【最新中稿作品】 lncRNA 编码新型蛋白质 、氨合成、肿瘤相关巨噬细胞等

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中稿作品解读

标题

A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers

DOI

https://doi.org/10.1002/anie.202206825

作者

Rongjie Cheng, Fanying Li, Maolei Zhang,

Xin Xia, Jianzhuang Wu, Xinya Gao, Huangkai Zhou, Zhi Zhang, Nunu Huang, Xuesong Yang,

Yaliang Zhang, Shunli Shen, Tiebang Kang, Zexian Liu, Feizhe Xiao, Hongwei Yao, Jianbo Xu,

Chao Yan & Nu Zhang

在大约 30% 的人类癌症中发现了RAS致癌基因的突变，但除 KRAS G12C突变体外，直接靶向 RAS 在临床上仍然被认为是不切实际的。在这里，我们报告RAS - ON (RASON) 是一种由长基因间非蛋白质编码 RNA 00673 ( LINC00673 ) 编码的新型蛋白质，是致癌 RAS 信号传导的正调节因子。

RASON 在胰腺导管腺癌 (PDAC) 患者中异常过表达，它促进体外人 PDAC 细胞系的增殖和体内肿瘤的生长。CRISPR/Cas9 介导的小鼠胚胎成纤维细胞中Rason敲除抑制 KRAS 介导的肿瘤转化。

Rason基因缺失在LSL-Kras G12D中消除致癌 KRAS 驱动的胰腺癌和肺癌肿瘤发生；Trp53 R172H/+小鼠。从机制上讲，RASON 直接与 KRAS G12D/V结合并抑制内在和 GTP 酶激活蛋白 (GAP) 介导的 GTP 水解，从而使 KRAS G12D/V维持在 GTP 结合的过度活跃状态。

在治疗上，RASON 的剥夺使 KRAS 突变胰腺癌细胞和患者来源的类器官对 EGFR 抑制剂敏感。我们的研究结果将 RASON 确定为致癌 KRAS 信号传导的关键调节因子和 KRAS 突变癌症的有前途的治疗靶点。

中稿作品·本周精选

ZHONGKEHUANCAI

01

Volume135, Issue11 March 6, 2023

标题

Stainless Steel-Like Passivation Inspires Persistent Silicon Anodes for Lithium-Ion Batteries

DOI

https://doi.org/10.1002/ange.202216557

Abstract（上下滑动查看）

Passivation of stainless steel by additives forming mass-transport blocking layers is widely practiced, where Cr element is added into bulk Fe−C forming the Cr2O3-rich protective layer. Here we extend the long-practiced passivation concept to Si anodes for lithium-ion batteries, incorporating the passivator of LiF/Li2CO3 into bulk Si. The passivation mechanism is studied by various ex situ characterizations, redox peak contour maps, thickness evolution tests, and finite element simulations. The results demonstrate that the passivation can enhance the (de)lithiation of Li-Si alloys, induce the formation of F-rich solid electrolyte interphase, stabilize the Si/LiF/Li2CO3 composite, and mitigate the volume change of Si anodes upon cycling. The 3D passivated Si anode can fully retain a high capacity of 3701 mAh g−1 after 1500 cycles and tolerate high rates up to 50C. This work provides insight into how to construct durable Si anodes through effective passivation.

02

March 10, 2023 Volume 8, Issue 3

标题

Electrodriven Chemical Looping Ammonia Synthesis Mediated by Lithium Imide

DOI

https://doi.org/10.1021/acsenergylett.2c02730

Abstract（上下滑动查看）

The chemical looping process for ammonia synthesis (CLAS) has advantages in avoiding competitive adsorptions of nitrogen and hydrogen and optimizing the thermodynamics and kinetics of a reaction step by step. Nitrogen carriers with favorable thermodynamic and kinetic properties are critical for such a process, especially under mild conditions. Recent studies have shown that alkali- and alkaline-earth-metal imides are attractive nitrogen carriers; however, the equilibrium concentration of NH3 in the hydrogenation of imides to ammonia and hydrides is low at atmospheric pressure. Moreover, the reaction rate of nitrogen fixation on the hydrides is slow. Here, we show that an electrodriven CLAS (ECLAS) mediated by a lithium imide is feasible in a LiCl–NaCl–KCl eutectic electrolytic cell with a nickel-foam electrode. We demonstrate that the reactions of lithium imide hydrogenation and lithium hydride nitridation are both promoted by the input of electric energy. The average ammonia production rate over such an electrodriven CLAS is ca. 8 times higher than that of a thermal-driven CLAS.

