Advanced Science最新文献_第2页

High Sugar Induced RCC2 Lactylation Drives Breast Cancer Tumorigenicity Through Upregulating MAD2L1.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202415530

Bowen Zheng, Yunhao Pan, Fengyuan Qian, Diya Liu, Danrong Ye, Bolin Yu, Seng Zhong, Wenfang Zheng, Xuehui Wang, Baian Zhou, Yuying Wang, Lin Fang

{"title":"High Sugar Induced RCC2 Lactylation Drives Breast Cancer Tumorigenicity Through Upregulating MAD2L1.","authors":"Bowen Zheng, Yunhao Pan, Fengyuan Qian, Diya Liu, Danrong Ye, Bolin Yu, Seng Zhong, Wenfang Zheng, Xuehui Wang, Baian Zhou, Yuying Wang, Lin Fang","doi":"10.1002/advs.202415530","DOIUrl":"https://doi.org/10.1002/advs.202415530","url":null,"abstract":"Lactylation is a novel post-translational modification mediated by lactate, widely present in the lysine residues of both histone and non-histone proteins. However, the specific regulatory mechanisms and downstream target proteins remain unclear. Herein, it is demonstrated that the RCC2 protein may serve as a critical link between material metabolism and cell division, promoting the rapid proliferation of breast cancer under high glucose conditions. Mechanistically, the activation of glycolysis leads to an increase in lactate. Then, acyltransferase KAT2A mediates RCC2 lactylation at K124, which assists RCC2 in recruiting free SERBP1, thereby stabilizing MAD2L1 mRNA. The lactylation of RCC2 mediates the activation of the cellular MAD2L1 signaling pathway and contributes to the progression of breast cancer. A small molecule inhibitor slows down cell proliferation by binding to the RCC2 active pocket and specifically blocking RCC2 lactylation. The findings elucidate the mechanism behind the upregulation of MAD2L1 in murine tumors associated with a high-sugar diet as reported in prior study and suggest a novel therapeutic strategy of targeting RCC2 lactylation to restrict the rapid proliferation of breast cancer cell in a high-lactate microenvironment.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2415530"},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202500128

Xinzhou Wang, Zhenyu Guo, Linjie Chen, Jing Sun, Kenny Yat Hong Kwan, Morgan Jones, Yan Michael Li, Yangyang Hu, Xueqiang Wang, Pooyan Makvandi, Xiangyang Wang, Qiuping Qian, Yunlong Zhou, Aimin Wu

{"title":"Synergistic Modulating of Mitochondrial Transfer and Immune Microenvironment to Attenuate Discogenic Pain.","authors":"Xinzhou Wang, Zhenyu Guo, Linjie Chen, Jing Sun, Kenny Yat Hong Kwan, Morgan Jones, Yan Michael Li, Yangyang Hu, Xueqiang Wang, Pooyan Makvandi, Xiangyang Wang, Qiuping Qian, Yunlong Zhou, Aimin Wu","doi":"10.1002/advs.202500128","DOIUrl":"https://doi.org/10.1002/advs.202500128","url":null,"abstract":"Discogenic pain, caused by intervertebral disc degeneration (IVDD), is a prevalent and challenging condition to treat effectively. Macrophage infiltration with neural ectopic in-growth resulting from structural disturbances within the intervertebral disc (IVD) is a major cause of discogenic pain. This work systematically reveals how nanoparticles can synergistically regulate the immune microenvironment and mitochondrial communication to attenuate discogenic pain. The antioxidant metal-polyphenol nanoparticle system can sequentially regulate macrophage phenotype and mitochondrial delivery efficiency. This strategy circumvents the necessity for mitochondrial isolation and preservation techniques that are typically required in conventional mitochondrial transplantation procedures. Furthermore, it facilitates the effective and sustained delivery of mitochondria to damaged cells. In vivo, this nanoparticle formulation effectively preserves the IVD height, maintains the structural integrity of the nucleus pulposus (NP), and restores pain thresholds. Thus, this nanoplatform offers an effective approach to traditional surgical treatments for discogenic pain, with significant potential for clinical application.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500128"},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep Learning-Based Ion Channel Kinetics Analysis for Automated Patch Clamp Recording (Adv. Sci. 12/2025)

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202570080

Shengjie Yang, Jiaqi Xue, Ziqi Li, Shiqing Zhang, Zhang Zhang, Zhifeng Huang, Ken Kin Lam Yung, King Wai Chiu Lai

引用次数: 0

Targeted Delivery of c(RGDfk)-Modified Liposomes to Bone Marrow Through In Vivo Hitchhiking Neutrophils for Multiple Myeloma Therapy (Adv. Sci. 12/2025)

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202570079

Huiwen Liu, Bo Zhang, Hongrui Chen, Honglan Wang, Xifeng Qin, Chunyan Sun, Zhiqing Pang, Yu Hu

引用次数: 0

Issue Information: (Adv. Sci. 12/2025)

