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ROS-sensitive PD-L1 siRNA cationic selenide nanogels for self-inhibition of autophagy and prevention of immune escape

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Bioactive Materials 2024年第11期41卷 597-610页

作者： Jie Gao Yonghua Zhai Weihong Lu Xianghe jiang Jingsheng Zhou Lili wu Longhai Du Chunqing Ou Xinyi Zhang Hanliang He jian Zhu Zhengbiao Zhang Meiyun Li Yan wu Xiangqiang Pan State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials Jiangsu Key Laboratory of Advanced Functional Polymer Design and ApplicationCollege of ChemistryChemical Engineering and Materials ScienceSoochow UniversitySuzhou215123China Changhai Clinical Research Unit Shanghai Changhai HospitalNaval Medical UniversityShanghai200433China Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices Shanghai200433China College of Life Science Mudanjiang Medical UniversityMudanjiang157011China Department of Orthopedics Jinshan HospitalFudan UniversityShanghai201508China The Department of Orthopedic Surgery Dushu Lake Hospital Affiliated to Soochow UniversitySuzhou215028China

In the field of cancer therapy,inhibiting autophagy has emerged as a promising ***,pharmacological disruption of autophagy can lead to the upregulation of programmed death-ligand 1(PD-L1),enabling tumor immune *** address this issue,we developed innovative ROS-responsive cationic poly(ethylene imine)(PEI)nanogels using selenol chemistry-mediated multicomponent reaction(MCR)*** procedure involved simple mixing of low-molecular-weight PEI(LMW PEI),γ-selenobutylacetone(γ-SBL),and poly(ethylene glycol)methacrylate(PEGMA).Through high-throughput screening,we constructed a library of AxSeyOz nanogels and identified the optimized A1.8Se3O0.5/siPD-L1 nanogels,which exhibited a size of approximately 200 nm,excellent colloidal stability,and the most effective PD-L1 silencing *** nanogels demonstrated enhanced uptake by tumor cells,excellent oxidative degradation ability,and inhibited autophagy by alkalinizing *** A1.8Se3O0.5/siPD-L1 nanogels significantly downregulated PD-L1 expression and increased the expression of major histocompatibility complex class I(MHC-I),resulting in robust proliferation of specific CD8+T cells and a decrease in MC38 tumor *** a result,the A1.8Se3O0.5/siPD-L1 nanogels inhibited tumor growth through self-inhibition of autophagy,upregulation of MHC-I,and downregulation of *** with dynamic diselenide bonds,the A1.8Se3O0.5/siPD-L1 nanogels showed synergistic antitumor efficacy through self-inhibition of autophagy and prevention of immune escape.

关键词： Multicomponent reaction ROS sensitive Cationic nanogel Autophagy inhibition Immune escape

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CYP1A1 Ile462Val polymorphism contributes to colorectal cancer risk:A meta-analysis

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World Journal of Gastroenterology 2011年第2期17卷 260-266页

作者： jian-Qiang Jin Yuan-Yuan Hu Yu-Ming Niu Gong-Li Yang Yu-Yu wu Wei-Dong Leng Ling-Yun Xia Department of Pathology Affiliated No. 4 Hospital of Soochow University Wuxi 214062 Jiangsu Province China Department of Stomatology Affiliated Taihe Hospital of HubeiUniversity of Medicine Shiyan 442000 Hubei Province China Department of Gastroenterology Affiliated TaiheHospital of Hubei University of Medicine Shiyan 442000 HubeiProvince China

AIM:To study the relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk by meta-analysis. METHODS:A meta-analysis was performed to investigate the relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk by reviewing the related studies until September *** were extracted and *** odds ratio(OR) with 95% confidence interval(CI) was used to assess the strength of relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk. RESULTS:Thirteen published case-control studies including 5336 cases and 6226 controls were acquired. The pooled OR with 95%CI indicated that CYP1A1 Ile462Val polymorphism was significantly related with colorectal cancer risk(Val/Val vs Ile/Ile:OR=1.47,95%CI:1.16-1.86,P=0.002;dominant model:OR= 1.33,95%CI:1.01-1.75,P=0.04;recessive model:OR=1.49,95%CI:1.18-1.88,P=0.0009) .Subgroup ethnicity analysis showed that CYP1A1 Ile462Val polymorphism was also significantly related with colorectal cancer risk in Europeans(Ile/Val vs Ile/Ile:OR=1.22,95%CI:1.05-1.42,P=0.008;dominant model:OR= 1.24,95%CI:1.07-1.43,P=0.004) and Asians(Val/ Val vs Ile/Ile:OR=1.40,95%CI:1.07-1.82,P=0.01;recessive model:OR=1.46,95%CI:1.12-1.89,P= 0.005) . CONCLUSION:CYP1A1 Ile462Val may be an increased risk factor for colorectal cancer.

