The 2023 MDPI Annual Report has
been released!
 
17 pages, 975 KiB  
Article
Proteomic Blood Profiles Obtained by Totally Blind Biological Clustering in Stable and Exacerbated COPD Patients
by Cesar Jessé Enríquez-Rodríguez, Sergi Pascual-Guardia, Carme Casadevall, Oswaldo Antonio Caguana-Vélez, Diego Rodríguez-Chiaradia, Esther Barreiro and Joaquim Gea
Cells 2024, 13(10), 866; https://doi.org/10.3390/cells13100866 - 17 May 2024
Abstract
Although Chronic Obstructive Pulmonary Disease (COPD) is highly prevalent, it is often underdiagnosed. One of the main characteristics of this heterogeneous disease is the presence of periods of acute clinical impairment (exacerbations). Obtaining blood biomarkers for either COPD as a chronic entity or [...] Read more.
Although Chronic Obstructive Pulmonary Disease (COPD) is highly prevalent, it is often underdiagnosed. One of the main characteristics of this heterogeneous disease is the presence of periods of acute clinical impairment (exacerbations). Obtaining blood biomarkers for either COPD as a chronic entity or its exacerbations (AECOPD) will be particularly useful for the clinical management of patients. However, most of the earlier studies have been characterized by potential biases derived from pre-existing hypotheses in one or more of their analysis steps: some studies have only targeted molecules already suggested by pre-existing knowledge, and others had initially carried out a blind search but later compared the detected biomarkers among well-predefined clinical groups. We hypothesized that a clinically blind cluster analysis on the results of a non-hypothesis-driven wide proteomic search would determine an unbiased grouping of patients, potentially reflecting their endotypes and/or clinical characteristics. To check this hypothesis, we included the plasma samples from 24 clinically stable COPD patients, 10 additional patients with AECOPD, and 10 healthy controls. The samples were analyzed through label-free liquid chromatography/tandem mass spectrometry. Subsequently, the Scikit-learn machine learning module and K-means were used for clustering the individuals based solely on their proteomic profiles. The obtained clusters were confronted with clinical groups only at the end of the entire procedure. Although our clusters were unable to differentiate stable COPD patients from healthy individuals, they segregated those patients with AECOPD from the patients in stable conditions (sensitivity 80%, specificity 79%, and global accuracy, 79.4%). Moreover, the proteins involved in the blind grouping process to identify AECOPD were associated with five biological processes: inflammation, humoral immune response, blood coagulation, modulation of lipid metabolism, and complement system pathways. Even though the present results merit an external validation, our results suggest that the present blinded approach may be useful to segregate AECOPD from stability in both the clinical setting and trials, favoring more personalized medicine and clinical research. Full article
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25 pages, 2682 KiB  
Review
Cytosolic and Acrosomal pH Regulation in Mammalian Sperm
by Julio C. Chávez, Gabriela Carrasquel-Martínez, Sandra Hernández-Garduño, Arturo Matamoros Volante, Claudia L. Treviño, Takuya Nishigaki and Alberto Darszon
Cells 2024, 13(10), 865; https://doi.org/10.3390/cells13100865 - 17 May 2024
Abstract
As in most cells, intracellular pH regulation is fundamental for sperm physiology. Key sperm functions like swimming, maturation, and a unique exocytotic process, the acrosome reaction, necessary for gamete fusion, are deeply influenced by pH. Sperm pH regulation, both intracellularly and within organelles [...] Read more.
As in most cells, intracellular pH regulation is fundamental for sperm physiology. Key sperm functions like swimming, maturation, and a unique exocytotic process, the acrosome reaction, necessary for gamete fusion, are deeply influenced by pH. Sperm pH regulation, both intracellularly and within organelles such as the acrosome, requires a coordinated interplay of various transporters and channels, ensuring that this cell is primed for fertilization. Consistent with the pivotal importance of pH regulation in mammalian sperm physiology, several of its unique transporters are dependent on cytosolic pH. Examples include the Ca2+ channel CatSper and the K+ channel Slo3. The absence of these channels leads to male infertility. This review outlines the main transport elements involved in pH regulation, including cytosolic and acrosomal pH, that participate in these complex functions. We present a glimpse of how these transporters are regulated and how distinct sets of them are orchestrated to allow sperm to fertilize the egg. Much research is needed to begin to envision the complete set of players and the choreography of how cytosolic and organellar pH are regulated in each sperm function. Full article
(This article belongs to the Special Issue The Cell Biology of Fertilization)
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19 pages, 10549 KiB  
Article
Antibody–Drug Conjugate Made of Zoledronic Acid and the Anti-CD30 Brentuximab–Vedotin Exert Anti-Lymphoma and Immunostimulating Effects
by Feliciana Morelli, Serena Matis, Roberto Benelli, Laura Salvini, Maria Raffaella Zocchi and Alessandro Poggi
Cells 2024, 13(10), 862; https://doi.org/10.3390/cells13100862 - 17 May 2024
Abstract
Relevant advances have been made in the management of relapsed/refractory (r/r) Hodgkin Lymphomas (HL) with the use of the anti-CD30 antibody–drug conjugate (ADC) brentuximab–vedotin (Bre–Ved). Unfortunately, most patients eventually progress despite the excellent response rates and tolerability. In this report, we describe an [...] Read more.
