Acta Biomaterialia
·
2025
·
IF 9.6
Yue Hu,Xi He,Ping Chen,Xiao-Li Tian,Rong Wang,Xiangrong Song,Xiao-Qi Yu,Ji Zhang
mRNA-based protein replacement therapy has become one of the most widely applied forms of mRNA therapy, with lipid nanoparticles (LNPs) being extensively studied as efficient delivery platforms for mRNA. However, existing LNPs tend to accumulate in the liver or kidneys after intravenous injection, highlighting the need to develop vectors capable of targeting specific organs. In this study, we synthesized a small library of ionizable lipids and identified PPz-2R 1 as a promising candidate, exhibiting lung-targeting capabilities, high mRNA transfection efficiency, and good stability through structure-activity relationship studies. In an in situ lung cancer model with PTEN deletion, precise delivery of PTEN mRNA to the lungs restored the cancer-suppressing function of the PTEN protein and successfully alleviated the immunosuppressive tumor microenvironment in the lungs by modulating immune cell activity and cytokine levels. Additionally, the upregulation of PD-L1 expression at the tumor site was triggered. Building on this, in vivo treatment with PTEN mRNA combined with anti-PD-1 therapy was tested in tumor-bearing mice. The results demonstrated that the combined treatment strategy effectively overcame immune escape, promoted T cell infiltration, improved survival rates over 60 days, and significantly inhibited tumor growth. Furthermore, the combination treatment was more effective than either therapy alone. This study presents an effective and practical strategy for the targeted treatment of lung diseases and relevant combination therapies. Statement of significance Lipid nanoparticles (LNPs) have been extensively studied as efficient delivery vectors for mRNA. However, it remains essential to develop vectors that can specifically target distinct organs. In this study, we designed and synthesized a series of piperazine-containing ionizable lipids and their analogues, which were initially explored as lung-targeting vectors for PTEN mRNA delivery. Through screening in both in vitro and in vivo experiments, we found that the leading LNPs-assisted PTEN mRNA-mediated protein supplementation therapy effectively downregulated Treg expression and activated immune cells, thereby reversing the immunosuppressive tumor microenvironment in a mouse model of lung cancer. Furthermore, when combined with anti-PD-1-mediated immunotherapy, the combination therapy exhibited the strongest tumor growth inhibition. This approach offers a novel strategy for the targeted treatment of lung diseases and associated combination therapies.
✓ 已验证
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Yuan Wang,Zhen Pan,Qianliang Wang,Yuexia Shu,Zhenyu Tan,Yujie Chen,Jieming He,Jia Wang,Jielin Wang,Jun Yan
Osteoporotic fractures typically exhibit delayed healing due to impaired cell recruitment, chronic inflammation, and disrupted neurovascular signaling. Sensory nerve signaling plays a crucial role in fracture repair, and its deficiency is a significant factor leading to delayed healing. Addressing these deficiencies is crucial to overcoming the challenges associated with delayed bone repair in osteoporosis. In this study, a smart composite hydrogel (denoted as OCS-MPC) was synthesized by embedding CGRP-functionalized polydopamine-coated MXene nanosheets (MXene/PDA/CGRP) into boronic acid-modified oxidized hyaluronic acid-crosslinked carboxymethyl chitosan (OHA-PBA/CMCS) hydrogel loaded with SDF-1. OCS-MPC hydrogel enables the controlled release of SDF-1 and CGRP, aiming to promote early callus formation and late-stage callus remodeling in osteoporotic fractures. Due to dynamic crosslinking via imine and borate ester bonds, OCS-MPC exhibits rapid gelation, injectability, and self-healing properties. In vitro experiments demonstrated excellent osteogenic, angiogenic, and neurogenic properties of OCS-MPC hydrogel. In vivo studies using an osteoporotic femoral fracture model showed that