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Acta Pharmaceutica Sinica B 2024年第3期14卷 1400-1411页

作者： Shuo wang Tian Liu Yuetong Huang Chaoying Du Danping wang Xiyan wang Qingzhi Lv Zhonggui He Yinglei Zhai bingjun Sun Jin Sun Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China School of Medical Devices Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy Binzhou Medical UniversityBinzhou 256600China

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.

关键词： Prodrugs Nanoassemblies Self-assembly Branched-chain fatty alcohols Disulfide bond Docetaxel Efficacy Safety

Vermicompost:In situ retardant of antibiotic resistome accumulation in cropland soils

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Journal of Environmental Sciences 2024年第7期141卷 277-286页

作者： Meirui Mu Fengxia Yang bingjun Han Guisheng Tian Keqiang Zhang Agro-Environmental Protection Institute Ministry of Agriculture and Rural AffairsTianjin 300191China Key Laboratory of Low-carbon Green Agriculture in North China Ministry of Agriculture and Rural Affairs P.R.ChinaBeijing 10083China Wuxue City Agriculture and Rural Bureau Wuhan 435400China

The dissemination of antibiotic resistance genes(ARGs)in soil has become a global environmental issue.Vermicomposting is gaining prominence in agricultural practices as a soil amendment to improve soil quality.However,its impact on soil ARGs remains unclear when it occurs in farmland.We comprehensively explored the evolution and fate of ARGs and their hosts in the field soil profiles under vermicompost application for more than 3years.Vermicompost application increased several ARG loads in soil environment but decreased the high-risk bla-ARGs(bla_(ampC),bla_(NDM),and bla_(GES-1))by log(0.04-0.43).ARGs in soil amended with vermicompost primarily occurred in topsoil(approximately 1.04-fold of unfertilized soil),but it is worth noting that their levels in the 40-60 cm soil layer were the same or even less than in the unfertilized soil.The microbial community structure changed in soil profiles after vermicompost application.Vermicompost application altered the microbial community structure in soil profiles,showing that the dominant bacteria(i.e.,Proteobacteria,Actinobacteriota,Firmicutes)were decreased 2.62%-5.48%with the increase of soil depth.A network analysis further revealed that most of ARG dominant host bacteria did not migrate from surface soil to deep soil.In particular,those host bacteria harboring high-risk bla-ARGs were primarily concentrated in the surface soil.This study highlights a lower risk of the propagation of ARGs caused by vermicompost application and provides a novel approach to reduce and relieve the dissemination of ARGs derived from animals in agricultural production.

关键词： Vermicompost application Antibiotic resistance genes Vertical migration Soil profile Agricultural soils

Targeted knockdown of PGAM5 in synovial macrophages efficiently alleviates osteoarthritis

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Bone Research 2024年第1期12卷 215-226页

作者： Yuhang Liu Ruihan Hao Jia Lv Jie Yuan Xuelei wang Churong Xu Ding Ma Zhouyi Duan bingjun Zhang Liming Dai Yiyun Cheng Wei Lu Xiaoling Zhang Department of Orthopedic Surgery Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine(SJTUSM)Shanghai 200092China National Facility for Translational Medicine Shanghai 200240China Shanghai Frontiers Science Center of Genome Editing and Cell Therapy Shanghai Key Laboratory of Regulatory BiologySchool of Life SciencesEast China Normal UniversityShanghai 200241China Department of Orthopaedic Surgery The Second Hospital of Shanxi Medical UniversityTaiyuan 030001China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthChinese Academy of SciencesShanghai 200031China School of Medicine Shanghai UniversityShanghai 200444China

