APL Bioengineering最新文献

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Single-pericyte nanomechanics measured by contraction cytometry. 通过收缩细胞仪测量单个冰细胞的纳米力学。
IF 6.6 3区 医学
APL Bioengineering Pub Date : 2024-08-09 eCollection Date: 2024-09-01 DOI: 10.1063/5.0213761
Md Mydul Islam, Ignas Gaska, Oluwamayokun Oshinowo, Adiya Otumala, Shashank Shekhar, Nicholas Au Yong, David R Myers
{"title":"Single-pericyte nanomechanics measured by contraction cytometry.","authors":"Md Mydul Islam, Ignas Gaska, Oluwamayokun Oshinowo, Adiya Otumala, Shashank Shekhar, Nicholas Au Yong, David R Myers","doi":"10.1063/5.0213761","DOIUrl":"10.1063/5.0213761","url":null,"abstract":"<p><p>Pericytes line the microvasculature throughout the body and play a key role in regulating blood flow by constricting and dilating vessels. However, the biophysical mechanisms through which pericytes transduce microenvironmental chemical and mechanical cues to mediate vessel diameter, thereby impacting oxygen and nutrient delivery, remain largely unknown. This knowledge gap is clinically relevant as numerous diseases are associated with the aberrant contraction of pericytes, which are unusually susceptible to injury. Here, we report the development of a high-throughput hydrogel-based pericyte contraction cytometer that quantifies single-cell contraction forces from murine and human pericytes in different microvascular microenvironments and in the presence of competing vasoconstricting and vasodilating stimuli. We further show that murine pericyte survival in hypoxia is mediated by the mechanical microenvironment and that, paradoxically, pre-treating pericytes to reduce contraction increases hypoxic cell death. Moreover, using the contraction cytometer as a drug-screening tool, we found that cofilin-1 could be applied extracellularly to release murine pericytes from hypoxia-induced contractile <i>rigor mortis</i> and, therefore, may represent a novel approach for mitigating the long-lasting decrease in blood flow that occurs after hypoxic injury.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the translational impact of type 1 diabetes on cerebral neurovascular function through ECoG-LSCI 通过 ECoG-LSCI 探索 1 型糖尿病对脑神经血管功能的转化影响
IF 6.6 3区 医学
APL Bioengineering Pub Date : 2024-08-08 DOI: 10.1063/5.0193267
Shaoyu Yen, Yuhling Wang, Lun-De Liao
{"title":"Exploring the translational impact of type 1 diabetes on cerebral neurovascular function through ECoG-LSCI","authors":"Shaoyu Yen, Yuhling Wang, Lun-De Liao","doi":"10.1063/5.0193267","DOIUrl":"https://doi.org/10.1063/5.0193267","url":null,"abstract":"Type 1 diabetes mellitus (T1DM) can result in complications such as retinopathy, nephropathy, and peripheral neuropathy, which can lead to brain dysfunction. In this study, we investigated the effects of T1DM on cerebral neurovascular function in mice. Streptozotocin (STZ) is known to induce T1DM in animals; thus, we used an STZ-induced diabetes model to evaluate the effects of hyperglycemia on brain morphology and neurovascular tissue. Neurovascular coupling is the connection between neuronal activity and cerebral blood flow that maintains brain function. The ECoG-LSCI technique combines electrocorticography (ECoG) and laser speckle contrast imaging (LSCI) to detect cortical spreading depression (CSD) as a marker of neurovascular coupling and measure corresponding neurovascular function. Our results suggested that in the STZ group, hyperglycemia affected excitatory neurotransmission and metabolism, leading to reductions in intercellular signaling, somatosensory evoked potential (SSEP) amplitudes, and CSD transmission rates. Western blot data further revealed that brain-derived neurotrophic factor (BDNF) and neuronal nuclear antigen levels were reduced in the STZ group. Abnormalities in glucose metabolism in the brain and increased phosphorylation of AKT and GSK3 are hypothesized to be responsible for these decreases. Overall, this study highlights the importance of glucose metabolism in normal brain physiology and demonstrates that hyperglycemia disrupts neurovascular coupling and affects cerebral neurovascular function and that the degree of CSD is positively correlated with the extent of brain tissue damage. Further research is essential to gain a complete understanding of the related mechanisms and the implications of these findings.","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141927323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids. 三维基质硬度可调节口腔鳞状细胞癌球的机械敏感性和表型改变。
IF 6.6 3区 医学
APL Bioengineering Pub Date : 2024-07-31 eCollection Date: 2024-09-01 DOI: 10.1063/5.0210134
