Traditional dielectric electrorheological fluid(ER)is based on the interaction of dielectric particle polarization,and the yield stress is low,which cannot meet the application requirements.The giant ER(GER)effect is ...Traditional dielectric electrorheological fluid(ER)is based on the interaction of dielectric particle polarization,and the yield stress is low,which cannot meet the application requirements.The giant ER(GER)effect is caused by orientations and interactions of polar molecules adsorbed on the particle surfaces.Despite the high yield stress,these polar molecules are prone to wear and fall off,resulting in a continuous reduction in shear stress of GER liquid,which is also not suitable for application.Here we introduce a new type of ER fluid called induced dipole dominant ER fluid(ID-ER),of which the particles contain oxygen vacancies or conductor microclusters both prepared by high energy ball milling(HEBM)technique.In the electric field E,oxygen vacancies or conductor microclusters form induced dipoles.Because the local electric field E_(loc) in the gaps between particles can be two to three orders of magnitude larger than E,the induced dipole moments must be large.The strong interactions of these induced dipoles make the yield stress of the ID-ER fluid reaching more than 100 kPa.Since there are oxygen vacancies or conductor microclusters everywhere in the particles,the particles will not lose the function due to surface wear during use.The experimental results show that the ID-ER fluid possesses the advantages of high shear stress,low current density,short response time,good temperature stability,long service life,and anti-settlement,etc.The comprehensive performance is much better than the existing ER materials,and also the preparation method is simple and easy to repeat,thus it should be a new generation of ER fluid suitable for practical applications.展开更多
The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 ...The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. Conditional deletion of SLIT3 in cathepsin K(CTSK)-positive cells, including osteoclasts, had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone resorption/formation parameters. Similar results were observed with the deletion of SLIT3 in Lys M-positive cells, including osteoclast lineage cells. Consistent with this finding, bone marrow chimeras made from Slit3-/-donors that lacked SLIT3 expression at all stages of osteoclast development displayed normal bone mass relative to controls. Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3,indicating that osteoblasts are the major source of skeletal SLIT3.展开更多
Objective To evaluate levels of lead(Pb) and cadmium(Cd) in the breast milk in the second postpartum month,to investigate the relationship between Pb/Cd levels in breast milk and some sociodemographic parameters,and t...Objective To evaluate levels of lead(Pb) and cadmium(Cd) in the breast milk in the second postpartum month,to investigate the relationship between Pb/Cd levels in breast milk and some sociodemographic parameters,and to explore whether these levels affect the infants' physical status or the mothers' psychological status(postpartum depression).Methods A cross-sectional study was conducted between November 2009 and December 2010.Altogether 170 healthy mothers were enrolled from Nanjing Maternity and Child Health Care Hospital.The inclusion criteria were:voluntary to participate in this study,healthy,with no chronic disease,breastfeeding in the second postpartum month,living in a suburban but not non-industrial area of Nanjing,and not occupationally exposed to toxic metals.All the mothers completed a questionnaire and were evaluated based on the Edinburgh Postpartum Depression Scale(EPDS) to identify the risk of postpartum depression.Pb and Cd levels in breast milk were determined by inductively coupled plasma mass spectroscopy.The infants of these mothers were examined for their z scores of weight for age,length for age,head circumference for age,and body mass index for age.Results The median breast milk levels of Pb and Cd were 40.6 μg/L and 0.67 μg/L,respectively.In 164(96.5%) of the 170 samples,Pb levels were higher than the limit reported by the World Health Organization(> 5 μg/L).Breast milk Cd level was > 1 μg/L in 54(31.8%) mothers.The mothers with a history of anemia had a higher breast milk Pb level than those without a history of anemia(41.1 μg/L vs.37.9 μg/L,P = 0.050).The median breast milk Cd level in those who were active and passive smokers