NATURE MATERIALS
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2026
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IF 38
Cao Qiannan,Yao Yingli,Zheng Wenming,Liu Hongqian,Jiang Mingxia,Xie Dayang,Zhang Siting,Su Pijun,Yuan Huilin,Chen Xiaoyuan,Fang Huapan,Tian Huayu
The clinical success of chimeric antigen receptor (CAR) T cell therapy requires scalable, non-invasive strategies for in vivo T cell engineering. Although mRNA delivery offers a promising alternative, lipid-nanoparticle-based carriers show limited efficiency for in vivo T cell transfection and typically require antibody conjugation. Here we report an inherent T cell-activating polymer–lipid nanoparticle that enables ligand-free, efficient mRNA transfection and activation of T cells in vivo. This mRNA delivery vehicle, composed of p -toluenesulfonyl arginine (RT)-modified oligoethylenimine-based lipid nanoparticles (ERTLNPs), preferentially mediated mRNA transfection in the spleen following systemic administration. Without exogenous stimulation, ERTLNPs intrinsically activated T cells, triggering robust mRNA expression and proliferation. Mechanistically, ERTLNPs engaged the PI3K/AKT/mTOR signalling axis to reprogram T cell metabolism, promoting expansion and restraining exhaustion. The systemic delivery of mRNA encoding fibroblast activation protein CAR via ERTLNPs contributed to the in situ generation of functional CAR T cells, which efficiently eliminated pathological fibroblasts in models of cancer and fibrosis, with minimal off-target effects. This ligand-free, metabolically reprogramming mRNA delivery system provides a clinically translatable approach for in vivo CAR T cell generation.
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高影响因子
CELL CYCLE
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2026
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IF 3.9
Yan Liu,Yue-Qi Geng,Li Jiang,Ai-Chun Liu
Multiple myeloma (MM) is an incurable malignancy of bone marrow plasma cells. Tumor-associated macrophages (TAMs) are the predominant immune cells in the bone marrow microenvironment of MM and play important roles in MM. The effect of RBMS1 on MM has not yet been reported. This study aimed to investigate the function of RBMS1 in MM. Through the analysis of GSE datasets, we identified RBMS1 as a potential pathogenic factor in MM. We further investigated the effects of RBMS1 on the proliferation of MM cells (RPMI8226, MM1S, and KMS11) and its regulation of TAM polarization. An animal model was established by intravenous injection of MM cells into 6-week-old male NOG mice. Bioinformatics analyses, including RRA, WGCNA, and GO enrichment, screened for potential pathogenic genes in MM. Kaplan – Meier survival identified RBMS1 as a prognostic marker associated with poor outcomes in MM. Functionally, RBMS1 enhanced MM cell proliferation, colony formation, and cell cycle. Moreover, RBMS1 promoted M2 polarization of macrophages, as evidenced by elevated levels of M2 macrophage markers, as well as increased CCL2 secretion. Consistently, in a male NOD/Shi-scid IL-2 Rγnull mouse xenograft model, RBMS1 accelerated tumor growth and enhanced M2 macrophage polarization. Mechanistically, RBMS1 bound to the 3’UTR of PDPK1 mRNA, enhancing its stability and activating the pro-tumorigenic β-catenin signaling pathway, thereby promoting tumor growth. Collectively, this study is the first to report the functional role of RBMS1 in MM and highlights the importance of the RBMS1/PDPK1/β-catenin signaling axis in MM, providing new insights for basic research on MM.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Liang Liu,Siyu Liu,Qiaobian He,Chengxiu Sun,Yisha Li,Shengran Li,Xifei Yu