OCS-MPC hydrogel enhanced MSCs recruitment via the SDF-1/CXCR4 signaling axis, significantly improving callus formation in the early stages of fracture repair. Additionally, OCS-MPC hydrogel significantly promoted callus mineralization and remodeling in the later stages of osteoporotic fracture healing through enhancing CGRP signaling. Immunofluorescence analysis further confirmed increased expression of TUBB3, CGRP, and CD31, indicating successful regeneration of the neurovascular network. These findings highlight the potential of OCS-MPC hydrogel in addressing both early and late-stage challenges of osteoporotic fracture healing, providing a promising therapeutic strategy for enhancing bone regeneration in osteoporotic patients.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Toxicology
·
2021
·
IF 0
Hu Xing,Luo Xiaoqiao,Zhou Zhisheng,Wang Rui,Hu Yaqin,Zhang Guimei,Zhang Guowen
1–Naphthaleneacetic acid (NAA), having high-quality biological activity and great yield-increasing potential in agricultural production, is a broad-spectrum plant growth regulator. Although NAA is of low toxicity, it can affect the balance of the human metabolism and damage the body if it is used in high quantity for a long time. In this study, the interaction of NAA with calf thymus DNA (ctDNA) was investigated under simulated human physiological acidity (pH 7.4) using fluorescence, ultraviolet-visible absorption, and circular dichroism spectroscopy combined with viscosity measurements and molecular simulation techniques. The quenching of the endogenous fluorescence of NAA by ctDNA, observed in the fluorescence spectrum experiment, was a mixed quenching process that mainly resulted from the formation of the NAA–ctDNA complex. NAA mainly interacted with ctDNA through hydrophobic interaction, and the binding constant and quenching constant at room temperature (298 K) were 0.60 × 105 L mol−1 and 1.58 × 104 L mol−1, respectively. Moreover, the intercalation mode between NAA and ctDNA was verified in the analysis of melting point, KI measurements, and the viscosity of ctDNA. The results were confirmed by molecular simulation, and it showed that NAA was enriched near the C–G base of ctDNA. As shown in circular dichroism spectra, the positive peak intensity of ctDNA intensified along with a certain degree of redshift, while the negative peak intensity decreased after binding with NAA, suggesting that the binding of NAA induced the transformation of the secondary structure of ctDNA from B-form to A-form. These researches will help to understand the hazards of NAA to the human body more comprehensively and concretely, to better guide the use of NAA in industry and agriculture.
✓ 已验证
DOI
MICROPOROUS AND MESOPOROUS MATERIALS
·
2017
·
IF 3.615
Chang Wang,Jiaqi Liu,Jiangfeng Yang,Jinping Li
Synthesis of ultra-high silica (SiO 2 /Al 2 O 3 > 1800) MFI type zeolite such as silicalite-1 is still considered to be luxury because of the long synthesis time (5–12 days). Here, this material with a highly uniform mesoporous (20 nm) structure was crystallized in a shorter time (20 h) using a crystal-seeds method when an appropriate amount of potassium fluoride was added. Characterization techniques including XRD , SEM, TEM and liquid nitrogen adsorption provided detailed information on the two kinds of porous structure silicalite-1. Due to the “smooth” adsorption surface of silicalite-1 containing few equilibrium ions, it is ideal for the separation of gas mixtures containing non-polar molecules with similar physical properties. Moreover, the CH 4 , N 2 , CO 2 and C 2 H 6 adsorption properties were also investigated. Microporous silicalite-1 has a high adsorption capacity for CH 4 , N 2 , CO 2 and C 2 H 6 and adsorption selectivity for CH 4 /N 2 , CO 2 /N 2 , CO 2 /CH 4 and C 2 H 6 /CH 4 . Although a lower adsorption capacity was observed for mesoporous silicalite-1, the pore size did not affect the outstanding adsorption selectivity, on the contrary, the selectivity of mesoporous silicalite-1 was improved.
