In this paper,we introduce the design principle of the oscillating excited spray cooling experimental device.We then designed an oscillating excited spray cooling experimental device.By using the device,the swaying mo...In this paper,we introduce the design principle of the oscillating excited spray cooling experimental device.We then designed an oscillating excited spray cooling experimental device.By using the device,the swaying motion can be realized through the control system,and the motion of the droplet under different vibration frequencies can be observed.By measuring the liquid flow rate and pressure,the changes in liquid flow rate,pressure,and temperature with time under different vibration frequencies were studied.The trajectory of the droplet and the temperature distribution of the droplet under different vibration frequencies could be observed.The device has a simple structure,is easy to control,and can achieve continuous observation of the spray cooling process.展开更多
We investigated the asymmetric tension-compression(T-C)behavior of ZA21 bars with bimodal and uniform structures through axial tension and compression tests.The results show that the yield strengths of bars having bim...We investigated the asymmetric tension-compression(T-C)behavior of ZA21 bars with bimodal and uniform structures through axial tension and compression tests.The results show that the yield strengths of bars having bimodal structure are 206.42 and 140.28 MPa under tension and compression,respectively,which are higher than those of bars having uniform structure with tensile and compressive yield strength of 183.71 and 102.86 MPa,respectively.Prismatic slip and extension twinning under tension and basal slip and extension twinning under compression dominate the yield behavior and induce the T-C asymmetry.However,due to the basal slip activated in fine grains under tension and the inhibition of extension twinning by fine grains under compression,the bimodal structure possesses a lower T-C asymmetry(0.68)compared to the uniform structure(0.56).Multiple extension twins occur during deformation,and the selection of twin variants depends on the Schmid factor of the six variants activated by parent grains.Furthermore,the strengthening effect of the bimodal structure depends on the grain size and the ratio of coarse and fine grains.展开更多
The formability of magnesium alloys at ambient temperature can be enhanced by alloying additions such as Ca and RE elements,which is ascribed to the weakened basal texture.To produce magnesium alloy sheets with excell...The formability of magnesium alloys at ambient temperature can be enhanced by alloying additions such as Ca and RE elements,which is ascribed to the weakened basal texture.To produce magnesium alloy sheets with excellent comprehensive performance,the evolution of texture characterization during fabrication process and subsequent effect of texture on mechanical properties are vital controlling factors.In this investigation,three experimental Mg-3Al series alloys were hot rolled and annealed to sheets with 1 mm thickness.The microstructure evolution during rolling and annealing process was investigated.Furthermore,the influence of texture on tensile properties along different tensile directions was also studied.The results show that weakened basal texture and refined grains were achieved with the co-addition of Ca and RE element.However,strengthening of mechanical properties wasn't obtained.During hot rolling process,microstructure was refined,second phase particles broken,and basal texture was increased.While basal texture was weakened during annealing process.Recrystallization behavior influenced by formation of second phase was dominated to attenuate basal texture.Tensile deformation behavior was controlled by basal slip and followed Schmid factor criterion.Moreover,the weakened basal texture and activation of non-basal slips during hot rolling process can contribute to diminish the anisotropy of tensile properties.展开更多
