Journal of the Mechanical Behavior of Biomedical Materials
·
2020
·
IF 3.372
Jingqiu Xu,Mingxing Li,Wenting Wang,Zhifang Wu,Chaoyang Wang,Xiaoting Jin,Ling Zhang,Wenxiang Jiang,Baiping Fu
Objectives The study investigated the effects of novel prime-&-rinse mode using MDP (10-methacryloyloxydecyl dihydrogenphosphate) and matrix metalloproteinase (MMPs) inhibitors on dentin microtensile bond strengths (MTBS) of self-etch adhesive, resin-dentin interface degradations, and activity of recombinant human (rh) MMP-8, -9. Materials and methods Eight experimental primers were prepared using 5% and 15% of MDP ethanol-aqueous (1:1) solution in combination with/without MMPs inhibitors (1%benzalkonium chloride (BAC), 1000 μm/mL polyvinylphosphonic acid (PVPA) and 15%proanthocyanidin (PA)). Ninety human mid-coronal dentin surfaces were applied with the experimental primers, water-sprayed and gently air-dried (prime-&-rinse mode), or not (control, self-etch mode). The specimens were bonded with self-etch adhesive (Clearfil S3 Bond) and composite resin (Clearfil Majesty). The resin-bonded specimens were prepared into multiple micro-beams for MTBS tests after 24 h and 1 yr of water storage. The resin-dentin interfaces were analyzed with SEM/TEM. The inhibitory effects of eight primers on rhMMP-8, 9 were determined. The data were analyzed using two-way ANOVA and LSD multiple comparisons tests. Results Compared with control, all the primers used in prime-&-rinse mode could significantly improve long-term dentin MTBS ( P < 0.05), while 5%MDP-BAC, 15%MDP and 15%MDP+MMPs inhibitors could significantly increase the short-term dentin MTBS ( P < 0.05). The SEM/TEM findings revealed that the resin-dentin interfaces were stable over time when the prime-&-rinse mode used. Eight primers possessed the high inhibitory ratio of rh MMP-8, 9. Conclusions The novel prime-&-rinse mode using 5%MDP-BAC, 15%MDP and 15%MDP+MMPs inhibitors could significantly increase the short- and long-term dentin MTBS of self-etch adhesive. This might be a supplement to contemporary dentin bonding strategies.
研究领域:
牙科学
·
材料科学
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-17
·
IF 10.435
Yang Linnan,Li Feng,Cao Yongsheng,Liu Qiang,Jing Guoxin,Niu Jintong,Sun Feiyue,Qian Yechang,Wang Shilong,Li Ang
The tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8+ T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.
研究领域:
癌症免疫学
·
纳米技术
·
分子生物学
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2026
·
IF 13.6
Bofu Ma,Miao Su,Boya Yu,Chaoran Chen,Zhihao Wang,Bianxia Liu,Xianzhu Yang,Xiaojiao Du,Jun Wang
Nanomaterials with intrinsic biological activity can directly participate in disease treatment, emerging as a pivotal focus in the development of next-generation therapeutics. In this study, we synthesized a library of cholesterol lipids bearing diverse tertiary amine head groups via a straightforward amidation reaction, then co-assembled them with amphiphilic polyethylene glycol-poly (lactic-co-glycolic acid) (PEG- b -PLGA) to formulate hybrid nanomaterials. Notably, the cholesterol derivative A3-Chol-formulated nanomaterials (A3-Chol@NP) polarized macrophages toward the pro-inflammatory M1 phenotype and enhanced phagocytosis of tumor cells. At the mechanistic level, A3-Chol@NP has been observed to preferentially interact with mitochondria in macrophages to produce mitochondrial reactive oxygen species (mtROS). This, in turn, activates ROS-NF-κB-iNOS and ROS-IRF5-IL-23 pathways, which have been identified as key factors in the macrophage polarization to M1-type. In the B16-F10 mouse melanoma model, A3-Chol@NP efficiently suppressed tumor growth via macrophage-mediated immunotherapy and completely blocked tumor progression when combined with anti-PD-L1 antibody.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NATURE MATERIALS
·
2025
·
IF 38.5
Lin Yi,Li Mengyao,Luo Zijin,Meng Yanan,Zong Yan,Ren Hongyu,Yu Xiaolu,Tan Xiaoqiong,Liu Fan,Wei Tuo,Cheng Qiang
Lipid nanoparticles for mRNA delivery and gene editing have the potential to transform the current therapeutic landscape. Nonetheless, a major bottleneck using this technology is the difficulty in achieving cell- and tissue-specific delivery and avoiding liver accumulation. Here we report the rational design of peptide ionizable lipids to assemble lipid nanoparticles with organ-selective mRNA delivery. Structure–activity and structure–selectivity relationship analyses enable us to obtain a general and predictable strategy for peptide ionizable lipid design. By incorporating artificial ionizable and natural amino acids and/or functional molecules into peptide ionizable lipids, we create lipid nanoparticles with tissue-specific targeting, including the lungs, liver, spleen, thymus and bone. In particular, lipid nanoparticles containing peptide lipids targeting the liver show comparable efficacy and safety compared with FDA-approved formulations. Furthermore, lipid nanoparticles with peptide lipids achieve the efficient co-delivery of PEmax mRNA and engineered prime editing guide RNA for prime editing of the liver and lungs. Overall, our platform offers a predictable methodology for the rational design of tissue-targeting lipid nanoparticles that might aid the development of improved mRNA-based gene editing therapeutics.
