Frontiers in Bioengineering and Biotechnology最新文献

{"title":"An explainable unsupervised learning approach for anomaly detection on corneal <i>in vivo</i> confocal microscopy images.","authors":"Ningning Tang, Qi Chen, Yunyu Meng, Daizai Lei, Li Jiang, Yikun Qin, Xiaojia Huang, Fen Tang, Shanshan Huang, Qianqian Lan, Qi Chen, Lijie Huang, Rushi Lan, Xipeng Pan, Huadeng Wang, Fan Xu, Wenjing He","doi":"10.3389/fbioe.2025.1576513","DOIUrl":"10.3389/fbioe.2025.1576513","url":null,"abstract":"<p><strong>Background: </strong><i>In vivo</i> confocal microscopy (IVCM) is a crucial imaging modality for assessing corneal diseases, yet distinguishing pathological features from normal variations remains challenging due to the complex multi-layered corneal structure. Existing anomaly detection methods often struggle to generalize across diverse disease manifestations. To address these limitations, we propose a Transformer-based unsupervised anomaly detection method for IVCM images, capable of identifying corneal abnormalities without prior knowledge of specific disease features.</p><p><strong>Methods: </strong>Our method consists of three submodules: an EfficientNet network, a Multi-Scale Feature Fusion Network, and a Transformer Network. A total of 7,063 IVCM images (95 eyes) were included for analysis. The model was trained exclusively on normal IVCM images to capture and differentiate structural variations across four distinct corneal layers: epithelium, sub-basal nerve plexus, stroma, and endothelium. During inference, anomaly scores were computed to distinguish pathological from normal images. The model's performance was evaluated on both internal and external datasets, and comparative analyses were conducted against existing anomaly detection methods, including generative adversarial networks (AnoGAN), generate to detect anomaly model (G2D), and discriminatively trained reconstruction anomaly embedding model (DRAEM). Additionally, explainable anomaly maps were generated to enhance the interpretability of model decisions.</p><p><strong>Results: </strong>The proposed method achieved an the areas under the receiver operating characteristic curve of 0.933 on internal validation and 0.917 on an external test dataset, outperforming AnoGAN, G2D, and DRAEM in both accuracy and generalizability. The model effectively distinguished normal and pathological images, demonstrating statistically significant differences in anomaly scores (p < 0.001). Furthermore, visualization results indicated that the detected anomalous regions corresponded to morphological deviations, highlighting potential imaging biomarkers for corneal diseases.</p><p><strong>Conclusion: </strong>This study presents an efficient and interpretable unsupervised anomaly detection model for IVCM images, effectively identifying corneal abnormalities without requiring labeled pathological samples. The proposed method enhances screening efficiency, reduces annotation costs, and holds great potential for scalable intelligent diagnosis of corneal diseases.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1576513"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An engineered adipose formulation decreases hepatic inflammation and fibrosis in a rodent model of metabolic dysfunction-associated steatotic liver disease.","authors":"Youngshim Choi, Yinyan Ma, Samson Tom, Alla Danilkovitch, Liqing Yu","doi":"10.3389/fbioe.2025.1579062","DOIUrl":"10.3389/fbioe.2025.1579062","url":null,"abstract":"<p><strong>Introduction: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive stage metabolic dysfunction-associated steatohepatitis (MASH) represent a leading cause of liver-related morbidity and mortality in the U.S. and worldwide. Given the high prevalence and rapid growth of MASLD, the economic and health burden, and MASH-associated morbidity and mortality, there is an unmet medical need for therapies that can stop, slow, or reverse the progression of MASLD. Adipose tissue plays a key role in metabolic health and MASLD pathogenesis through its regulation of energy metabolism and endocrine function. Metabolic dysfunction is often associated with a chronic state of low-grade inflammation in the body including adipose tissue.</p><p><strong>Methods: </strong>In this study, we tested an engineered adipose formulation (AF) composed of a combination of culture-expanded adipose stromal vascular fraction (SVF) cells and adipose tissue particulates in the treatment of MASLD. Human, rat, and mouse AFs (hAF, rAF, and mAF) showed anti-inflammatory activity, which was mediated predominantly by soluble factors present in the adipose particulate. <i>In vivo</i> effects of AFs were evaluated in two rodent models of MASLD: i) obese Zucker rats fed a high-fat, high-cholesterol, and high-fructose diet that mainly manifest hepatic steatosis; and ii) liver-specific CGI-58 knockout mice (LivKO) on a Western diet that display MASH pathologies.