关键词： CYP1A1 Polymorphism Colorectal cancer Meta-analysis

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Interventional Radionuclide Therapy of Hepatocellular Carcinoma： Assessment of Intratumoral Retention of HPMA Copolymers

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Chemical Research in Chinese Universities 2013年第1期29卷 183-188页

作者： YUAN jian-chao MIAO Cheng-ping ZENG Xian-wu GUO Hong-yun WANG Xiao-qi LIAO Shi-qi XIE Xiao-li Key Laboratory of Eco-environment-related Polymer Materials Ministry of Education Key Laboratory of Polymer Materials of Gansu Province College of Chemistry and Chemical Engineering Department of Nuclear Medicine Gansu Academy of Medical Sciences & Gansu Provincial Tumor Hospital Lanzhou 730050 P. R. China

To develop new radiopharmaceuticals for the interventional radionuclide therapy of recurrent hepatocellular carcinoma, poly（HPMA）-APMA-DTPA[HPMA=N-（2-hydroxypropyl） methacrylamide; APMA=N-（3-aminopropyl）methacrylamide; DTPA=diethylenetriaminepentaacetic acidl was synthesized by free radical precipitation polymerization in acetone/dimethylsulfoxide with N,N＇-azobis（isobutyronitrile） as the initiator. The copolymers were characterized with nuclear magnetic resonance（NMR） spectroscopy and gel permeation chromatography（GPC, Mn=2.2xl04, Mw/Mn=l.38）. Subsequently, poly（HPMA）-APMA-DTPA was conjugated with 99mTC radionuclide. Prolonged retention of poly（HPMA）-APMA-DTPA conjugate within the tumor tissues was demonstrated by single-photon emission computed tomography computed tomography（SPECT-CT） at 1, 2, 4 and 24 h following intra-tumoral injection of the conjugate to hepatocellular carcinoma xenografts in mice. DTPA-99mTc was also synthesized and characterized for comparison. The data suggest that the poly（HPMA）-APMA-DTPA conjugates might be useful for the interventional radionuclide therapy of recurrent hepatocellular carcinoma in humans.

关键词： Hepatocellular carcinoma Interventional radionuclide therapy HPMA copolymer Radiotracer

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7-羟基香豆素与三种芳香族氨基酸作用的荧光光谱研究

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光谱学与光谱分析 2013年第8期33卷 2117-2122页

作者：江欢朱燕舞王燕何建波合肥工业大学化学工程学院可控化学与材料化工安徽省重点实验室安徽合肥230009

运用荧光光谱和紫外光谱研究7-羟基香豆素UBM分别与色氨酸Trp,酪氨酸Tyr和苯丙氨酸Phe三种芳香族氨基酸的相互作用。结果表明在模拟人体生理条件下,UMB能引起上述氨基酸发生荧光猝灭,最大猝灭波长依次为347,303和282nm,猝灭机制均为静... 详细信息

运用荧光光谱和紫外光谱研究7-羟基香豆素UBM分别与色氨酸Trp,酪氨酸Tyr和苯丙氨酸Phe三种芳香族氨基酸的相互作用。结果表明在模拟人体生理条件下,UMB能引起上述氨基酸发生荧光猝灭,最大猝灭波长依次为347,303和282nm,猝灭机制均为静态猝灭,相互之间均以摩尔比1:1形成了复合物,且得到两种温度下UMB与Trp,Tyr和Phe反应的表观平衡常数Kc分别为298.15K时2.993×106,7.858×104和1.186×103 ***-1,310.15K时2.702×104,1.063×105和8.352×103 ***-1。热力学函数变化表明UMB与以上三种氨基酸结合作用较强,其中UMB-Trp相互作用力是氢键或范德华力,UMB-Tyr和UMB-Phe相互作用主要以疏水作用为主,同时都可能存在偶极-偶极之间的相互作用。

