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Local dose-dense chemotherapy for triple-negative breast cancer via minimally invasive implantation of 3D printed devices

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Asian Journal of Pharmaceutical sciences 2024年第1期19卷 69-85页

作者： Noehyun Myung Hyun-Wook Kang Department of biomedical Engineering Ulsan National Institute of Science and Technology(UNIST)Ulju-gun 44919South Korea

Dose-dense chemotherapy is the preferred first-line therapy for triple-negative breast cancer(TNBC),a highly aggressive disease with a poor prognosis.This treatment uses the same drug doses as conventional chemotherapy but with shorter dosing intervals,allowing for promising clinical outcomes with intensive treatment.However,the frequent systemic administration used for this treatment results in systemic toxicity and low patient compliance,limiting therapeutic efficacy and clinical benefit.Here,we report local dose-dense chemotherapy to treat TNBC by implanting 3D printed devices with timeprogrammed pulsatile release profiles.The implantable device can control the time between drug releases based on its internal microstructure design,which can be used to control dose density.The device is made of biodegradable materials for clinical convenience and designed for minimally invasive implantation via a trocar.Dose density variation of local chemotherapy using programmable release enhances anti-cancer effects in vitro and in vivo.Under the same dose density conditions,device-based chemotherapy shows a higher anticancer effect and less toxic response than intratumoral injection.We demonstrate local chemotherapy utilizing the implantable device that simulates the drug dose,number of releases,and treatment duration of the dose-dense AC(doxorubicin and cyclophosphamide)regimen preferred for TNBC treatment.Dose density modulation inhibits tumor growth,metastasis,and the expression of drug resistance-related proteins,including p-glycoprotein and breast cancer resistance protein.To the best of our knowledge,local dose-dense chemotherapy has not been reported,and our strategy can be expected to be utilized as a novel alternative to conventional therapies and improve anti-cancer efficiency.

关键词： Dose-dense chemotherapy Triple-negative breast cancer 3D printing Pulsatile release Local drug delivery systems

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Multilevel Attention Unet Segmentation Algorithmfor Lung Cancer Based on CT Images

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Computers, Materials & Continua 2024年第2期78卷 1569-1589页

作者： Huan Wang Shi Qiu Benyue Zhang Lixuan Xiao Xi’an institute of Optics and Precision Mechanics Chinese Academy of SciencesXi’anChina School of biomedical Engineering Fourth Military Medical UniversityXi’anChina University of Illinois at Urbana Champion ChampaignUSA

Lung cancer is a malady of the lungs that gravely jeopardizes human health.Therefore,early detection and treatment are paramount for the preservation of human life.Lung computed tomography(CT)image sequences can explicitly delineate the pathological condition of the lungs.To meet the imperative for accurate diagnosis by physicians,expeditious segmentation of the region harboring lung cancer is of utmost significance.We utilize computer-aided methods to emulate the diagnostic process in which physicians concentrate on lung cancer in a sequential manner,erect an interpretable model,and attain segmentation of lung cancer.The specific advancements can be encapsulated as follows:1)Concentration on the lung parenchyma region:Based on 16-bit CT image capturing and the luminance characteristics of lung cancer,we proffer an intercept histogram algorithm.2)Focus on the specific locus of lung malignancy:Utilizing the spatial interrelation of lung cancer,we propose a memory-based Unet architecture and incorporate skip connections.3)Data Imbalance:In accordance with the prevalent situation of an overabundance of negative samples and a paucity of positive samples,we scrutinize the existing loss function and suggest a mixed loss function.Experimental results with pre-existing publicly available datasets and assembled datasets demonstrate that the segmentation efficacy,measured as Area Overlap Measure(AOM)is superior to 0.81,which markedly ameliorates in comparison with conventional algorithms,thereby facilitating physicians in diagnosis.

