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Differential Responses of Transplanted Stem Cells to Diseased Environment Unveiled by a Molecular NIR-II Cell Tracker

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Research 2021年第1期2021卷 935-950页

作者： Hao Chen Huaxiao Yang Chen Zhang Si Chen Xin Zhao Mark Zhu Zhiming Wang Yuebing Wang Hung-Ta Wo Kai Li Zhen Cheng Center for Molecular Imaging Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Molecular Imaging Program at Stanford(MIPS) Bio-X Programand Department of RadiologyCanary Center at Stanford for Cancer Early DetectionStanford UniversityStanfordCA 94305-5344USA University of North Texas Biomedical EngineeringDentonTX 76207USA Department of Biomedical Engineering Southern University of Science and TechnologyShenzhenGuangdong 518055China Department of Neurology Xiangya HospitalCentral South UniversityXiangya Road 88ChangshaHunan 410008China Stanford Cardiovascular Institute StanfordCA 94305USA Division of Cardiology Department of Internal MedicineChang Gung Memorial HospitalLinkouTaiwan33305China

Stem cell therapy holds high promises in regenerative *** major challenge of clinical translation is to precisely and quantitatively evaluate the in vivo cell distribution,migration,and engraftment,which cannot be easily achieved by current *** address this issue,for the first time,we have developed a molecular cell tracker with a strong fluorescence signal in the second near-infrared(NIR-II)window(1,000-1,700 nm)for real-time monitoring of in vivo cell behaviors in both healthy and diseased animal *** NIR-II tracker(CelTrac1000)has shown complete cell labeling with low cytotoxicity and profound long-term tracking ability for 30 days in high spatiotemporal resolution for semiquantification of the biodistribution of transplanted stem *** advantage of the unique merits of CelTrac1000,the responses of transplanted stem cells to different diseased environments have been discriminated and ***,we also demonstrate CelTrac1000 as a universal and effective technique for ultrafast real-time tracking of the cellular migration and distribution in a 100μm single-cell cluster spatial resolution,along with the lung contraction and heart *** such,this NIR-II tracker will shift the optical cell tracking into a single-cell cluster and millisecond temporal resolution for better evaluating and understanding stem cell therapy,affording optimal doses and efficacy.

关键词： doses distribution holds

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Astrocytes in human central nervous system diseases: a frontier for new therapies

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Signal Transduction and Targeted Therapy 2023年第11期8卷 5233-5269页

作者： Alexei Verkhratsky Arthur Butt Baoman Li Peter Illes Robert Zorec Alexey Semyanov Yong Tang Michael V.Sofroniew International Joint Research Centre on Purinergic Signalling/School of Health and Rehabilitation Chengdu University of Traditional Chinese MedicineChengduChina Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangChina Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Achucarro Centre for Neuroscience IKERBASQUEBasque Foundation for ScienceBilbaoSpain Department of Stem Cell Biology State Research Institute Centre for Innovative MedicineLT-01102VilniusLithuania Institute of Biomedical and Biomolecular Sciences School of Pharmacy and Biomedical SciencesUniversity of PortsmouthPortsmouthUK Rudolf Boehm Institute for Pharmacology and Toxicology University of Leipzig04109LeipzigGermany Celica Biomedical Lab Cell EngineeringTechnology Park1000LjubljanaSlovenia Laboratory of Neuroendocrinology—Molecular Cell Physiology Institute of PathophysiologyUniversity of LjubljanaFaculty of MedicineLjubljanaSlovenia Department of Physiology Jiaxing University College of Medicine314033JiaxingChina Key Laboratory of Acupuncture for Senile Disease(Chengdu University of TCM) Ministry of Education/Acupuncture and Chronobiology Key Laboratory of Sichuan ProvinceChengduChina Department of Neurobiology David Geffen School of MedicineUniversity of CaliforniaLos AngelesCAUSA

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence of the central nervous system(CNS).Astroglia contribute to the pathophysiology of all neurological and neuropsychiatric disorders in ways that can be either beneficial or detrimental to disorder *** changes in astroglia can be primary or secondary and can result in gain or loss of *** respond to external,non-cell autonomous signals associated with any form of CNS pathology by undergoing complex and variable changes in their structure,molecular expression,and *** addition,internally driven,cell autonomous changes of astroglial innate properties can lead to CNS *** pathophysiology is complex,with different pathophysiological cell states and cell phenotypes that are context-specific and vary with disorder,disorder-stage,comorbidities,age,and ***,we classify astroglial pathophysiology into(i)reactive astrogliosis,(ii)astroglial atrophy with loss of function,(iii)astroglial degeneration and death,and(iv)astrocytopathies characterised by aberrant forms that drive *** review astroglial pathophysiology across the spectrum of human CNS diseases and disorders,including neurotrauma,stroke,neuroinfection,autoimmune attack and epilepsy,as well as neurodevelopmental,neurodegenerative,metabolic and neuropsychiatric *** cellular and molecular mechanisms of astroglial pathophysiology represents a new frontier to identify novel therapeutic strategies.

