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Enhanced oral drug delivery by mimicking natural amino acid and oligopeptide absorption route

Nano Research 2025年第2期18卷 525-540页

作者： Ruinan Wu Xiaoxing Fan Licheng Wu Liyun Xing Jinxia Kong Zhou Zhou Jingyuan Wen Lian Li Yuan Huang key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China School of Pharmacy Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1023New Zealand

Oral delivery of protein and peptide drugs presents considerable challenges due to their susceptibility to digestive enzymes in gastrointestinal(Gl)tract and low efficiency of transepithelial ***,inspired by efficient absorption of protein-based nutrients,we constructed several kinds of oral drug delivery systems by mimicking natural amino acid and oligopeptide absorption *** kinds of amino acids and two kinds of oligopeptides were chosen as targeting ligands to mediate transportation of orally administered nanoparticles(NPs).Liraglutide(Lira),a kind of glucagon like peptide-1(GLP-1)receptor agonist,was used as model *** functionalized NPs could protect Lira from enzymatic degradation in Gl ***,compared with amino acid-modified NPs,oligopeptide-modified NPs exhibited greater transepithelial transport efficiency and were primarily absorbed in the proximal small intestine due to the high expression and transportation mediated by proton coupled oligopeptide transporter 1(PEPT1).These Lira-loaded NPs could effectively control the blood glucose level,reduce plasma lipid level,and repair tissue damage on type 2 diabetic mice and even showed comparable hypoglycemic effects of subcutaneous injection(s.c.)free *** study demonstrates the potential of mimicking natural oligopeptide absorption route to enhance oral delivery of protein and peptide drugs.

关键词： oral drug delivery amino acid absorption route oligopeptide absorption route liraglutide

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Fisetin micelles precisely exhibit a radiosensitization effect by inhibiting PDGFRβ/STAT1/STAT3/Bcl-2 signaling pathway in tumor

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Chinese Chemical Letters 2025年第2期36卷 262-269页

作者： Yuanyuan Zeng Fang Liu Jun Wang Bianfei Shao Tao He Zhongzheng Xiang Yan Wang Shunyao Zhu Tian Yang Siting Yu Changyang Gong Lei Liu Department of Radiation Oncology Cancer CenterState Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer Hospital Chongqing key laboratory of translational Research for Cancer Metastasis and individualized Treatment Chongqing University Cancer Hospital Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University Department of Pharmacy The First Affiliated Hospital of Wannan Medical CollegeYijishan Hospital of Wannan Medical College Institute of Surgery Research Daping HospitalThird Military Medical University

It is of great significance to find safe and effective radiosensitizers. A primary investigation has been made on fisetin's modification of radiation effect, but its radiosensitization and related mechanisms still need to be deeply clarified. Furthermore, fisetin with high hydrophobicity is difficult to dissolve in water,severely limiting its research and application. In this study, we fabricated a safe and soluble radiosensitizer fisetin micelle for precisely enhancing radiotherapy by inhibiting platelet-derived growth factor receptor-β(PDGFRβ)/signal transducer and activator of transcription 1(STAT1)/signal transducer and activator of transcription 3(STAT3)/B cell lymphoma 2(Bcl-2) signaling pathway in the tumor. Systematic and detailed studies were performed to verify its radiosensitization effect in vitro and in vivo. On the cellular level, fisetin micelles selectively increased the radiosensitivity of tumor cells(CT26 and 4T1 cells)and had little effect on the sensitivity of normal mouse cells(L929 cells) to radiation. In the mouse models of colon and breast cancers, fisetin micelles showed an efficient radiosensitization capacity without apparent toxicity. Additionally, we first found that fisetin micelles played a radiotherapy sensitization role by inhibiting the PDGFRβ/STAT1/STAT3/Bcl-2 pathway activity. In general, this work not only confirmed that fisetin micelles precisely exhibit a radiosensitization effect in vitro and in vivo, but also profoundly explored its mechanisms underlying, to provide a theoretical and experimental basis for the clinical application of fisetin micelles.

