The Landscape of Autophagy-Related (ATG) Genes and Functional Characterization of TaVAMP727 to Autophagy in Wheat

Autophagy is an indispensable biological process and plays crucial roles in plant growth and plant responses to both biotic and abiotic stresses. This study systematically identified autophagy-related proteins (ATGs) in wheat and its diploid and tetraploid progenitors and investigated their genomic organization, structure characteristics, expression patterns, genetic variation, and regulation network. We identified a total of 77, 51, 29, and 30 ATGs in wheat, wild emmer, T. urartu and A. tauschii, respectively, and grouped them into 19 subfamilies. We found that these autophagy-related genes (ATGs) suffered various degrees of selection during the wheat’s domestication and breeding processes. The genetic variations in the promoter region of Ta2A_ATG8a were associated with differences in seed size, which might be artificially selected for during the domestication process of tetraploid wheat. Overexpression of TaVAMP727 improved the cold, drought, and salt stresses resistance of the transgenic Arabidopsis and wheat. It also promoted wheat heading by regulating the expression of most ATGs. Our findings demonstrate how ATGs regulate wheat plant development and improve abiotic stress resistance. The results presented here provide the basis for wheat breeding programs for selecting varieties of higher yield which are capable of growing in colder, drier, and saltier areas.

Identification of the Key Genes Associated with the Yak Hair Follicle Cycle

The development of hair follicles in yak shows significant seasonal cycles. In our previous research, transcriptome data including mRNAs and lncRNAs in five stages during the yak hair follicles (HFs) cycle were detected, but their regulation network and the hub genes in different periods are yet to be explored. This study aimed to screen and identify the hub genes during yak HFs cycle by constructing a mRNA-lncRNA co-expression network. A total of 5000 differently expressed mRNA (DEMs) and 729 differently expressed long noncoding RNA (DELs) were used to construct the co-expression network, based on weighted genes co-expression network analysis (WGCNA). Four temporally specific modules were considered to be significantly associated with the HFs cycle of yak. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the modules are enriched into Wnt, EMC-receptor interaction, PI3K-Akt, focal adhesion pathways, and so on. The hub genes, such as FER, ELMO1, PCOLCE, and HOXC13, were screened in different modules. Five hub genes (WNT5A, HOXC13, DLX3, FOXN1, and OVOL1) and part of key lncRNAs were identified for specific expression in skin tissue. Furthermore, immunofluorescence staining and Western blotting results showed that the expression location and abundance of DLX3 and OVOL1 are changed following the process of the HFs cycle, which further demonstrated that these two hub genes may play important roles in HFs development.

System analysis of VEGFA in renal cell carcinoma: The expression, prognosis, gene regulation network and regulation targets

Background VEGFA is one of the most important regulators of angiogenesis and plays a crucial role in cancer angiogenesis and progression. Recent studies have highlighted a relationship between VEGFA expression and renal cell carcinoma occurrence. However, the expression level, gene regulation network, prognostic value, and target prediction of VEGFA in renal cell carcinoma remain unclear. Therefore, system analysis of the expression, gene regulation network, prognostic value, and target prediction of VEGFA in patients with renal cell carcinoma is of great theoretical significance as there is a clinical demand for the discovery of new renal cell carcinoma treatment targets and strategies to further improve renal cell carcinoma treatment efficacy. Methods This study used multiple free online databases, including cBioPortal, TRRUST, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, Metascape, and TIMER for the abovementioned analysis. Results VEGFA was upregulated in patients with kidney renal clear cell carcinoma (KIRC) and kidney chromophobe (KICH), and downregulated in patients with kidney renal papillary cell carcinoma (KIRP). Moreover, genetic alterations of VEGFA were found in patients with renal cell carcinoma as follows: 4% (KIRC), 8% (KICH), and 4% (KIRP). The promoter methylation of VEGFA was lower and higher in patients with clinical stages of KIRC and stage 1 KIRP, respectively. VEGFA expression significantly correlated with KIRC and KIRP pathological stages. Furthermore, patients with KICH and KIRP having low VEGFA expression levels had a longer survival than those having high VEGFA expression levels. VEGFA and its neighboring genes functioned in the regulation of protein methylation and glycosylation, as well as muscle fiber growth and differentiation in patients with renal cell carcinoma. Gene Ontology enrichment analysis revealed that the functions of VEGFA and its neighboring genes in patients with renal cell carcinoma are mainly related to cell adhesion molecule binding, catalytic activity, acting on RNA, ATPase activity, actin filament binding, protease binding, transcription coactivator activity, cysteine-type peptidase activity, and calmodulin binding. Transcription factor targets of VEGFA and its neighboring genes in patients with renal cell carcinoma were found: HIF1A, TFAP2A, and ESR1 in KIRC; STAT3, NFKB1, and HIPK2 in KICH; and FOXO3, TFAP2A, and ETS1 in KIRP. We further explored the VEGFA-associated kinase (ATM in KICH as well as CDK1 and AURKB in KIRP) and VEGFA-associated microRNA (miRNA) targets (MIR-21 in KICH as well as MIR-213, MIR-383, and MIR-492 in KIRP). Furthermore, the following genes had the strongest correlation with VEGFA expression in patients with renal cell carcinoma: NOTCH4, GPR4, and TRIB2 in KIRC; CKMT2, RRAGD, and PPARGC1A in KICH; and FLT1, C6orf223, and ESM1 in KIRP. VEGFA expression in patients with renal cell carcinoma was positively associated with immune cell infiltration, including CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells. Conclusions This study revealed VEGFA expression and potential gene regulatory network in patients with renal cell carcinoma, thereby laying a foundation for further research on the role of VEGFA in renal cell carcinoma occurrence. Moreover, the study provides new renal cell carcinoma therapeutic targets and prognostic biomarkers as a reference for fundamental and clinical research.

