RNA modifications play pivotal roles in regulating RNA metabolism. Notably, they do not function in isolation, but crosstalk with DNA/protein modifications and other RNA modifications to form multi-layered regulatory networks that cooperatively fine-tune gene expression. In this review, we propose a two-dimensional, mutually exclusive “cis/trans” and “direct/indirect” framework to delineate the mechanisms and functions of four reciprocal modification axes including RNA-DNA, RNA-histone, RNA-non-histone, and RNA-RNA interactions. Furthermore, this RNA modification-centered crosstalk provides groundbreaking insights into translational applications across disease therapy, tissue engineering, and plant biotechnology. We also address current technical challenges and outline future directions to accelerate translational research.

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for safe and effective imaging tools to improve early diagnosis. In this study, we developed a hepatocyte-targeted T2 MRI contrast agent by functionalizing superparamagnetic iron oxide nanoparticles (SPIONs) with an ethoxybenzyl-polyethylene glycol ligand, yielding Fe3O4-EOB-PEG2000 NPs, inspired by the hepatocyte-selective features of Gd-EOB-DTPA. In vitro studies demonstrated preferential uptake of Fe3O4-EOB-PEG2000 NPs by hepatocytes over tumor cells, while in vivo imaging in both hepatocellular carcinoma and colorectal liver metastasis models revealed a distinct "black-liver/bright-tumor" contrast effect. Compared with nontargeted Fe3O4-mPEG2000 NPs, Fe3O4-EOB-PEG2000 NPs showed significantly improved tumor visibility in T2-weighted images. Furthermore, Fe3O4-EOB-PEG2000 NPs exhibited good biocompatibility and biosafety. This work highlights a strategy for enhancing T2 MRI contrast through hepatocyte targeting, providing a promising gadolinium-free alternative for safe and effective safe and effective diagnosis of liver tumors.

Iodine‐125 ( 125 I) brachytherapy, in combination with chemotherapy, is extensively utilized for tumor treatment. However, the primary challenge in concurrently implementing brachy‐chemotherapy involves integrating the in situ implantation of 125 I seeds with the systematic administration of chemotherapeutic agents. Therefore, a novel 125 I seed modified with titanium dioxide nanotubes ( 125 I@TNT) is proposed to establish a localized drug release system. The titanium dioxide nanotubes are fabricated through anodic oxidation, exhibiting a uniform diameter of ≈100 nm and a thickness of 1 µm. These nanotubes effectively loaded doxorubicin (29.16 µg DOX/seed) while meeting the quality standards for subsequent applications, such as outer diameter and leak‐proofness properties ( 125 I@TNT loaded with DOX is named 125 I@TNT‐DOX). In vivo distribution studies revealed that 125 I@TNT‐DOX delivered significantly more DOX concentrations to tumors compared to free DOX administered intravenously (5 mg kg −1 ) while delivering less DOX in the heart. Both in vitro and in vivo studies confirmed that apoptosis is the primary mechanism of cell death induced by 125 I@TNT‐DOX. Additionally, 125 I@TNT‐DOX effectively suppressed the growth of subcutaneous tumors in 4T1 and Hepa1‐6 tumor‐bearing mouse, surpassing other treatments, particularly the combination of 125 I seeds and intravenously administered DOX (5 mg kg −1 ). This system offers a promising strategy for enhancing concurrent brachy‐chemotherapy.

Iron plays a vital role in physiological processes due to its high oxygen affinity and efficient redox capability. However, perturbations in iron homeostasis, particularly in its labile forms that drive oxidative stress, have been implicated in a spectrum of pathologies, including infectious diseases, malignancies, and neurodegenerative disorders. Despite the critical importance of detecting labile Fe2+, conventional fluorescent and bioluminescent probes are constrained by inherent limitations, such as suboptimal sensitivity, elevated background noise, and inadequate tissue penetration depth. To overcome these challenges, we report the development of a novel caged luciferin analogue, O-Akalumine (O-Aka), designed with an Fe2+-specific switchable N-oxide bond to enable turn-on near-infrared (NIR) bioluminescence imaging of labile Fe2+. The bioluminescence emitted by O-Aka in the presence of native firefly luciferase is centered in the NIR spectrum (Amax = 677 nm), substantially improving signal penetration through biological tissues. Exhibiting low intrinsic background noise, high sensitivity, and deep tissue imaging capability, O-Aka effectively visualized exogenous Fe2+ in cellular models and a murine breast cancer model, as well as endogenous Fe2+ in an acute cardiac injury model. These results underscore the utility of O-Aka as a robust bioluminescent probe for elucidating the physiological and pathological roles of Fe2+ and exploring its potential anticancer mechanisms.

