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学者姓名：李昊
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Abstract ：
Immune checkpoint blockade based on antibodies has shown great clinical success in patients, but the transitory working manner leads to restricted therapeutic benefits. Herein, a genetically engineered adenovirus is developed as the vector to deliver CRISPR/Cas9 (sgCas9-AdV) to achieve permanent PD-L1 gene editing with efficiency up to 78.7% exemplified in Hepa 1-6 liver cancer cells. Furthermore, the sgCas9-AdV is loaded into hydrogel made by silk fiber (SgCas9-AdV/Gel) for in vivo application. The silk-gel not only promotes local retention of sgCas9-AdV in tumor tissue, but also masks them from host immune system, thus ensuring effectively gene transduction over 9 days. Bearing these advantages, the sgCas9-AdV/Gel inhibits Hepa 1-6 tumor growth with 100% response rate by single-dose injection, through efficient PD-L1 disruption to elicit a T cell-mediated antitumor response. In addition, the sgCas9-AdV/Gel is also successfully extended into other refractory tumors. In CT26 colon tumor characterized by poor response to anti-PD-L1, sgCas9-AdV/Gel is demonstrated to competent and superior anti-PD-L1 antibody to suppress tumor progression. In highly aggressive orthotopic 4T1 mouse breast tumor, such a therapeutic paradigm significantly inhibits primary tumor growth and induces a durable immune response against tumor relapse/metastasis. Thus, this study provides an attractive and universal strategy for immunotherapy.
Keyword ：
adenoviral vector adenoviral vector Cas9 Cas9 CRISPR CRISPR immunotherapy immunotherapy PD-L1 gene editing PD-L1 gene editing silk-gel silk-gel
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| GB/T 7714 | Wu, Ming , Li, Hao , Zhang, Cao et al. Silk-Gel Powered Adenoviral Vector Enables Robust Genome Editing of PD-L1 to Augment Immunotherapy across Multiple Tumor Models [J]. | ADVANCED SCIENCE , 2023 , 10 (12) . |
| MLA | Wu, Ming et al. "Silk-Gel Powered Adenoviral Vector Enables Robust Genome Editing of PD-L1 to Augment Immunotherapy across Multiple Tumor Models" . | ADVANCED SCIENCE 10 . 12 (2023) . |
| APA | Wu, Ming , Li, Hao , Zhang, Cao , Wang, Yingchao , Zhang, Cuilin , Zhang, Yuting et al. Silk-Gel Powered Adenoviral Vector Enables Robust Genome Editing of PD-L1 to Augment Immunotherapy across Multiple Tumor Models . | ADVANCED SCIENCE , 2023 , 10 (12) . |
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Precise control of cargo release is essential but still a great challenge for any drug delivery system. Irreversible electroporation (IRE), utilizing short high-voltage pulsed electric fields to destabilize the biological membrane, has been recently approved as a non-thermal technique for tumor ablation without destroying the integrity of adjacent collagenous structures. Due to the electro-permeating membrane ability, IRE might also have great potential to realize the controlled drug release in response to various input IRE parameters, which were tested in a red blood cell (RBC) model in this work. According to the mathematical simulation model of a round biconcave disc-like cell based on RBC shape and dielectric characteristics, the permeability and the pore density of the RBC membrane were found to quantitatively depend on the pulse parameters. To further provide solid experimental evidence, indocyanine green (ICG) and doxorubicin (DOX) were both loaded inside RBCs (RBC@DOX&ICG) and the drug release rates were found to be tailorable by microsecond pulsed electric field (mu sPEF). In addition, mu sPEF could effectively modulate the tumor stroma to augment therapy efficacy by increasing micro-vessel density and permeability, softening extracellular matrix, and alleviating tumor hypoxia. Benefiting from these advantages, this IRE-responsive RBC@DOX&ICG achieved a remarkably synergistic anti-cancer effect by the combination of mu sPEF and chemotherapy in the tumor-bearing mice model, with the survival time increasing above 90 days without tumor burden. Given that IRE is easily adaptable to different plasma membrane-based vehicles for delivering diverse drugs, this approach could offer a general applicability for cancer treatment. (c) 2023 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
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| GB/T 7714 | Peng, Wencheng , Yue, Yaqi , Zhang, Yuting et al. Scheduled dosage regimen by irreversible electroporation of loaded erythrocytes for cancer treatment [J]. | APL BIOENGINEERING , 2023 , 7 (4) . |
| MLA | Peng, Wencheng et al. "Scheduled dosage regimen by irreversible electroporation of loaded erythrocytes for cancer treatment" . | APL BIOENGINEERING 7 . 4 (2023) . |
