Viruses-Basel
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2022
·Vol. 14
·期 11
·2431
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IF 5.818
Jing Zheng,Wenyuan Chen,Hao Xiao,Fan Yang,Xiaowu Li,Jingdong Song,Lingpeng Cheng,Hongrong Liu
GP4, a newRalstonia solanacearumphage, is a short-tailed phage. Few structures ofRalstonia solanacearumphages have been resolved to near-atomic resolution until now. Here, we present a 3.7 Å resolution structure of the GP4 head by cryo-electron microscopy (cryo-EM). The GP4 head contains 540 copies of major capsid protein (MCP) gp2 and 540 copies of cement protein (CP) gp1 arranged in an icosahedral shell with a triangulation number T = 9. The structures of gp2 and gp1 show a canonical HK97-like fold and an Ig-like fold, respectively. The trimeric CPs stick on the surface of the head along the quasi-threefold axis of the icosahedron generating a sandwiched three-layer electrostatic complementary potential, thereby enhancing the head stability. The assembly pattern of the GP4 head provides a platform for the further exploration of the interaction betweenRalstonia solanacearumand corresponding phages.Keywords:Ralstonia solanacearumphage;icosahedral head;triangulation number T = 9;trimeric CP;Cryo-EM
研究领域:
病毒学
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结构生物学
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微生物学
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DOI
PubMed
高影响因子
POLYMER DEGRADATION AND STABILITY
·
2021
·
IF 5.03
Zsófia Kovács,Ákos Pomázi,Andrea Toldy
The complexity of recycling crosslinked polymer composites has promoted the use of thermoplastic in situ polymerisable matrices, including ε-caprolactam-based polyamide 6 (PA6) in long-fibre reinforced composites. Their uptake by the automotive industry has created a need for adequate flame retardancy, which poses several challenges: flame retardants may hinder the in situ polymerisation reaction; moreover, the fibre reinforcement can filter out the additives not soluble in ε-caprolactam during liquid moulding composite processing, such as thermoplastic resin transfer moulding (T-RTM). We discussed the feasibility of the flame retardancy of ε-caprolactam-based PA6 and its composites, including the solubility of the additives in ε-caprolactam and their effect on the polymerisation reaction and fire performance. We evaluated the correlations between the flame retardant structure and the inhibition of polymerisation. Finally, we briefly summarised the composite processing and coating technologies suitable for preparing flame retarded ε-caprolactam-based PA6 matrix and composite systems, as well as the most often used tests for their characterisation.
研究领域:
材料科学
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高分子化学
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DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Ming Zhao,Chunting He,Xueyun Zheng,Min Jiang,Zhiqiang Xie,Hongjiao Wei,Shujun Zhang,Ying Lin,Jiaheng Zhang,Xun Sun
Vaccines represent one of the most powerful and cost-effective innovations for controlling a wide range of infectious diseases caused by various viruses and bacteria. Unlike mRNA and DNA-based vaccines, subunit vaccines carry no risk of insertional mutagenesis and can be lyophilized for convenient transportation and long-term storage. However, existing adjuvants are often associated with toxic effect and reactogenicity, necessitating expanding the repertoire of adjuvants with better biocompatibility, for instance, designing self-adjuvating polymeric carriers. We herein report a novel subunit vaccine delivery platform constructed via in situ free radical polymerization of C7A (2-(Hexamethyleneimino) ethyl methacrylate) and acrylamide around the surface of individual protein antigens. Using ovalbumin (OVA) as a model antigen, we observed substantial increases in both diameter (∼70 nm) and surface potential (−1.18 mV) following encapsulation, referred to as n( OVA )C7A. C7A's ultra pH sensitivity with a transition pH around 6.9 allows for rapid protonation in acidic environments. This property facilitates crucial processes such as endosomal escape and major histocompatibility complex (MHC)-I-mediated antigen presentation, culminating in the substantial CD8 + T cell activation. Additionally, compared to OVA nanocapsules without the C7A components and native OVA without modifications, we observed heightened B cell activation within the germinal center, along with remarkable increases in serum antibody and cytokine production. It's important to note that mounting evidence suggests that adjuvant effects, particularly its targeted stimulation of type I interferons (IFNs), can contribute to advantageous adaptive immune responses. Beyond its exceptional potency, the nanovaccine also demonstrated robust formation of immune memory and exhibited a favorable biosafety profile. These findings collectively underscore the promising potential of our nanovaccine in the realm of immunotherapy and vaccine development.