The Relationship Between the Network of Non-coding RNAs-Molecular Targets and N6-Methyladenosine Modification in Colorectal Cancer

Recent accumulating researches implicate that non-coding RNAs (ncRNAs) including microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNAs) play crucial roles in colorectal cancer (CRC) initiation and development. Notably, N6-methyladenosine (m6A) methylation, the critical posttranscriptional modulators, exerts various functions in ncRNA metabolism such as stability and degradation. However, the interaction regulation network among ncRNAs and the interplay with m6A-related regulators has not been well documented, particularly in CRC. Here, we summarize the interaction networks and sub-networks of ncRNAs in CRC based on a data-driven approach from the publications (IF > 6) in the last quinquennium (2016–2021). Further, we extend the regulatory pattern between the core m6A regulators and m6A-related ncRNAs in the context of CRC metastasis and progression. Thus, our review will highlight the clinical potential of ncRNAs and m6A modifiers as promising biomarkers and therapeutic targets for improving the diagnostic precision and treatment of CRC.

Causal Mediation of Stress Reduction in Family Dementia Caregivers: A Focus on Mindfulness

Although mindfulness therapies have demonstrated benefits for reducing stress and improving psychological symptoms in family dementia caregivers, the mechanisms underlying these salutary effects are unknown. We report a causal mediation pathway to improvement of stress symptoms in family dementia caregivers with Mentalizing Imagery Therapy (MIT), which employs mindfulness and guided imagery tools to reduce stress and improve understanding of self and others. In a randomized controlled trial of short-term 4-week MIT (N=24) versus a psychosocial support group (N=22), MIT demonstrated superior benefit for reducing perceived stress (p=.006). Increased trait mindfulness was a causal mediator of this effect (p=.02). Neuroimaging pre and post intervention found that increased mindfulness was associated with strengthened connectivity of the dorsolateral prefrontal cortex with an emotion regulation network (p<.001). The results are discussed in light of theories of cognitive control and may inform the design of future studies aimed at reducing family caregiver stress.

Analysis of circRNA regulatory network in myocardial tissue of type 1 diabetic mice

Type 1 diabetes mellitus, also called insulin-dependent diabetes is associated with elevated blood glucose concentration arising from the inability of the pancreas to produce insulin. Diabetic cardiomyopathy is a major cause of death in diabetic patients. CircRNAs have been reported to participate in various human diseases, including diabetic cardiomyopathy. In this study, the regulation network of circRNA in type 1 diabetes mellitus was investigated. Streptozotocin treatment was implemented to induce type 1 diabetes mellitus in the mouse model, and echocardiography was implemented to detect the heart function of the type 1 diabetes mellitus mouse. Also, the qRT-PCR assay was used to identify the circRNA expression in type 1 diabetes mellitus mouse myocardial tissue. Findings showed that heart function of type 1 diabetes mellitus mouse was significantly damaged than control group mouse and cardiac hypertrophy in type 1 diabetes mellitus mouse, circRNAs were aberrantly regulated in type 1 diabetes mellitus mouse myocardial tissue. The following circRNAs were mmu_circ_0001560, mmu_circ_0001800, mmu_circ_0001801, mmu_circ_0002281 and mmu_circ_0000614 were expressed low in type 1 diabetes mellitus mouse myocardial tissue. In conclusion, type 1 diabetes mellitus caused alterations in the regulation network of circRNAs.