Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeuti...Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.展开更多
The dynamics of a unidirectional nonlinear delayed-coupling chaos system is investigated. Based on the local Hopf bifurcation at the zero equilibrium, we prove the global existence of periodic solutions using a global...The dynamics of a unidirectional nonlinear delayed-coupling chaos system is investigated. Based on the local Hopf bifurcation at the zero equilibrium, we prove the global existence of periodic solutions using a global Hopf bifurcation result due to Wu and a Bendixson’s criterion for higher dimensional ordinary differential equations due to Li & Muldowney.展开更多
This work aimed to clarify the interaction between the fetus and pregnant patients with gestational diabetes mellitus(GDM),the lipid metabolomics analysis of the fetal umbilical cord blood of GDM patients and normal p...This work aimed to clarify the interaction between the fetus and pregnant patients with gestational diabetes mellitus(GDM),the lipid metabolomics analysis of the fetal umbilical cord blood of GDM patients and normal pregnant women were performed to screen out the specific lipid metabolites for pathogenesis of GDM.From 2019–2020,21 patients with GDM and 22 normal pregnant women were enrolled in Hexian Memorial Hospital,Panyu District,Guangzhou.The general information such as weight,height,age,body mass index(BMI)before pregnancy were analyzed.Non-targeted metabonomic detection and analysis were performed in umbilical cord plasma using LCMS method.The age,BMI,delivery methods,and infant weight were different between GDM and control.There were 167 lipid metabolites in umbilical cord blood associated with GDM.Among them,158 upregulated and 9 downregulated in GDM.There were 13 dysregulated metabolites with C<30,including Lyso-phosphatidyl-colines LPC 16:0,18:2,18:1,18:0,20:4 and 22:6,glycerophosphocholines PC O-16:1,oleoylcarnitine CAR 18:2 and 18:1,dihexosylceramides Hex2Cer 13:0;2O,phosphatidylethanolamine PE O-22:6_2:0 and PE O-22:6_3:0 and sphingomyelin SM 8:0;2O/11:0.Those metabolites were associated with glycerophospholipid metabolism and sphingolipid metabolism.Therefore,Lyso-phosphatidyl-colines,glycerophosphocholines,oleoylcarnitine,dihexosylceramides,phosphatidylethanolamine,and sphingomyelin were main lipid metabolites of GDM,which might be used for diagnosis and treatment of GDM.展开更多
OBJECTIVE To investigate the correlation of E-cadherin expression with clinicopathological parameters and prognosis of patients with oral squa- mous cell carcinoma. METHODS We examined the expression of the protein E-...OBJECTIVE To investigate the correlation of E-cadherin expression with clinicopathological parameters and prognosis of patients with oral squa- mous cell carcinoma. METHODS We examined the expression of the protein E-cadherin in 43 oral squamous cell carcinoma (SCC) surgical speciments by SABC im- munohistochemistry. RESULTS There was a significant correlation between the level of E- cadherin expression and tumor stage (P=0.024), invasive pattern (P= 0.009) and lymph node metastasis (P=0.023). No relation was found with age (P=0.084), sex (P= 1.356) and differentiation (P=0.877). Using the Kaplan-Meier method we demonstrated that those cases which showed E-cadherin expression (-) or (+) had a significantly poorer prognosis compared those cases which showed expression (++) or (+++) (P= 0.0146). CONCLUSION E -cadherin, is an important indicator of clinical diag- noses and prognositic marker for oral SCC patients.展开更多