Osteoarthritis(OA)is a common degenerative disease worldwide and new therapeutics that target inflammation and the crosstalk between immunocytes and chondrocytes are being developed to prevent and treat OA.These attempts involve repolarizing pro-inflammatory M1 macrophages into the anti-inflammatory M2 phenotype in synovium.In this study,we found that phosphoglycerate mutase 5(PGAM5)significantly increased in macrophages in OA synovium compared to controls based on histology of human samples and single-cell RNA sequencing results of mice models.To address the role of PGAM5 in macrophages in OA,we found conditional knockout of PGAM5 in macrophages greatly alleviated OA symptoms and promoted anabolic metabolism of chondrocytes in vitro and in vivo.Mechanistically,we found that PGAM5 enhanced M1 polarization via AKT-mTOR/p38/ERK pathways,whereas inhibited M2 polarization via STAT6-PPARγpathway in murine bone marrow-derived macrophages.Furthermore,we found that PGAM5 directly dephosphorylated Dishevelled Segment Polarity Protein 2(DVL2)which resulted in the inhibition ofβ-catenin and repolarization of M2 macrophages into M1 macrophages.Conditional knockout of both PGAM5 andβ-catenin in macrophages significantly exacerbated osteoarthritis compared to PGAM5-deficient mice.Motivated by these findings,we successfully designed mannose modified fluoropolymers combined with siPGAM5 to inhibit PGAM5 specifically in synovial macrophages via intra-articular injection,which possessed desired targeting abilities of synovial macrophages and greatly attenuated murine osteoarthritis.Collectively,these findings defined a key role for PGAM5 in orchestrating macrophage polarization and provides insights into novel macrophage-targeted strategy for treating OA.

关键词： osteoarthritis metabolism inhibited

Spatial heterogeneity and compositional profiles of dissolved organic matter in farmland soils across China' Mainland

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Journal of Environmental Sciences 2024年第3期137卷 593-603页

作者： bingjun Han Liyuan Chen Kang Xiao Yang Liu Dong Cao Lu Yu Yujun Li Shu Tao Wenxin Liu Key Laboratory for Earth Surface Processes College of Urban and Environmental SciencesPeking UniversityBeijing 100871China Beijing Yanshan Earth Critical Zone National Research Station College of Resources and EnvironmentUniversity of Chinese Academy of SciencesBeijing 101408China Center for Water and Ecology State Key Joint Laboratory of Environment Simulation and Pollution ControlSchool of EnvironmentTsinghua UniversityBeijing 100084China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental ScienceChinese Academy of SciencesBeijing 100085China

Dissolved organic matter(DOM) plays an essential role in many geochemical processes,however its complexity, chemical diversity, and molecular composition are poorly understood. Soil samples were collected from 500 vegetable fields in administrative regions of China' Mainland, of which 122 were selected for further investigation. DOM properties were characterized by three-dimensional excitation-emission matrix(3D-EEM) fuorescence spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry(FTICRMS)(field intensity is 15 Tesla). Our results indicated that the main constituents were UVA humic-like substances, humic-like substances, fulvic acid-like substances, and tyrosine-like substances. A total of 10,989 molecular formulae with a mass range of 100.04 to 799.59 Da were detected, covering the mass spectrometric information of the soil samples from 27 different regions. CHO and CHON molecules were dominant in DOM, whereas lignin, tannins,and aromatic substances served as the main components. The results of cluster analysis revealed that the soil properties in Jiangxi Province were considerably different from those in other regions. The key backgrounds of the DOM molecular characteristics in the vegetablefield soil samples across China' Mainland were provided at the molecular level, with large abundance and great variability.

