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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin li qianfeng Zhang Zhiqian li Long Ren Dayi Pan Qiyong Gong Zhongwei Gu Hao Cai Kui Luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-L1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their application.To address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor effect.In this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into mB4S.After internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP secretion.Meanwhile,diABZI effectively activated the STING pathway.Treatment with mB4S in combination with an anti-PD-L1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-L1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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Rice melatonin deficiency causes premature leaf senescence via DNA methylation regulation

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The Crop Journal 2024年第3期12卷 721-731页

作者： Yue Lu Ahmed Gharib Rujia Chen Hanyao Wang Tianyun Tao Zhihao Zuo Qing Bu Yanze Su Yaoqing li Yanmo Luo Hamdi F.El-Mowafi Zhichao Wang qianfeng Huang Shuting Wang Yang Xu Pengcheng li Chenwu Xu Zefeng Yang Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding/Zhongshan Biological Breeding Laboratory/Key Laboratory of Plant Functional Genomics of the Ministry of Education Agriculture College of Yangzhou UniversityYangzhou 225009JiangsuChina Jiangsu Co-Innovation Center for Modern Production Technology of Grain Crops Jiangsu Key Laboratory of Crop Genetics and PhysiologyYangzhou UniversityYangzhou 225009JiangsuChina National Institute of Laser Enhanced Sciences(NILES) Cairo UniversityGiza 12613Egypt Rice Research Department Field Crops Research InstituteAgricultural Research CenterSakhaKafr El-Sheikh 33717Egypt

In a study of DNA methylation changes in melatonin-deficient rice mutants,mutant plants showed premature leaf senescence during grain-filling and reduced grain yield.Melatonin deficiency led to transcriptional reprogramming,especially of genes involved in chlorophyll and carbon metabolism,redox regulation,and transcriptional regulation,during dark-induced leaf senescence.Hypomethylation of mCG and mCHG in the melatonin-deficient rice mutants was associated with the expression change of both protein-coding genes and transposable element-related genes.Changes in gene expression and DNA methylation in the melatonin-deficient mutants were compensated by exogenous application of melatonin.A decreased S-adenosyl-L-methionine level may have contributed to the DNA methylation variations in rice mutants of melatonin deficiency under dark conditions.

关键词： Melatonin Premature leaf senescence Rice DNA methylation Epigenetic regulation

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Starch biosynthesis in cereal endosperms: An updated review over the last decade

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Plant Communications 2021年第5期2卷 1-22页

作者： lichun Huang Hongyan Tan Changquan Zhang qianfeng li Qiaoquan liu Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding State Key Laboratory of Hybrid RiceKey Laboratory of Plant Functional Genomics of the Ministry of EducationCollege of AgricultureYangzhou UniversityYangzhou 225009China Co-Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province Key Laboratory of Crop Genetics and Physiology of Jiangsu ProvinceYangzhou UniversityYangzhou 225009China

Starch is a vital energy source for living organisms and is a key raw material and additive in the food and non-food industries.Starch has received continuous attention in multiple research fields.The endosperm of cereals(e.g.,rice,corn,wheat,and barley)is the most important site for the synthesis of storage starch.Around 2010,several excellent reviews summarized key progress in various fields of starch research,serving as important references for subsequent research.In the past 10 years,many achievements have been made in the study of starch synthesis and regulation in cereals.The present review provides an update on research progress in starch synthesis of cereal endosperms over the past decade,focusing on new enzymes and non-enzymatic proteins involved in starch synthesis,regulatory networks of starch synthesis,and the use of elite alleles of starch synthesis-related genes in cereal breeding programs.We also provide perspectives on future research directions that will further our understanding of cereal starch biosynthesis and regulation to support the rational design of ideal quality grain.

关键词： cereal starch biosynthesis regulation network endosperm development quality improvement

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湿热力作用下粉砂质泥岩开裂特性研究

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湖南大学学报（自然科学版） 2024年第1期51卷 126-136页

作者：曾铃郭雨查焕奕高乾丰黎繁卞汉兵桥梁工程安全控制教育部重点实验室(长沙理工大学) 湖南长沙410114 长沙理工大学土木工程学院湖南长沙410114 长沙理工大学交通运输工程学院湖南长沙410114

为探究湿热力作用下粉砂质泥岩的开裂特性,开展裂隙演化试验,得到湿热力单因素及多因素耦合循环作用下粉砂质泥岩的裂隙演化规律,同时利用X射线衍射、扫描电镜研究其微观结构变化特征,分析宏观和微观试验结果关联性,揭示湿热力作用下粉... 详细信息