A hydroxyl radical-specific fluorescent probe, CC-7, enables selective, real-time visualization of intracellular ˙OH levels in cancer therapy.

Reactive oxygen species (ROS), including hydroxyl and superoxide radicals, play crucial roles in disease development and are recognized as indicators for cancer and inflammation. Although these radicals possess paramagnetism due to unpaired electrons, their high reactivity and low in vivo concentrations challenge MRI detectability. In this study, we utilized iron-titanium dioxide nanodots modified by citric acid (Fe-TiO2-CA) as catalysts in the Fenton reaction to efficiently convert hydrogen peroxide, a diamagnetic molecule, into paramagnetic hydroxyl radicals. This conversion maintained the concentration of hydroxyl radicals within the detectable range for MRI. Our results demonstrated that Fe-TiO2-CA significantly shortened the T1 relaxation time in H2O2 solutions. Importantly, this approach successfully enabled in vivo imaging of areas with elevated hydrogen peroxide concentrations typical of cancerous and inflamed tissues. These findings highlight the potential of Fenton reaction catalysts as innovative diagnostic tools for MRI-based detection of diseases with elevated hydrogen peroxide levels.

Small-cell neuroendocrine cervical carcinoma (SCNCC) is a rare yet aggressive gynecological malignancy associated with dismal clinical outcomes. Its rarity has led to a limited number of retrospective studies and an absence of prospective research, posing significant challenges for evidence-based treatment approaches. As a result, most gynecologic oncology centers have limited experience with this tumor, emphasizing the urgent need for a comprehensive review and summary. This article systematically reviews the pathogenesis, immunohistochemical and molecular characteristics, prognostic factors, and clinical management of gynecologic SCNCC. We specifically focused on reviewing the distinct genomic characteristics of SCNCC identified via next-generation sequencing technologies, including loss of heterozygosity (LOH), somatic mutations, structural variations (SVs), and microRNA alterations. The identification of these actionable genomic events offers promise for discovering new molecular targets for drug development and enhancing therapeutic outcomes. Additionally, we delve deeper into key clinical challenges, such as determining the optimal treatment modality between chemoradiation and surgery for International Federation of Gynecology and Obstetrics (FIGO) stage I phase patients within a precision stratification framework, as well as the role of targeted therapy within the homologous recombination (HR) pathway, immune checkpoint inhibitors (ICIs), and prophylactic cranial irradiation (PCI) in the management of SCNCC. Finally, we anticipate the utilization of multiple SCNCC models, including cancer tissue-originated spheroid (CTOS) lines and patient-derived xenografts (PDXs), to decipher driver events and develop individualized therapeutic strategies for clinical application.

目的 检测ATR抑制剂VE-822对人乳腺癌细胞MCF-7的细胞增殖、周期及凋亡的影响,初步探讨其机制.方法 采用对数生长期的人乳腺癌细胞MCF-7,给予不同浓度梯度ATR抑制剂VE-822干预24h、48h、72h,DMSO为对照组.CCK-8法检测各组MCF-7细胞增殖抑制情况,流式细胞术(Flowcytometry,FCM)检测其对细胞周期及凋亡的影响,并采用western blot检测p-ATR、p-chk1、BRCA1、rad51、γ-H2AX蛋白的表达.结果 VE-822处理组较DMSO对照组的MCF-7细胞增殖抑制率随药物浓度的增加而呈现剂量依赖效应,差异有统计学意义(P<0.05).实验组中MCF-7细胞发生G1/S期阻滞,并伴有细胞凋亡增加,差异有统计学意义(P<0.05).实验组中p-ATR、p-chk1、BRCA1、rad51蛋白含量较对照组降低,差异有统计学意义(P<0.05).实验组中 γ-H2AX蛋白含量较对照组升高,差异有统计学意义(P<0.05).结论 ATR抑制剂VE-822可明显抑制体外人乳腺癌细胞MCF-7增殖、诱导细胞周期阻滞和细胞凋亡,其机制可能与抑制同源重组修复(homologous recombinational repair,HRR)和非同源重组修复(non-homologous end joining,NHEJ)有关.