| APA | Peng, Wencheng , Yue, Yaqi , Zhang, Yuting , Li, Hao , Zhang, Cao , Wang, Peiyuan et al. Scheduled dosage regimen by irreversible electroporation of loaded erythrocytes for cancer treatment . | APL BIOENGINEERING , 2023 , 7 (4) . |
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Combinatorial photothermal and immunotherapy have demonstrated great potential to remove primary tumors, suppress metastases, and prevent tumor recurrence. However, this strategy still confronts patients with many limitations, such as complex components, sophisticated construction, and inadequate therapeutic efficacy. In this work, small molecules of porphyrin derivatives (PPor) which can self-assemble into monodispersed nanoparticles without supplement of any other ingredients or surfactants are developed. The formed PPor nanoparticles (PPor NPs) exhibit highly photothermal conversion efficiency of 70% and NIR-II luminous abilities originate from the strong intramolecular charge transfer (ICT) effect of D-A structure under 808 nm laser irradiation, thus achieving NIR-II fluorescence imaging guided photothermal therapy (PTT) against primary tumors with a high cure rate. More importantly, tumor-associated antigens (TAAs), together with damage-associated molecular patterns (DAMPs) released from PTT-treated cancer cells, are proved to elicit immune responses to some degree. After combination with programmed cell death-1 (PD-1) antibodies, a robust systematic antitumor immunity is generated to restrain both primary and abscopal tumors growth, prolong survival, and prevent pulmonary metastasis on an aggressive 4T1 murine breast tumor model. Thus, this study provides a promising therapeutic paradigm with porphyrin derivatives nano-assembly as phototheranostic agents for the treatment of aggressive tumors with high efficiency.
Keyword ：
NIR-II fluorescence imaging NIR-II fluorescence imaging PD-1 antibodies PD-1 antibodies photothermal-immunotherapy photothermal-immunotherapy porphyrin derivatives porphyrin derivatives self-assembly self-assembly
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| GB/T 7714 | Cao, Yanbing , Wei, De , Yang, Lixia et al. Nanoplatform Self-Assembly from Small Molecules of Porphyrin Derivatives for NIR-II Fluorescence Imaging Guided Photothermal-Immunotherapy [J]. | ADVANCED HEALTHCARE MATERIALS , 2022 , 11 (11) . |
| MLA | Cao, Yanbing et al. "Nanoplatform Self-Assembly from Small Molecules of Porphyrin Derivatives for NIR-II Fluorescence Imaging Guided Photothermal-Immunotherapy" . | ADVANCED HEALTHCARE MATERIALS 11 . 11 (2022) . |
| APA | Cao, Yanbing , Wei, De , Yang, Lixia , Luo, Zijin , Yu, Peiwen , Li, Hao et al. Nanoplatform Self-Assembly from Small Molecules of Porphyrin Derivatives for NIR-II Fluorescence Imaging Guided Photothermal-Immunotherapy . | ADVANCED HEALTHCARE MATERIALS , 2022 , 11 (11) . |
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Intestinal enteritis is a main issue in crucian carp production which results in massive economic loss. Traditional antibiotics used for disease prevention of crucian carp (Carassius carassius) have been banned, thus an alternative approach needs to be identified. In this study, the bioactive peptide was evaluated as a diet supplement for preventing intestinal inflammation in crucian carp. Intestinal inflammation was induced by intrarectal admin-istration of a 2,4,6-trinitrobenzene sulfonic acid (TNBS) solution. The fish samples were fed with different diets for 14 days. The disease activity index (DAI), which included, fish swimming, food intake, anal inflammation, body surface, and ascites was determined daily. Intestine segments were stained with haematoxylin and eosin (H. E.) for histopathological analysis. The expression of cytokines, including interleukin-1 beta (IL-1 beta), interleukin-8 (IL -8), tumor necrosis factor alpha (TNF-alpha), and myeloperoxidase (MPO) in crucian carp were determined. In TNBS-induced groups, the DAI scores were dramatically increased compared to the control group. The histopatho-logical analysis showed that the damage of the fish intestine after the injection of TNBS. The relative expression levels of pro-inflammation cytokines (TNF-alpha, IL-1 beta, IL-8, MPO) were significantly increased compared to the control group on day 1. In the TNBS-induced group feed with a diet supplemented with bioactive peptide, the symptoms of intestinal inflammation were relieved on day 3 and the mRNA expression levels of pro -inflammation cytokines (TNF-alpha, IL-1 beta, IL-8, MPO) were reduced compared to day 1. On day 7, the fish sam-ples enrofloxacin group and bioactive peptide group were recovered from TNBS-induced intestinal inflammation. This study showed that the fish diet supplemented with bioactive peptide could help to prevent and recover from intestinal inflammation. Thus, the bioactive peptide can be used as a replacement for antibiotics to prevent disease in aquaculture production.
