Complex brain diseases seriously endanger human health,and early diagnostic biomarkers and effective treatments are currently lacking.Due to ethical constraints on human research,establishing monkey models is crucial ...Complex brain diseases seriously endanger human health,and early diagnostic biomarkers and effective treatments are currently lacking.Due to ethical constraints on human research,establishing monkey models is crucial to address these issues.With the rapid development of technology,transgenic monkey models of a range of brain diseases,especially autism spectrum disorder(ASD),have been successfully established.However,to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies,there is still a lack of a standard tool,i.e.,a system for collecting and analyzing the daily behaviors of brain disease model monkeys.Therefore,with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes,we established a standard daily behavior collection and analysis system,including behavioral data collection protocols and a monkey daily behavior ethogram(MDBE)for rhesus and cynomolgus monkeys,which are the most commonly used non-human primates in model construction.Then,we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,Text Revision(DSM-5-TR),which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms.We then established a sub-ethogram(ASD monkey core behavior ethogram(MCBE-ASD))specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE.Subsequently,we demonstrated the high reproducibility of the system.展开更多
Aspect-Based Sentiment Analysis(ABSA)is a fundamental area of research in Natural Language Processing(NLP).Within ABSA,Aspect Sentiment Quad Prediction(ASQP)aims to accurately identify sentiment quadruplets in target ...Aspect-Based Sentiment Analysis(ABSA)is a fundamental area of research in Natural Language Processing(NLP).Within ABSA,Aspect Sentiment Quad Prediction(ASQP)aims to accurately identify sentiment quadruplets in target sentences,including aspect terms,aspect categories,corresponding opinion terms,and sentiment polarity.However,most existing research has focused on English datasets.Consequently,while ASQP has seen significant progress in English,the Chinese ASQP task has remained relatively stagnant.Drawing inspiration from methods applied to English ASQP,we propose Chinese generation templates and employ prompt-based instruction learning to enhance the model’s understanding of the task,ultimately improving ASQP performance in the Chinese context.Ultimately,under the same pre-training model configuration,our approach achieved a 5.79%improvement in the F1 score compared to the previously leading method.Furthermore,when utilizing a larger model with reduced training parameters,the F1 score demonstrated an 8.14%enhancement.Additionally,we suggest a novel evaluation metric based on the characteristics of generative models,better-reflecting model generalization.Experimental results validate the effectiveness of our approach.展开更多
Objective:The aim of this study was to investigate how the tumor immune microenvironment differs regarding tumor genomics,as well as its impact on prognoses and responses to immunotherapy in East Asian patients with n...Objective:The aim of this study was to investigate how the tumor immune microenvironment differs regarding tumor genomics,as well as its impact on prognoses and responses to immunotherapy in East Asian patients with non-small cell lung cancer(NSCLC).Methods:We performed an integrated analysis using publicly available data to identify associations between anti-programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)immunotherapy efficacy and classic driver oncogene mutations in East Asian NSCLC patients.Four pooled and clinical cohort analyses were used to correlate driver oncogene mutation status and tumor microenvironment based on PD-L1 and CD8+tumor-infiltrating lymphocytes(TILs).Immune infiltrating patterns were also established for genomic NSCLC subgroups using the CIBERSORT algorithm.Results:Based on East Asian NSCLC patients,TIDE analyses revealed that for anti-PD-1/PD-L1 immunotherapy,epidermal growth factor receptor(EGFR)-mutant and anaplastic lymphoma kinase(ALK)-rearranged tumors yielded inferior responses;however,although Kirsten rat sarcoma viral oncogene homolog(KRAS)-mutant tumors responded better,the difference was not statistically significant(EGFR:P=0.037;ALK:P<0.001;KRAS:P=0.701).Pooled and clinical cohort analyses demonstrated tumor immune microenvironment heterogeneities correlated with oncogenic patterns.The results showed remarkably higher PD-L1-and TIL-positive KRAS-mutant tumors,suggesting KRAS mutations may drive an inflammatory phenotype with adaptive immune resistance.However,the EGFR-mutant or ALK-rearranged groups showed a remarkably higher proportion of PD-L1-/TIL-tumors,suggesting an uninflamed phenotype with immunological ignorance.Notably,similar to triple wild-type NSCLC tumors,EGFR L858R-mutant tumors positively correlated with an inflammatory phenotype,suggesting responsiveness to anti-PD-1/PD-L1 immunotherapy(P<0.05).Furthermore,the CIBERSORT algorithm results revealed that EGFR-mutant and ALK-rearranged tumors were characterized by an enriched resting memory CD4+T cell population(P<0.001),as well as a lack of CD8+T cells(P<0.01),and activated memory CD4+T cells(P=0.001).Conclusions:Our study highlighted the complex relationships between immune heterogeneity and immunotherapeutic responses in East Asian NSCLC patients regarding oncogenic dependence.展开更多
Dear editor,The pandemic of coronavirus disease-19(COVID-19)has lasted for more than three years,causing lots of extra death and posing a serious threat to public health.This pandemic swept the last global safety isla...Dear editor,The pandemic of coronavirus disease-19(COVID-19)has lasted for more than three years,causing lots of extra death and posing a serious threat to public health.This pandemic swept the last global safety island in a matter of months,coinciding with the switch of zero-COVID policy of China.The causative agent,SARS-CoV-2,spreads globally and then lurks in the population with sporadic outbreaks in local areas.Meanwhile,the sequelae of convalescent COVID-19 patients receded slowly.The pantissue tropism of SARS-CoV-2 results in a wide range of symptoms in patients,including cardiovascular disorders.Cardiac complications occur in 20%–44%of hospitalized patients,which is an independent risk factor for COVID-19 mortality(Ma et al.,2022;Patone et al.,2022).Survivors of acute COVID-19 also have a substantial risk of cardiovascular disease burden lasting up to one year(Xie et al.,2022).展开更多