Maulee Sheth, Manju Sharma, Maria Lehn, HasanAl Reza, Takanori Takebe, Vinita Takiar, Trisha Wise-Draper, Leyla Esfandiari
{"title":"Three-dimensional matrix stiffness modulates mechanosensitive and phenotypic alterations in oral squamous cell carcinoma spheroids.","authors":"Maulee Sheth, Manju Sharma, Maria Lehn, HasanAl Reza, Takanori Takebe, Vinita Takiar, Trisha Wise-Draper, Leyla Esfandiari","doi":"10.1063/5.0210134","DOIUrl":"10.1063/5.0210134","url":null,"abstract":"<p><p>Extracellular biophysical cues such as matrix stiffness are key stimuli tuning cell fate and affecting tumor progression <i>in vivo</i>. However, it remains unclear how cancer spheroids in a 3D microenvironment perceive matrix mechanical stiffness stimuli and translate them into intracellular signals driving progression. Mechanosensitive Piezo1 and TRPV4 ion channels, upregulated in many malignancies, are major transducers of such physical stimuli into biochemical responses. Most mechanotransduction studies probing the reception of changing stiffness cues by cells are, however, still limited to 2D culture systems or cell-extracellular matrix models, which lack the major cell-cell interactions prevalent in 3D cancer tumors. Here, we engineered a 3D spheroid culture environment with varying mechanobiological properties to study the effect of static matrix stiffness stimuli on mechanosensitive and malignant phenotypes in oral squamous cell carcinoma spheroids. We find that spheroid growth is enhanced when cultured in stiff extracellular matrix. We show that the protein expression of mechanoreceptor Piezo1 and stemness marker CD44 is upregulated in stiff matrix. We also report the upregulation of a selection of genes with associations to mechanoreception, ion channel transport, extracellular matrix organization, and tumorigenic phenotypes in stiff matrix spheroids. Together, our results indicate that cancer cells in 3D spheroids utilize mechanosensitive ion channels Piezo1 and TRPV4 as means to sense changes in static extracellular matrix stiffness, and that stiffness drives pro-tumorigenic phenotypes in oral squamous cell carcinoma.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11293878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A high throughput cell stretch device for investigating mechanobiology in vitro. 用于研究体外机械生物学的高通量细胞拉伸装置。
IF 6.6 3区 医学
APL Bioengineering Pub Date : 2024-06-26 eCollection Date: 2024-06-01 DOI: 10.1063/5.0206852
Stephen J P Pratt, Christopher M Plunkett, Guray Kuzu, Ton Trinh, Joshua Barbara, Paula Choconta, Doug Quackenbush, Truc Huynh, Anders Smith, S Whitney Barnes, Joel New, James Pierce, John R Walker, James Mainquist, Frederick J King, Jimmy Elliott, Scott Hammack, Rebekah S Decker
{"title":"A high throughput cell stretch device for investigating mechanobiology <i>in vitro</i>.","authors":"Stephen J P Pratt, Christopher M Plunkett, Guray Kuzu, Ton Trinh, Joshua Barbara, Paula Choconta, Doug Quackenbush, Truc Huynh, Anders Smith, S Whitney Barnes, Joel New, James Pierce, John R Walker, James Mainquist, Frederick J King, Jimmy Elliott, Scott Hammack, Rebekah S Decker","doi":"10.1063/5.0206852","DOIUrl":"https://doi.org/10.1063/5.0206852","url":null,"abstract":"<p><p>Mechanobiology is a rapidly advancing field, with growing evidence that mechanical signaling plays key roles in health and disease. To accelerate mechanobiology-based drug discovery, novel <i>in vitro</i> systems are needed that enable mechanical perturbation of cells in a format amenable to high throughput screening. Here, both a mechanical stretch device and 192-well silicone flexible linear stretch plate were designed and fabricated to meet high throughput technology needs for cell stretch-based applications. To demonstrate the utility of the stretch plate in automation and screening, cell dispensing, liquid handling, high content imaging, and high throughput sequencing platforms were employed. Using this system, an assay was developed as a biological validation and proof-of-concept readout for screening. A mechano-transcriptional stretch response was characterized using focused gene expression profiling measured by RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Gen sequencing. Using articular chondrocytes, a gene expression signature containing stretch responsive genes relevant to cartilage homeostasis and disease was identified. The possibility for integration of other stretch sensitive cell types (e.g., cardiovascular, airway, bladder, gut, and musculoskeletal), in combination with alternative phenotypic readouts (e.g., protein expression, proliferation, or spatial alignment), broadens the scope of high throughput stretch and allows for wider adoption by the research community. This high throughput mechanical stress device fills an unmet need in phenotypic screening technology to support drug discovery in mechanobiology-based disease areas.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11210978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adsorption of monoclonal antibody fragments at the water-oil interface: A coarse-grained molecular dynamics study. 单克隆抗体片段在水油界面的吸附:粗粒度分子动力学研究。
