The use of steel slag,which is a by-product of the steel manufacture,in the construction of asphalt pavement would contribute to waste reduction and environment protection.Using rubber asphalt at the same time can imp...The use of steel slag,which is a by-product of the steel manufacture,in the construction of asphalt pavement would contribute to waste reduction and environment protection.Using rubber asphalt at the same time can improve the performance of asphalt mixture.This study investigates the influence of steel slag content on the road performance,thermal conductivity and outdoor temperature distribution of steel slag rubber asphalt mixtures(SSRAM),and calculates the cumulative stress in surface layer.At a certain range of concentration,the steel slag additive improved the deformation resistance and low-temperature cracking resistance of the mixtures.The SSRAM with 40%steel slag content has the best deformation resistance while SSRAM with 60%steel slag content performed well in low-temperature cracking resistance.The thermal conductivity of the SSRAM with different steel slag content(0%,20%,40%,60%,80%,and 100%)was 1.994,2.188,2.239,2.255,2.288,and 2.295 W/(m·K),respectively.Measurements of the outdoor temperature distribution further confirmed that steel slag increased the thermal conductivity of the mixtures,thereby increasing the cumulative temperature difference between the top and bottom layers.The temperature stress and temperature-stress ratio of the SSRAM with 40%steel slag were 0.43 MPa and 0.24,while the SSRAM with 100%steel slag were 0.58 MPa and 0.36.The stress and stress ratio were much higher in the SSRAM with 100%steel slag than in the specimen with 40%steel slag.Accordingly,the maximum accumulated temperature stress aggrandized and caused early temperature cracks in the surface layer.The optimum content of steel slag was 40%.展开更多
Bio-oil recycled asphalt binders in road engineering can help solve the problem of oil shortage and reduce the environmental pollution and sustainability.This paper investigated the road performance of the aged asphal...Bio-oil recycled asphalt binders in road engineering can help solve the problem of oil shortage and reduce the environmental pollution and sustainability.This paper investigated the road performance of the aged asphalt binder by adding bio-oil so that the aged asphalt binder could be reused to reach purpose of reuse.The residual soybean oil was selected as rejuvenator and blended with aged asphalt binder at 0%,2%,4%,and 6%,respectively.The results showed that bio-oil increased the penetration of aged asphalt binder,the penetration of bio-oil recycled asphalt binder with a bio-oil content of 6%reached the standard of 70#matrix asphalt binder.The addition of bio-oil reduced the viscosity,mixing and compaction temperature of aged asphalt binder.As a common knowledge,bio-oil helps to increase the lightweight components of the aged asphalt binder,which diminishes the high-temperature rutting resistance of bio-oil recycled asphalt binders.The high-temperature deformation resistance of bio-oil recycled asphalt binders had not decreased linearly with the bio-oil dosage.Meanwhile,the hightemperature performance of the bio-oil recycled asphalt binder with a 6%bio-oil was superior to matrix asphalt binder.Bio-oil increased the light components of the aged asphalt binder,thus reducing the high-temperature rheological properties of bio-oil recycled asphalt binders as the bio-oil dosage increases.The above test results showed that the bio-oil could restore the aged asphalt binder to the initial level to reach the reuse target.展开更多
Objective: To study the expressions of Bcl-2 and Bax proteins and explore the relationships between them and apoptosis in gastric carcinoma and precancerous lesions. Methods: TUNEL method was used to detect apoptosis ...Objective: To study the expressions of Bcl-2 and Bax proteins and explore the relationships between them and apoptosis in gastric carcinoma and precancerous lesions. Methods: TUNEL method was used to detect apoptosis and im- munohistochemical staining method was used to detect the expressions of Bcl-2 and Bax proteins in 70 cases of chronic gastritis, 49 cases of intestinal metaplasia, 64 cases of dysplasia and 81 cases of gastric carcinoma. Results: The positive incidences of Bcl-2 and Bax were the highest in severe dysplasia. In intestinal metaplasia and dysplasia, positive incidences of Bcl-2 and Bax were higher than those in chronic gastritis and gastric carcinoma. During the process of evolvement from chronic gastritis to intestinal metaplasia then to dysplasia, apoptosis indexes gradually rise up to mid-high dysplasia, which reached the highest point, then it began to fall down, when it reached the lowest point in gastric carcinoma. There were nega- tive correlations between the expressions of Bcl-2, Bax proteins and apoptosis. Conclusion: The expression of Bcl-2 may be an early behavior in the gastric carcinogenesis. Bax had antagonistic effect to Bcl-2. Detections of Bcl-2 and Bax may be beneficial to the early diagnosis of gastric tumor and precancerous lesions.展开更多
