“磨玻璃影”特征的早期肺腺癌中MPP成分的突变特征分析及ZNF469基因的探索

背景与目的目前,肺癌依然是我国发病率和死亡率最高的恶性肿瘤。而在早期肺腺癌(lung adenocarcinoma,LUAD)中,微乳头(micropapillary,MPP)成分尤其常见,且通常表现出高侵袭性,其与早期转移、淋巴浸润的风险以及患者的5年生存率显著相关。本研究旨在探究以磨玻璃影(ground-glass opacities,GGOs)为特征的早期LUAD中MPP成分和非MPP成分的异同,寻找MPP成分所特有的突变特征,并分析锌指蛋白家族的ZNF469基因与早期LUAD预后以及免疫浸润的关系。方法收集31例LUAD恶性肺结节,采用显微解剖法将其分为成对的MPP和非MPP成分。对早期恶性肺结节组分进行全外显子组测序(whole-exome sequencing,WES),利用maftools、非负矩阵分解(Nonnegative Matrix Factorization,NMF)法、Sigminer等方法进行突变特征分析,以揭示侵袭性LUAD中MPP组分相比于其他肿瘤组织所特有的基因组突变特征。利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)的LUAD数据库中ZNF469的表达情况,探讨其与肺癌预后的关系;利用GeneMANIA数据库以及基因本体(Gene Ontology,GO)、京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析探索LUAD中与ZNF469相关基因的互作网络及信号通路;利用TIMER和TISIDB数据库分析ZNF469表达与LUAD中免疫细胞浸润水平的相关性。结果MPP成分具有较多的基因组变异,相比于非MPP成分的肿瘤组织,癌症体细胞突变目录(Catalogue of Somatic Mutations in Cancer,COSMIC)的13号突变特征(胞苷脱氨酶家族,APOBEC)是MPP成分所特有的,这提示其参与了MPP成分对LUAD早期侵袭过程的促进作用;并且APOBEC特征高的MPP样本具有更高的肿瘤突变负荷(tumor mutational burden,TMB),提示这些患者更能从免疫治疗中获益。LUAD中突变ZNF469的表达高于正常组织,与LUAD患者的不良预后有关。基因互作网络分析以及GO和KEGG富集分析发现,COL6A1、COL1A1、COL1A2、TGFB2、MMP2、COL8A2、C2CD4C等与ZNF469具有相互作用,且主要与编码胶原蛋白、参与细胞外基质构成有关。ZNF469表达与肿瘤的免疫浸润呈正相关。结论本研究揭示了中国人群侵袭性LUAD中MPP成分的特有突变特征,并发现突变ZNF469的高表达影响LUAD预后与免疫浸润,推测ZNF469可作为LUAD潜在的诊断及预后生物标志物。

On establishment of novel constitutive model for directionally solidified nickel-based superalloys utilizing machine learning methods

To enhance the accuracy of mechanical simulation in the directional solidification process of turbine blades for heavy-duty gas turbines,a new constitutive model that employs machine learning methods was developed.This model incorporates incremental learning and transfer learning,thus improves the predictive accuracy and generalization performance.To account for the anisotropy of the directionally solidified alloy,a deformation direction parameter is added to the model,enabling prediction of the stress-strain relationship of the alloy under different deformation directions.The predictive capabilities of both models are evaluated using correlation coefficient(R),average relative error(δ),and value of relative error(RE).Compared to the traditional model,the machine learning constitutive model achieves higher prediction accuracy and better generalization performance.This offers a new approach for the establishment of flow constitutive models for other directionally solidified and single-crystal superalloys.

FEZF1-AS1在非小细胞肺癌中的研究进展

现如今越来越多的证据表明,长非编码RNA(long non-coding RNA,lncRNA)在肿瘤发生及发展中起着重要的作用。作为一种新发现的lncRNA,FEZ家族锌指1反义RNA1(FEZ family zinc finger 1-antisense RNA 1,FEZF1-AS1)在非小细胞肺癌(non-small cell lung cancer,NSCLC)等恶性肿瘤中表达上调,且FEZF1-AS1的异常表达与NSCLC患者的临床特征及预后有关。此外,FEZF1-AS1可以通过多种机制调节肺癌细胞增殖、迁移和侵袭等生物学过程,可能是潜在的NSCLC治疗新靶点。本文就FEZF1-AS1在NSCLC中的最新研究进展进行阐述。

Overview of Relation between Mineral Nutrient Elements and Growth and Development of Fruit Trees

Mineral nutrition is the material basis for growth and development,yield and quality of fruit trees. It exerts a great effect on the growth and development,fruit quality,yield,and resistance of fruit trees. On the basis of reading a large number of references both at home and abroad,this paper elaborated the relationship between mineral nutrient elements and growth and fruit yield and quality of fruit trees,so as to make proper fertilizer mixing,balance the fertilizer application,promote growth and development of fruit trees,and increase the yield of fruit trees and improve the fruit quality.