Dendrimer-functionalized LNPs provide a strategy to enhance tumor vaccine efficacy. • Choline phosphate-modified PAMAM improves biosafety and mRNA transfection efficiency. • PC7A-modified dendrimers activate STING signaling and promote DC maturation. Polyamine-based lipid nanoparticles (LNPs) are considered a highly promising strategy for tumor therapy due to their exceptional endosomal release and cytoplasmic transfection efficiency. However, the high density of amino groups in polyamine-based lipid nanoparticles leads to low biosafety and immunogenicity, resulting in suboptimal tumor efficacy. Here, we report functional components synthesized by modifying polyamide amine (PAMAM) dendrimers with choline phosphate (CP) group, linoleic acid chains (L18), and a nitrogenous heterocycles (PC7A) molecule to enhance the mRNA delivery efficiency and immunogenicity against tumors associated with standard LNPs. Incorporating functional components into LNPs enables the effective disruption of endosomal structures—while ensuring biosafety—thereby facilitating the efficient and stable delivery of antigenic mRNA. Simultaneously, PC7A, acting as an activator of interferon gene stimulating factors, promotes dendritic cells (DCs) maturation, further enhancing the immunogenicity of LNPs. After the injection of the nanovaccines into mice, the massive generation and recruitment of tumor-specific cytotoxic T cells further enhanced the efficacy of immunotherapy, providing a new strategy for the synergistic enhancement of LNP-based functional components in tumor vaccines. Modifying dendrimers with choline phosphate (CP) groups, linoleic acid (L18), and nitrogen-containing seven-membered heterocyclic molecule (PC7A) can effectively improve the performance of mRNA-LNPs. These enhancements include reduced biotoxicity, increased endosome escape, and STING pathway activation-mediated immunogenicity, which can effectively improve the efficacy of vaccines in cancer treatment. Download: Download high-res image (133KB) Download: Download full-size image
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高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Xiuguang Wang,Qiao Luo,Bojin Cao,Heng Bai,Yaru Jia,Jiangfeng Ge,Shuxiang Wang,Yuhua Weng,Luwei Li,Kun Ge,Xing-Jie Liang,Jinchao Zhang
Ionizable lipidoids show high delivery efficiency and tunable organ selectivity in the lipid nanoparticle (LNP) platform, but limited substrate options constrain their structural variety and performance. This study presents a regio-divergent strategy combining ring-opening and Michael addition reactions of diamines to construct a preliminary library of fifteen ionizable lipidoids from three starting materials: diamine, acrylate, and epoxide. Within this library, scaffold 3T2 exhibited excellent delivery efficiency. Further linker and hydrophobic tail optimization led to E16N4Ac18, which showed spleen-targeting after systemic administration. Inhalation delivery of mRNA@E16N4Ac18-LNPs achieved a 2.4-fold higher transfection efficiency than commercial SM-102. This regio-divergent approach offers a conceptual and practical framework for mRNA delivery lipidoid design.
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高影响因子
EUROPEAN POLYMER JOURNAL
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2026
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IF 6.8
Ruijun Wang,Saqirila Saqirila,Ying Zhao,Hangai Bai,Yonghui Wang,Hai Xiao,Huricha Baigude,Naikang Gao
Aminated curdlan derivatives are excellent carriers for delivery of short interfering RNA (siRNA), but their efficiency for mRNA delivery has not been explored. Degradable polymers like poly(β-amino ester) can deliver mRNA due to their biodegradability which is essential for timely release of mRNA cargo upon entering the cell. Herein, we report the synthesis of curdlan derivatives bearing α- or β-amino ester branches for brain targeted mRNA delivery. The β-amino ester functionalized curdlan (denoted by 6AC-MEP) efficiently encapsulated mRNA to form polymeric nanoparticles (PNPs), which readily entered neural cells and initiated the expression of cargo mRNA in vitro . In mouse traumatic brain injury (TBI) model, systemic administration of 6AC-MEP PNPs carrying luciferase mRNA resulted in the strong luminescent signal in the perilesional region of the brain. Two consecutive administrations of 6AC-MEP PNPs loaded with brain-derived neurotrophic factor (BDNF) mRNA resulted in strong expression of BDNF in the ipsilateral hemisphere of TBI mouse brain. The overexpression of BDNF in the brain reduced TBI-induced edema in the brain and improved cognitive function. Taken together, our data suggested 6AC-MEP PNP is a promising carrier for targeted delivery of therapeutic mRNAs.