关键词： Fisetin Platelet-derived growth factor receptor-β Polymetric micelles Radiosensitizer Radiotherapy

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Advances in genotypic antimicrobialresistance testing: a comprehensive review

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Science China(Life Sciences) 2025年第1期68卷 130-143页

作者： Boheng Duan Xianjun Zeng Junping Peng Huan Kui College of Nanchang University Nanchang 330031China Department of imaging The Second Affiliated Hospital of Nanchang UniversityNanchang 330038China NHC key laboratory of Systems Biology of Pathogens National Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China key laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China key laboratory of Pathogen Infection Prevention and Control(Ministry of Education) State Key Laboratory of Respiratory Health and MultimorbidityNational Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China

Antimicrobial resistance(AMR)represents a substantial threat to global public health,complicating the treatment of common infections and leading to prolonged illness and escalated healthcare *** effectively combat AMR,timely and accurate detection is crucial for AMR surveillance and individual-based *** antibiotic resistance testing(AST)has long been considered the gold standard in clinical applications,serving as the foundation for clinical AMR diagnosis and optimized *** has significantly contributed to ensuring patients′health and the development of novel *** advancements in automated culture-based AST technologies,inherent limitations impede the widespread use of phenotypic AST in AMR *** AST technologies offer a promising alternative option,exhibiting advantages of rapidity,high sensitivity,and *** the continuous advancement and expanding applications of genotypic AST technologies,such as microfluidics,mass spectrometry,and high-resolution melting curve analysis,new vigor has been injected into the development and clinical implementation of genotypic AST *** this narrative review,we discuss the principles,applications,and advancements of emerging genotypic AST methods in clinical *** comprehensive review aims to highlight the significant scientific potential of emerging genotypic AST technologies in clinical AMR diagnosis,providing insights to enhance existing methods and explore novel approaches.

关键词： antimicrobial resistance(AMR) genotypic antibiotic resistance testing(AST) AST technologies review

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Machine learning in echocardiography-based prediction model of cardiovascular diseases

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中华医学杂志(英文版) 2025年第2期138卷 228-230页

作者： Yasheng Zubaire Zhao Ruohan Zhu Ye Zhang Zisang Lv Qing Xie Mingxing Zhang Li Department of Ultrasound Medicine Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China Clinical Research Center for medical imaging in Hubei Province Wuhan Hubei China Hubei Province key laboratory of Molecular imaging Wuhan Hubei China

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Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： XIANG LI WENKE JIN LIFENG WU HUAN WANG XIN XIE WEI HUANG BO LIU State key laboratory of Southwestern Chinese Medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

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Biomaterial-based strategies:a new era in spinal cord injury treatment

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Neural Regeneration Research 2025年第12期20卷 3476-3500页

作者： Shihong Zhu Sijun Diao Xiaoyin Liu Zhujun Zhang Fujun Liu Wei Chen Xiyue Lu Huiyang Luo Xu Cheng Qiang Liao Zhongyu Li Jing Chen Department of Neurosurgery West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengduSichuan ProvinceChina Department of Ophthalmology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Pharmacy West China HospitalWest China Medical SchoolSichuan UniversityChengduSichuan ProvinceChina

Enhancing neurological recovery and improving the prognosis of spinal cord injury have gained research attention *** cord injury is associated with a complex molecular and cellular *** complexity has prompted researchers to elucidate the underlying pathophysiological mechanisms and changes and to identify effective treatment *** approaches for spinal cord injury repair include surgery,oral or intravenous medications,and administration of neurotrophic factors;however,the efficacy of these approaches remains inconclusive,and serious adverse reactions continue to be a *** advancements in tissue engineering and regenerative medicine,emerging strategies for spinal cord injury repair now involve nanoparticle-based nanodelivery systems,scaffolds,and functional recovery techniques that incorporate biomaterials,bioengineering,stem cell,and growth factors as well as three-dimensional *** biomaterial scaffolds should not only provide structural support for neuron migration,adhesion,proliferation,and differentiation but also mimic the mechanical properties of natural spinal cord ***,these scaffolds should facilitate axon growth and neurogenesis by offering adjustable topography and a range of physical and biochemical *** three-dimensionally interconnected porous structure and appropriate physicochemical properties enabled by three-dimensional biomimetic printing technology can maximize the potential of biomaterials used for treating spinal cord ***,correct selection and application of scaffolds,coupled with successful clinical translation,represent promising clinical objectives to enhance the treatment efficacy for and prognosis of spinal cord *** review elucidates the key mechanisms underlying the occurrence of spinal cord injury and regeneration post-injury,including neuroinflammation,oxidative stress,axon regeneration,and *** review also briefly dis