Steel slag is regarded as one of the most widespread solid by-products of steel smelting with little commercial value.It can play a vital role in the construction industry especially in the field of transportation inf...Steel slag is regarded as one of the most widespread solid by-products of steel smelting with little commercial value.It can play a vital role in the construction industry especially in the field of transportation infrastructure construction.However,there are few evaluation systems established on the high-temperature deformation and low-temperature fracture behavior of steel slag rubber asphalt mixture(SSRAM).This study explores the perfor-mance of SSRAM by uniaxial penetration test,Semi-Circular Bending(SCB)test and evaluates test data through regression analysis.The uniaxial penetration test results shows that the failure deformation of SSRAM increases with the increase of steel slag content.According to the minimum allowable permanent deformation(R TS-min),the deformation of SSRAM should be controlled within 3 mm.Meanwhile,the cracking index of the SSRAM surface layer calculated at low temperature can meet the design requirements.The SCB test results show that the stress peak degradation rate(specimens with 10 mm notch are compared with 0 mm)of SSRAM with 40%steel slag content is 20.04%.That means proper steel slag content makes the stress peak degradation rate of SSRAM reaches the lowest value.The calculation results of fracture energy density(J_(1C))show that the steel slag additive reduced the fracture energy density of SSRAM.However,it is still proved that SSRAM with 40%steel slag has the best low-temperature fracture performance based on critical fracture toughness(K_(1C))and fracture stress peak.Further-more,the crack propagation velocity parametric equation of SSRAM is proposed through fracture mechanics theory and the increase of velocity is exponential.Considering the high-temperature deformation resistance and low-temperature fracture property,the SSRAM surface layer with 40%steel slag content showed a batter application potential.展开更多
Objective: To investigate the apoptosis effect of TNF-α on HepG2 cells and its mechanism in vitro. Methods: HepG2 cells were treated with TNF-α (400 U/mL). HepG2 cells treated with TNF-α for 24 h and apoptosis was ...Objective: To investigate the apoptosis effect of TNF-α on HepG2 cells and its mechanism in vitro. Methods: HepG2 cells were treated with TNF-α (400 U/mL). HepG2 cells treated with TNF-α for 24 h and apoptosis was proved by DNA fragments on gel electrophoresis. Fluorescent quantitative real-time PCR was used to detect Fas and FasL expression. HepG2 cells treated by TNF-α were co-cultivated with normal HepG2 cells. Apoptosis of HepG2 cells was determined by the method of FACS. Results: After 24 h TNF-α treatment, DNA was collapsed into fragments to form DNA ladder in gel elec- trophoresis; FasL expression increases and induces HepG2 cells apoptosis. By FACS, 98.4% of the co-cultivated cells were apoptosis, but 16.5% cells in control group were apoptosis. Conclusion: TNF-α can induce apoptosis of HepG2 cells in vitro. FasL expression on TNF-α pre-treated HepG2 cells increased and these cells can lead normal HepG2 cells to apoptosis. This may attribute to the cure of virus hepatitis and hepatoma.展开更多
In order to improve the utilization of milling materials,save stone resources and reduce milling energy consumption,the aged Styrene-butadiene-styrene(SBS)modified asphalt was used as a binder to prepare AC-16 asphal...In order to improve the utilization of milling materials,save stone resources and reduce milling energy consumption,the aged Styrene-butadiene-styrene(SBS)modified asphalt was used as a binder to prepare AC-16 asphalt mixture to simulate old asphalt pavement materials.First,the test and discrete element simulation results of uniaxial compression tests were used to calibrate the parameters of the parallel bonding contact model between asphalt mortar and aggregates.On this basis,a microscopic model of the asphalt mixture was established to simulate the old asphalt pavement.Then,the discrete element software PFC(Particle Flow Code)was used to simulate the milling process of the old asphalt pavement.Analyzed the force of the cutting tool and the utilization rate of milling materials,and the optimal milling speed and milling depth were determined.Finally,the energy consumption in the milling process was measured.It is concluded that in the process of milling the old asphalt pavement,using a cutting angle of 42°,milling speed of 0.5 m/s and milling depth of 20 mm can reduce the wear of the cutting tool.In this case,the direct utilization rate of milling materials is 85.3%,and the rate of energy consumption reduction is 33.53%.After parameter optimization,the utilization rate of milling materials can be increased by 17.4%.展开更多