Relevant advances have been made in the management of relapsed/refractory (r/r) Hodgkin Lymphomas (HL) with the use of the anti-CD30 antibody–drug conjugate (ADC) brentuximab–vedotin (Bre–Ved). Unfortunately, most patients eventually progress despite the excellent response rates and tolerability. In this report, we describe an ADC composed of the aminobisphosphonate zoledronic acid (ZA) conjugated to Bre–Ved by binding the free amino groups of this antibody with the phosphoric group of ZA. Liquid chromatography–mass spectrometry, inductively coupled plasma–mass spectrometry, and matrix-assisted laser desorption ionization–mass spectrometry analyses confirmed the covalent linkage between the antibody and ZA. The novel ADC has been tested for its reactivity with the HL/CD30+ lymphoblastoid cell lines (KMH2, L428, L540, HS445, and RPMI6666), showing a better titration than native Bre–Ved. Once the HL-cells are entered, the ADC co-localizes with the lysosomal LAMP1 in the intracellular vesicles. Also, this ADC exerted a stronger anti-proliferative and pro-apoptotic (about one log fold) effect on HL-cell proliferation compared to the native antibody Bre–Ved. Eventually, Bre–Ved–ZA ADC, in contrast with the native antibody, can trigger the proliferation and activation of cytolytic activity of effector-memory Vδ2 T-lymphocytes against HL-cell lines. These findings may support the potential use of this ADC in the management of r/r HL. Full article
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26 pages, 5593 KiB  
Article
hTERT-Immortalized Mesenchymal Stem Cell-Derived Extracellular Vesicles: Large-Scale Manufacturing, Cargo Profiling, and Functional Effects in Retinal Epithelial Cells
by Jessica Hindle, Anastasia Williams, Yuriy Kim, Dongsung Kim, Kajal Patil, Pooja Khatkar, Quinn Osgood, Collin Nelson, David A. Routenberg, Marissa Howard, Lance A. Liotta, Fatah Kashanchi and Heather Branscome
Cells 2024, 13(10), 861; https://doi.org/10.3390/cells13100861 - 17 May 2024
Abstract
As the economic burden associated with vision loss and ocular damage continues to rise, there is a need to explore novel treatment strategies. Extracellular vesicles (EVs) are enriched with various biological cargo, and there is abundant literature supporting the reparative and immunomodulatory properties [...] Read more.
As the economic burden associated with vision loss and ocular damage continues to rise, there is a need to explore novel treatment strategies. Extracellular vesicles (EVs) are enriched with various biological cargo, and there is abundant literature supporting the reparative and immunomodulatory properties of stem cell EVs across a broad range of pathologies. However, one area that requires further attention is the reparative effects of stem cell EVs in the context of ocular damage. Additionally, most of the literature focuses on EVs isolated from primary stem cells; the use of EVs isolated from human telomerase reverse transcriptase (hTERT)-immortalized stem cells has not been thoroughly examined. Using our large-scale EV-manufacturing platform, we reproducibly manufactured EVs from hTERT-immortalized mesenchymal stem cells (MSCs) and employed various methods to characterize and profile their associated cargo. We also utilized well-established cell-based assays to compare the effects of these EVs on both healthy and damaged retinal pigment epithelial cells. To the best of our knowledge, this is the first study to establish proof of concept for reproducible, large-scale manufacturing of hTERT-immortalized MSC EVs and to investigate their potential reparative properties against damaged retinal cells. The results from our studies confirm that hTERT-immortalized MSC EVs exert reparative effects in vitro that are similar to those observed in primary MSC EVs. Therefore, hTERT-immortalized MSCs may represent a more consistent and reproducible platform than primary MSCs for generating EVs with therapeutic potential. Full article
(This article belongs to the Section Cellular Pathology)
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12 pages, 3877 KiB  
Article
A Scalable Histological Method to Embed and Section Multiple Brains Simultaneously
by Divine C. Nwafor, Stanley A. Benkovic, Briana L. Clary, Allison L. Brichacek, H. Wayne Lambert, Matthew J. Zdilla and Candice M. Brown
Cells 2024, 13(10), 860; https://doi.org/10.3390/cells13100860 - 17 May 2024
Abstract
The preparation and processing of rodent brains for evaluation by immunohistochemistry is time-consuming. A large number of mouse brains are routinely used in experiments in neuroscience laboratories to evaluate several models of human diseases. Thus, methods are needed to reduce the time associated [...] Read more.
The preparation and processing of rodent brains for evaluation by immunohistochemistry is time-consuming. A large number of mouse brains are routinely used in experiments in neuroscience laboratories to evaluate several models of human diseases. Thus, methods are needed to reduce the time associated with processing brains for histology. A scalable method was developed to embed, section, and stain multiple mouse brains using supplies found in any common histology laboratory. Section collection schemes can be scaled to provide identical bregma locations between adjacent sections for immunohistochemistry, facilitating comprehensive, high-quality immunohistochemistry. As a result, sectioning and staining times are considerably reduced as sections from multiple blocks are stained simultaneously. This method improves on previous procedures and allows multiple embedding and subsequent immunostaining of brains easily with a dramatically reduced time requirement. Furthermore, we expand this method for use in numerous mouse tissues, rat brain tissue, and post-mortem human brain and arterial tissues. In summary, this procedure allows the processing of many rodent or human tissues from perfusion through microscopy in 10 days or less. Full article
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16 pages, 6529 KiB  
Article
Lung Transplant Immunomodulation with Genetically Engineered Mesenchymal Stromal Cells—Therapeutic Window for Interleukin-10
by Antti I. Nykänen, Andrea Mariscal, Allen Duong, Aadil Ali, Akihiro Takahagi, Xiaohui Bai, Guan Zehong, Betty Joe, Mamoru Takahashi, Manyin Chen, Hemant Gokhale, Hongchao Shan, David M. Hwang, Catalina Estrada, Jonathan Yeung, Tom Waddell, Tereza Martinu, Stephen Juvet, Marcelo Cypel, Mingyao Liu, John E. Davies and Shaf Keshavjeeadd Show full author list remove Hide full author list
Cells 2024, 13(10), 859; https://doi.org/10.3390/cells13100859 - 17 May 2024
Abstract
Lung transplantation results are compromised by ischemia–reperfusion injury and alloimmune responses. Ex vivo lung perfusion (EVLP) is used to assess marginal donor lungs before transplantation but is also an excellent platform to apply novel therapeutics. We investigated donor lung immunomodulation using genetically engineered [...] Read more.
