JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Chongzheng Yan,Zhichao Kong,Yuxue Pan,Zhipeng Fu,Kun Han,Xiaotian Zhao,Jing Zhang,Longyu Bo,Weiyi Sun,Jinxin Gao,Xianghui Dong,Zuolin Zheng,Xiao Yue,Peng Sun,Xinyi Jiang,Chen Chen
Chimeric antigen receptor microglia (CAR-M)-mediated amyloid-β oligomers (AβO) phagocytosis shows great promise in Alzheimer's disease (AD) treatment, however, the limited AβO degradation of CAR-M compromises their anti-AβO potency. This work here reports an in situ engineered agonistic anti-C-type lectin domain containing 7 A (CLEC7A) nanobody to accelerate AβO degradation of CAR-M, augmenting their anti-AβO efficacy. Specifically, with the intranasal-delivered microglia-targeting lipid nanoparticles (LNP), this work generates an AβO-specific degradation-potentiated CAR-M by introducing dual mRNAs encoding AβO-specific CAR and anti-CLEC7A nanobody into the cerebral microglia. These data show that these engineered CAR-M exhibited superior phagocytic function and promoted intracellular AβO degradation via activating CLEC7A-spleen tyrosine kinase (SYK) signaling pathway through the local secretion of anti-CLEC7A nanobody. In the APP/PS1 mouse model of AD, these in situ reprogrammed CAR-M significantly reduced cerebral Aβ levels, suppressed neuroinflammation, and restored cognitive function. In sum, these findings demonstrate that potentiating AβO degradation within CAR-M effectively alleviates AD pathology, providing a promising therapeutic strategy for AD with broad application in other neurodegenerative diseases.
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PubMed
高影响因子
Frontiers in Immunology
·
2024
·
IF 5.7
Tang Lei,Sun Qinyi,Li Mengyuan,Yu Xiaoxiao,Meng Jinguo,Zhang Yun,Ma Yuxiao,Zeng Aizhong,Li Zhuolan,Liu Yuanyuan,Xu Xinyu,Guo Wei
Background: Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs.Methods: We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the in vitro and in vivo efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods.Results: The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model.Conclusions: This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.
研究领域:
肿瘤学
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免疫治疗
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分子生物学
·
癌症研究
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DOI
高影响因子
JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS
·
2026
·
IF 6.7
Qiming Zhang,Chengyang Cao,Chong Xia,Qi Liao,Yang Ren,Hongyun Hu
Pyrolytic resource recovery of waste tires has been widely implemented at engineering scale, with truck tires as the dominant feedstock, whereas passenger car tires (PCTs) remain difficult to valorize because they generally yield low-value pyrolysis products. In this study, a NaOH–Na 2 CO 3 eutectic molten-salt strategy was investigated for regulating tar composition and simultaneously producing low-ash, low-sulfur char. Passenger car tires (PCTs) and truck tires (TTs) were used as feedstocks to compare product distribution, tar composition, gas properties, and the migration behavior of ash and sulfur in chars under conventional pyrolysis and molten salt pyrolysis. The molten salt system markedly regulated waste-tire pyrolysis product distribution, although the governing pathways were strongly feedstock-dependent. For PCT, molten salt pyrolysis increased tar yield from 33.00% to 38.20%, raised aliphatic hydrocarbons from 34.85% to 56.56%, and limonene accounted for 64.02% of the aliphatic hydrocarbon fraction in PCT-MS. These changes suggest that the molten salt medium promoted the release of primary volatiles and suppressed the secondary aromatization of high-value aliphatic products. Meanwhile, at 425 °C, the ash removal efficiency of PCT char increased from only 1.42% under conventional pyrolysis to 89.08% under molten-salt pyrolysis, while its total sulfur content decreased from 2.59 wt% to 0.75 wt%, indicating effective ash and sulfur removal. By contrast, the molten salt mainly weakened the strong char-forming tendency of TT, reducing the char yield from 60.67% to 43.65% and increasing the lower heating value (LHV) of the pyrolysis gas from 10.23 to 15.49 MJ/Nm 3 . Overall, NaOH-Na 2 CO 3 molten salt can contribute to the simultaneous recovery of high-quality tar and low-ash, low-sulfur char from PCT by enhancing heat and mass transfer, regulating secondary reactions of volatiles, and promoting ash and sulfur migration. The approach offers a feasible route for the high-value pyrolytic utilization of underused passenger car tires.