The significant role of the polyelectrolytic nature of non-collagenous proteins (NCPs) in regulating the in vivo mineralization of collagen provides important insights for scientists searching for analogues of NCPs to...The significant role of the polyelectrolytic nature of non-collagenous proteins (NCPs) in regulating the in vivo mineralization of collagen provides important insights for scientists searching for analogues of NCPs to achieve in vitro collagen mineralization. Polyampholyte carboxymethyl chitosan (CMC) has both carboxyl and amino groups, which allows it to act as a cationic or anionic polyelectrolyte below or above its isoelectric point (IP), respectively. In this study, CMC was employed as the analogue of NCPs to stabilize amorphous calcium phosphate (ACP) under acidic conditions (pH < 3.5) via the formation of CMC/ACP nanocomplexes. In the presence of both ACP nanoparticles and acid collagen molecules, ACP nanoparticles could be integrated into collagen fibrils during the process of collagen self-assembly and achieve intrafibrillar mineralization of collagen in vitro (i.e., synchronous self-assembly/mineralization (SSM) of collagen). This mode of mineralization is different from established mechanisms in which mineralization follows the self-assembly (MFS) of collagen. Thus, SSM provides a new strategy for developing materials from mineralized collagen scaffolds.展开更多
Polarization aberration of hyper-numerical-aperture projection optics should be measured accurately in order to control it exactly and ensure favorable imaging performance.A hybrid calibration method combining the Fou...Polarization aberration of hyper-numerical-aperture projection optics should be measured accurately in order to control it exactly and ensure favorable imaging performance.A hybrid calibration method combining the Fourier analysis method and the eigenvalue calibration method is proposed.A wide-view-angle Mueller polarimeter(WMP)is exemplified to demonstrate the capability of the proposed calibration method,which can calibrate the polarimeter and determine the error budget of polarizing elements in the polarimeter.In addition,an experimental setup and a WMP are developed in-house to implement the hybrid calibration method.展开更多
Akt aberrant activation accelerated tumor development and metastasis,and our previous study identified silent information regulator 6(SIRT6)as a novel and critical tumor suppressor in colorectal cancer(CRC)downstream ...Akt aberrant activation accelerated tumor development and metastasis,and our previous study identified silent information regulator 6(SIRT6)as a novel and critical tumor suppressor in colorectal cancer(CRC)downstream of Akt.1 However,the function of SIRT6 in cancer progression has not been fully elucidated.In the present study,we found that except for inducing apoptosis,SIRT6 could serve as a crucial regulator to initiate autophagy by directly interacting with and activating ULK1.More importantly,we also reported autophagy regulation in a SIRT6-dependent indirect manner,namely,SIRT6 competitively bound to PUMA,which led to the release of ULK1.Of note,autophagy inhibition enhanced the pro-apoptotic effect of Midostaurin both in vitro and in vivo.Summarily,SIRT6 induced apoptosis accompanied by protective autophagy,and SIRT6 promoted autophagy by directly interacting with ULK1 and competitive binding to PUMA.This new insight identified the dual function of SIRT6 on apoptosis and autophagy,which has attractive clinical applications in cancer therapy.展开更多
Sol-gel-derived nano-powders of lead magnesium niobate and lead titanate solid solutions (PMN-PT or PMNT) were prepared from lead acetate trihydrate (Pb(CH3COO)2·3H2O), magnesium acetate trihydrate (Mg(CH3- COO)2...Sol-gel-derived nano-powders of lead magnesium niobate and lead titanate solid solutions (PMN-PT or PMNT) were prepared from lead acetate trihydrate (Pb(CH3COO)2·3H2O), magnesium acetate trihydrate (Mg(CH3- COO)2·3H2O), niobium ethoxide (Nb(OC2H5)5) and titanium isopropoxide (Ti(OCH(CH3)2)4). The key steps in the prepa- ration process were discussed. The crystalline phases in the powders were investigated using X-ray diffraction (XRD) analysis and the size of grains was observed by field-emission scanning electron microscopy (SEM). These powders, with good dispersion characteristics and narrow grain size distribution (ranging from 50 nm to 200 nm), may be used to prepare PMNT thick films and ceramics.展开更多
基金National Natural Science Foundation of China(Grant No.81273297)Shenyang Science and Technology Plan.Public Health R&D Special Project(21-173-9-67).