关键词： Dissolved organic matter(DOM) Fourier transform ion cyclotron resonance mass(FTICR-MS) Excitation-emission matrix(EEM) Vegetable-field soils China' Mainland

Balancing efficacy and safety of doxorubicin-loaded albumin nanoparticles utilizing pH-sensitive doxorubicin-fatty acid prodrugs

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Nano Research 2024年第6期17卷 5491-5500页

作者： Yuanhao Yu Shiyi Zuo Jiaxuan Song Lingxiao Li Tian Liu Jiayu Guo Yaqiao Li Danping wang Qi Lu Helin wang Dun Zhou Zhonggui He Xiaohong Liu bingjun Sun Jin Sun School of Pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmacy The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China

Albumin nanoparticles(ANPs)offer unique advantages for antitumor drug delivery system,including non-immunogenicity and inherent tumor-targeting capacity.At present,only a few products,such as ABRAXANE®and FYARRO™,have been approved for clinical applications.The poor affinity of doxorubicin(DOX)for albumin,coupled with its numerous severe adverse reactions,poses challenges in the fabrication of desirable albumin nanoparticles loaded with DOX.In this study,we developed prodrugs by conjugating fatty acids of varying lengths with DOX.Our aim was to investigate the balance between efficacy and safety through the selection of appropriate modules.We synthesized five pH-sensitive doxorubicin-fatty acid prodrugs.Compared to free DOX,all DOX prodrug ANPs exhibited a uniform size distribution with desirable sizes of 150 nm.Additionally,DOX prodrugs with hydrazone bonds remained intact in blood circulation while releasing DOX within tumor cells.Significantly,the characteristics of prodrug ANPs were considerably influenced by the length of fatty acids,impacting their in vivo pharmacokinetics,antitumor effectiveness and tumor accumulation.This research offers a detailed understanding of the length of fatty acid influence on DOX-fatty acid prodrug-based ANPs,and it builds a good platform for creating ANPs which prioritize high drug loading,high efficiency,and minimal side effects.

关键词： fatty acid prodrug albumin doxorubicin pH-sensitive bond nanomedicines

Conspicuous cruciform silk decorations deflect avian predator attacks

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Integrative Zoology 2022年第5期17卷 689-703页

作者： bingjun wang Long YU Nina MA Zengtao ZHANG Deyong GONG Rui LIU Daiqin LI Shichang ZHANG Centre for Behavioural Ecology and Evolution&State Key Laboratory of Biocatalysis and Enzyme Engineering School of Life SciencesHubei UniversityWuhanHubeiChina Department of Biological Sciences National University of SingaporeSingapore

Although camouflage as an effective antipredator defense strategy is widespread across animals,highly conspicuous color patterning is not uncommon either.Many orb-web spiders adorn their webs with extra bright white silk.These conspicuous decorations are hypothesized to deter predators by warning the presence of sticky webs,camouflaging spiders,acting as a decoy,or intimidating predators by their apparent size.The decorations may also deflect predator attacks from spiders.However,empirical evidence for this deflection function remains limited.Here,we tested this hypothesis using the X-shaped silk cruciform decorations built by females of Argiope minuta.We employed visual modeling to quantify the conspicuousness of spiders and decorations from a perspective of avian predators.Then,we determined actual predation risk on spiders using naïve chicks as predators.Spider bodies and decorations were conspicuous against natural backgrounds to the avian visual systems.Chicks attacked the spider main bodies significantly less frequently on the decorated webs than on the undecorated webs,thus reducing predation risk.When both spiders and decorations were present,chicks also attacked the spider main bodies and their legs or decorations,and not randomly:they attacked the legs or decorations sooner and more frequently than they attacked the main bodies,independent of the ratio of the surface area between the decoration and spider size.Despite the increase in detectability,incorporating a conspicuous cruciform decoration to the web effectively defends the spider by diverting the attack toward the decoration or leg,but not by camouflaging or intimidating,thus,supporting the deflection hypothesis.

