Journal of Biological Engineering最新文献

{"title":"Stabilizing milk-derived extracellular vesicles (mEVs) through lyophilization: a novel trehalose and tryptophan formulation for maintaining structure and Bioactivity during long-term storage.","authors":"Alan B Dogan, Spencer R Marsh, Rachel J Tschetter, Claire E Beard, Md R Amin, L Jane Jourdan, Robert G Gourdie","doi":"10.1186/s13036-024-00470-z","DOIUrl":"10.1186/s13036-024-00470-z","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are widely investigated for their implications in cell-cell signaling, immune modulation, disease pathogenesis, cancer, regenerative medicine, and as a potential drug delivery vector. However, maintaining integrity and bioactivity of EVs between Good Manufacturing Practice separation/filtration and end-user application remains a consistent bottleneck towards commercialization. Milk-derived extracellular vesicles (mEVs), separated from bovine milk, could provide a relatively low-cost, scalable platform for large-scale mEV production; however, the reliance on cold supply chain for storage remains a logistical and financial burden for biologics that are unstable at room temperature. Herein, we aim to characterize and engineer a freeze-dried, mEV formulation that can be stored at room temperature without sacrificing structure/bioactivity and can be reconstituted before delivery. In addition to undertaking established mEV assays of structure and function on our preparations, we introduce a novel, efficient, high throughput assay of mEV bioactivity based on Electric Cell Substrate Impedance Sensing (ECIS) in Human dermal fibroblast monolayers. By adding appropriate excipients, such as trehalose and tryptophan, we describe a protective formulation that preserves mEV bioactivity during long-term, room temperature storage. Our identification of the efficacy of tryptophan as a novel additive to mEV lyophilization solutions could represent a significant advancement in stabilizing small extracellular vesicles outside of cold storage conditions.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"4"},"PeriodicalIF":5.7,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lithium-doped calcium silicate cement regulates the immune microenvironment and promotes M2 macrophage polarization for enhancing bone regeneration.","authors":"Yen-Hong Lin, Cheng-Yu Chen, Kun-Hao Chen, Ting-You Kuo, Tsung-Li Lin, Ming-You Shie","doi":"10.1186/s13036-024-00467-8","DOIUrl":"https://doi.org/10.1186/s13036-024-00467-8","url":null,"abstract":"<p><p>Bone defects present a significant challenge in orthopedics and trauma surgery, necessitating innovative approaches to stimulate effective bone regeneration. This study investigated the potential of lithium-doped calcium silicate (LiCS) cement to enhance bone regeneration and modulate the immune microenvironment to promote tissue repair. We synthesized a LiCS ceramic powder and performed comprehensive analyses of its physicochemical properties, including phase composition, morphology, setting time, and mechanical strength. The results demonstrated that the incorporation of lithium into calcium silicate significantly increased the diametral tensile strength (DTS) and facilitated hydroxyapatite formation compared with undoped calcium silicate. In vitro assays revealed that the LiCS cement enhanced the proliferation, adhesion, and spread of Wharton's jelly mesenchymal stem cells (WJMSCs). Additionally, Li-CS cement exhibited remarkable immunomodulatory properties by reducing pro-inflammatory cytokines and increasing anti-inflammatory cytokines, promoting the polarization of macrophages towards the M2 phenotype. The presence of Li in the cement also significantly improved the osteogenic differentiation of WJMSCs, as evidenced by elevated levels of alkaline phosphatase and osteocalcin expression. These findings underscore the dual functional capabilities of the LiCS cement in enhancing osteogenesis and modulating the immune environment, making it a promising material for bone tissue engineering and regeneration.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"3"},"PeriodicalIF":5.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesizing hybrid copper phosphate (Cu₃(PO₄)₂) nanoflowers using Cu⁺² and shed snakeskin: antioxidant, antibacterial, anticancer, guaiacol, anionic, and cationic dye degradation properties.","authors":"Cagri Caglar Sinmez, Fatih Doğan Koca","doi":"10.1186/s13036-024-00464-x","DOIUrl":"https://doi.org/10.1186/s13036-024-00464-x","url":null,"abstract":"<p><strong>Background: </strong>Synthesis of organic@inorganic hNFs is achieved by the coordination of organic compounds containing amine, amide, and diol groups with bivalent metals. The use of bio-extracts containing these functional groups instead of expensive organic inputs such as DNA, enzymes, and protein creates advantages in terms of cost and applicability. In this study, the application potentials (antioxidant, antibacterial, anticancer, guaiacol, anionic, and cationic dye degradation) of hybrid (organic@inorganic) nanoflowers (hNFs) synthesized with Cu⁺² and snakeskin (SSS) were proposed.