关键词： 7-羟基香豆素芳香族氨基酸荧光光谱法紫外光谱法

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Soil mineral nitrogen and yield-scaled soil N2O emissions lowered by reducing nitrogen application and intercropping with soybean for sweet maize production in southern China

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Journal of Integrative Agriculture 2017年第11期16卷 2586-2596页

作者： TANG Yi-ling YU Ling-ling GUAN Ao-mei ZHOU Xian-yu WANG Zhi-guo GOU Yong-gang WANG jian-wu Institute of Tropical and Subtropical Ecology~Key Laboratory of Agro-environment in the Tropics Ministry of Agriculture/KeyLaboratory of Agroecology and Rural Environment of Guangdong Regular Higher Education Institutions South China AgriculturalUniversity Guangzhou 510642 P.R. China

The increasing demand for fresh sweet maize （Zea mays L. saccharata） in southern China has prioritized the need to find solutions to the environmental pollution caused by its continuous production and high inputs of chemical nitrogen fertilizers. A promising method for improving crop production and environmental conditions is to intercrop sweet maize with legumes. Here, a three-year field experiment was conducted to assess the influence of four different cropping systems （sole sweet maize （SS）, sole soybean （SB）, two rows sweet maize-three rows soybean （S2B3） intercropping, and two rows sweet maize-four rows soybean （S2B4） intercropping）, together with two rates of N fertilizer application （300 and 360 kg N ha-1） on grain yield, residual soil mineral N, and soil N2O emissions in southern China. Results showed that in most case, inter- cropping achieved yield advantages （total land equivalent ratio （TLER=0.87-1.25） was above one）. Moreover, intercropping resulted in 39.8% less soil mineral N than SS at the time of crop harvest, averaged over six seasons （spring and autumn in each of the three years of the field experiment）. Generally, intercropping and reduced-N application （300 kg N ha-1） produced lower cumulative soil N20 and yield-scaled soil N20 emissions than SS and conventionaI-N application （360 kg N ha-l）, respectively. $2B4 intercropping with reduced-N rate （300 kg N ha-~） showed the lowest cumulative soil N20 （mean value=0.61 kg ha-1） and yield-scaled soil N20 （mean value=0.04 kg t-1） emissions. Overall, intercropping with reduced-N rate maintained sweet maize production, while also reducing environmental impacts. The system of S2B4 intercropping with reduced-N rate may be the most sustainable and environmentally friendly cropping system.

关键词： sweet maize-soybean intercrop cropping system N fertilizer rate grain yield soil mineral N soil NzO emissions

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A high-throughput screening method for breeding Aspergillus niger with 12C6+ ion beam-improved cellulase

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Nuclear Science and Techniques 2017年第1期28卷 1-7页

作者： bo-Ling jiang Shu-Yang Wang Yu-Chen Wang Ji-Hong Chen Wen-jian Li Jing Liu Wei Hu Guo-Qing Xiao Miao-Ying Dong Fu-Qiang Xu Institute of Modern Physics Chinese Academy of Sciences509 Nanchang Rd Lanzhou 730000 China University of Chinese Academy of Sciences No. 19A Yuquan Road Beijing 100049 China Lanzhou University 222 South Tianshui RoadLanzhou 730000 Gansu Province China Gansu Agricultural University Lanzhou 730000 Gansu Province China

In this study,a high-throughput screening method was established through the 24-square deep-well microliter plate(MTP) fermentation and micro-plate detection for large-scale screening of the *** was suitable for screening a large number of mutants and improving the breeding efficiency after heavy-ion beam *** strains showed higher cellulase activity compared with the initial strain after the screening of plate and MTP *** filter paper activity and β-glucosidase activity of Aspergillus niger H11201 had increased 38.74 and 63.23%separately compared with *** H11 by shaking flask fermentation,and it was genetically stable after being passaged to nine *** results indicate that the high-throughput screening method can be used for the quick breeding of *** with high cellulase activity.