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高影响因子
Cancer & Metabolism
·
2025
·Vol. 13
·期 1
·1-17
·
IF 5.3
Li Hao,Gong Tingyue,Zhao Yongheng,Luo Yang,Tang Shuibin,Wang Tingfeng,Lin Haiping,Zhong Ming
Purpose Cancer cells rely on serine biosynthesis for growth, but its regulation in colorectal cancer (CRC) remains not well understood. This study identifies the m 5 C methyltransferase NSUN2 (NOP2/Sun domain family, member 2) as a key regulator of serine biosynthesis, revealing a novel mechanism driving CRC progression. Methods The expression and prognostic value of NSUN2 were evaluated using bioinformatics analyses and immunohistochemistry (IHC) assays. The effects of NSUN2 on cellular serine biosynthesis, intracellular reactive oxygen species (ROS) levels, and apoptosis levels were analyzed both in vitro and in vivo. Additionally, RNA sequencing, Methylated RNA Immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP), and RNA stability assays were utilized to screen and validate the association between NSUN2 and phosphoglycerate dehydrogenase (PHGDH). Results NSUN2 was found to be highly expressed in CRC and associated with poor patient survival. PHGDH, a direct downstream target of NSUN2, plays a crucial role in NSUN2-mediated serine biosynthesis. Furthermore, inhibition of NSUN2 significantly reduced the intracellular NADH/NAD + and NADPH/NADP + ratios, leading to an increase in ROS levels and apoptosis levels, thereby inhibiting CRC progression. Additionally, NSUN2 enhances PHGDH expression and mRNA stability by binding to the “reader” protein m 5 C-Aly/REF export factor (ALYREF). Conclusions This study identified a novel NSUN2/ALYREF/m 5 C-PHGDH axis might be promising therapeutic targets for CRC.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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RNA生物学
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代谢调控
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PubMed
高影响因子
CELL RESEARCH
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2026
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IF 25.9
Liao Kun,Cao Fen,Wei Chen,Qian Zheng-Yu,Hu Hong-Rong,Pan Wen-Feng,Feng Zi-Qing,Lian Sen-mao,Xiao Zi-Xuan,Sheng Hui,Mo Hai-Yu,Zhao Yi-Xuan,Wu Qi-Nian,Zeng Zhao-Lei,Li Bo,Xu Rui-Hua,Ju Huai-Qiang
Methionine metabolism generates the substrate S-adenosylmethionine (SAM), which regulates epigenetic modifications crucial for various cellular processes, particularly tumorigenesis. However, whether methionine metabolism involves epigenetic mechanisms independent of SAM and what roles such mechanisms play in tumorigenesis remain unclear. We show here that the adenosylhomocysteinase (AHCY)–adenosine complex increases mRNA m 6 A levels in a non-global manner, promoting fatty acid synthesis and tumorigenesis. Adenosine increases mRNA m 6 A levels by binding to the methionine metabolism enzyme AHCY to form a complex, rather than depending on adenosine receptors. The AHCY–adenosine complex facilitates AHCY dimerization, with adenosine being crucial for dimer stability. AHCY dimers hinder the binding of fat mass and obesity-associated protein (FTO) at the Q86 site to RNA containing the VWDRACH motif, increasing m 6 A levels and upregulating lipogenesis genes, especially ACACA and SCD1, thus leading to reprogramming of lipid metabolism. Conversely, AHCY mutants that have lost dimerization or FTO-binding ability but retain hydrolase activity suppress lipogenesis and tumor growth without significantly affecting methionine catabolism mediated by AHCY. Loss of AHCY in mice and disruption of AHCY dimerization in tumor cells and patient-derived xenograft models restricted tumor growth. Our findings demonstrate a key SAM-independent link between methionine metabolism and mRNA m 6 A modification that affects demethylase substrate specificity. This novel link between the methionine cycle and lipid metabolism suggests new strategies for anticancer therapy.
