BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological proce...BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological processes and various diseases,its role in gastric cancer(GC),particularly its expression and prognostic significance,remains poorly understood.In this study,we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC.Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.AIM To explore the expression of KRT80 in GC and its impact on the prognosis of patients.METHODS KRT80 expression in GC tissues was analyzed using Western blotting,quantitative reverse transcription PCR,multiple immunofluorescence staining,and immunohistochemistry.Survival analysis was conducted using the Kaplan-Meier method with the log-rank test.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1(EEF1A1)as a binding protein of KRT80.RESULTS Integrating our experimental findings with multiple published studies,we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin.Moreover,we have preliminarily verified the interaction between KRT80 and EEF1A1.Therefore,this study provides a novel perspective on overcoming oxaliplatin resistance in GC.CONCLUSION Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC,suggesting its potential as a novel prognostic biomarker.展开更多
The synergistic regulatory effect of the ethylene transcription factor MdERF2 and ubiquitin ligase MdPUB17 on apple(Malus domestica)epidermal wax was examined by transferring the pRI101-MdPUB17-MdERF2 dual overexpress...The synergistic regulatory effect of the ethylene transcription factor MdERF2 and ubiquitin ligase MdPUB17 on apple(Malus domestica)epidermal wax was examined by transferring the pRI101-MdPUB17-MdERF2 dual overexpression vector(PUB17-ERF2),the empty vector(pRI101),the pRI101-MdPUB17 overexpression vector(PUB17),and the pRI101-MdERF2 overexpression vector(ERF2)into Agrobacterium tumefaciens,respectively,to infect apple callus and fruits with water as the control(CK).The levels of expression of the genes related to the biosynthesis,transport,composition,content,and structure of wax in the callus and/or fruits were studied under different treatments.The synergistic treatment of PUB17-ERF2 resulted in a decrease in the expression levels of MdCER1,MdCER6,MdLACS2,MdWSD1,MdABCG11,MdPAS2,MdFATB,and MdKASII genes as induced by the sole treatment of ERF2.Moreover,in the treatment of PUB17-ERF2,the mass distribution density of the wax was observed to be intermediate between the ERF2 and PUB17 treatments.Furthermore,ERF2 was found to increase the contents of alkanes,alcohols,and ketones,while significantly decreasing the contents of fatty acids and esters.In contrast,PUB17 responded oppositely.When treated with PUB17-ERF2,the effects of PUB17 and ERF2 were observed to counteract each other,which resulted in intermediate levels of these compounds.Additionally,the fruit in the ERF2,PUB17 and PUB17-ERF2 treatments had a different waxy microstructure.Overall,the findings indicate that both ERF2 and PUB17 have an impact on the gene expression,wax composition,content,and microstructure in apple epidermis.Importantly,the co-expression of MdPUB17 and MdERF2 demonstrates their synergistic regulation of the biosynthesis of wax in the apple epidermis.展开更多
In recent years,with the rapid development of the new energy vehicle industry,industry-education integration has become an important way to improve the teaching quality of new energy vehicle majors.Industry-education ...In recent years,with the rapid development of the new energy vehicle industry,industry-education integration has become an important way to improve the teaching quality of new energy vehicle majors.Industry-education integration mainly refers to the effective connection of the education chain,talent chain with the industrial chain and innovation chain through deepening school-enterprise cooperation.This can not only promote resource sharing and complementary advantages between schools and enterprises but also effectively improve students’practical abilities and professional qualities,thus providing strong talent support and intellectual guarantee for the sustainable and healthy development of the new energy vehicle industry.In this regard,this article first expounds on the significance of the teaching reform of new energy vehicle majors from the perspective of industry-education integration,and then proposes effective teaching reform strategies,hoping to provide some reference for relevant education researchers.展开更多
Chrysanthemum morifolium cv.‘Huaihuang’has ornamental,edible,medicinal,and tea product uses.However,its field growth,yield,and quality are negatively affected by black spot disease caused by Alternaria sp.(Strain:HQ...Chrysanthemum morifolium cv.‘Huaihuang’has ornamental,edible,medicinal,and tea product uses.However,its field growth,yield,and quality are negatively affected by black spot disease caused by Alternaria sp.(Strain:HQJH10092301;GenBank accession number:KF688111).In this study,we transcriptionally and transgenically characterized a new cultivar,‘Huaiju 2#’(Henan Traditional Chinese Medicine Plant Cultivar identification number:2016002),which was bred from‘Huaihuang’and shows resistance to Alternaria sp.Numerous‘Huaiju 2#’plants were inoculated with Alternaria sp.for three or five days.Metabolic analysis showed increases in both salicylic acid(SA)and jasmonic acid(JA)in infected plants compared to the control.Protein activity analysis also revealed a significant increase in defense enzyme activities in infected plants.RNA-Seq of plants infected for 3 or 5 days produced a total of 58.6 GB of clean reads.Among these reads,16,550 and 13,559 differentially expressed genes(DEGs)were identified in Cm_3 dpi(sample from 3 days post-inoculation labeled as Cm_3 dpi)and Cm_5 dpi(sample from 5 days post-inoculation labeled as Cm_5 dpi),respectively,compared with their controls(Cm_0 d:a mixture samples from 0 d(before inoculation)and those treated with sterile distilled water at 3 dpi and 5 dpi).Gene annotation and cluster analysis of the DEGs revealed a variety of defense responses to Alternaria sp.infection,which were characterized by increases in resistance(R)proteins and the reactive oxygen species(ROS),Ca2+,mitogen-activated protein kinase(MAPK),and JA signaling pathways.In particular,SA signaling was highly responsive to Alternaria sp.infection.The qPCR analysis of 12 DEG candidates supported their differential expression characterized by using the RNA-Seq data.One candidate was CmNPR1(nonexpressor of pathogenesis-related gene 1),an important positive regulator of SA in systemic acquired resistance(SAR).Overexpression of CmNPR1 in‘Huaiju 2#’increased the resistance of transgenic plants to black spot.These findings indicate that the SA response pathway is likely involved in the defense of‘Huaiju 2#’against Alternaria sp.pathogens.展开更多
