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BackgroundOne of the most prevalent hematological system cancers is acute myeloid leukemia (AML). Efferocytosis-related genes (ERGs) and N6-methyladenosine (m6A) have an important significance in the progression of cancer, and the metastasis of tumors.MethodsThe AML-related data were collected from The Cancer Genome Atlas (TCGA; TCGA-AML) database and Gene Expression Omnibus (GEO; GSE9476, GSE71014, and GSE13159) database. The “limma” R package and Venn diagram were adopted to identify differentially expressed ERGs (DE-ERGs). The m6A related-DE-ERGs were obtained by Spearman analysis. Subsequently, univariate Cox and Least Absolute Shrinkage and Selection Operator (LASSO) were used to construct an m6A related-ERGs risk signature for AML patients. The possibility of immunotherapy for AML was explored. The pRRophetic package was adopted to calculate the IC50 of drugs for the treatment of AML. Finally, the expression of characterized genes was validated by quantitative reverse transcription-PCR (qRT-PCR).ResultsBased on m6A related-DE-ERGs, a prognostic model with four characteristic genes (UCP2, DOCK1, SLC14A1, and SLC25A1) was constructed. The risk score of model was significantly associated with the immune microenvironment of AML, with four immune cell types, 14 immune checkpoints, 20 HLA family genes and, immunophenoscore (IPS) all showing differences between the high- and low-risk groups. A total of 56 drugs were predicted to differ between the two groups, of which Erlotinib, Dasatinib, BI.2536, and bortezomib have been reported to be associated with AML treatment. The qRT-PCR results showed that the expression trends of DOCK1, SLC14A1 and SLC25A1 were consistent with the bioinformatics analysis.ConclusionIn summary, 4 m6A related- ERGs were identified and the corresponding prognostic model was constructed for AML patients. This prognostic model effectively stratified the risk of AML patients.

Abstract Association is the basic unit of plant community classification. Exploring the distribution of plant associations can help improve our understanding of biodiversity conservation. Different associations depend on different habitats and studying the association level is important for ecological restoration, regional ecological protection, regulating the ecological balance, and maintaining biodiversity. However, previous studies have only focused on suitable distribution areas for species and not on the distribution of plant associations. Larix gmelinii is a sensitive and abundant species that occurs along the southern margin of the Eurasian boreal forests, and its distribution is closely related to permafrost. In this study, 420 original plots of L. gmelinii forests were investigated. We used a Maxent model and the ArcGIS software to project the potential geographical distribution of L. gmelinii associations in the future (by 2050 and 2070) according to the climate scenarios RCP 2.6, RCP 4.5, and RCP 8.5. We used the multi‐classification logistic regression analysis method to obtain the response of the suitable area change for the L. gmelinii alliance and associations to climate change under different climate scenarios. Results revealed that temperature is the most crucial factor affecting the distribution of L. gmelinii forests and most of its associations under different climate scenarios. Suitable areas for each association type are shrinking by varying degrees, especially due to habitat loss at high altitudes in special terrains. Different L. gmelinii associations should have different management measures based on the site conditions, composition structure, growth, development, and renewal succession trends. Subsequent research should consider data on biological factors to obtain more accurate prediction results.

Abstract Background Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC. Methods The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR. Results SRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo. Conclusions Taken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.

Proton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma (EAC) in patients with BE has still been controversial. The current systematic review and meta-analysis was designed to evaluate the association between PPIs and the risk of EAC or high-grade dysplasia (HGD) in patients with BE.A systematic literature search of studies reporting the association between PPIs and the risk of EAC and/or HGD in patients with BE was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Next, literature was screened using previously established criteria and relevant data were extracted from included studies. Finally, the software program Review Manage 5.2 was applied to aggregate data and analyze the results.Nine observational studies, comprising five cohort and four case-control studies (including a total of 5712 patients with BE), were identified. Upon meta-analysis, PPIs were found to have no association with the risk of EAC and/or HGD in patients with BE (unadjusted OR 0.43, 95% CI 0.17-1.08). Analysis for duration response relationship revealed no significant trend toward protection against EAC or HGD with PPIs usage for >2~3 years (one study using 7-year cutoff) when compared to usage for shorter time periods (PPIs usage >2~3 years vs.