Keyword ：
Bioactive peptide Bioactive peptide Crucian carp Crucian carp Histology Histology Proinfilammatory molecules Proinfilammatory molecules TNBS TNBS
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| GB/T 7714 | Huang, Meijuan , Wei, Xinyao , Wu, Tiecheng et al. Inhibition of TNBS-induced intestinal inflammation in crucian carp (Carassius carassius) by oral administration of bioactive Bioactive food derived peptides [J]. | FISH & SHELLFISH IMMUNOLOGY , 2022 , 131 : 999-1005 . |
| MLA | Huang, Meijuan et al. "Inhibition of TNBS-induced intestinal inflammation in crucian carp (Carassius carassius) by oral administration of bioactive Bioactive food derived peptides" . | FISH & SHELLFISH IMMUNOLOGY 131 (2022) : 999-1005 . |
| APA | Huang, Meijuan , Wei, Xinyao , Wu, Tiecheng , Li, Mengyan , Zhou, Lei , Chai, Libing et al. Inhibition of TNBS-induced intestinal inflammation in crucian carp (Carassius carassius) by oral administration of bioactive Bioactive food derived peptides . | FISH & SHELLFISH IMMUNOLOGY , 2022 , 131 , 999-1005 . |
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目的:为使微藻裂殖壶菌提取DHA后的废弃物藻粕能被再利用,研究其酶解产物抑制肠道炎症的功效,为替代现有抗生素提供试验依据。方法:采用胰蛋白酶水解藻粕,透析后获得肽混合物(MESH),添加到含有维生素AD的饲料里。分别以草鱼和鳗鱼为淡水养殖及海洋鱼类代表性测试动物,构建三硝基苯磺酸(TNBS)肠炎模型,并灌注等体积磷酸盐缓冲溶液(PBS)为阴性对照组,抗生素恩诺沙星为阳性对照组,分别于灌注的1,3,7d解剖测试动物,通过疾病活动指数评分、髓过氧化物酶(MPO)活性的变化以及肠道病理组织变化等方面,对鱼肠炎程度进行综合评定。结果:经TNBS诱导,MESH组和恩诺沙星组均可预防治疗草鱼和鳗鱼的肠炎症...
Keyword ：
抗生素 抗生素 肠道炎症 肠道炎症 裂殖壶菌酶解肽 裂殖壶菌酶解肽
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| GB/T 7714 | 李孟研 , 柴力彬 , 张延杰 et al. 微藻裂殖壶菌藻粕酶解肽抑制水产鱼类肠道炎症的功效研究 [J]. | 中国食品学报 , 2020 , 20 (08) : 56-64 . |
| MLA | 李孟研 et al. "微藻裂殖壶菌藻粕酶解肽抑制水产鱼类肠道炎症的功效研究" . | 中国食品学报 20 . 08 (2020) : 56-64 . |
| APA | 李孟研 , 柴力彬 , 张延杰 , 邝丽红 , 李昊 . 微藻裂殖壶菌藻粕酶解肽抑制水产鱼类肠道炎症的功效研究 . | 中国食品学报 , 2020 , 20 (08) , 56-64 . |
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Objective: In order to enable the reuse of waste algal meal after the extraction of DHA by microalgae Schizochytrium sp., this project conducted studies on the efficacy of its enzymatic hydrolysis products to inhibit intestinal inflammation, and laid a solid experimental foundation for the application of its replacement of existing antibiotics. Method: Trypsin was used to hydrolyze the algal meal, and the peptide mixture(MESH) was obtained after dialysis. It was added to the feed containing vitamin AD. Grass carp and eel was used for freshwater farming and marine fish as representative test animal for constructing trinitrobenzenesulfonic acid(TNBS) enteritis model. Negative control group were used of equal volume phosphate buffer solution(PBS), and positive control group were used antibiotic enrofloxacin. The test animals were dissected 1, 3 days and 7 days after infusion, respectively. The disease activity index scores, changes in myeloperoxidase (MPO) activity, and changes in intestinal pathological tissues were used to comprehensively assess the degree of fish enteritis. Results: After induction by TNBS, both MESH group and enrofloxacin group could prevent and treat the enteritis symptoms of grass carp and eel. Among them, the MESH group had more significant prevention and treatment effects on enteritis than the enrofloxacin group. Conclusion: Microalgae Schizochytrium sp. meal enzymatically active peptide MESH compound feed vitamin AD can effectively inhibit aquatic fish enteritis, and can replace the existing antibiotics used in enteritis. © 2020, Editorial Office of Journal of CIFST. All right reserved.