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202570081

引用次数: 0

STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202500296

Laura Gehrcken, Christophe Deben, Evelien Smits, Jonas R M Van Audenaerde

{"title":"STING Agonists and How to Reach Their Full Potential in Cancer Immunotherapy.","authors":"Laura Gehrcken, Christophe Deben, Evelien Smits, Jonas R M Van Audenaerde","doi":"10.1002/advs.202500296","DOIUrl":"https://doi.org/10.1002/advs.202500296","url":null,"abstract":"As cancer continues to rank among the leading causes of death, the demand for novel treatments has never been higher. Immunotherapy shows promise, yet many solid tumors such as pancreatic cancer or glioblastoma remain resistant. In these, the \"cold\" tumor microenvironment with low immune cell infiltration and inactive anti-tumoral immune cells leads to increased tumor resistance to these drugs. This resistance has driven the development of several drug candidates, including stimulators of interferon genes (STING) agonists to reprogram the immune system to fight off tumors. Preclinical studies demonstrated that STING agonists can trigger the cancer immunity cycle and increase type I interferon secretion and T cell activation, which subsequently induces tumor regression. Despite promising preclinical data, biological and physical challenges persist in translating the success of STING agonists into clinical trials. Nonetheless, novel combination strategies are emerging, investigating the combination of these agonists with other immunotherapies, presenting encouraging preclinical results. This review will examine these potential combination strategies for STING agonists and assess the benefits and challenges of employing them in cancer immunotherapy.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500296"},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Nano-Immunomodulatory Systems for the Treatment of Acute Kidney Injury.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202409190

Chenli Zhang, Zeli Xiang, Pengfei Yang, Ling Zhang, Jun Deng, Xiaohui Liao

{"title":"Advances in Nano-Immunomodulatory Systems for the Treatment of Acute Kidney Injury.","authors":"Chenli Zhang, Zeli Xiang, Pengfei Yang, Ling Zhang, Jun Deng, Xiaohui Liao","doi":"10.1002/advs.202409190","DOIUrl":"https://doi.org/10.1002/advs.202409190","url":null,"abstract":"Acute kidney injury (AKI) occurs when there is an imbalance in the immune microenvironment, leading to ongoing and excessive inflammation. Numerous immunomodulatory therapies have been suggested for the treatment of AKI, the current immunomodulatory treatment delivery systems are suboptimal and lack efficiency. Given the lack of effective treatment, AKI can result in multi-organ dysfunction and even death, imposing a significant healthcare burden on both the family and society. This underscores the necessity for innovative treatment delivery systems, such as nanomaterials, to better control pathological inflammation, and ultimately enhance AKI treatment outcomes. Despite the modification of numerous immunomodulatory nanomaterials to target the AKI immune microenvironment with promising therapeutic results, the literature concerning their intersection is scarce. In this article, the pathophysiological processes of AKI are outlined, focusing on the immune microenvironment, discuss significant advances in the comprehension of AKI recovery, and describe the multifunctionality and suitability of nanomaterial-based immunomodulatory treatments in managing AKI. The main obstacles and potential opportunities in the swiftly advancing research field are also clarified.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2409190"},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of CD38^high Monocyte as a Candidate Diagnostic Biomarker and Therapeutic Target for Sepsis.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202500457

Ning Hua, Limin Kong, Li Fan, Yanan Bai, Yujun Zhou, Yanfang Zhang, Qingwei Zhao, Xiaoyang Lu, Hongyu Yang, Hangyang Li, Peili Ding, Yuyu Nan, Qinghua Ji, Ping Yang, Lu Li, Yijing Xin, Lijuan Zhao, Wei Yang, Wenqiao Yu, Saiping Jiang

{"title":"Identification of CD38high Monocyte as a Candidate Diagnostic Biomarker and Therapeutic Target for Sepsis.","authors":"Ning Hua, Limin Kong, Li Fan, Yanan Bai, Yujun Zhou, Yanfang Zhang, Qingwei Zhao, Xiaoyang Lu, Hongyu Yang, Hangyang Li, Peili Ding, Yuyu Nan, Qinghua Ji, Ping Yang, Lu Li, Yijing Xin, Lijuan Zhao, Wei Yang, Wenqiao Yu, Saiping Jiang","doi":"10.1002/advs.202500457","DOIUrl":"https://doi.org/10.1002/advs.202500457","url":null,"abstract":"Sepsis is characterized by a systemic host response to infection. Monocytes, as major mediators of acute infection, are implicated in complications among critically ill patients. Identifying key monocyte subsets and their activation states is essential for diagnosis and delineating new therapeutic targets for sepsis. Here, single cell transcriptome sequencing and mass cytometry are used to assess alterations in the composition and function of peripheral monocytes of patients with sepsis, and CD38high monocytes in circulation are specifically accumulated within the first 24 h of sepsis. CD38high monocytes are detectable by conventional flow cytometry to discriminate sepsis and sterile inflammation, and are associated with 28-day mortality in bacterial sepsis. Targeting CD38 therapy markedly reduces inflammatory response in primary monocytes and in sepsis mice model. Mechanistically, CD38high monocytes in sepsis exhibit hyperactivated glycolysis with activation of hypoxia-inducible factor-1α (HIF-1α) due to NAD+ consumption. Glycolytic metabolite methylglyoxal (MGO) is found to regulate expression of CD38, establishing a CD38-HIF-1α/glycolysis/MGO loop that exacerbates sepsis-induced immune dysregulation. These findings demonstrate that CD38high monocytes might serve as a candidate diagnostic biomarker and therapeutic target for sepsis.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2500457"},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MAGEA6 Engages a YY1-Dependent Transcription to Dictate Perineural Invasion in Colorectal Cancer.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202501119