关键词： Lung cancer computed tomography computer-aided diagnosis Unet segmentation

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A Novel Retrograde AAV Variant for Functional Manipulation of Cortical Projection Neurons in Mice and Monkeys

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Neuroscience Bulletin 2024年第1期40卷 90-102页

作者： Yefei Chen Jingyi Wang Jing Liu Jianbang Lin Yunping Lin Jinyao Nie Qi Yue Chunshan Deng Xiaofei Qi Yuantao Li Ji Dai Zhonghua Lu Department of Anesthesiology Shenzhen Maternity and Child Healthcare HospitalThe First School of Clinical MedicineSouthern Medical UniversityShenzhen 518027China Shenzhen Technological Research Center for Primate Translational Medicine Shenzhen Key Laboratory for Molecular Biology of Neural DevelopmentShenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China University of Chinese Academy of sciences Beijing 100049China CAS Key Laboratory of Brain Connectome and Manipulation the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Guangdong Provincial Key Laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China biomedical Research institute Hubei University of MedicineShiyan 442000China Faculty of Life and Health sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Retrograde adeno-associated viruses(AAVs)are capable of infecting the axons of projection neurons and serve as a powerful tool for the anatomical and functional characterization of neural networks.However,few retro-grade AAV capsids have been shown to offer access to cor-tical projection neurons across different species and enable the manipulation of neural function in non-human primates(NHPs).Here,we report the development of a novel retro-grade AAV capsid,AAV-DJ8R,which efficiently labeled cortical projection neurons after local administration into the striatum of mice and macaques.In addition,intrastriatally injected AAV-DJ8R mediated opsin expression in the mouse motor cortex and induced robust behavioral alterations.Moreover,AAV-DJ8R markedly increased motor cortical neuron firing upon optogenetic light stimulation after viral delivery into the macaque putamen.These data demonstrate the usefulness of AAV-DJ8R as an efficient retrograde tracer for cortical projection neurons in rodents and NHPs and indicate its suitability for use in conducting functional interrogations.

关键词： Retrograde AAV Capsid variant Cortical projection neuron Optogenetics Monkey

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Neurogenic potential of NG2 in neurotrauma:a systematic review

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Neural Regeneration Research 2024年第12期19卷 2673-2683页

作者： Yuri R.Rigo Radharani Benvenutti Luis V.Portela Nathan R.Strogulski Departamento de Bioquímica Instituto de Ciências Básicas da SaúdeUniversidade Federal do Rio Grande do Sul(UFRGS)Porto AlegreBrazil School of Pharmacy and Biomolecular sciences RCSI University of Medicine and Health SciencesDublinIreland School of Biochemistry and Immunology Trinity Biomedical Sciences InstituteTrinity College DublinUniversity of DublinDublinIreland

Regenerative approaches towards neuronal loss following traumatic brain or spinal cord injury have long been considered a dogma in neuroscience and remain a cutting-edge area of research.This is reflected in a large disparity between the number of studies investigating primary and secondary injury as therapeutic to rgets in spinal co rd and traumatic brain injuries.Significant advances in biotechnology may have the potential to reshape the current state-of-the-art and bring focus to primary injury neurotrauma research.Recent studies using neural-glial factor/antigen 2(NG2)cells indicate that they may differentiate into neurons even in the developed brain.As these cells show great potential to play a regenerative role,studies have been conducted to test various manipulations in neurotrauma models aimed at eliciting a neurogenic response from them.In the present study,we systematically reviewed the experimental protocols and findings described in the scientific literature,which were peer-reviewed original research articles(1)describing preclinical experimental studies,(2)investigating NG2 cells,(3)associated with neurogenesis and neurotrauma,and(4)in vitro and/or in vivo,available in PubMed/MEDLINE,Web of Science or SCOPUS,from 1998 to 2022.Here,we have reviewed a total of 1504 papers,and summarized findings that ultimately suggest that NG2 cells possess an inducible neurogenic potential in animal models and in vitro.We also discriminate findings of NG2 neurogenesis promoted by different pharmacological and genetic approaches over functional and biochemical outcomes of traumatic brain injury and spinal co rd injury models,and provide mounting evidence for the potential benefits of manipulated NG2 cell ex vivo transplantation in primary injury treatment.These findings indicate the feasibility of NG2 cell neurogenesis strategies and add new players in the development of therapeutic alternatives for neurotrauma.