研究领域:
生物技术
·
遗传学
·
纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MECHANICAL SCIENCES
·
2022
·
IF 6.772
Yiheng Sun,Guijing Dou,Kang Wu,Peijian Chen,Taihua Zhang,Guangjian Peng
Characterization of the rupture behavior is of great significance to evaluate the service life for microcapsules. Due to the small dimension, complex core-shell structure and curved surface of microcapsules, it is challenging to quantitatively determine the rupture position and rupture strength. In the present work, a microsphere-compression model for characterizing the rupture behavior of microcapsules was established. Through the quantitative investigation of the compression rupture behaviors of microcapsules from the extended finite element models, the cracks were found to initiate at the same parallel circle (latitude) of microcapsule where the curvature change of the deformed shell (i.e., prime vertical strain) is the largest. With the increase of compression displacement, microcapsules show three crack propagation modes. Based on such findings, a maximum prime vertical strain criterion, i.e., cracks initiate when the maximum prime vertical strain exceeds a critical value, for estimating the rupture initiation of microcapsules under compression was proposed. The proposed criterion was validated by both numerical simulations and experiments. It demonstrates that the critical prime vertical strain of rupture is independent of the microcapsule dimensions and is an intrinsic parameter to judge the rupture of microcapsules. The critical prime vertical strain of rupture for n-hexadecane@PMMA microcapsules is 0.023±0.003. The proposed model avoids complicated stress analysis and provides an intrinsic criterion.
研究领域:
材料科学
·
力学
✓ 已验证
产品关联
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2026
·
IF 19.9
Siyu Guo,Xueting Ren,Xijiao Ren,Jinming He,Huocheng Yang,Wei Zhou,Menghuan Li,Lulu Wang,Yan Hu,Zhong Luo
The melanoma microenvironment is hallmarked by severe hypoxia and excessive regulatory T cells (Tregs), which significantly limits anti-melanoma efficacy of radiotherapy by impairing both its tumoricidal and immunostimulatory potential. Here, we report a supramolecular aptamer-engineered DNA di-tetrahedron nanoplatform (AEN) as a neoadjuvant treatment of melanoma radiotherapy, aiming to improve the radio-immunotherapeutic responses through dynamically remodeling the melanoma microenvironment. Specifically, DNA tetrahedra are separately loaded with vascular endothelial growth factor A inhibitor Thalidomide (Thal) and Treg-inhibitory drug Epirubicin (EPI) via DNA intercalation, followed by modification with plrogrammed death-ligand 1 (PD-L1) or cytotoxic T-lymphocyte-associated protein 4 (CTLA4) vascular endothelial growth factor A (VEGF-A)-binding aptamers and further conjugation with i-motif or chain-1 motifs to generate aptPD-L1-TDN@Thal and aptCTLA-4-TDN@EPI components, which eventually self-assemble into a di-tetrahedron through complementary binding between i-motif and chain-1. AENs dissociate into aptPD-L1-TDN@Thal and aptCTLA-4-TDN@EPI in acidic melanoma microenvironment, which are then taken up by PD-L1-overexpressing melanoma cells and CTLA4-overexpressing Tregs through ligand-mediated endocytosis. Thal inhibits tumor-intrinsic vascular endothelial growth factor A (VEGFA) signaling to normalize tumor vasculature for relieving hypoxia, while EPI inhibits Treg-intrinsic Foxp3-p65 signaling to abolish their immunosuppressive activity. The AEN treatment effectively remodels the melanoma microenvironment into a radiosensitive and immunosupportive state for enhancing the radio-immunotherapy response, providing an approach for melanoma radiotherapy in the clinic.
