eLife
·
2024
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IF 6.4
Junjun Yao,Shaoxing Dai,Ran Zhu,Ju Tan,Qiancheng Zhao,Yu Yin,Jiansen Sun,Xuewei Du,Longjiao Ge,Jianhua Xu,Chunli Hou,Nan Li,Jun Li,Weizhi Ji,Chuhong Zhu,Runrui Zhang,Tianqing Li
While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.
研究领域:
神经科学
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分子生物学
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干细胞生物学
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发育生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Xiejun Zhao,Xiangchuan Qin,Ruizhe Wang,Yawen Wang,Yinli He,Yuchen Wang,Kefeng Li,Peipei Zhang,Chen Yang,Menghan Wang,Yingtong Dong,Xue Shi,Jia Ma,Jiye Zhang,Xiaojiao Li
Inefficient priming, poor recruitment, and inadequate reinvigoration of T cells challenges the therapy of PD-L1-resistant tumors. Herein, a pH-responsive charge-reversal nanoplatform integrating coactivator-associated arginine methyltransferase 1 (CARM1) inhibitor (iCARM1) and poliovirus receptor siRNA (siPVR) is developed. Upon tumor penetration, iCARM1 released in tumor cells facilitates T cell priming by epigenetically activating cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling-mediated dendritic cell maturation. Meanwhile, in T cells, iCARM1 facilitates their recruitment by upregulating CXC-chemokine receptor 3 (CXCR3) expression. The released siPVR silences pvr to reinvigorate T cells. This epigenetic nanoagonist induces a robust immune response, dramatically suppresses tumor growth, metastasis, and relapse, and confers durable protection against secondary tumor challenge. Multiple PD-L1-resistant models demonstrate the broad applicability of this strategy. This study thus represents an innovative approach for facilitating multilevel T cell responses to combat PD-L1-resistant tumors.
研究领域:
癌症免疫治疗
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纳米医学
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表观遗传学
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分子生物学
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免疫学
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信号转导
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RNA干扰
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
·
2025
·
IF 8.9
Xin Wei,Mingzhu Zuo,Qiongwen Liang,Shiwei Zhang,Jingmei Wang,Zhanfeng Li,Wenguang Yang,Fang Ma,Wangxiao He,Tianya Liu
Microsatellite-stable colorectal cancer (MSS-CRC) is characterized by poor immune infiltration and immune evasion, leading to rapid tumor progression and limited efficacy of current immunotherapies. The bioinformatics analysis revealed that the hyperactivation of the Wnt/β-catenin signaling pathway in MSS-CRC is instrumental in mediating immune suppression. Although inhibiting this pathway presents a therapeutic opportunity, no Wnt inhibitors have been clinically approved due to Wnt's essential role in maintaining tissue homeostasis, with inhibition in normal cells causing significant toxicity. To address it, we discovered that Wnt activation in colorectal cancer cells enhances macropinocytosis, particularly favoring the uptake of glycosylated proteins to meet increased nutrient demands. Building on this insight, we developed a glycosylated human serum albumin (GHSA) co-assembled with carnosic acid (CA), termed glycosylated human serum albumin-carnosic acid (GHSACA), which is selectively internalized by Wnt-activated colorectal cancer cells. This approach not only reduces off-target toxicity but also effectively inhibits the Wnt pathway, resulting in notable tumor inhibition and immune reactivation in murine models, while maintaining a favorable safety profile. This strategy offers a promising therapeutic solution by combining selective Wnt inhibition with enhanced immune activation in MSS-CRC, and highlights the potential of leveraging disease-specific cellular uptake mechanisms for designing nanomedicines, advancing the development of precision-targeted cancer therapies.
研究领域:
肿瘤学
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免疫治疗
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分子生物学
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纳米医学
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生物信息学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yue Gao,Suriguga Meng,Wenxin Liu,Yu Zhang,Yanling Zhang,Alideertu Dong,Lei Zhang
In situ reactivation of hydrogels remains a long-standing key challenge in chemistry and materials science. Herein, we first report an ultraconvenient in situ renewable antibacterial hydrogel prepared via a facile physical contact-triggered strategy based on an ultrafast chlorine transfer pathway. We discover that the as-proposed hydrogel with a programmable 3D network cross-linked by noncovalent bonds and physical interactions can serve as a smart platform for selective active chlorine transfer at the hydrogel/hydrogel interface. Systematic experiments and density functional theory prove that the N-halamine glycopolymers integrated into the hydrogel system work as a specific renewable biocide, permitting the final hydrogel to be recharged in situ within 1 min under ambient conditions. Due to its strength and durability, pathogen specificity, and biocompatibility, coupled with its rapid in situ reactivation, this antibacterial hydrogel holds great potential for in vivo biomedical use and circulating water disinfection. We envision this proposed strategy will pave a new avenue for the development of in situ renewable smart hydrogels for real-world applications.
研究领域:
化学
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材料科学
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生物材料
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）