during pregnancy was significantly higher than that in non-smokers(0.88 μg/L vs.0.00 μg/L,P = 0.025).The breast milk Cd level in the mothers not taking iron and vitamin supplements for 2 months postpartum was higher than in those taking the supplements(iron supplement:0.74 μg/L vs.0.00 μg/L,P = 0.025;vitamin supplement:0.78 μg/L vs.0.00 μg/L,P = 0.005).Breast milk Cd level at the second postpartum month was negatively correlated with the z scores of head circumference(r = 0.248,P = 0.042) and weight for age at birth(r = 0.241,P = 0.024) in girls.No correlation was found between the breast milk Pb/Cd levels and the EPDS scores.Conclusion Considering the high levels of Pb and Cd in breast milk in this study,breast milk monitoring programs are necessary.展开更多
Staghorn stones have always been a challenge for urologists,especially in some special situations,such as horseshoe kidney,ectopic kidney,paediatric kidney,and solitary kidney.The treatment of these staghorn stones mu...Staghorn stones have always been a challenge for urologists,especially in some special situations,such as horseshoe kidney,ectopic kidney,paediatric kidney,and solitary kidney.The treatment of these staghorn stones must be aggressive because they can lead to renal function loss and serious complications.The gold-standard management for staghorn stones is surgical treatment with the aim of clearing the stones and preserving renal function.Treatment methods for staghorn stones have developed rapidly,such as extracorporeal shock wave lithotripsy,retrograde intrarenal surgery,percutaneous nephrolithotomy and laparoscopy and open surgery.Whether the standard procedures for staghorn stones can also apply to these stones in special situations is still not agreed upon.The decision should be made individually according to the circumstances of the patient.In this review,we evaluates the previous studies and comments on the management of staghorn stones under special situations in the hope of guiding the optimal choice for urologists.展开更多
Various factors can induce cell degeneration by altering the phenotype and metabolism of cells.Mitochondria play an essential role in cellular homeostasis and function,rendering aging processes highly associated with ...Various factors can induce cell degeneration by altering the phenotype and metabolism of cells.Mitochondria play an essential role in cellular homeostasis and function,rendering aging processes highly associated with mitochondrial function and status.Herein,we describe an aging-prone phenotype of murine skin cells caused by depletion of Rad6B(Ube2b),an E2 ubiquitin-conjugating enzyme.In this study,using Masson’s trichrome,we showed that loss of Rad6B causes physiological structure changes in mouse skin with age.In addition,a combination of western blotting experiments,transmission electron microscopy and employment of immunofluorescence staining revealed that depletion of Rad6B was characterized by an abnormal mitochondrial metabolic profile,including decreased mitochondrial biosynthesis and mitochondrial complex activities,increased ROS production and suppressed mitophagy resulting in metabolic disorders.Taken together,these results highlight an important relationship between Rad6B and skin senescence,suggesting that Rad6B plays an indispensable role in maintaining a healthy mitochondrial network and intracellular homeostasis.展开更多
The giant electrorheological (ER) fluid is based on the principle of a polar molecule dominated electrorheological (PM-ER) effect. The response of the shear stress for PM-ER fluid in alternate electric fields with...The giant electrorheological (ER) fluid is based on the principle of a polar molecule dominated electrorheological (PM-ER) effect. The response of the shear stress for PM-ER fluid in alternate electric fields with triangle/square wave forms for different frequencies has been studied. The results show that the shear stress cannot well follow the rapid change of electric field and the average shear stresses of PM-ER fluids decrease with the increasing frequency of the applied field due to the response decay of the shear stress on applied field. The behavior is quite different from that of traditional ER fluids. However, the average shear stress of PM-ER fluid in a square wave electric field of iE at low frequency can keep at high value. The obtained knowledge must be helpful for the design and operation of PM-ER fluids in the applications.展开更多