关键词： diseases epilepsy degeneration

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Smart Nanopipette Technology for Studying 2D and 3D Cancer Models

Smart Nanopipette Technology for Studying 2D and 3D Cancer M...

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International Conference on Manipulation, Manufacturing and Measurement on the Nanoscale (3M-NANO)

作者： Alexander Vaneev Roman Timoshenko Vasilii Kolmogorov Roman Akasov Saida Karshieva Elizaveta Koudan Alexander Majouga Peter Gorelkin Alexander Erofeev Laboratory of Biophysics National University of Science and Technology ‘‘MISIS Moscow Russia Laboratory of Molecular Pharmacology I.M. Sechenov First Moscow State Medical University Moscow Russia Center for Biomedical Engineering National University of Science and Technology ‘‘MISIS Moscow Russia Department of Physical Materials Science National University of Science and Technology ‘‘MISIS Moscow Russia

ISBN: (数字)9798350362107

ISBN: (纸本)9798350362114

This study presents a novel approach for studying 3D spheroids using glass nanopipettes and nanoelectrodes. The innovative application of these tools allows the investigation of spheroids from multiple perspectives. The first demonstration of this approach involved the use of scanning ion conductance microscopy (SICM), which enabled the spheroidal surface topography of U87MG (human glioblastoma) to be obtained for the first time. This was complemented by the mapping of Young's module. Furthermore, the electrochemical approach enabled the internal oxygen, reactive oxygen species(ROS) profiles to be obtained within the spheroids formed from primary cortical neurons and U87MG spheroids, representing a novel advancement in this field. The principal advantage of nanocapillary-based electrodes is their ability to perform minimally invasive measurements in the interior regions of spheroids, thereby facilitating precise electrochemical detection of oxygen and ROS levels at a given spheroid depth. This technological advance represents a significant step forward, opening up new opportunities for minimally invasive, high-resolution spheroid studies that can improve the development of therapies for tumor and neurodegenerative diseases.

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Sex-based Disparities in Brain Aging: A Focus on Parkinson's Disease

arXiv

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arXiv 2023年

作者： Beheshti, Iman Booth, Samuel Ko, Ji Hyun Department of Human Anatomy and Cell Science University of Manitoba WinnipegMB Canada Kleysen Institute for Advanced Medicine Health Science Centre WinnipegMB Canada Graduate Program in Biomedical Engineering University of Manitoba WinnipegMB Canada

INTRODUCTION: Parkinson’s disease (PD) is linked to faster brain aging. Sex is recognized as an important factor in PD, such that males are twice as likely as females to have the disease and have more severe symptoms and a faster progression rate. Despite previous research, there remains a significant gap in understanding the function of sex in the process of brain aging in PD patients. METHODS: The T1-weighted MRI-driven brain-predicted age difference (i.e., brain-PAD: the actual age subtracted from the brain-predicted age) was computed in a group of 373 PD patients (mean age ± SD: 61.37 ± 9.81, age range: 33–85, 34% female) from the Parkinson’s Progression Marker Initiative database using a robust brain-age estimation framework that was trained on 949 healthy subjects. Linear regression models were used to investigate the association between brain-PAD and clinical variables in PD, stratified by sex. All female PD patients were used in the correlational analysis while the same number of males were selected based on propensity score matching method considering age, education level, age of symptom onset, and clinical symptom severity. RESULTS: Despite both patient groups being matched for demographics, motor and non-motor symptoms, it was observed that males with Parkinson's disease (PD-M) exhibited a significantly higher mean brain age-delta than their female counterparts (PD-F) (t(256)= 2.50, p = 0.012). In the propensity score-matched PD-M group (PD-M*), brain-PAD was found to be associated with a decline in general cognition, a worse degree of sleep behavior disorder, reduced visuospatial acuity, and caudate atrophy. Conversely, no significant links were observed between these factors and brain-PAD in the PD-F group. DISCUSSION: Having 'older' looking brains in PD-M than PD-F supports the idea that sex plays a vital function in PD, such that the PD mechanism may be different in males and females. This study has the potential to broaden our understanding of dissim

