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Acidic/hypoxia dual-alleviated nanoregulators for enhanced treatment of tumor chemo-immunotherapy

Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 136-152页

作者： Xiaoju Guo Xiaoxiao Chen jiayi Ding Feng Zhang Shunyang Chen Xin Hu Shiji Fang Lin Shen Chenying Lu Zhongwei Zhao jianfei Tu Gaofeng Shu Minjiang Chen jiansong ji Lishui Central Hospital Shaoxing UniversityShaoxing 312000China Zhejiang Key Laboratory of Imaging and Interventional Medicine Imaging Diagnosis and Interventional Minimally Invasive InstituteThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Clinical College of The Affiliated Central Hospital School of MedicineLishui UniversityLishui 323000China Key Laboratory of Precision Medicine of Lishui Lishui 323000China

Chemotherapy plays a crucial role in triple-negative breast cancer (TNBC) treatment as it not only directly kills cancer cells but also induces immunogenic cell death. However, the chemotherapeutic efficacy was strongly restricted by the acidic and hypoxic tumor environment. Herein, we have successfully formulated PLGA-based nanoparticles concurrently loaded with doxorubicin (DOX), hemoglobin (Hb) and CaCO3 by a CaCO3-assisted emulsion method, aiming at the effective treatment of TNBC. We found that the obtained nanomedicine (DHCaNPs) exhibited effective drug encapsulation and pH-responsive drug release behavior. Moreover, DHCaNPs demonstrated robust capabilities in neutralizing protons and oxygen transport. Consequently, DHCaNPs could not only serve as oxygen nanoshuttles to attenuate tumor hypoxia but also neutralize the acidic tumor microenvironment (TME) by depleting lactic acid, thereby effectively overcoming the resistance to chemotherapy. Furthermore, DHCaNPs demonstrated a notable ability to enhance antitumor immune responses by increasing the frequency of tumor-infiltrating effector lymphocytes and reducing the frequency of various immune-suppressive cells, therefore exhibiting a superior efficacy in suppressing tumor growth and metastasis when combined with anti-PD-L1 (αPD-L1) immunotherapy. In summary, this study highlights that DHCaNPs could effectively attenuate the acidic and hypoxic TME, offering a promising strategy to figure out an enhanced chemo-immunotherapy to benefit TNBC patients.

关键词： CaCO3-based nanoparticles Hypoxia attenuation Acidity neutralization Reversal of chemotherapy resistance Enhanced chemo-immunotherapy

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Mesenchymal stem cell-derived extracellular vesicles in skin wound healing:roles,opportunities and challenges

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Military Medical Research 2024年第3期11卷 400-429页

作者： jia-Yi Ding Min-jiang Chen Ling-Feng Wu Gao-Feng Shu Shi-ji Fang Zhao-Yu Li Xu-Ran Chu Xiao-Kun Li Zhou-Guang Wang jian-Song ji Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research Institute of Imaging Diagnosis and Minimally Invasive Intervention Researchthe Fifth Affiliated Hospital of Wenzhou Medical UniversityZhejiangLishui 323000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)School of Pharmaceutical ScienceWenzhou Medical UniversityWenzhou 325035ZhejiangChina Clinical College of the Affiliated Central Hospital School of MedicineLishui UniversityLishui 323000ZhejiangChina Department of Overseas Education College Jimei UniversityXiamen 361021FujianChina Department of Medicine II Internal MedicineCardio-Pulmonary Institute(CPI)Universities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Justus-Liebig University Giessen35392 GiessenGermany Pulmonary and Critical Care Department of Medicine VInternal MedicineInfectious Diseases and Infection ControlUniversities of Giessen and Marburg Lung Center(UGMLC)Member of the German Center for Lung Research(DZL)Justus-Liebig University Giessen35392 GiessenGermany

Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.