It is widely recognized that tumor immune microenvironment(TIME)plays a crucial role in tumor progression,metastasis,and therapeutic response.Despite several noninvasive strategies have emerged for cancer diagnosis an...It is widely recognized that tumor immune microenvironment(TIME)plays a crucial role in tumor progression,metastasis,and therapeutic response.Despite several noninvasive strategies have emerged for cancer diagnosis and prognosis,there are still lack of efective radiomic-based model to evaluate TIME status,let alone predict clinical outcome and immune checkpoint inhibitor(ICIs)response for hepatocellular carcinoma(HCC).In this study,we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response.A total of 301 patients who underwent magnetic resonance imaging(MRI)examinations were enrolled in our study.The intra-tumoral expression of 17 immune-related molecules were evaluated using co-detection by indexing(CODEX)technology,and we construct Immunoscore(IS)with the least absolute shrinkage and selection operator(LASSO)algorithm and Cox regression method to evaluate TIME.Of 6115 features extracted from MRI,fve core features were fltered out,and the Radiomic Immunoscore(RIS)showed high accuracy in predicting TIME status in testing cohort(area under the curve=0.753).More importantly,RIS model showed the capability of predicting therapeutic response to anti-programmed cell death 1(PD-1)immunotherapy in an independent cohort with advanced HCC patients(area under the curve=0.731).In comparison with previously radiomicbased models,our integrated RIS model exhibits not only higher accuracy in predicting prognosis but also the potential guiding signifcance to HCC immunotherapy.展开更多
To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel r...To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.展开更多
A three-dimensional finite element model (3D FEM) is built using ABAQUS to analyze the dynamic response of a concrete pavement structure with an asphalt isolating layer under moving loads. The 3D model is prepared a...A three-dimensional finite element model (3D FEM) is built using ABAQUS to analyze the dynamic response of a concrete pavement structure with an asphalt isolating layer under moving loads. The 3D model is prepared and validated in the state of no asphalt isolating layer. Stress and deflection at the critical load position are calculated by changing thickness, modulus of isolating layer and the combination between the isolating layer and concrete slab. Analysis result shows that the stress and deflection of the concrete slab increase with the increase of thickness. The stress and deflection of the concrete slab decrease with the increase of combination between the isolating layer and concrete slab. The influence of changing the isolating layer modulus to the stress and deflection of the concrete slab is not significant. From the results, asphalt isolating layer design is suggested in concrete pavement.展开更多
Following the publication of the US National Research Council (N RC) report " Toward PrecMon Medicine." Building a Knowledge Network for Biomedical Research and a New Taxonomy of Diseases" in 2011 [1], several n...Following the publication of the US National Research Council (N RC) report " Toward PrecMon Medicine." Building a Knowledge Network for Biomedical Research and a New Taxonomy of Diseases" in 2011 [1], several nations have announced that their national research programs would definitely head toward this direction. Now,展开更多
Synaptotagmin (Syt) constitutes a family of membrane-trafficking proteins, so far nearly 20 Syts have been discovered. Extensive work showed that synatotagmins were a potential Ca^2+ sensor for regulated exocytosis...Synaptotagmin (Syt) constitutes a family of membrane-trafficking proteins, so far nearly 20 Syts have been discovered. Extensive work showed that synatotagmins were a potential Ca^2+ sensor for regulated exocytosis. This study was to investigate the expression and location of synaptotagmin II (Syt2) in RBL-2H3 (RBL) and its role in regulating exocytosis of RBL. The expression of Syt2 in RBL was confirmed by Western blot. The recombinant expression vector pEGFP-N1-Syt2 was constructed and transfected into RBL by electroporation, the stable transfectant RBL-Syt2-S expressing fusion protein Syt2-EGFP were obtained and Syt2 was highly concentrated at plasma membrane with little detected in cytoplasm. To analyze the role of Syt2 during exocytosis of RBL, the release of cathepsin D was assayed by immunoblotting. Compared with control, the release of cathepsin D by RBL-Syt2-S was markedly decreased. The results indicated that Syt2 played a negative regulation in exocytosis of lysosomes in RBL. Cellular & Molecular Immunology. 2005;2(3):205-209.展开更多
Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several ...Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several types of cancers,and ferroptosis inducers can be used to promote ferroptosis in tumor cells and play an anti-tumor role.However,the specificity and efficacy of ferroptosis inducers remain unsatisfactory.Here,a new mitochondria-targeted photosensitizer(PS)with aggregation-induced emission(AIE)characteristic named TCSVP was designed,which efficiently generates ROS in mitochondria after light exposure.TCSVP administration significantly sensitizes tumor cells to ferroptosis inducer(RSL3)-mediated cell death by specifically and light-dependently triggering a moderate ROS generation in vitro and in vivo.Mechanically,the expression levels of ferroptosis related proteins Acyl-CoA synthetase long-chain family member 4(FACL4/ACSL4)and cyclooxygenase-2(COX2)were increased in TCSVP/RSL3-treated cells after light exposure,coupled with decreased Glutathione peroxidase 4(GPX4)activity and excessive malondialdehyde(MDA)accumulation.This study declared that light-induced moderate ROS generation within mitochondria in cancer cells by AIE-PS can be used to enhance the specificity and efficacy of ferroptosis inducers,bringing a new synergistic strategy for tumor intervention.展开更多
A recent study by Hoon Kim et al.published in Nature Genetics demonstrated that extrachromosomal DNA(ecDNA)-based oncogene amplification frequently occurs in most cancer types and that it is different from chromosomal...A recent study by Hoon Kim et al.published in Nature Genetics demonstrated that extrachromosomal DNA(ecDNA)-based oncogene amplification frequently occurs in most cancer types and that it is different from chromosomal amplification.1 The authors further showed that ecDNA in multiple cancer types leads to poor outcomes in patients;thus,ecDNA is a novel potential diagnostic or therapeutic target for tumor treatment(Fig.1).展开更多
基金This research was funded by the Department of Transportation of Hebei Province(Grant No.TH1-202019).
文摘The use of steel slag,which is a by-product of the steel manufacture,in the construction of asphalt pavement would contribute to waste reduction and environment protection.Using rubber asphalt at the same time can improve the performance of asphalt mixture.This study investigates the influence of steel slag content on the road performance,thermal conductivity and outdoor temperature distribution of steel slag rubber asphalt mixtures(SSRAM),and calculates the cumulative stress in surface layer.At a certain range of concentration,the steel slag additive improved the deformation resistance and low-temperature cracking resistance of the mixtures.The SSRAM with 40%steel slag content has the best deformation resistance while SSRAM with 60%steel slag content performed well in low-temperature cracking resistance.The thermal conductivity of the SSRAM with different steel slag content(0%,20%,40%,60%,80%,and 100%)was 1.994,2.188,2.239,2.255,2.288,and 2.295 W/(m·K),respectively.Measurements of the outdoor temperature distribution further confirmed that steel slag increased the thermal conductivity of the mixtures,thereby increasing the cumulative temperature difference between the top and bottom layers.The temperature stress and temperature-stress ratio of the SSRAM with 40%steel slag were 0.43 MPa and 0.24,while the SSRAM with 100%steel slag were 0.58 MPa and 0.36.The stress and stress ratio were much higher in the SSRAM with 100%steel slag than in the specimen with 40%steel slag.Accordingly,the maximum accumulated temperature stress aggrandized and caused early temperature cracks in the surface layer.The optimum content of steel slag was 40%.
文摘Bio-oil recycled asphalt binders in road engineering can help solve the problem of oil shortage and reduce the environmental pollution and sustainability.This paper investigated the road performance of the aged asphalt binder by adding bio-oil so that the aged asphalt binder could be reused to reach purpose of reuse.The residual soybean oil was selected as rejuvenator and blended with aged asphalt binder at 0%,2%,4%,and 6%,respectively.The results showed that bio-oil increased the penetration of aged asphalt binder,the penetration of bio-oil recycled asphalt binder with a bio-oil content of 6%reached the standard of 70#matrix asphalt binder.The addition of bio-oil reduced the viscosity,mixing and compaction temperature of aged asphalt binder.As a common knowledge,bio-oil helps to increase the lightweight components of the aged asphalt binder,which diminishes the high-temperature rutting resistance of bio-oil recycled asphalt binders.The high-temperature deformation resistance of bio-oil recycled asphalt binders had not decreased linearly with the bio-oil dosage.Meanwhile,the hightemperature performance of the bio-oil recycled asphalt binder with a 6%bio-oil was superior to matrix asphalt binder.Bio-oil increased the light components of the aged asphalt binder,thus reducing the high-temperature rheological properties of bio-oil recycled asphalt binders as the bio-oil dosage increases.The above test results showed that the bio-oil could restore the aged asphalt binder to the initial level to reach the reuse target.