Objective:The proportion of patients with stageⅠlung adenocarcinoma(LUAD)has dramatically increased with the prevalence of low-dose computed tomography use for screening.Up to 30%of patients with stageⅠLUAD experien...Objective:The proportion of patients with stageⅠlung adenocarcinoma(LUAD)has dramatically increased with the prevalence of low-dose computed tomography use for screening.Up to 30%of patients with stageⅠLUAD experience recurrence within 5 years after curative surgery.A robust risk stratification tool is urgently needed to identify patients who might benefit from adjuvant treatment.Methods:In this first investigation of the relationship between metabolic reprogramming and recurrence in stageⅠLUAD,we developed a recurrence-associated metabolic signature(RAMS).This RAMS was based on metabolism-associated genes to predict cancer relapse and overall prognoses of patients with stageⅠLUAD.The clinical significance and immune landscapes of the signature were comprehensively analyzed.Results:Based on a gene expression profile from the GSE31210 database,functional enrichment analysis revealed a significant difference in metabolic reprogramming that distinguished patients with stageⅠLUAD with relapse from those without relapse.We then identified a metabolic signature(i.e.,RAMS)represented by 2 genes(ACADM and RPS8)significantly related to recurrence-free survival and overall survival times of patients with stageⅠLUAD using transcriptome data analysis of a training set.The training set was well validated in a test set.The discriminatory power of the 2 gene metabolic signature was further validated using protein values in an additional independent cohort.The results indicated a clear association between a high risk score and a very poor patient prognosis.Stratification analysis and multivariate Cox regression analysis showed that the RAMS was an independent prognostic factor.We also found that the risk score was positively correlated with inflammatory response,the antigen-presenting process,and the expression levels of many immunosuppressive checkpoint molecules(e.g.,PD-L1,PD-L2,B7-H3,galectin-9,and FGL-1).These results suggested that high risk patients had immune response suppression.Further analysis revealed that anti-PD-1/PD-L1 immunotherapy did not have significant benefits for high risk patients.However,the patients could respond better to chemotherapy.Conclusions:This study is the first to highlight the relationship between metabolic reprogramming and recurrence in stageⅠLUAD,and is the first to also develop a clinically feasible signature.This signature may be a powerful prognostic tool and help further optimize the cancer therapy paradigm.展开更多
Aspect-Based Sentiment Analysis(ABSA)is one of the essential research in the field of Natural Language Processing(NLP),of which Aspect Sentiment Quad Prediction(ASQP)is a novel and complete subtask.ASQP aims to accura...Aspect-Based Sentiment Analysis(ABSA)is one of the essential research in the field of Natural Language Processing(NLP),of which Aspect Sentiment Quad Prediction(ASQP)is a novel and complete subtask.ASQP aims to accurately recognize the sentiment quad in the target sentence,which includes the aspect term,the aspect category,the corresponding opinion term,and the sentiment polarity of opinion.Nevertheless,existing approaches lack knowledge of the sentence’s syntax,so despite recent innovations in ASQP,it is poor for complex cyber comment processing.Also,most research has focused on processing English text,and ASQP for Chinese text is almost non-existent.Chinese usage is more casual than English,and individual characters contain more information.We propose a novel syntactically enhanced neural network framework inspired by syntax knowledge enhancement strategies in other NLP studies.In this framework,part of speech(POS)and dependency trees are input to the model as auxiliary information to strengthen its cognition of Chinese text structure.Besides,we design a relation extraction module,which provides a bridge for the overall extraction of the framework.A comparison of the designed experiments reveals that our proposed strategy outperforms the previous studies on the key metric F1.Further experiments demonstrate that the auxiliary information added to the framework improves the final performance in different ways.展开更多
Objective： To discuss the diagnosis and differential diagnosis of granulocytic sarcoma （GS）. Methods： Six cases were reported in this paper. They were assessed by pathologists. Immunohistochemistry （IHC） stain a...Objective： To discuss the diagnosis and differential diagnosis of granulocytic sarcoma （GS）. Methods： Six cases were reported in this paper. They were assessed by pathologists. Immunohistochemistry （IHC） stain and routine hematoxylin and eosin （H＆E） stain were applied. Results： All patients involved in different anatomic sites respectively including skin, lymph node, soft tissue, breast, cervix and penis. All cases were previously error diagnoses. Three of them were initially diagnosed as non-Hodgkin lymphoma （NHL）. One case of cervical lymph node lesion was first considered as metastasized carcinoma by clinician. One biopsied skin sample was initially reported as Karposi＇s sarcoma. And one breast case was suspicious of the Iobular carcinoma with the frozen samples without antecedent clinical history information. GS was accompanied with acute myeloid leukemia （AML） in one case and with acute lymphocytic leukemia （ALL） in one case. Histopathologically, blastic, immature and differentiated variants were found in four, one and one, respectively. Immunohistochemistry （IHC） showed that myeloperoxidase （MPO） and lysozyme were both found to be positive in all cases, CD43 was found in 5 of 6 cases. Three of six cases were CD68, CD15 and LCA positive. CD34 and CDl17 were positive in 1/5 and 1/6 cases, respectively. However, CD20 and CD3 were negative in all cases. Conclusion： GS was uncommon and it may be misdiagnosed easily in routine practice. Each area had its own character, but they had the common features too. It can be correctly diagnosed by combination of H＆E stain, IHC stain, peripheral blood and bone marrow. MPO and Lysozyme were necessary for the nature of granulocytes. In addition, CD43, CD68 and CD15 were very helpful.展开更多
In this paper, we discuss the uniform convergence of the simple upwind scheme on the Shishkin mesh and the Bakhvalov-Shishkin mesh for solving a singularly perturbed Robin boundary value problem, and investigate the m...In this paper, we discuss the uniform convergence of the simple upwind scheme on the Shishkin mesh and the Bakhvalov-Shishkin mesh for solving a singularly perturbed Robin boundary value problem, and investigate the midpoint upwind scheme on the Shishkin mesh and the Bakhvalov-Shishkin mesh to achieve better uniform convergence. The elaborate ε-uniform pointwise estimates are proved by using the comparison principle and barrier functions. The numerical experiments support the theoretical results for the schemes on the meshes.展开更多