Background:Lung adenocarcinoma is one of the most common pathological types of lung malignant tumor with high morbidity and mortality.Long non-coding RNAs are gradually recognized to play crucial roles in tumor occurr...Background:Lung adenocarcinoma is one of the most common pathological types of lung malignant tumor with high morbidity and mortality.Long non-coding RNAs are gradually recognized to play crucial roles in tumor occurrence and development.Necroptosis is a newly established way for cell programmed death,undertaking essential roles in anti-tumor.Therefore,identifying necroptosis-related l ong non-coding RNAs and based on them to evaluate the signatures of l ung adenocarcinoma is essential for patients’survival prediction and therapy.Methods:We collected data from the public database and performed the least absolute shrinkage to construct a 13-lncRNAs prognostic model.Based on the Consensus Clustering,ESTIMATE,CIRERSORT,and weighted gene co-expression network analysis to identify the immune signatures.Results:This study identified a 13-lncRNAs prognostic model.The model’s prediction accuracy was evaluated by receiver operating characteristic and independent-prognosis analysis;besides,a Gene Expression Omnibus dataset was applied for external validation.Furthermore,we analyzed the immune features of subgroups in multiple dimensions.A consensus clustering analysis based on the 41 genes was implemented to separate lung adenocarcinoma patients into two subgroups.We compared the features of subgroups in multiple dimensions,including survival,immune microenvironment,immune cells infiltration and gene co-expression network analysis.Conclusion:W e established a prognosis necroptosis-related risk model to predict lung adenocarcinoma patients’prognosis and systematically understood the correlation between immune and necroptosis.This study can applicate in clinical to predict the prognosis of lung adenocarcinoma patients and provide new insight into lung adenocarcinoma immune therapy.展开更多
Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma(DLBCL).Using whole exome/genome sequencing,RNA-sequencing,and fluorescence in situ hybridi...Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma(DLBCL).Using whole exome/genome sequencing,RNA-sequencing,and fluorescence in situ hybridization in 337 newly diagnosed DLBCL patients,we established a simplified 38-gene algorithm(termed‘LymphPlex’)based on the information on mutations of 35 genes and rearrangements of three genes(BCL2,BCL6,and MYC),identifying seven distinct genetic subtypes:TP53Mut(TP53 mutations),MCD-like(MYD88,CD79B,PIM1,MPEG1,BTG1,TBL1XR1,PRDM1,IRF4 mutations),BN2-like(BCL6 fusion,NOTCH2,CD70,DTX1,BTG2,TNFAIP3,CCND3 mutations),N1-like(NOTCH1 mutations),EZB-like(BCL2 fusion,EZH2,TNFRSF14,KMT2D,B2M,FAS,CREBBP,ARID1A,EP300,CIITA,STAT6,GNA13 mutations,with or without MYC rearrangement),and ST2-like(SGK1,TET2,SOCS1,DDX3X,ZFP36L1,DUSP2,STAT3,IRF8 mutations).Extended validation of 1001 DLBCL patients revealed clinical relevance and biological signature of each genetic subtype.TP53Mut subtype showed poor prognosis,characterized by p53 signaling dysregulation,immune deficiency,and PI3K activation.MCD-like subtype was associated with poor prognosis,activated B-cell(ABC)origin,BCL2/MYC double-expression,and NF-κB activation.BN2-like subtype showed favorable outcome within ABC-DLBCL and featured with NF-κB activation.N1-like and EZB-like subtypes were predominated by ABC-DLBCL and germinal center B-cell(GCB)-DLBCL,respectively.EZB-like-MYC+subtype was characterized by an immunosuppressive tumor microenvironment,while EZB-like-MYC-subtype by NOTCH activation.ST2-like subtype showed favorable outcome within GCB-DLBCL and featured with stromal-1 modulation.Genetic subtype-guided targeted agents achieved encouraging clinical response when combined with immunochemotherapy.Collectively,LymphPlex provided high efficacy and feasibility,representing a step forward to the mechanism-based targeted therapy in DLBCL.展开更多
DNA is highly vulnerable to spontaneous and environmental timely damage in living cells.DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently.Human ce...DNA is highly vulnerable to spontaneous and environmental timely damage in living cells.DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently.Human cells possess several DNA damage response(DDR)mechanisms to protect the integrity of their genome.Clarification of the mechanisms under-lying the DNA damage response following lethal damage will facilitate the identification of therapeutic targets for cancers.Histone post-translational modifications(PTMs)have been indicated to play different roles in the repair of DNA damage.In this context,histone PTMs regulate recruitment of downstream effectors,and facilitate appropriate repair response.This review outlines the current understanding of different histone PTMs in response to DNA dam-age repair,besides,enumerates the role of new type PTMs such as histone succinylation and crotonylation in regulating DNA damage repair processes.展开更多
Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investi...Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple (≥3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P < 0.001) and OS (68.5% vs. 85.8%, P=0.001) than those without multiple abnormal immunologic markers.Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P= 0.008, P < 0.001) and OS (P = 0.003, P < 0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P= 0.001) and age > 60 years for OS (P= 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.展开更多
Nanoscale Kirkendall effect has been widely used for rationally fabricating high-quality hollow nanocrystals, but often requires the intrinsic diffusion coefficient of out-diffusion materials higher than that of in-di...Nanoscale Kirkendall effect has been widely used for rationally fabricating high-quality hollow nanocrystals, but often requires the intrinsic diffusion coefficient of out-diffusion materials higher than that of in-diffusion components. Here we demonstrate an unexpected Kirkendall effect that occurs in diffusing intrinsically faster Cu atoms into Pd icosahedra, leading to the formation of PdCu alloyed hollow nanocrystals. The control experiment with Pd octahedra replacing icosahedra indicates the critical role of twin boundaries in facilitating such unexpected Kirkendall effect. In addition, geometric phase analysis and density functional theory calculation show that out-diffusion of Pd atoms in the icosahedra is faster than in-diffusion of Cu atoms, particularly through the twin boundaries, upon the strain gradient with an inward distribution from tensile to compressive strains. The unexpected Kirkendall effect is also found in the interdiffusion of Ag and Pd atoms in Pd icosahedra. Our finds break the limitation of the intrinsic diffusion coefficient for the synthesis of hollow nanocrystals through Kirkendall effect and are expected to enormously enrich the family of hollow nanocrystals which have shown great potential in broad areas, such as fine chemical production, energy storage and conversion, and environmental protection. This work also provides a deep understanding in the diffusion behavior of atoms upon the strain gradient.展开更多
基金Project supported by the National Key Research and Development Program of China(Grant No.2017YFA0403000)the National Natural Science Foundation of China(Grant No.11874430).
文摘Traditional dielectric electrorheological fluid(ER)is based on the interaction of dielectric particle polarization,and the yield stress is low,which cannot meet the application requirements.The giant ER(GER)effect is caused by orientations and interactions of polar molecules adsorbed on the particle surfaces.Despite the high yield stress,these polar molecules are prone to wear and fall off,resulting in a continuous reduction in shear stress of GER liquid,which is also not suitable for application.Here we introduce a new type of ER fluid called induced dipole dominant ER fluid(ID-ER),of which the particles contain oxygen vacancies or conductor microclusters both prepared by high energy ball milling(HEBM)technique.In the electric field E,oxygen vacancies or conductor microclusters form induced dipoles.Because the local electric field E_(loc) in the gaps between particles can be two to three orders of magnitude larger than E,the induced dipole moments must be large.The strong interactions of these induced dipoles make the yield stress of the ID-ER fluid reaching more than 100 kPa.Since there are oxygen vacancies or conductor microclusters everywhere in the particles,the particles will not lose the function due to surface wear during use.The experimental results show that the ID-ER fluid possesses the advantages of high shear stress,low current density,short response time,good temperature stability,long service life,and anti-settlement,etc.The comprehensive performance is much better than the existing ER materials,and also the preparation method is simple and easy to repeat,thus it should be a new generation of ER fluid suitable for practical applications.