关键词： Mesenchymal stem cell(MSC) Extracellular vesicles(EVs) Wound repair Engineered nanoparticles

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Trend of Developing Aqueous Liquid and Gel Electrolytes for Sustainable,Safe,and High‑Performance Li‑Ion Batteries

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Nano-Micro Letters 2024年第1期16卷 17-34页

作者： Donghwan ji Jaeyun Kim School of Chemical Engineering Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&Technology(SAIHST)Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Biomedical Institute for Convergence at SKKU(BICS) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Institute of Quantum Biophysics(IQB) Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Present Address:Department of NanoEngineering University of California San DiegoLa JollaSan DiegoCA 92093USA

Current lithium-ion batteries(LIBs)rely on organic liquid electrolytes that pose significant risks due to their flammability and toxicity.The potential for environmental pollution and explosions resulting from battery damage or fracture is a critical concern.Water-based(aqueous)electrolytes have been receiving attention as an alternative to organic electrolytes.However,a narrow electrochemicalstability window,water decomposition,and the consequent low battery operating voltage and energy density hinder the practical use of aqueous electrolytes.Therefore,developing novel aqueous electrolytes for sustainable,safe,high-performance LIBs remains challenging.This Review first commences by summarizing the roles and requirements of electrolytes–separators and then delineates the progression of aqueous electrolytes for LIBs,encompassing aqueous liquid and gel electrolyte development trends along with detailed principles of the electrolytes.These aqueous electrolytes are progressed based on strategies using superconcentrated salts,concentrated diluents,polymer additives,polymer networks,and artificial passivation layers,which are used for suppressing water decomposition and widening the electrochemical stability window of water of the electrolytes.In addition,this Review discusses potential strategies for the implementation of aqueous Li-metal batteries with improved electrolyte–electrode interfaces.A comprehensive understanding of each strategy in the aqueous system will assist in the design of an aqueous electrolyte and the development of sustainable and safe high-performance batteries.

关键词： Lithium-ion battery(LIB) Aqueous electrolyte Gel electrolyte Electrochemical stability window Li dendrite

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Photocatalytic activation of sulfite by N-doped porous biochar/MnFe_(2)O_(4) interface-driven catalyst for efficient degradation of tetracycline

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Green Energy & Environment 2024年第3期9卷 481-494页

作者： Long Cheng Yuanhui ji jiangsu Province Hi-Tech Key Laboratory for Biomedical Research School of Chemistry and Chemical EngineeringSoutheast UniversityNanjing211189China

A novel photo-catalytic system composed of N-doped biochars(NBCs),MnFe_(2)O_(4) and sulfite activation under ultraviolet(NBCs/MnFe_(2)O_(4)/sulfite/UV)was constructed to realize the efficient eliminate of tetracycline(TC).As the carrier of MnFe_(2)O_(4),NBCs were synthesized from alfalfa,which has large specific surface area,graphite like structure and hierarchical porous structure.The adsorption isotherm indicated that NBCs/MnFe_(2)O_(4)-2:1 had the best adsorption performance for TC(347.56 mg g^(-1)).Through synergistic adsorption and photocatalysis,the removal rate of TC reached 84%,which was significantly higher than that of MnFe_(2)O_(4).Electrochemical impedance spectroscopy(EIS)and Photoluminescence(PL)characterization results showed that the introduction of NBCs improved the separation efficiency of photogenerated electron and hole pairs and enhanced the photocatalytic performance.Moreover,the adsorption,degradation mechanism and degradation path of TC by the catalyst were systematically analyzed by coupling HPLC–MS measurement with the theoretical calculation.Considering the advantages of excellent degradation performance,low cost,easy separation and environmental friendliness of NBCs/MnFe_(2)O_(4),this work was expected to provide a new path for the practical application of biochar.