Cold atmospheric plasmas(CAPs)have shown great applicability in agriculture.Many kinds of CAP sources have been studied in agricultural applications to promote plant growth and cure plant diseases.We briefly review th...Cold atmospheric plasmas(CAPs)have shown great applicability in agriculture.Many kinds of CAP sources have been studied in agricultural applications to promote plant growth and cure plant diseases.We briefly review the state-of-the-art stimulating effects of atmospheric-pressure dielectricbarrier-discharge(AP-DBD)plasmas,after the direct or indirect treatment of plants for growth promotion and disease control.We then discuss the special demands on the characteristics of the CAP sources for their applications in plant mutation breeding.An atmospheric and room temperature plasma(ARTP)jet generator with a large plasma irradiation area,a high enough concentration of chemically reactive species and a low gas temperature is designed for direct plant mutagenesis.Experimental measurements of the electrical,thermal and optical features of the ARTP generator are conducted.Then,an ARTP-P(ARTP for plant mutagenesis)mutation breeding machine is developed,and a typical case of plant mutation breeding by the ARTP-P mutation machine is presented using Coreopsis tinctoria Nutt.seeds.Physical and agricultural experiments show that the newly-developed ARTP-P mutation breeding machine with a large irradiation area can generate uniform CAP jets with high concentrations of chemically reactive species and mild gas temperatures,and have signiflcant mutagenesis effects on the Coreopsis tinctoria Nutt.seeds.The ARTP-P mutation breeding machine may provide a platform for systematic studies on mutation mechanisms and results for various plant seeds under different operating conditions in future research.展开更多
This paper focuses on the distribution of passenger flow in Huoying Station,Line 13 of Beijing subway system.The transformation measures taken by Line 13 since operation are firstly summarized.Then the authors elabora...This paper focuses on the distribution of passenger flow in Huoying Station,Line 13 of Beijing subway system.The transformation measures taken by Line 13 since operation are firstly summarized.Then the authors elaborate the facilities and equipment of this station,especially the node layout and passenger flow field.An optimization scheme is proposed to rapidly distribute the passenger flow in Huoying Station by adjusting the operation time of the escalator in the direction of Xizhimen.The authors adopt Queuing theory and Anylogic simulation software to simulate the original and the optimized schemes of Huoying Station to distribute the passenger flow.The results of the simulation indicate that the optimized scheme could effectively alleviate the traffic congestion in the hall of Huoying Station,and the pedestrian density in other places of the hall is lowered;passengers could move freely in the hall and no new congestion points would form.The rationality of the scheme is thus proved.展开更多
An efficient high-order numerical method for supersonic reactive flows is proposed in this article.The reactive source term and convection term are solved separately by splitting scheme.In the reaction step,an adaptiv...An efficient high-order numerical method for supersonic reactive flows is proposed in this article.The reactive source term and convection term are solved separately by splitting scheme.In the reaction step,an adaptive time-step method is presented,which can improve the efficiency greatly.In the convection step,a third-order accurate weighted essentially non-oscillatory（WENO）method is adopted to reconstruct the solution in the unstructured grids.Numerical results show that our new method can capture the correct propagation speed of the detonation wave exactly even in coarse grids,while high order accuracy can be achieved in the smooth region.In addition,the proposed adaptive splitting method can reduce the computational cost greatly compared with the traditional splitting method.展开更多
The fundamental understanding of the effects of rare earth(RE)on the phase transformation of Fe-based alloys is essential in the development of advanced RE-containing high strength steels.In this work,we investigated ...The fundamental understanding of the effects of rare earth(RE)on the phase transformation of Fe-based alloys is essential in the development of advanced RE-containing high strength steels.In this work,we investigated the effects of La and Ce on the martensitic phase transformation of Fe in terms of the driving force and minimum energy path(MEP)using the first-principles calculations.The calculations of formation energy show that the RE substitution increases the stabilization of fcc-Fe and decreases that of bcc-Fe,thus decreasing the driving force of phase transformation.Meanwhile,the analysis based on the generalized solid-state nudged elastic band(G-SSNEB)method indicates that in the RE-containing systems,an additional energy barrier appears when the phase transformation proceeds along the Bain transition path to c/a ratio of 1.14 in the FM state,which is associated with a sudden decrease in magnetization due to the hybridization between the orbits of the RE atoms and those of the nearest neighbor Fe atoms.The results of potential-energy surfaces(PES)confirm that magnetic ordering and lattice volume change simultaneously with the Bain transition,and in comparison to pure Fe,the variation between the onset and the end structural volumes of the phase transformation is slight for the REcontaining Fe systems.展开更多
Organic solar cells(OSCs)have attracted huge attention because of their unique merits[1−3].In last few years,thanks to the design of new materials and device engineering,the power conversion efficiencies(PCEs)of OSCs ...Organic solar cells(OSCs)have attracted huge attention because of their unique merits[1−3].In last few years,thanks to the design of new materials and device engineering,the power conversion efficiencies(PCEs)of OSCs have surpassed 18%[4−8].The PM6:Y6 cells are efficient binary cells,offering high PCEs over 16%[9−11].The high performance originates from the efficient free charge generation and the ground state dipole field at the donor-acceptor interface that promotes the exciton dissociation[12].展开更多