基金an Award Program for the Minjiang Scholar Professorship in Fujian Province, a start-up grant from Xiamen University and support from the National Natural Science Foundation of China (81972034 to RX)supported by the NIH grant DP5OD021351supported by NIH grants (R01AR068970, AR071463)。
文摘The axon guidance cue SLIT3 was identified as an osteoanabolic agent in two recent reports. However, these reports conflict in their nomination of osteoblasts versus osteoclasts as the key producers of skeletal SLIT3 and additionally offer conflicting data on the effects of SLIT3 on osteoclastogenesis. Here, aiming to address this discrepancy, we found no observable SLIT3 expression during human or mouse osteoclastogenesis and the only modest SLIT3-mediated effects on osteoclast differentiation. Conditional deletion of SLIT3 in cathepsin K(CTSK)-positive cells, including osteoclasts, had no effect on the number of osteoclast progenitors, in vitro osteoclast differentiation, overall bone mass, or bone resorption/formation parameters. Similar results were observed with the deletion of SLIT3 in Lys M-positive cells, including osteoclast lineage cells. Consistent with this finding, bone marrow chimeras made from Slit3-/-donors that lacked SLIT3 expression at all stages of osteoclast development displayed normal bone mass relative to controls. Taken in context, multiple lines of evidence were unable to identify the physiologic function of osteoclast-derived SLIT3,indicating that osteoblasts are the major source of skeletal SLIT3.
基金supported by Nanjing Maternity and Child Health Care Hospital
文摘Objective To evaluate levels of lead(Pb) and cadmium(Cd) in the breast milk in the second postpartum month,to investigate the relationship between Pb/Cd levels in breast milk and some sociodemographic parameters,and to explore whether these levels affect the infants' physical status or the mothers' psychological status(postpartum depression).Methods A cross-sectional study was conducted between November 2009 and December 2010.Altogether 170 healthy mothers were enrolled from Nanjing Maternity and Child Health Care Hospital.The inclusion criteria were:voluntary to participate in this study,healthy,with no chronic disease,breastfeeding in the second postpartum month,living in a suburban but not non-industrial area of Nanjing,and not occupationally exposed to toxic metals.All the mothers completed a questionnaire and were evaluated based on the Edinburgh Postpartum Depression Scale(EPDS) to identify the risk of postpartum depression.Pb and Cd levels in breast milk were determined by inductively coupled plasma mass spectroscopy.The infants of these mothers were examined for their z scores of weight for age,length for age,head circumference for age,and body mass index for age.Results The median breast milk levels of Pb and Cd were 40.6 μg/L and 0.67 μg/L,respectively.In 164(96.5%) of the 170 samples,Pb levels were higher than the limit reported by the World Health Organization(> 5 μg/L).Breast milk Cd level was > 1 μg/L in 54(31.8%) mothers.The mothers with a history of anemia had a higher breast milk Pb level than those without a history of anemia(41.1 μg/L vs.37.9 μg/L,P = 0.050).The median breast milk Cd level in those who were active and passive smokers during pregnancy was significantly higher than that in non-smokers(0.88 μg/L vs.0.00 μg/L,P = 0.025).The breast milk Cd level in the mothers not taking iron and vitamin supplements for 2 months postpartum was higher than in those taking the supplements(iron supplement:0.74 μg/L vs.0.00 μg/L,P = 0.025;vitamin supplement:0.78 μg/L vs.0.00 μg/L,P = 0.005).Breast milk Cd level at the second postpartum month was negatively correlated with the z scores of head circumference(r = 0.248,P = 0.042) and weight for age at birth(r = 0.241,P = 0.024) in girls.No correlation was found between the breast milk Pb/Cd levels and the EPDS scores.Conclusion Considering the high levels of Pb and Cd in breast milk in this study,breast milk monitoring programs are necessary.