为探究湿热力作用下粉砂质泥岩的开裂特性,开展裂隙演化试验,得到湿热力单因素及多因素耦合循环作用下粉砂质泥岩的裂隙演化规律,同时利用X射线衍射、扫描电镜研究其微观结构变化特征,分析宏观和微观试验结果关联性,揭示湿热力作用下粉砂质泥岩裂隙扩展机制.研究结果表明:粉砂质泥岩裂隙发育表现为增长-平缓趋势;在单因素循环作用中,湿度循环(浸水~烘干)最易造成粉砂质泥岩开裂,温度循环(5~60℃)次之,荷载循环(0~50 kPa)最弱;在多因素耦合循环作用中,裂隙发育程度排序为:湿热力>湿热>湿力>热力,验证了湿度循环致裂性最强的结论.湿热力耦合循环作用15次后裂隙率达0.92%,裂隙条数增至30条,平均长度延伸至60.58 mm,而平均宽度稳定在0.47 mm左右.孔隙率与裂隙率的灰关联度最大,为0.813,即微观结构变化中孔隙发育与裂隙扩展的关联程度最大.湿热力耦合循环作用中,湿度循环引起黏土矿物晶层间距变化,导致颗粒破碎、孔隙扩张形成微裂隙,温度循环使试样产生差异性热应力、水分分布,促使微裂隙发育贯通,荷载作用增加尖端应力,最终导致裂隙网络形成.

关键词：边坡工程粉砂质泥岩湿热力作用裂隙发育微观结构

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由“肠道微生态”浅谈从“脑”防治骨质疏松症

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中国骨质疏松杂志 2024年第6期30卷 884-888页

作者：李育光朱换平张鑫李鑫生谢潜锋甘肃中医药大学甘肃兰州730000 甘肃省中医院甘肃兰州730050

骨质疏松症是临床常见的一种以骨密度和骨质量下降为特征的慢性代谢性骨科疾病。应用中医理论对骨质疏松症探讨已有诸多文献,但大多仅局限于从五脏论述。该文通过总结归纳现代分子生物学关于肠道微生态相关研究,探讨脑-肠道微生态-骨质... 详细信息

骨质疏松症是临床常见的一种以骨密度和骨质量下降为特征的慢性代谢性骨科疾病。应用中医理论对骨质疏松症探讨已有诸多文献,但大多仅局限于从五脏论述。该文通过总结归纳现代分子生物学关于肠道微生态相关研究,探讨脑-肠道微生态-骨质疏松症三者之间相关性,用现代微生态学的观点揭示从中医奇恒之府“脑”防治骨质疏松症的科学内涵,为中医防治骨质疏松症提供新思路,同时充实完善中医奇恒之府的科学实质。

关键词：骨质疏松症肠道微生态脑-肠-骨轴脑

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不同硬度地面对功能性踝关节不稳患者步态协调性的影响

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中国康复理论与实践 2024年第3期30卷 345-351页

作者：马乾峰李立张伟丁健许贻林毛文慧南京师范大学体育科学学院江苏南京市210023 美国佐治亚南方大学运动健康科学系美国佐治亚州30460 江苏省体育科学研究所江苏南京市210033

目的探索不同硬度地面对功能性踝关节不稳(FAI)患者步态协调性的影响。方法 2023年5月至7月,采用Qualisys红外光学运动捕捉系统对南京师范大学15例右侧FAI患者协调性和变异性进行测试。采集并截取步态周期数据,运用Matlab计算耦合角和... 详细信息

目的探索不同硬度地面对功能性踝关节不稳(FAI)患者步态协调性的影响。方法 2023年5月至7月,采用Qualisys红外光学运动捕捉系统对南京师范大学15例右侧FAI患者协调性和变异性进行测试。采集并截取步态周期数据,运用Matlab计算耦合角和耦合角标准差,比较在不同硬度地面上的差异。结果在冠状面,髋-踝关节耦合角在支撑中期和支撑后期硬地面大于软地面,其他步态阶段以及髋-膝关节、膝-踝关节各步态阶段均小于软地面(P <0.05);在矢状面,髋-踝关节和膝-踝关节耦合角在支撑中期和支撑后期硬地面小于软地面,其他步态阶段以及髋-膝关节各步态阶段均大于软地面(P <0.01);在水平面,髋-膝关节耦合角在支撑后期硬地面小于软地面,摆动前期和髋-踝关节承重期均大于软地面(P <0.05)。与硬地面相比,软地面上耦合角标准差仅在矢状面髋-膝关节承重期小于硬地面,其余均大于硬地面(P <0.05)。结论 FAI患者在三维面内各步态阶段在软地面上表现出更多的远端主导,即踝关节内翻跖屈优势增加,髋关节优势减少;协调变异性普遍高于硬地面。表明FAI患者在软地面上步行时会增加复发性外踝扭伤风险。

