Research最新文献

{"title":"PRMT1-Mediated PARP1 Methylation Drives Lung Metastasis and Chemoresistance via P65 Activation in Triple-Negative Breast Cancer.","authors":"Jinhui Zhang, Zirui Huang, Cailu Song, Song Wu, Jindong Xie, Yutian Zou, Xiaoming Xie, Tao Wu, Han Yang, Hailin Tang","doi":"10.34133/research.0854","DOIUrl":"10.34133/research.0854","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, characterized by a high propensity for metastasis, poor prognosis, and limited treatment options. Research has demonstrated a substantial correlation between the expression of protein arginine N-methyltransferase 1 (PRMT1) and enhanced proliferation, metastasis, and poor outcomes in TNBC. However, the specific role of PRMT1 in lung metastasis and chemoresistance remains unclear. Single-cell RNA sequencing coupled with bioinformatics analysis was employed to identify pertinent genes within metastatic TNBC samples. Functional assays, including cell cycle, apoptosis, wound healing, Transwell migration, colony formation, and Cell Counting Kit-8 Assay (CCK-8), were conducted to evaluate the role of PRMT1. The interaction between PRMT1 and PARP1 was validated by mass spectrometry (MS) and immunoprecipitation. Downstream signaling pathways were explored, with a focus on P65 activation. Enzyme-linked immunosorbent assay was used to quantify the effect of PRMT1 on interleukin-1β secretion. Our study identified a significant association between elevated PRMT1 expression and both lung metastasis and chemoresistance in TNBC. PRMT1 boosts TNBC cell growth, invasion, and lung metastasis. Additionally, high PRMT1 expression contributed to increased resistance to docetaxel in TNBC. Mechanistically, PRMT1 methylates PARP1. On the one hand, this methylation promotes the DNA damage repair ability of PAPA1. On the other hand, it in turn modulates the NF-κB signaling pathway. This modulation enhances the stemness of tumor cells and induces immune suppression within the tumor microenvironment, thereby exacerbating chemoresistance in TNBC. PRMT1 drives lung metastasis and chemoresistance in TNBC through PARP1 methylation and P65 activation. These findings position PRMT1 as a promising biomarker and therapeutic target to overcome resistance and limit metastatic progression in TNBC.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0854"},"PeriodicalIF":10.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12415337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery-Graded Programmable Micelles Achieve Enhanced Tumor Starvation through Combined Glutamine Deprivation and Angiogenesis Inhibition.","authors":"Xuan Wei, Jiamin Cheng, Meijuan Geng, Siyu Chen, Liyang Gong, Siyu Meng, Keying Chen, Ziyan Wang, Zhang Yuan, Kaiyong Cai, Liangliang Dai","doi":"10.34133/research.0858","DOIUrl":"10.34133/research.0858","url":null,"abstract":"<p><p>The inhibition of dependent glutamine metabolism is an effective treatment for triple-negative breast cancer (TNBC) starvation, but it is limited by compensatory glycolysis and inadequate delivery efficiency. Herein, we construct a pH-responsive size/charge-reprogrammed micelle with hierarchical delivery characteristics for TNBC suppression with glutamine depletion and vessel blockade. It consists of a positively charged prodrug micelle chemically grafted with the glutamine transport inhibitor V9302 as the inner core layer, the neovascular disruptor CA4P adsorbed in the middle layer, and a pH-responsive peelable polymer as the outer shell. The nanosystem PPD/PPQV@C could effectively reduce size and reverse charge in response to the tumor acidic microenvironment by removing the outer polymer PPD, as accompanying the release of CA4P. Furthermore, the remaining PPQV could responsively release V9302 in the cytoplasm of tumor cells, improving the bioavailability of cargoes and overcoming permeability barrier through precise hierarchical release strategy. Importantly, V9302 and CA4P localized in the tumor intracellular and extracellular matrix could effectively block TNBC-dependent glutamine metabolism and inhibit compensatory nutrient by blocking angiogenesis, achieving the desired tumor suppression with prolonged survival time. This work exhibits a smart nanoplatform for efficient TNBC treatment via dual blockade of the dependent glutamine metabolism and angiogenesis.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"5 ","pages":"0858"},"PeriodicalIF":10.