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高影响因子
FUEL PROCESSING TECHNOLOGY
·
2018
·
IF 3.956
Zheng Yang,Xian-Yong Wei,Min Zhang,Dao-Guang Teng,Ya-Nan Wang,Zhong-Qiu Liu,Zhi-Min Zong
A novel and highly active magnetic solid superacid (MSSA) with extraordinary separable and recyclable properties was facilely developed by impregnating trifluoromethanesulfonic acid onto mesoporous zirconia coated ferroferric oxide nanoparticles . The extraction residue (ER) from Piliqing subbituminous coal was subjected to non-catalytic hydrocracking (NCHC) and catalytic hydrocracking (CHC) in cyclohexane over MSSA at 300 °C. Detailed molecular compositions of the soluble portions from NCHC (SP NCHC ) and CHC (SP CHC ) were characterized with a Fourier transform infrared spectrometer and gas chromatograph/mass spectrometer (GC/MS). As a result, the yield of SP CHC is remarkably higher than that of SP NCHC and most of the GC/MS-detectable compounds in SP CHC are arenes, while SP NCHC contains alkanes, arenes, arenols, and ketones , indicating that MSSA effectively catalyzed the cleavage of C ar -C alk bridged bonds connecting some aromatic rings (ARs) and side chains on some ARs in the ER. Di(1-naphthyl)methane (DNM) and 9-benzylphenanthrene (9-BP) were used as coal-related model compounds (CRMCs) and their CHCs were investigated to further probe the catalysis of MSSA in the CHC of the ER. The result suggests that MSSA is highly active for cleaving the C ar -C alk bond in the CRMCs and generating naphthalene and phenanthrene under mild conditions. Based on the exploration of controlling reactions, the catalytic mechanism was discussed. MSSA could be easily separated and still active for the CHC of DNM after 3-times recycle.
研究领域:
化学工程
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煤炭化学
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Tengteng Yuan,Shujie Lv,Wei Zhang,Yanan Tang,Hong Chang,Zihan Hu,Liang Fang,Jiaojiao Du,Sifan Wu,Xinli Yang,Yangfu Guo,Ruihan Guo,Zongrui Ge,Lei Wang,Caiyun Zhang,Rulin Wang,Weidong Chen
Paeoniflorin (PF) has a certain therapeutic effect on cholestasis liver injury. To further improve the bioavailability of PF and play its pharmacological role in liver protection, PF-phospholipid complex micelles (PF-PLC micelles) were prepared based on our previous research on PF-PLC. The protective effects of PF and PF-PLC micelles on cholestasis liver injury induced by 17α-ethynylestradiol (EE) were compared, and the possible mechanisms were further explored. Herein, we showed that PF-PLC micelles effectively improved liver function, alleviated liver pathological damage, and localized infiltration of inflammatory cells. Mechanism studies indicated that PF-PLC micelles treatment could suppress the TLR4/MyD88/NF-κB pathway, and further reduce the levels of pro-inflammatory factors. Meanwhile, our experimental results demonstrated that the beneficial effect of PF-PLC micelles on EE-induced cholestasis may be achieved by the upregulation of nuclear receptors and metabolic enzymes (PXR/CAR/UGT1A1). All these results indicate that PF-PLC micelles have great potential in the treatment of cholestatic liver disease.
研究领域:
药理学
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肝病学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Xueting Liu,Yajing Zhu,Yutong Jing,Yuheng Zhu,Lichuan Wu,Wenqian Nong
Bacteria deep in the wound can cause prolonged inflammation and dysfunctional angiogenesis, impeding healing and potentially leading to chronic conditions, disability, or even death. To address this, we developed a double-layer metal-organic framework (MOF) microneedle (MN) patch system (GCM-MN-CSH), designed to accelerate the healing of infected wounds through programmed therapy. The GCM-MN-CSH system consists of a hydrocaffeic acid-modified chitosan (CSH) hydrogel patch and a metformin (Met)-loaded Ga-Car-MOF (GCM)-based γ-polyglutamic acid matrix MN array (GCM-MN). The GCM nanoparticles were incorporated in the MN tips. The deep, localized penetration of GCM-MN, combined with the multifunctional activity of GCM, enables effective delivery of GCM nanoparticles into the dermis. These nanoparticles acid-response release Ga 3+ ions and benzylpenicillin carboxylate, which possess antimicrobial activity, as well as Met, which promotes tissue regeneration. The adhesive CSH patch not only helps create a controlled, moist environment at the wound site but also provides antimicrobial properties on the surface. Together, the components of the GCM-MN-CSH system work synergistically to control infection, reduce inflammation, stimulate tissue proliferation, support tissue remodeling, and ultimately enable programmed wound healing. This advanced system offers a promising therapeutic platform for the management of infected wounds.