关键词： High-throughput screening method Aspergillus niger H11 Cellulase 12C6+ ion beam

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Endoscopic mucosal resection-precutting vs conventional endoscopic mucosal resection for sessile colorectal polyps sized 10-20 mm

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World Journal of Gastroenterology 2022年第45期28卷 6397-6409页

作者： Xue-Qun Zhang jian-Zhong Sang Lei Xu Xin-Li Mao bo Li Wan-Lin Zhu Xiao-Yun Yang Chao-Hui Yu Department of Gastroenterology The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of Gastroenterology Renmin Hospital of Yuyao CityYuyao 315499Zhejiang ProvinceChina Department of Gastroenterology Ningbo First HospitalNingbo 315010Zhejiang ProvinceChina Department of Gastroenterology Taizhou HospitalTaizhou 317099Zhejiang ProvinceChina Department of Gastroenterology The Central Hospital of Lishui CityLishui 323020Zhejiang ProvinceChina Department of Gastroenterology Jinhua Municipal Central HospitalJinhua 321099Zhejiang ProvinceChina

BACKGROUND The optimal method to remove sessile colorectal lesions sized 10-20 mm remains *** and incomplete resection are major limitations in current practice,such as endoscopic mucosal resection(EMR)and cold or hot snare ***,EMR with circumferential precutting(EMR-P)has emerged as an effective technique,but the quality of current evidence in comparative studies of conventional EMR(CEMR)and EMR-P is *** To investigate whether EMR-P is superior to CEMR in removing sessile colorectal *** This multicenter randomized controlled trial involved seven medical institutions in *** with colorectal polyps sized 10-20 mm were enrolled and randomly assigned to undergo EMR-P or ***-P was performed following submucosal injection,and a circumferential mucosa incision(precutting)was conducted using a snare *** outcomes included a comparison of the rates of en bloc and R0 resection,defined as one-piece resection and one-piece resection with histologically assessed clear margins,*** A total of 110 patients in the EMR-P group and 110 patients in the CEMR group were finally *** the per-protocol analysis,the proportion of en bloc resections was 94.3%[95%confidence interval(CI):88.2%-97.4%]in the EMR-P group and 86%(95%CI:78.2%-91.3%)in the CEMR group(P=0.041),while subgroup analysis showed that for lesions>15 mm,EMR-P also resulted in a higher en bloc resection rate(92.0%vs 58.8%P=0.029).The proportion of R0 resections was 81.1%(95%CI:72.6%-87.4%)in the EMR-P group and 76.6%(95%CI:68.8%-84.4%)in the CEMR group(P=0.521).The EMR-P group showed a longer median procedure time(6.4 vs 3.0 min;P15 mm in diameter,with higher R0

关键词： Colorectal polyps Medium size Polypectomy Endoscopic mucosal resection with circumferential precutting Conventional endoscopic mucosal resection

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常压和真空下CS_2的光氧化反应

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环境科学 2005年第2期26卷 45-49页

作者：王晓吴洪波陈建民复旦大学环境科学与工程系上海200433

利用原位FTIR、XPS和GC MS等技术手段 ,研究了常温紫外光辐照下常压及真空状态中 ,CS2 的光氧化反应 .结果表明 ,常压及真空状态下CS2 光氧化反应的产物均为COS、SO2 、CO和CO2 ,反应均遵循表观一级反应动力学规律 ,但中间产物COS的浓... 详细信息

利用原位FTIR、XPS和GC MS等技术手段 ,研究了常温紫外光辐照下常压及真空状态中 ,CS2 的光氧化反应 .结果表明 ,常压及真空状态下CS2 光氧化反应的产物均为COS、SO2 、CO和CO2 ,反应均遵循表观一级反应动力学规律 ,但中间产物COS的浓度变化有较大的差异 .常压下COS浓度先迅速增大 ,然后减少 ;真空条件下COS浓度增加到常压下COS浓度的1/ 10后基本持平 ,然后逐渐减小 ,整个变化趋势缓慢 ;2种条件下CS2 的半衰期分别为 31. 6s和 39. 8s ,中间产物COS降解98%所需时间分别为 5 5min和 2 2min .在相同的光照条件下 ,O2 浓度的增加有助于CS2 光氧化反应的进行 .以CS2 光氧化中间产物COS为初始物的光氧化反应主要产物为CO2 和SO2 ,后者可以进一步被氧化为SO2 -4.适量增加O2 的浓度可以促进COS光氧化反应的进行 ,但O2 的浓度增加至一定程度后反应速率基本保持恒定 .以上结论对揭示CS2 和COS的源和汇以及全球S物质循环具有重要价值 .