文摘Objective: To study the expressions of Bcl-2 and Bax proteins and explore the relationships between them and apoptosis in gastric carcinoma and precancerous lesions. Methods: TUNEL method was used to detect apoptosis and im- munohistochemical staining method was used to detect the expressions of Bcl-2 and Bax proteins in 70 cases of chronic gastritis, 49 cases of intestinal metaplasia, 64 cases of dysplasia and 81 cases of gastric carcinoma. Results: The positive incidences of Bcl-2 and Bax were the highest in severe dysplasia. In intestinal metaplasia and dysplasia, positive incidences of Bcl-2 and Bax were higher than those in chronic gastritis and gastric carcinoma. During the process of evolvement from chronic gastritis to intestinal metaplasia then to dysplasia, apoptosis indexes gradually rise up to mid-high dysplasia, which reached the highest point, then it began to fall down, when it reached the lowest point in gastric carcinoma. There were nega- tive correlations between the expressions of Bcl-2, Bax proteins and apoptosis. Conclusion: The expression of Bcl-2 may be an early behavior in the gastric carcinogenesis. Bax had antagonistic effect to Bcl-2. Detections of Bcl-2 and Bax may be beneficial to the early diagnosis of gastric tumor and precancerous lesions.
基金This research was funded by the Department of Transportation of Hebei Province(Grant No.TH1-202019)。
文摘Steel slag is regarded as one of the most widespread solid by-products of steel smelting with little commercial value.It can play a vital role in the construction industry especially in the field of transportation infrastructure construction.However,there are few evaluation systems established on the high-temperature deformation and low-temperature fracture behavior of steel slag rubber asphalt mixture(SSRAM).This study explores the perfor-mance of SSRAM by uniaxial penetration test,Semi-Circular Bending(SCB)test and evaluates test data through regression analysis.The uniaxial penetration test results shows that the failure deformation of SSRAM increases with the increase of steel slag content.According to the minimum allowable permanent deformation(R TS-min),the deformation of SSRAM should be controlled within 3 mm.Meanwhile,the cracking index of the SSRAM surface layer calculated at low temperature can meet the design requirements.The SCB test results show that the stress peak degradation rate(specimens with 10 mm notch are compared with 0 mm)of SSRAM with 40%steel slag content is 20.04%.That means proper steel slag content makes the stress peak degradation rate of SSRAM reaches the lowest value.The calculation results of fracture energy density(J_(1C))show that the steel slag additive reduced the fracture energy density of SSRAM.However,it is still proved that SSRAM with 40%steel slag has the best low-temperature fracture performance based on critical fracture toughness(K_(1C))and fracture stress peak.Further-more,the crack propagation velocity parametric equation of SSRAM is proposed through fracture mechanics theory and the increase of velocity is exponential.Considering the high-temperature deformation resistance and low-temperature fracture property,the SSRAM surface layer with 40%steel slag content showed a batter application potential.
文摘Objective: To investigate the apoptosis effect of TNF-α on HepG2 cells and its mechanism in vitro. Methods: HepG2 cells were treated with TNF-α (400 U/mL). HepG2 cells treated with TNF-α for 24 h and apoptosis was proved by DNA fragments on gel electrophoresis. Fluorescent quantitative real-time PCR was used to detect Fas and FasL expression. HepG2 cells treated by TNF-α were co-cultivated with normal HepG2 cells. Apoptosis of HepG2 cells was determined by the method of FACS. Results: After 24 h TNF-α treatment, DNA was collapsed into fragments to form DNA ladder in gel elec- trophoresis; FasL expression increases and induces HepG2 cells apoptosis. By FACS, 98.4% of the co-cultivated cells were apoptosis, but 16.5% cells in control group were apoptosis. Conclusion: TNF-α can induce apoptosis of HepG2 cells in vitro. FasL expression on TNF-α pre-treated HepG2 cells increased and these cells can lead normal HepG2 cells to apoptosis. This may attribute to the cure of virus hepatitis and hepatoma.