关键词：功能性踝关节不稳地面硬度步态协调模式协调变异性

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A rare Waxy allele coordinately improves rice eating and cooking quality and grain transparency

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Journal of Integrative Plant Biology 2021年第5期63卷 889-901页

作者： Changquan Zhang Yong Yang Shengjie Chen Xueju liu Jihui Zhu lihui Zhou Yan Lu qianfeng li Xiaolei Fan Shuzhu Tang Minghong Gu Qiaoquan liu Key Laboratory of Crop Genomics and Molecular Breeding of Jiangsu Province State Key Laboratory of Hybrid RiceYangzhou UniversityYangzhou 225009China Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genetics and Physiology/Co‐Innovation Center for Modern Production Technology of Grain Crops of Jiangsu Province Yangzhou UniversityYangzhou 225009China State Key Laboratory of Agrobiotechnology School of Life SciencesThe Chinese University of Hong KongHong KongChina

In rice(Oryza sativa), amylose content(AC) is the major factor that determines eating and cooking quality(ECQ). The diversity in AC is largely attributed to natural allelic variation at the Waxy(Wx)locus. Here we identified a rare Wx allele, Wx^(mw) ,which combines a favorable AC, improved ECQ and grain transparency. Based on a phylogenetic analysis of Wx genomic sequences from 370 rice accessions, we speculated that Wx^(mw) may have derived from recombination between two important natural Wx alleles, Wx^(in) and Wx^(b). We validated the effects of Wx^(mw) on rice grain quality using both transgenic lines and near-isogenic lines(NILs). When introgressed into the japonica Nipponbare(NIP) background, Wx^(mw) resulted in a moderate AC that was intermediate between that of NILs carrying the Wx^(b)allele and NILs with the Wx^(mp) allele. Notably, mature grains of NILs fixed for Wx^(mw) had an improved transparent endosperm relative to soft rice. Further, we introduced Wx^(mw) into a high-yielding japonica cultivar via molecular marker-assisted selection: the introgressed lines exhibited clear improvements in ECQ and endosperm transparency. Our results suggest that Wx^(mw) is a promising allele to improve grain quality, especially ECQ and grain transparency of high-yielding japonica cultivars, in rice breeding programs.

关键词： allelic variation amylose content(AC) eating and cooking quality(ECQ) grain appearance Oryza sativa L. Waxy

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由脑命门相关探讨老年性骨质疏松症的防治研究进展

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中国骨质疏松杂志 2024年第6期30卷 916-920页

作者：李鑫生朱换平李育光张鑫谢潜锋王文霞甘肃中医药大学甘肃兰州730000 甘肃省中医院甘肃兰州730050 陇南市第一人民医院甘肃陇南746000

随着我国人口老龄化的加剧,老年性骨质疏松症(senile osteoporosis,SOP)已严重威胁到老年人生命健康,成为重大的公共卫生挑战亟待解决。明确该病的发病机制是防治的关键。中医学认为脑与命门密切相关,命门贯属于脑。脑髓失养,命门火衰... 详细信息

随着我国人口老龄化的加剧,老年性骨质疏松症(senile osteoporosis,SOP)已严重威胁到老年人生命健康,成为重大的公共卫生挑战亟待解决。明确该病的发病机制是防治的关键。中医学认为脑与命门密切相关,命门贯属于脑。脑髓失养,命门火衰是该病发生的根源。现代研究发现,中医温补命门的针灸和中药复方,可作用于下丘脑及其靶腺轴,调节骨代谢紊乱,改善SOP症状。因此,笔者试从脑命门相关理论出发,综合国内外相关文献,探讨SOP发病机制和中医药防治最新进展,以期为SOP提供新的防治思路。

关键词：脑命门相关下丘脑老年性骨质疏松症中医中药

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Wx^lv、the Ancestral Allele of Rice Waxy Gene