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高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Hui Li,Siyi Pan,Xiaoyun Xu
Flavonoids are natural active components. They distribute widely in edible plants with high activity of anti-inflammation. Inhibition of cyclooxygenase-2(COX-2) was determined by real-time fluorescent quantitative olymerase chain reaction (RTFQ-PCR). And structure characteristics of flavonoids for COX-2 inhibition were mainly analyzed by a quantitative structure activity relationship (QSAR) model. Descriptors such as SMR_VSA5, vsurf_DD12, reactive were the top three important independent variables to COX-2 mRNA inhibiton in RAW264.7. Low SMR_VSA5 value meant a lower molecular refractivity resulting in a lower COX-2 mRNA inhibition. High vsurf_DD12 value related to poor molecular balance and showed profound adverse to COX-2 mRNA inhibition. Reactive group in this paper referred to C2–C3 double bond contributed negatively to COX-2 mRNA inhibition. Glycosidic and C3–OH substitutions may lower SMR_VSA5 value. It indicated that flavanones such as hesperetin , naringenin , liquiritigenin were efficient to repress COX-2 mRNA and they were potential anti-inflammatory natural products. Further, substitution with a glucopyranosyl at C-6 resulted in a poorer molecule balance than that at C-8 and a lower COX-2 mRNA inhibiton accordingly. This may expain why orientin and vitexin exhibited better anti-inflammatory activity than their isomers homoorientin and isovitexin . Also, methoxyl groups at C-4’ may also be a favorable flavonoid structural characteristic for COX-2 mRNA inhibiton. These results provide valuable information on understanding the high anti-inflammatory activity of flavonoids.
研究领域:
药理学
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分子生物学
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化学
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PubMed
高影响因子
CELLULAR SIGNALLING
·
2025
·
IF 3.7
Qiuyun Wu,Qianyi Zhang,Chunmeng Jin,Xue Liu,Hongmin Yu
Background Silicosis, one of the serious occupational diseases, is mainly manifested by pulmonary fibrosis induced by long-term exposure to silica particles in workplace. Evidence demonstrates that circular RNAs (circRNAs) are interesting regulators of pulmonary fibrosis process. So, further elucidation of the role of circRNAs may provide a new perspective into mechanisms driving pulmonary fibrosis and silicosis. Methods The characteristics of circRNA homer scaffold protein 1 (hsa_circ_0006916, circHOMER1) was assessed using Actinomycin D, RNase R, and nucleoplasmic separation assay. The histopathological examination and Enzyme-linked immunosorbent assay (ELISA) were used to confirm circHOMER1 function in mouse lung tissues under silica particle exposure. The expression of circHOMER1, human antigen R (HuR) and NADPH oxidase 4 (NOX4) was identified by western blot or RT-qPCR assay. The RNA immunoprecipitation (RIP) assay and plasmid co-transfection were used to analyze the interaction between circHOMER1, HuR and NOX4. Results We confirmed an upregulated circHOMER1 in silicosis fibrosis. Functional assays showed that the knockdown of circHOMER1 suppressed the viability of fibroblasts and the production of fibrotic molecules and alleviated the histology fibrotic changes in lung tissues from mouse exposed to silica particles. Mechanistically, we found that circHOMER1 directly bound to HuR and promoted its protein expression in fibroblasts. And, circHOMER1 further regulated HuR/NOX4 signaling axis through HuR to stabilize NOX4 mRNA, which enhanced the production of reactive oxygen species (ROS), thereby promoting the silicosis fibrosis process. Conclusion This study revealed the role of circHOMER1 in silica-induced pulmonary fibrosis, suggesting that the inhibition of circHOMER1 may be a potential therapeutic approach to relieve the pathological process of silicosis.
研究领域:
分子生物学
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肺病学
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职业医学
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PubMed
高影响因子
CYTOKINE
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2023
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IF 3.8
Wei Liu,Hui Zeng
Background Ulcerative colitis (UC) is a chronic and uncontrolled inflammatory bowel disease. N 6 -methyladenine (m 6 A) is a reversible mRNA modification method. IGF2BP2 is an RNA-binding protein regulated by m 6 A methylation. However, understanding of m 6 A-related proteins in UC is limited. This study was to analyze the function and related mechanism of IGF2BP2 in UC. Methods The UC models were established by dextran sulfate sodium (DSS) in NCM460 cells and mice. The expression of IGF2BP2 and GPX4 in UC were detected by qPCR and western blot. The effects of IGF2BP2 on inflammation, ferroptosis and colon injury were measured by gain- and loss-of-function experiments. This study conducted a clinical evaluation of mice using the Disease Activity Index score. The molecular mechanism of IGF2BP2 in ferroptosis were analyzed by m 6 A RNA methylation quantification kit, RNA immunoprecipitation-qPCR analysis, and RNA stability assay. Results IGF2BP2 and GPX4 were under-expressed in DSS-treated UC. IGF2BP2 enhanced the stability of GPX4 mRNA modified by m 6 A. IGF2BP2 overexpression repressed the ROS, MDA, and iron levels but enhanced the GSH and GPX4 levels in DSS-triggered NCM460 cells, which were partially reversed by GPX4 silencing. In UC mice, IGF2BP2 high-expression ameliorated symptoms, Disease Activity Index score, pathological changes, inflammatory reaction, and ferroptosis, which were also partly neutralized by GPX4 inhibition. Conclusions IGF2BP2 augmented the GPX4 expression by the m 6 A modification to weaken UC progression via suppressing ferroptosis.