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411305/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Focusing on Microenvironmental Disturbance to Potentiate Reparative Ability of Neural Stem Cell After Stroke.","authors":"Hongfei Ge, Haomiao Wang, Rong Hu","doi":"10.34133/research.0829","DOIUrl":"10.34133/research.0829","url":null,"abstract":"<p><p>Ischemic stroke (IS), a common neurological disease, lacks satisfactory treatments worldwide. Neural stem cell (NSC) therapy is a promising strategy for stroke, while microenvironmental disturbance, including but not limited to acidosis, oxidative stress, and excessive neuroinflammation, restricts the therapeutic potential of endogenous and exogenous NSC post-IS. The present study introduces the effect of common disturbance on NSC and the underlying mechanism to screen out feasible methods aiming to potentiate the reparative capacity of NSC following IS.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0829"},"PeriodicalIF":10.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12411917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct Identification of O-Glycopeptides by Low-Temperature Assisted Nanopore Technique.","authors":"Jia-Hong Wang, Wenjing Ma, Zheng-Li Hu, Zhaobing Gao, Yi-Tao Long, Tiehai Li, Yi-Lun Ying","doi":"10.34133/research.0850","DOIUrl":"10.34133/research.0850","url":null,"abstract":"<p><p>O-glycopeptides are highly expressed in various human cancers and play a key role in cancer progression and metastasis, making them promising biomarkers for early diagnostics. However, the inherent complexity and heterogeneity of glycans pose a major challenge for the simultaneous and precise analysis of multiple glycopeptides. Here, we developed a low-temperature nanopore technique capable of simultaneously discriminating 4 truncated O-glycopeptides with varied glycoforms. This method enables the direct identification and relative quantification of O-glycopeptides from a mixture, achieving a discrimination accuracy of 92.9%. This general strategy holds promise for the label-free analysis of glycopeptide biomarkers, with potential applications in cancer diagnostics.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0850"},"PeriodicalIF":10.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12410930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"E-SegNet: E-Shaped Structure Networks for Accurate 2D and 3D Medical Image Segmentation.","authors":"Wei Wu, Xin Yang, Chenggui Yao, Ou Liu, Qi Zhao, Jianwei Shuai","doi":"10.34133/research.0869","DOIUrl":"10.34133/research.0869","url":null,"abstract":"<p><p>U-structure has become a foundational approach in medical image segmentation, consistently demonstrating strong performance across various segmentation tasks. Most current models are based on this framework, customizing encoder-decoder components to achieve higher accuracy across various segmentation challenges. However, this often comes at the cost of increased parameter counts, which inevitably limit their practicality in real-world applications. In this study, we provide an E-shaped segmentation framework that discards the traditional step-by-step resolution recovery decoding process, instead directly aggregating multi-scale features extracted by the encoder at each stage for deep cross-level integration. Additionally, we propose an innovative multi-scale large-kernel convolution (MLKConv) module, designed to enhance high-level feature representation by effectively capturing both local and global contextual information. Compared to U-structure, the proposed E-structured approach substantially reduces parameters while delivering superior performance, especially in complex segmentation tasks. Based on this structure, we develop 2 segmentation networks specifically for 2-dimensional (2D) and 3D medical images. 2D E-SegNet is evaluated on four 2D segmentation benchmark datasets (Synapse multi-organ, ACDC, Kvasir-Seg, and BUSI), while 3D E-SegNet is assessed on four 3D segmentation benchmark datasets (Synapse, ACDC, NIH Pancreas, and Lung). Experimental results demonstrate that our approach outperforms the current leading U-shaped models across multiple datasets, achieving new state-of-the-art (SOTA) performance with fewer parameters. In summary, our research introduces a novel approach to medical image segmentation, offering potential improvements and contributing to ongoing advancements in the field. Our code is publicly available on https://github.com/zhaoqi106/E-SegNet.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0869"},"PeriodicalIF":10.