Keyword ：
Algae Algae Antibiotics Antibiotics Enzymatic hydrolysis Enzymatic hydrolysis Fish Fish Mesh generation Mesh generation Microorganisms Microorganisms Pathology Pathology Peptides Peptides
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| GB/T 7714 | Li, Mengyan , Chai, Libin , Zhang, Yanjie et al. Studies on the Effect of Microalgae Schizochytrium sp. Algal Meal Enzymatic Hydrolysis Peptide on Inhibiting Intestinal Inflammation of Aquatic Fish [J]. | Journal of Chinese Institute of Food Science and Technology , 2020 , 20 (8) : 56-64 . |
| MLA | Li, Mengyan et al. "Studies on the Effect of Microalgae Schizochytrium sp. Algal Meal Enzymatic Hydrolysis Peptide on Inhibiting Intestinal Inflammation of Aquatic Fish" . | Journal of Chinese Institute of Food Science and Technology 20 . 8 (2020) : 56-64 . |
| APA | Li, Mengyan , Chai, Libin , Zhang, Yanjie , Kuang, Lihong , Li, Hao . Studies on the Effect of Microalgae Schizochytrium sp. Algal Meal Enzymatic Hydrolysis Peptide on Inhibiting Intestinal Inflammation of Aquatic Fish . | Journal of Chinese Institute of Food Science and Technology , 2020 , 20 (8) , 56-64 . |
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Bioengineered marine microalgae Schizochytrium sp. is currently used to produce docosahexaenoic acid (DHA). However, following DHA extraction, the remaining protein-rich materials are not well utilized. In this study, we report that marine microalgae bioengineered Schizochytrium sp. hydrolysate (MESH), which exhibits a unique peptide profile as identified by Ultra Performance Liquid Chromatography coupled with Q-TOF mass spectrometry(UPLC/Q-TOF-MS), ameliorated bowel inflammation in mice. In a mouse model of experimentalcolitis induced by dextran sulfate sodium, compared with the control mice, the mice treated with MESH were highly resistant to colitis, as demonstrated by marked reductions in body weight loss, clinical colitis scores, colonic histological damage, and colonic inflammation. Mechanistically, MESH attenuated the induction of pro-inflammatory cytokines and increased the induction of anti-inflammatory cytokines. MESH also promoted the proliferation of colonic crypt stem cells and progenitor cells required for crypt repair. Collectively, these results reveal a previously unrecognized role of MESH as a potential anti-inflammatory treatment for colitis.
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| GB/T 7714 | Wang, Xiaoli , Wang, Heng , Pierre, Joseph F. et al. Marine microalgae bioengineered Schizochytrium sp. meal hydrolysates inhibits acute inflammation [J]. | SCIENTIFIC REPORTS , 2018 , 8 . |
| MLA | Wang, Xiaoli et al. "Marine microalgae bioengineered Schizochytrium sp. meal hydrolysates inhibits acute inflammation" . | SCIENTIFIC REPORTS 8 (2018) . |
| APA | Wang, Xiaoli , Wang, Heng , Pierre, Joseph F. , Wang, Sheng , Huang, Huifang , Zhang, Jun et al. Marine microalgae bioengineered Schizochytrium sp. meal hydrolysates inhibits acute inflammation . | SCIENTIFIC REPORTS , 2018 , 8 . |
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对工厂化养殖模式、网箱养殖模式养殖的大黄鱼和野生大黄鱼进行了肌肉常规营养成分、氨基酸和脂肪酸的分析比较.研究结果表明,工厂化养殖模式和网箱养殖模式的大黄鱼粗蛋白含量均显著低于野生大黄鱼(P<0.05),粗脂肪含量均显著高于野生大黄鱼(P<0.05).工厂化养殖模式的大黄鱼必需氨基酸总量、呈味氨基酸总量和氨基酸总量均显著高于网箱养殖大黄鱼,但显著低于野生大黄鱼(P<0.05).工厂化养殖模式的大黄鱼多不饱和脂肪酸以及二十碳五烯酸+二十二碳六烯酸均显著高于网箱养殖的而显著低于野生大黄鱼(P<0.05).工厂化养殖模式养殖大黄鱼可以生产出肉质营养结构和风味优于传统网箱养殖的大黄鱼.