研究领域:
免疫学
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疫苗开发
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纳米技术
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生物医学工程
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Jinlian Liu,Ke Song,Bingqi Lin,Zhenfeng Chen,Zirui Zuo,Yixing Fang,Qi He,Xiaodan Yao,Zhifeng Liu,Qiaobing Huang,Xiaohua Guo
Neutrophils and T lymphocytes are closely related to occurrence of immunosuppression in sepsis. Studies have shown that neutrophil apoptosis decreases and T lymphocyte apoptosis increases in sepsis immunosuppression, but the specific mechanism involved remains unclear. In the present study, we found Toll-like Receptor 2 (TLR2) and programmed death-ligand 1 (PD-L1) were significantly activated in bone marrow neutrophils of wild-type mice after LPS treatment and that they were attenuated by treatment with C29, an inhibitor of TLR2. PD-L1 activation inhibits neutrophil apoptosis, whereas programmed death protein 1 (PD-1) activation promotes apoptosis of T lymphocytes, which leads to immunosuppression. Mechanistically, when sepsis occurs, pro-inflammatory factors and High mobility group box-1 protein (HMGB1) passively released from dead cells cause the up-regulation of PD-L1 through TLR2 on neutrophils. The binding of PD-L1 and PD-1 on T lymphocytes leads to increased apoptosis of T lymphocytes and immune dysfunction, eventually resulting in the occurrence of sepsis immunosuppression. In vivo experiments showed that the HMGB1 inhibitor glycyrrhizic acid (GA) and the TLR2 inhibitor C29 could inhibit the HMGB1/TLR2/PD-L1 pathway, and improving sepsis-induced lung injury. In summary, this study shows that HMGB1 regulates PD-L1 and PD-1 signaling pathways through TLR2, which leads to immunosuppression.
研究领域:
免疫学
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传染病学
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分子生物学
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DOI
PubMed
高影响因子
iScience
·
2023
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IF 5.8
Zhijie Zhang,Jiangzhou Shi,Qifang Wu,Zijian Zhang,Xiaoyan Liu,Anqi Ren,Guanlin Zhao,Ge Dong,Han Wu,Jiaxuan Zhao,Yuan Zhao,Jia Hu,Hui Li,Tongcun Zhang,Fuling Zhou,Haichuan Zhu
Dexamethasone (Dex) plays a critical role in T-ALL treatment, but the mechanisms of Dex resistance are poorly understood. Here, we demonstrated that the expression of JUN was regulated in Dex-resistant T-ALL cell lines and patient samples. JUN knockdown increased the sensitivity to Dex. Moreover, the survival data showed that high expression of JUN related to poor prognosis of T-ALL patients. Then, we generated dexamethasone-resistant clones and conducted RNA-seq and ATAC-seq. We demonstrated that the upregulation of JUN was most significant and regulated by JNK pathway in Dex-resistant cells. High-throughput screening showed that HIF1α inhibitors synergized with Dex could enhance Dex resistance cells death in vitro and in vivo. Additionally, JUN combined and stabilized HIF1α in Dex resistance cells. These results reveal a new mechanism of Dex resistance in T-ALL and provide experimental evidence for the potential therapeutic benefit of targeting the JNK-JUN-HIF1α axis for T-ALL treatment.
研究领域:
肿瘤学
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免疫学
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分子生物学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
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IF 12.8
Weihan Zhang,Shijun Yuan,Zipeng Zhang,Shunli Fu,Shujun Liu,Jinhu Liu,Qingping Ma,Zhenxing Xia,Panpan Gu,Shuying Gao,Zhiyue Zhang,Xinke Zhang,Yongjun Liu,Na Zhang
Tumor cells transmit various immunosuppressive signals and induce a dysfunctional state in T cells, which essentially leads to immune escape and tumor progression. However, developing effective strategies to counteract the domestication of T cells by tumor cells remains a challenge. Here, we prepared pH-responsive lipid nanoparticles (NL/PLDs) co-loaded with PCSK9 shRNA, lonidamine (LND), and low-dose doxorubicin (DOX). NL/PLDs can awaken domesticated T cells function by sending pro-activation, pro-recognition, and pro-killing signals by increasing tumor immunogenicity, increasing the expression of major histocompatibility complex I (MHC-I) on tumor cells, and alleviating the suppression effect of tumor-secreted lactic acid (LA) on the T cell effector function, respectively. In melanoma-bearing mice, NL/PLDs effectively relieved tumor immunosuppressive microenvironment (TIME) and enhanced the antitumor immunity mediated by CD8 + T cells. Furthermore, when combined with aPD-1, NL/PLDs demonstrated strong antitumor effects and increased immunotherapeutic efficacy. This regulatory strategy provides new insights for enhancing immunotherapy by regulating tumor immunosuppressive signals and shows significant potential for clinical tumor treatment.