1,3,5-Triazine molecules represent a class of molecules that may have been prebiotic information carriers in a primordial soup in early Earth and their excited state dynamics has received attention in recent years.In ...1,3,5-Triazine molecules represent a class of molecules that may have been prebiotic information carriers in a primordial soup in early Earth and their excited state dynamics has received attention in recent years.In our previous study,one component with lifetime longer than100 ps was discovered in 2-amino-1,3,5-trainzine(2-AT),but its nature has not been revealed.In this study,excited state dynamics of 2-AT is studied in different solvents by using femtosecond time-resolved transient absorption and fluorescence upconversion spectroscopy.Interestingly,an equilibrium state consisting of the brightππ^(*)and dark nπ^(*)states in 2-AT is directly observed in aqueous solution and its dynamics is solvent sensitive.The whole picture of the excited state deactivation mechanism of 2-AT is proposed based on our spectroscopy results.展开更多
The performances of turbine blades have a significant impact on the energy conversion efficiency of vertical solar power plants.In the present study,such a relationship is assessed by considering two kinds of airfoil ...The performances of turbine blades have a significant impact on the energy conversion efficiency of vertical solar power plants.In the present study,such a relationship is assessed by considering two kinds of airfoil blades,designed by using the Wilson theory.In particular,numerical simulations are conducted using the SST K−ω model and assuming a wind speed of 3–6 m/s and seven or eight blades.The two airfoils are the NACA63121(with a larger chord length)and the AMES63212;It is shown that the torsion angle of the former is smaller,and its wind drag ratio is larger;furthermore,the resistance is increased by about 66.3%on average.Within the scope of the study,the results show that the NACA63212 airfoil is better than the AMES63212 airfoil in terms of power,with an average improvement of about 2.8%.The simulation results have a certain guiding significance for selecting turbine blade airfoils and improving turbine efficiency.展开更多
In this letter, excited state dynamics of TPZ2, a centrosymmetric PRODAN dye, has been studied by using several time-resolved spectroscopy techniques. Fluorescence quantum yield of TPZ2 is found to be 0.50 in both ace...In this letter, excited state dynamics of TPZ2, a centrosymmetric PRODAN dye, has been studied by using several time-resolved spectroscopy techniques. Fluorescence quantum yield of TPZ2 is found to be 0.50 in both acetonitrile and ethanol solution. The radiative decay rate of the excited state of TPZ2 is determined to be 2.0×10^8 s^-1. Meanwhile, highly efficient triplet state and singlet oxygen generation have been observed in TPZ2 and the intersystem crossing（ISC） rate is determined to be 2.0×10^8s^-1. The almost identical ISC and non-radiative decay rates indicate that ISC is the only non-radiative decay pathway in TPZ2. Thus, dual excited state（S1） deactivation mechanism（50/50, fluorescence/ISC） of TPZ2 is proposed.Because of this unique property, TPZ2 has the potential to be used as biocompatible imaging and photodynamic therapy agent in the same time.展开更多
Kondo semimetal CeRu4Sn6 is attracting renewed attention due to the theoretically predicted nontrivial topology in its electronic band structure. We report hydrostatic and chemical pressure effects on the transport pr...Kondo semimetal CeRu4Sn6 is attracting renewed attention due to the theoretically predicted nontrivial topology in its electronic band structure. We report hydrostatic and chemical pressure effects on the transport properties of single- and poly-crystalline samples. The electrical resistivity p （T） is gradually enhanced by applying pressure over a wide temperature range from room temperature down to 25 mK. Two thermal activation gaps estimated from high- and low-temperature windows are found to increase with pressure. A flat p（T） observed at the lowest temperatures below 300 mK appears to be robust against both pressure and field. This feature as well as the increase of the energy gaps calls for more intensive investigations with respect to electron correlations and band topology.展开更多
Objective:To explore the cardioprotective mechanism of Wenxin Granules regulating the expression of apoptosis-related genes in cardiomyocytes.Methods:A rat model of myocardial infarction was established and randomly d...Objective:To explore the cardioprotective mechanism of Wenxin Granules regulating the expression of apoptosis-related genes in cardiomyocytes.Methods:A rat model of myocardial infarction was established and randomly divided into model group,Wenxin granule low-dose group,Wenxin granule high-dose group,metoprolol group and sham operation group.the left ventricular end systole anterior wall thickness(LVAWs),end systole inner diameter(LVIDs),end systole posterior wall thickness(LVPWs),end-diastolic anterior wall thickness(LVAWd),end-diastolic inner diameter(LVIDd),end-diastolic posterior wall thickness(LVPWd)and left ventricular ejection fraction(LVEF)were detected by echocardiography in each group after 2 weeks of treatment.Hematoxylin eosin(HE)staining was used to observe the changes in the cardiac structure of rats in each group.Real-time PCR(Real-time PCR)was used to detect the relative expression of mammalian B-cell lymphoma-2(BCL-2),BCL-2 related X protein(BAX),Caspase-9(Caspase-9),and Caspase-3(Caspase-3)mRNA.TUNEL staining was used to detect changes in the apoptotic rate of rat cardiomyocytes in each group.Results:Compared with the sham operation group,the LVAWs,LVPWs,LVPWd and LVEF of the model group were significantly reduced(P<0.05,P<0.01),and LVIDs and LVIDd were significantly increased(P<0.05,P<0.01).Severe pathological ischemia injury of heart tissue.The relative expression of BCL-2 mRNA and the ratio of BCL-2/BAX in the model group were significantly reduced(P<0.01),while the relative expression of BAX,Caspase-9 and Caspase-3 mRNA was significantly increased(P<0.01).The apoptosis rate was significantly increased(P<0.01).In the low-dose and high-dose groups of Wenxin Granules and the Metoprolol group,LVAWs,LVPWs,LVPW d,and LVEF of rats in each administration group increased significantly(P<0.05,P<0.01),LVIDs,LVIDd was significantly reduced(P<0.05,P<0.01),the pathological damage of the heart tissue was improved,the expression of BCL-2 mRNA and the ratio of BCL-2/BAX were significantly increased(P<0.05,P<0.01),BAX,The expression of Caspase-9 and Caspase-3 mRNA was significantly reduced(P<0.05,P<0.01),and the apoptotic rate of myocardial cells was significantly reduced(P<0.01).Conclusion:Wenxin granule can play a cardioprotective role by regulating the gene expression of BCL-2/BAX/Caspase apoptosis pathway.展开更多