In this work,we develop a novel computational method,referred to as SCT-Z-FDTD,which integrates the Z-transform finite-difference time-domain algorithm with a scale-compressed technique incorporating wave vectors.The ...In this work,we develop a novel computational method,referred to as SCT-Z-FDTD,which integrates the Z-transform finite-difference time-domain algorithm with a scale-compressed technique incorporating wave vectors.The proposed approach fa-cilitates accurate modeling of electromagnetic wave propagation through multi-layered anisotropic media,enabling precise evalua-tion of reflection and refraction coefficients over short time intervals.On first place,considering constitutive relationship between electromagnetic fields(E,H)and fluxes(D,B),Z-transform is employed to the anisotropic Maxwell’s curl equations for completing discrete-time form,and then the transverse wave vectors are exploited along a single direction to design the electromagnetic numerical differential process.After that,with the analysis corresponding flow chart,the plane waves are employed with different modes such as transverse electromagnetic,transverse electric,and transverse magnetic to detect the specific propagation.To further verify lower memory and higher efficiency,we select various multi-layered examples with anisotropies for executing the proposed method.Compared with the popular commercial software COMSOL,those data from multi-layered computation are quite consistent with the approximate trend the 2nd-order error convergence.展开更多
Background:Although immune checkpoint inhibitors(ICIs)against programmed cell death protein 1(PD-1)and its ligand PD-L1 have demonstrated potency towards treating patients with non-small cell lung carcinoma(NSCLC),the...Background:Although immune checkpoint inhibitors(ICIs)against programmed cell death protein 1(PD-1)and its ligand PD-L1 have demonstrated potency towards treating patients with non-small cell lung carcinoma(NSCLC),the potential association between Kirsten rat sarcoma viral oncogene homolog(KRAS)oncogene substitutions and the efficacy of ICIs remains unclear.In this study,we aimed to find point mutations in the KRAS gene resistant to ICIs and elucidate resistance mechanism.Methods:The association between KRAS variant status and the efficacy of ICIs was explored with a clinical cohort(n=74),and confirmed with a mouse model.In addition,the tumor immune microenvironment(TIME)of KRASmutant NSCLC,such as CD8+tumor-infiltrating lymphocytes(TILs)and PD-L1 level,was investigated.Cell lines expressing classic KRAS substitutions were used to explore signaling pathway activation involved in the formation of TIME.Furthermore,interventions that improved TIME were developed to increase responsiveness to ICIs.Results:We observed the inferior efficacy of ICIs in KRAS-G12D-mutant NSCLC.Based upon transcriptome data and immunostaining results from KRAS-mutant NSCLC,KRAS-G12D point mutation negatively correlated with PD-L1 level and secretion of chemokines CXCL10/CXCL11 that led to a decrease in CD8+TILs,which in turn yielded an immunosuppressive TIME.The analysis of cell lines overexpressing classic KRAS substitutions further revealed that KRAS-G12D mutation suppressed PD-L1 level via the P70S6K/PI3K/AKT axis and reduced CXCL10/CXCL11 levels by down-regulating high mobility group protein A2(HMGA2)level.Notably,paclitaxel,a chemotherapeutic agent,upregulated HMGA2 level,and in turn,stimulated the secretion of CXCL10/CXCL11.Moreover,PD-L1 blockade combined with paclitaxel significantly suppressed tumor growth compared with PD-L1 inhibitor monotherapy in a mouse model with KRAS-G12D-mutant lung adenocarcinoma.Further analyses revealed that the combined treatment significantly enhanced the recruitment of CD8+TILs via the up-regulation of CXCL10/CXCL11 levels.Results of clinical study also revealed the superior efficacy of chemo-immunotherapy in patients with KRAS-G12D-mutant NSCLC compared with ICI monotherapy.Conclusions:Our study elucidated the molecular mechanism by which KRASG12D mutation drives immunosuppression and enhances resistance of ICIs in NSCLC.Importantly,our findings demonstrate that ICIs in combination with chemotherapy may be more effective in patients with KRAS-G12D-mutant NSCLC.展开更多
A simple and effective model of heat conduction across thin films is set up and molecular dynamics simulations are implemented to explore the thermal conductivity of nanoscale thin dielectric films in the direction pe...A simple and effective model of heat conduction across thin films is set up and molecular dynamics simulations are implemented to explore the thermal conductivity of nanoscale thin dielectric films in the direction perpendicular to the film plane. Solid argon is selected as the model system due to its reliable experimental data and potential function. Size effects of the thermal conductivity across thin films are found by computer simulations: in a film thickness range of 2-10 nm, the conductivity values are remarkably lower than the corresponding bulk experimental data and increase as the thickness increases. The consistency between the approximate solution of the phonon Boltzmann transport equation and the simulation results ascribes the thermal conductivity size effect to the phonon scattering at film boundaries.展开更多
Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)...Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)plays an instrumental role in aerobic glycolysis and tumor progression.However,whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer(SCLC)is largely unclear.In this study,we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC.Methods:Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts.CSC-like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model.Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133.The expression levels of CD133-associated and CSC-relevant proteins were evaluated by immunoblotting,immunoprecipitation,immunofluorescence,and immunohistochemistry assay.RNA expression levels of Nanog,POU5F1,Lin28,HK2,Prominin-1 were analyzed through quantitative reverse transcription PCR.Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay.CD133+cells were sorted by flow cytometry using an anti-CD133 antibody.Results:We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts.HK2 depletion inhibited CSC stemness and promoted CSC differentiation.Mechanistically,nonmitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels.The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin-specific protease 11(USP11)to CD133,thereby inhibiting CD133 polyubiquitylation and degradation.HK2-mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators,SCLC cell stemness,and tumor growth in mice.In addition,HK2 expression was positively correlated with CD133 expression in human SCLC specimens,and their expression levels were associated with poor prognosis of SCLC patients.Conclusions:These results revealed a critical non-metabolic function of HK2 in promotion of cancer cell stemness.Our findings provided new insights into the multifaceted roles of HK2 in tumor development.展开更多
Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the...Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.展开更多
Canonical ensemble Monte Carlo simulations have been carried out to investigate thethermodynamic properties of two-dimensional fluids subjected to truncated Lennard-Jones 12-6 potential. The simulations of thermodynam...Canonical ensemble Monte Carlo simulations have been carried out to investigate thethermodynamic properties of two-dimensional fluids subjected to truncated Lennard-Jones 12-6 potential. The simulations of thermodynamic states sweep across liquid-vapor regime over a wide range of thermodynamic conditions. Simulated isotherms behave van der Waals loop-like characteristics in the liquid-vapor phase-transition region. It suggests a continuous isothermal phase transition in the case of micro system, in which the system size prohibits phase separation. Two-dimensional dimensionless van der Waals equation of states has been obtained from theoretical analysis. By fitting simulated data to this equation, temperature-dependent parameters in the equation have been determined.展开更多
Dear Editor,In recent years,the rapid development of immunotherapy has brought survival benefits for lung squamous cell carcinoma(LUSC)patients who have rare treatment options.Nevertheless,there are still some patient...Dear Editor,In recent years,the rapid development of immunotherapy has brought survival benefits for lung squamous cell carcinoma(LUSC)patients who have rare treatment options.Nevertheless,there are still some patients with immunotherapy resistance,which is the root cause of the low benefit rate and disease progression of the overall population,and it is an urgent problem to be solved.Except for tumor mutation burden,the tumor immune microenvironment(TIME)as characterized by infiltration of CD8+tumor-infiltrating lymphocytes(TILs)and PD-L1 expression has been associated with the efficacy of immune checkpoint inhibitors(ICIs).In our previous studies,we have demonstrated that psoriasin,also known as S100 calcium-binding protein A7(S100A7),not only accelerates tumor progression via the activation of the p-Erk pathway in LUSC and the p-Erk and p-FAK pathways in esophageal squamous cell carcinomas(ESCC)but also remodels the tumor microenvironment by promoting angiogenesis and M2 macrophage infiltration in ESCC.1,2 However,the role of S100A7 in the TIME and immunotherapy efficacy in LUSC remains to be elucidated.展开更多
Small-cell lung cancer(SCLC)is a highly malignant cancer with characteristics of rapid growth,abundant angiogenesis,and early distant metastasis that accounts for about 15%of lung cancers.With the wide application of ...Small-cell lung cancer(SCLC)is a highly malignant cancer with characteristics of rapid growth,abundant angiogenesis,and early distant metastasis that accounts for about 15%of lung cancers.With the wide application of low-dose computed tomography screening in recent years,the incidence of early limited-stage SCLC has increased dramatically.展开更多
Bladder cancer represents one of the most prevalent malignant tumors affecting the urinary system.As per data disclosed by the National Cancer Registration Center of China in 2019,the incidence of bladder cancer was 5...Bladder cancer represents one of the most prevalent malignant tumors affecting the urinary system.As per data disclosed by the National Cancer Registration Center of China in 2019,the incidence of bladder cancer was 5.80 per 100,000 in 2015,placing it as the thirteenth most common systemic malignancy.Bladder cancer poses a substantial threat to public health in China,underlining the critical importance of standardizing diagnosis and treatment to enhance clinical outcomes.This clinical practice guideline for bladder cancer centers on the etiologies,clinical presentations,and diagnostic procedures for suspected bladder cancer,in addition to the histopathology and staging of urothelial bladder cancer.展开更多
Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein comple...Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of heme-binding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by heme-agarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.展开更多
基金supported by the Key-Area Research and Development Program of Guangdong Province(No.2019B030335001)the STI2030-Major Projects(No.2021ZD0200900)+9 种基金the National Key Research and Development Program of China(Nos.2021YFF0702700 and 2018YFA0801403)the National Natural Science Foundation of China(Nos.81960422,32100801,82101241,82360226,82160923,82260929,82374425,and 32460194)the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(No.XDB32060200)the STI2030-Major Projects(Nos.2022ZD0205200 and 2022ZD0212700)the Science and Technology Department of Yunnan Province(Nos.202305AH340006 and 202305AH340007)the Yunnan Fundamental Research Projects(Nos.202201AT070153 and 202201AT070139)the Science and Technology Project of Yunnan Province(No.202101AY070001-001)the Yunnan Revitalization Talent Support Program(No.YNWR-QNBJ2019-043)the CAS“Light of West China”Programthe Yunnan Revitalization Talents Support Plan。
文摘Complex brain diseases seriously endanger human health,and early diagnostic biomarkers and effective treatments are currently lacking.Due to ethical constraints on human research,establishing monkey models is crucial to address these issues.With the rapid development of technology,transgenic monkey models of a range of brain diseases,especially autism spectrum disorder(ASD),have been successfully established.However,to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies,there is still a lack of a standard tool,i.e.,a system for collecting and analyzing the daily behaviors of brain disease model monkeys.Therefore,with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes,we established a standard daily behavior collection and analysis system,including behavioral data collection protocols and a monkey daily behavior ethogram(MDBE)for rhesus and cynomolgus monkeys,which are the most commonly used non-human primates in model construction.Then,we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition,Text Revision(DSM-5-TR),which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms.We then established a sub-ethogram(ASD monkey core behavior ethogram(MCBE-ASD))specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE.Subsequently,we demonstrated the high reproducibility of the system.
基金supported by the National Key Research and Development Program(Nos.2021YFF0901705,2021YFF0901700)the State Key Laboratory of Media Convergence and Communication,Communication University of China+1 种基金the Fundamental Research Funds for the Central Universitiesthe High-Quality and Cutting-Edge Disciplines Construction Project for Universities in Beijing(Internet Information,Communication University of China).