✓ 已验证
产品关联
DOI
高影响因子
Metabolites
·
2022
·Vol. 12
·期 5
·410
·
IF 5.581
Jieping Zhang,Shaomin Zou,Yijing Zhang,Ziqing Yang,Wencong Wang,Manqi Meng,Junyan Feng,Peng Zhang,Lishi Xiao,Mong-Hong Lee,Lekun Fang
Chemoresistance limits treatment outcomes in colorectal cancer (CRC) patients. A dimeric metabolite of indole-3-carbinol, 3,3′-diindolylmethane (DIM) is abundant in cruciferous vegetables and has shown anticancer efficacy. The role of DIM in regulating chemosensitivity in CRC remains unknown. In this study, we demonstrated that DIM treatment inhibits the malignant progression of CRC. RNA sequencing indicated that pyrimidine synthesis genes are attenuated by DIM treatment. Stable 13C-labeled glucose tracing revealed that DIM inhibits de novo pyrimidine biosynthesis in CRC. DIM increases 5-FU cytotoxicity in CRC via regulation of the expression of pyrimidine metabolism-related genes. DIM synergizes with 5-FU to enhance its inhibitory effects on CRC both in vivo and in vitro. Our results suggest that DIM improves the therapeutic outcomes of FU-based chemotherapy in CRCs by inhibiting pyrimidine metabolism, identifying a new strategy for clinical therapy.Keywords:colorectal cancer;3,3′-Diindolylmethane;chemosensitivity;pyrimidine metabolism
研究领域:
肿瘤学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2020
·
IF 6.155
Lin Chen,Mingyu Hu,Jun Guo,Xiaoyu Chong,Jing Feng
As candidate thermal/environmental barrier coatings (T/EBCs), the structure characteristics and comprehensive properties of monoclinic-prime (m') RETaO 4 (RE = Yb, Lu, Sc) with excellent Al 2 O 3 /SiO 2 chemical compatibility are studied. Excellent thermal insulation protection will be provided by m'RETaO 4 due to their low thermal conductivity (∼1.6 W m −1 K −1 , 900 °C) and prominent thermal radiation resistance, which is much better than those of YSZ (∼2.5 W m −1 K −1 , 1000 °C) and La 2 Zr 2 O 7 (∼2.0 W m −1 K −1 , 900 °C). The thermal expansion coefficients (TECs) are 3.0–8.0 × 10 -6 K −1 (200−1200 °C), which is suitable for T/EBCs applications. Furthermore, absence of phase transition and extraordinary chemical compatibility with Al 2 O 3 /SiO 2 up to 1500 °C indicate the potential application prospect. The documented governing mechanisms of m'RETaO 4 properties will enable researchers to promote their application in the future investigation.
研究领域:
材料科学
·
工程热物理
✓ 已验证
产品关联
DOI
高影响因子
EMBO JOURNAL
·
2020
·Vol. 39
·期 16
·e103631
·
IF 9.889
Xianping Wang,Jihong Gong,Le Zhu,Shen Wang,Xiaoyu Yang,Yuanyuan Xu,Xiaofei Yang,Cong Ma
Priming of synaptic vesicles involves Munc13-catalyzed transition of the Munc18-1/syntaxin-1 complex to the SNARE complex in the presence of SNAP-25 and synaptobrevin-2; Munc13 drives opening of syntaxin-1 via the MUN domain while Munc18-1 primes SNARE assembly via domain 3a. However, the underlying mechanism remains unclear. In this study, we have identified a number of residues in domain 3a of Munc18-1 that are crucial for Munc13 and Munc18-1 actions in SNARE complex assembly and synaptic vesicle priming. Our results showed that two residues (Q301/K308) at the side of domain 3a mediate the interaction between the Munc18-1/syntaxin-1 complex and the MUN domain. This interaction enables the MUN domain to drive the opening of syntaxin-1 linker region, thereby leading to the extension of domain 3a and promoting synaptobrevin-2 binding. In addition, we identified two residues (K332/K333) at the bottom of domain 3a that mediate the interaction between Munc18-1 and the SNARE motif of syntaxin-1. This interaction ensures Munc18-1 to persistently associate with syntaxin-1 during the conformational change of syntaxin-1 from closed to open, which reinforces the role of Munc18-1 in templating SNARE assembly. Taken together, our data suggest a mechanism by which Munc13 activates the Munc18-1/syntaxin-1 complex and enables Munc18-1 to prime SNARE assembly.