In recent years,relevant government departments have achieved the goal of reduction and harmless application through the development and implementation of municipal waste incineration power plants,in order to advocate...In recent years,relevant government departments have achieved the goal of reduction and harmless application through the development and implementation of municipal waste incineration power plants,in order to advocate ecological and environmental protection.At present,in order to further achieve the goal of sustainable development,municipal waste incineration power plants have actively responded to the national call and requirements as well as made overall arrangements for the energy-saving design and optimization design of their internal system.Therefore,with the concept of sustainable development,this paper studies and analyzes the problems of the HVAC design as well as suggests related strategies for municipal waste incineration power plants in order to provide relevant reference.展开更多
To the Editor:Co-reactivation of cytomegalovirus(CMV)and Epstein–Barr virus(EBV)is common after haploidentical stem cell transplantation(haplo-SCT)and can lead to potentially life-threatening complications.[1,2]Adopt...To the Editor:Co-reactivation of cytomegalovirus(CMV)and Epstein–Barr virus(EBV)is common after haploidentical stem cell transplantation(haplo-SCT)and can lead to potentially life-threatening complications.[1,2]Adoptive immunotherapy with virus-specific T lymphocytes(VSTs)is a critical treatment option that has shown promising results in controlling CMV and EBV infections in several clinical studies,providing protection for 70–90%of patients.[3]Multi-virus-specific T cell lines offer an advanced method for simultaneously addressing multiple challenging viral infections.However,data regarding its long-term efficacy are limited.Additionally,clinical trials with multi-virus-specific T cells have predominantly focused on single virus reactivation,leaving gaps in our understanding of the effectiveness of VSTs during multivirus co-reactivation.Antigenic competition may affect the expansion of virus-specific T cells in vitro during the generation of multi-virus-specific cell lines.Whether in vivo competition among infused cells compromises the efficacy of adoptively transferred VSTs remains unclear.展开更多
Erythropoiesis is a crucial process in hematopoiesis,yet it remains highly susceptible to disruption by various diseases,which significantly contribute to the global challenges of anemia and blood shortages.Current tr...Erythropoiesis is a crucial process in hematopoiesis,yet it remains highly susceptible to disruption by various diseases,which significantly contribute to the global challenges of anemia and blood shortages.Current treatments like erythropoietin(EPO)or glucocorticoids often fall short,especially for hereditary anemias such as Diamond-Blackfan anemia(DBA).To uncover new erythropoiesis-stimulating agents,we devised a screening system using primary human hematopoietic stem and progenitor cells(HSPCs).We discovered that BRAF inhibitors(BRAFi),commonly used to treat BRAF^(V600E) melanoma,can unexpectedly and effectively promote progenitor cell proliferation by temporarily delaying erythroid differentiation.Notably,these inhibitors exhibited pronounced efficacy even under cytokine-restricted conditions and in patient samples of DBA.Mechanistically,although these BRAFi inhibit the MAPK cascade in BRAF^(V600E) mutant cells,they paradoxically act as amplifiers in wild-type BRAF cells,potently enhancing the cascade.Furthermore,we found that while the oncogenic BRAF^(V600E) mutation disrupts hematopoiesis and erythropoiesis through AP-1 hyperactivation,BRAFi minimally impact HSPC self-renewal and differentiation.In vivo studies have shown that BRAFi can enhance human hematopoiesis and erythropoiesis in severe immunodeficient mouse models and alleviate anemia in the Rpl11 haploinsufficiency DBA model,as well as other relevant anemia models.This discovery underscores the role of the MAPK pathway in hematopoiesis and positions BRAFi as a promising therapeutic option for improving hematopoietic reconstitution and treating anemias,including DBA.展开更多
In the process of collating the raw data,the authors noticed three images in Fig.4 were used incorrectly.They made an inadvertent mistake by arranging the figure of M2 Group into M2+LY294002 Group in Fig.4k during the...In the process of collating the raw data,the authors noticed three images in Fig.4 were used incorrectly.They made an inadvertent mistake by arranging the figure of M2 Group into M2+LY294002 Group in Fig.4k during the revision process.展开更多
To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham...To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.展开更多
Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy...Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy.However,the applicability of existing predictive models,CAR-HEMATOTOX(CAR-HT)for lymphoma,acute lymphoblastic leukemia-HEMATOTOX(ALL-HT)for B-ALL,and the early ICAHT prediction model(e IPM),remains uncertain across different hematologic malignancies.Methods:We prospectively analyzed 119 patients who received CAR-T therapy between January 2022 and June2025,including B-ALL(n=62),T-ALL/non-Hodgkin's lymphoma(NHL)(n=25),and multiple myeloma(MM,n=32).The CAR-HT,ALL-HT,and e IPM models were evaluated for their ability to predict ICAHT severity and survival outcomes.Results:Grade 3 ICAHT occurred in 32.3%of B-ALL,40.0%of T-ALL/NHL,and 25.0%of MM patients,while grade 4 rates were 33.9%,20.0%,and 6.3%,respectively.CAR-HT classified 67.2%of patients as high-risk,and ALL-HT identified 56.3%of ALL/NHL patients as high-risk.In both models,high-risk groups experienced significantly more prolonged neutropenia than low-risk groups(CAR-HT:17.7 vs.5.3 d,P<0.001;ALL-HT:21.3 vs.7.7 d,P<0.001).Both e IPMpre and e IPMpost strongly correlated with grade 3-4 ICAHT(P<0.001).Importantly,survival analysis showed that e IPMpre stratification distinguished outcomes:1-year overall survival(OS)was 65%in medium+high-risk vs.84%in low-risk patients(P=0.006),and 1-year disease-free survival(DFS)was 44%vs.73%(P<0.001).Similar predictive accuracy was observed with e IPMpost.Conclusions:The CAR-HT,ALL-HT,and e IPM models consistently identify patients at high risk for severe ICAHT across B-ALL,T-ALL/NHL,and MM.Among these,the e IPM stands out as a promising universal tool for survival prediction.These models provide valuable prognostic insights that can guide supportive care and inform treatment planning in CAR-T therapy.展开更多
基金Supported by National Natural Science Foundation of China,No.874063.