</p><p><strong>Results: </strong>Subcutaneous implantation of hAF and rAF in obese Zucker rats significantly reduced hepatic triglycerides. In LivKO mice, mAF reduced hepatic inflammation and fibrosis, though not steatosis, as evidenced by significant decreases in hepatic M1 macrophages and mRNAs for proinflammatory and fibrogenic genes. Immunogenicity testing demonstrated that allogeneic rAF did not induce an immune response, whereas, as anticipated, xenogeneic hAF in rats triggered anti-hAF antibody formation. Despite an immune response against xenogeneic hAF, treatment of rats with hAF ameliorated hepatic steatosis.</p><p><strong>Discussion: </strong>AF has the potential to treat MASH. Future studies focused on the optimization of AF composition, optimal dose and treatment regimen are warranted.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1579062"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experiences, learnings and perspectives in the regulation of agricultural biotechnology: the view from Argentina.","authors":"Dalia M Lewi, Perla Godoy, Facundo Simeone","doi":"10.3389/fbioe.2025.1600642","DOIUrl":"10.3389/fbioe.2025.1600642","url":null,"abstract":"<p><p>Argentina has established itself as global leader in setting enabling regulations for agricultural biotechnology. Between 2020 and 2023 the responsible administration strengthened this position through the adoption of innovative regulations for New Breeding Techniques and fostering broad international collaboration. The experience accumulated during this period serves to illustrate best practices, current shortcomings, anticipate future challenges, and point to the solutions that the sector will need in the next few years.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1600642"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A low-cost, open-source device to evaluate limb stiffness in a rabbit model of cerebral palsy.","authors":"Preston R Steele, Joel Feldmann, Katharina A Quinlan, Marin Manuel","doi":"10.3389/fbioe.2025.1554775","DOIUrl":"10.3389/fbioe.2025.1554775","url":null,"abstract":"<p><strong>Background: </strong>Movement disorders such as cerebral palsy (CP) are frequently associated with joint and muscle stiffness, often evaluated using subjective clinical methods like the Modified Ashworth Scale or Tardieu Scale. These approaches lack precision and reproducibility, particularly in preclinical models, limiting their utility in translational research.</p><p><strong>Methods: </strong>This study presents the development of a low-cost, open-source torquemeter device tailored for use in a neonatal rabbit model of CP. The device is designed to quantify joint stiffness objectively by measuring torque across a range of controlled joint rotation speeds, a key factor in evaluating hypertonia associated with spasticity and dystonia. The construction process is straightforward, with all components being either commercially available or 3D-printable and requiring only basic assembly tools.</p><p><strong>Results: </strong>The torquemeter demonstrated precise, reproducible measurements of torque and joint stiffness in pilot studies, validating its applicability in preclinical settings. By eliminating subjective biases, the device provides robust data to assess the effectiveness of therapeutic interventions targeting spasticity.</p><p><strong>Conclusion: </strong>This low-cost torquemeter offers an accessible, reliable tool for preclinical movement disorder research. Its ability to quantify limb stiffness with high precision enhances the evaluation of treatment strategies in CP models, paving the way for improved therapeutic development and outcomes.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1554775"},"PeriodicalIF":4.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recapitulating the bone extracellular matrix through 3D bioprinting using various crosslinking chemistries.","authors":"Laurens Parmentier, Edward Vermeersch, Sandra Van Vlierberghe","doi":"10.3389/fbioe.2025.1506122","DOIUrl":"10.3389/fbioe.2025.1506122","url":null,"abstract":"<p><p>Bioprinting allows to spatially organize cellular niches influencing mechanobiology into tissue engineered constructs thereby aiming to achieve a similar functional complexity as the various tissues present within bone. Natural polymer hydrogel matrices are favorably selected as part of many bioinks thanks to their level of mimicry with the bone osteoid matrix. More specifically, a variety of biophysical and biochemical cues targeting osteogenesis can be presented towards cells encapsulated in bioprinted