Lung transplantation results are compromised by ischemia–reperfusion injury and alloimmune responses. Ex vivo lung perfusion (EVLP) is used to assess marginal donor lungs before transplantation but is also an excellent platform to apply novel therapeutics. We investigated donor lung immunomodulation using genetically engineered mesenchymal stromal cells with augmented production of human anti-inflammatory hIL-10 (MSCsIL-10). Pig lungs were placed on EVLP for 6 h and randomized to control (n = 7), intravascular delivery of 20 × 106 (n = 5, low dose) or 40 × 106 human MSCs IL-10 (n = 6, high dose). Subsequently, single-lung transplantation was performed, and recipient pigs were monitored for 3 days. hIL-10 secretion was measured during EVLP and after transplantation, and immunological effects were assessed by cytokine profile, T and myeloid cell characterization and mixed lymphocyte reaction. MSCIL-10 therapy rapidly increased hIL-10 during EVLP and resulted in transient hIL-10 elevation after lung transplantation. MSCIL-10 delivery did not affect lung function but was associated with dose-related immunomodulatory effects, with the low dose resulting in a beneficial decrease in apoptosis and lower macrophage activation, but the high MSCIL-10 dose resulting in inflammation and cytotoxic CD8+ T cell activation. MSCIL-10 therapy during EVLP results in a rapid and transient perioperative hIL-10 increase and has a therapeutic window for its immunomodulatory effects. Full article
(This article belongs to the Section Cell and Gene Therapy)
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14 pages, 1770 KiB  
Review
Prime Editing and DNA Repair System: Balancing Efficiency with Safety
by Karim Daliri, Jürgen Hescheler and Kurt Paul Pfannkuche
Cells 2024, 13(10), 858; https://doi.org/10.3390/cells13100858 - 17 May 2024
Abstract
Prime editing (PE), a recent progression in CRISPR-based technologies, holds promise for precise genome editing without the risks associated with double-strand breaks. It can introduce a wide range of changes, including single-nucleotide variants, insertions, and small deletions. Despite these advancements, there is a [...] Read more.
Prime editing (PE), a recent progression in CRISPR-based technologies, holds promise for precise genome editing without the risks associated with double-strand breaks. It can introduce a wide range of changes, including single-nucleotide variants, insertions, and small deletions. Despite these advancements, there is a need for further optimization to overcome certain limitations to increase efficiency. One such approach to enhance PE efficiency involves the inhibition of the DNA mismatch repair (MMR) system, specifically MLH1. The rationale behind this approach lies in the MMR system’s role in correcting mismatched nucleotides during DNA replication. Inhibiting this repair pathway creates a window of opportunity for the PE machinery to incorporate the desired edits before permanent DNA repair actions. However, as the MMR system plays a crucial role in various cellular processes, it is important to consider the potential risks associated with manipulating this system. The new versions of PE with enhanced efficiency while blocking MLH1 are called PE4 and PE5. Here, we explore the potential risks associated with manipulating the MMR system. We pay special attention to the possible implications for human health, particularly the development of cancer. Full article
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28 pages, 13846 KiB  
Article
Insights into PCSK9-LDLR Regulation and Trafficking via the Differential Functions of MHC-I Proteins HFE and HLA-C
by Sepideh Mikaeeli, Ali Ben Djoudi Ouadda, Alexandra Evagelidis, Rachid Essalmani, Oscar Henrique Pereira Ramos, Carole Fruchart-Gaillard and Nabil G. Seidah
Cells 2024, 13(10), 857; https://doi.org/10.3390/cells13100857 - 17 May 2024
Abstract
PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9’s C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified “protein X”. The M2 repeat was [...] Read more.
PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9’s C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified “protein X”. The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be “protein X” candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9’s function have yet to be determined. Herein, we compared the implication of MHC-I-like proteins such as HFE (involved in iron homeostasis) and HLA-C on the extracellular function of PCSK9. Our data revealed that the M2 domain regulates the intracellular sorting of the PCSK9-LDLR complex to lysosomes, and that HFE is a new target of PCSK9 that inhibits its activity on the LDLR, whereas HLA-C enhances its function. This work suggests the potential modulation of PCSK9’s functions through interactions of HFE and HLA-C. Full article
(This article belongs to the Collection Research Advances in Cellular Metabolism)
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27 pages, 2596 KiB  
Review
Role of Vasoactive Hormone-Induced Signal Transduction in Cardiac Hypertrophy and Heart Failure
by Naranjan S. Dhalla, Karina O. Mota, Vijayan Elimban, Anureet K. Shah, Carla M. L. de Vasconcelos and Sukhwinder K. Bhullar
Cells 2024, 13(10), 856; https://doi.org/10.3390/cells13100856 - 17 May 2024
Abstract
Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably preceded by adaptive or maladaptive cardiac hypertrophy, several biochemical mechanisms have been proposed to explain the development of cardiac [...] Read more.