The limited wide applicability of commercial Mg alloys is mainly attributed to the poor corrosion resistance.Addition of alloying elements is the simplest and effective method to improve the corrosion properties.Based...The limited wide applicability of commercial Mg alloys is mainly attributed to the poor corrosion resistance.Addition of alloying elements is the simplest and effective method to improve the corrosion properties.Based on the low-cost alloy composition design,the corro-sion behavior of commercial Mg-3Al-1Zn(AZ31)alloy bearing minor Ca or Sn element was characterized by scanning Kelvin probe force microscopy,hydrogen evolution,electrochemical measurements,and corrosion morphology analysis.Results revealed that the potential differ-ence of Al_(2)Ca/α-Mg and Mg_(2)Sn/α-Mg was(230±19)mV and(80±6)mV,respectively,much lower than that of Al_(8)Mn_(5)/α-Mg(430±31)mV in AZ31 alloy,which illustrated that AZ31-0.2Sn alloy performed the best corrosion resistance,followed by AZ31-0.2Ca,while AZ31 al-loy exhibited the worst corrosion resistance.Moreover,Sn dissolved into matrix obviously increased the potential ofα-Mg and participated in the formation of dense SnO_(2) film at the interface of matrix,while Ca element was enriched in the corrosion product layer,resulting in the cor-rosion product layer of AZ31-0.2Ca/Sn alloys more compact,stable,and protective than AZ31 alloy.Therefore,AZ31 alloy bearing 0.2wt%Ca or Sn element exhibited excellent balanced properties,which is potential to be applied in commercial more comprehensively.展开更多
Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six ...Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six groups:a normal control group,a model group,apositive control(domperidone)group and low-,middle-and high-dose CSD groups.A rat model of FD was established by constantly squeezing their tails.The rats were administered CSD(0.16g/mL,0.32g/mL,0.64g/mL)or domperidone(0.3 g/L)via intragastric gavage for four weeks.The gastric emptying rate was detected at 4 weeks post-administration.Apoptosis of GSMCs was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and the mitochondrial morphology was observed by transmission electron microscopy.The expression of Bcl-2and Bax was measured by immunohistochemistry.Results:FD resulted in marked reduction of gastric emptying rate,severe gastric tissue damage and mitochondria injury,but were reversed by CSD treatment(P<0.05).The apoptosis-induced protein Bax was markedly down-regulated by CSD,whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased(P<0.05).Furthermore,CSD could protect the FD rats against GSMCs apoptosis manifested by a decreased in TUNEL-positive cells(P<0.05).Conclusion:CSD could alleviate GSMCs apoptosis in FD rats,possibly by the modulation of Bcl-2 and Bax expression,and the suppression of mitochondria injury.展开更多
Objective:Immune checkpoint inhibitors(ICIs)have achieved remarkable results in cancer treatments.However,there is no effective predictive biomarker for gastrointestinal(GI)cancer.Methods:We conducted integrative anal...Objective:Immune checkpoint inhibitors(ICIs)have achieved remarkable results in cancer treatments.However,there is no effective predictive biomarker for gastrointestinal(GI)cancer.Methods:We conducted integrative analyses of the genomic and survival data of ICI-treated GI cancer patients from the Memorial Sloan Kettering Cancer Center cohort(MSK-GI,n=227),the Janjigian cohort(n=40),and the Peking University Cancer Hospital&Institute cohort(PUCH,n=80)to determine the possible associations between DNA damage response and repair(DDR)gene mutations and clinical outcomes.Data from The Cancer Genome Atlas database were analyzed to determine the possible correlations between DDR gene mutations and the tumor microenvironment.Results:In the MSK cohort,the presence of≥2 DDR gene mutations was correlated with prolonged overall survival(OS).The Janjigian and PUCH cohorts further confirmed that subgroups with≥2 DDR gene mutations displayed a prolonged OS and a higher durable clinical benefit.Furthermore,the DDR gene mutation load could be considered as an independent prognostic factor,and exhibited a potential predictive value for survival in GI cancer patients treated with ICIs.Mechanistically,we showed that the presence of≥2 DDR gene mutations was correlated with higher levels of tumor mutation burden,neoantigen,and T cell infiltration.Conclusions:The DDR gene mutation status was correlated with favorable clinical outcomes in GI cancer patients receiving ICIs,which could serve as a potential biomarker to guide patient selection for immunotherapy.展开更多
Aluminosilicate small pore zeolites belonging to ABC-6 family play crucially important roles in the high methanol conversion with the high selectivity of light olefins,gas separation and storage,and selective catalyti...Aluminosilicate small pore zeolites belonging to ABC-6 family play crucially important roles in the high methanol conversion with the high selectivity of light olefins,gas separation and storage,and selective catalytic reduction of NO_(x).In this work,we report a general method,called the epitaxial growth approach,for designing ABC-6 family small pore zeolites.It is mainly realized through the epitaxial growth on the nonporous SOD-type zeolite in the presence of inorganic cations(Na^(+)and K^(+))combined with a variety of organic structure directing