constructs. This review focusses on delineating bioprinting targeting osteogenesis based on the printing approach (deposition-versus light-based bioprinting) and crosslinking chemistry utilized (chain- versus step-growth crosslinking). Moreover, the cell-biomaterial interactions at play within these constructs are addressed in line with currently established mechanobiology concepts. The delicate interplay between the presented cues from the encapsulating matrix, the used printing process and the maturity, source and concentration of the used cell type finally dictates the osteoregenerative outcome of a bioprinted construct. Given the advantages towards cell encapsulation associated with step-growth systems, there is a huge need to evaluate these systems in comparison to the heavily reported chain-growth systems (predominantly gelatin-methacryloyl or GelMA) towards the bioprinting of constructs serving osteogenesis. Moreover, multiple bioprinting strategies should be combined to tackle key challenges in the field and enable functional and scalable hierarchical constructs serving osteogenesis with incorporation of vascularization and innervation.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1506122"},"PeriodicalIF":4.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Generation of decellularized human brain tissue for investigating cell-matrix interactions: a proof-of-concept study.","authors":"Roemel Jeusep Bueno, Camila Fernández-Zapata, Maren Salla, Juliana Campo Garcia, Aylin Alacam, Oliver Klein, Chotima Böttcher, Helena Radbruch, Friedemann Paul, Sarah C Starossom, Rafaela V Silva, Carmen Infante-Duarte","doi":"10.3389/fbioe.2025.1578467","DOIUrl":"10.3389/fbioe.2025.1578467","url":null,"abstract":"<p><p>The brain extracellular matrix (ECM) regulates myelin repair and regeneration following a demyelinating event by interacting with neuronal progenitors and immune cells. Therefore, generation and characterization of decellularized human brain tissue (DHBT) in regions with distinct neuroregenerative capacities are essential to determine factors modulating the cellular regenerative behavior. We have established an effective decellularization protocol for the human neural stem cell (NSC)-rich subventricular zone (SVZ) as well as, frontal cortex (FC) and white matter (WM), and defined region-specific matrisomes with comparative proteomics. Subsequently, as proof-of-concept, survival and differentiation of NSCs and monocytes within the DHBT were investigated. The proteomic analysis of the DHBT confirmed the retention of matrisome proteins such as COL4A1, FBB, NCAN, ANXA2. Unique to the SVZ were LGI3 and C1QB, while annexins, S100A and TGM2 were found in FC; S100B was exclusive to the WM. NSCs cultured within WM and FC acquired an astrocytic phenotype, but both astrocytic and oligodendrocytic phenotypes were promoted by the SVZ DHBT. Moreover, imaging mass cytometry analysis indicated an anti-inflammatory phenotype differentiation of monocytes seeded on SVZ and WM. Thus, the established model is suitable for investigation of ECM properties and assessment of cell-matrix interactions.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1578467"},"PeriodicalIF":4.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking efficiency in column chromatography with packed bed supporting inserts.","authors":"Romone M Fancy, David H Abraham, Matthew R Taylor, Cole McMullin, Nicholas S Brann, Daniel M Bailey, David I Brown, Heather Bethea Horne, Leslie S Wolfe","doi":"10.3389/fbioe.2025.1613174","DOIUrl":"10.3389/fbioe.2025.1613174","url":null,"abstract":"<p><p>To purify increasing amounts of biotherapeutics more efficiently, the use of high flow rates or greater resin bed heights during downstream chromatography steps is a tantalizing option. A limitation of utilizing high flow rates is the differential pressure generated by packed chromatography resin beds. As a resin bed height increases, the resin is susceptible to compression. By increasing the permeability of a packed resin bed through control of the hydraulic radius, column pressure-flow dynamics can be improved. Chromatography column performance using a commercially available Protein A resin was assessed with and without OMEGA, a column insert designed to modulate the hydraulic radius of the column by providing vertical supports through the packed resin bed. OMEGA was shown to reduce the effective hydraulic radius of packed resin beds, increase the permeability of packed columns by 44%-73%, and yield a 42%-50% decrease in pressure differential across the resin bed at a comparable linear velocity. The structural support provided by OMEGA enables higher operational flow rates and increased resin bed height without impact to either dynamic binding capacity or purified product quality. With the OMEGA column insert, scale-up hurdles are mitigated, and faster downstream processing times are unlocked across column geometries.