基金This work was financed by a grant from the National Natural Science Foundation of China(No.81800624).
文摘Staghorn stones have always been a challenge for urologists,especially in some special situations,such as horseshoe kidney,ectopic kidney,paediatric kidney,and solitary kidney.The treatment of these staghorn stones must be aggressive because they can lead to renal function loss and serious complications.The gold-standard management for staghorn stones is surgical treatment with the aim of clearing the stones and preserving renal function.Treatment methods for staghorn stones have developed rapidly,such as extracorporeal shock wave lithotripsy,retrograde intrarenal surgery,percutaneous nephrolithotomy and laparoscopy and open surgery.Whether the standard procedures for staghorn stones can also apply to these stones in special situations is still not agreed upon.The decision should be made individually according to the circumstances of the patient.In this review,we evaluates the previous studies and comments on the management of staghorn stones under special situations in the hope of guiding the optimal choice for urologists.
基金funded by the National Natural Science Foundation of China(Grant Nos.82071695 and 81772907 to DW and No.82060535 to YT)the Fundamental Research Funds for the Central Universities(Grant lzujbky-2017-k12 to DW).
文摘Various factors can induce cell degeneration by altering the phenotype and metabolism of cells.Mitochondria play an essential role in cellular homeostasis and function,rendering aging processes highly associated with mitochondrial function and status.Herein,we describe an aging-prone phenotype of murine skin cells caused by depletion of Rad6B(Ube2b),an E2 ubiquitin-conjugating enzyme.In this study,using Masson’s trichrome,we showed that loss of Rad6B causes physiological structure changes in mouse skin with age.In addition,a combination of western blotting experiments,transmission electron microscopy and employment of immunofluorescence staining revealed that depletion of Rad6B was characterized by an abnormal mitochondrial metabolic profile,including decreased mitochondrial biosynthesis and mitochondrial complex activities,increased ROS production and suppressed mitophagy resulting in metabolic disorders.Taken together,these results highlight an important relationship between Rad6B and skin senescence,suggesting that Rad6B plays an indispensable role in maintaining a healthy mitochondrial network and intracellular homeostasis.
基金Project supported by the National Key R&D Program of China(Grant No.2017YFA0403000)the National Natural Science Foundation of China(Grant No.11574355)
文摘The giant electrorheological (ER) fluid is based on the principle of a polar molecule dominated electrorheological (PM-ER) effect. The response of the shear stress for PM-ER fluid in alternate electric fields with triangle/square wave forms for different frequencies has been studied. The results show that the shear stress cannot well follow the rapid change of electric field and the average shear stresses of PM-ER fluids decrease with the increasing frequency of the applied field due to the response decay of the shear stress on applied field. The behavior is quite different from that of traditional ER fluids. However, the average shear stress of PM-ER fluid in a square wave electric field of iE at low frequency can keep at high value. The obtained knowledge must be helpful for the design and operation of PM-ER fluids in the applications.
文摘Background:Lung adenocarcinoma is one of the most common pathological types of lung malignant tumor with high morbidity and mortality.Long non-coding RNAs are gradually recognized to play crucial roles in tumor occurrence and development.Necroptosis is a newly established way for cell programmed death,undertaking essential roles in anti-tumor.Therefore,identifying necroptosis-related l ong non-coding RNAs and based on them to evaluate the signatures of l ung adenocarcinoma is essential for patients’survival prediction and therapy.Methods:We collected data from the public database and performed the least absolute shrinkage to construct a 13-lncRNAs prognostic model.Based on the Consensus Clustering,ESTIMATE,CIRERSORT,and weighted gene co-expression network analysis to identify the immune signatures.Results:This study identified a 13-lncRNAs prognostic model.The model’s prediction accuracy was evaluated by receiver operating characteristic and independent-prognosis analysis;besides,a Gene Expression Omnibus dataset was applied for external validation.Furthermore,we analyzed the immune features of subgroups in multiple dimensions.A consensus clustering analysis based on the 41 genes was implemented to separate lung adenocarcinoma patients into two subgroups.We compared the features of subgroups in multiple dimensions,including survival,immune microenvironment,immune cells infiltration and gene co-expression network analysis.Conclusion:W e established a prognosis necroptosis-related risk model to predict lung adenocarcinoma patients’prognosis and systematically understood the correlation between immune and necroptosis.This study can applicate in clinical to predict the prognosis of lung adenocarcinoma patients and provide new insight into lung adenocarcinoma immune therapy.
