traditional high thermal conductivity materials being ineffective at protecting internal metal components.In this study,continuous carbon fiber reinforced Li_(2)O-Al_(2)O_(3)-SiO_(2)(C_(f)/LAS)glass ceramic composites doped with SiC particles(SiC_(p))were prepared by slurry immersion winding and hot pressing sintering.Effect of matrix crystallinity on ablative properties of the composites under ultra-high heat flux was investigated.By utilizing heat absorption and low thermal conductivity characteristics associated with SiO_(2)gasification within composite materials,both surface and internal temperatures of these materials are effectively reduced,thereby ensuring the safe operation of aircraft and electronic devices.Results indicate that the average linear ablation rate of composites doped with 10%(in mass)of SiC_(p)significantly decreases at a heat flux of 20 MW/m^(2).Transmission electron microscope observation reveals that the doped glass matrix exhibits increased crystallinity,reduced internal stress,and minimized lattice distortion,thereby enhancing the composites’high-temperature performance.However,excessive SiC_(p)doping leads to reduced crystallinity and deteriorated ablation performance.Ultimately,the average linear ablation rate of C_(f)/LAS composites with 10%(in mass)SiC_(p)at 20 MW/m^(2)heat flux is comparable to that of commercial carbon/carbon composites,accompanied by providing lower thermal conductivity and higher bending strength.This novel high-performance C_(f)/LAS composite is cost-effective,short-cycled,and suitable for mass production,offering promising potential for widespread application in ablation-resistant components of hypersonic vehicles.展开更多
The discovery of high-temperature superconductivity in bilayer nickelate La_(3)Ni_(2)O_(7)under high-pressure conditions has spurred extensive efforts to stabilize superconductivity at ambient pressure.Recently,the re...The discovery of high-temperature superconductivity in bilayer nickelate La_(3)Ni_(2)O_(7)under high-pressure conditions has spurred extensive efforts to stabilize superconductivity at ambient pressure.Recently,the realization of superconductivity in compressively strained La_(3)Ni_(2)O_(7)thin films grown on the SrLaAlO_(4)substrates,with a T_(c)exceeding 40 K,represents a significant step toward this goal.Here,we investigate the influence of film thickness and carrier doping on the electronic structure of La_(3)Ni_(2)O_(7)thin films,ranging from 0.5 to 3 unit cells,using first-principles calculations.For a 2 unit-cell film with an optimal doping concentration of 0.3 hole per formula unit(0.15 hole/Ni),the Ni-d_(z^(2))interlayer bonding state crosses the Fermi level,resulting in the formation ofγpockets at the Fermi surface.These findings align with angle-resolved photoemission spectroscopy experimental data.Our results provide theoretical validation for the recent experimental discovery of ambient-pressure superconductivity in La_(3)Ni_(2)O_(7)thin films and underscore the significant impact of film thickness and carrier doping on electronic property modulation.展开更多
Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stage...Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stages,this process results in cirrhosis and liver failure.The disease belongs to cholangiopathies.The review addressed historical questions concerning:The history of the first mention of this disease;how its nomenclature was formed;when specific serological tests were discovered and their importance in the diagnosis of PBC;the history of ursodeoxycholic and other bile acids for the treatment of PBC;and the significance of modern data on impaired bicarbonate production by cholangiocytes in the pathogenesis of PBC.展开更多
基金supported by the Natural Science Foundation of Guangdong Province of China(Grant No.2025A1515011071)the National Natural Science Foundation of China(Grant Nos.92065110,11974048,and 12074334)the Beijing Municipal Natural Science Foundation Key Research Topics(Grant No.Z230006)。
文摘Recent studies have successfully demonstrated high-Tc superconductivity in bilayer nickelate La3Ni2O7.However,research on modulating the structural and transport characteristics of La3Ni2O7 films by applying“chemical”compressive pressure through cation substitution is still limited.Here,we address this issue in the La_(3−x)Nd_(x)Ni_(2)O_(7)(x=0,1.0,1.5,2.0,and 2.5)thin film samples.It was found that using Nd3+with a smaller radius instead of La3+can reduce the c-axis lattice constant and shift the metal-insulator transition(MIT)temperature TMIT.To probe the origin of the MIT at cryogenic temperatures,experimental measurements of magnetoresistance were conducted,and theoretical analysis was carried out using the Kondo model,Hikami-Larkin-Nagaoka equation,and other methods.The results indicate that as Nd doping rises,the contributions of the Kondo effect and two-dimensional weak localization(WL)first decrease and then increase.The total contribution of WL and the Kondo effect in the mid-doped La_(1.5)Nd_(1.5)Ni_(2)O_(7)sample was the smallest,which to some extent explains the changes in TMIT.The Kondo effect dominates in other La_(3−x)Nd_(x)Ni_(2)O_(7)(x=0,1.0,2.0,and 2.5)samples.This work demonstrates that cation doping has a significant impact on bilayer nickelates,providing experimental evidence for understanding the physical mechanism of the MIT in bilayer nickelates.
基金funded by the Major Research Plan of the National Natural Science Foundation of China(No.92159202)the National Key Research and Development Program of China(No.2021YFA1100500)+1 种基金the Leading Innovation Team Project of Hangzhou Medical College(No.CXLJ202401)the Key Research and Development Plan of Zhejiang Provincial Department of Science and Technology(No.2024C03051)。
文摘Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.
