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A supramolecular nanoprodrug for prevention of gallstone formation

Chinese Chemical Letters 2025年第2期36卷 354-359页

作者： Xiangjun Zhang Xiaodi Yang Yan Wang Zhongping Xu Sisi Yi Tao Guo Yue Liao Xiyu Tang Jianxiang Zhang Ruibing Wang College of Pharmacy Chongqing Medical University Chongqing university Fuling Hospital Department of Pharmaceutics College of PharmacyThird Military Medical University (Army Medical University) Yu-Yue Pathology Scientific Research Center state Key Laboratory of Trauma and Chemical Poisoning Third Military Medical University (Army Medical University) state Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macau

Cholelithiasis affects approximately 10%-20% of the adult population globally. And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones. Hydroxypropyl-β-cyclodextrin(HPCD) is a supramolecular host compound that can solubilize cholesterol, potentially serving as a preventative or therapeutic agent for cholelithiasis. However, we found that the administration of HPCD treatment did not impede the formation of gallstones in mice, mainly attributed to the pre-complexation of its cavity during the transition process. Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle(HPCD-NP), which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection. In the bile, the HPCD-NP degraded into free HPCD, bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization, leading to gallstones regression. Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies, HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.

关键词： Gallstone Hepatobiliary transport Host-guest interaction Hydroxypropyl-β-cyclodextrin Solubilization

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In situ formed fluorescent gold nanoclusters inhibit hair follicle regeneration in oxidative stress microenvironment via suppressing NFκB signal pathway

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Chinese Chemical Letters 2025年第2期36卷 284-288页

作者： Xiangdong Lai Tengfei Liu Zengchao Guo Yihan Wang Jiang Xiao Qingxiu Xia Xiaohui Liu Hui Jiang Xuemei Wang state Key Laboratory of Digital medical Engineering School of Biological Science and Medical Engineering Southeast University

Skins expose to kinds of risk factors for damage, such as the hormone drugs, skin care products and ultraviolet radiation, which is accompanied by the production of excessive reactive oxygen species(ROS)and eventually leads to hypertrichosis. This skin disease is not aesthetically pleasing and even causes psychological and spiritual problems such as inferiority, anxiety and irritability. Current therapies are limited and often unsatisfactory, such as pharmacological and physical therapies, which have adverse effects and cause the irreversible destruction of hair follicles. Gold nanoclusters have good biocompatibility and their biosynthesis in vivo is responsive to oxidative stress microenvironment(OSM), which could be a safe and effective drug for ROS-induced skin injury. In our study, we demonstrated that zero valence fluorescent gold nanoclusters(FGNCs) were in situ biosynthesized in the plucking-induced damaged skin but not in the normal skin after the administration of gold precursors(+3), while FGNCs inhibited hair follicle regeneration by negatively regulating nuclear transcription factor kappa B(NFκB)-mediated inflammatory response signaling pathway(NFκB/tumor necrosis factor-α(TNF-α) axis). This OSM-responsive in situ biosynthesis method is facile and safe and holds great promise for curing hypertrichosis associated with skin dermatitis and injury.

关键词： Fluorescent gold nanoclusters Hair follicle regeneration Oxidative stress microenvironment Reactive oxygen species Skin injury

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Engineering strategies of biomaterial-assisted exosomes for skin wound repair:Latest advances and challenges

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Chinese Chemical Letters 2025年第1期36卷 99-109页

作者： Yang Xu Le Ma Yang Wang Chunmeng Shi Institute of Rocket Force Medicine State Key Laboratory of Trauma and Chemical PoisoningThird Military Medical University(Army Medical University)Chongqing 400038China

The treatment of skin wounds,especially chronic wounds,remains a critical clinical challenge and places a heavy burden on patients and healthcare *** recent years,the engineering strategy of using biomaterial-assisted exosomes has emerged as a powerful tool for skin *** to treatments such as debridement and regular dressing changes,the design of biomaterial-assisted exosomes not only maintains the bioactivity of exosomes at the wound site but also provides an appropriate microenvironment for the repair of complex tissues,thereby accelerating wound *** review systematically introduces the general characteristics of exosomes and their functions in skin wound healing,highlights recent advances in classification of natural exosomes and engineering methods which enriching their functions in intercellular ***,various emerging and innovative approaches based on biomaterials delivery of exosomes are comprehensively *** review seeks to bring an in-depth understanding of bioactive dressings based on exosomes therapeutic strategies,aiming to facilitate new clinical application value.