✓ 已验证
DOI
高影响因子
Nano Research
·
2024
·
IF 9.5
Zhu Shengjie,Huang Danqing,Luan Qichen,Li Yang,Gan Jingjing,Zhao Yuanjin,Sun Lingyun
Macrophages play a pivotal role in systemic lupus erythematosus (SLE) therapy. Efforts have been made to develop multifunctional drug delivery systems capable of directing macrophage polarization. Here, we present a novel hyaluronic acid methacrylate (HAMA) hydrogel microparticle encapsulating multiple cytokines for SLE remission though enhancing macrophage functions. The HAMA microparticles loaded with monocyte chemotactic protein-1 (MCP-1) and interleukin-4 (IL-4) were fabricated by using a microfluidic technology. The released MCP-1 facilitates the aggregation of inflammatory macrophages, after which IL-4 induces the macrophage phenotype shift from inflammatory M1 to immune-protective M2, thus restoring immune balance. We have demonstrated in MRL/lpr mice that the hydrogel microparticles could improve their efficacy of intraperitoneal drug delivery, modulate immune function, and attenuate the disease symptoms. These results suggest that our proposed microparticles delivery platform has potential clinical value for treating autoimmune diseases.
✓ 已验证
DOI
高影响因子
Heliyon
·
2023
·
IF 4
Chuan Jiang,Chaonan Wang,Weizhong Qu,Yuanyuan Wang,Hua Wang,Xin Wei,Mingyan Wang,Qianqian He,Yihan Wang,Lirong Yuan,Yonggang Gao
Depression is a complex and prevalent mental illness. Cherry leaf is a traditional Chinese herbal medicine, which has confirmed to exert a certain antidepressant effect, but its potential neural regulation mechanism is not clear. This paper aims to investigate the improved action of cherry leaf decoction (CLD) on chronic unpredictable mild stress (CUMS) rats and its potential neural regulation mechanism by verifying the role and function of NMDAR regulatory target α2δ-1 in depression due to CUMS. Male SD rats were subjected to random stressors persisting for 5 weeks to establish the CUMS depression rat model. CLD could effectively alleviate depression-like behaviors of CUMS rats in behavioral tests including sucrose preference test, forced swimming test, tail suspension test and open field test. After the administration of the CLD, the expression of corticotropic-releasing hormone (CRH) in the hypothalamus was inhibited. Moreover, the levels of CRH, adrenal cortical hormone (ACTH) and corticosterone (CORT) in serum also decreased significantly. CUMS upregulated the expressions of α2δ-1, N-methyl- d -aspartate receptor 1 (NR1), NR2A and NR2B, and enhanced the binding ability to of α2δ-1 and NR1, which were reversed by CLD. The results demonstrated that CLD could ameliorate depression-like behaviors due to CUMS, which was related to the fact that CLD down-regulated α2δ-1 level and interfered with α2δ-1 binding to NR1, thereby reducing NMDAR expression and ultimately inhibiting HPA axis activity.
✓ 已验证
DOI
高影响因子
MICROCHIMICA ACTA
·
2021
·Vol. 188
·期 10
·1-10
·
IF 5.833
Zheng Delun,Chen Min,Peng Jingjun,Chen Jiayang,Chen Tufeng,Chen Yaowen,Huang Linjia,Gao Wenhua
HKUST-1 MOFs and its derivative HKUST-CuO were coupled with TiO 2 nanoparticles to form the heterogeneous composites of HKUST-1/TiO 2 and HKUST-CuO/TiO 2 based on their well-suitable bandgap energies (Eg). Compared with mono-component HKUST-1 or HKUST-CuO, the prepared composites displayed photoelectrochemical (PEC) response due to the synergistic effect from their heterogeneous structure. Higher photocurrent response was obtained on HKUST-CuO/TiO 2 -modified ITO electrode (HKUST-CuO/TiO 2 /ITO), which could be attributed to the hollow structure with a thin shell of HKUST-CuO greatly enhancing visible spectra harvesting. The CuO component in HKUST-CuO not only could accelerate electron transfer on the heterojunction interface but also effectively separate the photo-generated charge carriers (e −1 /h + ). Based on the excellent PEC performance of prepared photoactive composite material, under visible-light excitation ( λ ≥ 420 nm) and with a working potential of 0 V (vs. Ag/AgCl), the S1 (probe DNA)/HKUST-CuO/TiO 2 /ITO PEC platform was successfully fabricated for colitoxin DNA detection without using ascorbic acid (AA) as an electron donor. Compared with the analysis results on S1/HKUST-1/TiO 2 /ITO electrode, S1/HKUST-CuO/TiO 2 /ITO displayed a wider linear response range from 1.0 × 10 −6 to 4.0 × 10 −1 nM with a lower detection limit of 3.73 × 10 −7 nM (S/ N = 3), the linear regression equation was Δ I (10 −6 A) =0.5549–0.1858 log ( C S2 /M), which confirmed the HKUST-CuO could improve sensitivity because of its prominent PEC property. The relative standard deviation (RSD) of the PEC sensor for target DNA detection of 2.0 × 10 −4 nM was 7.4%. The proposed DNA biosensor also possessed good specificity and stability. Hence, this reported work was a promising strategy for molecular diagnosis in the bio-analysis field. Graphical abstract
(A) Schematic illustration of the preparation process of the proposed PEC biosensors for colitoxin DNA detection. (B) The preparation process of HKUST-1 and HKUST-CuO.