基金supported by the National Key Research and Development Projects of China(Grant Nos.2023YFA1406103,2024YFA1611302,2024YFA1409200,and 2022YFA1403402)the National Natural Science Foundation of China(Grant Nos.12374142,12304170,12025408,12404179,and U23A6003)+2 种基金Beijing National Laboratory for Condensed Matter Physics(Grant No.2024BNLCMPKF005)the Chinese Academy of Sciences President’s International Fellowship Initiative(Grant No.2024PG0003)supported by the Synergetic Extreme Condition User Facility(SECUF,https://cstr.cn/31123.02.SECUF)。
文摘The recent discovery of superconductivity in La_(3)Ni_(2)O_(7-δ)with a transition temperature Tc close to 80 K at high pressures has attracted significant attention,due particularly to a possible density wave(DW)transition occurring near the superconducting dome.Identifying the type of DW order is crucial for understanding the origin of superconductivity in this system.However,owing to the presence of La4Ni3O10 and other intergrowth phases in La_(3)Ni_(2)O_(7-δ)samples,extracting the intrinsic information from the La_(3)Ni_(2)O_(7) phase is challenging.In this study,we employed ^(139)La nuclear quadrupole resonance(NQR)measurements to eliminate the influence of other structural phases in the sample and obtain microscopic insights into the DW transition in La_(3)Ni_(2)O_(7-δ).Below the DW transition temperature T_(DW)∼153 K,we observe a distinct splitting in the±5/2↔±7/2 transition of the NQR resonance peak at the La(2)site,while only a line broadening is seen in the±3/2↔±5/2 transition peak.Through further analysis of the spectra,we show that the line splitting is due to a unidirectional charge modulation.A magnetic line broadening is also observed below T_(DW),accompanied by a large enhancement of the spin-lattice relaxation rate,indicating the formation of magnetically ordered moments in the DW state.Our results suggest a simultaneous formation of charge-and spin-density wave orders in La_(3)Ni_(2)O_(7-δ),thereby offering critical insights into the electronic correlations in Ni-based superconductors.
基金National Natural Science Foundation of China(U23A6014,52103357)。
文摘In a high heat flux ablative environment,the surface temperature of aircraft rises rapidly,leading to traditional high thermal conductivity materials being ineffective at protecting internal metal components.In this study,continuous carbon fiber reinforced Li_(2)O-Al_(2)O_(3)-SiO_(2)(C_(f)/LAS)glass ceramic composites doped with SiC particles(SiC_(p))were prepared by slurry immersion winding and hot pressing sintering.Effect of matrix crystallinity on ablative properties of the composites under ultra-high heat flux was investigated.By utilizing heat absorption and low thermal conductivity characteristics associated with SiO_(2)gasification within composite materials,both surface and internal temperatures of these materials are effectively reduced,thereby ensuring the safe operation of aircraft and electronic devices.Results indicate that the average linear ablation rate of composites doped with 10%(in mass)of SiC_(p)significantly decreases at a heat flux of 20 MW/m^(2).Transmission electron microscope observation reveals that the doped glass matrix exhibits increased crystallinity,reduced internal stress,and minimized lattice distortion,thereby enhancing the composites’high-temperature performance.However,excessive SiC_(p)doping leads to reduced crystallinity and deteriorated ablation performance.Ultimately,the average linear ablation rate of C_(f)/LAS composites with 10%(in mass)SiC_(p)at 20 MW/m^(2)heat flux is comparable to that of commercial carbon/carbon composites,accompanied by providing lower thermal conductivity and higher bending strength.This novel high-performance C_(f)/LAS composite is cost-effective,short-cycled,and suitable for mass production,offering promising potential for widespread application in ablation-resistant components of hypersonic vehicles.
基金supported by the National Key R&D Program of China(Gran Nos.2022YFA1402304 and 2022YFA1402802)the National Natural Science Foundation of China(Grant Nos.12494591,12122405,12274169,and 92165204)+4 种基金Program for Science and Technology Innovation Team in Zhejiang(Grant No.2021R01004)Guangdong Provincial Key Laboratory of Magnetoelectric Physics and Devices(Grant No.2022B1212010008)Guangdong Fundamental Research Center for Magnetoelectric Physics(2024B0303390001)Guangdong Provincial Quantum Science Strategic Initiative(Grant No.GDZX2401010)the Fundamental Research Funds for the Central Universities。
文摘The discovery of high-temperature superconductivity in bilayer nickelate La_(3)Ni_(2)O_(7)under high-pressure conditions has spurred extensive efforts to stabilize superconductivity at ambient pressure.Recently,the realization of superconductivity in compressively strained La_(3)Ni_(2)O_(7)thin films grown on the SrLaAlO_(4)substrates,with a T_(c)exceeding 40 K,represents a significant step toward this goal.Here,we investigate the influence of film thickness and carrier doping on the electronic structure of La_(3)Ni_(2)O_(7)thin films,ranging from 0.5 to 3 unit cells,using first-principles calculations.For a 2 unit-cell film with an optimal doping concentration of 0.3 hole per formula unit(0.15 hole/Ni),the Ni-d_(z^(2))interlayer bonding state crosses the Fermi level,resulting in the formation ofγpockets at the Fermi surface.These findings align with angle-resolved photoemission spectroscopy experimental data.Our results provide theoretical validation for the recent experimental discovery of ambient-pressure superconductivity in La_(3)Ni_(2)O_(7)thin films and underscore the significant impact of film thickness and carrier doping on electronic property modulation.
文摘Primary biliary cholangitis(PBC)is a chronic cholestatic liver disease characterized by damage and loss of the epithelial lining of small intrahepatic bile ducts,leading to ductopenia and cholestasis.In advanced stages,this process results in cirrhosis and liver failure.The disease belongs to cholangiopathies.The review addressed historical questions concerning:The history of the first mention of this disease;how its nomenclature was formed;when specific serological tests were discovered and their importance in the diagnosis of PBC;the history of ursodeoxycholic and other bile acids for the treatment of PBC;and the significance of modern data on impaired bicarbonate production by cholangiocytes in the pathogenesis of PBC.