IF 6.6 3区 医学
APL Bioengineering Pub Date : 2024-06-25 eCollection Date: 2024-06-01 DOI: 10.1063/5.0207959
Suman Saurabh, Li Lei, Zongyi Li, John M Seddon, Jian R Lu, Cavan Kalonia, Fernando Bresme
{"title":"Adsorption of monoclonal antibody fragments at the water-oil interface: A coarse-grained molecular dynamics study.","authors":"Suman Saurabh, Li Lei, Zongyi Li, John M Seddon, Jian R Lu, Cavan Kalonia, Fernando Bresme","doi":"10.1063/5.0207959","DOIUrl":"10.1063/5.0207959","url":null,"abstract":"<p><p>Monoclonal antibodies (mAbs) can undergo structural changes due to interaction with oil-water interfaces during storage. Such changes can lead to aggregation, resulting in a loss of therapeutic efficacy. Therefore, understanding the microscopic mechanism controlling mAb adsorption is crucial to developing strategies that can minimize the impact of interfaces on the therapeutic properties of mAbs. In this study, we used MARTINI coarse-grained molecular dynamics simulations to investigate the adsorption of the Fab and Fc domains of the monoclonal antibody COE3 at the oil-water interface. Our aim was to determine the regions on the protein surface that drive mAb adsorption. We also investigate the role of protein concentration on protein orientation and protrusion to the oil phase. While our structural analyses compare favorably with recent neutron reflectivity measurements, we observe some differences. Unlike the monolayer at the interface predicted by neutron reflectivity experiments, our simulations indicate the presence of a secondary diffused layer near the interface. We also find that under certain conditions, protein-oil interaction can lead to a considerable distortion in the protein structure, resulting in enhanced adsorption behavior.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11211994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations. 用于探测人类成纤维细胞从单细胞到群体的实时活化的动态报告器。
IF 6.6 3区 医学
APL Bioengineering Pub Date : 2024-06-24 eCollection Date: 2024-06-01 DOI: 10.1063/5.0166152
Samantha E Cassel, Breanna M Huntington, Wilfred Chen, Pedro Lei, Stelios T Andreadis, April M Kloxin
{"title":"Dynamic reporters for probing real-time activation of human fibroblasts from single cells to populations.","authors":"Samantha E Cassel, Breanna M Huntington, Wilfred Chen, Pedro Lei, Stelios T Andreadis, April M Kloxin","doi":"10.1063/5.0166152","DOIUrl":"https://doi.org/10.1063/5.0166152","url":null,"abstract":"<p><p>Activation of fibroblasts is pivotal for wound healing; however, persistent activation leads to maladaptive processes and is a hallmark of fibrosis, where disease mechanisms are only partially understood. Human <i>in vitro</i> model systems complement <i>in vivo</i> animal models for both hypothesis testing and drug evaluation to improve the identification of therapeutics relevant to human disease. Despite advances, a challenge remains in understanding the dynamics of human fibroblast responses to complex microenvironment stimuli, motivating the need for more advanced tools to investigate fibrotic mechanisms. This work established approaches for assessing the temporal dynamics of these responses using genetically encoded fluorescent reporters of alpha smooth muscle actin expression, an indicator of fibroblast activation. Specifically, we created a toolset of human lung fibroblast reporter cell lines from different origins (male, female; healthy, idiopathic pulmonary fibrosis) and used three different versions of the reporter with the fluorescent protein modified to exhibit different temporal stabilities, providing temporal resolution of protein expression processes over a range of timescales. Using this toolset, we demonstrated that reporters provide insight into population shifts in response to both mechanical and biochemical cues that are not detectable by traditional end point assessments with differential responses based on cell origin. Furthermore, individual cells can also be tracked over time, with opportunities for comparison to complementary end point measurements. The establishment of this reporter toolset enables dynamic cell investigations that can be translated into more complex synthetic culture environments for elucidating disease mechanisms and evaluating therapeutics for lung fibrosis and other complex biological processes more broadly.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11209894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Multicompartment duct platform to study epithelial-endothelial crosstalk associated with lung adenocarcinoma. 研究与肺腺癌相关的上皮-内皮串联的多室导管平台。