Hao Wang, Kexin He, Ruixue Huo, Weihan Li, Shan Zhang, Lu-Ju Jiang, Hao Wu, Minhao Yu, Shu-Heng Jiang, Junli Xue

{"title":"MAGEA6 Engages a YY1-Dependent Transcription to Dictate Perineural Invasion in Colorectal Cancer.","authors":"Hao Wang, Kexin He, Ruixue Huo, Weihan Li, Shan Zhang, Lu-Ju Jiang, Hao Wu, Minhao Yu, Shu-Heng Jiang, Junli Xue","doi":"10.1002/advs.202501119","DOIUrl":"https://doi.org/10.1002/advs.202501119","url":null,"abstract":"Perineural invasion (PNI), characterized by tumor cells surrounding and invading nerves, is associated with poor prognosis in colorectal cancer (CRC). Understanding the mechanisms of PNI is crucial for developing targeted therapies to impede tumor progression. In this study, clinical information and transcriptome data are obtained from the TCGA database. Stable MAGEA6 knockdown CRC cell lines are established to investigate the impact of MAGEA6 on CRC malignancy. Immunohistochemical staining is used to assess the clinical significance of MAGEA6. Rectal orthotopic and sciatic nerve invasion models are employed to verify the role of MAGEA6 in PNI. Schwann cells (SCs) infiltration and recruitment by CRC cells are assessed using ssGSEA and co-culture experiments. The results reveal that MAGEA6 is a key regulator of PNI, with its expression correlating with poor prognosis. MAGEA6 knockdown reduces CRC cell migration, invasion, and PNI ability. Moreover, CRC cells recruit SCs, with CXCL1 promoting SCs migration. Mechanistically, MAGEA6 inhibits YY1 ubiquitination, stabilizing YY1 expression and enhancing SC recruitment via YY1-mediated CXCL1 transcription. These findings suggest that MAGEA6 enhances CRC invasiveness and PNI by stabilizing YY1, which upregulates CXCL1 secretion and promotes SC recruitment. This interaction underscores the critical role of MAGEA6 in PNI and highlights a potential therapeutic target in CRC.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2501119"},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

OcuPair, a Novel Photo-crosslinkable PAMAM Dendrimer-Hyaluronic Acid Hydrogel Bandage/Bioadhesive for Corneal Injuries and Temporary Corneal Repair.

IF 14.3 1区材料科学

Advanced Science Pub Date : 2025-03-27 DOI: 10.1002/advs.202417731

Siva P Kambhampati, Rishi Sharma, Hui Lin, Santiago Appiani, Jeffrey L Cleland, Samuel C Yiu, Rangaramanujam M Kannan

{"title":"OcuPair, a Novel Photo-crosslinkable PAMAM Dendrimer-Hyaluronic Acid Hydrogel Bandage/Bioadhesive for Corneal Injuries and Temporary Corneal Repair.","authors":"Siva P Kambhampati, Rishi Sharma, Hui Lin, Santiago Appiani, Jeffrey L Cleland, Samuel C Yiu, Rangaramanujam M Kannan","doi":"10.1002/advs.202417731","DOIUrl":"https://doi.org/10.1002/advs.202417731","url":null,"abstract":"Traumatic corneal injuries are a leading cause of blindness among military personnel. These injuries need immediate attention in the combat zone, but treatment options are limited as life-saving measures are often prioritized. To address this critical gap, we have developed OcuPairTM, a two-component hydrogel system that consists of i) an injectable viscoelastic filler that stabilizes the ocular cavity and prevents hypotony. ii) An in situ photo-curable adhesive hydrogel comprising of methacrylated, hydroxyl PAMAM dendrimer and hyaluronic acid engineered to form a transparent, flexible, and robust bandage within 90 seconds, adhering to the corneal surface and ensuring a water-tight seal securing full-thickness corneal wounds. Ex vivo studies demonstrated that the adhesive hydrogel is mechanically robust and withstands intraocular pressures beyond physiological range. In a rabbit corneal injury model, OcuPairTM effectively sealed complex full-thickness wounds and preserved the eye with favorable clinical outcomes for 5 days with no toxicity over 30 days. In this study, we have validated the pilot scale synthesis, formulation optimization, GMP scale-up, and IDE-enabling GLP toxicity, essential for clinical translation as a battlefield-ready solution.","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":" ","pages":"e2417731"},"PeriodicalIF":14.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0