Background: PD-L1 expression on tumor-infiltrating lymphocytes (TILs) has recently been reported as a biomarker for colorectal cancer (CRC). However, the prognostic and clinical significance of PD-L1 on TILs in CRC remains controversial. We performed this meta-analysis to evaluate the association between the PD-L1 expression on TILs and clinicopathological features and prognosis of CRC patients. Methods: A comprehensive literature search for relevant studies published up to Feb 2020 was performed using Medline, Embase, and Web of Science. Odds ratio (OR) with 95% CI was selected to appraise the correlation between PD-L1 expression on TILs with prognostic and clinicopathological characteristics of CRC patients. Begg's and Egger's test were used to assess publication bias. The statistical analysis was conducted using Stata software. Results: A total of 19 studies including 5,213 CRC cases were included in this meta-analysis. The pooled results showed that PD-L1 overexpression on TILs was relevant to longer OS (OR = 1.36, 95% CI = 1.19 - 1.55, p < 0.01) and longer DFS/RFS (OR = 1.22, 95% CI = 1.03 - 1.44, p = 0.02). Moreover, CRC patients with high expression of PD-L1 on TILS was associated with lower T stage (OR = 2.30, 95% CI = 1.85 - 2.87, p < 0.01), less lymph node invasion (OR = 1.48, 95% CI = 1.03 - 2.13, p = 0.03), less distant metastasis (OR = 2.56, 95% CI = 1.81 - 3.64, p < 0.01), earlier TNM stage (OR = 1.93, 95% CI = 1.34 - 2.66, p < 0.01), later tumor grade (OR = 0.38, 95% CI = 0.23 - 0.62, p < 0.01) and high MSI status (OR = 0.36, 95% CI = 0.25 - 0.52, p < 0.01). But it is not related to tumor size, tumor differentiation, MMR status, BRAF mutant, and KRAS mutant. Conclusions: This meta-analysis revealed that PD-L1 expression on TILs can serve as a significant biomarker for positive prognosis and clinicopathological features of CRC. Our results may provide some useful information when using PD-L1 expression to predict the survival of CRC patients and to select the beneficial CRC patients from PD-1/PD-L1 antibody treatment. [ABSTRACT FROM AUTHOR]

De novo organ regeneration is an excellent biological system for the study of fundamental questions regarding stem cell initiation, cell fate determination, and hormone signaling. Despite the general belief that auxin and cytokinin responses interact to regulate de novo organ regeneration, the molecular mechanisms underlying such a cross talk are little understood. Here, we show that spatiotemporal biosynthesis and polar transport resulted in local auxin distribution in Arabidopsis (Ambidopsis thaliana), which in turn determined the cytokinin response during de novo shoot regeneration. Genetic and pharmacological interference of auxin distribution disrupted the cytokinin response and ATP/ADP ISOPENTENYLTRANSFERASE5 (AtIPT5) expression, affecting stem cell initiation and meristem formation. Transcriptomic data suggested that AUXIN RESPONSE FACTOR3 (ARF3) mediated the auxin response during de novo organ regeneration. Indeed, mutations in ARF3 caused ectopic cytokinin biosynthesis via the misexpression of AtIPT5, and this disrupted organ regeneration. We further showed that ARF3 directly bound to the promoter of AtIPT5 and negatively regulated AtIPT5 expression. The results from this study thus revealed an auxin-cytokinin cross talk mechanism involving distinct intermediate signaling components required for de novo stem cell initiation and shed new light on the mechanisms of organogenesis in planta. [ABSTRACT FROM AUTHOR]