IF 6.6 3区 医学
APL Bioengineering Pub Date : 2024-06-17 eCollection Date: 2024-06-01 DOI: 10.1063/5.0207228
Keith A Gagnon, Jessie Huang, Olivia T Hix, Veronica W Hui, Anne Hinds, Esther Bullitt, Jeroen Eyckmans, Darrell N Kotton, Christopher S Chen
{"title":"Multicompartment duct platform to study epithelial-endothelial crosstalk associated with lung adenocarcinoma.","authors":"Keith A Gagnon, Jessie Huang, Olivia T Hix, Veronica W Hui, Anne Hinds, Esther Bullitt, Jeroen Eyckmans, Darrell N Kotton, Christopher S Chen","doi":"10.1063/5.0207228","DOIUrl":"10.1063/5.0207228","url":null,"abstract":"<p><p>Previous lung-on-chip devices have facilitated significant advances in our understanding of lung biology and pathology. Here, we describe a novel lung-on-a-chip model in which human induced pluripotent stem cell-derived alveolar epithelial type II cells (iAT2s) form polarized duct-like lumens alongside engineered perfused vessels lined with human umbilical vein endothelium, all within a 3D, physiologically relevant microenvironment. Using this model, we investigated the morphologic and signaling consequences of the KRAS<sup>G12D</sup> mutation, a commonly identified oncogene in human lung adenocarcinoma (LUAD). We show that expression of the mutant KRAS<sup>G12D</sup> isoform in iAT2s leads to a hyperproliferative response and morphologic dysregulation in the epithelial monolayer. Interestingly, the mutant epithelia also drive an angiogenic response in the adjacent vasculature that is mediated by enhanced secretion of the pro-angiogenic factor soluble uPAR. These results demonstrate the functionality of a multi-cellular <i>in vitro</i> platform capable of modeling mutation-specific behavioral and signaling changes associated with lung adenocarcinoma.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.6,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Parallel on-chip micropipettes enabling quantitative multiplexed characterization of vesicle mechanics and cell aggregates rheology. 可对囊泡力学和细胞聚集流变学进行定量多路复用表征的并行芯片上微量移液器。
IF 6 3区 医学
APL Bioengineering Pub Date : 2024-06-12 eCollection Date: 2024-06-01 DOI: 10.1063/5.0193333
Sylvain Landiech, Marianne Elias, Pierre Lapèze, Hajar Ajiyel, Marine Plancke, Blanca González-Bermúdez, Adrian Laborde, Fabien Mesnilgrente, David Bourrier, Debora Berti, Costanza Montis, Laurent Mazenq, Jérémy Baldo, Clément Roux, Morgan Delarue, Pierre Joseph
{"title":"Parallel on-chip micropipettes enabling quantitative multiplexed characterization of vesicle mechanics and cell aggregates rheology.","authors":"Sylvain Landiech, Marianne Elias, Pierre Lapèze, Hajar Ajiyel, Marine Plancke, Blanca González-Bermúdez, Adrian Laborde, Fabien Mesnilgrente, David Bourrier, Debora Berti, Costanza Montis, Laurent Mazenq, Jérémy Baldo, Clément Roux, Morgan Delarue, Pierre Joseph","doi":"10.1063/5.0193333","DOIUrl":"10.1063/5.0193333","url":null,"abstract":"<p><p>Micropipette aspiration (MPA) is one of the gold standards for quantifying biological samples' mechanical properties, which are crucial from the cell membrane scale to the multicellular tissue. However, relying on the manipulation of individual home-made glass pipettes, MPA suffers from low throughput and no automation. Here, we introduce the sliding insert micropipette aspiration method, which permits parallelization and automation, thanks to the insertion of tubular pipettes, obtained by photolithography, within microfluidic channels. We show its application both at the lipid bilayer level, by probing vesicles to measure membrane bending and stretching moduli, and at the tissue level by quantifying the viscoelasticity of 3D cell aggregates. This approach opens the way to high-throughput, quantitative mechanical testing of many types of biological samples, from vesicles and individual cells to cell aggregates and explants, under dynamic physico-chemical stimuli.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11184969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141421356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An optimized convolutional neural network architecture for lung cancer detection. 用于肺癌检测的优化卷积神经网络架构