Partial removal of the pulmonary artery in video-assisted thoracic surgery for non-small cell lung cancer

Lobectomy with partial removal of the pulmonary artery in video-assisted thoracic surgery （VATS） currently remains a challenge for thoracic surgeons. We were interested in introducing pulmonary vessel blocking techniques in open thoracic surgery into video-assisted thoracic surgery （VATS） procedures. In this study, we reported a surgical technique simultaneously blocking the pulmonary artery and the pulmonary vein for partial removal of the pulmonary artery under VATS. Seven patients with non-small-cell lung cancer （NSCLC） received lobectomy with partial removal of the pulmonary artery using the technique between December 2007 and March 2012. Briefly, rather than using a small clamp on the distal pulmonary artery to the area of invading cancer, we replaced a vascular clamp with a ribbon and Hem-o-lock clip to block the preserved pulmonary veins so as to prevent back bleeding and yield a better view for surgeons. The mean occlusion time of the pulmonary artery and pulmonary veins were 44.0±10.0 and 41.3±9.7 minutes, respectively. The mean repair time of the pulmonary artery was 25.3±13.7 minutes. No complications occurred. No patients showed abnormal blood flow through the reconstructed vessel. There were no local recurrences on the pulmonary artery. In conclusion, the technique for blocking the pulmonary artery and veins is feasible and safe in VATS and reduces the risk of abrupt intraoperative bleeding and the chance of converting to open thoracotomy, and extends the indications of VATS lobectomy.

SYNTHESIS OF 3-ARYL-1(2H, 4H) ACRIDONES AND THEIR DERIVATIVES

Aryl -1 (2H, 4H) acridones and the related acridine-fused pyridine, Pyrimidines and quinolines were synthes ized. The compounds syntbeszied have been hot reported until now. The structures of all the compounds synthes lied were characterzied by elemental analysis. IR and 1HNMR spectra.

Fiber‑Shaped Fluidic Pumps for Wearable Applications

Soft fluidic devices are important for wearable applications involving mass and heat transfer.Based on charge injection electrohydrodynamics,a fluidic fiber pump made of polyurethane and copper wires has been reported to show outstanding performances in terms of pressure,flow rate and power density.Its flexible fiber shape allows integration compatible with textiles,opening new possibilities in the ever-growing field of wearable technology.

Variations in length of stay among survived very preterm infants admitted to Chinese neonatal intensive care units

Background This study aimed to describe length of stay(LOS)to discharge and site variations among very preterm infants(VPIs)admitted to 57 Chinese neonatal intensive care units(NICUs)and to investigate factors associated with LOS for VPIs.Methods This retrospective multicenter cohort study enrolled all infants<32 weeks’gestation and admitted to 57 NICUs which had participated in the Chinese Neonatal Network,within 7 days after birth in 2019.Exclusion criteria included major congenital anomalies,NICU deaths,discharge against medical advice,transfer to non-participating hospitals,and missing discharge date.Two multivariable linear models were used to estimate the association of infant characteristics and LOS.Results A total of 6580 infants were included in our study.The overall median LOS was 46 days[interquartile range(IQR):35-60],and the median corrected gestational age at discharge was 36 weeks(IQR:35-38).LOS and corrected gestational age at discharge increased with decreasing gestational age.The median corrected gestational age at discharge for infants at 24 weeks,25 weeks,26 weeks,27-28 weeks,and 29-31 weeks were 41 weeks,39 weeks,38 weeks,37 weeks and 36 weeks,respectively.Significant site variation of LOS was identified with observed median LOS from 33 to 71 days in different hospitals.Conclusions The study provided concurrent estimates of LOS for VPIs which survived in Chinese NICUs that could be used as references for medical staff and parents.Large variation of LOS independent of infant characteristics existed,indicating variation of care practices requiring further investigation and quality improvement.

Meiotic nuclear divisions 1(MND1)fuels cell cycle progression by activating a KLF6/E2F1 positive feedback loop in lung adenocarcinoma