agents(OSDAs).In this case,a series of ABC-6 family small pore zeolites such as ERI-,SWY-,LEV-,AFX-,and PTT-type zeolites have been successfully synthesized within a few hours.More importantly,the advanced focused ion beam(FIB)and the low-dose high-resolution transmission electron microscopy(HRTEM)imaging technique have been utilized for unraveling the zeolite heterojunction at the atomic level during the epitaxial growth process.It turns out(222)crystallographic planes of the SOD-type zeolite substrate provide unique pre-building units,which facilitate the growth of targeted ABC-6 family small pore zeolites along its c-axis.Moreover,the morphologies of ERI-type zeolite can also be tuned through the epitaxial growth approach,achieving a longer lifetime in the methanol conversion.展开更多
Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival benefits.Our preclinical data showed the promi...Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival benefits.Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC.This proof-of-concept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a confirmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable toxicity profile.Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2(NTRK2)was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR expression.Notably,knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment.Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.展开更多
Magnetite-functionalized biochar(MBC)is a promising engineered material for remediation of antibiotic-contaminated fields.However,sorption mechanisms of ionizable organic compounds such as sulfonamide antibiotics(SAs)...Magnetite-functionalized biochar(MBC)is a promising engineered material for remediation of antibiotic-contaminated fields.However,sorption mechanisms of ionizable organic compounds such as sulfonamide antibiotics(SAs)on MBC are still unclear.This study employed four representative SAs including sulfamethazine(SMT),sulfamerazine(SMR),sulfadiazine(SDZ),and sulfamethoxazole(SMX),to compare the difference in sorption on MBC.Results showed that the sorption capacities and affinities of the four SAs varied with their substituents,hydrophobic properties,and dissociation constants(pKa).Synergistic effect during co-pyrolysis with Fe^(3+)enhanced the sorption performance of MBC towards SAs compared to original BC.Spectral methods confirmed structural changes of MBC such as the variance in oxygen-containing groups and defective/graphitized phases.Results of modeling pH-dependent sorption revealed that H-bonding orπ-bond assisted H-bonding determined the sorption affinities and capacities of SAs.In particular,the SAs with lower pKa were thermodynamically favorable to form H-bonding with MBC via proton exchange with water molecules.Quantum calculation results quantified the contributions of H-bonding strengths and found that the energies of H-bonding were correlated with affinities of SAs.Moreover,contributions of oxygencontaining groups instead of minerals dominated the H-bonding energies.Mechanistic insights from this study can be valuable in exploring engineered BC composites for practical application in field remediation.展开更多
MoVTeNbO_(x) catalysts were prepared through a high-pressure hydrothermal method,in which the crystalline structure and properties of the catalysts were tuned by varying the system pressure(0-12.0 MPa).Results showed ...MoVTeNbO_(x) catalysts were prepared through a high-pressure hydrothermal method,in which the crystalline structure and properties of the catalysts were tuned by varying the system pressure(0-12.0 MPa).Results showed that the system pressure had a significant influence on the structure and catalytic performance of MoVTeNbO_(x).Under 3.0 MPa,MoVTeNbO_(x) prepared possessed the highest content of M1 phase(90.6%)and V5+content(60.7%),exhibiting a uniform short and thick needle-like morphology.Also,it showed excellent selectivity(79.1%)and yield(52.8%)to acrylic acid at the catalytic temperature of 380℃.However,under 4.4 and 11.6 MPa,the characteristic peaks of M1 shifted to a certain extent and the morphology changed from short and thick to slender.As a result,the V5+content of M1(001)plane decreased,resulting in a remarkable decline of the selectivity to acrylic acid.Moreover,DFT simulation results showed that the anti-bond orbital energy of V-O bond is the highest under 3.0 MPa,while further increase of pressure leads to obvious extrusion between atoms in the internal structure of MoVTeNbO_(x).Moreover,it was clear that the lower the anti-bond orbital energy of V-O bond,the lower the selectivity to acrylic acid.展开更多