IF 6 3区 医学
APL Bioengineering Pub Date : 2024-06-11 eCollection Date: 2024-06-01 DOI: 10.1063/5.0208520
Sameena Pathan, Tanweer Ali, Sudheesh P G, Vasanth Kumar P, Divya Rao
{"title":"An optimized convolutional neural network architecture for lung cancer detection.","authors":"Sameena Pathan, Tanweer Ali, Sudheesh P G, Vasanth Kumar P, Divya Rao","doi":"10.1063/5.0208520","DOIUrl":"10.1063/5.0208520","url":null,"abstract":"<p><p>Lung cancer, the treacherous malignancy affecting the respiratory system of a human body, has a devastating impact on the health and well-being of an individual. Due to the lack of automated and noninvasive diagnostic tools, healthcare professionals look forward toward biopsy as a gold standard for diagnosis. However, biopsy could be traumatizing and expensive process. Additionally, the limited availability of dataset and inaccuracy in diagnosis is a major drawback experienced by researchers. The objective of the proposed research is to develop an automated diagnostic tool for screening of lung cancer using optimized hyperparameters such that convolutional neural network (CNN) model generalizes well for universally obtained computerized tomography (CT) slices of lung pathologies. The aforementioned objective is achieved in the following ways: (i) Initially, a preprocessing methodology specific to lung CT scans is formulated to avoid the loss of information due to random image smoothing, and (ii) a sine cosine algorithm optimization algorithm (SCA) is integrated in the CNN model, to optimally select the tuning parameters of CNN. The error rate is used as an objective function, and the SCA algorithm tries to minimize. The proposed method successfully achieved an average classification accuracy of 99% in classification of lung scans in normal, benign, and malignant classes. Further, the generalization ability of the proposed model is tested on unseen dataset, thereby achieving promising results. The quantitative results prove the efficacy of the system to be used by radiologists in a clinical scenario.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Collagen density regulates tip-stalk cell rearrangement during angiogenesis via cellular bioenergetics. 胶原蛋白密度通过细胞生物能调节血管生成过程中的顶茎细胞重排。
IF 6 3区 医学
APL Bioengineering Pub Date : 2024-06-10 eCollection Date: 2024-06-01 DOI: 10.1063/5.0195249
Wenjun Wang, Matthew R Zanotelli, Lindsey N Sabo, Emily D Fabiano, Natalie M Goldfield, Chloe Le, Elle P Techasiriwan, Santiago Lopez, Emily D Berestesky, Cynthia A Reinhart-King
{"title":"Collagen density regulates tip-stalk cell rearrangement during angiogenesis via cellular bioenergetics.","authors":"Wenjun Wang, Matthew R Zanotelli, Lindsey N Sabo, Emily D Fabiano, Natalie M Goldfield, Chloe Le, Elle P Techasiriwan, Santiago Lopez, Emily D Berestesky, Cynthia A Reinhart-King","doi":"10.1063/5.0195249","DOIUrl":"10.1063/5.0195249","url":null,"abstract":"<p><p>Tumor vasculature plays a crucial role in tumor progression, affecting nutrition and oxygen transportation as well as the efficiency of drug delivery. While targeting pro-angiogenic growth factors has been a significant focus for treating tumor angiogenesis, recent studies indicate that metabolism also plays a role in regulating endothelial cell behavior. Like cancer cells, tumor endothelial cells undergo metabolic changes that regulate rearrangement for tip cell position during angiogenesis. Our previous studies have shown that altered mechanical properties of the collagen matrix regulate angiogenesis and can promote a tumor vasculature phenotype. Here, we examine the effect of collagen density on endothelial cell tip-stalk cell rearrangement and cellular energetics during angiogenic sprouting. We find that increased collagen density leads to an elevated energy state and an increased rate of tip-stalk cell switching, which is correlated with the energy state of the cells. Tip cells exhibit higher glucose uptake than stalk cells, and inhibition of glucose uptake revealed that invading sprouts rely on glucose to meet elevated energy requirements for invasion in dense matrices. This work helps to elucidate the complex interplay between the mechanical microenvironment and the endothelial cell metabolic status during angiogenesis, which could have important implications for developing new anti-cancer therapies.</p>","PeriodicalId":46288,"journal":{"name":"APL Bioengineering","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11170328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141318492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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