文摘Aspect-Based Sentiment Analysis(ABSA)is a fundamental area of research in Natural Language Processing(NLP).Within ABSA,Aspect Sentiment Quad Prediction(ASQP)aims to accurately identify sentiment quadruplets in target sentences,including aspect terms,aspect categories,corresponding opinion terms,and sentiment polarity.However,most existing research has focused on English datasets.Consequently,while ASQP has seen significant progress in English,the Chinese ASQP task has remained relatively stagnant.Drawing inspiration from methods applied to English ASQP,we propose Chinese generation templates and employ prompt-based instruction learning to enhance the model’s understanding of the task,ultimately improving ASQP performance in the Chinese context.Ultimately,under the same pre-training model configuration,our approach achieved a 5.79%improvement in the F1 score compared to the previously leading method.Furthermore,when utilizing a larger model with reduced training parameters,the F1 score demonstrated an 8.14%enhancement.Additionally,we suggest a novel evaluation metric based on the characteristics of generative models,better-reflecting model generalization.Experimental results validate the effectiveness of our approach.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81802299,81502514,and 81702841)the Fundamental Research Funds for the Central Universities(Grant No.3332018070)+4 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant Nos.2016-I2M-1-001 and 2017-I2M-1-005)the National Key Basic Research Development Plan(Grant No.2018YFC1312105)the Graduate Innovation Funds of Peking Union Medical College(Grant No.2019-1002-06)the China Postdoctoral Science Foundation Grant(Grant No.2019M650568)the Guangci Distinguished Young Scholars Training Program(Grant No.GCQN-2018-A09).
文摘Objective:The aim of this study was to investigate how the tumor immune microenvironment differs regarding tumor genomics,as well as its impact on prognoses and responses to immunotherapy in East Asian patients with non-small cell lung cancer(NSCLC).Methods:We performed an integrated analysis using publicly available data to identify associations between anti-programmed death 1(PD-1)/programmed death-ligand 1(PD-L1)immunotherapy efficacy and classic driver oncogene mutations in East Asian NSCLC patients.Four pooled and clinical cohort analyses were used to correlate driver oncogene mutation status and tumor microenvironment based on PD-L1 and CD8+tumor-infiltrating lymphocytes(TILs).Immune infiltrating patterns were also established for genomic NSCLC subgroups using the CIBERSORT algorithm.Results:Based on East Asian NSCLC patients,TIDE analyses revealed that for anti-PD-1/PD-L1 immunotherapy,epidermal growth factor receptor(EGFR)-mutant and anaplastic lymphoma kinase(ALK)-rearranged tumors yielded inferior responses;however,although Kirsten rat sarcoma viral oncogene homolog(KRAS)-mutant tumors responded better,the difference was not statistically significant(EGFR:P=0.037;ALK:P<0.001;KRAS:P=0.701).Pooled and clinical cohort analyses demonstrated tumor immune microenvironment heterogeneities correlated with oncogenic patterns.The results showed remarkably higher PD-L1-and TIL-positive KRAS-mutant tumors,suggesting KRAS mutations may drive an inflammatory phenotype with adaptive immune resistance.However,the EGFR-mutant or ALK-rearranged groups showed a remarkably higher proportion of PD-L1-/TIL-tumors,suggesting an uninflamed phenotype with immunological ignorance.Notably,similar to triple wild-type NSCLC tumors,EGFR L858R-mutant tumors positively correlated with an inflammatory phenotype,suggesting responsiveness to anti-PD-1/PD-L1 immunotherapy(P<0.05).Furthermore,the CIBERSORT algorithm results revealed that EGFR-mutant and ALK-rearranged tumors were characterized by an enriched resting memory CD4+T cell population(P<0.001),as well as a lack of CD8+T cells(P<0.01),and activated memory CD4+T cells(P=0.001).Conclusions:Our study highlighted the complex relationships between immune heterogeneity and immunotherapeutic responses in East Asian NSCLC patients regarding oncogenic dependence.
文摘Dear editor,The pandemic of coronavirus disease-19(COVID-19)has lasted for more than three years,causing lots of extra death and posing a serious threat to public health.This pandemic swept the last global safety island in a matter of months,coinciding with the switch of zero-COVID policy of China.The causative agent,SARS-CoV-2,spreads globally and then lurks in the population with sporadic outbreaks in local areas.Meanwhile,the sequelae of convalescent COVID-19 patients receded slowly.The pantissue tropism of SARS-CoV-2 results in a wide range of symptoms in patients,including cardiovascular disorders.Cardiac complications occur in 20%–44%of hospitalized patients,which is an independent risk factor for COVID-19 mortality(Ma et al.,2022;Patone et al.,2022).Survivors of acute COVID-19 also have a substantial risk of cardiovascular disease burden lasting up to one year(Xie et al.,2022).
基金supported by the National Natural Science Foundation of China(Grant Nos.81802299 and 81502514)the Fundamental Research Funds for the Central Universities(Grant No.3332018070)+3 种基金the CAMS Innovation Fund for Medical Sciences(Grant Nos.2016-I2M-1-001 and 2017-I2M-1-005)the National Key R&D Program of China(Grant Nos.2018YFC1312100 and 2018YFC1312102)the National Key Basic Research Development Plan(Grant No.2018YFC1312105)the Graduate Innovation Funds of Peking Union Medical College(Grant No.2019-1002-06)。
文摘Objective:The proportion of patients with stageⅠlung adenocarcinoma(LUAD)has dramatically increased with the prevalence of low-dose computed tomography use for screening.Up to 30%of patients with stageⅠLUAD experience recurrence within 5 years after curative surgery.A robust risk stratification tool is urgently needed to identify patients who might benefit from adjuvant treatment.Methods:In this first investigation of the relationship between metabolic reprogramming and recurrence in stageⅠLUAD,we developed a recurrence-associated metabolic signature(RAMS).This RAMS was based on metabolism-associated genes to predict cancer relapse and overall prognoses of patients with stageⅠLUAD.The clinical significance and immune landscapes of the signature were comprehensively analyzed.Results:Based on a gene expression profile from the GSE31210 database,functional enrichment analysis revealed a significant difference in metabolic reprogramming that distinguished patients with stageⅠLUAD with relapse from those without relapse.We then identified a metabolic signature(i.e.,RAMS)represented by 2 genes(ACADM and RPS8)significantly related to recurrence-free survival and overall survival times of patients with stageⅠLUAD using transcriptome data analysis of a training set.The training set was well validated in a test set.The discriminatory power of the 2 gene metabolic signature was further validated using protein values in an additional independent cohort.The results indicated a clear association between a high risk score and a very poor patient prognosis.Stratification analysis and multivariate Cox regression analysis showed that the RAMS was an independent prognostic factor.We also found that the risk score was positively correlated with inflammatory response,the antigen-presenting process,and the expression levels of many immunosuppressive checkpoint molecules(e.g.,PD-L1,PD-L2,B7-H3,galectin-9,and FGL-1).These results suggested that high risk patients had immune response suppression.Further analysis revealed that anti-PD-1/PD-L1 immunotherapy did not have significant benefits for high risk patients.However,the patients could respond better to chemotherapy.Conclusions:This study is the first to highlight the relationship between metabolic reprogramming and recurrence in stageⅠLUAD,and is the first to also develop a clinically feasible signature.This signature may be a powerful prognostic tool and help further optimize the cancer therapy paradigm.