关键词： Machine learning

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Employing texture features of chest x-ray images and machine learning in covid-19 detection and classification

Mendel

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Mendel 2021年第1期27卷 9-17页

作者： Alquran, Hiam Alsleti, Mohammad Alsharif, Roaa Qasmieh, Isam Abu Alqudah, Ali Mohammad Harun, Nor Hazlyna Binti Department of Biomedical Systems and Informatics Engineering Yarmouk University Irbid21163 Jordan The Institute of Biomedical Technology King Hussein Medical Center Royal Jordanian Medical Service Amman11855 Jordan College of applied medical Sciences Radiological Science Program King Saud University Jeddah21435 Saudi Arabia Data Science Research Lab School of Computing Universiti Utara Malaysia Sintok Kedah06010 Malaysia

The novel coronavirus (nCoV-19) was first detected in December 2019. It had spread worldwide and was declared coronavirus disease (COVID-19) pandemic by March 2020. Patients presented with a wide range of symptoms affecting multiple organ systems predominantly the lungs. Severe cases required intensive care unit (ICU) admissions while there were asymptomatic cases as well. Although early detection of the COVID-19 virus by Real-time reverse transcription-polymerase chain reaction (RT-PCR) is effective, it is not efficient;as there can be false negatives, it is time consuming and expensive. To increase the accuracy of in-vivo detection, radiological image-based methods like a simple chest X-ray (CXR) can be utilized. This reduces the false negatives as compared to solely using the RT-PCR technique. This paper employs various image processing techniques besides extracted texture features from the radiological images and feeds them to different artificial intelligence (AI) scenarios to distinguish between normal, pneumonia, and COVID-19 cases. The best scenario is then adopted to build an automated system that can segment the chest region from the acquired image, enhance the segmented region then extract the texture features, and finally, classify it into one of the three classes. The best overall accuracy achieved is 93.1% by exploiting Ensemble classifier. Utilizing radiological data to conform to a machine learning format reduces the detection time and increase the chances of survival. © 2021, Brno University of Technology. All rights reserved.

关键词： COVID-19

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PepTune: De Novo Generation of Therapeutic Peptides with Multi-Objective-Guided Discrete Diffusion

arXiv

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arXiv 2024年

作者： Tang, Sophia Zhang, Yinuo Chatterjee, Pranam Department of Biomedical Engineering Duke University United States Management and Technology Program University of Pennsylvania United States Center of Computational Biology Duke-NUS Medical School Singapore Department of Computer Science Duke University United States Department of Biostatistics and Bioinformatics Duke University United States

Peptide therapeutics, a major class of medicines, have achieved remarkable success across diseases such as diabetes and cancer, with landmark examples such as GLP-1 receptor agonists revolutionizing the treatment of type-2 diabetes and obesity. Despite their success, designing peptides that satisfy multiple conflicting objectives, such as target binding affinity, solubility, and membrane permeability, remains a major challenge. Classical drug development and target structure-based design are ineffective for such tasks, as they fail to optimize global functional properties critical for therapeutic efficacy. Existing generative frameworks are largely limited to continuous spaces, unconditioned outputs, or single-objective guidance, making them unsuitable for discrete sequence optimization across multiple properties. To address this, we present PepTune, a multi-objective discrete diffusion model for the simultaneous generation and optimization of therapeutic peptide SMILES. Built on the Masked Discrete Language Model (MDLM) framework, PepTune ensures valid peptide structures with bond-dependent masking schedules and penalty-based objectives. To guide the diffusion process, we propose a Monte Carlo Tree Search (MCTS)-based strategy that balances exploration and exploitation to iteratively refine Pareto-optimal sequences. MCTS integrates classifier-based rewards with search-tree expansion, overcoming gradient estimation challenges and data sparsity. Using PepTune, we generate diverse, chemically modified peptides optimized for multiple therapeutic properties, including target binding affinity, membrane permeability, solubility, hemolysis, and non-fouling for various disease-relevant targets. In total, our results demonstrate that MCTS-guided masked discrete diffusion is a powerful and modular approach for multi-objective sequence design in discrete state spaces. © 2024, CC BY-NC-ND.