基金supported,in part,by research funding from the National Key R&D Program of China,National Natural Science Foundation of China (81830007,82130004,81670176,and 82070204)Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support (20152206,20152208,and 202218)+1 种基金Clinical Research Plan of Shanghai Hospital Development Center (SHDC2020CR1032B,SHDC2022CRD033)Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine (DLY201601).
文摘Genetic classification helps to disclose molecular heterogeneity and therapeutic implications in diffuse large B-cell lymphoma(DLBCL).Using whole exome/genome sequencing,RNA-sequencing,and fluorescence in situ hybridization in 337 newly diagnosed DLBCL patients,we established a simplified 38-gene algorithm(termed‘LymphPlex’)based on the information on mutations of 35 genes and rearrangements of three genes(BCL2,BCL6,and MYC),identifying seven distinct genetic subtypes:TP53Mut(TP53 mutations),MCD-like(MYD88,CD79B,PIM1,MPEG1,BTG1,TBL1XR1,PRDM1,IRF4 mutations),BN2-like(BCL6 fusion,NOTCH2,CD70,DTX1,BTG2,TNFAIP3,CCND3 mutations),N1-like(NOTCH1 mutations),EZB-like(BCL2 fusion,EZH2,TNFRSF14,KMT2D,B2M,FAS,CREBBP,ARID1A,EP300,CIITA,STAT6,GNA13 mutations,with or without MYC rearrangement),and ST2-like(SGK1,TET2,SOCS1,DDX3X,ZFP36L1,DUSP2,STAT3,IRF8 mutations).Extended validation of 1001 DLBCL patients revealed clinical relevance and biological signature of each genetic subtype.TP53Mut subtype showed poor prognosis,characterized by p53 signaling dysregulation,immune deficiency,and PI3K activation.MCD-like subtype was associated with poor prognosis,activated B-cell(ABC)origin,BCL2/MYC double-expression,and NF-κB activation.BN2-like subtype showed favorable outcome within ABC-DLBCL and featured with NF-κB activation.N1-like and EZB-like subtypes were predominated by ABC-DLBCL and germinal center B-cell(GCB)-DLBCL,respectively.EZB-like-MYC+subtype was characterized by an immunosuppressive tumor microenvironment,while EZB-like-MYC-subtype by NOTCH activation.ST2-like subtype showed favorable outcome within GCB-DLBCL and featured with stromal-1 modulation.Genetic subtype-guided targeted agents achieved encouraging clinical response when combined with immunochemotherapy.Collectively,LymphPlex provided high efficacy and feasibility,representing a step forward to the mechanism-based targeted therapy in DLBCL.
基金supported by National Natural Science Foundation of China(No.82071695,82060535)Natural Science Foundation of Gansu Province,China(No.21JR7RA450)。
文摘DNA is highly vulnerable to spontaneous and environmental timely damage in living cells.DNA damage may cause genetic instability and increase cancer risk if the damages are not repaired timely and efficiently.Human cells possess several DNA damage response(DDR)mechanisms to protect the integrity of their genome.Clarification of the mechanisms under-lying the DNA damage response following lethal damage will facilitate the identification of therapeutic targets for cancers.Histone post-translational modifications(PTMs)have been indicated to play different roles in the repair of DNA damage.In this context,histone PTMs regulate recruitment of downstream effectors,and facilitate appropriate repair response.This review outlines the current understanding of different histone PTMs in response to DNA dam-age repair,besides,enumerates the role of new type PTMs such as histone succinylation and crotonylation in regulating DNA damage repair processes.