关键词： biomaterials growth factors nanoparticles neural regeneration scaffolds spinal cord injury stem cells therapy strategies tissue engineering

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Beyond the tumor region:Peritumoral radiomics enhances prognostic accuracy in locally advanced rectal cancer

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World Journal of Gastroenterology 2025年第8期31卷 49-65页

作者： Zhi-Ying Liang Mao-Li Yu Hui Yang Hao-Jiang Li Hui Xie Chun-Yan Cui Wei-Jing Zhang Chao Luo Pei-Qiang Cai Xiao-Feng Lin Kun-Feng Liu Lang Xiong Li-Zhi Liu Bi-Yun Chen Department of Radiology State Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060Guangdong ProvinceChina Department of Radiology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina West China School of Medicine Sichuan UniversityChengdu 610041Sichuan ProvinceChina Department of medical imaging First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000Jiangxi ProvinceChina

BACKGROUND The peritumoral region possesses attributes that promote cancer growth and ***,the potential prognostic biomarkers in this region remain relatively underexplored in *** To investigate the prognostic value and importance of peritumoral radiomics in locally advanced rectal cancer(LARC).METHODS This retrospective study included 409 patients with biopsy-confirmed LARC treated with neoadjuvant chemoradiotherapy and *** were divided into training(n=273)and validation(n=136)*** on intratumoral and peritumoral radiomic features extracted from pretreatment axial high-resolution small-field-of-view T2-weighted images,multivariate Cox models for progression-free survival(PFS)prediction were developed with or without clinicoradiological features and evaluated with Harrell’s concordance index(C-index),calibration curve,and decision curve *** stratification,Kaplan-Meier analysis,and permutation feature importance analysis were *** The comprehensive integrated clinical-radiological-omics model(ModelICRO)integrating seven peritumoral,three intratumoral,and four clinicoradiological features achieved the highest C-indices(0.836 and 0.801 in the training and validation sets,respectively).This model showed robust calibration and better clinical net benefits,effectively distinguished high-risk from low-risk patients(PFS:97.2%vs 67.6%and 95.4%vs 64.8%in the training and validation sets,respectively;both P<0.001).Three most influential predictors in the comprehensive ModelICRO were,in order,a peritumoral,an intratumoral,and a clinicoradiological ***,the peritumoral model outperformed the intratumoral model(C-index:0.754 vs 0.670;P=0.015);peritumoral features significantly enhanced the performance of models based on clinicoradiological or intratumoral features or their *** Peritumoral radiomics holds greater prognostic value than intratumoral radiomics for predicting PFS in L

关键词： Rectal cancer Peritumoral radiomics Intratumoral radiomics Prognosis analysis Variable importance analysis Tumor microenvironment

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Recent Strategies and Advances in Hydrogel‑Based Delivery Platforms for Bone Regeneration

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Nano-Micro Letters 2025年第3期17卷 389-439页

作者： Xiao Wang Jia Zeng Donglin Gan Kun Ling Mingfang He Jianshu Li Yongping Lu Scientific and Technological Innovation Center for Biomedical Materials and Clinical Research Guangyuan Key Laboratory of Multifunctional Medical HydrogelGuangyuan Central HospitalGuangyuan 628000People’s Republic of China Jiangsu Collaborative Innovation Center of Biomedical Functional Materials Jiangsu Key Laboratory of Bio‑Functional MaterialsSchool of Chemistry and Materials ScienceNanjing Normal UniversityNanjing 210023People’s Republic of China College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065People’s Republic of China

Bioactive molecules have shown great promise for effectively regulating various bone formation processes,rendering them attractive therapeutics for bone ***,the widespread application of bioactive molecules is limited by their low accumulation and short half-lives in *** have emerged as ideal carriers to address these challenges,offering the potential to prolong retention times at lesion sites,extend half-lives in vivo and mitigate side effects,avoid burst release,and promote adsorption under physiological *** review systematically summarizes the recent advances in the development of bioactive molecule-loaded hydrogels for bone regeneration,encompassing applications in cranial defect repair,femoral defect repair,periodontal bone regeneration,and bone regeneration with underlying ***,this review discusses the current strategies aimed at improving the release profiles of bioactive molecules through stimuli-responsive delivery,carrier-assisted delivery,and sequential ***,this review elucidates the existing challenges and future directions of hydrogel encapsulated bioactive molecules in the field of bone regeneration.