文摘BACKGROUND Keratin 80(KRT80),a type I intermediate filament protein,is a member of the keratin family with specialized functions in epithelial tissues.While KRT80 has been implicated in both normal physiological processes and various diseases,its role in gastric cancer(GC),particularly its expression and prognostic significance,remains poorly understood.In this study,we investigated the role and underlying molecular mechanisms of KRT80 in oxaliplatin resistance in GC.Our analysis revealed that KRT80 is significantly upregulated in GC tissues and is associated with poor clinical prognosis.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.AIM To explore the expression of KRT80 in GC and its impact on the prognosis of patients.METHODS KRT80 expression in GC tissues was analyzed using Western blotting,quantitative reverse transcription PCR,multiple immunofluorescence staining,and immunohistochemistry.Survival analysis was conducted using the Kaplan-Meier method with the log-rank test.The role of KRT80 in GC cell proliferation was assessed through in vitro and in vivo assays.Immunoprecipitation and mass spectrometry analyses identified elongation factor 1-alpha 1(EEF1A1)as a binding protein of KRT80.RESULTS Integrating our experimental findings with multiple published studies,we found that increased KRT80 expression is associated with poor prognosis in GC and promotes resistance to oxaliplatin.Moreover,we have preliminarily verified the interaction between KRT80 and EEF1A1.Therefore,this study provides a novel perspective on overcoming oxaliplatin resistance in GC.CONCLUSION Increased KRT80 expression predicts poor prognosis and promotes oxaliplatin resistance in GC,suggesting its potential as a novel prognostic biomarker.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32272384 and 32172278)。
文摘The synergistic regulatory effect of the ethylene transcription factor MdERF2 and ubiquitin ligase MdPUB17 on apple(Malus domestica)epidermal wax was examined by transferring the pRI101-MdPUB17-MdERF2 dual overexpression vector(PUB17-ERF2),the empty vector(pRI101),the pRI101-MdPUB17 overexpression vector(PUB17),and the pRI101-MdERF2 overexpression vector(ERF2)into Agrobacterium tumefaciens,respectively,to infect apple callus and fruits with water as the control(CK).The levels of expression of the genes related to the biosynthesis,transport,composition,content,and structure of wax in the callus and/or fruits were studied under different treatments.The synergistic treatment of PUB17-ERF2 resulted in a decrease in the expression levels of MdCER1,MdCER6,MdLACS2,MdWSD1,MdABCG11,MdPAS2,MdFATB,and MdKASII genes as induced by the sole treatment of ERF2.Moreover,in the treatment of PUB17-ERF2,the mass distribution density of the wax was observed to be intermediate between the ERF2 and PUB17 treatments.Furthermore,ERF2 was found to increase the contents of alkanes,alcohols,and ketones,while significantly decreasing the contents of fatty acids and esters.In contrast,PUB17 responded oppositely.When treated with PUB17-ERF2,the effects of PUB17 and ERF2 were observed to counteract each other,which resulted in intermediate levels of these compounds.Additionally,the fruit in the ERF2,PUB17 and PUB17-ERF2 treatments had a different waxy microstructure.Overall,the findings indicate that both ERF2 and PUB17 have an impact on the gene expression,wax composition,content,and microstructure in apple epidermis.Importantly,the co-expression of MdPUB17 and MdERF2 demonstrates their synergistic regulation of the biosynthesis of wax in the apple epidermis.
基金the research result of“Reform and Practical Exploration of the New Energy Vehicle Complete Vehicle Control System Maintenance Course Based on Professional Integration and Hierarchical Training”(JTYSJZW2022B05)the Teaching Steering Committee for Transportation Majors in Guangdong Higher Vocational Colleges and the Education Reform Project of the Guangdong Provincial Department of Education(KCSZ04021).
文摘In recent years,with the rapid development of the new energy vehicle industry,industry-education integration has become an important way to improve the teaching quality of new energy vehicle majors.Industry-education integration mainly refers to the effective connection of the education chain,talent chain with the industrial chain and innovation chain through deepening school-enterprise cooperation.This can not only promote resource sharing and complementary advantages between schools and enterprises but also effectively improve students’practical abilities and professional qualities,thus providing strong talent support and intellectual guarantee for the sustainable and healthy development of the new energy vehicle industry.In this regard,this article first expounds on the significance of the teaching reform of new energy vehicle majors from the perspective of industry-education integration,and then proposes effective teaching reform strategies,hoping to provide some reference for relevant education researchers.
基金funded by the Joint Funds of the National Natural Science Foundation of China(No.U1704120)the National Natural Science Foundation of China(No.31372105).
文摘Chrysanthemum morifolium cv.‘Huaihuang’has ornamental,edible,medicinal,and tea product uses.However,its field growth,yield,and quality are negatively affected by black spot disease caused by Alternaria sp.(Strain:HQJH10092301;GenBank accession number:KF688111).In this study,we transcriptionally and transgenically characterized a new cultivar,‘Huaiju 2#’(Henan Traditional Chinese Medicine Plant Cultivar identification number:2016002),which was bred from‘Huaihuang’and shows resistance to Alternaria sp.Numerous‘Huaiju 2#’plants were inoculated with Alternaria sp.for three or five days.Metabolic analysis showed increases in both salicylic acid(SA)and jasmonic acid(JA)in infected plants compared to the control.Protein activity analysis also revealed a significant increase in defense enzyme activities in infected plants.RNA-Seq of plants infected for 3 or 5 days produced a total of 58.6 GB of clean reads.Among these reads,16,550 and 13,559 differentially expressed genes(DEGs)were identified in Cm_3 dpi(sample from 3 days post-inoculation labeled as Cm_3 dpi)and Cm_5 dpi(sample from 5 days post-inoculation labeled as Cm_5 dpi),respectively,compared with their controls(Cm_0 d:a mixture samples from 0 d(before inoculation)and those treated with sterile distilled water at 3 dpi and 5 dpi).Gene annotation and cluster analysis of the DEGs revealed a variety of defense responses to Alternaria sp.infection,which were characterized by increases in resistance(R)proteins and the reactive oxygen species(ROS),Ca2+,mitogen-activated protein kinase(MAPK),and JA signaling pathways.In particular,SA signaling was highly responsive to Alternaria sp.infection.The qPCR analysis of 12 DEG candidates supported their differential expression characterized by using the RNA-Seq data.One candidate was CmNPR1(nonexpressor of pathogenesis-related gene 1),an important positive regulator of SA in systemic acquired resistance(SAR).Overexpression of CmNPR1 in‘Huaiju 2#’increased the resistance of transgenic plants to black spot.These findings indicate that the SA response pathway is likely involved in the defense of‘Huaiju 2#’against Alternaria sp.pathogens.