研究领域:
肿瘤学
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免疫学
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纳米技术
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药理学
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2025
·Vol. 192
·期 2
·1-11
·
IF 5.3
Zhang Xiaoyu,Sun Ruimeng,Zheng Haoran,Qi Yanfei
A spherical nucleic acid (SNA, AuNPs-aptamer) into CRISPR/Cas12a system combined with poly T-template copper nanoparticles as fluorescence reporter was fabricated to establish an amplification-free sensitive method for Staphylococcus aureus ( S. aureus ) detection. This method, named PTCas12a, utilizes the concept that the bifunction of SNA recognizes the S. aureus and triggers the Cas12a cleavage activity. Then, the Cas12a enzyme cleaves the Poly T40 to generate a signal change in Poly T-Cu fluorescence, indicating the presence or absence of the target bacteria. The PTCas12a platform demonstrated a detection limit as low as 3.0 CFU/mL (3 N/S) in a wide response range of 1.0 × 10 1 –1.0 × 10 6 CFU/mL for S. aureus detection, which holds significant potential in ensuring food safety and preventing the spread of diseases. Graphical abstract
研究领域:
生物技术
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医学诊断
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食品安全
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DOI
PubMed
高影响因子
AICHE JOURNAL
·
2021
·Vol. 67
·期 8
·e17252
·
IF 3.993
Hu Li,Zisheng Zhang,Guanlun Sun,Suli Liu,Liangcheng An,Xingang Li,Hong Li,Xin Gao
As an attractive alternative technology for the separation of long chain olefin and paraffin, a novel silver-based deep eutectic solvent (Ag-DES) was prepared and utilized for 1-octene/n-octane separations. Comprehensive reactive extraction separation experiments were performed to highlight the Ag-DES concentration and operating temperature discriminations using compounds with different ratio of 1-octene/n-octane. The novel Ag-DES showed optimal separation performance regarding 1-octene/n-octane and possessed the highest levels separation selectivity in the range 3.57–16.11 with excellent circulation stability in our best knowledge. Furthermore, FT-Raman measurements and quantum chemistry calculation were performed to elucidate the interaction mechanism of Ag-DES in the separation of 1-octene and n-octane, which revealed that both chemical complexation and strong physical attraction existed in the complex of Ag-DES and 1-octene rather than n-octane. A practical process was proposed for the separation of olefin and paraffin, which indicates that an advanced separation technology could largely reduce the energy consumption. This study lends important insight for the development of Ag-DES reactive extraction separation process for the energy-efficient long chain α-olefins purification from F-T synthesis products.
研究领域:
化学工程
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能源科学
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DOI
高影响因子
JOURNAL OF MEMBRANE SCIENCE
·
2024
·
IF 8.4
Na Yang,Keting Li,Yufan Hao,Longfei Zhang,Yongli Sun,Luhong Zhang,Bin Jiang
Polyethyleneimine (PEI) nanofiltration (NF) membranes hold great application prospects in lithium extraction from salt lakes due to their high positive charge properties. However, the poor permeability of the membranes caused by the dense separation layer structure severely hinders their further application. Herein, a functional end-capping strategy was employed to address this problem by adding the effective end-capping reagent, Girard's Reagent T (GRT), to the PEI aqueous phase as the co-reaction reagent. Under the dual functions of the end-capping effect and the quaternary ammonium groups of GRT, the looseness and positive charge of the membrane were simultaneously optimized. After the modification of GRT, the looser structure of the PEI/GRT NF membrane improved its pure water flux (PWF) to 115 L m −2 h −1 at 6 bar, which was around 3.7 times higher than that of the original PEI NF membrane. Meanwhile, the enhanced positive charge (from −8 to 9 mV, pH = 7) of the membrane bottom surface allowed it to maintain the high rejection rate of MgCl 2 at 97.2 %. Besides, the PEI/GRT NF membrane exhibited good Mg 2+ /Li + selectivity (S Mg 2+ /Li + = 22.7, 2000 ppm, Mg 2+ /Li + mass ratio: 20:1). Therefore, this study provides a simple and feasible strategy for the preparation of high-permeable PEI NF membranes with good Mg 2+ /Li + separation performance.