Background:Considering the increase in the proportion of lung adenocarcinoma(LUAD)cases among all lung cancers and its considerable contribution to cancer-related deaths worldwide,we sought to identify novel oncogenes to provide potential targets and facilitate a better understanding of the malignant progression of LUAD.Methods:The results from the screening of transcriptome and survival analyses according to the integrated Gene Expression Omnibus(GEO)datasets and The Cancer Genome Atlas(TCGA)data were combined,and a promising risk biomarker called meiotic nuclear divisions 1(MND1)was selectively acquired.Cell viability assays and subcutaneous xenograftmodelswere used to validate the oncogenic role ofMND1 in LUADcell proliferation and tumor growth.Aseries of assays,including mass spectrometry,co-immunoprecipitation(Co-IP),and chromatin immunoprecipitation(ChIP),were performed to explore the underlying mechanism.Results:MND1 up-regulation was identified to be an independent risk factor for overall survival in LUAD patients evaluated by both tissue microarray staining and third party data analysis.In vivo and in vitro assays showed that MND1 promoted LUAD cell proliferation by regulating cell cycle.The results of the Co-IP,ChIP and dual-luciferase reporter assays validated that MND1 competitively bound to tumor suppressor Kruppel-like factor 6(KLF6),and thereby protecting E2F transcription factor 1(E2F1)from KLF6-induced transcriptional repression.Luciferase reporter and ChIP assays found that E2F1 activated MND1 transcription by binding to its promoter in a feedback manner.Conclusions:MND1,KLF6,and E2F1 form a positive feedback loop to regulate cell cycle and confer DDP resistance in LUAD.MND1 is crucial for malignant progression and may be a potential therapeutic target in LUAD patients.

LncRNA LINC00525 suppresses p21 expression viamRNA decay and triplex-mediated changes in chromatin structure in lung adenocarcinoma

Background:Emerging evidence suggests that long noncoding RNAs(lncRNAs)play crucial roles in various cancers.In the present study,we aim to investigate the function and molecular mechanism of an up-regulated and survivalassociated lncRNA,LINC00525,in lung adenocarcinoma(LUAD).Methods:The expression level of LINC00525 in tissueswas determined by quantitative reverse transcription polymerase chain reaction(RT-qPCR)and in situ hybridization(ISH).The functional role of LINC00525 in LUAD was investigated using gain-and loss-of-function approaches,both in vivo and in vitro.RNA pull-down,RNA immunoprecipitation(RIP),chromatin immunoprecipitation(ChIP),triplex-capture assay,dual-luciferase assay,gene expression microarray,and bioinformatics analysis were used to investigate the potential underlying mechanisms involved.Results:LINC00525 is highly expressed in LUAD cells and tissues.Survival analysis indicated that upregulation of LINC00525 was associated with poor prognosis in patients with LUAD patients.Knockdown of LINC00525 inhibited cell proliferation and cell cycle progression in vitro.In xenograft models,LINC00525 knockdown suppressed tumor growth and tumorigenesis of tumorbearing mice.Mechanistically,LINC00525 epigenetically suppressed p21 transcription by guiding Enhancer Of Zeste 2 Polycomb Repressive Complex 2 Subunit(EZH2)to the p21 promoter through an formation of RNA-DNA triplex with the p21 promoter,leading to increased trimethylation of lysine 27 on histone 3(H3K27me3)of the p21 promoter.In addition,LINC00525 repressed p21 expression post-transcriptionally by enhancing p21mRNA decay.LINC00525 promoted p21mRNAdecay by competitively binding toRNABindingMotif Single Stranded Interacting Protein 2(RBMS2).Conclusion:Our findings demonstrate that LINC00525 promotes the progression of LUAD by reducing the transcription and stability of p21 mRNA in concert with EZH2 and RBMS2,thus suggesting that LINC00525 may be a potential therapeutic target for clinical intervention in LUAD.

RNA m^(6) A modification: Mapping methods, roles, and mechanisms in acute myeloid leukemia

N^(6)-Methyladenosine(m^(6)A)is the most abundant modification in eukaryotic mRNA,and plays important biological functions via regulating RNA fate determination.Recent studies have shown that m^(6)A modification plays a key role in hematologic malignancies,including acute myeloid leukemia.The current growth of epitranscriptomic research mainly benefits from technological progress in detecting RNA m^(6)A modification in a transcriptome-wide manner.In this review,we first briefly summarize the latest advances in RNA m^(6)A biology by focusing on writers,readers,and erasers of m^(6)A modification,and describe the development of high-throughput methods for RNA m^(6)A mapping.We further discuss the important roles of m^(6)A modifiers in acute myeloid leukemia,and highlight the identification of potential inhibitors for AML treatment by targeting of m^(6)A modifiers.Overall,this review provides a comprehensive summary of RNA m^(6)A biology in acute myeloid leukemia.

Molecular mechanisms for stemness maintenance of acute myeloid leukemia stem cells

Human acute myeloid leukemia(AML)is a fatal hematologic malignancy characterized with accumulation of myeloid blasts and differentiation arrest.The development of AML is associated with a serial of genetic and epigenetic alterations mainly occurred in hematopoietic stem and progenitor cells(HSPCs),which change HSPC state at the molecular and cellular levels and transform them into leukemia stem cells(LSCs).LSCs play critical roles in leukemia initiation,progression,and relapse,and need to be eradicated to achieve a cure in clinic.Key to successfully targeting LSCs is to fully understand the unique cellular and molecular mechanisms for maintaining their stemness.Here,we discuss LSCs in AML with a focus on identification of unique biological features of these stem cells to decipher the molecular mechanisms of LSC maintenance.