Keyword ：
大黄鱼 大黄鱼 工厂化养殖模式 工厂化养殖模式 比较分析 比较分析 肉质 肉质
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| GB/T 7714 | 阮成旭 , 袁重桂 , 陶翠丽 et al. 不同养殖模式对大黄鱼肉质的影响 [J]. | 水产科学 , 2017 , 36 (5) : 623-627 . |
| MLA | 阮成旭 et al. "不同养殖模式对大黄鱼肉质的影响" . | 水产科学 36 . 5 (2017) : 623-627 . |
| APA | 阮成旭 , 袁重桂 , 陶翠丽 , 陈强 , 林文相 , 李昊 . 不同养殖模式对大黄鱼肉质的影响 . | 水产科学 , 2017 , 36 (5) , 623-627 . |
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为制备并鉴定盐酸克伦特罗(CLB)完全抗原CLB-BSA,采用重氮法将盐酸克伦特罗(CLB)和牛血清白蛋白(BSA)进行偶联,通过SDS-PAGE凝胶电泳、紫外全波长扫描、傅里叶红外光谱法等进行鉴定,现有盐酸克伦特罗完全抗原鉴定方法未曾采用过傅里叶红外光谱法.结果表明:本方法成功地制备了完全抗原,偶联比在9~13.通过投料比与偶联比关系的探究,可知当CLB与BSA的投料比例小于80:1时,偶联比随着投料比例的增加而升高,但当投料比大于80:1时,偶联比反而下降,为了节约成本,投料比应控制在80:1以下.
Keyword ：
偶联比 偶联比 制备 制备 完全抗原 完全抗原 盐酸克伦特罗 盐酸克伦特罗 鉴定 鉴定
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| GB/T 7714 | 陈艺宏 , 张琛卿 , 贺延志 et al. 盐酸克伦特罗完全抗原的鉴定 [J]. | 生物化工 , 2017 , 3 (1) : 5-9 . |
| MLA | 陈艺宏 et al. "盐酸克伦特罗完全抗原的鉴定" . | 生物化工 3 . 1 (2017) : 5-9 . |
| APA | 陈艺宏 , 张琛卿 , 贺延志 , 张宏 , 王玉帅 , 李昊 . 盐酸克伦特罗完全抗原的鉴定 . | 生物化工 , 2017 , 3 (1) , 5-9 . |
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本发明公开了一种微藻蛋白酶解肽在制备预防及治疗肠炎药物中的应用。所述的微藻蛋白酶解肽具体是以裂殖壶菌藻粕的下脚料为原材料，经酶解、离心、超滤等步骤，获得分子量为300~850 Da、具有抗炎效果的生物活性肽。将该生物活性肽制备成药物，能用于预防或治疗肠炎。该生物活性肽性质稳定可靠，无毒无害无污染。而且把藻粕变成保健或者医药产品等，提升了其利用价值，具有显著的经济和社会的效益。
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| GB/T 7714 | 李昊 , 卓燕发 , 贺延志 et al. 微藻蛋白酶解肽在制备预防及治疗肠炎药物中的应用 : CN201710353174.X[P]. | 2017/5/18 . |
| MLA | 李昊 et al. "微藻蛋白酶解肽在制备预防及治疗肠炎药物中的应用" : CN201710353174.X. | 2017/5/18 . |
| APA | 李昊 , 卓燕发 , 贺延志 , 曾青竹 , 张琛卿 . 微藻蛋白酶解肽在制备预防及治疗肠炎药物中的应用 : CN201710353174.X. | 2017/5/18 . |
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