Heart failure is the common concluding pathway for a majority of cardiovascular diseases and is associated with cardiac dysfunction. Since heart failure is invariably preceded by adaptive or maladaptive cardiac hypertrophy, several biochemical mechanisms have been proposed to explain the development of cardiac hypertrophy and progression to heart failure. One of these includes the activation of different neuroendocrine systems for elevating the circulating levels of different vasoactive hormones such as catecholamines, angiotensin II, vasopressin, serotonin and endothelins. All these hormones are released in the circulation and stimulate different signal transduction systems by acting on their respective receptors on the cell membrane to promote protein synthesis in cardiomyocytes and induce cardiac hypertrophy. The elevated levels of these vasoactive hormones induce hemodynamic overload, increase ventricular wall tension, increase protein synthesis and the occurrence of cardiac remodeling. In addition, there occurs an increase in proinflammatory cytokines and collagen synthesis for the induction of myocardial fibrosis and the transition of adaptive to maladaptive hypertrophy. The prolonged exposure of the hypertrophied heart to these vasoactive hormones has been reported to result in the oxidation of catecholamines and serotonin via monoamine oxidase as well as the activation of NADPH oxidase via angiotensin II and endothelins to promote oxidative stress. The development of oxidative stress produces subcellular defects, Ca2+-handling abnormalities, mitochondrial Ca2+-overload and cardiac dysfunction by activating different proteases and depressing cardiac gene expression, in addition to destabilizing the extracellular matrix upon activating some metalloproteinases. These observations support the view that elevated levels of various vasoactive hormones, by producing hemodynamic overload and activating their respective receptor-mediated signal transduction mechanisms, induce cardiac hypertrophy. Furthermore, the occurrence of oxidative stress due to the prolonged exposure of the hypertrophied heart to these hormones plays a critical role in the progression of heart failure. Full article
(This article belongs to the Collection Cardiomyocytes, Myocardial Hypertrophy, and Heart Failure)
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8 pages, 2382 KiB  
Case Report
Brugada Syndrome and Pulmonary Atresia with Intact Interventricular Septum: Fortuitous Finding or New Genetic Connection?
by Miguel Fogaça-da-Mata, Estefanía Martínez-Barrios, Lorenzo Jiménez-Montañés, José Cruzalegui, Fredy Chipa-Ccasani, Andrea Greco, Sergi Cesar, Núria Díez-Escuté, Patricia Cerralbo, Irene Zschaeck, Marcos Clavero Adell, Ariadna Ayerza-Casas, Daniel Palanca-Arias, Marta López, Oscar Campuzano, Josep Brugada and Georgia Sarquella-Brugada
Genes 2024, 15(5), 638; https://doi.org/10.3390/genes15050638 - 17 May 2024
Abstract
Brugada syndrome is a rare arrhythmogenic syndrome associated mainly with pathogenic variants in the SCN5A gene. Right ventricle outflow tract fibrosis has been reported in some cases of patients diagnosed with Brugada syndrome. Pulmonary atresia with an intact ventricular septum is characterized by [...] Read more.
Brugada syndrome is a rare arrhythmogenic syndrome associated mainly with pathogenic variants in the SCN5A gene. Right ventricle outflow tract fibrosis has been reported in some cases of patients diagnosed with Brugada syndrome. Pulmonary atresia with an intact ventricular septum is characterized by the lack of a functional pulmonary valve, due to the underdevelopment of the right ventricle outflow tract. We report, for the first time, a 4-year-old boy with pulmonary atresia with an intact ventricular septum who harbored a pathogenic de novo variant in SCN5A, and the ajmaline test unmasked a type-1 Brugada pattern. We suggest that deleterious variants in the SCN5A gene could be implicated in pulmonary atresia with an intact ventricular septum embryogenesis, leading to overlapping phenotypes. Full article
(This article belongs to the Special Issue Genetics of Congenital Heart Diseases)
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21 pages, 4847 KiB  
Article
Inverse and Proportional Trans Modulation of Gene Expression in Human Aneuploidies
by Shuai Zhang, Ruixue Wang, Ludan Zhang, James A. Birchler and Lin Sun
Genes 2024, 15(5), 637; https://doi.org/10.3390/genes15050637 - 17 May 2024
Abstract
Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried [...] Read more.
Genomic imbalance in aneuploidy is often detrimental to organisms. To gain insight into the molecular basis of aneuploidies in humans, we analyzed transcriptome data from several autosomal and sex chromosome aneuploidies. The results showed that in human aneuploid cells, genes located on unvaried chromosomes are inversely or proportionally trans-modulated, while a subset of genes on the varied chromosomes are compensated. Less genome-wide modulation is found for sex chromosome aneuploidy compared with autosomal aneuploidy due to X inactivation and the retention of dosage sensitive regulators on both sex chromosomes to limit the effective dosage change. We also found that lncRNA and mRNA can have different responses to aneuploidy. Furthermore, we analyzed the relationship between dosage-sensitive transcription factors and their targets, which illustrated the modulations and indicates genomic imbalance is related to stoichiometric changes in components of gene regulatory complexes.In summary, this study demonstrates the existence of trans-acting effects and compensation mechanisms in human aneuploidies and contributes to our understanding of gene expression regulation in unbalanced genomes and disease states. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
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25 pages, 14550 KiB  
Article
Impact Response Features and Penetration Mechanism of UHMWPE Subjected to Handgun Bullet
by Yihui Zhu, Yang Song, Wei Wu, Jie Ma, Zhuangqing Fan, Yaoke Wen, Cheng Xu, Min Xia and Weifeng Da
Polymers 2024, 16(10), 1427; https://doi.org/10.3390/polym16101427 - 17 May 2024
Abstract
Ensuring military and police personnel protection is vital for urban security. However, the impact response mechanism of the UHMWPE laminate used in ballistic helmets and vests remains unclear, making it hard to effectively protect the head, chest, and abdomen. This study utilized 3D-DIC [...] Read more.