关键词： Argiope minuta cruciform decoration predator deflection visual defense visual modeling

Ultra-antifreeze,ultra-stretchable,transparent,and conductive hydrogel for multi-functional flexible electronics as strain sensor and triboelectric nanogenerator

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Nano Research 2022年第6期15卷 5461-5468页

作者： Xinhuan Dai Yong Long Bing Jiang Wenbin Guo Wei Sha Jiangwen wang Zifeng Cong Jiwei Chen bingjun wang Weiguo Hu Chinese Academy of Sciences Center for Excellence in Nanoscience Beijing Key Laboratory of Micro-nano Energy and SensorBeijing Institute of Nanoenergy and NanosystemsChinese Academy of SciencesBeijing 101400China School of Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049China Center on Nanoenergy Research School of Physical Science and TechnologyGuangxi UniversityNanning 530004China

Conductive hydrogels have become one of the most promising candidates for flexible electronics due to their excellent mechanical flexibility,durability of deformation,and good electrical conductivity.However,in real applications,severe environments occur frequently,such as extremely cold weather.General hydrogels always lack anti-freeze and anti-dehydration abilities.Consequently,the functions of electronic devices based on traditional hydrogels will quickly fail in extreme environments.Therefore,the development of environmentally robust hydrogels that can withstand extremely low temperatures,overcome dehydration,and ensure the stable operation of electronic devices has become increasingly important.Here,we report a kind of graphene oxide(GO)incorporated polyvinyl alcohol-polyacrylamide(PVA-PAAm)double network hydrogel(GPPDhydrogel)which shows excellent anti-freeze ability.The GPPD-hydrogel exhibits not only good flexibility and ultra-high stretchability up to 2,000%,but ensures a high sensitivity when used as the strain sensor at−50°C.More importantly,when serving as the electrode of a sandwich-structural triboelectric nanogenerator(TENG),the GPPD-hydrogel endows the TENG high and stable output performances even under−80°C.Besides,the GPPD-hydrogel is demonstrated long-lasting moisture retention over 100 days.The GPPD-hydrogel provides a reliable and promising candidate for the new generation of wearable electronics.

关键词： triboelectric nanogenerators antifreeze ultra-stretchable hydrogels strain sensors multi-functional flexible electronics

Flexible,stretchable,and transparent InGaN/GaN multiple quantum wells/polyacrylamide hydrogel-based light emitting diodes

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Nano Research 2022年第6期15卷 5492-5499页

作者： Jiwei Chen Jiangwen wang Keyu Ji Bing Jiang Xiao Cui Wei Sha bingjun wang Xinhuan Dai Qilin Hua Lingyu Wan Weiguo Hu Center on Nanoenergy Research School of Physical Science and TechnologyGuangxi UniversityNanning 530004China CAS Center for Excellence in Nanoscience Beijing Key Laboratory of Micro-nano Energy and SensorBeijing Institute of Nanoenergy and NanosystemsChinese Academy of SciencesBeijing 100083China School of Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049China

Visualization is a direct,efficient,and simple interface method to realize the interaction between human and machine,whereas the flexible display unit,as the major bottleneck,still deeply hinders the advances of wearable and virtual reality devices.To obtain flexible optoelectronic devices,one of the effective methods is to transfer a high-efficient and long-lifetime inorganic optoelectronic film from its rigid epitaxial substrate to a foreign flexible/soft substrate.Additionally,piezo-phototronic effect is a fundamental theory for guiding the design of flexible optoelectronic devices.Herein,we demonstrate a flexible,stretchable,and transparent InGaN/GaN multiple quantum wells(MQWs)/polyacrylamide(PAAM)hydrogel-based light emitting diode coupling with the piezo-phototronic effect.The quantum well energy band and integrated luminous intensity(increased by more than 31.3%)are significantly modulated by external mechanical stimuli in the device.Benefiting from the small Young's modulus of hydrogel and weak Van der Waals force,the composite film can endure an extreme tensile condition of about 21.1%stretching with negligible tensile strains transmitted to the InGaN/GaN MQWs.And the stable photoluminescence characteristics can be observed.Moreover,the hydrogen-bond adsorption and excellent transparency of the hydrogel substrate greatly facilitate the packaging and luminescence of the optoelectronic device.And thus,such a novel integration scheme of inorganic semiconductor materials and organic hydrogel materials would help to guide the robust stretchable optoelectronic devices,and show great potential in emerging wearable devices and virtual reality applications.