研究领域:
神经科学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
FUEL
·
2023
·
IF 7.4
Xinxing Wu,Zhiwei Fan,Shadrick Mwansa,Chen Huang,Qiang Yong
Exogenous ash penalties cause straw pulp residues to exhibit low autohydrolysis performance due to an organic–inorganic colloid medium. In this study, H 2 O 2 was applied following the soil organism to oxidize the organic components playing a role in the buffer system by increasing the negative charge on the surface of the particulate ash, thus reducing the acid buffer and cation exchange capacity of the pretreated wheat straw pulp residue (WSPR). The results showed that with the enzymatic efficiency increasing concentrations (0–3%) of H 2 O 2 , the enzymatic efficiencies of pretreated WSPR improved significantly with increasing H 2 O 2 concentration (0–3%) from 49.73 to 88.27%. A linear correlation was observed between these increases and the accessibility of the substrate to the enzymes, the substrate's surface charge, and the lignin's available surface area. The addition of 2% H 2 O 2 in WSPR autohydrolysis was able to increase the production of glucose and xylooligosaccharides by 1.58 and 2.38 times, respectively. This work demonstrated an innovative option for producing fermentable sugars from WSPR by effectively abolishing the self-buffering effects during autohydrolysis.
研究领域:
生物化学
·
可再生资源与环境科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF DENTISTRY
·
2025
·
IF 5.5
Bing Liang,Xiaolu Chen,Yi Sun,Xinni Pan,Ye Lin,Qi Gao,Ling Zhang,Yuedan Xu
Objectives This study introduced the prime-and-rinse approach with an methacryloyloxydecyl dihydrogen phosphate (MDP)-containing primer to augment the performance of modified self-etch adhesives loaded with amorphous fluorinated calcium phosphate (AFCP) nanoparticles. Methods The modified self-etch adhesive was acquired by adding 20 wt% AFCP nanoparticles into Clearfil S3 Bond. An experimental primer containing 15 wt% MDP was prepared. The bond performance was assessed through micro-tensile bond strength (MTBS) tests. Additionally, a single-layer collagen model and demineralized dentin were used to investigate mineralization characteristics. Cytotoxicity was evaluated using a modified transwell insert model on human dental pulp stem cells. Results The incorporation of AFCP nanoparticles into the Clearfil S3 Bond led to a significant reduction in MTBS. While the application of MDP primer could improve the bond performance of modified Clearfil S3 Bond. The MDP primer further augmented the mineralization of single-layer collagen model and demineralized dentin induced by modified self-etched adhesive. The relative cell viability was around 100 % in all groups in the study. Clinical significance These results indicated that the prime-and-rinse approach with MDP primer not only compensated for the reduced bond strength caused by the incorporation of AFCP nanoparticles but also enhanced mineralization capabilities and maintained biocompatibility, offering a promising strategy for improving the longevity of dental restorations.
研究领域:
牙科学
·
材料科学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Agrochem
·
2026
·
IF 9.2
Cuiyun Zhou,Qinghong Zeng,Chang Tang,Dan Sun,Zixuan Li,Shuilan Zhang,Tao Zheng,Zhaoyang Zhang,Mengke Wang,Shun He,Wa Gao
Nanomaterials offer new opportunities for sustainable control of crop diseases caused by soil-borne pathogens. Here, cobalt-encapsulated nitrogen-doped carbon nanotubes (Co@N-CNTs) with tubular and bamboo-like morphologies were synthesized and evaluated against tomato bacterial wilt. Co@N-CNTs showed strong antibacterial activity against Ralstonia solanacearum in vitro , with the tubular morphology being more effective. Mechanistic analyses indicated that Co@N-CNTs induced reactive oxygen species-mediated oxidative damage in R. solanacearum , resulting in DNA damage, cytoplasmic leakage, and membrane disruption. In pot experiments, Co@N-CNTs reduced disease severity and delayed progression, with efficacy comparable to Zhongshengmycin. Transcriptomic and biochemical analyses showed tissue-specific regulation of plant defense, reducing infection-induced SA accumulation in stems while enhancing the expression of several defense-related genes in leaves, whereas JA contents were not significantly altered. Co@N-CNTs showed no detectable adverse effects on tomato growth and exhibited low acute toxicity to Italian honeybees. Collectively, these findings demonstrate that Co@N-CNTs can control soil-borne bacterial diseases and hold promise for sustainable agriculture.
✓ 已验证
产品关联
DOI
高影响因子