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Molecular Plant 2019年第8期12卷 1157-1166页

作者： Changquan Zhang Jihui Zhu Shengjie Chen Xiaolei Fan qianfeng li Yan Lu Min Wang Hengxiu Yu Chuandeng Yi Shuzhu Tang Minghong Gu Qiaoquan liu Key Laboratory of Plant Functional Genomics of the Ministry of Education/Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding College of AgricultureYangzhou UniversityYangzhou 225009China Co-lnnovation Center for Modern Production Technology of Grain Crops of Jiangsu Province/Key Laboratory of Crop Genetics and Physiology of Jiangsu Province Yangzhou UniversityYangzhou 225009China

In rice grains,the Waxy (Wx) gene is responsible for the synthesis of amylose,the most important determinant for eating and cooking quality.The effects of several Wx alleles on amylose content and the taste of cooked rice have been elucidated.However,the relationship between artificial selection and the evolution of various Wx alleles as well as their distribution remain unclear.Here we report the identification of an ancestral allele,Wx^lv,which dramatically affects the mouthfeel of rice grains by modulating the size of amylose molecules.We demonstrated that WF originated directly from wild rice,and the three major Wx alleles in cultivated rice (Wx^b,Wx^a,and Wx^in) differentiated after the substitution of one base pair at the functional sites.These data indicate that the Wx^lv allele played an important role in artificial selection and domestication.The findings also shed light on the evolution of various Wx alleles,which have greatly contributed to improving the eating and cooking quality of rice.

关键词： Oryza sativa Waxy eating and cooking quality allelic variation artificial selection

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类鼻疽伯克霍尔德菌基因BPSL1972缺失株的构建及其生物学特性分析

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中国热带医学 2024年第6期24卷 644-651,679页

作者：朱侨田申王彦双李雪苗章越李欣泽夏乾峰海南医学院热带医学院海南海口571199 海南医学院第二附属医院海南海口570216

目的研究可能的外排泵基因BPSL1972在类鼻疽伯克霍尔德菌(Burkholderia pseudomallei, Bp)中的生物学功能,以完善Bp的耐药形成机制。方法以Bp海南标准菌株HNBP001为对象,通过同源重组和电击转化分别构建BPSL1972基因敲除株及其回补株... 详细信息

目的研究可能的外排泵基因BPSL1972在类鼻疽伯克霍尔德菌(Burkholderia pseudomallei, Bp)中的生物学功能,以完善Bp的耐药形成机制。方法以Bp海南标准菌株HNBP001为对象,通过同源重组和电击转化分别构建BPSL1972基因敲除株及其回补株,通过酶切酶联的方法构建BPSL1972编码蛋白表达载体,通过His标签蛋白表达试剂盒对BPSL1972编码的蛋白表达,通过Western Blot技术对表达的蛋白进行验证,通过微量肉汤法、K-B法、比浊法、试管法、结晶紫染色和CCK-8试剂盒,依次比较了其在药敏、生长、生物膜形成和细胞毒力上的变化,通过Protscale在线网站、Protparam在线网站预测理化性质,利用SignalP 5.0在线网站预测BPSL1972编码蛋白的信号肽以及Smart在线网站预测了BPSL1972编码蛋白的跨膜结构域及基因功能,通过Phyre 2在线网站对BPSL1972编码蛋白3D结构进行构建并进行同源性分析。结果预测结果显示,BPSL1972编码蛋白是一类中性稳定的疏水性蛋白,其具有一个脂蛋白信号肽及一个跨膜结构区,属于RND外排泵系统,具有2个脂蛋白外膜外排蛋白,可能介导大环内酯类抗生素的耐药,其3D建模结果显示其与VceC和镰刀酸外排蛋白高度同源,可能介导离子活化剂的外排。测序结果显示缺失株和回补株构建成功。但缺失株在各生物学特性上与野生株无差异,并且对头孢类、喹诺酮类、碳青霉烯类、氨基糖苷类、四环素类等抗生素及脱氧胆酸钠等表面活性剂也无明显差异。结论在Bp中可能存在能够代替BPSL1972的基因,或者BPSL1972可能为LysR家族的辅助基因,而这种辅助基因是次要的,因此导致了其缺失后没有发生功能变化,其对其他抗生素如镰刀酸是否存在耐药性及具体的代替或辅助功能还有待后续研究。

关键词：类鼻疽伯克霍尔德菌外排泵耐药

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