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteogenomic Analysis Identifies Clinically Relevant Subgroups of Collecting Duct Carcinoma.","authors":"Yuanyuan Qu, Xiaoru Pei, Jinwen Feng, Xin Yan, Linhui Zhang, Jun Wang, Xin Yao, Jiasheng Bian, Yu Gan, Hualei Gan, Xuewen Jiang, Ping Yang, Maoping Cai, Liqing Li, Xinqiang Wu, Weiwei Jing, Chao Zhang, Jianyuan Zhao, Hailiang Zhang, Guohai Shi, Xiang Zhou, Dingwei Ye, Chen Ding","doi":"10.34133/research.0859","DOIUrl":"10.34133/research.0859","url":null,"abstract":"<p><p>Collecting duct carcinoma (CDC) is a rare but aggressive form of renal cell carcinoma (RCC) that has limited understanding and an undefined systemic therapeutic regimen. Herein, we conducted a comprehensive proteogenomic analysis of CDC tumors and normal adjacent tissues to elucidate the biology of the disease. CDC exhibited high heterogeneity in tumor mutational burden, and enhanced ribosome biogenesis was the most striking malignant feature of CDC, even compared with other common kidney carcinomas. Genomic data indicated that <i>UTP6</i> and <i>HN1</i> amplification on chromosome 17q were associated with the activations of ribosome biogenesis and cell migration, respectively, which were relevant to tumor proliferation and metastasis. Proteomic-based classification identified 3 clusters, among which, tumors overexpressing ribosome biogenesis signaling (GP1) clustered into the most aggressive subtype, while tumors with increased energy metabolism (GP3) exhibited significant sensitivity to anti-vascular endothelial growth factor agents. Immune subtyping revealed a complex immune landscape of CDC. Additionally, increased RPF2, contributing to ribosome production, was validated to be associated with malignant phenotypes, and targeting RPF2 could exert an anti-oncogenic role by disrupting ribosome biogenesis and perturbing the MDM2-p53 interaction.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0859"},"PeriodicalIF":10.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ligustilide Suppresses Macrophage-Mediated Intestinal Inflammation and Restores Gut Barrier via EGR1-ADAM17-TNF-α Pathway in Colitis Mice.","authors":"Yanyang Li, Yequn Wu, Jing Liang, Peiqi Chen, Shihua Xu, Yumei Wang, Zhi Jiang, Xudong Zhu, Chaozhan Lin, Yang Yu, Hailin Tang","doi":"10.34133/research.0864","DOIUrl":"10.34133/research.0864","url":null,"abstract":"<p><p>Ulcerative colitis is a chronic nonspecific intestinal inflammatory disease, which usually occurs in the rectal and colonic mucosa and submucosa. Ligustilide, a major component derived from <i>Angelica sinensis</i> (Oliv.) Diels, exerts anti-inflammation effect. However, its impact and molecular mechanism on colitis remain obscure. In this study, in vivo and in vitro experiments verified that ligustilide protected against colitis by suppressing macrophage-mediated inflammation and repairing intestinal barrier. Of note, we utilized a thermal proteome profiling strategy to preliminarily find early growth response factor 1 (EGR1) as a target of ligustilide. Cellular thermal shift assay, drug affinity responsive target stability, and surface plasmon resonance analysis revealed that ligustilide directly targeted His386 to bind to EGR1. Furthermore, RNA-sequencing, dual luciferase reporter gene assay, and rescue experiments illustrated that ligustilide disturbed the nuclear translocation of EGR1 and broke its combination with a disintegrin and metalloproteinase 17 (ADAM17) promoter, thereby inhibiting ADAM17 transcription and downstream tumor necrosis factor-α (TNF-α) production, as well as expression of inflammatory proteins cyclooxygenase 2 and inducible nitric oxide synthase. Finally, the in vivo experiment with EGR1 overexpression proved that EGR1 was essential for the protective effects of ligustilide on colitis mice. Taken together, our study demonstrates that ligustilide targets EGR1 to inhibit the EGR1-ADAM17-TNFα pathway, thus alleviating macrophage-mediated intestinal inflammation and restoring gut barrier.