关键词： Biochar MnFe_(2)O_(4) Sulfite Adsorption Photocatalysis

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Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery

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Asian Journal of Pharmaceutical Sciences 2022年第6期17卷 908-923页

作者： Gaofeng Shu Lin Shen jiayi Ding Junchao Yu Xiaoxiao Chen Xiaoju Guo Enqi Qiao Yaning Chen Chenying Lu Zhongwei Zhao Yongzhong Du Minjiang Chen jiansong ji Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research Institute of Imaging Diagnosis and Minimally Invasive Intervention ResearchThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000China Department of radiology Lishui Hospital of Zhejiang UniversitySchool of MedicineLishui 323000China Institute of Pharmaceutics College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Shaoxing University School of Medcine Shaoxing 312000China

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma(HCC).Here,a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin(FMPDA/Gd^(3+)/DOX)was prepared as an effective theranostic agent for magnetic resonance imaging(MRI)-guided chemo-photothermal therapy of HCC.It was found that FMPDA/Gd^(3+)/DOX had a high photothermal conversion efficiency of 33.4%and excellent T1-MRI performance with a longitudinal relaxivity(r1)value of 14.966 m M^(-1)·s^(-1).Moreover,the results suggested that FMPDA/Gd^(3+)/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells,which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors.The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd^(3+)/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality.Overall,our study demonstrated that FMPDA/Gd^(3+)/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics.

关键词： Mesoporous polydopamine Fucoidan P-selectin target Platelets bridge Cancer theranostics

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Small Cycles Property of Some Cremer Rational Maps and Polynomials

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Chinese Annals of Mathematics,Series B 2024年第1期45卷 123-136页

作者： Rong FU ji ZHOU Faculty of Science Yibin UniversityYibin 644000SichuanChina Department of Mathematical Sciences Sichuan Normal UniversityChengdu 610066China

This paper concerns the linearization problem on rational maps of degree d≥2 and polynomials of degree d>2 from the perspective of non-linearizability.The authors introduce a set l_(∞) of irrational numbers and show that if α∈l_(∞),then any rational map is not linearizable and has infinitely many cycles in every neighborhood of the fixed point with multiplier λ=e^(2πiα),Adding more constraints to cubic polynomials,they discuss the above problems by polynomial-like maps.For the family of polynomials,with the help of Yoccoz's method,they obtain its maximum dimension of the set in which the polynomials are non-linearizable.

关键词： Irrationally indifferent fixed point Linearization problem Small cycles property

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Soft coarse-grained particle model for particle-fluid systems

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Particuology 2024年第1期84卷 178-193页

作者： Yanhao Ye ji Xu Wei Ge State Key Laboratory of Multiphase Complex Systems Institute of Process EngineeringChinese Academy of SciencesBeijing100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049China Innovation Academy for Green Manufacture Chinese Academy of SciencesBeijing100190China

By modeling a group of neighboring real particles as a single coarse-grained particle(CGP),discrete particle method(DPM)is now capable of simulating industrial-scale particle-fluid systems.However,a systematic approach to determine the CGP properties and develop their interaction models is still lacking,which casts uncertainty on the predictivity of the method.In this study,collisions between predefined particle groups are analyzed to construct kernel functions for modeling the CGPs and then the model parameters are determined by equating the statistical properties of the CGPs and the real particles in the physical process studied.This approach is implemented for homogeneous cooling of granular gas,then demonstrated effective in simulating experimental fluidized beds.

关键词： Coarse-grain(CG) Discrete particle method(DPM) Fluidized bed Multi-scale simulation

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Semi-derived Ringel-Hall algebras and Hall algebras of odd-periodic relative derived categories

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Science China Mathematics 2024年第8期67卷 1735-1760页

作者： ji Lin Liangang Peng Department of Mathematics and Statistics Fuyang Normal University School of Mathematics Sichuan University

Let t be a positive integer and A be a hereditary abelian category satisfying some finiteness conditions. We define the semi-derived Ringel-Hall algebra of A from the category CZ/t（A） of Z/t-graded complexes and obtain a natural basis of the semi-derived Ringel-Hall algebra. Moreover, we describe the semiderived Ringel-Hall algebra by the generators and defining relations. In particular, if t is an odd integer, we show an embedding of the derived Hall algebra of the odd-periodic relative derived category in the extended semi-derived Ringel-Hall algebra.