关键词： Exosomes Biomaterials Hydrogel Delivery system Wound healing

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A dual drug-loaded tumor vasculature-targeting liposome for tumor vasculature disruption and hypoxia-enhanced chemotherapy

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Chinese Chemical Letters 2025年第1期36卷 397-402页

作者： Cheng-Zhe Gao Hao-Ran Jia Tian-Yu Wang Xiao-Yu Zhu Xiaofeng Han Fu-Gen Wu state Key Laboratory of Digital medical Engineering Jiangsu Key Laboratory for Biomaterials and DevicesSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 211189China

Vascular disrupting agents(VDAs)can destroy tumor vasculature and lead to tumor ischemia and hypoxia,resulting in tumor ***,VDAs are easy to induce the upregulation of genes that are associated with cancer cell drug resistance and angiogenesis in tumor ***-activated chemotherapy will be an ideal supplement to VDAs therapy since it can help to fully utilize the ischemia and hypoxia induced by VDAs to realize a synergistic antitumor therapeutic ***,we design a liposome whose surface is modified with a tumor-homing peptide Cys-Arg-Glu-Lys-Ala(CREKA,which can specifically target tumor vessels and stroma)and whose aqueous cavity and lipid bilayer are loaded by a hypoxia-activatable drug banoxantrone dihydrochloride(AQ4N)and a VDA combretastatin A4(CA4),***4 can selectively target vascular endothelial cells and destroy the tumor blood vessels,which will cause the rapid inhibition of blood flow in tumor and enhance the hypoxia in the tumor *** a consequence,AQ4N can exert its boosted cytotoxicity under the enhanced hypoxic *** as-prepared liposome with a uniform particle size exhibits good stability and high cancer cell killing efficacy in *** addition,in vivo experiments confirm the excellent tumortargeting/accumulation,tumor vasculature-damaging,and tumor inhibition effects of the *** work develops a liposomal which can achieve safe and effective tumor suppression without external stimulus excitation by only single injection,and is expected to benefit the future development of effective antitumor liposomal drugs.

关键词： Tumor-homing peptide Liposome Vascular disrupting agents Chemotherapy Hypoxia-activated

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DNA walker induced “signal on” fluorescence aptasensor strategy for rapid and sensitive detection of extracellular vesicles in gastric cancer

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Chinese Chemical Letters 2025年第2期36卷 328-331页

作者： Gaojian Yang Zhiyang Li Rabia Usman Zhu Chen Yuan Liu Song Li Hui Chen Yan Deng Yile Fang Nongyue He state Key Laboratory of Digital medical Engineering School of Biological Science and Medical Engineering Southeast University Department of Clinical Laboratory the Affiliated Drum Tower Hospital of Nanjing University Medical School Hunan Key Laboratory of Biomedical Nanomaterials and Devices Hunan University of Technology Institute of Cytology and Genetics School of Basic Medical Sciences Hengyang Medical School University of South China Institute for Future Sciences University of South China

The extracellular vesicles show great potential as a noninvasive biomarker for the early detection of cancer. Hence, there is an urgent requirement to create biosensors that are time-saving, simple, and easily scalable in order to accomplish rapid, sensitive, and quantitative detection of extracellular vesicles. In this study, we present a self-propelled DNA walker powered by endonuclease *** CI, which enables the development of a “signal on” sensing platform for the rapid and highly sensitive detection of extracellular vesicles. The DNA motor employed tracks made of streptavidin magnetic beads, which consisted of substrate strands labeled with fluorescein and motor strands locked by aptamers. The aptamer recognition of the target protein on extracellular vesicles unlocked the motor strand, initiating the DNA motor process. After replacing the optimal buffer solution containing the endonuclease *** I, the motor strands autonomously moved along the streptavidin magnetic beads track, continuously releasing fluorescent molecules and producing detectable fluorescence signals. Under optimal conditions, the detection range was from 2×10～4particles/mL to 2×10～9particles/mL, with a detection limit of 2.9×10～3particles/mL,demonstrating excellent selectivity. This method has demonstrated good selectivity in different tumorderived extracellular vesicles and performs well in complex biological samples. The ability to effectively analyze surface proteins of extracellular vesicles in a short period of time gives our DNA walker a tremendous potential for developing simple and cost-effective clinical diagnostic devices.