关键词：二硫化碳羰基硫光氧化 FTIR

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Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu(Plecoglossus altivelis)to subsequent Pseudomonas plecoglossicida-induced infection

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Zoological Research 2022年第4期43卷 648-665页

作者： Xiang-Yu wu Jin-bo Xiong Chen-Jie Fei Ting Dai Ting-Fang Zhu Zi-Yue Zhao Jing Pan Li Nie Jiong Chen State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products Ningbo UniversityNingboZhejiang 315211China Laboratory of Biochemistry and Molecular Biology School of Marine SciencesMeishan CampusNingbo UniversityNingboZhejiang 315211China Collaborative Innovation Center for Zhejiang Marine High-Efficiency and Healthy Aquaculture School of Marine SciencesNingbo UniversityNingboZhejiang 315211China

With the rapid development of intensive farming,the aquaculture industry uses a great many antibiotics for the prevention and treatment of bacterial *** their therapeutic functions,the overuse and accumulation of antibiotics also pose a threat to aquaculture *** the present study,ayu(Plecoglossus altivelis)was used as a fish model to study the impacts of ciprofloxacin(CIP)overuse on intestinal homeostasis and immune response during subsequent Pseudomonas plecoglossicida *** on 16S rRNA gene amplification and Illumina sequencing,we found that CIP pre-exposure caused significant variation in intestinal microbiota,including increased species richness,altered microbiota composition and interaction networks,and increased metabolic ***,immunohistochemical analysis indicated that CIP pre-exposure resulted in severe mucosal layer damage,goblet cell reduction,and epithelial cell necrosis of the intestinal barrier in infected *** real-time polymerase chain reaction(qRT-PCR)showed that disruption of intestinal homeostasis impaired systemic antiinfection immune responses in the intestine,gill,spleen,and head kidney,while inhibiting IL-1β,TNF-α,and IL-10 expression and promoting TGF-β*** findings indicated that CIP administration can directly affect intestinal microbiota composition and intestinal integrity in ayu *** perturbation of intestinal homeostasis is likely responsible for the lower survival rate of hosts following subsequent infection as the capacity to mount an effective immune response is *** study also provides preliminary clues for understanding the effects of antibiotic overuse on higher vertebrates through trophic transfer.

关键词： Ciprofloxacin Microbiota Intestinal barrier Immune responses Ayu

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Combined acupuncture and HuangDiSan treatment affects behavior and synaptophysin levels in the hippocampus of senescence-accelerated mouse prone 8 after neural stem cell transplantation

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Neural Regeneration Research 2018年第3期13卷 541-548页

作者： Chun-lei Zhou Lan Zhao Hui-yan Shi jian-wei Liu liang-wei Shi bo-hong Kan Zhen Li lian-chun Yu Jing-xian Han Tianjin First Center Hospital Tianjin China First Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin China Tianjin Key Laboratory of Acupuncture and Moxibustion Tianjin China Tianjin University of Traditional Chinese Medicine Tianjin China

Sanjiao acupuncture and HuangDiSan can promote the proliferation, migration and differentiation of exogenous neural stem cells in senescence-accelerated mouse prone 8 （SAMP8） mice and can improve learning and memory impairment and behavioral function in dementia-model mice. Thus, we sought to determine whether Sanjiao acupuncture and HuangDiSan can elevate the effect of neural stem cell transplantation in Alzheimer’s disease model mice. Sanjiao acupuncture was used to stimulate Danzhong （CV17）, Zhongwan （CV12）,Qihai （CV6）, bilateral Xuehai （SP10） and bilateral Zusanli （ST36） 15 days before and after implantation of neural stem cells （5 × 10^5） into the hippocampal dentate gyrus of SAMP8 mice. Simultaneously, 0.2 mL HuangDiSan, containing Rehmannia Root and Chinese Angelica,was intragastrically administered. Our results demonstrated that compared with mice undergoing neural stem cell transplantation alone,learning ability was significantly improved and synaptophysin mRNA and protein levels were greatly increased in the hippocampus of mice undergoing both Sanjiao acupuncture and intragastric administration of HuangDiSan. We conclude that the combination of Sanjiao acupuncture and HuangDiSan can effectively improve dementia symptoms in mice, and the mechanism of this action might be related to the regulation of synaptophysin expression.

关键词： nerve regeneration neurons neurodegeneration Alzheimer's disease microenvironment Chinese medicine behavior neural stem cell transplantation synaptophysin neural regeneration

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