</p><p><strong>Results: </strong>Morphology, presence, and composition of elements of Cu and SSS-coordinated hNFs (Cu@SSS hNFs) were shown through FE-SEM-EDX spectroscopy. According to FE-SEM findings, hNFs synthesized with 0.5 ml and 1 ml extract have diameters of 12.81 and 3 µm, respectively. Diffraction peaks of hNFs determined by XRD were consistent with JCPDS Card 00-022 -0548. Cu@SSS NFs showed antioxidant properties depending on time through DPPH scavenging behavior (ability (R²: 0.5612, IC₅₀: 2.07 mg/ml). Cu@SSS hNFs synthesized coordination of SSS and Cu degraded (75%) methylene blue at the highest pH 9 condition. However, hNFs highest degraded (68%) brilliant blue in an acidic PBS medium. hNFs oxidized guaiacol depending on exposure time. Cu@SSS hNFs demonstrated antibacterial properties towards Gram (-/ +) pathogen strains (MIC: 60 µg/ml). The catalytic and antimicrobial properties of hNFs were mentioned by the Fenton reaction. The cytotoxicity of Cu@SSS hNFs on the lung carcinoma (A549) cell line was shown to be concentration-dependent by the MTT test assay (IC₅₀: 56.4 µg/ml).</p><p><strong>Conclusion: </strong>As a result, Cu-based hNFs synthesized by using an organic waste (SSS) might be improved for environmental and biomedical applications.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"19 1","pages":"1"},"PeriodicalIF":5.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11697820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced metabolic Engineering strategies for the sustainable production of free fatty acids and their derivatives using yeast.","authors":"Tisa Rani Saha, Nam Kyu Kang, Eun Yeol Lee","doi":"10.1186/s13036-024-00473-w","DOIUrl":"10.1186/s13036-024-00473-w","url":null,"abstract":"<p><p>The biological production of lipids presents a sustainable method for generating fuels and chemicals. Recognized as safe and enhanced by advanced synthetic biology and metabolic engineering tools, yeasts are becoming versatile hosts for industrial applications. However, lipids accumulate predominantly as triacylglycerides in yeasts, which are suboptimal for industrial uses. Thus, there have been efforts to directly produce free fatty acids and their derivatives in yeast, such as fatty alcohols, fatty aldehydes, and fatty acid ethyl esters. This review offers a comprehensive overview of yeast metabolic engineering strategies to produce free fatty acids and their derivatives. This study also explores current challenges and future perspectives for sustainable industrial lipid production, particularly focusing on engineering strategies that enable yeast to utilize alternative carbon sources such as CO₂, methanol, and acetate, moving beyond traditional sugars. This review will guide further advancements in employing yeasts for environmentally friendly and economically viable lipid production technologies.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"73"},"PeriodicalIF":5.7,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glutathione peroxidase 4 overexpression induces anomalous subdiffusion and impairs glioblastoma cell growth.","authors":"Nahom Teferi, Akalanka Ekanayake, Stephenson B Owusu, Thomas O Moninger, Jann N Sarkaria, Alexei V Tivanski, Michael S Petronek","doi":"10.1186/s13036-024-00472-x","DOIUrl":"10.1186/s13036-024-00472-x","url":null,"abstract":"<p><p>Glioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression. This led to the hypothesis that GPx4 expression negatively influences GBM cell growth. This study utilizes a doxycycline inducible GPx4 overexpression model to test this hypothesis. Consistently, the overexpression of GPx4 significantly impairs cell growth and colony formation while also causing an accumulation of cells in G1/G0 phase of the cell cycle. From a biophysical perspective, GPx4 overexpressing cells have significantly greater surface area, increased Young's modulus, and experience anomalous sub-diffusion as opposed to normal diffusion associated with Brownian motion. Moreover, analysis of patient derived GBM cells reveal that cell growth rates, plating efficiency, and Young's modulus are all inversely proportional to GPx4 expression. Therefore, GPx4 appears to be a biophysical regulator of GBM cell growth that warrants further mechanistic investigation in its role in GBM progression.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"72"},"PeriodicalIF":5.7,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic control of the plasmid copy number maintained without antibiotics in Escherichia coli.","authors":"Geunyung Park, Jina Yang, Sang Woo Seo","doi":"10.1186/s13036-024-00460-1","DOIUrl":"10.1186/s13036-024-00460-1","url":null,"abstract":"<p><strong>Background: </strong>Manipulating the gene expression is the key strategy to optimize the metabolic flux. Not only transcription, translation, and post-translation level control, but also the dynamic plasmid copy number (PCN) control has been studied. The dynamic PCN control systems that have been developed to date are based on the understanding of origin replication mechanisms, which limits their application to specific origins of replication and requires the use of antibiotics for plasmid maintenance. In this study, we developed a dynamic PCN control system for Escherichia coli that is maintained without antibiotics. This is achieved by regulating the transcription level of the translation initiation factor IF-1 (infA), an essential gene encoded on the plasmid, while deleting it from the plasmid-bearing host cell.