关键词： neural-glial antigen 2 neural-glial factor 2 neuron differentiation NG2 cell regeneration spinal cord injury(SCI) traumatic brain injury(TBI)

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N6-methyladenosine facilitates mitochondrial fusion of colorectal cancer cells via induction of GSH synthesis and stabilization of OPA1 mRNA

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National Science Review 2024年第3期11卷 72-91页

作者： Jiawang Zhou Haisheng Zhang Ke Zhong Lijun Tao Yu Lin Guoyou Xie Yonghuang Tan You Wu Yunqing Lu Zhuojia Chen Jiexin Li Xin Deng Qin Peng Zigang Li Hongsheng Wang Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical Sciences Sun Yat-sen University Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South China and Collaborative Innovation Center for Cancer Medicine Department of biomedical sciences City University of Hong Kong institute of Systems and Physical Biology Shenzhen Bay Laboratory

Mitochondria undergo fission and fusion that are critical for cell survival and cancer development, while the regulatory factors for mitochondrial dynamics remain elusive. Herein we found that RNA m6A accelerated mitochondria fusion of colorectal cancer（CRC） cells. Metabolomics analysis and function studies indicated that m6A triggered the generation of glutathione（GSH） via the upregulation of RRM2B——a p53-inducible ribonucleotide reductase subunit with anti-reactive oxygen species potential. This in turn resulted in the mitochondria fusion of CRC cells. Mechanistically, m6A methylation of A1240 at 3 UTR of RRM2B increased its m RNA stability via binding with IGF2BP2. Similarly, m6A methylation of A2212 at the coding sequence（CDS） of OPA1——an essential GTPase protein for mitochondrial inner membrane fusion——also increased m RNA stability and triggered mitochondria fusion. Targeting m6A through the methyltransferase inhibitor STM2457 or the dm6ACRISPR system significantly suppressed mitochondria fusion. In vivo and clinical data confirmed the positive roles of the m6A/mitochondrial dynamics in tumor growth and CRC progression. Collectively, m6A promoted mitochondria fusion via induction of GSH synthesis and OPA1 expression, which facilitated cancer cell growth and CRC development.

关键词： m6A mitochondrial fusion glutathione OPA1 colorectal cancer

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Inflammatory bowel disease(ulcerative colitis type)severity shows inverse correlation with semen parameters and testosterone levels

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Asian Journal of Andrology 2024年第2期26卷 155-159页

作者： Darmadi Darmadi Cennikon Pakpahan Rajender Singh Ankur Saharan Wanly Syahrizal Pasaribu Hermansyah Hermansyah Andri Rezano Department of Internal Medicine Faculty of MedicineUniversitas Sumatera UtaraMedan 20155Indonesia Andrology Study Program Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Department of biomedical sciences Faculty of MedicineUniversitas AirlanggaSurabaya 60132Indonesia Division of Endocrinology Central Drug Research InstituteLucknowUtar Pradesh 226031India Amity University LucknowUttar Pradesh 226010India Department of biomedical sciences Faculty of MedicineUniversitas PadjadjaranSumedang 45363Indonesia

Individuals with inflammatory bowel disease(IBD)have been reported to be at an increased risk of infertility and sexual dysfunction.Although the relationship between them remains unclear,IBD severity is suspected to affect hormone levels and fertility.To analyze the impact of IBD severity on semen parameters and sex hormone levels in ulcerative colitis-type IBD(UC-IBD),we conducted a cross-sectional study involving 120 patients with UC-IBD in Adam Malik General Hospital,Medan,Indonesia.The patients were classified into three groups based on the Mayo score for Uc,followed by a comparison of various semen and hormone parameters among these groups.In addition to the cross-sectional analysis,a simple correlation test was conducted irrespective of the patient grouping.Sperm concentration,motility,and morphology were found to decline significantly with an increase in IBD severity.Without classifying patients with IBD into subgroups,the Mayo score showed negative correlations with sperm concentration(r=-0.375,P<0.0001),rapid progressive motility(r=-0.660,P<0.0001),free testosterone(r=-0.732,P<0.0001),and total testosterone(r=-0.721,P<0.0001),and positivecorrelations with immotile sperm(r=0.660,P<0.0001),abnormal morphology(r=0.657,P<0.0001),and sex hormone-binding globulin(SHBG;r=0.278,P=0.002).Sperm concentration,motility,and morphology declined significantly with the severity of IBD.This study suggests a significant negative impact of IBD severityonsemenqualityand sexhormones.