基金supported by the National Key Research and Development Program of China(No.2016YFD0102106)National Natural Science Foundation of China(Nos.11475103,21627812)。
文摘Cold atmospheric plasmas(CAPs)have shown great applicability in agriculture.Many kinds of CAP sources have been studied in agricultural applications to promote plant growth and cure plant diseases.We briefly review the state-of-the-art stimulating effects of atmospheric-pressure dielectricbarrier-discharge(AP-DBD)plasmas,after the direct or indirect treatment of plants for growth promotion and disease control.We then discuss the special demands on the characteristics of the CAP sources for their applications in plant mutation breeding.An atmospheric and room temperature plasma(ARTP)jet generator with a large plasma irradiation area,a high enough concentration of chemically reactive species and a low gas temperature is designed for direct plant mutagenesis.Experimental measurements of the electrical,thermal and optical features of the ARTP generator are conducted.Then,an ARTP-P(ARTP for plant mutagenesis)mutation breeding machine is developed,and a typical case of plant mutation breeding by the ARTP-P mutation machine is presented using Coreopsis tinctoria Nutt.seeds.Physical and agricultural experiments show that the newly-developed ARTP-P mutation breeding machine with a large irradiation area can generate uniform CAP jets with high concentrations of chemically reactive species and mild gas temperatures,and have signiflcant mutagenesis effects on the Coreopsis tinctoria Nutt.seeds.The ARTP-P mutation breeding machine may provide a platform for systematic studies on mutation mechanisms and results for various plant seeds under different operating conditions in future research.
基金This research is supported by Beijing Municipal Natural Science Foundation(9204023)Ministry of Education“Tiancheng Huizhi”Innovation and Education Promotion Foundation(2018A01012).
文摘This paper focuses on the distribution of passenger flow in Huoying Station,Line 13 of Beijing subway system.The transformation measures taken by Line 13 since operation are firstly summarized.Then the authors elaborate the facilities and equipment of this station,especially the node layout and passenger flow field.An optimization scheme is proposed to rapidly distribute the passenger flow in Huoying Station by adjusting the operation time of the escalator in the direction of Xizhimen.The authors adopt Queuing theory and Anylogic simulation software to simulate the original and the optimized schemes of Huoying Station to distribute the passenger flow.The results of the simulation indicate that the optimized scheme could effectively alleviate the traffic congestion in the hall of Huoying Station,and the pedestrian density in other places of the hall is lowered;passengers could move freely in the hall and no new congestion points would form.The rationality of the scheme is thus proved.
基金supported by the National Natural Science Foundation of China(Grants 51476152,11302213,and 11572336)
文摘An efficient high-order numerical method for supersonic reactive flows is proposed in this article.The reactive source term and convection term are solved separately by splitting scheme.In the reaction step,an adaptive time-step method is presented,which can improve the efficiency greatly.In the convection step,a third-order accurate weighted essentially non-oscillatory（WENO）method is adopted to reconstruct the solution in the unstructured grids.Numerical results show that our new method can capture the correct propagation speed of the detonation wave exactly even in coarse grids,while high order accuracy can be achieved in the smooth region.In addition,the proposed adaptive splitting method can reduce the computational cost greatly compared with the traditional splitting method.
基金Project supported by the National Natural Science Foundation of China(5196103052161008)+3 种基金the Natural Science Foundation of Inner Mongolia(2019MS05013)Youth Innovation Talent Project of Baotouthe Innovation Fund of Inner Mongolia University of Science and Technology(2019QDL-B15)the Central Government Guides Local Science and Technology Development Fund Projects of China。
文摘The fundamental understanding of the effects of rare earth(RE)on the phase transformation of Fe-based alloys is essential in the development of advanced RE-containing high strength steels.In this work,we investigated the effects of La and Ce on the martensitic phase transformation of Fe in terms of the driving force and minimum energy path(MEP)using the first-principles calculations.The calculations of formation energy show that the RE substitution increases the stabilization of fcc-Fe and decreases that of bcc-Fe,thus decreasing the driving force of phase transformation.Meanwhile,the analysis based on the generalized solid-state nudged elastic band(G-SSNEB)method indicates that in the RE-containing systems,an additional energy barrier appears when the phase transformation proceeds along the Bain transition path to c/a ratio of 1.14 in the FM state,which is associated with a sudden decrease in magnetization due to the hybridization between the orbits of the RE atoms and those of the nearest neighbor Fe atoms.The results of potential-energy surfaces(PES)confirm that magnetic ordering and lattice volume change simultaneously with the Bain transition,and in comparison to pure Fe,the variation between the onset and the end structural volumes of the phase transformation is slight for the REcontaining Fe systems.
基金supported by the National Natural Science Foundation of China(21875067,11604099,51811530011)the Fundamental Research Funds for the Central Central Universities,Shanghai Rising-Star(19QA1403100)+6 种基金East China Normal University Multifunctional Platform for Innovationthe STINT grant(CH2017-7163)the National Natural Science Foundation of China(51803060)the Science and Technology Program of Guangdong Province(2018A030313045)the National Key Research and Development Program of China(2017YFA0206600)the National Natural Science Foundation of China(51773045,21772030,51922032,21961160720)for financial supportthe open project of State Key Laboratory of Luminescent Materials and Devices(2021-skllmd-07).
文摘Organic solar cells(OSCs)have attracted huge attention because of their unique merits[1−3].In last few years,thanks to the design of new materials and device engineering,the power conversion efficiencies(PCEs)of OSCs have surpassed 18%[4−8].The PM6:Y6 cells are efficient binary cells,offering high PCEs over 16%[9−11].The high performance originates from the efficient free charge generation and the ground state dipole field at the donor-acceptor interface that promotes the exciton dissociation[12].
基金supported by Shanghai Rising-Star Program(No.19QA1402800)。
文摘1,3,5-Triazine molecules represent a class of molecules that may have been prebiotic information carriers in a primordial soup in early Earth and their excited state dynamics has received attention in recent years.In our previous study,one component with lifetime longer than100 ps was discovered in 2-amino-1,3,5-trainzine(2-AT),but its nature has not been revealed.In this study,excited state dynamics of 2-AT is studied in different solvents by using femtosecond time-resolved transient absorption and fluorescence upconversion spectroscopy.Interestingly,an equilibrium state consisting of the brightππ^(*)and dark nπ^(*)states in 2-AT is directly observed in aqueous solution and its dynamics is solvent sensitive.The whole picture of the excited state deactivation mechanism of 2-AT is proposed based on our spectroscopy results.