Cervical cancer remains one of the main factors leading to tumor-related death worldwide. Many strategies of cancer treatment such as chemotherapy are developed and used nowadays. However, for the cancer chemotherapy resistance, reduction of the limitation of cancer chemotherapy efficacy is one of the aims of several oncology teams. Moreover, the cyclin-dependent kinase 4/6-cyclin D-retinoblastoma protein-E2F pathway is an important mechanism for cell cycle control and its dysregulation is one of the key factors for cancers development including cervical cancer. Ribociclib is one of the selective CDK4/6 inhibitors and is a new therapeutic approach showing promise as a good strategy of therapy in many human cancers. However, there are not the studies regarding the investigation of effects of Ribociclib in cervical cancer yet. In the present study, by western blotting and immunofluorescence assay, we found respectively that CDK4, CDK6 and cyclin D1 are highly expressed and are mostly localized in the nucleus with some localized in the cytoplasm of cervical cancer cell lines. Moreover, Ribociclib induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited C33A cell proliferation in dose - dependent manner following by decreased expression of certain related genes such as CDK4, CDK6, E2F1, P-Rb, and increased Bax expression. In C33A xenografts, Ribociclib inhibited tumor growth associated with decreased expressions of CDK4, CDK6, cyclin D1, Rb and Ki-67, and also significantly increased tumor cell apoptosis. However, we didn't find side effect of Ribociclib concerning heart, liver and kidney perturbation and any Ribociclib anti-tumor effects on HeLa in vitro and in vivo which may be due to Hela cell infection by HPV. Based on our findings, the Rb-E2F pathway can be considered as an important factor in human cervical cancer pathogenesis and as a mechanism of Ribociclib, a potential strategy of treatment for the improvement of new therapeutic measures for the treatment of HPV-negative cervical cancer which application for HPV-positive cervical cancer is desired in further study.

Ubiquitinating enzyme damaged-DNA binding protein 2 (DDB2) is a rind of DDB1 and CUL4-associated factors (DCAF), and identifies belonging to the family of ubiquitinating E3 enzymes. DDB2 combines with CUL4-DDB1 to form the ubiquitin ligase complex, and identifies targets protein substrate specificity to make the substrate ubiquitin and degradation. It affects the development of tumors through various pathways, such as DNA damage repair, cell cycle regulation and apoptosis, cell invasion and metastasis, cell premature senescence, cell proliferation and cancer stem cell population. This paper reviews the progress of the relationship between DDB2 and the development, treatment and prognosis judgment of tumors.

Clear cell renal cell carcinoma (ccRCC) is one of the most common malignant carcinomas and its molecular mechanisms remain unclear. Long noncoding RNA (lncRNA) could bind sites of miRNA which affect the expression of mRNA according to the competing endogenous (ceRNA) theory. The aim of the present study was to construct a ceRNA network and to identify key lncRNA to predict survival prognosis. We identified differentially expressed mRNA, lncRNA and miRNA between tumor tissues and normal tissues from The Cancer Genome Atlas database. Then, using bioinformatics tools, we explored the connection of 89 lncRNA, 10 miRNA and 22 mRNA, and we constructed the ceRNA network. Furthermore, we analyzed the functions and pathways of 22 differentially expressed mRNA. Then, univariate and multivariate Cox regression analyses of these 89 lncRNA and overall survival were explored. Nine lncRNA were finally screened out in the training group. The patients were divided into high-risk and low-risk groups according to the 9 lncRNA and low-risk scores having better clinical overall survival (P < .01). Furthermore, the receiver operating characteristic curve demonstrates the predicted role of the 9 lncRNA. The 9-lncRNA signature was successfully proved in the testing group and the entire group. Finally, multivariate Cox regression analysis and stratification analysis further proved that the 9-lncRNA signature was an independent factor to predict survival. In summary, the present study provides a deeper understanding of the lncRNA-related ceRNA network in ccRCC and suggests that the 9-lncRNA signature could serve as an independent biomarker to predict survival in ccRCC patients.