关键词： hereditary abelian categories the categories of $\mathbb{Z}/t$-graded complexes semi-derived Ringel-Hall algebras derived Hall algebras

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Boosting electrocatalytic nitrate reduction to ammonia via Cu_(2)O/Cu(OH)_(2)heterostructures promoting electron transfer

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Nano Research 2024年第6期17卷 4898-4907页

作者： jing Geng Sihan ji Anhui Province International Research Center on Advanced Building Materials School of Materials Science and Chemical EngineeringAnhui Jianzhu UniversityHefei 230601China Anhui Province Key Laboratory of Advanced Building Materials Anhui Jianzhu UniversityHefei 230601China School of Energy Materials and Chemical Engineering Hefei UniversityHefei 230601China

Electrocatalytic nitrate(NO_(3)^(−))reduction to ammonia(NH_(3))offers a viable approach for sustainable NH_(3)production and environmental denitrification.Copper(Cu)possesses a distinctive electronic structure,which can augment the reaction kinetics of NO_(3)^(−)and impede hydrogen evolution reaction(HER),rendering it a promising contender for the electrosynthesis of NH_(3)from NO_(3)^(−).Nevertheless,the role of Cu_(2)O in copper-based catalysts still requires further investigation for a more comprehensive understanding.Herein,the Cu_(2)O/Cu(OH)_(2)heterostructures are successfully fabricated through liquid laser irradiation using CuO nanoparticles as a precursor.Experimental and theoretical researches reveal that Cu_(2)O/Cu(OH)_(2)heterostructure exhibits enhanced electrocatalytic performance for NO_(3)^(−)to NH_(3)because Cu(OH)_(2)promotes electron transfer and reduces the valence state of Cu active site in Cu_(2)O.At−0.6 V(vs.reversible hydrogen electrode(RHE)),the NH_(3)yield reaches its maximum at 1630.66±29.72μg·h^(−1)·mgcat^(−1),while the maximum of Faraday efficiency(FE)is 76.95%±5.51%.This study expands the technical scope of copper-based catalyst preparation and enhances the understanding of the electrocatalytic mechanism of NO_(3)^(−)to NH_(3).

关键词： Cu_(2)O/Cu(OH)_(2)heterostructures electron transfer ammonia synthesis electrocatalysts nitrate

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Detection and analysis of serum bile acid profile in patients with colonic polyps

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World Journal of Clinical Cases 2024年第13期12卷 2160-2172页

作者： Xin ji Hong Chen School of Medicine Southeast UniversityNanjing 210009Jiangsu ProvinceChina Department of Gastroenterology Zhongda Hospital Southeast UniversityNanjing 210009Jiangsu ProvinceChina

BACKGROUND Analyzing the variations in serum bile acid(BA)profile can provide a certain biological basis for early warning and prevention of various diseases.There is currently no comprehensive study on the relationship between the serum BA profile and colonic polyps.AIM To study the serum BA profile detection results of patients with colonic polyps,and analyze the correlation between BA and colonic polyps.METHODS From January 1,2022,to June 1,2023,204 patients with colonic polyps who were diagnosed and treated at Zhongda Hospital Southeast University were chosen as the study subjects,and 135 non-polyp people who underwent physical examination were chosen as the control group.Gathering all patients'clinical information,typical biochemical indicators,and BA profile.RESULTS Compared with the control group,the serum levels of taurocholic acid,glycocholic acid,glycochenodeoxycholic acid,and taurochenodeoxycholic acid in the colonic polyp group were significantly higher than those in the control group,while the content of deoxycholic acid(DCA)was lower than that in the control group(P<0.05).When colonic polyps were analyzed as subgroups,it was shown that there was a strong correlation between changes in the BA profile and polyp diameter,location,morphology,pathological kind,etc.CONCLUSION The serum BA profile showed significant changes in patients with colonic polyps,with a significant increase in primary conjugated BA content and a decrease in secondary free bile acid DCA content.There is a certain correlation between primary free BA and pathological parameters of polyps.

关键词： Serum Bile acid profile Colonic polyps Bile acid metabolism

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