文摘The performances of turbine blades have a significant impact on the energy conversion efficiency of vertical solar power plants.In the present study,such a relationship is assessed by considering two kinds of airfoil blades,designed by using the Wilson theory.In particular,numerical simulations are conducted using the SST K−ω model and assuming a wind speed of 3–6 m/s and seven or eight blades.The two airfoils are the NACA63121(with a larger chord length)and the AMES63212;It is shown that the torsion angle of the former is smaller,and its wind drag ratio is larger;furthermore,the resistance is increased by about 66.3%on average.Within the scope of the study,the results show that the NACA63212 airfoil is better than the AMES63212 airfoil in terms of power,with an average improvement of about 2.8%.The simulation results have a certain guiding significance for selecting turbine blade airfoils and improving turbine efficiency.
基金funded by the National Natural Science Foundation of China (No. 11674101)
文摘In this letter, excited state dynamics of TPZ2, a centrosymmetric PRODAN dye, has been studied by using several time-resolved spectroscopy techniques. Fluorescence quantum yield of TPZ2 is found to be 0.50 in both acetonitrile and ethanol solution. The radiative decay rate of the excited state of TPZ2 is determined to be 2.0×10^8 s^-1. Meanwhile, highly efficient triplet state and singlet oxygen generation have been observed in TPZ2 and the intersystem crossing（ISC） rate is determined to be 2.0×10^8s^-1. The almost identical ISC and non-radiative decay rates indicate that ISC is the only non-radiative decay pathway in TPZ2. Thus, dual excited state（S1） deactivation mechanism（50/50, fluorescence/ISC） of TPZ2 is proposed.Because of this unique property, TPZ2 has the potential to be used as biocompatible imaging and photodynamic therapy agent in the same time.
基金Project supported by the Ministry of Science and Technology of China(Grant Nos.2015CB921303 and 2017YFA0303103)the National Natural Science Foundation of China(Grant Nos.11474332 and 11774404)the Chinese Academy of Sciences through the Strategic Priority Research Program(Grant No.XDB07020200)
文摘Kondo semimetal CeRu4Sn6 is attracting renewed attention due to the theoretically predicted nontrivial topology in its electronic band structure. We report hydrostatic and chemical pressure effects on the transport properties of single- and poly-crystalline samples. The electrical resistivity p （T） is gradually enhanced by applying pressure over a wide temperature range from room temperature down to 25 mK. Two thermal activation gaps estimated from high- and low-temperature windows are found to increase with pressure. A flat p（T） observed at the lowest temperatures below 300 mK appears to be robust against both pressure and field. This feature as well as the increase of the energy gaps calls for more intensive investigations with respect to electron correlations and band topology.
基金National Natural Science Foundation of China(No.81673895)Outstanding Young Talents Project of Beijing University of Chinese Medicine(No.BUCM-2019-JCRC008)。
文摘Objective:To explore the cardioprotective mechanism of Wenxin Granules regulating the expression of apoptosis-related genes in cardiomyocytes.Methods:A rat model of myocardial infarction was established and randomly divided into model group,Wenxin granule low-dose group,Wenxin granule high-dose group,metoprolol group and sham operation group.the left ventricular end systole anterior wall thickness(LVAWs),end systole inner diameter(LVIDs),end systole posterior wall thickness(LVPWs),end-diastolic anterior wall thickness(LVAWd),end-diastolic inner diameter(LVIDd),end-diastolic posterior wall thickness(LVPWd)and left ventricular ejection fraction(LVEF)were detected by echocardiography in each group after 2 weeks of treatment.Hematoxylin eosin(HE)staining was used to observe the changes in the cardiac structure of rats in each group.Real-time PCR(Real-time PCR)was used to detect the relative expression of mammalian B-cell lymphoma-2(BCL-2),BCL-2 related X protein(BAX),Caspase-9(Caspase-9),and Caspase-3(Caspase-3)mRNA.TUNEL staining was used to detect changes in the apoptotic rate of rat cardiomyocytes in each group.Results:Compared with the sham operation group,the LVAWs,LVPWs,LVPWd and LVEF of the model group were significantly reduced(P<0.05,P<0.01),and LVIDs and LVIDd were significantly increased(P<0.05,P<0.01).Severe pathological ischemia injury of heart tissue.The relative expression of BCL-2 mRNA and the ratio of BCL-2/BAX in the model group were significantly reduced(P<0.01),while the relative expression of BAX,Caspase-9 and Caspase-3 mRNA was significantly increased(P<0.01).The apoptosis rate was significantly increased(P<0.01).In the low-dose and high-dose groups of Wenxin Granules and the Metoprolol group,LVAWs,LVPWs,LVPW d,and LVEF of rats in each administration group increased significantly(P<0.05,P<0.01),LVIDs,LVIDd was significantly reduced(P<0.05,P<0.01),the pathological damage of the heart tissue was improved,the expression of BCL-2 mRNA and the ratio of BCL-2/BAX were significantly increased(P<0.05,P<0.01),BAX,The expression of Caspase-9 and Caspase-3 mRNA was significantly reduced(P<0.05,P<0.01),and the apoptotic rate of myocardial cells was significantly reduced(P<0.01).Conclusion:Wenxin granule can play a cardioprotective role by regulating the gene expression of BCL-2/BAX/Caspase apoptosis pathway.
文摘In recent years,relevant government departments have achieved the goal of reduction and harmless application through the development and implementation of municipal waste incineration power plants,in order to advocate ecological and environmental protection.At present,in order to further achieve the goal of sustainable development,municipal waste incineration power plants have actively responded to the national call and requirements as well as made overall arrangements for the energy-saving design and optimization design of their internal system.Therefore,with the concept of sustainable development,this paper studies and analyzes the problems of the HVAC design as well as suggests related strategies for municipal waste incineration power plants in order to provide relevant reference.