文摘In order to improve the utilization of milling materials,save stone resources and reduce milling energy consumption,the aged Styrene-butadiene-styrene(SBS)modified asphalt was used as a binder to prepare AC-16 asphalt mixture to simulate old asphalt pavement materials.First,the test and discrete element simulation results of uniaxial compression tests were used to calibrate the parameters of the parallel bonding contact model between asphalt mortar and aggregates.On this basis,a microscopic model of the asphalt mixture was established to simulate the old asphalt pavement.Then,the discrete element software PFC(Particle Flow Code)was used to simulate the milling process of the old asphalt pavement.Analyzed the force of the cutting tool and the utilization rate of milling materials,and the optimal milling speed and milling depth were determined.Finally,the energy consumption in the milling process was measured.It is concluded that in the process of milling the old asphalt pavement,using a cutting angle of 42°,milling speed of 0.5 m/s and milling depth of 20 mm can reduce the wear of the cutting tool.In this case,the direct utilization rate of milling materials is 85.3%,and the rate of energy consumption reduction is 33.53%.After parameter optimization,the utilization rate of milling materials can be increased by 17.4%.
基金National Natural Science Foundation of China(U21A20376,81988101,81790633 and 81830054)National Science Foundation of Shanghai(21XD1404600,17ZR143800,21JC1406600 and 22140901000)Project of Shanghai Municipal Commission of Health(2022LJ024).
文摘It is widely recognized that tumor immune microenvironment(TIME)plays a crucial role in tumor progression,metastasis,and therapeutic response.Despite several noninvasive strategies have emerged for cancer diagnosis and prognosis,there are still lack of efective radiomic-based model to evaluate TIME status,let alone predict clinical outcome and immune checkpoint inhibitor(ICIs)response for hepatocellular carcinoma(HCC).In this study,we developed a radiomic model to evaluate TIME status within the tumor and predict prognosis and immunotherapy response.A total of 301 patients who underwent magnetic resonance imaging(MRI)examinations were enrolled in our study.The intra-tumoral expression of 17 immune-related molecules were evaluated using co-detection by indexing(CODEX)technology,and we construct Immunoscore(IS)with the least absolute shrinkage and selection operator(LASSO)algorithm and Cox regression method to evaluate TIME.Of 6115 features extracted from MRI,fve core features were fltered out,and the Radiomic Immunoscore(RIS)showed high accuracy in predicting TIME status in testing cohort(area under the curve=0.753).More importantly,RIS model showed the capability of predicting therapeutic response to anti-programmed cell death 1(PD-1)immunotherapy in an independent cohort with advanced HCC patients(area under the curve=0.731).In comparison with previously radiomicbased models,our integrated RIS model exhibits not only higher accuracy in predicting prognosis but also the potential guiding signifcance to HCC immunotherapy.
基金supported by the National Natural Science Foundation of China(Grant No.81972492)National Science Fund for Young Scholars(Grant No.21904107)+7 种基金Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(Grant No.LR19C050001)Hangzhou Agriculture and Society Advancement Program(Grant No.20190101A04)Westlake Startup Grantresearch funds from the National Cancer Centre Singapore and Singapore General Hospital,Singaporethe National Key R&D Program of China(Grant No.2016YFC0901704)Zhejiang Innovation Discipline Project of Laboratory Animal Genetic Engineering(Grant No.201510)the Netherlands Cancer Society(Grant No.NKI 2014-6651)The Netherlands Organization for Scientific Research(NWO)-Middelgroot(Grant No.91116017)
文摘To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been developed.For optimal performance,they require the fragment ion spectra of targeted peptides as prior knowledge.In this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples.To build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker.We then applied the workflow to generate DPHL,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer samples.This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)patients.Thereafter,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated.As a second application,the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DLBCL)patients and 18 healthy control subjects.Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM.These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery.DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000.