</p><p><strong>Results: </strong>When validated using GFP as a reporter protein, our system demonstrated a 22-fold dynamic range in PCN within the CloDF13 origin. The system was employed to determine the optimal copy number of the plasmid carrying the cad gene, which converts an intermediate of the tricarboxylic acid cycle (TCA cycle) to itaconic acid. By optimizing the PCN, we could achieve an itaconic acid titer of 3 g/L, which is 5.3-fold higher than the control strain.</p><p><strong>Conclusions: </strong>Our system offers a strategy to identify the optimal expression level of genes that have a competitive relationship with metabolic pathways crucial for the growth of the host organism. This approach can potentially be applied to other bacterial hosts by substituting the sensing module or the essential gene.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"71"},"PeriodicalIF":5.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11660809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and verification of diagnostic biomarkers for deep infiltrating endometriosis based on machine learning algorithms.","authors":"Shanping Shi, Chao Huang, Xiaojian Tang, Hua Liu, Weiwei Feng, Chen Chen","doi":"10.1186/s13036-024-00466-9","DOIUrl":"10.1186/s13036-024-00466-9","url":null,"abstract":"<p><p>This study addresses the challenges in the early diagnosis of deep infiltrating endometriosis (DIE) by exploring the potential role of the deubiquitinating enzyme USP14. By analyzing the GSE141549 dataset from the Gene Expression Omnibus (GEO) database, using bioinformatics methods and three machine learning algorithms (LASSO, Random Forest, and Support Vector Machine), the key feature gene USP14 was identified. The results indicated that USP14 is significantly upregulated in DIE and exhibits good predictive value (AUC = 0.786). Further analysis revealed the important role of USP14 in muscle function, cellular growth factor response, and maintenance of chromosome structure, and its close association with various immune cell functions. Immunohistochemical staining confirmed the high expression of USP14 in DIE tissues. This study provides a new molecular target for the early diagnosis of DIE, which holds significant clinical implications and potential application value.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"70"},"PeriodicalIF":5.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590220/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering Saccharomyces cerevisiae for the production of natural osmolyte glucosyl glycerol from sucrose and glycerol through Ccw12-based surface display of sucrose phosphorylase.","authors":"Tea Martinić Cezar, Nenad Marđetko, Antonija Trontel, Antonia Paić, Anita Slavica, Renata Teparić, Bojan Žunar","doi":"10.1186/s13036-024-00468-7","DOIUrl":"10.1186/s13036-024-00468-7","url":null,"abstract":"<p><strong>Background: </strong>Yeast Saccharomyces cerevisiae is widely recognised as a versatile chassis for constructing microbial cell factories. However, producing chemicals from toxic, highly concentrated, or cell-impermeable substrates, or chemicals dependent on enzymatic reactions incompatible with the yeast's intracellular environment, remains challenging. One such chemical is 2-O-(α-D-glucopyranosyl)-sn-glycerol (glucosyl glycerol, αGG), a natural osmolyte used in the cosmetics and healthcare industries. This compound can be synthesised in a one-enzyme reaction from sucrose and glycerol by Leuconostoc mesenteroides sucrose phosphorylase (SucP), an enzyme which, in a low-water, glycerol-rich, phosphate-free environment, transfers the glucosyl moiety from sucrose to glycerol.</p><p><strong>Results: </strong>In this study, we engineered a yeast microbial cell factory for αGG production. For this purpose, we first focused on the abundant yeast GPI-anchored cell wall protein Ccw12 and used our insights to develop a miniature Ccw12-tag, which adds only 1.1 kDa to the enzyme of interest while enabling its covalent attachment to the cell wall. Next, we Ccw12-tagged SucP and expressed it in an invertase-negative strain of yeast S. cerevisiae from the PHO5 promoter, i.e., promoter strongly induced under phosphate-free conditions. Such SucP isoform, covalently C-terminally anchored to the outer cell surface, produced extracellularly 37.3 g l^- 1 (146 mM) of αGG in five days, while the underlying chassis metabolised reaction by-products, thereby simplifying downstream processing.</p><p><strong>Conclusions: </strong>The here-described S. cerevisiae strain, displaying C-terminally anchored sucrose phosphorylase on its cell surface, is the first eukaryotic microbial cell factory capable of a one-step αGG production from the readily available substrates sucrose and glycerol.