Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a ...Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a valuable molecular target for the treatment of LUAD.Methods:Using multiple databases,we screened for hub genes in LUAD using Cytoscape and explored the expression and prognosis of DLG associated protein 5(DLGAP5)in LUAD.We investigated the genetic variation,functional enrichment,and epigenetic activity of DLGAP5.Furthermore,we evaluated the relationship between the tumor microenvironment(TME)and DLGAP5.Results:Our study identified 10 hub genes in LUAD:CDC45,KIAA0101,DLGAP5,CDT1,NCAPG,CCNB1,CDCA5,CDC20,KIF11,and AURKA.We discovered that DLGAP5 was overexpressed and associated with poor prognosis in LUAD.DLGAP5 exhibited an overall genetic variation frequency of 2%,and its DNA promoter was hypomethylated in LUAD(p<0.05).The expression of DLGAP5 in LUAD showed a positive correlation with the majority of N6-methyladenosine(m6A)-methylation genes.Additionally,DLGAP5 was primarily associated with the cell cycle in LUAD.Notably,there was a significant favorable association between DLGAP5 and CD274,CTLA4,HAVCR2,and LAG3 in LUAD.Conclusion:DLGAP5 may be a therapeutic target for LUAD,as it affects cancer cells proliferation and development through the regulation of cell-cycle checkpoints and modulation of immune cell infiltration and immune checkpoints in the TME.展开更多
Background:Tryptophan metabolism is involved in esophageal carcinogenesis.However,its genetic mechanisms remain unclear.This study aimed to investigate the effect of genetic variants that encode tryptophan metabolism ...Background:Tryptophan metabolism is involved in esophageal carcinogenesis.However,its genetic mechanisms remain unclear.This study aimed to investigate the effect of genetic variants that encode tryptophan metabolism on susceptibility to esophageal cancer(EC)and elucidate the mechanisms underlying genetic variation in EC progression.Methods:Age-and sex-matched cohorts of 167 patients with EC and 236 healthy controls were enrolled in this study.The concentrations of tryptophan and its metabolites were determined by self-assembled high-performance liquid chromatography-tandem mass spectrometry.High-throughput sequencing techniques were utilized to detect candidate coding genetic variants,and dominant genetic models were used to elucidate the genotypic associations.Results:Tryptophan metabolism was significantly imbalanced in patients with EC,with elevated indolepropionic acid(IPA)levels reducing the risk of EC susceptibility.ACSM2B rs73530508(A>G)mutation was associated with higher IPA levels in vivo(P?0.0004,false discovery rate[FDR]?0.0092)and significantly reduced the risk of EC susceptibility(odds ratio[OR]:0.576,Padj?0.0161).Mediation effect analysis indicated that singlenucleotide polymorphism may inhibit carcinogenesis by reducing IPA metabolism and excretion with a mediation effect of 45.54%.Conclusions:This study identifies the potential mechanism of ACSM2B rs73530508(A>G)in esophageal carcinogenesis and its role in driving increased IPA levels,thereby suppressing the risk of development.展开更多
Dynamic surface patterns(DSPs)have attracted significant interest in anti-counterfeiting,enabling information to be stored,encrypted and decrypted in response to external stimuli.However,creating dynamic surface patte...Dynamic surface patterns(DSPs)have attracted significant interest in anti-counterfeiting,enabling information to be stored,encrypted and decrypted in response to external stimuli.However,creating dynamic surface patterns,capable of controlling wrinkling time and independently modulating different information in both wrinkled and fluorescent states,remains a tremendous challenge.These limit DSPs to further enhance tamper-proofing capacity and extend the information storage density.Here,a rationally designed patterning strategy based on controllable elastic modulus was demonstrated to fabricate self-erasable dynamic surface patterns(S-DSPs)that increase information storage density.These novel S-DSPs strategically integrated amino co-oligomers(ACOs)with the 9-anthracenemethanol(9-AM)as skin layers,designing a bilayer multi-encoding system which could carry several different types of information with wrinkled and fluorescent patterns.The ACOs with relatively low molecular weight can endow the elastic modulus of skin layers with a wide range of regulation.As a result,the difference between the compressive strain and the critical wrinkle strain in the bilayer system would be precisely modulated by photo-dimerization to form quick-response(minimum<1 min)and self-erasable(3 min–8 days)wrinkled patterns for S-DSPs.Meanwhile,the fluorescence pattern could be independently erased and reprogrammed without affecting the change in the wrinkle pattern under modulus-controlled conditions.Moreover,controllable self-erasure in S-DSPs significantly develops tamper-proof capabilities in a supply chain.This original strategy could provide a new approach to the tamper-proof,high-density,and multi-encoded information storage in the product security or inkless printing.展开更多
基金funded by the supporting funds for scientific research of the Sixth Affiliated Hospital,Sun Yat-sen University(P20200217202404781).