Ensuring military and police personnel protection is vital for urban security. However, the impact response mechanism of the UHMWPE laminate used in ballistic helmets and vests remains unclear, making it hard to effectively protect the head, chest, and abdomen. This study utilized 3D-DIC technology to analyze UHMWPE laminate’s response to 9 mm lead-core pistol bullets traveling at 334.93 m/s. Damage mode and response characteristics were revealed, and an effective numerical calculation method was established that could reveal the energy conversion process. The bullet penetrated by 1.03 mm, causing noticeable fiber traction, resulting in cross-shaped failure due to fiber compression and aggregation. Bulge transitioned from circular to square, initially increasing rapidly, then slowing. Maximum in-plane shear strain occurred at ±45°, with values of 0.0904 and −0.0928. Model accuracy was confirmed by comparing strain distributions. The investigation focused on bullet-laminate interaction and energy conversion. Bullet’s kinetic energy is converted into laminate’s kinetic and internal energy, with the majority of erosion energy occurring in the first four equivalent sublaminates and the primary energy change in the system occurring at 75 μs in the fourth equivalent sublayer. The results show the damage mode and energy conversion of the laminate, providing theoretical support for understanding the impact response mechanism and improving the efficiency of protective energy absorption. Full article
(This article belongs to the Special Issue Mechanical Behaviors and Properties of Polymer Materials)
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19 pages, 16063 KiB  
Article
Comparison of Printable Biomaterials for Use in Neural Tissue Engineering: An In Vitro Characterization and In Vivo Biocompatibility Assessment
by Miguel Etayo-Escanilla, Noelia Campillo, Paula Ávila-Fernández, José Manuel Baena, Jesús Chato-Astrain, Fernando Campos, David Sánchez-Porras, Óscar Darío García-García and Víctor Carriel
Polymers 2024, 16(10), 1426; https://doi.org/10.3390/polym16101426 - 17 May 2024
Abstract
Nervous system traumatic injuries are prevalent in our society, with a significant socioeconomic impact. Due to the highly complex structure of the neural tissue, the treatment of these injuries is still a challenge. Recently, 3D printing has emerged as a promising alternative for [...] Read more.
Nervous system traumatic injuries are prevalent in our society, with a significant socioeconomic impact. Due to the highly complex structure of the neural tissue, the treatment of these injuries is still a challenge. Recently, 3D printing has emerged as a promising alternative for producing biomimetic scaffolds, which can lead to the restoration of neural tissue function. The objective of this work was to compare different biomaterials for generating 3D-printed scaffolds for use in neural tissue engineering. For this purpose, four thermoplastic biomaterials, ((polylactic acid) (PLA), polycaprolactone (PCL), Filaflex (FF) (assessed here for the first time for biomedical purposes), and Flexdym (FD)) and gelatin methacrylate (GelMA) hydrogel were subjected to printability and mechanical tests, in vitro cell–biomaterial interaction analyses, and in vivo biocompatibility assessment. The thermoplastics showed superior printing results in terms of resolution and shape fidelity, whereas FD and GelMA revealed great viscoelastic properties. GelMA demonstrated a greater cell viability index after 7 days of in vitro cell culture. Moreover, all groups displayed connective tissue encapsulation, with some inflammatory cells around the scaffolds after 10 days of in vivo implantation. Future studies will determine the usefulness and in vivo therapeutic efficacy of novel neural substitutes based on the use of these 3D-printed scaffolds. Full article
(This article belongs to the Special Issue Biocompatible and Biodegradable Polymers for Medical Applications II)
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18 pages, 8533 KiB  
Article
Liquid Crystal Orientation and Shape Optimization for the Active Response of Liquid Crystal Elastomers
by Jorge Luis Barrera, Caitlyn Cook, Elaine Lee, Kenneth Swartz and Daniel Tortorelli
Polymers 2024, 16(10), 1425; https://doi.org/10.3390/polym16101425 - 17 May 2024
Abstract
Liquid crystal elastomers (LCEs) are responsive materials that can undergo large reversible deformations upon exposure to external stimuli, such as electrical and thermal fields. Controlling the alignment of their liquid crystals mesogens to achieve desired shape changes unlocks a new design paradigm that [...] Read more.