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"69"},"PeriodicalIF":5.7,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual-inducible control system for multistep biosynthetic pathways.","authors":"Andrés Felipe Carrillo Rincón, Alexandra J Cabral, Andras Gyorgy, Natalie G Farny","doi":"10.1186/s13036-024-00462-z","DOIUrl":"10.1186/s13036-024-00462-z","url":null,"abstract":"<p><strong>Background: </strong>The successful production of industrially relevant natural products hinges on two key factors: the cultivation of robust microbial chassis capable of synthesizing the desired compounds, and the availability of reliable genetic tools for expressing target genes. The development of versatile and portable genetic tools offers a streamlined pathway to efficiently produce a variety of compounds in well-established chassis organisms. The σ⁷⁰lac and tet expression systems - adaptations of the widely used lac and tet regulatory systems developed in our laboratory - have shown effective regulation and robust expression of recombinant proteins in various Gram-negative bacteria. Understanding the strengths and limitations of these regulatory systems in controlling recombinant protein production is essential for progress in this area.</p><p><strong>Results: </strong>To assess their capacity for combinatorial control, both the σ⁷⁰lac and tet expression systems were combined into a single plasmid and assessed for their performance in producing fluorescent reporters as well as the terpenoids lycopene and β-carotene. We thoroughly characterized the induction range, potential for synergistic effects, and metabolic costs of our dual σ⁷⁰lac and tet expression system in the well-established microorganisms Escherichia coli, Pseudomonas putida, and Vibrio natriegens using combinations of fluorescent reporters. The dynamic range and basal transcriptional control of the σ⁷⁰ expression systems were further improved through the incorporation of translational control mechanisms via toehold switches. This improvement was assessed using the highly sensitive luciferase reporter system. The improvement in control afforded by the integration of the toehold switches enabled the accumulation of a biosynthetic intermediate (lycopene) in the β-carotene synthesis pathway.</p><p><strong>Conclusion: </strong>This study presents the development and remaining challenges of a set of versatile genetic tools that are portable across well-established gammaproteobacterial chassis and capable of controlling the expression of multigene biosynthetic pathways. The enhanced σ⁷⁰ expression systems, combined with toehold switches, facilitate the biosynthesis and study of enzymes, recombinant proteins, and natural products, thus providing a valuable resource for producing a variety of compounds in microbial cell factories.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"68"},"PeriodicalIF":5.7,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A rotenone organotypic whole hemisphere slice model of mitochondrial abnormalities in the neonatal brain.","authors":"Brendan Butler, Malcolm Renney, Kristin Bennett, Gisele Charpentier, Elizabeth Nance","doi":"10.1186/s13036-024-00465-w","DOIUrl":"10.1186/s13036-024-00465-w","url":null,"abstract":"<p><p>Mitochondrial abnormalities underscore a variety of neurologic injuries and diseases and are well-studied in adult populations. Clinical studies identify critical roles of mitochondria in a wide range of developmental brain injuries, but models that capture mitochondrial abnormalities in systems representative of the neonatal brain environment are lacking. Here, we develop an organotypic whole-hemisphere (OWH) brain slice model of mitochondrial dysfunction in the neonatal brain. We extended the utility of complex I inhibitor rotenone (ROT), canonically used in models of adult neurodegenerative diseases, to inflict mitochondrial damage in OWH slices from term-equivalent rats. We quantified whole-slice health over 6 days of exposure for a range of doses represented in ROT literature. We identified 50 nM ROT as a suitable exposure level for OWH slices to inflict injury without compromising viability. At the selected exposure level, we confirmed exposure- and time-dependent mitochondrial responses showing differences in mitochondrial fluorescence and nuclear localization using MitoTracker imaging in live OWH slices and dysregulated mitochondrial markers via RT-qPCR screening. We leveraged the regional structures present in OWH slices to quantify cell density and cell death in the cortex and the midbrain regions, observing higher susceptibilities to damage in the midbrain as a function of exposure and culture time. We supplemented these findings with analysis of microglia and mature neurons showing time-, region-, and exposure-dependent differences in microglial responses. We demonstrated changes in tissue microstructure as a function of region, culture time, and exposure level using live-video epifluorescence microscopy of extracellularly diffusing nanoparticle probes in live OWH slices. Our results highlight severity-, time-, and region-dependent responses and establish a complimentary model system of mitochondrial abnormalities for high-throughput or live-tissue experimental needs.</p>","PeriodicalId":15053,"journal":{"name":"Journal of Biological Engineering","volume":"18 1","pages":"67"},"PeriodicalIF":5.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142621040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}