文摘Introduction:The difficulty in treating lung adenocarcinoma(LUAD)is caused by a shortage of knowledge about the biological mechanisms and a lack of treatment choices.Objectives:The aim of this study was to identify a valuable molecular target for the treatment of LUAD.Methods:Using multiple databases,we screened for hub genes in LUAD using Cytoscape and explored the expression and prognosis of DLG associated protein 5(DLGAP5)in LUAD.We investigated the genetic variation,functional enrichment,and epigenetic activity of DLGAP5.Furthermore,we evaluated the relationship between the tumor microenvironment(TME)and DLGAP5.Results:Our study identified 10 hub genes in LUAD:CDC45,KIAA0101,DLGAP5,CDT1,NCAPG,CCNB1,CDCA5,CDC20,KIF11,and AURKA.We discovered that DLGAP5 was overexpressed and associated with poor prognosis in LUAD.DLGAP5 exhibited an overall genetic variation frequency of 2%,and its DNA promoter was hypomethylated in LUAD(p<0.05).The expression of DLGAP5 in LUAD showed a positive correlation with the majority of N6-methyladenosine(m6A)-methylation genes.Additionally,DLGAP5 was primarily associated with the cell cycle in LUAD.Notably,there was a significant favorable association between DLGAP5 and CD274,CTLA4,HAVCR2,and LAG3 in LUAD.Conclusion:DLGAP5 may be a therapeutic target for LUAD,as it affects cancer cells proliferation and development through the regulation of cell-cycle checkpoints and modulation of immune cell infiltration and immune checkpoints in the TME.
基金funded by the 2022 Guangdong Province Clinical Drug Research Fund Project(Clinical Treatment Precision Medicine Special Project)(No:2022JZ21)the 2022 Bai Qiu En-Qiu Suo-Pharmacy Scientific Research Capacity Building Project(No:Z04JKM2021005)+3 种基金the 2022 Guangdong Science and Technology Innovation Strategic Project(“Major ProjcetstTask List”)Shan Fu Ke Letter[2022]124(No:STKJ202209072)the 2022 Special Fund for Hospital Pharmaceutical Research of Guangdong Province Hospital Association(No:YXKY202204)the 2023 Guangdong Provincial Hospital Pharmacist Youth Trust Research Fund(Qingyue Pharmacy Fund)(No:2023QNTJ14)the 2024 Guangdong Provincial Hospital Pharmaceutical Research Foundation(No:2024A05).
文摘Background:Tryptophan metabolism is involved in esophageal carcinogenesis.However,its genetic mechanisms remain unclear.This study aimed to investigate the effect of genetic variants that encode tryptophan metabolism on susceptibility to esophageal cancer(EC)and elucidate the mechanisms underlying genetic variation in EC progression.Methods:Age-and sex-matched cohorts of 167 patients with EC and 236 healthy controls were enrolled in this study.The concentrations of tryptophan and its metabolites were determined by self-assembled high-performance liquid chromatography-tandem mass spectrometry.High-throughput sequencing techniques were utilized to detect candidate coding genetic variants,and dominant genetic models were used to elucidate the genotypic associations.Results:Tryptophan metabolism was significantly imbalanced in patients with EC,with elevated indolepropionic acid(IPA)levels reducing the risk of EC susceptibility.ACSM2B rs73530508(A>G)mutation was associated with higher IPA levels in vivo(P?0.0004,false discovery rate[FDR]?0.0092)and significantly reduced the risk of EC susceptibility(odds ratio[OR]:0.576,Padj?0.0161).Mediation effect analysis indicated that singlenucleotide polymorphism may inhibit carcinogenesis by reducing IPA metabolism and excretion with a mediation effect of 45.54%.Conclusions:This study identifies the potential mechanism of ACSM2B rs73530508(A>G)in esophageal carcinogenesis and its role in driving increased IPA levels,thereby suppressing the risk of development.
基金This work was supported by the National Natural Science Foundations of China(Nos.51903058,51873042,and 51833011)Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education(No.PCFM-2922A02)Guangzhou Basic and Applied Basic Research Foundation(No.202201010382).
文摘Dynamic surface patterns(DSPs)have attracted significant interest in anti-counterfeiting,enabling information to be stored,encrypted and decrypted in response to external stimuli.However,creating dynamic surface patterns,capable of controlling wrinkling time and independently modulating different information in both wrinkled and fluorescent states,remains a tremendous challenge.These limit DSPs to further enhance tamper-proofing capacity and extend the information storage density.Here,a rationally designed patterning strategy based on controllable elastic modulus was demonstrated to fabricate self-erasable dynamic surface patterns(S-DSPs)that increase information storage density.These novel S-DSPs strategically integrated amino co-oligomers(ACOs)with the 9-anthracenemethanol(9-AM)as skin layers,designing a bilayer multi-encoding system which could carry several different types of information with wrinkled and fluorescent patterns.The ACOs with relatively low molecular weight can endow the elastic modulus of skin layers with a wide range of regulation.As a result,the difference between the compressive strain and the critical wrinkle strain in the bilayer system would be precisely modulated by photo-dimerization to form quick-response(minimum<1 min)and self-erasable(3 min–8 days)wrinkled patterns for S-DSPs.Meanwhile,the fluorescence pattern could be independently erased and reprogrammed without affecting the change in the wrinkle pattern under modulus-controlled conditions.Moreover,controllable self-erasure in S-DSPs significantly develops tamper-proof capabilities in a supply chain.This original strategy could provide a new approach to the tamper-proof,high-density,and multi-encoded information storage in the product security or inkless printing.