Liquid crystal elastomers (LCEs) are responsive materials that can undergo large reversible deformations upon exposure to external stimuli, such as electrical and thermal fields. Controlling the alignment of their liquid crystals mesogens to achieve desired shape changes unlocks a new design paradigm that is unavailable when using traditional materials. While experimental measurements can provide valuable insights into their behavior, computational analysis is essential to exploit their full potential. Accurate simulation is not, however, the end goal; rather, it is the means to achieve their optimal design. Such design optimization problems are best solved with algorithms that require gradients, i.e., sensitivities, of the cost and constraint functions with respect to the design parameters, to efficiently traverse the design space. In this work, a nonlinear LCE model and adjoint sensitivity analysis are implemented in a scalable and flexible finite element-based open source framework and integrated into a gradient-based design optimization tool. To display the versatility of the computational framework, LCE design problems that optimize both the material, i.e., liquid crystal orientation, and structural shape to reach a target actuated shapes or maximize energy absorption are solved. Multiple parameterizations, customized to address fabrication limitations, are investigated in both 2D and 3D. The case studies are followed by a discussion on the simulation and design optimization hurdles, as well as potential avenues for improving the robustness of similar computational frameworks for applications of interest. Full article
(This article belongs to the Special Issue Modeling and Simulations of Smart and Responsive Polymers)
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13 pages, 4117 KiB  
Article
The Air Permeability and the Porosity of Polymer Materials Based on 3D-Printed Hybrid Non-Woven Needle-Punched Fabrics
by Victor Nazarov, Alexander Dedov, Fedor Doronin, Mikhail Savel’ev, Andrey Evdokimov and Georgy Rytikov
Polymers 2024, 16(10), 1424; https://doi.org/10.3390/polym16101424 - 17 May 2024
Abstract
The possibility of controlling the porosity and, as a result, the permeability of fibrous non-woven fabrics was studied. Modification of experimental samples was performed on equipment with adjustable heating and compression. It was found that the modification regimes affected the formation of the [...] Read more.
The possibility of controlling the porosity and, as a result, the permeability of fibrous non-woven fabrics was studied. Modification of experimental samples was performed on equipment with adjustable heating and compression. It was found that the modification regimes affected the formation of the porous structure. We found that there was a relationship between the permeability coefficient and the porosity coefficient of the materials when the modification speed and temperature were varied. A model is proposed for predicting the permeability for modified material with a given porosity. As the result, a new hybrid composite material with reversible dynamic color characteristics that changed under the influence of ultraviolet and/or thermal exposure was produced. The developed technology consists of: manufacture of the non-woven needle-punched fabrics, surface structuring, material extrusion, additive manufacturing (FFF technology) and the stencil technique of ink-layer adding. In our investigation, we (a) obtained fibrous polymer materials with a porosity gradient in thickness, (b) determined the dependence of the material’s porosity coefficient on the speed and temperature of the modification and (c) developed a model for calculating the porosity coefficient of the materials with specified technological parameters. Full article
(This article belongs to the Special Issue Functional Hybrid Polymeric Composites)
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15 pages, 7414 KiB  
Article
A New Approach to Carbon Nanotube Filament Nanostructuring for Additive Manufacturing
by Fedor Doronin, Mikhail Savel’ev, Georgy Rytikov, Andrey Evdokimov and Victor Nazarov
Polymers 2024, 16(10), 1423; https://doi.org/10.3390/polym16101423 - 17 May 2024
Abstract
A new technique of additive prototyping filament volumetric nanostructuring based on the high-speed mechanical mixing of acrylonitrile-butadiene-styrene (ABS) copolymer granules and single-walled carbon nanotube (CNT) powder (without prior dispersion in solvents) is considered. The morphological spectra of scanning electron microscopy (SEM) images of [...] Read more.
A new technique of additive prototyping filament volumetric nanostructuring based on the high-speed mechanical mixing of acrylonitrile-butadiene-styrene (ABS) copolymer granules and single-walled carbon nanotube (CNT) powder (without prior dispersion in solvents) is considered. The morphological spectra of scanning electron microscopy (SEM) images of nanostructured filament slice surfaces were obtained and characterized with the original mathematical simulation. The relations of structural changes in the “ingredient-matrix” polymer system with dielectric and mechanical properties of the ABS-based filaments were established. The supplementation of 1.5 mass.% of CNT powder to the ABS filament composition leads to the tensile strength increasing from 36 ± 2 to 42 ± 2 MPa. It is shown that the greater the average biharmonic amplitude and the morphological spectrum localization radius of the slice surfaces’ SEM images, the lower the electrical resistance of the corresponding nanostructured filaments. The possibility of carbon nanotube-modified filament functional layers forming using the extrusion additive prototyping technique (FFF) on the surface of plasma-chemically modified PET substrates (for the creation of load cell elements) is experimentally demonstrated. Full article
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13 pages, 1593 KiB  
Article
Lyophilized Emulsions of Thymol and Eugenol Essential Oils Encapsulated in Cellulose
by Koranit Shlosman, Dmitry M. Rein, Rotem Shemesh and Yachin Cohen
Polymers 2024, 16(10), 1422; https://doi.org/10.3390/polym16101422 - 17 May 2024
Abstract
Efforts to tap into the broad antimicrobial, insecticidal, and antioxidant activities of essential oils (EOs) are limited due to their strong odor and susceptibility to light and oxidation. Encapsulation of EOs and subsequent drying overcome these limitations and extend their applications. This study [...] Read more.