✓ 已验证
DOI
高影响因子
Frontiers in Materials
·
2020
·
IF 2.705
Li Xinxi,Liu Long,Li Shumin,Guo Lin,Li Bin,Zhang Guoqing
Spinel lithium manganese oxide (LiMn2O4) based Li-ion battery (LIB) is attractive for hybrid/full electric vehicles because of its abundant resources and easy preparation. However, operation under an elevated temperature could cause severe capacity fading of the spinel cathodes. In this work, 1, 3-propane sultone (PS) is investigated as an electrolyte additive for improving the cyclability of the LiMn2O4/graphite LIB at elevated temperature. The charge and discharge measurement proves that PS can significantly enhance the cyclability of 053048-type LiMn2O4/graphite pouch cell at 60°C. Compared to the cell without additive, the capacity retention of the cell using electrolyte with 5% PS increases from 52 to 71% after 180 cycles. The improved cyclability is attributable to the modification of the solid electrolyte interface (SEI) on both positive and negative sides of the LiMn2O4/graphite cell by PS, which effectively prevents anode and cathode from structural breakdown and inhibits the electrolyte decomposition.
✓ 已验证
DOI
高影响因子
CRYSTENGCOMM
·
2022
·Vol. 24
·期 14
·2697-2704
·
IF 3.756
Siyu Zhang,Xiaomin Zhang,Lei Dong,Shengjie Zhu,Yangyang Yuan,Lei Xu
In this work, Pt nanoparticles (NPs) were directly encapsulated into MFI-type zeolite (Pt@S-1) via a steam-assisted dry-gel conversion method. The synthesis process included the disaggregation of Pt immobilized SiO2–SH spheres and the in situ crystallization for the synthesis of Pt@S-1. The Pt NPs remained stable during the whole crystallization process and the average size of Pt NPs in the synthesized Pt@S-1 was from 1.54 to 2.34 nm. The highest encapsulation degree of Pt NPs was calculated as 93.8% and decreased slightly to 84.9% with the increase of Pt loading. Owing to the high encapsulation degree of Pt NPs in MFI crystals, the size of Pt NPs after calcination at 800 °C only grew up to 3.19 nm showing significantly high thermal stability. The uniform microporous pores of silicalite-1 zeolite as well as the small size and stable Pt NPs endow the Pt@S-1 catalyst with high activity and stability in the nitrobenzene hydrogenation reaction.
✓ 已验证
DOI
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2024
·
IF 3.3
Guang Yang,Xin Shi,Meixia Zhang,Kaiwen Wang,Xin Tian,Xiaofeng Wang
Oral squamous cell carcinoma (OSCC) is the most common oral malignancy. DEAD/H-box helicase 11 (DDX11), a DNA helicase, has been implicated in the progression of several cancers. Yet, the precise function of DDX11 in OSCC is poorly understood. The DDX11 expression in OSCC cells and normal oral keratinocytes was evaluated in the Gene Expression Omnibus database (GSE146483 and GSE31853). SCC-4 and CAL-27 cells expressing doxycycline-inducible DDX11 or DDX11 shRNA were generated by lentiviral infection. The role of DDX11 in OSCC cells was determined by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, colony formation assay, flow cytometry assay, TUNEL staining, and western blot. The effects of DDX11 on tumor growth were explored in a xenograft nude mouse model. The relationship between DDX11 and transcription factor Yin Yang-1 (YY1) was researched using the dual luciferase report assay and chromatin immunoprecipitation assay. DDX11 expression was significantly upregulated in OSCC cells. Knockdown of DDX11 inhibited cell proliferation, induced cell cycle arrest, and suppressed PI3K-AKT pathway, while DDX11 overexpression showed opposite effects. The number of apoptotic cells was increased in DDX11 silenced cells. DDX11 upregulation or knockdown accelerated or suppressed tumor growth in vivo, respectively. Moreover, the YY1 bound and activated the DDX11 promoter, resulting in increasing DDX11 expression. Forced expression DDX11 reversed the anticancer effects of YY1 silencing on OSCC cells. DDX11 has tumor-promoting function in OSCC and is transcriptionally regulated by YY1, indicating that DDX11 may serve as a potential target for the OSCC treatment.