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1613174"},"PeriodicalIF":4.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mini review: Apple improvement, traditional approaches, biotechnology options, and regulatory considerations.","authors":"Amy L Klocko","doi":"10.3389/fbioe.2025.1617110","DOIUrl":"10.3389/fbioe.2025.1617110","url":null,"abstract":"<p><p>Apples are a popular and globally important crop. The fruits are eaten fresh, pressed for juice, fermented as cider, processed into sauce, dried, and more. There are thousands of different cultivars, a small subset of which are grown on a commercial scale. Genetic analysis has shown that, as a group, domestic apples have a complicated genetic background, with contributions from multiple wild species. By contrast, most of the highly produced commercialized modern cultivars share a narrow range of genetic diversity. However, as apples are outcrossing, propagated vegetatively, and long-lived, wild and heirloom varieties can be maintained and are valuable sources of genetic diversity for desirable traits. Apples are also amenable to genetic transformation, and work in this area has resulted in improved resistance to diseases and a commercialized non-browning variety, the Arctic™ Apple. Traditional breeding, breeding guided by modern genetic knowledge, and biotechnology all contribute to the overall process of apple cultivar development and represent an important example of how many approaches can be used in crop improvement. As global biosafety regulations continue to develop and change, countries will be tasked with developing guidelines for both the creation and import of apple trees and apple products.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1617110"},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12175005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autotrophic bacterial production of polyhydroxyalkanoates using carbon dioxide as a sustainable carbon source.","authors":"Ganesan Sathiyanarayanan, Sandra Esteves","doi":"10.3389/fbioe.2025.1545438","DOIUrl":"10.3389/fbioe.2025.1545438","url":null,"abstract":"<p><p>The persistence of fossil fuel-based plastics poses significant environmental challenges, prompting increased research into biodegradable polyhydroxyalkanoate (PHA) polymers derived from cost-effective and sustainable resources. Different microorganisms can produce PHA amongst carbon dioxide (CO₂)-assimilating autotrophic organisms, particularly noteworthy in carbon capture and utilization (CCU). Autotrophic bacteria have evolved to utilize either light (photoautotrophy) or inorganic chemicals (chemolithoautotrophy) to capture CO₂, which powers their primary and secondary metabolic activities. This review explores the diversity of PHA-producing autotrophs, the metabolic pathways implicated in autotrophic PHA accumulation, and recent progress in photoautotrophs and chemolithoautotrophs regarding PHA synthesis using CO₂. Additionally, microbial electrosynthesis for converting CO₂ to PHA is also discussed. Genetic engineering strategies are also emphasized for the autotrophic synthesis of PHA. This review also addresses the challenges and prospects for sustainable PHA production using CO₂.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1545438"},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginger-derived exosome-like nanoparticles: a representative of plant-based natural nanostructured drug delivery system.","authors":"Houhe Liu, Yi Deng, Jiayan Li, Wen Lin, Chongzhi Liu, Xiaofei Yang, Zunzhen Zhou, Yuan Jiang","doi":"10.3389/fbioe.2025.1569889","DOIUrl":"10.3389/fbioe.2025.1569889","url":null,"abstract":"<p><p>In recent years, the research on plant-derived exosome-like nanoparticles (PELNs) has attracted increasing attention. Among these, ginger-derived exosome-like nanoparticles (GELNs) stand out due to their specific pharmacological activity and their role as reliable carriers for delivering both hydrophilic and hydrophobic drugs, as well as small RNAs, making them a noteworthy representative of plant-based natural nanostructured drug delivery systems (DDS). In this review, we first introduce the characteristics and engineering methods of GELN-based DDS to brush up on our current understanding and then focus on research progress to summarize their therapeutic application scope and challenges.</p>","PeriodicalId":12444,"journal":{"name":"Frontiers in Bioengineering and Biotechnology","volume":"13 ","pages":"1569889"},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12174126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}