研究领域:
生物医学工程
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药学
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伤口愈合
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纳米技术
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材料科学
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DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
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2017
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IF 5.099
Zheng-Hai Du,Jun Xia,Xiao-Chen Sun,Xue-Nan Li,Cong Zhang,Hua-Shan Zhao,Shi-Yong Zhu,Jin-Long Li
Di-(2-ethylhexyl)-phthalate (DEHP) is causing serious health hazard in wildlife animal and human through environment and food chain, including the effect of brain development and impacted neurobehavioral outcomes. However, DEHP exposure caused cerebellar toxicity in bird remains unclear. To evaluate DEHP-exerted potential neurotoxicity in cerebellum, male quails were exposed with 0, 250, 500 and 750 mg/kg BW/day DEHP by gavage treatment for 45 days. Neurobehavioral abnormality and cerebellar histopathological alternation were observed in DEHP-induced quails. DEHP exposure increased the contents of total Cytochrome P450s (CYPs) and Cytochrome b5 (Cyt b5) and the activities of NADPH-cytochrome c reductase (NCR) and aniline-4-hydeoxylase (AH) in quail cerebellum. The expression of nuclear xenobiotic receptors (NXRs) and the transcriptions of CYP enzyme isoforms were also influenced in cerebellum by DEHP exposure. These results suggested that DEHP exposure caused the toxic effects of quail cerebellum. DEHP exposure disrupted the cerebellar CYP enzyme system homeostasis via affecting the transcription of CYP enzyme isoforms. The cerebellar P450arom and CYP3A4 might be biomarkers in evaluating the neurotoxicity of DEHP in bird. Finally, this study provided new evidence that DEHP-induced toxic effect of quail cerebellum was associated with activating the NXRs responses and disrupting the CYP enzyme system homeostasis.
研究领域:
环境毒理学
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神经毒理学
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分子生物学
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DOI
PubMed
高影响因子
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
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2015
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IF 6.332
Lushan Yu,Zhangting Wang,Minmin Huang,Yingying Li,Kui Zeng,Jinxiu Lei,Haihong Hu,Baian Chen,Jing Lu,Wen Xie,Su Zeng
The constitutive androstane receptor (CAR) is a key sensor in xenobiotic detoxification and endobiotic metabolism. Increasing evidence suggests that CAR also plays a role in energy metabolism by suppressing the hepatic gluconeogenesis and lipogenesis . In this study, we investigated the effects of two evodia alkaloids, rutaecarpine ( Rut ) and evodiamine ( Evo ), on gluconeogenesis and lipogenesis through their activation of the human CAR (hCAR). We found that both Rut and Evo exhibited anti-lipogenic and anti-gluconeogenic effects in the hyperlipidemic HepG2 cells. Both compounds can potently activate hCAR, and treatment of cells with hCAR antagonists reversed the anti-lipogenic and anti-gluconeogenic effects of Rut and Evo . The anti-gluconeogenic effect of Rut and Evo was due to the CAR-mediated inhibition of the recruitment of forkhead box O1 (FoxO1) and hepatocyte nuclear factor 4α (HNF4α) onto the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene promoters. In vivo, we showed that treatment of mice with Rut improved glucose tolerance in a CAR-dependent manner. Our results suggest that the evodia alkaloids Rut and Evo may have a therapeutic potential for the treatment of hyperglycemia and type 2 diabetes. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors : New Tricks for An Old Dog, edited by Dr. Wen Xie.
研究领域:
药理学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
Obesity
·
2015
·Vol. 24
·期 2
·368-378
·
IF 3.734
Ziquan Lv,Jinquan Cheng,Suli Huang,Yanwei Zhang,Shuang Wu,Yangshen Qiu,Yijie Geng,Qian Zhang,Guanqin Huang,Quan Ma,Xing Xie,Shiquan Zhou,Tangchun Wu,Yuebin Ke
Objective Di(2-ethylhexyl) phthalate (DEHP) is reported to cause obesity and hypothyroidism in both humans and rodents, but the underlying mechanisms were largely unknown. This study was designed to clarify the effects and the mechanisms of DEHP on the pathogenesis of obesity and hypothyroidism and to discover the relationship between them. Methods Male C3H/He mice were treated with DEHP for 5 weeks, and the body weight, food intake, and body temperature were recorded during the exposure. After exposure, key organs and serum were analyzed by Q-PCR, Western blot, and ELISA. Results DEHP induced significant body weight gain and adipogenesis in all exposure groups except for 0.05 mg/kg. Marked hyperphagia and daytime hypothermia were also observed, which were accompanied by disturbed hypothalamic neuropeptide expression and reduced BAT UCP1 expression. In addition, WAT lipid metabolism was significantly deceased at low dose (0.5 mg/kg) and increased at high dose (50 and 200 mg/kg). DEHP also induced hypothyroidism, which was probably attributed to the combined effects of hepatic CAR activation and hypothalamic TRH inhibition induced by hypothalamic leptin resistance. Conclusions Chronic DEHP exposure could induce obesity by interrupting energy homeostasis, which is probably due to the synergistic effects of hypothyroidism and hypothalamic leptin resistance.