Protein tyrosine kinases(PTKs)are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways.Their basal function is essential for maintaining no...Protein tyrosine kinases(PTKs)are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways.Their basal function is essential for maintaining normal cell growth and differentiation.However,aberrant activation of PTKs caused by various factors can deviate cell function from the expected trajectory to an abnormal growth state,leading to carcinogenesis.Inhibiting the aberrant PTK function could inhibit tumor growth.Therefore,tyrosine kinase inhibitors(TKIs),target-specific inhibitors of PTKs,have been used in treating malignant tumors and play a significant role in targeted therapy of cancer.Currently,drug resistance is the main reason for limiting TKIs efficacy of cancer.The increasing studies indicated that tumor microenvironment,cell death resistance,tumor metabolism,epigenetic modification and abnormal metabolism of TKIs were deeply involved in tumor development and TKI resistance,besides the abnormal activation of PTK-related signaling pathways involved in gene mutations.Accordingly,it is of great significance to study the underlying mechanisms of TKIs resistance and find solutions to reverse TKIs resistance for improving TKIs efficacy of cancer.Herein,we reviewed the drug resistance mechanisms of TKIs and the potential approaches to overcome TKI resistance,aiming to provide a theoretical basis for improving the efficacy of TKIs.展开更多
The corrosion performances of rolled AZ31 alloy with addition of Y and Gd were comparatively investigated. The corrosion rates of AZ31 alloy modified with Y and Gd were 3.3 and 3.7 mm/y immersing for 24 h in 3.5 wt% N...The corrosion performances of rolled AZ31 alloy with addition of Y and Gd were comparatively investigated. The corrosion rates of AZ31 alloy modified with Y and Gd were 3.3 and 3.7 mm/y immersing for 24 h in 3.5 wt% NaCl solution, respectively, which were much lower than that of AZ31 alloy(23.6 mm/y). The remarkable improvement in corrosion performance by adding Y or Gd was ascribed to preferentially form less noble Al_(2)Y or Al_(6)GdMn_(6) and more protective corrosion product layer, resulting in the reduction in H_(2) evolution rate and the enhancement of passivity.展开更多
基金The Natural Science Foundation of the Jiangsu Higher Education Institutions of China(22KJD580001)Jiangsu Maritime Institute Innovation Technology Funding Project(kicx2020-2)。
文摘In this paper,we introduce the design principle of the oscillating excited spray cooling experimental device.We then designed an oscillating excited spray cooling experimental device.By using the device,the swaying motion can be realized through the control system,and the motion of the droplet under different vibration frequencies can be observed.By measuring the liquid flow rate and pressure,the changes in liquid flow rate,pressure,and temperature with time under different vibration frequencies were studied.The trajectory of the droplet and the temperature distribution of the droplet under different vibration frequencies could be observed.The device has a simple structure,is easy to control,and can achieve continuous observation of the spray cooling process.
基金financially supported by the National Natural Science Foundation of China (No. 52275305)the Fundamental Research Funds for the Central Universities (No. FRF-IC-20-10)the China Postdoctoral Science Foundation (No. 2021M700378)
文摘We investigated the asymmetric tension-compression(T-C)behavior of ZA21 bars with bimodal and uniform structures through axial tension and compression tests.The results show that the yield strengths of bars having bimodal structure are 206.42 and 140.28 MPa under tension and compression,respectively,which are higher than those of bars having uniform structure with tensile and compressive yield strength of 183.71 and 102.86 MPa,respectively.Prismatic slip and extension twinning under tension and basal slip and extension twinning under compression dominate the yield behavior and induce the T-C asymmetry.However,due to the basal slip activated in fine grains under tension and the inhibition of extension twinning by fine grains under compression,the bimodal structure possesses a lower T-C asymmetry(0.68)compared to the uniform structure(0.56).Multiple extension twins occur during deformation,and the selection of twin variants depends on the Schmid factor of the six variants activated by parent grains.Furthermore,the strengthening effect of the bimodal structure depends on the grain size and the ratio of coarse and fine grains.
基金The authors would like to thank the financial support of Fundamental Research Funds for the Central Universities(No.2302019FRF-IC-19-018)Aviation Science Foundation Project(No.20181174001).