关键词： Hydrogel Bone regeneration Bioactive molecules Drug delivery Nano-/microscale carriers

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Plasma metabolomics combined with mass spectrometry imaging reveals crosstalk between tumor and plasma in gastric cancer genesis and metastasis

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Chinese Chemical Letters 2025年第1期36卷 506-512页

作者： Yanhua Chen Xian Ding Jun Zhou Zhaoying Wang Yunhai Bo Ying Hu Qingce Zang Jing Xu Ruiping Zhang Jiuming He Fen Yang Zeper Abliz key laboratory of Mass Spectrometry imaging and Metabolomics(State Ethnic Affairs Commission) Center for Imaging and Systems BiologyCollege of Life and Environmental SciencesMinzu University of ChinaBeijing 100081China State key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(Ministry of Education) Center of Drug Clinical TrialPeking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering Research Center of Food Environment and Public Health Minzu University of ChinaBeijing 100081China key laboratory of Ethnomedicine of Ministry of Education School of PharmacyMinzu University of ChinaBeijing 100081China key laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of BioBankPeking University Cancer Hospital and InstituteBeijing 100142China Pharmacy Department of Beijing Chao–Yang Hospital Capital Medical UniversityBeijing 100020China

Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor *** elevated mortality rates are primarily due to its proclivity for late-stage *** the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and *** this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and *** results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor ***,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.

关键词： Metabolomics Spatial-resolved metabolomics Gastric cancer Blood-tumor metabolic crosstalk Lipid peroxidation

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In vivo self-assembled bispecific fluorescence probe for early detection of bladder cancer and metastasis

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Science Bulletin 2025年第3期70卷 407-418页

作者： Da-Yong Hou Ni-Yuan Zhang Peng Zhang Xiang-Peng Li Jiong-Cheng Wu Mei-Yu Lv Zhi-Jia Wang Xing-Jie Hu Jian-Xiao Liang Hong-Lei Wang Yue-Ze Wang Hui-Hui You Hong-Wei An Hao Wang Wanhai Xu NHC key laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in UrologyHarbin Medical UniversityHarbin 150001China Department of PET-CT/MRI Harbin Medical University Cancer HospitalHarbin 150001China CAS key laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST)Beijing 100190China

Tumor metastasis accounts for over 90%of tumor-related deaths,prompting the development of fluorescently labeled tumor-specific molecular imaging agents for differentiating tumors from normal ***,early detection of metastasis lesions by tracking tumor markers alone has proven to be ***,we reported a glycopeptide-based bispecific fluorescence probe(bsProbe)for earlier detection of bladder cancer and *** simultaneously recognition(tumor&tumor microenvironment)and in vivo self-assembly,the tumor accumulation of bsProbe(12.3%ID/g)was obviously increased by∼6 fold compared with that in CXCR4 specific fluorescence probe(sProbe),indicating the obvious advantages of bsProbe over existing tumor metastasis detection ***,bsProbe substantially broadens the tumor diagnosis window and enhances the detection signal to noise ratio(SNR:approximately 9.5),permitting early diagnosis of lung micro-metastasis(∼1 mm),precise identifying of tumor boundaries and micro-tumors in orthotopic tumor *** importantly,bsProbe was demonstrated to distinguish malignant from benign specimen with a specificity of 90.48%and sensitivity of 92.22%in 195 clinical specimens of bladder cancer *** together,this novel synergetic targeting(CD206×CXCR4)strategy provides an attractive method for earlier detection of bladder cancer and metastasis,which might be further extended to the imaging-guided surgery of clinical invisible tumors.

关键词： Self-assembly Peptide Nanomaterial Fluorescence imaging Bladder cancer

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