基金supported by the National Key R&D Program of China(2022YFA1304000)the National Natural Science Foundation of China(81972823)+3 种基金the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32121004)the Guangdong Special Support Program innovation team(2019BT02N054)the Open Research Fund of State Key Laboratory of Cellular Stress Biology,Xiamen University(SKLCSB2019KF013)the Fundamental Research Funds for the Central University(20720220003)。
基金research funding from the National Natural Science Foundation of China (Nos.81520108003, 81670716, and 81830007)Chang Jiang Scholars Program, the Shanghai Commission of Science and Technology (No.16JC1405800)+2 种基金Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support (Nos.20152206 and 20152208)Clinical Research Plan of SHDC (No.16CR2017A)Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine (No.DLY201601).
文摘Autoimmune diseases (ADs) increase the risk of non-Hodgkin's lymphoma and contribute to poor prognosis of patients. However, the association between immunologic markers and clinical outcome has rarely been investigated. This study aims to analyze the prognostic value of pretreatment immunologic markers in newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively reviewed the data on 502 patients with DLBCL treated in our institution from January 2013 to March 2018. Survival functions were estimated using Kaplan Meier method and Cox regression model. The 3-year progression free survival (PFS) and overall survival (OS) rates were 70.2% and 80.9%, respectively, and the complete remission (CR) rate was 78.1%. Among the patients, those with multiple (≥3) abnormal immunologic markers had significantly shorter 3-year PFS (52.7% vs. 77.3%, P < 0.001) and OS (68.5% vs. 85.8%, P=0.001) than those without multiple abnormal immunologic markers.Multivariate analysis revealed that the presence of multiple abnormal immunologic markers and the elevated serum levels of lactate dehydrogenase were the independent adverse prognostic factors for PFS (P= 0.008, P < 0.001) and OS (P = 0.003, P < 0.001). Meanwhile, advanced Ann Arbor stage was an independent adverse prognostic factor for PFS (P= 0.001) and age > 60 years for OS (P= 0.014). In conclusion, the immunologic status was closely related to lymphoma progression, and this study provides new insights into the risk stratification of patients with DLBCL.
基金This work was supported by the National Science Foundation of China(Nos.51522103,51871200,and 61721005)and the National Program for Support of Top-Notch Young Professionals.
文摘Nanoscale Kirkendall effect has been widely used for rationally fabricating high-quality hollow nanocrystals, but often requires the intrinsic diffusion coefficient of out-diffusion materials higher than that of in-diffusion components. Here we demonstrate an unexpected Kirkendall effect that occurs in diffusing intrinsically faster Cu atoms into Pd icosahedra, leading to the formation of PdCu alloyed hollow nanocrystals. The control experiment with Pd octahedra replacing icosahedra indicates the critical role of twin boundaries in facilitating such unexpected Kirkendall effect. In addition, geometric phase analysis and density functional theory calculation show that out-diffusion of Pd atoms in the icosahedra is faster than in-diffusion of Cu atoms, particularly through the twin boundaries, upon the strain gradient with an inward distribution from tensile to compressive strains. The unexpected Kirkendall effect is also found in the interdiffusion of Ag and Pd atoms in Pd icosahedra. Our finds break the limitation of the intrinsic diffusion coefficient for the synthesis of hollow nanocrystals through Kirkendall effect and are expected to enormously enrich the family of hollow nanocrystals which have shown great potential in broad areas, such as fine chemical production, energy storage and conversion, and environmental protection. This work also provides a deep understanding in the diffusion behavior of atoms upon the strain gradient.