ADVANCED MATERIALS
·
2026
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IF 29.1
Qiu Wang,Yi Lin,Jiahui Xiao,Keqing Xu,Zijin Luo,Hongyu Ren,Fan Liu,Lu Jia,Tuo Wei,Qiang Cheng
Highly efficient mRNA lipid nanoparticle (LNP) often presents potential safety risks. Here, we establish a structure–activity relationship framework for peptide ionizable lipids (PILs) to facilitate the rational design of safe and effective mRNA-LNPs. The PIL structure comprises three modular components: building block, side-chain length, and hydrophobic tail. Through systematic optimization, a lead compound (Dab4) with four building blocks and a moderate side chain length was identified, demonstrating minimized hepatotoxicity while maintaining superior delivery performance. Leveraging this framework, a series of Dab4-derived PILs with three tail types, including alkyl (a-tail), ester (aat-tail), and hydroxyl (e-tail), were synthesized. This tail chemistry determined organ tropism, with B12-a13Dab4 (a-tail) showing optimal performance in the liver. The B12-a13Dab4 LNP exhibited significantly higher hepatic delivery efficiency and markedly improved biosafety compared with the FDA-approved SM-102 formulation. Moreover, B12-a13Dab4 LNP efficiently triggers in vivo prime editing by co-delivering PE7 mRNA and epegRNA, and achieves significant therapeutic effects in a Hereditary Tyrosinemia Type 1 (HT-1) model through repeated delivery fumarylacetoacetate hydrolase (FAH) mRNA. This study establishes rational design principles for PILs that strike a balance between efficacy and safety, offering a versatile mRNA-LNP platform for the advancement of gene editing and protein replacement therapies.
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF ORAL SCIENCES
·
2019
·Vol. 127
·期 6
·547-555
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IF 1.81
Mingxing Li,Jingqiu Xu,Ling Zhang,Chaoyang Wang,Xiaoting Jin,Yan Hong,Baiping Fu,Matthias Hannig
This study investigated the effects of the prime-and-rinse approach, using a 10-methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primer, on the short- and long-term dentin microtensile bond strengths (MTBSs) of mild self-etch adhesives. Half of sixty human midcoronal dentin surfaces were polished as control (self-etch approach), and the other half were polished and further treated with a 15% MDP-containing primer and thoroughly sprayed with water as prime-and-rinse approach. The dentin surfaces were treated with a self-etch adhesive, and a composite resin was placed on the surfaces. The following materials were used: Clearfil S3 Bond+Clearfil Majesty; G-Bond+Gradia Direct; Adper Easy One+Z250; and i Bond+Charisma. The MTBS was examined after 24 h and 14 months in water storage. The resin–dentin interfaces were analysed using scanning electron microscopy/transmission electron microscopy. Pretreated dentin surfaces were further analysed using scanning electron microscopy and micro-Raman spectroscopy. Compared with the self-etch approach, the prime-and-rinse approach significantly increased the dentin MTBS, regardless of the duration of storage. The scanning electron microscopy/transmission electron microscopy findings revealed that the prime-and-rinse approach removed most of the dentin smear layer. The Raman spectra of the MDP-treated dentin reveal the characteristic spectra of collagen, hydroxyapatite, and the monomer. Therefore, the prime-and-rinse approach using MDP-containing primers prior to the application of mild self-etch adhesives significantly increases the short- and long-term MTBS of dentin.
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DOI
高影响因子
Research
·
2026
·
IF 12.9
Lishi Jie,Jun Mao,Li Zhang,Houyu Fu,Xiaochen Li,Taiyang Liao,Yibao Wei,Deren Liu,Jiaojiao Du,Peng Wu,Songjiang Yin,Nongshan Zhang,Meng Cao,Peimin Wang
Knee osteoarthritis (KOA) is clinically characterized by recurrent and progressively worsening episodes;however, its underlying pathological mechanisms remain incompletely understood. Phenotypic changesand the specific migration of circulating monocytes may be key factors contributing to the recurrenceand progressive exacerbation of synovial inflammation in KOA. In this study, we report a specificsubtype of circulating monocytes in KOA that highly express IL1A, IL1R1, TNF, CXCL12, CXCL3,CXCL2, CCL20, and G0S2. These monocytes exhibit a trained immune phenotype, and their CXCR4-dependent migration to the synovium exacerbates synovial inflammation. HMGB1 (high mobility groupprotein B1) primes the trained immunity of this subtype, resulting in increased chromatin accessibility,and the transcriptional storage of multiple pro-inflammatory factors enables them to exhibit a morepositive inflammatory response when restimulated by HMGB1. In addition, we find that MyD88,downstream of HMGB1, recruits cytoplasmic IRF1 to the nucleus, and then stabilizes IRF1 in chromatinthrough SUMOylation of TRIM28 to exert transcriptional activity and epigenetic enhancement of pro-inflammatory factor expression. Finally, we found that KOA inflammation was effectively attenuated byblocking HMGB1. Taken together, this study reveals the mechanism by which trained immunity ofcirculating monocyte promote the progression of synovial inflammation, support a future therapeuticapproach in the management of KOA.Keywordsknee osteoarthritis; trained immunity; HMGB1; IRF1; SUMOylation; CXCL12; CXCR4
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DOI
高影响因子
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