✓ 已验证
DOI
PubMed
高影响因子
Green Chemical Engineering
·
2023
·
IF 0
Jian Yang,Jia Zhang,Enrico Benassi,Xuemei Li,Hailong Liu,Weiguo Fang,Junying Tian,Chungu Xia,Zhiwei Huang
Al 2 O 3 -supported monometallic Ni, Co, and bimetallic Ni–Co nanocatalysts originated from layered double hydroxide precursors were synthesized by co-precipitation method, and used for the synthesis of useful 5-amino-1-pentanol (5-AP) and 1,5-pentanediol (1,5-PD) by reductive amination (RA) or direct hydrogenation of biofurfural-derived 2-hydroxytetrahydropyran (2-HTHP), respectively. In both reactions, the yield of the target products decreased monotonously with the increasing amounts of Co in the NiCo/Al 2 O 3 catalysts, owing probably to the replacement of highly reactive Ni by Co component with inferior hydrogenation activity at the low reaction temperature of 60 °C. However, the incorporation of Co could improve the reducibility of the NiCo/Al 2 O 3 bimetallic catalysts and promote the reaction stability of the catalysts, especially for Ni 2 Co 1 /Al 2 O 3 , in both reactions with over 180 h time-on-stream. Characterization of the catalysts before and after the reaction showed that the incorporating Co could inhibit the sintering of metal particles and hinder the surface oxidation of the more reactive Ni 0 species, thanks to the formation of Ni–Co alloy in the bimetallic catalysts. DFT-based modeling of the reaction mechanisms is also performed, supporting the reaction pathway proposed previously and also the much higher activity of Ni in the RA of 2-HTHP as compared with Co.
✓ 已验证
DOI
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2020
·
IF 3.573
Xiaopo Niu,Xiaoxue Li,Gang Yuan,Fuxiang Feng,Miao Wang,Xiangwen Zhang,Qingfa Wang
Hollow hierarchical silicalite-1 zeolite encapsulated Pt and PtNi bimetals (Pt@HS-1 and PtNi@HS-1) were successfully synthesized via a ship-in-bottle strategy and employed for hydroconversion of methyl stearate into aviation fuel range alkanes in a fixed-bed reactor. Their morphologies, texture, and acidity were characterized by field-emission scanning electron microscopy, field-emission transmission electron microscopy, X-ray diffraction, nitrogen adsorption and desorption, hydrogen temperature-programmed reduction, X-ray photoelectron spectroscopy, inductively coupled plasma optical emission spectrometry, ammonia temperature-programmed desorption, and CO pulse chemisorption. The bimetallic catalysts (PtNi/S-1 and PtNi@HS-1) showed higher catalytic activity and selectivity to aviation fuel owing to the stronger cleavage ability related to the introduction of Ni species. Moreover, aviation fuel selectivity was significantly improved on the hollow hierarchical encapsulated catalysts than their precursors, ascribed to the extended contact time between reactants and active sites. A maximum aviation fuel selectivity of 45% was obtained for the PtNi@HS-1 catalyst at 360 °C under 3 MPa. Furthermore, the PtNi@HS-1 catalyst exhibited superior catalytic stability and selectivity than the PtNi/S-1 catalyst during the stability test. This indicates that the hollow hierarchical encapsulated structure plays crucial roles in enhancing aviation fuel selectivity and catalytic performance.
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）