基金supported by the National Key Research and Development Program(No.2021YFF0901705,2021YFF0901700)the StateKey Laboratory ofMedia Convergence and Communication,Communication University of China+1 种基金the Fundamental Research Funds for the Central Universitiesthe High-quality and Cutting-edge Disciplines Construction Project for Universities in Beijing(Internet Information,Communication University of China).
文摘Aspect-Based Sentiment Analysis(ABSA)is one of the essential research in the field of Natural Language Processing(NLP),of which Aspect Sentiment Quad Prediction(ASQP)is a novel and complete subtask.ASQP aims to accurately recognize the sentiment quad in the target sentence,which includes the aspect term,the aspect category,the corresponding opinion term,and the sentiment polarity of opinion.Nevertheless,existing approaches lack knowledge of the sentence’s syntax,so despite recent innovations in ASQP,it is poor for complex cyber comment processing.Also,most research has focused on processing English text,and ASQP for Chinese text is almost non-existent.Chinese usage is more casual than English,and individual characters contain more information.We propose a novel syntactically enhanced neural network framework inspired by syntax knowledge enhancement strategies in other NLP studies.In this framework,part of speech(POS)and dependency trees are input to the model as auxiliary information to strengthen its cognition of Chinese text structure.Besides,we design a relation extraction module,which provides a bridge for the overall extraction of the framework.A comparison of the designed experiments reveals that our proposed strategy outperforms the previous studies on the key metric F1.Further experiments demonstrate that the auxiliary information added to the framework improves the final performance in different ways.
文摘Objective： To discuss the diagnosis and differential diagnosis of granulocytic sarcoma （GS）. Methods： Six cases were reported in this paper. They were assessed by pathologists. Immunohistochemistry （IHC） stain and routine hematoxylin and eosin （H＆E） stain were applied. Results： All patients involved in different anatomic sites respectively including skin, lymph node, soft tissue, breast, cervix and penis. All cases were previously error diagnoses. Three of them were initially diagnosed as non-Hodgkin lymphoma （NHL）. One case of cervical lymph node lesion was first considered as metastasized carcinoma by clinician. One biopsied skin sample was initially reported as Karposi＇s sarcoma. And one breast case was suspicious of the Iobular carcinoma with the frozen samples without antecedent clinical history information. GS was accompanied with acute myeloid leukemia （AML） in one case and with acute lymphocytic leukemia （ALL） in one case. Histopathologically, blastic, immature and differentiated variants were found in four, one and one, respectively. Immunohistochemistry （IHC） showed that myeloperoxidase （MPO） and lysozyme were both found to be positive in all cases, CD43 was found in 5 of 6 cases. Three of six cases were CD68, CD15 and LCA positive. CD34 and CDl17 were positive in 1/5 and 1/6 cases, respectively. However, CD20 and CD3 were negative in all cases. Conclusion： GS was uncommon and it may be misdiagnosed easily in routine practice. Each area had its own character, but they had the common features too. It can be correctly diagnosed by combination of H＆E stain, IHC stain, peripheral blood and bone marrow. MPO and Lysozyme were necessary for the nature of granulocytes. In addition, CD43, CD68 and CD15 were very helpful.
文摘In this paper, we discuss the uniform convergence of the simple upwind scheme on the Shishkin mesh and the Bakhvalov-Shishkin mesh for solving a singularly perturbed Robin boundary value problem, and investigate the midpoint upwind scheme on the Shishkin mesh and the Bakhvalov-Shishkin mesh to achieve better uniform convergence. The elaborate ε-uniform pointwise estimates are proved by using the comparison principle and barrier functions. The numerical experiments support the theoretical results for the schemes on the meshes.
基金supported by the National Natural Science Foundation of China(NSFC)(Grant No.62101333)the Program for Excellent Scientific and Innovation Research Team(Grant No.2022AH010002)the 2024 Anhui Province University Science and Engineering Teachers’Internship Program in Enterprises(Grant No.2024jsqygz02).
文摘In this work,we develop a novel computational method,referred to as SCT-Z-FDTD,which integrates the Z-transform finite-difference time-domain algorithm with a scale-compressed technique incorporating wave vectors.The proposed approach fa-cilitates accurate modeling of electromagnetic wave propagation through multi-layered anisotropic media,enabling precise evalua-tion of reflection and refraction coefficients over short time intervals.On first place,considering constitutive relationship between electromagnetic fields(E,H)and fluxes(D,B),Z-transform is employed to the anisotropic Maxwell’s curl equations for completing discrete-time form,and then the transverse wave vectors are exploited along a single direction to design the electromagnetic numerical differential process.After that,with the analysis corresponding flow chart,the plane waves are employed with different modes such as transverse electromagnetic,transverse electric,and transverse magnetic to detect the specific propagation.To further verify lower memory and higher efficiency,we select various multi-layered examples with anisotropies for executing the proposed method.Compared with the popular commercial software COMSOL,those data from multi-layered computation are quite consistent with the approximate trend the 2nd-order error convergence.