研究领域:
材料科学
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环境工程
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DOI
高影响因子
TALANTA
·
2024
·
IF 5.6
Meixiang Xue,Shuangxi Cai,Ye Deng,Fang Luo,Jianhui Huang,Zhenyu Lin
T-2 toxin, a hazardous mycotoxin often present in cereals and products based on cereals, poses a substantial risk to humans and animals due to its high toxicity. The development of uncomplicated, quick and highly sensitive methods for detecting T-2 toxin is imperative. In this work, a portable sensing system was constructed using water column height as a readout device in combination with a controlled release system, which allows for an accurate quantitative analysis of T-2 toxin without the need for expensive instrumentation or skilled technicians. Hyaluronic acid (HA) hydrogel was constructed by double cross-linked DNA/aptamer hybrids with polyethyleneimine (PEI) and embedded with platinum nanoparticles (Pt NPs). The aptamer specifically bound to T-2 toxin in its presence, resulting in the disruption of the hydrogel and subsequent release of the Pt NPs. These Pt NPs were later mixed with a solution of H 2 O 2 in a confined reaction flask, leading to the decomposition of H 2 O 2 into O 2 . A glass capillary tube containing a column of red water had been inserted into the cap of the reaction flask, and the low solubility of O 2 led to an increase in pressure within the reaction unit, causing the red water column to rise. There is a good linear correlation between the height of the capillary liquid level and the T-2 toxin concentration in the range of 20 ng/mL to 6 μg/mL. The system has been successfully used to detect T-2 toxin in samples of barley tea and corn.
研究领域:
生物传感技术
·
食品安全检测
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Keying Liang,Shengsheng Mei,Xiangzheng Gao,Shanshan Peng,Jinbiao Zhan
Purpose T-DM1 is an antibody–drug conjugate (ADC) consisting of trastuzumab and DM1 linked together. T-DM1 binds to human epidermal growth factor receptor-2 (HER2) in tumors and then triggers the endocytosis of T-DM1 and release of payload. Therefore, endocytosis efficacy is considered as a critical step for the initiation of T-DM1 therapy; however, the endocytosis mechanism of T-DM1 remains poorly understood. Meanwhile, HER2 is regarded as an internalization-resistant receptor, which hinders the endocytosis and effectiveness of T-DM1. The present study is to explore the T-DM1 endocytosis pathway, which may provide insights into the internalization mechanism of ADCs and help to improve efficacy.Methods Confocal microscopy and flow cytometry were used to analyse T-DM1 intracellular trafficking and endocytosis efficiency, while Western blot assay was performed to detect T-DM1 degradation.Results We found that intracellular T-DM1 was increased to 50% within 12 h. T-DM1 was colocalized with cholera toxin B (CTxB), a lipid raft marker, within 2 h and then degraded in lysosome. Upon overexpression of caveolin-1 (CAV-1) and utilization of caveolae/lipid-raft disruptors, we found that temporal CAV-1 upregulation significantly facilitated T-DM1 endocytosis and degradation, whereas nystatin and lovastatin disrupted caveolae/lipid-raft structure and inhibited T-DM1 degradation. We demonstrate that T-DM1 internalizes through the lipid raft-mediated endocytosis in a CAV-1 dependent manner, rather than through the clathrin-mediated endocytosis in HER2-positive cancer cells.Conclusion Our findings suggest that modulation of the caveolae/lipid-raft mediated endocytosis may be a possible option for improving the clinical therapeutic effect of T-DM1 because it plays a key role in regulating T-DM1 internalization.
研究领域:
肿瘤学
·
细胞生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Kexin Zhang,Zhen Xu,Zexiu Xiao,Fei Cao,Jing Wang,Yuandong Xu,Winson M.J. Ma,Sihui Long,Gao-Feng Zha
Lipid nanoparticles (LNPs) have emerged as a clinically validated platform for cancer immunotherapy; however, challenges remain in optimizing RNA delivery and promoting synergistic immune activation. To address these issues, we developed a modified LNP system that incorporates α-galactosylceramide (α-GalCer), a CD1d-binding glycolipid known to activate invariant natural killer T (iNKT) cells. Through structural optimization, we created the α-GalCer-LNP (G-LNP), which offers three primary advantages over conventional four-component LNPs: (1) enhanced mRNA transfection efficiency due to improved endosomal/lysosomal escape, (2) increased capacity for in vivo DC transfection, leading to robust activation of tumor-specific CD8 + T cells via MHC-I and iNKT cells via the CD1d pathway, and (3) reprogramming of the tumor microenvironment, resulting in a 1.5-fold increase in iNKT cell infiltration and sustained elevation of IFN-γ (>24 h) in lymph nodes. In a TC-1 cervical carcinoma model, G-LNP induced complete tumor regression in 100 % of treated mice (compared to 42.85 % for standard LNP) and provided long-term protection against tumor rechallenge (lasting >100 days). Mechanistic studies showed that G-LNP preferentially targets CD11c + DC in the lymph nodes, facilitating coordinated antigen presentation and innate immune activation. This five-component engineering strategy establishes a versatile platform to enhance the functionality of LNPs for the development of next-generation cancer vaccines.
研究领域:
免疫学
·
肿瘤学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
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