Efforts to tap into the broad antimicrobial, insecticidal, and antioxidant activities of essential oils (EOs) are limited due to their strong odor and susceptibility to light and oxidation. Encapsulation of EOs and subsequent drying overcome these limitations and extend their applications. This study characterized freeze-dried (lyophilized) emulsions of eugenol (EU) and thymol (TY) EOs, encapsulated by chemically unmodified cellulose, a sustainable and low-cost resource. High-resolution scanning electron microscopy showed successful lyophilization. While the observed “flake-like” structure of the powders differed significantly from that of the emulsified microcapsules, useful properties were retained. Fourier transform infrared spectroscopy confirmed the presence of EOs in their corresponding powders and thermo-gravimetric analysis demonstrated high encapsulation efficiency (87–88%), improved thermal stability and resistance to evaporation, and slow EO release rates in comparison to their free forms. The lightweight and low-cost cellulose encapsulation, together with the results showing retained properties of the dried powder, enable the use of EOs in applications requiring high temperatures, such as EO incorporation into polymer films, that can be used to protect agricultural crops from microbial infections. Full article
(This article belongs to the Special Issue Polysaccharide-Based Materials: Developments and Properties)
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21 pages, 12476 KiB  
Article
Al-Rich Titanites from Mont Blanc Alpine Fissures: Evidence of Ti-Nb-Y-REE Mobility during Water–Rock Interactions
by Michel Cathelineau and Chantal Peiffert
Crystals 2024, 14(5), 472; https://doi.org/10.3390/cryst14050472 - 17 May 2024
Abstract
Titanites can be excellent markers of element transfer in medium-temperature retrograde metamorphism. Euhedral titanites from several alpine fissures from Mont Blanc, particularly those of Périades and Courtes, crystallised at the end of the main quartz stage and are synchronous with the formation of [...] Read more.
Titanites can be excellent markers of element transfer in medium-temperature retrograde metamorphism. Euhedral titanites from several alpine fissures from Mont Blanc, particularly those of Périades and Courtes, crystallised at the end of the main quartz stage and are synchronous with the formation of green biotites and albite before chlorite formation. Micro-XRF, SEM, electron probe, and LA-ICP-MS analyses show that these titanites have a wide range of Al2O3 content from 1 to 8%, are dominated by -OH versus F, and have a wide range of Nb (up to 4500 ppm), Y (up to 3000 ppm), Zr (up to 1800 ppm), and Sn (up to 1400 ppm) concentrations. The allanite from the granite, partly destabilised into epidote, is the most likely source of Nb, Y, Zr, Sn, and REE. Titanites are enriched in HREE and show variations in LREE depending on the studied sites. Like quartz, they formed at around 400 ± 20 °C, which is compatible with the formation of green biotites after the destabilisation of granite Fe-Mg silicates. This early stage of fluid circulation, synchronous with the Mont Blanc massif uplift, is therefore marked by the titanite formation at the transition between the biotite and chlorite stability fields. Full article
(This article belongs to the Section Mineralogical Crystallography and Biomineralization)
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8 pages, 7054 KiB  
Communication
Role of Longitudinal Temperature Gradients in Eliminating Interleaving Inclusions in Casting of Monocrystalline Silicon Ingots
by Lindong Li and Changbo Fu
Crystals 2024, 14(5), 471; https://doi.org/10.3390/cryst14050471 - 17 May 2024
Abstract
Infrared analysis reveals the presence of interwoven inclusions, primarily comprised of silicon nitride and silicon carbide, in the casting process of monocrystalline silicon ingots. This study investigates how the longitudinal temperature gradient affects the removal of inclusions during the casting of monocrystalline silicon [...] Read more.
Infrared analysis reveals the presence of interwoven inclusions, primarily comprised of silicon nitride and silicon carbide, in the casting process of monocrystalline silicon ingots. This study investigates how the longitudinal temperature gradient affects the removal of inclusions during the casting of monocrystalline silicon ingots through simulations and comparative experiments. Two monocrystalline silicon ingots were cast, each using different longitudinal temperature gradients: one employing smaller gradients and the other conventional gradients. CGSim (Version Basic CGSim 23.1) simulation software was utilized to analyze the melt flow and temperature distribution during the growth process of quasi–monocrystalline silicon ingots. The findings indicate that smaller longitudinal temperature gradients lead to a more robust upward flow of molten silicon at the solid–liquid interface, effectively carrying impurities away from this interface and preventing their inclusion formation. Analysis of experimental photoluminescence and IR results reveals that although inclusions may not be observed, impurities persist but are gradually displaced to the top of the silicon melt through a stable growth process. Full article
(This article belongs to the Special Issue Crystallization Process and Simulation Calculation, Second Edition)
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14 pages, 8409 KiB  
Article
Surface Enhancement of Titanium-Based Coatings on Commercial Hard Steel Cutting Tools
by Minh Nhat Dang, Surinder Singh, Hannah J. King, John H. Navarro-Devia, Hoang Le, Thomas G. Pattison, Rosalie K. Hocking, Scott A. Wade, Guy Stephens, Angelo Papageorgiou, Armando Manzano and James Wang
Crystals 2024, 14(5), 470; https://doi.org/10.3390/cryst14050470 - 17 May 2024
Abstract
This study investigates the mechanical properties, surface integrity, and chemical configuration of PVD-coated high-speed steel (HSS) cutting tools, with a particular focus on titanium nitride (TiN) and titanium aluminium nitride (TiAlN) coatings. A range of characterisation methodologies were employed to examine the impact [...] Read more.