基金National Natural Science Foundation of China,Grant/Award Numbers:82072590,81502514,81802299Graduate Innovation Funds of Peking Union Medical College,Grant/Award Number:2019-1002-06+3 种基金National Key Basic Research Development Plan,Grant/Award Number:2018YFC1312105National Key R&D Program of China,Grant/Award Numbers:2018YFC1312100,2018YFC1312102Fundamental Research Funds for the Central Universities,Grant/Award Number:3332018070CAMS Innovation Fund for Medical Sciences,Grant/Award Numbers:2016-I2M-1-001,2017-I2M-1-005。
文摘Background:Although immune checkpoint inhibitors(ICIs)against programmed cell death protein 1(PD-1)and its ligand PD-L1 have demonstrated potency towards treating patients with non-small cell lung carcinoma(NSCLC),the potential association between Kirsten rat sarcoma viral oncogene homolog(KRAS)oncogene substitutions and the efficacy of ICIs remains unclear.In this study,we aimed to find point mutations in the KRAS gene resistant to ICIs and elucidate resistance mechanism.Methods:The association between KRAS variant status and the efficacy of ICIs was explored with a clinical cohort(n=74),and confirmed with a mouse model.In addition,the tumor immune microenvironment(TIME)of KRASmutant NSCLC,such as CD8+tumor-infiltrating lymphocytes(TILs)and PD-L1 level,was investigated.Cell lines expressing classic KRAS substitutions were used to explore signaling pathway activation involved in the formation of TIME.Furthermore,interventions that improved TIME were developed to increase responsiveness to ICIs.Results:We observed the inferior efficacy of ICIs in KRAS-G12D-mutant NSCLC.Based upon transcriptome data and immunostaining results from KRAS-mutant NSCLC,KRAS-G12D point mutation negatively correlated with PD-L1 level and secretion of chemokines CXCL10/CXCL11 that led to a decrease in CD8+TILs,which in turn yielded an immunosuppressive TIME.The analysis of cell lines overexpressing classic KRAS substitutions further revealed that KRAS-G12D mutation suppressed PD-L1 level via the P70S6K/PI3K/AKT axis and reduced CXCL10/CXCL11 levels by down-regulating high mobility group protein A2(HMGA2)level.Notably,paclitaxel,a chemotherapeutic agent,upregulated HMGA2 level,and in turn,stimulated the secretion of CXCL10/CXCL11.Moreover,PD-L1 blockade combined with paclitaxel significantly suppressed tumor growth compared with PD-L1 inhibitor monotherapy in a mouse model with KRAS-G12D-mutant lung adenocarcinoma.Further analyses revealed that the combined treatment significantly enhanced the recruitment of CD8+TILs via the up-regulation of CXCL10/CXCL11 levels.Results of clinical study also revealed the superior efficacy of chemo-immunotherapy in patients with KRAS-G12D-mutant NSCLC compared with ICI monotherapy.Conclusions:Our study elucidated the molecular mechanism by which KRASG12D mutation drives immunosuppression and enhances resistance of ICIs in NSCLC.Importantly,our findings demonstrate that ICIs in combination with chemotherapy may be more effective in patients with KRAS-G12D-mutant NSCLC.
基金the National Natural Science Foundation of China (Grant No. 59776013).
文摘A simple and effective model of heat conduction across thin films is set up and molecular dynamics simulations are implemented to explore the thermal conductivity of nanoscale thin dielectric films in the direction perpendicular to the film plane. Solid argon is selected as the model system due to its reliable experimental data and potential function. Size effects of the thermal conductivity across thin films are found by computer simulations: in a film thickness range of 2-10 nm, the conductivity values are remarkably lower than the corresponding bulk experimental data and increase as the thickness increases. The consistency between the approximate solution of the phonon Boltzmann transport equation and the simulation results ascribes the thermal conductivity size effect to the phonon scattering at film boundaries.
基金Ministry of Science and Technology of the People’s Republic of China,Grant/Award Number:2020YFA0803300National Natural Science Foundation of China,Grant/Award Numbers:82188102,82030074,82122053,32100574+10 种基金Beijing Municipal Science&Technology Commission,Grant/Award Number:Z191100006619115R&D Program of Beijing Municipal Education commission,Grant/Award Number:KJZD20191002302CAMS Innovation Fund for Medical Science,Grant/Award Numbers:2021-1-I2M-012,2021-I2M-1-067Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences,Grant/Award Number:2021-PT310-001Key-Area Research and Development Program of Guangdong Province,Grant/Award Number:2021B0101420005Sanming Project of Medicine in Shenzhen,Grant/Award Numbers:SZSM201612097,SZSM201812062Aiyou Foundation,Grant/Award Number:KY201701Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2020QH191Zhejiang Natural Science Foundation-Key Project,Grant/Award Number:LD21H160003Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang,Grant/Award Number:2019R01001Zhimin Lu is the Kuancheng Wang Distinguished Chair。
文摘Background:Maintenance of cancer stem-like cell(CSC)stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self-renewal and tumor progression.As a key glycolytic enzyme,hexokinase 2(HK2)plays an instrumental role in aerobic glycolysis and tumor progression.However,whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer(SCLC)is largely unclear.In this study,we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC.Methods:Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts.CSC-like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model.Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133.The expression levels of CD133-associated and CSC-relevant proteins were evaluated by immunoblotting,immunoprecipitation,immunofluorescence,and immunohistochemistry assay.RNA expression levels of Nanog,POU5F1,Lin28,HK2,Prominin-1 were analyzed through quantitative reverse transcription PCR.Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay.CD133+cells were sorted by flow cytometry using an anti-CD133 antibody.Results:We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts.HK2 depletion inhibited CSC stemness and promoted CSC differentiation.Mechanistically,nonmitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels.The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin-specific protease 11(USP11)to CD133,thereby inhibiting CD133 polyubiquitylation and degradation.HK2-mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators,SCLC cell stemness,and tumor growth in mice.In addition,HK2 expression was positively correlated with CD133 expression in human SCLC specimens,and their expression levels were associated with poor prognosis of SCLC patients.Conclusions:These results revealed a critical non-metabolic function of HK2 in promotion of cancer cell stemness.Our findings provided new insights into the multifaceted roles of HK2 in tumor development.