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0864"},"PeriodicalIF":10.7,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3D Genome Engineering: Current Advances and Therapeutic Opportunities in Human Diseases.","authors":"Xing Jiang, Xiaoli Wang, Song Shen, Shangguo Hou, Chen Yu","doi":"10.34133/research.0865","DOIUrl":"10.34133/research.0865","url":null,"abstract":"<p><p>Dynamic chromatin 3-dimensional (3D) conformation is a key mechanism regulating gene expression and cellular function during development and disease. Elucidating the structure, functional dynamics, and spatiotemporal organization of the 3D genome requires integrating multiple experimental approaches, including chromatin conformation capture techniques, precise genome manipulation tools, and advanced imaging technologies. Notably, CRISPR/Cas systems have emerged as a revolutionary genome-editing platform, offering unprecedented opportunities for manipulating 3D genome organization and investigating disease mechanisms. This review systematically examines recent advances in CRISPR-based mammalian 3D genome engineering and explores the therapeutic potential of 3D genome engineering strategies in disease intervention.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0865"},"PeriodicalIF":10.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent Advances in Metasurfaces: From THz Biosensing to Microwave Wireless Communications.","authors":"Yue Wang, Xiang Zhang, Yuxiang Wang, Yunfei Liu, Jiaxue Li, Xiangdong Chen, Zijian Cui, Shah Nawaz Burokur, Jingdi Zhang, Xiaoguang Zhao, Kuang Zhang, Zheng You","doi":"10.34133/research.0820","DOIUrl":"10.34133/research.0820","url":null,"abstract":"<p><p>In recent years, important progress has been made in the field of biosensing and wireless communications by using metamaterials and metasurfaces. These technologies enable efficient manipulation of electromagnetic waves through judiciously designed subwavelength structural units. This review begins by focusing on the design and optimization of terahertz metasurface sensors, emphasizing their unique advantages in biomedical diagnostics. It explores key technical challenges, such as material selection, device integration, and development of robust sensor for surface-specific modifications. Furthermore, the review discusses how metasurfaces, particularly as reconfigurable intelligent surfaces, dynamically modulate electromagnetic wave propagation in the microwave communications domain to enhance signal quality, improve communication efficiency, and showcase their potential in 5G and future 6G technologies. Finally, a comprehensive overview is provided regarding the challenges and future research directions for metamaterial and metasurface technologies in both biosensing and wireless communications, with the ultimate goal of promoting their applications in point-of-care devices and efficient communication systems.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0820"},"PeriodicalIF":10.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GCDH Acetylation Orchestrates DNA Damage Response and Autophagy via Mitochondrial ROS to Suppress Hepatocellular Carcinoma Progression.","authors":"Wei Tian, Yue Yang, Lili Meng, Chao Ge, Yuqi Liu, Canxue Zhang, Zhihong Huang, Chi Zhang, Hua Tian","doi":"10.34133/research.0862","DOIUrl":"10.34133/research.0862","url":null,"abstract":"<p><p>Metabolic enzyme dysregulation promotes hepatocellular carcinoma (HCC) progression through metabolic reprogramming and lysine acetylation. Glutaryl-CoA dehydrogenase (GCDH), a key enzyme in lysine metabolism, has been demonstrated to play an essential role in modulating lysine crotonylation, which impacts the progression of HCC. However, the specific mechanisms by which GCDH influences lysine acetylation in HCC have not been completely clarified. In this study, GCDH was found to be acetylated at lysine 438 by acetyltransferase P300 and deacetylated by HDAC1. GCDH K438 acetylation was critical for its tumor-suppressive function in HCC cells. Overexpression of GCDH led to elevated levels of reactive oxygen species (ROS) and reduced oxidative phosphorylation (OXPHOS), thereby triggering ATR/Chk1-mediated DNA damage repair dysfunction and promoting autophagy in HCC cells. Furthermore, our investigation demonstrated that decreased GCDH expression was markedly associated with shorter overall survival in HCC patients and served as an independent prognostic indicator. Collectively, our findings demonstrate that the acetylation of GCDH at lysine 438 (K438), mediated by P300 and HDAC1, plays a vital role in the tumor-suppressive activities of HCC cells. GCDH inhibits HCC progression through ROS-mediated DNA repair dysfunction and autophagy.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 ","pages":"0862"},"PeriodicalIF":10.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144966838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}