This study investigates the mechanical properties, surface integrity, and chemical configuration of PVD-coated high-speed steel (HSS) cutting tools, with a particular focus on titanium nitride (TiN) and titanium aluminium nitride (TiAlN) coatings. A range of characterisation methodologies were employed to examine the impact of pre-coating surface conditions on the resulting coatings. This impact includes the effects of gas bubble production and unequal distribution of elements, which are two unwanted occurrences. Notwithstanding these difficulties, coatings applied on surfaces that were highly polished exhibited more consistency in their mechanical and elemental characteristics, with a thickness ranging from 2 to 4 µm. The study of mechanical characteristics confirms a significant increase in hardness, from an initial value of roughly 1000 HV0.5 for untreated tools to 1300 HV0.5 for tools with physical vapour deposition (PVD) coatings. Although PVD coatings produced on an industrial scale might not exceed the quality of coatings manufactured in a laboratory, they do offer substantial enhancements in terms of hardness. This study highlights the significant importance of thorough surface preparation in achieving enhanced coating performance, hence contributing to the efforts to prolong the lifespan of tools and enhance their performance even under demanding operational circumstances. Full article
(This article belongs to the Section Crystalline Metals and Alloys)
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2 pages, 136 KiB  
Editorial
Nanotechnology in Catalysis, 2nd Edition
by Maria J. Sabater
Catalysts 2024, 14(5), 331; https://doi.org/10.3390/catal14050331 - 17 May 2024
Abstract
Catalysis is considered a central field in nanoscience and nanotechnology, given that the use of nanoscale structures has played a central role in the development of nanomaterials such as catalysts (nanocatalysts) for decades [...] Full article
(This article belongs to the Special Issue Nanotechnology in Catalysis, 2nd Edition)
17 pages, 4179 KiB  
Article
A Wireless Noninvasive Blood Pressure Measurement System Using MAX30102 and Random Forest Regressor for Photoplethysmography Signals
by Michelle Annice Tjitra, Nagisa Eremia Anju, Dodi Sudiana and Mia Rizkinia
Computers 2024, 13(5), 125; https://doi.org/10.3390/computers13050125 - 17 May 2024
Abstract
Hypertension, often termed “the silent killer”, is associated with cardiovascular risk and requires regular blood pressure (BP) monitoring. However, existing methods are cumbersome and require medical expertise, which is worsened by the need for physical contact, particularly during situations such as the coronavirus [...] Read more.
Hypertension, often termed “the silent killer”, is associated with cardiovascular risk and requires regular blood pressure (BP) monitoring. However, existing methods are cumbersome and require medical expertise, which is worsened by the need for physical contact, particularly during situations such as the coronavirus pandemic that started in 2019 (COVID-19). This study aimed to develop a cuffless, continuous, and accurate BP measurement system using a photoplethysmography (PPG) sensor and a microcontroller via PPG signals. The system utilizes a MAX30102 sensor and ESP-WROOM-32 microcontroller to capture PPG signals that undergo noise reduction during preprocessing. Peak detection and feature extraction algorithms were introduced, and their output data were used to train a machine learning model for BP prediction. Tuning the model resulted in identifying the best-performing model when using a dataset from six subjects with a total of 114 records, thereby achieving a coefficient of determination of 0.37/0.46 and a mean absolute error value of 4.38/4.49 using the random forest algorithm. Integrating this model into a web-based graphical user interface enables its implementation. One probable limitation arises from the small sample size (six participants) of healthy young individuals under seated conditions, thereby potentially hindering the proposed model’s ability to learn and generalize patterns effectively. Increasing the number of participants with diverse ages and medical histories can enhance the accuracy of the proposed model. Nevertheless, this innovative device successfully addresses the need for convenient, remote BP monitoring, particularly during situations like the COVID-19 pandemic, thus making it a promising tool for cardiovascular health management. Full article
(This article belongs to the Special Issue Machine and Deep Learning in the Health Domain 2024)
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22 pages, 5829 KiB  
Article
Enhancing Brain Segmentation in MRI through Integration of Hidden Markov Random Field Model and Whale Optimization Algorithm
by Abdelaziz Daoudi and Saïd Mahmoudi
Computers 2024, 13(5), 124; https://doi.org/10.3390/computers13050124 - 17 May 2024
Abstract
The automatic delineation and segmentation of the brain tissues from Magnetic Resonance Images (MRIs) is a great challenge in the medical context. The difficulty of this task arises out of the similar visual appearance of neighboring brain structures in MR images. In this [...] Read more.
The automatic delineation and segmentation of the brain tissues from Magnetic Resonance Images (MRIs) is a great challenge in the medical context. The difficulty of this task arises out of the similar visual appearance of neighboring brain structures in MR images. In this study, we present an automatic approach for robust and accurate brain tissue boundary outlining in MR images. This algorithm is proposed for the tissue classification of MR brain images into White Matter (WM), Gray Matter (GM) and Cerebrospinal Fluid (CSF). The proposed segmentation process combines two algorithms, the Hidden Markov Random Field (HMRF) model and the Whale Optimization Algorithm (WOA), to enhance the treatment accuracy. In addition, we use the Whale Optimization Algorithm (WOA) to optimize the performance of the segmentation method. The experimental results from a dataset of brain MR images show the superiority of our proposed method, referred to HMRF-WOA, as compared to other reported approaches. The HMRF-WOA is evaluated on multiple MRI contrasts, including both simulated and real MR brain images. The well-known Dice coefficient (DC) and Jaccard coefficient (JC) were used as similarity metrics. The results show that, in many cases, our proposed method approaches the perfect segmentation with a Dice coefficient and Jaccard coefficient above 0.9. Full article
(This article belongs to the Special Issue Advanced Image Processing and Computer Vision)
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