文摘The formability of magnesium alloys at ambient temperature can be enhanced by alloying additions such as Ca and RE elements,which is ascribed to the weakened basal texture.To produce magnesium alloy sheets with excellent comprehensive performance,the evolution of texture characterization during fabrication process and subsequent effect of texture on mechanical properties are vital controlling factors.In this investigation,three experimental Mg-3Al series alloys were hot rolled and annealed to sheets with 1 mm thickness.The microstructure evolution during rolling and annealing process was investigated.Furthermore,the influence of texture on tensile properties along different tensile directions was also studied.The results show that weakened basal texture and refined grains were achieved with the co-addition of Ca and RE element.However,strengthening of mechanical properties wasn't obtained.During hot rolling process,microstructure was refined,second phase particles broken,and basal texture was increased.While basal texture was weakened during annealing process.Recrystallization behavior influenced by formation of second phase was dominated to attenuate basal texture.Tensile deformation behavior was controlled by basal slip and followed Schmid factor criterion.Moreover,the weakened basal texture and activation of non-basal slips during hot rolling process can contribute to diminish the anisotropy of tensile properties.
基金This work is financially supported by the Fundamental Research Funds for the Central Universities,China(Nos.2302017FRF-IC-17-001,2302018FRF-IC-18-004,232019 FRF-IC-19-018,and 2302020FRF-IC-20-10)the China Postdoctoral Science Foundation(No.2021M700378).
文摘The limited wide applicability of commercial Mg alloys is mainly attributed to the poor corrosion resistance.Addition of alloying elements is the simplest and effective method to improve the corrosion properties.Based on the low-cost alloy composition design,the corro-sion behavior of commercial Mg-3Al-1Zn(AZ31)alloy bearing minor Ca or Sn element was characterized by scanning Kelvin probe force microscopy,hydrogen evolution,electrochemical measurements,and corrosion morphology analysis.Results revealed that the potential differ-ence of Al_(2)Ca/α-Mg and Mg_(2)Sn/α-Mg was(230±19)mV and(80±6)mV,respectively,much lower than that of Al_(8)Mn_(5)/α-Mg(430±31)mV in AZ31 alloy,which illustrated that AZ31-0.2Sn alloy performed the best corrosion resistance,followed by AZ31-0.2Ca,while AZ31 al-loy exhibited the worst corrosion resistance.Moreover,Sn dissolved into matrix obviously increased the potential ofα-Mg and participated in the formation of dense SnO_(2) film at the interface of matrix,while Ca element was enriched in the corrosion product layer,resulting in the cor-rosion product layer of AZ31-0.2Ca/Sn alloys more compact,stable,and protective than AZ31 alloy.Therefore,AZ31 alloy bearing 0.2wt%Ca or Sn element exhibited excellent balanced properties,which is potential to be applied in commercial more comprehensively.
基金supported by the National Natural Science Foundation of China(No.81360544)
文摘Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six groups:a normal control group,a model group,apositive control(domperidone)group and low-,middle-and high-dose CSD groups.A rat model of FD was established by constantly squeezing their tails.The rats were administered CSD(0.16g/mL,0.32g/mL,0.64g/mL)or domperidone(0.3 g/L)via intragastric gavage for four weeks.The gastric emptying rate was detected at 4 weeks post-administration.Apoptosis of GSMCs was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and the mitochondrial morphology was observed by transmission electron microscopy.The expression of Bcl-2and Bax was measured by immunohistochemistry.Results:FD resulted in marked reduction of gastric emptying rate,severe gastric tissue damage and mitochondria injury,but were reversed by CSD treatment(P<0.05).The apoptosis-induced protein Bax was markedly down-regulated by CSD,whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased(P<0.05).Furthermore,CSD could protect the FD rats against GSMCs apoptosis manifested by a decreased in TUNEL-positive cells(P<0.05).Conclusion:CSD could alleviate GSMCs apoptosis in FD rats,possibly by the modulation of Bcl-2 and Bax expression,and the suppression of mitochondria injury.
基金supported by the National Key Research and Development Program of China(Grant Nos.2018YFC1313302 and 2017YFC1308900)the Beijing Municipal Science and Technology Commission Program(Grant No.Z141107002514013)the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority(Grant No.XXT19).