关键词： Aptamer Detection Extracellular vesicles Nt.BbvCI Streptavidin magnetic beads

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Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han Tang Jianian Hu Siying Kang Song Qin Department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina state Key Laboratory of medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

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Effectiveness of Lianhua Qingwen Granule and Jingyin Gubiao Prescription in Omicron BA.2 Infection and Hospitalization:A Real-World Study of 56,244 Cases in Shanghai,China

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Chinese Journal of Integrative Medicine 2025年第1期31卷 11-18页

作者： ZHANG Yu-jie LIU Guo-jian ZHANG Han LIU Chen CHEN Zhi-qiang XIAN Ji-shu SONG Da-li LIU Zhi YANG Xue WANG Ju ZHANG Zhe ZHANG Lu-ying FENG Hua ZHANG Yan-qi TAN Liang Department of Basic Medicine Army Medical UniversityChongqing400038China Department of Radiology The First Affiliated Hospital of the Army Medical UniversityChongqing400038China Department of Pediatrics The First Affiliated Hospital of the Army Medical UniversityChongqing400038China Department of Neurosurgery The First Affiliated Hospital of the Army Medical UniversityChongqing400038China state Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR519000China Department of Health Statistics College of Military Preventive MedicineArmy Medical UniversityChongqing400038China Department of Critical Care Medicine The First Affiliated Hospital of the Army Medical UniversityChongqing400038China

Objective: To examine the effectiveness of Chinese medicine(CM) Lianhua Qingwen Granule(LHQW) and Jingyin Gubiao Prescription(JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. Methods: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group(23,702 cases), LHQW group(11,576 cases), JYGB group(12,112 cases), and dual combination of LHQW and JYGB group(8,854 cases). The length of stay(LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. Results: Patients aged 41–60 years, with nadir cycle threshold(CT) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching(PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS(both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups(P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS(P=0.032). Conclusions: Patients with a nadir CT value <25were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.

关键词： Lianhua Qingwen Granule Jingyin Gubiao Prescription Chinese medicine Omicron COVID-19

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CSF multi-omics of intracerebral hemorrhage from onset to reperfusion underscores lipid metabolism in functional outcome

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Science Bulletin 2025年第2期70卷 162-166页

作者： Yibin Jiang Sin Man Lam Shuixian Zhang Huan Miao Yong Zhou Qian Zhang Tengyuan Zhou Hui Feng Ning Ding Haomiao Wang Ran Luo Yi Yin Hua Feng Guanghou Shui Rong Hu Department of Neurosurgery and Key Laboratory of Neurotrauma Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China state Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Chongqing Key Laboratory on Big Data for Bio Intelligence Chongqing University of Posts and TelecommunicationsChongqing 400065China Clinical medical Research Center Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China

Constituting 6.5%to 19.6%of all stroke cases worldwide,non-traumatic intracerebral hemorrhage(ICH)represents the most devastating form of stroke,with aging,male gender,and hypertension being important risk factors that predispose individuals to ICH[1,2].Injuries following episodes of ICH can be classified into two forms,namely(1)primary injury arising from mechanical pressure exerted by the hematoma on adjacent tissues,(2)secondary injury resulting from oxidative stress and inflammation mediated by blood cell degradation products and coagulation factors[3].

关键词： metabolism hemorrhage intracerebral

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Three-dimensional models:from cell culture to Patient-Derived Organoid and its application to future liposarcoma research

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Oncology Research 2025年第1期33卷 1-13页

作者： SAYUMI TAHARA SYDNEY RENTSCH FERNANDA COSTAS CASAL DE FARIA PATRICIA SARCHET ROMA KARNA FEDERICA CALORE RAPHAEL E.POLLOCK Department of Surgery Division of Surgical OncologyThe James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA Department of Cancer Biology and Genetics The James Comprehensive Cancer CenterThe Ohio State University Wexner Medical CenterColumbusOH 43210USA

Liposarcoma is one of the most common soft tissue sarcomas,however,its occurrence rate is still rare compared to other *** to its rarity,in vitro experiments are an essential approach to elucidate liposarcoma *** cell culture-based research(2D cell culture)is still playing a pivotal role,while several shortcomings have been recently under *** vivo,mouse models are usually adopted for pre-clinical analyses with expectations to overcome the issues of 2D cell ***,they do not fully recapitulate human dedifferentiated liposarcoma(DDLPS)***,three-dimensional(3D)culture systems have been the recent research focus in the cell biology field with the expectation to overcome at the same time the disadvantages of 2D cell culture and in vivo animal models and fill in the gap between *** the liposarcoma rarity,we believe that 3D cell culture techniques,including 3D cell cultures/co-cultures,and Patient-Derived tumor Organoids(PDOs),represent a promising approach to facilitate liposarcoma investigation and elucidate its molecular mechanisms and effective therapy *** this review,we first provide a general overview of 3D cell cultures compared to 2D cell *** then focus on one of the recent 3D cell culture applications,Patient-Derived Organoids(PDOs),summarizing and discussing several PDO ***,we discuss the current and future applications of PDOs to sarcoma,particularly in the field of liposarcoma.

关键词： Cell culture Liposarcoma Patient-Derived Organoid(PDO) Spheroid Three-dimensional(3D)cell culture

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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong Li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-Lan Xu Hua Ma Zai-Long Chi state Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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