研究领域:
毒理学
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内分泌学
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代谢
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DOI
PubMed
高影响因子
Metabolic Engineering Communications
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2022
·
IF 0
Yushi Liu,Wan-Qiu Liu,Shuhui Huang,Huiling Xu,Haofan Lu,Changzhu Wu,Jian Li
Fatty acid-derived products such as alkanes, fatty aldehydes, and fatty alcohols have many applications in the chemical industry. These products are predominately produced from fossil resources, but their production processes are often not environmentally friendly. While microbes like Escherichia coli have been engineered to convert fatty acids to corresponding products, the design and optimization of metabolic pathways in cells for high productivity is challenging due to low mass transfer, heavy metabolic burden, and intermediate/product toxicity. Here, we describe an E. coli -based cell-free protein synthesis (CFPS) platform for in vitro conversion of long-chain fatty acids to value-added chemicals with product selectivity, which can also avoid the above issues when using microbial production systems. We achieve the selective biotransformation by cell-free expression of different enzymes and the use of different conditions (e.g., light and heating) to drive the biocatalysis toward different final products. Specifically, in response to blue light, cell-free expressed fatty acid photodecarboxylase (CvFAP, a photoenzyme) was able to convert fatty acids to alkanes with approximately 90% conversion. When the expressed enzyme was switched to carboxylic acid reductase (CAR), fatty acids were reduced to corresponding fatty aldehydes, which, however, could be further reduced to fatty alcohols by endogenous reductases in the cell-free system. By using a thermostable CAR and a heating treatment, the endogenous reductases were deactivated and fatty aldehydes could be selectively accumulated (>97% in the product mixture) without over-reduction to alcohols. Overall, our cell-free platform provides a new strategy to convert fatty acids to valuable chemicals with notable properties of operation flexibility, reaction controllability, and product selectivity.
研究领域:
代谢工程
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生物技术
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化学工程
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生物化学
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DOI
PubMed
ADVANCED FUNCTIONAL MATERIALS
·
2024
·
IF 18.5
Liyang Wang,Leong Chi Cheng,Yu Chen,Huajuan Zhai,Zhiyong Chen,Tingting Ren,Leimei Xu,Jiandong Ding,Junjun Qiu,Keqin Hua,Lin Yu
Reproductive health concerns like Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome are prevalent in today's society. MRKH syndrome is a condition that severely affects women's sexual life, fertility, and mental health and has a high prevalence of one out of 5000 female births. Vaginoplasty is the primary method to regain patients’ reproductive health. However, conventional vaginoplasty faces various challenges, including complex and non-customized treatment procedures causing intense pains and complications. To bring new advances to vaginoplasty, a 3D-printed hydrogel scaffold is developed to provide satisfactory mechanical support and bioactivity for accelerating defect repair after surgery. The hydrogel scaffold consisting of gelatin methacryloyl (gelMA) and carrageenan (Car) is custom 3D-printed using an ambient temperature printing system. Furthermore, the scaffold undergoes dual-crosslinking through chemical crosslinking of gelMA and ionic crosslinking of Car with magnesium ions (Mg 2+ ). This dual-crosslinking strategy substantially improves the overall mechanical properties of the scaffold and introduces bioactive Mg 2+ . The sustained release of Mg 2+ plus the extracts from the dual-crosslinked scaffold significantly promotes cell proliferation, migration and angiogenesis. In a preclinical rat model with penetrating genital tract defects mimicking vaginoplasty, the implantation of dual-crosslinked scaffold repairs the penetrating wounds to near-normal levels within one week, showing potential as an alternative for better regaining reproductive health.
研究领域:
组织工程
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生殖健康
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生物医学工程
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生物材料
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）