文摘Objective:Immune checkpoint inhibitors(ICIs)have achieved remarkable results in cancer treatments.However,there is no effective predictive biomarker for gastrointestinal(GI)cancer.Methods:We conducted integrative analyses of the genomic and survival data of ICI-treated GI cancer patients from the Memorial Sloan Kettering Cancer Center cohort(MSK-GI,n=227),the Janjigian cohort(n=40),and the Peking University Cancer Hospital&Institute cohort(PUCH,n=80)to determine the possible associations between DNA damage response and repair(DDR)gene mutations and clinical outcomes.Data from The Cancer Genome Atlas database were analyzed to determine the possible correlations between DDR gene mutations and the tumor microenvironment.Results:In the MSK cohort,the presence of≥2 DDR gene mutations was correlated with prolonged overall survival(OS).The Janjigian and PUCH cohorts further confirmed that subgroups with≥2 DDR gene mutations displayed a prolonged OS and a higher durable clinical benefit.Furthermore,the DDR gene mutation load could be considered as an independent prognostic factor,and exhibited a potential predictive value for survival in GI cancer patients treated with ICIs.Mechanistically,we showed that the presence of≥2 DDR gene mutations was correlated with higher levels of tumor mutation burden,neoantigen,and T cell infiltration.Conclusions:The DDR gene mutation status was correlated with favorable clinical outcomes in GI cancer patients receiving ICIs,which could serve as a potential biomarker to guide patient selection for immunotherapy.
基金supported by National Key Research and Development Project of China(No.2022YFE0113800)National Natural Science Foundation of China(Nos.22288101,21972136,21991090 and 21991091)Key Research Program of Frontier Sciences,Chinese Academy of Sciences(No.QYZDB-SSW-JSC040)。
文摘Aluminosilicate small pore zeolites belonging to ABC-6 family play crucially important roles in the high methanol conversion with the high selectivity of light olefins,gas separation and storage,and selective catalytic reduction of NO_(x).In this work,we report a general method,called the epitaxial growth approach,for designing ABC-6 family small pore zeolites.It is mainly realized through the epitaxial growth on the nonporous SOD-type zeolite in the presence of inorganic cations(Na^(+)and K^(+))combined with a variety of organic structure directing agents(OSDAs).In this case,a series of ABC-6 family small pore zeolites such as ERI-,SWY-,LEV-,AFX-,and PTT-type zeolites have been successfully synthesized within a few hours.More importantly,the advanced focused ion beam(FIB)and the low-dose high-resolution transmission electron microscopy(HRTEM)imaging technique have been utilized for unraveling the zeolite heterojunction at the atomic level during the epitaxial growth process.It turns out(222)crystallographic planes of the SOD-type zeolite substrate provide unique pre-building units,which facilitate the growth of targeted ABC-6 family small pore zeolites along its c-axis.Moreover,the morphologies of ERI-type zeolite can also be tuned through the epitaxial growth approach,achieving a longer lifetime in the methanol conversion.
基金supported by the National Natural Science Foundation of China(No.92159106,82073230)the National Youth Top-Level Talent Support Program(“Ten Thousand Talents Scheme”)(12Y4962).
文摘Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival benefits.Our preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing ESCC.This proof-of-concept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a confirmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable toxicity profile.Transcriptome analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2(NTRK2)was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR expression.Notably,knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib treatment.Our study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.
基金Zhejiang Shuren University Basic Scientific Research Special Funds(No.2023XZ004).
文摘Magnetite-functionalized biochar(MBC)is a promising engineered material for remediation of antibiotic-contaminated fields.However,sorption mechanisms of ionizable organic compounds such as sulfonamide antibiotics(SAs)on MBC are still unclear.This study employed four representative SAs including sulfamethazine(SMT),sulfamerazine(SMR),sulfadiazine(SDZ),and sulfamethoxazole(SMX),to compare the difference in sorption on MBC.Results showed that the sorption capacities and affinities of the four SAs varied with their substituents,hydrophobic properties,and dissociation constants(pKa).Synergistic effect during co-pyrolysis with Fe^(3+)enhanced the sorption performance of MBC towards SAs compared to original BC.Spectral methods confirmed structural changes of MBC such as the variance in oxygen-containing groups and defective/graphitized phases.Results of modeling pH-dependent sorption revealed that H-bonding orπ-bond assisted H-bonding determined the sorption affinities and capacities of SAs.In particular,the SAs with lower pKa were thermodynamically favorable to form H-bonding with MBC via proton exchange with water molecules.Quantum calculation results quantified the contributions of H-bonding strengths and found that the energies of H-bonding were correlated with affinities of SAs.Moreover,contributions of oxygencontaining groups instead of minerals dominated the H-bonding energies.Mechanistic insights from this study can be valuable in exploring engineered BC composites for practical application in field remediation.