文摘Advanced LUAD shows limited response to treatment including immune therapy.With the development of sequencing omics,it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers.Using GSE72094(n=386)and GSE31210(n=226)gene expression profile data in the GEO database,we identified genes associated with lung adenocarcinoma(LUAD)death using tools such as“edgeR”and“maftools”and visualized the characteristics of these genes using the“circlize”R package.We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods.By calculating the cell death index(CDI)of each individual,we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis(PCA)and Kaplan-Meier analysis.We also used the“ConsensusClusterPlus”tool for unsupervised clustering of LUAD subtypes based on model genes.In addition,we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses.We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort.Finally,we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments.The study utilized the TCGA-LUAD cohort(n=493)and identified 2,901 genes that are differentially expressed in patients with LUAD.Through KEGG and GO enrichment analysis,these genes were found to be involved in a wide range of biological pathways.The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores.By comparing the overall survival(OS)outcomes of patients with different CDI values,it was found that increased CDI levels were significantly associated with lower OS rates.In addition,the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing.Finally,a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis.The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models.Relationship between programmed cell death(PCD)signature models and drug reactivity.After evaluating the median inhibitory concentration(IC50)of various drugs in LUAD samples,statistically significant differences in IC50 values were found in cohorts with high and low CDI status.Specifically,Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort,while Olaparib,Oxaliplatin,SB216763,and Axitinib had lower values.These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy.Therefore,this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics.The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients.
文摘The dynamics of a unidirectional nonlinear delayed-coupling chaos system is investigated. Based on the local Hopf bifurcation at the zero equilibrium, we prove the global existence of periodic solutions using a global Hopf bifurcation result due to Wu and a Bendixson’s criterion for higher dimensional ordinary differential equations due to Li & Muldowney.
基金This work was supported by Basic and Applied Basic Research Projects of Guangzhou Basic Research Program(Grant No.202102080582).
文摘This work aimed to clarify the interaction between the fetus and pregnant patients with gestational diabetes mellitus(GDM),the lipid metabolomics analysis of the fetal umbilical cord blood of GDM patients and normal pregnant women were performed to screen out the specific lipid metabolites for pathogenesis of GDM.From 2019–2020,21 patients with GDM and 22 normal pregnant women were enrolled in Hexian Memorial Hospital,Panyu District,Guangzhou.The general information such as weight,height,age,body mass index(BMI)before pregnancy were analyzed.Non-targeted metabonomic detection and analysis were performed in umbilical cord plasma using LCMS method.The age,BMI,delivery methods,and infant weight were different between GDM and control.There were 167 lipid metabolites in umbilical cord blood associated with GDM.Among them,158 upregulated and 9 downregulated in GDM.There were 13 dysregulated metabolites with C<30,including Lyso-phosphatidyl-colines LPC 16:0,18:2,18:1,18:0,20:4 and 22:6,glycerophosphocholines PC O-16:1,oleoylcarnitine CAR 18:2 and 18:1,dihexosylceramides Hex2Cer 13:0;2O,phosphatidylethanolamine PE O-22:6_2:0 and PE O-22:6_3:0 and sphingomyelin SM 8:0;2O/11:0.Those metabolites were associated with glycerophospholipid metabolism and sphingolipid metabolism.Therefore,Lyso-phosphatidyl-colines,glycerophosphocholines,oleoylcarnitine,dihexosylceramides,phosphatidylethanolamine,and sphingomyelin were main lipid metabolites of GDM,which might be used for diagnosis and treatment of GDM.
文摘OBJECTIVE To investigate the correlation of E-cadherin expression with clinicopathological parameters and prognosis of patients with oral squa- mous cell carcinoma. METHODS We examined the expression of the protein E-cadherin in 43 oral squamous cell carcinoma (SCC) surgical speciments by SABC im- munohistochemistry. RESULTS There was a significant correlation between the level of E- cadherin expression and tumor stage (P=0.024), invasive pattern (P= 0.009) and lymph node metastasis (P=0.023). No relation was found with age (P=0.084), sex (P= 1.356) and differentiation (P=0.877). Using the Kaplan-Meier method we demonstrated that those cases which showed E-cadherin expression (-) or (+) had a significantly poorer prognosis compared those cases which showed expression (++) or (+++) (P= 0.0146). CONCLUSION E -cadherin, is an important indicator of clinical diag- noses and prognositic marker for oral SCC patients.