03

March 8, 2023 Volume 23, Issue 5

标题

One-Dimensional Rod-like Tobacco Mosaic Virus Promotes Macrophage Polarization for a Tumor-Suppressive Microenvironment

DOI

https://doi.org/10.1021/acs.nanolett.2c03809

Abstract（上下滑动查看）

The phenotype of tumor-associated macrophages plays an important role in their function of regulating the tumor immune microenvironment. The M1-phenotype macrophages display tumor-killing and immune activating functions. Here we show that the tobacco mosaic virus (TMV), a rod-like plant virus, can polarize macrophages to an M1 phenotype and shape a tumor-suppressive microenvironment. RAW 264.7 cells and bone marrow derived-macrophages (BMDMs) can recognize TMV via Toll-like receptor-4, and then the MAPK and NF-κB signaling pathways are activated, leading to the production of pro-inflammatory factors. Furthermore, the in vivo assessments on a subcutaneous co-injection tumor model show that the TMV-polarized BMDMs shape a tumor-suppressive microenvironment, resulting in remarkable delay of 4T1 tumor growth. Another in vivo assessment on an established tumor model indicates the high tumor-metastasis-inhibiting capacity of TMV-polarized BMDMs. This work suggests a role for this plant virus in macrophage-mediated therapeutic approaches and provides a strategy for tumor immunotherapy.

04

Volume 13 (2); 2023

标题

Enhancer RNA promotes resistance to radiotherapy in bone-metastatic prostate cancer by m6A modification

DOI

https://www.thno.org/v13p0596

Abstract（上下滑动查看）

Rationale: Prostate cancer metastasizes to the bone with the highest frequency and exhibits high resistance to 177Lu-prostate-specific membrane antigen (PSMA) radioligand therapy. Little is known about bone metastatic prostate cancer (mPCa) resistance to radiation.

Methods: We filtered the metastatic eRNA using RNA-seq, MeRIP-seq, RT-qPCR and bioinformation. Western blot, RT-qPCR, CLIP, co-IP and RNA pull-down assays were used for RNA/protein interaction, RNA or protein expression examination. MTS assay was used to determine cell viability in vitro, xenograft assay was used to examine the tumor growth in mice.

Results: In this study, we screened and identified bone-specific N6 adenosine methylation (m6A) on enhancer RNA (eRNA) that played a post-transcriptional functional role in bone mPCa and was correlated with radiotherapy (RT) resistance. Further data demonstrated that RNA-binding protein KHSRP recognized both m6A at eRNA and m6Am at 5'-UTR of mRNA to block RNA degradation from exoribonuclease XRN2. Depletion of the MLXIPe/KHSRP/PSMD9 regulatory complex inhibited tumor growth and RT sensitization of bone mPCa xenograft in vitro and in vivo.

Conclusions: Our findings indicate that a bone-specific m6A-modified eRNA plays a vital role in regulating mPCa progression and RT resistance and might be a novel specific predictor for cancer RT.

Keywords: Bone metastatic prostate cancer, m6A, Enhancer RNA, m6Am, Radiotherapy.

05

Volume2, Issue3 November, 2022

06

Volume41, Issue5 1 March, 2023

标题

Inside Back Cover

DOI

https://doi.org/10.1002/cjoc.202390054

Abstract（上下滑动查看）

The inside back cover picture showed the liquid-liquid interface (LLI) self-assembly structure as a new substrate for analytical sensing. There were two methods to promote self-assembly at the LLI. On the one hand, strategies for promoting assembly of NPs at the LLI have been developed through the addition of chemical modifiers, promoters, or external voltage. On the other hand, in order to avoid the potential interferences of chemical promoters, shaking organic solution and aqueous solution was proposed as an alternative way to form uniform NPs array at the LLI based on emulsification mechanism. Such strategies to fabricate uniform SERS substrate based on the LLI were demonstrated to be efficient to improve the reproducibility of SERS analysis, which are potentially applicable for practical applications. More details are discussed in the article by Zhang et al. on page 569—580.

07

Issue 5, March 07 2023

08

Volume43, Issue9 2022

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