关键词： InGaN/GaN multiple quantum wells hydrogel light emitting diode(LED) piezo-phototronic effect

Fine-tuning the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies via branched aliphatic functionalization

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Nano Research 2024年第4期17卷 2908-2918页

作者： Guanting Li Fengli Xia Hongying Xiao Shunzhe Zheng Shuwen Fu Han Qiao Qianhui Jin Xuanbo Zhang Dun Zhou Chutong Tian Jin Sun Zhonggui He bingjun Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China Department of Pharmaceutics College of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China Emergency Department The First Affiliated Hospital of Jinzhou Medical UniversityJinzhou 121001China

Small-molecule prodrug nanoassemblies have emerged as efficient antitumor drug delivery systems.However,in the case of camptothecins-based prodrug nanoassemblies,linear aliphatic side chain modification often results in rod-shaped or irregularly shaped nanoassemblies,which are highly unfavorable for sterilization through filtration,and may cause capillary blockage upon intravenous injection.The rational design of camptothecins-based prodrug nanoassemblies remains a challenge.Herein,we propose that branched aliphatic alcohol(BAA)functionalization could fine-tune the structure-tolerance-antitumor efficacy axis of prodrug nanoassemblies.Correspondingly,four SN38-BAA prodrugs were synthesized by conjugating 7-ethyl-10-hydroxycamptothecin(SN38)with BAAs of varying lengths via a tumor redox-responsive disulfide bond,which self-assemble into uniform spherical nanoparticles.The length of BAA was found to significant impact the multiple drug delivery process,including colloidal stability,drug release profiles and pharmacokinetics.Overall,SN38-C21 NPs(SN38-11-heneicosanol nanoparticles),featuring the longest BAA,showcased multiple therapeutic advantages,ultimately culminating the optimal antitumor efficacy and tolerance.The findings underscore the potential of BAA functionalization in strengthening the therapeutic outcomes of prodrug nanoassemblies,and provide valuable insights for developing translational camptothecins-based nanomedicines.

关键词： prodrug nanoassembly self-assembly antitumor efficacy tolerance 7-ethyl-10-hydroxycamptothecin(SN_(3)8)

Assessment of tree-ring mercury radial translocation and age effect in Masson pine:Implications for historical atmospheric mercury reconstruction

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Journal of Environmental Sciences 2024年第4期138卷 266-276页

作者： Xu Liu Xun wang Dingyong wang College of Resources and Environment Southwest UniversityChongqing 400715China State Key Laboratory of Environmental Geochemistry Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China

The tree ring has been regarded as an emerging archive to reconstruct historical atmospheric mercury(Hg)trends,but with the large knowledge gaps in the reliability.In this study,we comprehensively evaluated the Hg source,radial translocation and age effect of Masson pine(Pinus massoniana)tree ring at Mt.Jinyun in Chongqing,to assess the suitability of such tree ring as the archive of atmospheric Hg.Results showed that distinct variabilities among Masson pine tree-ring Hg concentration profiles.The Hg concentration significantly increased along with stem height(P<0.05),indicating the Hg in tree rings mainly derived from foliage uptake atmospheric Hg.We found a distinct age effect that the tree ring of young trees had the higher Hg concentration.Besides,we used the advection-diffusion model to demonstrate how Hg concentration shifted by the advection or/and diffusion in tree rings.The modeling results showed that the advection induced radial translocation during the young growth period of tree was a plausible mechanism to result in the tree-ring Hg record largely different from the trend of anthropogenic Hg emissions in Chongqing.We finally suggest that in further Hg dendrochemistry,better discarding the tree-ring Hg profile of the young growth period to reduce impacts of the radial translocation and age effect.

关键词： Masson pine Tree-ring mercury Radial translocation Tree age effect