基金This study was funded by The National Key R&D Program of China(2017YFC1308702,2017YFC1311000,2018YFC1312100)the Beijing Municipal Science&Technology Commission(Z181100006218032,Z181100001918002)+1 种基金the CAMS Initiative for Innovative Medicine(2017-I2M-1-005,2017-I2M-2-003,2019-I2M-2-002)Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2017PT32001,2017PT32017).
文摘Background:Cancer cells reprogram metabolism for proliferation.Phosphoglycerate kinase 1(PGK1),as a glycolytic enzyme and newly identified protein kinase,coordinates glycolysis and mitochondrial metabolism.However,the clini-cal significance of PGK1 expression and function in cancer progression is unclear.Here,we investigated the relation-ship between the progression and prognosis of multiple cancer types and PGK1 expression and its function in the mitochondrial metabolism regulation.Methods:We performed pan-cancer analyses of PGK1 mRNA level and DNA methylation in 11,908 tumor tissues and 1582 paired normal tissues across 34 cancer types in The Cancer Genome Atlas datasets.Using specific antibodies against PGK1 S203 and PDHK1 T338 phosphorylation,we performed immunohistochemistry with tissue microarray assay in additional 818 cancer cases with 619 paired normal tissues from five cancer types.Results:The PGK1 mRNA level was significantly elevated with hypomethylation in promotor regions and associated with advanced TNM stage in 15 and four cancer types,respectively.In breast carcinoma,elevated PGK1 mRNA level and promoter hypomethylation were associated with poor prognosis.Positively correlated PGK1 S203 and PDHK1 T338 phosphorylation levels were significantly associated with short overall survival(OS)in cancers of the breast,liver,lung,stomach,and esophagus and with advanced TNM stage in breast and esophageal cancers.PGK1 pS203 and PDHK1 pT338 were also independent predictors of short OS in liver,lung,and stomach cancer.Conclusions:The elevated expression,promoter hypomethylation,and phosphorylation of PGK1 and PDHK1 were related with disease progression and short OS in diverse types of cancer.PGK1 and PDHK1 phosphorylation may be potential prognostic biomarkers.
文摘Canonical ensemble Monte Carlo simulations have been carried out to investigate thethermodynamic properties of two-dimensional fluids subjected to truncated Lennard-Jones 12-6 potential. The simulations of thermodynamic states sweep across liquid-vapor regime over a wide range of thermodynamic conditions. Simulated isotherms behave van der Waals loop-like characteristics in the liquid-vapor phase-transition region. It suggests a continuous isothermal phase transition in the case of micro system, in which the system size prohibits phase separation. Two-dimensional dimensionless van der Waals equation of states has been obtained from theoretical analysis. By fitting simulated data to this equation, temperature-dependent parameters in the equation have been determined.
基金National Natural Science Foundation of China(grant numbers 32170923,82103011)Beijing Natural Science Foundation(grant number 7214248)+2 种基金CAMS Innovation Fund for Medical Sciences(grant number 2021-I2M-1-050)Youth Elite Scientists Sponsorship Program by CAST(grant number 2019QNRC001)Beijing Nova Program of Science and Technology(grant number Z191100001119049).
文摘Dear Editor,In recent years,the rapid development of immunotherapy has brought survival benefits for lung squamous cell carcinoma(LUSC)patients who have rare treatment options.Nevertheless,there are still some patients with immunotherapy resistance,which is the root cause of the low benefit rate and disease progression of the overall population,and it is an urgent problem to be solved.Except for tumor mutation burden,the tumor immune microenvironment(TIME)as characterized by infiltration of CD8+tumor-infiltrating lymphocytes(TILs)and PD-L1 expression has been associated with the efficacy of immune checkpoint inhibitors(ICIs).In our previous studies,we have demonstrated that psoriasin,also known as S100 calcium-binding protein A7(S100A7),not only accelerates tumor progression via the activation of the p-Erk pathway in LUSC and the p-Erk and p-FAK pathways in esophageal squamous cell carcinomas(ESCC)but also remodels the tumor microenvironment by promoting angiogenesis and M2 macrophage infiltration in ESCC.1,2 However,the role of S100A7 in the TIME and immunotherapy efficacy in LUSC remains to be elucidated.
文摘Small-cell lung cancer(SCLC)is a highly malignant cancer with characteristics of rapid growth,abundant angiogenesis,and early distant metastasis that accounts for about 15%of lung cancers.With the wide application of low-dose computed tomography screening in recent years,the incidence of early limited-stage SCLC has increased dramatically.
文摘Bladder cancer represents one of the most prevalent malignant tumors affecting the urinary system.As per data disclosed by the National Cancer Registration Center of China in 2019,the incidence of bladder cancer was 5.80 per 100,000 in 2015,placing it as the thirteenth most common systemic malignancy.Bladder cancer poses a substantial threat to public health in China,underlining the critical importance of standardizing diagnosis and treatment to enhance clinical outcomes.This clinical practice guideline for bladder cancer centers on the etiologies,clinical presentations,and diagnostic procedures for suspected bladder cancer,in addition to the histopathology and staging of urothelial bladder cancer.
文摘Heme is a key cofactor in aerobic life, both in eukaryotes and prokaryotes. Because of the high reactivity of ferrous protoporphyrin IX, the reactions of heme in cells are often carried out through heme-protein complexes. Traditionally studies of heme-binding proteins have been approached on a case by case basis, thus there is a limited global view of the distribution of heme-binding proteins in different cells or tissues. The procedure described here is aimed at profiling heme-binding proteins in mouse tissues sequentially by 1) purification of heme-binding proteins by heme-agarose, an affinity chromatographic resin; 2) isolation of heme-binding proteins by SDS-PAGE or two-dimensional electrophoresis; 3) identification of heme-binding proteins by mass spectrometry. In five mouse tissues, over 600 protein spots were visualized on 2DE gel stained by Commassie blue and 154 proteins were identified by MALDI-TOF, in which most proteins belong to heme related. This methodology makes it possible to globally characterize the heme-binding proteins in a biological system.