基金supported by National Natural Science Foundation of China grants(No.81773893)National Major Scientific and Technological Special Project for“Significant New Drugs Development”(No.2017ZX09301060001)+2 种基金Hubei Province Key R&D Programme(No.2020BED017 and 2020BGB004)Jiangxi Province“Thousand Talents Plan”of Scientific and Technological Innovation(No.JXSQ2019201105)Fundamental Research Funds for the Central Universities“South-Central University for Nationalities”(No.CZP20025 and No.CZP20047)
基金financial support of the project from the National Natural Science Foundation of China (Nos. 31870947 and 81571016)
文摘The significant role of the polyelectrolytic nature of non-collagenous proteins (NCPs) in regulating the in vivo mineralization of collagen provides important insights for scientists searching for analogues of NCPs to achieve in vitro collagen mineralization. Polyampholyte carboxymethyl chitosan (CMC) has both carboxyl and amino groups, which allows it to act as a cationic or anionic polyelectrolyte below or above its isoelectric point (IP), respectively. In this study, CMC was employed as the analogue of NCPs to stabilize amorphous calcium phosphate (ACP) under acidic conditions (pH < 3.5) via the formation of CMC/ACP nanocomplexes. In the presence of both ACP nanoparticles and acid collagen molecules, ACP nanoparticles could be integrated into collagen fibrils during the process of collagen self-assembly and achieve intrafibrillar mineralization of collagen in vitro (i.e., synchronous self-assembly/mineralization (SSM) of collagen). This mode of mineralization is different from established mechanisms in which mineralization follows the self-assembly (MFS) of collagen. Thus, SSM provides a new strategy for developing materials from mineralized collagen scaffolds.
基金supported by the Major Scientific Instrument Development Project of National Natural Science Foundation of China(No.11627808)National Natural Science Foundation of China(No.61435005)National Science and Technology Major Project(No.2017ZX02101006-001)。
文摘Polarization aberration of hyper-numerical-aperture projection optics should be measured accurately in order to control it exactly and ensure favorable imaging performance.A hybrid calibration method combining the Fourier analysis method and the eigenvalue calibration method is proposed.A wide-view-angle Mueller polarimeter(WMP)is exemplified to demonstrate the capability of the proposed calibration method,which can calibrate the polarimeter and determine the error budget of polarizing elements in the polarimeter.In addition,an experimental setup and a WMP are developed in-house to implement the hybrid calibration method.
基金supported by the National Natural Science Foundation of China(No.82273172)the Natural Science Foundation of Hunan Province(No.2019JJ40366,2020JJ4182)the Fundamental Research Funds for the Central Universities of Central South University(No.2022ZZTS0964).
文摘Akt aberrant activation accelerated tumor development and metastasis,and our previous study identified silent information regulator 6(SIRT6)as a novel and critical tumor suppressor in colorectal cancer(CRC)downstream of Akt.1 However,the function of SIRT6 in cancer progression has not been fully elucidated.In the present study,we found that except for inducing apoptosis,SIRT6 could serve as a crucial regulator to initiate autophagy by directly interacting with and activating ULK1.More importantly,we also reported autophagy regulation in a SIRT6-dependent indirect manner,namely,SIRT6 competitively bound to PUMA,which led to the release of ULK1.Of note,autophagy inhibition enhanced the pro-apoptotic effect of Midostaurin both in vitro and in vivo.Summarily,SIRT6 induced apoptosis accompanied by protective autophagy,and SIRT6 promoted autophagy by directly interacting with ULK1 and competitive binding to PUMA.This new insight identified the dual function of SIRT6 on apoptosis and autophagy,which has attractive clinical applications in cancer therapy.
文摘Sol-gel-derived nano-powders of lead magnesium niobate and lead titanate solid solutions (PMN-PT or PMNT) were prepared from lead acetate trihydrate (Pb(CH3COO)2·3H2O), magnesium acetate trihydrate (Mg(CH3- COO)2·3H2O), niobium ethoxide (Nb(OC2H5)5) and titanium isopropoxide (Ti(OCH(CH3)2)4). The key steps in the prepa- ration process were discussed. The crystalline phases in the powders were investigated using X-ray diffraction (XRD) analysis and the size of grains was observed by field-emission scanning electron microscopy (SEM). These powders, with good dispersion characteristics and narrow grain size distribution (ranging from 50 nm to 200 nm), may be used to prepare PMNT thick films and ceramics.