基金funded by the National Key Research and Development Program of China(No.2022YFA0103300)Being Nova Program(No.20220484076)+2 种基金Major Program of the National Natural Science Foundation of China(Nos.82070184 and 82293630)Beijing Municipal Science&Technology Commission(No.Z211100002921071)Peking University Clinical Scientist Training Program(No.BMU2024PYJH012).
文摘To the Editor:Co-reactivation of cytomegalovirus(CMV)and Epstein–Barr virus(EBV)is common after haploidentical stem cell transplantation(haplo-SCT)and can lead to potentially life-threatening complications.[1,2]Adoptive immunotherapy with virus-specific T lymphocytes(VSTs)is a critical treatment option that has shown promising results in controlling CMV and EBV infections in several clinical studies,providing protection for 70–90%of patients.[3]Multi-virus-specific T cell lines offer an advanced method for simultaneously addressing multiple challenging viral infections.However,data regarding its long-term efficacy are limited.Additionally,clinical trials with multi-virus-specific T cells have predominantly focused on single virus reactivation,leaving gaps in our understanding of the effectiveness of VSTs during multivirus co-reactivation.Antigenic competition may affect the expansion of virus-specific T cells in vitro during the generation of multi-virus-specific cell lines.Whether in vivo competition among infused cells compromises the efficacy of adoptively transferred VSTs remains unclear.
基金support from the National Key R&D Program of China(2022YFA1103300)SLS-Qidong Innovation Fund(8410101639)+3 种基金the Peking-Tsinghua Center for Life Sciences and School of Life Sciences,Peking University to H.-Y.L.grant support from the Zhejiang Provincial Natural Science Foundation of China(LR20C070001)“Leading Goose”R&D Program(2024C03089)the Science and Technology Department of Zhejiang Province(Key Project,2021C03011)”to X.G.
文摘Erythropoiesis is a crucial process in hematopoiesis,yet it remains highly susceptible to disruption by various diseases,which significantly contribute to the global challenges of anemia and blood shortages.Current treatments like erythropoietin(EPO)or glucocorticoids often fall short,especially for hereditary anemias such as Diamond-Blackfan anemia(DBA).To uncover new erythropoiesis-stimulating agents,we devised a screening system using primary human hematopoietic stem and progenitor cells(HSPCs).We discovered that BRAF inhibitors(BRAFi),commonly used to treat BRAF^(V600E) melanoma,can unexpectedly and effectively promote progenitor cell proliferation by temporarily delaying erythroid differentiation.Notably,these inhibitors exhibited pronounced efficacy even under cytokine-restricted conditions and in patient samples of DBA.Mechanistically,although these BRAFi inhibit the MAPK cascade in BRAF^(V600E) mutant cells,they paradoxically act as amplifiers in wild-type BRAF cells,potently enhancing the cascade.Furthermore,we found that while the oncogenic BRAF^(V600E) mutation disrupts hematopoiesis and erythropoiesis through AP-1 hyperactivation,BRAFi minimally impact HSPC self-renewal and differentiation.In vivo studies have shown that BRAFi can enhance human hematopoiesis and erythropoiesis in severe immunodeficient mouse models and alleviate anemia in the Rpl11 haploinsufficiency DBA model,as well as other relevant anemia models.This discovery underscores the role of the MAPK pathway in hematopoiesis and positions BRAFi as a promising therapeutic option for improving hematopoietic reconstitution and treating anemias,including DBA.
文摘In the process of collating the raw data,the authors noticed three images in Fig.4 were used incorrectly.They made an inadvertent mistake by arranging the figure of M2 Group into M2+LY294002 Group in Fig.4k during the revision process.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82070367).
文摘To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100%.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.
基金supported by National Key Research and Development Plan of China(No.2022YFC2502606,2021YFA1100902)Beijing Nova Program of Science and Technology(No.20230484446)+2 种基金Peking University People’s Hospital(No.RZ2024-01)Joint Research Project of the Shijiazhuang-Peking University Cooperation Program,Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501200)National Natural Science Foundation of China(No.82350105,82270228)。
文摘Objective:Immune effector cell-associated hematotoxicity(ICAHT),characterized by prolonged cytopenia and delayed hematopoietic recovery,is a common complication following chimeric antigen receptor T(CAR-T)cell therapy.However,the applicability of existing predictive models,CAR-HEMATOTOX(CAR-HT)for lymphoma,acute lymphoblastic leukemia-HEMATOTOX(ALL-HT)for B-ALL,and the early ICAHT prediction model(e IPM),remains uncertain across different hematologic malignancies.Methods:We prospectively analyzed 119 patients who received CAR-T therapy between January 2022 and June2025,including B-ALL(n=62),T-ALL/non-Hodgkin's lymphoma(NHL)(n=25),and multiple myeloma(MM,n=32).The CAR-HT,ALL-HT,and e IPM models were evaluated for their ability to predict ICAHT severity and survival outcomes.Results:Grade 3 ICAHT occurred in 32.3%of B-ALL,40.0%of T-ALL/NHL,and 25.0%of MM patients,while grade 4 rates were 33.9%,20.0%,and 6.3%,respectively.CAR-HT classified 67.2%of patients as high-risk,and ALL-HT identified 56.3%of ALL/NHL patients as high-risk.In both models,high-risk groups experienced significantly more prolonged neutropenia than low-risk groups(CAR-HT:17.7 vs.5.3 d,P<0.001;ALL-HT:21.3 vs.7.7 d,P<0.001).Both e IPMpre and e IPMpost strongly correlated with grade 3-4 ICAHT(P<0.001).Importantly,survival analysis showed that e IPMpre stratification distinguished outcomes:1-year overall survival(OS)was 65%in medium+high-risk vs.84%in low-risk patients(P=0.006),and 1-year disease-free survival(DFS)was 44%vs.73%(P<0.001).Similar predictive accuracy was observed with e IPMpost.Conclusions:The CAR-HT,ALL-HT,and e IPM models consistently identify patients at high risk for severe ICAHT across B-ALL,T-ALL/NHL,and MM.Among these,the e IPM stands out as a promising universal tool for survival prediction.These models provide valuable prognostic insights that can guide supportive care and inform treatment planning in CAR-T therapy.
