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Abstract The three-stranded DNA-RNA triplex hybridization is involved in various biological processes, including gene expression regulation, DNA repair, and chromosomal stability. However, the DNA-RNA triplex mediating mechanisms underlying tumorigenesis remain to be fully elucidated. Here, we show that peptidylprolyl isomerase A (PPIA) serves as anchor to recruit GAU1 lncRNA by interacting with exon 4 of GAU1 and enhances the formation of SENP5/GAU1 DNA-lncRNA triplex. Intriguingly, TFR4 region of GAU1 exon 3 and TTS4 region of SENP5 promoter DNA constitute fragments forming the SENP5/GAU1 triplex. The SENP5/GAU1 triplex subsequently triggers the recruitment of the methyltransferase SET1A to exon 1 of GAU1, leading to the enrichment of H3K4 trimethylation and the activation of SENP5 transcription for driving the tumorigenesis of gastric cancer in vitro and in vivo. Our study reveals a mechanism of PPIA-guided SENP5/GAU1 DNA-lncRNA triplex formation in tumorigenesis and providing a concept in the dynamics of isomerase assisted DNA-RNA hybridization.

Abstract The spatial co-presence of aberrant long non-coding RNAs (lncRNAs) and abnormal coding genes contributes to malignancy development in various tumors. However, precise coordinated mechanisms underlying this phenomenon in tumorigenesis remains incompletely understood. Here, we show that Prohibitin 2 (PHB2) orchestrates the transcription of an oncogenic CASC15-New-Isoform 2 (CANT2) lncRNA and the coding tumor-suppressor gene CCBE1, thereby accelerating melanoma tumorigenesis. In melanoma cells, PHB2 initially accesses the open chromatin sites at the CANT2 promoter, recruiting MLL2 to augment H3K4 trimethylation and activate CANT2 transcription. Intriguingly, PHB2 further binds the activated CANT2 transcript, targeting the promoter of the tumor-suppressor gene CCBE1. This interaction recruits histone deacetylase HDAC1 to decrease H3K27 acetylation at the CCBE1 promoter and inhibit its transcription, significantly promoting tumor cell growth and metastasis both in vitro and in vivo. Our study elucidates a PHB2-mediated mechanism that orchestrates the aberrant transcription of lncRNAs and coding genes, providing an intriguing epigenetic regulatory model in tumorigenesis.

Abstract Multiple gene abnormalities are major drivers of tumorigenesis. NF-κB p65 overactivation and cGAS silencing are important triggers and genetic defects that accelerate tumorigenesis. However, the simultaneous correction of NF-κB p65 and cGAS abnormalities remains to be further explored. Here, we propose a novel Induced Dual-Target Rebalance (IDTR) strategy for simultaneously correcting defects in cGAS and NF-κB p65. By using our IDTR approach, we showed for the first time that oncolytic adenovirus H101 could reactivate silenced cGAS, while silencing GAU1 long noncoding RNA (lncRNA) inhibited NF-κB p65 overactivation, resulting in efficient in vitro and in vivo antitumor efficacy in colorectal tumors. Intriguingly, we further demonstrated that oncolytic adenoviruses reactivated cGAS by promoting H3K4 trimethylation of the cGAS promoter. In addition, silencing GAU1 using antisense oligonucleotides significantly reduced H3K27 acetylation at the NF-κB p65 promoter and inhibited NF-κB p65 transcription. Our study revealed an aberrant therapeutic mechanism underlying two tumor defects, cGAS and NF-κB p65, and provided an alternative IDTR approach based on oncolytic adenovirus and antisense oligonucleotides for efficient therapeutic efficacy in tumors.

Abstract Bimetallic PtRu are promising electrocatalysts for hydrogen oxidation reaction in anion exchange membrane fuel cell, where the activity and stability are still unsatisfying. Here, PtRu nanowires were implanted with a series of oxophilic metal atoms (named as i-M-PR), significantly enhancing alkaline hydrogen oxidation reaction (HOR) activity and stability. With the dual doping of In and Zn atoms, the i-ZnIn-PR/C shows mass activity of 10.2 A mgPt+Ru −1 at 50 mV, largely surpassing that of commercial Pt/C (0.27 A mgPt −1) and PtRu/C (1.24 A mgPt+Ru −1). More importantly, the peak power density and specific power density are as high as 1.84 W cm−2 and 18.4 W mgPt+Ru −1 with a low loading (0.1 mg cm−2) anion exchange membrane fuel cell. Advanced experimental characterizations and theoretical calculations collectively suggest that dual doping with In and Zn atoms optimizes the binding strengths of intermediates and promotes CO oxidation, enhancing the HOR performances. This work deepens the understanding of developing novel alloy catalysts, which will attract immediate interest in materials, chemistry, energy and beyond.

Urban parks enhance residents’ quality of life and health by fostering a harmonious relationship between people and nature, so effective park design needs to prioritize ecological protection, sustainable landscapes, and practical spatial structures to achieve these benefits. This study takes the typical case of urban park renovation and reconstruction—Kowloon Walled City Park—as an example to conduct research and divides the interior of the park into four types of areas: contemporary built-up area; historical relic area; natural–folk custom area; and ecological conservation area. Based on 405 valid questionnaire data for respondents, this study conducts empirical research using a combination of the Semantic Differential (SD) method, Importance Performance Analysis (IPA) model, and unordered multivariate logit choice model, comprehensively describes and analyzes individual spatial perception and preferences, and further discusses the potential factors affecting individual perception preferences. The results show that there are differences in many characteristics between different areas in Kowloon Walled City Park. At the same time, people generally prefer park areas that integrate modern and traditional elements, natural and cultural environments, and pay attention to the balance between naturalness and sociality in park design. These results provide useful information for planners, developers, and others, as well as data for designing urban park construction with higher practical value and natural benefits.

Pt-based nanoparticles (NPs) have been widely used in catalysis. However, this suffers from aggregation and/or sintering at working conditions. We demonstrate a robust strategy for stabilizing PtCo NPs under high temperature with strong interaction between M-N-C and PtCo NPs with Pt-M-N coordination, namely, "atom glue." Such atom glue for stabilizing Pt-based NPs can be extended to Zn, Mn, Fe, Ni, Co, and Cu, being a versatile strategy for stabilizing PtCo NPs, which substantially promotes the performance toward oxygen reduction reaction (ORR) and fuel cell. Impressively, the mass activity (MA) reaches 2.99 A mgPt-1 for ORR over g-Zn-N-C/PtCo, and 79.3% of the initial MA is maintained after 90K cycles in fuel cell. This work provides a versatile strategy for stabilizing Pt-based NPs via atom glue, which is likely to spark widespread interest across various fields. [ABSTRACT FROM AUTHOR]