基金supports by the National Natural Science Foundation of China(no.21706165)Natural Science Foundation of Liaoning Province,China(no.2021-MS-255)+1 种基金LiaoNing Revitalization Talents Program(no.XLYC2002001)Shenyang Young and Middle-aged Science and Technology Innovation Talent Support Program,China(no.RC210184).
文摘MoVTeNbO_(x) catalysts were prepared through a high-pressure hydrothermal method,in which the crystalline structure and properties of the catalysts were tuned by varying the system pressure(0-12.0 MPa).Results showed that the system pressure had a significant influence on the structure and catalytic performance of MoVTeNbO_(x).Under 3.0 MPa,MoVTeNbO_(x) prepared possessed the highest content of M1 phase(90.6%)and V5+content(60.7%),exhibiting a uniform short and thick needle-like morphology.Also,it showed excellent selectivity(79.1%)and yield(52.8%)to acrylic acid at the catalytic temperature of 380℃.However,under 4.4 and 11.6 MPa,the characteristic peaks of M1 shifted to a certain extent and the morphology changed from short and thick to slender.As a result,the V5+content of M1(001)plane decreased,resulting in a remarkable decline of the selectivity to acrylic acid.Moreover,DFT simulation results showed that the anti-bond orbital energy of V-O bond is the highest under 3.0 MPa,while further increase of pressure leads to obvious extrusion between atoms in the internal structure of MoVTeNbO_(x).Moreover,it was clear that the lower the anti-bond orbital energy of V-O bond,the lower the selectivity to acrylic acid.
文摘Protein tyrosine kinases(PTKs)are a class of proteins with tyrosine kinase activity that phosphorylate tyrosine residues of critical molecules in signaling pathways.Their basal function is essential for maintaining normal cell growth and differentiation.However,aberrant activation of PTKs caused by various factors can deviate cell function from the expected trajectory to an abnormal growth state,leading to carcinogenesis.Inhibiting the aberrant PTK function could inhibit tumor growth.Therefore,tyrosine kinase inhibitors(TKIs),target-specific inhibitors of PTKs,have been used in treating malignant tumors and play a significant role in targeted therapy of cancer.Currently,drug resistance is the main reason for limiting TKIs efficacy of cancer.The increasing studies indicated that tumor microenvironment,cell death resistance,tumor metabolism,epigenetic modification and abnormal metabolism of TKIs were deeply involved in tumor development and TKI resistance,besides the abnormal activation of PTK-related signaling pathways involved in gene mutations.Accordingly,it is of great significance to study the underlying mechanisms of TKIs resistance and find solutions to reverse TKIs resistance for improving TKIs efficacy of cancer.Herein,we reviewed the drug resistance mechanisms of TKIs and the potential approaches to overcome TKI resistance,aiming to provide a theoretical basis for improving the efficacy of TKIs.
基金financially supported by the Fundamental Research Funds for the Central Universities(No.FRF-IC-20-10)。
文摘The corrosion performances of rolled AZ31 alloy with addition of Y and Gd were comparatively investigated. The corrosion rates of AZ31 alloy modified with Y and Gd were 3.3 and 3.7 mm/y immersing for 24 h in 3.5 wt% NaCl solution, respectively, which were much lower than that of AZ31 alloy(23.6 mm/y). The remarkable improvement in corrosion performance by adding Y or Gd was ascribed to preferentially form less noble Al_(2)Y or Al_(6)GdMn_(6) and more protective corrosion product layer, resulting in the reduction in H_(2) evolution rate and the enhancement of passivity.