基金funded by the Program of Department of Transport of Hebei Province,China(No. 2011023)
文摘A three-dimensional finite element model (3D FEM) is built using ABAQUS to analyze the dynamic response of a concrete pavement structure with an asphalt isolating layer under moving loads. The 3D model is prepared and validated in the state of no asphalt isolating layer. Stress and deflection at the critical load position are calculated by changing thickness, modulus of isolating layer and the combination between the isolating layer and concrete slab. Analysis result shows that the stress and deflection of the concrete slab increase with the increase of thickness. The stress and deflection of the concrete slab decrease with the increase of combination between the isolating layer and concrete slab. The influence of changing the isolating layer modulus to the stress and deflection of the concrete slab is not significant. From the results, asphalt isolating layer design is suggested in concrete pavement.
文摘Following the publication of the US National Research Council (N RC) report " Toward PrecMon Medicine." Building a Knowledge Network for Biomedical Research and a New Taxonomy of Diseases" in 2011 [1], several nations have announced that their national research programs would definitely head toward this direction. Now,
基金This work was supported by a grant from the Nationa NaturaI Science Foundation of China(No.C30100169).
文摘Synaptotagmin (Syt) constitutes a family of membrane-trafficking proteins, so far nearly 20 Syts have been discovered. Extensive work showed that synatotagmins were a potential Ca^2+ sensor for regulated exocytosis. This study was to investigate the expression and location of synaptotagmin II (Syt2) in RBL-2H3 (RBL) and its role in regulating exocytosis of RBL. The expression of Syt2 in RBL was confirmed by Western blot. The recombinant expression vector pEGFP-N1-Syt2 was constructed and transfected into RBL by electroporation, the stable transfectant RBL-Syt2-S expressing fusion protein Syt2-EGFP were obtained and Syt2 was highly concentrated at plasma membrane with little detected in cytoplasm. To analyze the role of Syt2 during exocytosis of RBL, the release of cathepsin D was assayed by immunoblotting. Compared with control, the release of cathepsin D by RBL-Syt2-S was markedly decreased. The results indicated that Syt2 played a negative regulation in exocytosis of lysosomes in RBL. Cellular & Molecular Immunology. 2005;2(3):205-209.
基金supported by the National Natural Science Foundation of China(81790633,61922047,81830054,81902412,81903184,81988101,91859205,21788102,51620105009)the Innovation Program of Shanghai Municipal Education Commission(2019-01-07-0007-E00065,21XD1404600)+4 种基金the Research Grants Council of Hong Kong(16306620,N_HKUST609/19 and C6014-20W)the Innovation and Technology Commission(ITC-CNERC14SC01,ITCPD/17-9,MHP/047/19 and ITS/301/18FX)the support of Shanghai Key Laboratory of Hepato-biliary Tumor BiologyMilitary Key Laboratory on Signal Transductionsupported by the Innovation Program of Shanghai Municipal Education Commission。
文摘Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid peroxidation and lethal reactive oxygen species(ROS).To date,misregulated ferroptosis has been implicated in several types of cancers,and ferroptosis inducers can be used to promote ferroptosis in tumor cells and play an anti-tumor role.However,the specificity and efficacy of ferroptosis inducers remain unsatisfactory.Here,a new mitochondria-targeted photosensitizer(PS)with aggregation-induced emission(AIE)characteristic named TCSVP was designed,which efficiently generates ROS in mitochondria after light exposure.TCSVP administration significantly sensitizes tumor cells to ferroptosis inducer(RSL3)-mediated cell death by specifically and light-dependently triggering a moderate ROS generation in vitro and in vivo.Mechanically,the expression levels of ferroptosis related proteins Acyl-CoA synthetase long-chain family member 4(FACL4/ACSL4)and cyclooxygenase-2(COX2)were increased in TCSVP/RSL3-treated cells after light exposure,coupled with decreased Glutathione peroxidase 4(GPX4)activity and excessive malondialdehyde(MDA)accumulation.This study declared that light-induced moderate ROS generation within mitochondria in cancer cells by AIE-PS can be used to enhance the specificity and efficacy of ferroptosis inducers,bringing a new synergistic strategy for tumor intervention.
基金supported by the National Natural Sciences Foundation of China(grant NSFC-81472651)Zhejiang Provincial Natural Sciences Foundation(LY20H160016).
文摘A recent study by Hoon Kim et al.published in Nature Genetics demonstrated that extrachromosomal DNA(ecDNA)-based oncogene amplification frequently occurs in most cancer types and that it is different from chromosomal amplification.1 The authors further showed that ecDNA in multiple cancer types leads to poor outcomes in patients;thus,ecDNA is a novel potential diagnostic or therapeutic target for tumor treatment(Fig.1).