关键词： Trees (mathematics)

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Nanoarchitectonics of europium vanadate nanoparticles decorated carbon nanofibers for electrochemical detection of fungicide in fruits

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Journal of the Taiwan Institute of Chemical Engineers 2024年 161卷

作者： Huang, Song-Jeng Gokulkumar, Kumar Govindasamy, Mani Albaqami, Munirah D. Wabaidur, Saikh Mohammad Department of Mechanical Engineering National Taiwan University of Science and Technology Taipei City106335 Taiwan Department of Research and Innovation Saveetha School of Engineering SIMATS Chennai602105 India International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City243303 Taiwan Department of Chemistry College of Science King Saud University Riyadh11451 Saudi Arabia

Background: Fungicides, like carbendazim, have effects on male fertility. There have been sufficient studies conducted on certain chemical compounds to indicate a selective action at the epididymis level. To prevent contamination of food products with fungicides, most of the governments have established rules for the use of fungicides. However, even though this type of fungicide is primarily used in agriculture. More probably, it's contaminated with fruits and vegetables. In particular, carbendazim is one of the major fungicides in the agricultural usage Methods: This research work developed a europium vanadate (EuVO4) nanoparticle decorated carbon nanofiber (CNF) composites by hydrothermal-sonochemical approach. Based on this composite, Carbendazim sensing is developed through electrochemical oxidation based on EuVO4/f-CNF modified Glassy Carbon Electrode (GCE). By combining EuVO4 and f-CNF with the GCE, carbendazim detection can be highly effective. GCEs are rigid, making them ideal for depositing EuVO4/f-CNF, while their expansive surface area makes it possible to immobilize a greater amount of EuVO4/f-CNF, which could increase the Carbendazim sensing ability of the resulting modified GCEs with EuVO4/f-CNF. Main Findings: : The carbendazim sensing was actualized by the electrocatalytic oxidation of carbendazim on the composite modified electrode, and it is demonstrating a linear range of 0.125 to 23.875 – 33.81 to 131.375 µM with a remarkably limit of detection of 0.00612 µM. The EuVO4/f-CNF /GCE also showcased an excellent degree of stability, retaining 96.5 % of its initial activity even after 30 days. This research highlights the potential of EuVO4/f-CNF modified GCEs as robust, and efficient platform for the carbendazim detection under electrochemical approach. © 2024 Taiwan Institute of Chemical Engineers

关键词： Carbon nanofibers

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Noninvasive Low-Frequency Pulsed Focused Ultrasound Therapy for Rheumatoid Arthritis in Mice

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Research 2023年第3期2022卷 205-219页

作者： Xuqiao Hu Fei Li Jieying Zeng Zhenru Zhou Zhaoyang Wang Jing Chen Dongyan Cao Yifan Hong Laixin Huang Yongsheng Chen Jinfeng Xu Fajn Dong Rongmin Yu Harong Zhen Department of Ultrasound First Affiliated Hospital of Southern University of Science and TechnologySecond Clinical Medical College of Jinan University(Shenzhen People's Hospital)Shenzhen 518020China integrated Chinese and Western Medicine Postdoctoral Research Station Jinan UniversityGuangzhou 510632China Paul C.Lauterbur Research Center for Biomedical Imaging Institute of Biomedical and Health EngineeringShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueShenzhen University TownShenzhen 518055China Shanghai Cancer Institute Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032China institute of Molecular Physiology Institute of Cancer ResearchShenzhen Bay LaboratoryShenzhen 518132P.R.China Department of Pharmacology College of PharmacyJinan University601 Huangpu Avenue WestGuangzhou 510632China Biotechnological Institute of Chinese Materia Medica Jinan University601 Huangpu Avenue WestGuangzhou 510632China

Rheumatoid arthritis(RA)is a common autoimmune disease characterized by chronic and progressive inflammation of the *** ultrasound therapy is an increasingly attractive alternative for treating RA owing to its noninvasiveness;however,it remains unclear which immune subsets respond to ultrasound *** this study,we showed that spleen-targeted low-frequency pulsed focused ultrasound(LFPFU)effectively improved the severity of arthritis in an arthritis mouse model established in DBA/1J ***,we performed in-depth immune profiling of spleen samples from RA mice,RA mice that underwent ultrasound therapy,and healthy controls using mass cytometry along with extensive antibody panels and identified the immune composition of 14 cell populations,including CD4^(+)/CD8^(+)T cells,B cells,natural killer cells,and dendritic ***,multidimensional analysis according to cell-surface markers and phenotypes helped in identifying 4 and 5 cell subpopulations among T and myeloid cells,respectively,with 6 T cell subsets and 3 myeloid cell subsets responsive to ultrasound therapy among the 3 *** these cell subsets,CD8^(+)T cell subsets showed a unique response to ultrasound stimulation in RA ***,CD8^(+)T cells show a noticeable correlation with the degree of arthritis progression and could serve as an indicator for spleen-focused ultrasound-based ***,single-cell RNA sequencing of spleen cells revealed the importance of T,B,and myeloid cell populations in the anti-inflammatory *** results elucidated the unique cell subsets and transcriptome of splenic cells responsive to LFPFU and demonstrated the potential of spleen-focused ultrasound stimulation in the treatment of inflammatory diseases.