关键词： inflammatory bowel disease reproductive health sexual health sperm parameter testosterone

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Theoretical study of the nonlinear force-loading control in single-molecule stretching experiments

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Communications in Theoretical Physics 2024年第4期76卷 167-175页

作者： Xingyu Qi Zilong Guo Shimin Le Hu Chen Research institute for Biomimetics and Soft Matter Fujian Provincial Key Lab for Soft Functional Materials ResearchDepartment of PhysicsXiamen UniversityXiamen 361005China Center of biomedical Physics Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000China

Force spectrum measurements with constant loading rates are widely used in single-molecule manipulation experiments to study the mechanical stability and force response of biomolecules.Force-dependent transition rates can be obtained from the transition force distribution,but it is limited to the force range with non-zero force distribution.Although constant loading rate control can be realized with magnetic tweezers,the loading rate range is limited due to the slow movement of permanent magnets.Non-linear exponential and exponential squared force loading functions are more feasible in magnetic tweezers,while there is no theoretical result available for these two kinds of non-linear force loading functions.In this study,we solved the unfolding process of a protein following Bell's model under nonlinear exponential and exponential squared force loading functions,which offer a broader range of unfolding force distribution compared to the traditional constant loading rate experiments.Furthermore,we derived two force loading functions,which can produce uniform unfolding force distribution.This research contributes fundamental equations for the analysis of experimental data obtained through single-molecule manipulation under nonlinear force loading controls,paving the way for the use of nonlinear force control in magnetic tweezer experiments.

关键词： single-molecule manipulation magnetic tweezers force loading transition rates force distribution

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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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Biological scaffold as potential platforms for stem cells:Current development and applications in wound healing

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World Journal of Stem Cells 2024年第4期16卷 334-352页

作者： Jie-Yu Xiang Lin Kang Zi-Ming Li Song-Lu Tseng Li-Quan Wang Tian-Hao Li Zhu-Jun Li Jiu-Zuo Huang Nan-Ze Yu Xiao Long Department of Plastic and Reconstructive Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China biomedical Engineering Facility Institute of Clinical MedicinePeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100021China

Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

关键词： Stem-cell-based therapy Biological scaffolds Wound healing Extracellular matrix mimicry Cellular activities enhancement Scaffold characteristics

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LKB1 depletion-mediated epithelial-mesenchymal transition induces fibroblast activation in lung fibrosis

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Genes & Diseases 2024年第3期11卷 417-426页

作者： Zijian Xu Elizabeth R.Davies Liudi Yao Yilu Zhou Juanjuan Li Aiman Alzetani Ben G.Marshall David Hancock Tim Wallis Julian Downward Rob M.Ewing Donna E.Davies Mark G.Jones Yihua Wang Biological sciences Faculty of Environmental and Life SciencesUniversity of SouthamptonSouthampton SO171BJUK clinical and Experimental sciences Faculty of MedicineUniversity of SouthamptonSouthampton SO166YDUK institute for Life sciences University of SouthamptonSouthampton SO171BJUK NIHR Southampton biomedical Research Centre University Hospital SouthamptonSouthampton SO166YDUK University Hospital Southampton Southampton SO166YDUK Oncogene Biology The Francis Crick InstituteLondon NW11ATUK

The factors that determine fibrosis progression or normal tissue repair are largely unknown.We previously demonstrated that autophagy inhibition-mediated epithelial-mesenchymal transition(EMT)in human alveolar epithelial type Il(ATIl)cells augments local myofibroblast differentiation in pulmonary fibrosis by paracrine signaling.Here,we report that liver kinase B1(LKB1)inactivation in ATIl cells inhibits autophagy and induces EMT as a conse-quence.In IPF lungs,this is caused by the down-regulation of CAB39L,a key subunit within the LKB1 complex.3D co-cultures of ATIl cells and MRC5 lung fibroblasts coupled with RNA sequencing(RNA-seq)confirmed that paracrine signaling between LKB1-depleted ATIl cells and fibroblasts augmented myofibroblast differentiation.Together,these data suggest that reduced autophagy caused by LKB1 inhibition can induce EMT in ATIl cells and contribute to fibrosis via aberrant epithelial-fibroblast crosstalk.

关键词： CAB39L Crosstalk EMT LKB1 Pulmonary fibrosis

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