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高影响因子
Cancer Biomarkers
·
2019
·Vol. 24
·期 4
·469-475
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IF 2.859
Qin Yujing,Li Wenxue,Long Yingli,Zhan Zhijia
OBJECTIVE: This study aims to determine the correlation between p-cofilin expression and cisplatin resistance in patients with ovarian cancer, and also to investigate the role of p-cofilin in prognosis. PATIENTS AND METHODS: The ovarian cancer cell line A2780/DDP resistant to cisplatin was prepared. The cell resistance to cisplatin was measured via MTT assay. The cell invasion capacity was identified via Transwell assay. The mRNA expression and protein level was evaluated via semi-quantitative PCR and Western blot, respectively. The tumor tissues of patients with cisplatin-resistant ovarian cancer were collected. The relationship between prognosis and p-cofilin expression was analyzed. RESULTS: The growth rate of A2780 was similar to that of A2780/DDP. The sensitivity of A2780 to cisplatin was significantly higher than that of A2780/DDP (p< 0.01). The migration capacity of A2780/DDP was significantly increased compared to that of A2780 (p< 0.01), indicating that the cisplatin-resistant cell lines were successfully constructed. Both CFL1 mRNA level and p-cofilin level in A2780/DDP was significantly higher than that in A2780 (p< 0.01). The p-cofilin level in cancer tissues in patients with cisplatin-resistant ovarian cancer was significantly higher than that in patients with cisplatin-sensitive ovarian cancer (p< 0.01). The cisplatin resistance was positively correlated with the p-cofilin expression level (r= 0.802, p= 0.023). The survival time of patients with normal or low level of p-cofilin was significantly longer than that of patients with high expression. CONCLUSION: The cisplatin resistance of ovarian cancer is closely related to the expression level of p-cofilin, which affects the prognosis of patients with ovarian cancer.
研究领域:
肿瘤学
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分子生物学
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癌症研究
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PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2023
·
IF 8.9
Xuanjun Guo,Ruihua Zhang,Qian Jin,Niannian Cao,Jingjing Shi,Xingxing Zong,Xuejun Chen,Chen Wang,Xuefeng Li,Sen Pang,Liqin Li
Azoxystrobin, a strobilurin widely used to control rice diseases, has raised concerns about possible adverse effects on aquatic ecosystems. At present, very little is known about the effects of azoxystrobin on courtship and aggressive behavior and the potential underlying mechanisms. In the present study, after exposing adult male and female zebrafish to worst-case scenario concentrations of azoxystrobin (0, 2 μg/L, 20 μg/L, and 200 μg/L) for 42 d, we observed a decrease in courtship behavior and an increase in aggressive behavior in both male and female zebrafish. In addition, to elucidate the molecular mechanism of the behavioral effects of azoxystrobin, we quantified the changes in the concentrations of kisspeptin, 5-HT, GnIH, and their corresponding receptor mRNA expression in the brain. The results showed that 200 μg/L azoxystrobin decreased the concentrations of kisspeptin and increased the concentration of GnIH in both male and female zebrafish brain. In addition, azoxystrobin also significantly reduced 5-HT concentration in female zebrafish brain. Further investigation revealed that altered courtship and aggressive behavior were associated with the expression levels of genes (kiss1, kiss2, gnrh3, gnrhr3, 5ht1a, and 5ht2a) involved in kisspeptin-GnIH signaling pathway. In conclusion, our study suggested that azoxystrobin may impair courtship and aggressive behavior in zebrafish by interfering with the kisspeptin-GnIH signaling pathway, which may have more profound effects on natural zebrafish populations.
研究领域:
环境毒理学
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行为生物学
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神经内分泌学
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PubMed
高影响因子
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