关键词： spleen stimulation Focus

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A nanotherapeutic strategy to target drug-tolerant cells and overcome EGFR tyrosine kinase inhibitor resistance in lung cancer

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Cancer Communications 2023年第4期43卷 503-507页

作者： Tatiana Shaurova Lingyue Yan Yafei Su Laurie James Rich Vui King Vincent-Chong Hannah Calkins Saraswati Pokharel Martin Petkovich Mukund Seshadri Yun Wu Pamela Anne Hershberger Department of Pharmacology and Therapeutics Roswell Park Comprehensive Cancer CenterBuffaloNew YorkUSA Department of Biomedical Engineering University at Buffalothe State University of New YorkBuffaloNew YorkUSA Cell Stress and Biophysical Oncology Graduate Program Roswell Park Comprehensive Cancer CenterBuffaloNew YorkUSA Fujifilm-Visual Sonics Corporation TorontoOntarioCanada Department of Oral Oncology Roswell Park Comprehensive Cancer CenterBuffaloNew YorkUSA Department of Pathology Roswell Park Comprehensive Cancer CenterBuffaloNew YorkUSA Cancer Research Institute School of MedicineQueens UniversityKingstonOntarioCanada

Dear Editor,For patientswith epidermal growth factor receptor(EGFR)mutant non-small cell lung cancer(NSCLC),EGFR tyrosine kinase inhibitors(TKIs)are used as the first-line treatment[1,2].Despite initial therapeutic responses,patients invariably experience disease progression due to acquired drug resistance[3].Resistance arises,in part,because a subset of cancer cells undergoes epithelial-mesenchymal transition(EMT)and remains viable despite exposure to EGFR TKI concentrations that eliminate the bulk population[4].The surviving cells can be re-sensitized to treatment by prolonged culture in the absence of EGFR TKIs,indicating a transient.

关键词： therapeutic viable resistance

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Prediction tools for assessing functional impacts of gene mutations in Clear Cell Renal Cell Carcinoma: A comparative study

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Computers in Biology and Medicine 2025年第Pt A期192卷 110187-110187页

作者： Yang, Cheng-Hong Lin, Guan-Cheng Wu, Chih-Hsien Chen, Jin-Bor Chuang, Li-Yeh Department of Information Management Tainan University of Technology Tainan Taiwan Department of Electronic Engineering National Kaohsiung University of Science and Technology Kaohsiung Taiwan Drug Development and Value Creation Research Center Kaohsiung Taiwan Ph. D. Program in Biomedical Engineering Kaohsiung Medical University Kaohsiung Taiwan Division of Nephrology Department of Internal Medicine Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine Taiwan Department of Chemical Engineering & Institute of Biotechnology and Chemical Engineering I-Shou University Kaohsiung Taiwan Taiwan

Renal cell carcinoma (RCC) is a well-known malignancy characterized by specific gene mutations that elevate its occurrence. It can be categorized into clear cell RCC (ccRCC), papillary RCC, and chromophobe RCC, which account for approximately 85 % of all primary RCC cases. The mutations typically involve single-nucleotide variants (SNVs) that lead to amino acid substitutions, which influence various biological functions, including gene expression. Therefore, predicting the functional consequences of RCC-related single-nucleotide polymorphisms (SNPs), including substitutions, insertions, deletions, and duplications, is crucial for the effective clinical management of RCC. In recent years, the accessibility and popularity of tools for predicting SNP functional variations have grown, especially in research concerning the potential risks associated with key gene mutations in cancer. Accordingly, this study focused on commonly mutated genes in ccRCC, namely VHL, BAP1, PBRM1, and SETD2. Public data from sources such as The Cancer Genome Atlas and the National Center for Biotechnology Information were used to identify 61 gene mutation positions. Nine nonsynonymous mutation prediction tools were used for analysis, namely SIFT, Polyphen-2, Mutation Assessor, Fathmm, MutPred, CHASM, Revel, Provean, and SNP&GO. The tools were evaluated by their statistical performance, prediction distribution, and receiver operating characteristic curves. The three tools with the highest accuracy for predicting the functional consequences of mutations in the four frequently mutated genes associated with ccRCC were SIFT (accuracy of 0.75), Provean (0.7), and Polyphen-2 (0.69). These findings offer valuable insights into predicting ccRCC-related gene mutation effects, but further research and validation are essential to support their clinical applications. © 2025

关键词： Transcription

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