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14 pages, 7505 KB  
Article
A Proposal for an Ultrasensitive Label-Free Optical BioMEMS Platform Based on a DBR-Michelson Interferometer for Cancer Detection and Therapeutic Applications
by Bocar Ndiaye, Naima Brahiti, Kazem Nouri, Taha Azad and Kian Jafari
Sensors 2026, 26(18), 5913; https://doi.org/10.3390/s26185913 (registering DOI) - 18 Sep 2026
Abstract
Early detection of cancer remains challenging due to the extremely low concentration of biomarkers present during initial disease stages. Dysregulation of key signaling pathways, including cyclin-dependent kinase (CDK) networks, drives uncontrolled cell proliferation and tumor progression, underscoring the need for highly sensitive, label-free [...] Read more.
Early detection of cancer remains challenging due to the extremely low concentration of biomarkers present during initial disease stages. Dysregulation of key signaling pathways, including cyclin-dependent kinase (CDK) networks, drives uncontrolled cell proliferation and tumor progression, underscoring the need for highly sensitive, label-free biosensing technologies. Conventional analytical methods such as ELISA and PCR offer reliable detection but require complex sample preparation, fluorescent labeling, and long processing times, limiting their suitability for rapid diagnostics. This work introduces a novel label-free Biological Micro-Opto-Electro-Mechanical System (BioMEMS) platform based on an unbalanced Michelson interferometer with DBR mirrors to interrogate the minute spectral shifts induced by biomolecular interactions. A microcantilever is suspended above a silicon-on-insulator (SOI) waveguide, where the specific binding of biomarkers generates compressive surface stress, causing a downward deflection that reduces the cantilever-to-waveguide gap. This displacement modulates the effective refractive index of the sensing arm through enhanced evanescent-field coupling. The resulting phase variation is further detected through the high-sensitivity Michelson interferometric architecture, enabling ultrasensitive spectral interrogation. Numerical simulations using COMSOL Multiphysics demonstrate a narrow full width at half maximum (FWHM) of 27.6 nm, a quality factor (Q) of 53.34, and an overall sensitivity of 75.74 µm/(N/m). These results highlight the potential of the proposed platform for early cancer detection and precise monitoring of dysregulated signaling pathways. Full article
(This article belongs to the Special Issue Advances in Biosensing and BioMEMS for Biomedical Engineering)
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32 pages, 6014 KB  
Review
Boosting Solar Cell Efficiency Through Plasma-Driven Light Management Strategies: A Review
by Shuayl Alotaibi, Awad M. Bakry, Lamiaa S. El-Sherif and Safwat Hassaballa
Sci 2026, 8(9), 246; https://doi.org/10.3390/sci8090246 - 7 Sep 2026
Viewed by 279
Abstract
Background: The optical losses in the form of reflections, parasitic absorption, and scattering limit photovoltaic efficiency. This review examines plasma-assisted surface engineering as an effective tool for improving light management in solar cells. Plasma-based methods, including etching, oxidation, deposition, and texturing, enable precise [...] Read more.
Background: The optical losses in the form of reflections, parasitic absorption, and scattering limit photovoltaic efficiency. This review examines plasma-assisted surface engineering as an effective tool for improving light management in solar cells. Plasma-based methods, including etching, oxidation, deposition, and texturing, enable precise control of surface morphology and chemistry, lowering reflectance, enhancing light trapping, and passivating defects. Methods: In contrast to wet-chemical or high-temperature processes, plasma processes are dry, low-temperature, scalable, and can be used with silicon, perovskite, thin-film, and organic solar cells, as well as tandem structures. The fundamentals of optical losses are described, along with the principles of radio-frequency (RF), inductively coupled plasma (ICP), microwave, and atmospheric plasma systems and their distinctive advantages for controlling ion and reactive-species generation. Key applications reviewed include black-silicon texturing by ICP reactive-ion etching (ICP-RIE), anti-reflective/passivation coatings by plasma-enhanced chemical vapor deposition (PECVD), and interface activation by atmospheric plasma. Results: Among performance improvements are a reflectance of less than 2%, a photocurrent increase of 10–20%, and longer carrier lifetime. Conclusions: The advantages of plasma compared to lithography and sol–gel processes are in the precision and affordability of the method. The difficulties include damage caused by the processing, uniformity over extensive areas, and environmental stress resistance. Future directions rely on low-temperature plasmas for flexible PV, machine-learning-guided process optimization, and hybrid plasma–laser systems. This synthesis of otherwise fragmented studies is intended to support the implementation of plasma-based methods in next-generation, high-efficiency, and sustainable solar production. Full article
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24 pages, 14935 KB  
Article
Interfacial Redox Engineering of TiO2 Nanocomposites Using Green Tea-Derived Ligands and Silver
by Valentina Nikšić, Dušan Sredojević, Miriama Malček Šimunková, Andrea Pirković, Ana Milivojević, Vlasta Brezová and Vesna Lazić
Molecules 2026, 31(17), 3123; https://doi.org/10.3390/molecules31173123 - 6 Sep 2026
Viewed by 331
Abstract
Titanium dioxide (TiO2) is a widely studied semiconductor whose interfacial redox properties strongly influence its photocatalytic and biological performance. In this work, TiO2 nanomaterials were surface-functionalized with green tea waste extract (GT) and subsequently impregnated with silver to obtain redox-active [...] Read more.
Titanium dioxide (TiO2) is a widely studied semiconductor whose interfacial redox properties strongly influence its photocatalytic and biological performance. In this work, TiO2 nanomaterials were surface-functionalized with green tea waste extract (GT) and subsequently impregnated with silver to obtain redox-active nanocomposites with tunable optical and biological properties. HPLC, FTIR, diffuse reflectance spectroscopy (DRS), and density functional theory (DFT) analyses demonstrated the formation of an organic–inorganic interface through adsorption of green tea-derived ligands. DFT calculations revealed complementary interfacial roles of the adsorbed constituents, with epigallocatechin gallate (EGCG) inducing interfacial charge-transfer (ICT) states that enable visible-light absorption, as reflected by the decrease in the apparent optical bandgap from ~3.48 eV for pristine TiO2 to ~1.83 eV for TiO2/EGCG. ICP-OES analysis further quantified the Ag loading in TiO2/GT/Ag at 5.1 wt%. Electron paramagnetic resonance (EPR) experiments demonstrated that GT functionalization shifts the interfacial redox balance toward radical scavenging by suppressing excessive radical generation, whereas silver incorporation partially restores oxidative pathways, particularly under irradiation. These differences in interfacial redox behavior directly translate into distinct biological responses. TiO2/GT/Ag showed the strongest antimicrobial activity, with visible-light enhancement observed predominantly against Staphylococcus aureus, while TiO2/GT/Ag reduced H2O2-induced oxidative stress in non-malignant cells and promoted intracellular reactive oxygen species generation in cancer cells. These findings demonstrate that engineering the organic–inorganic interface through plant-derived ligands and silver incorporation provides an effective strategy for tuning the interfacial redox properties and light-responsive biological performance of TiO2-based nanomaterials, thereby expanding their potential for antimicrobial and biomedical applications. Full article
(This article belongs to the Special Issue High-Value Utilization of Food and Agricultural By-Products)
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23 pages, 2701 KB  
Hypothesis
Modulation of Host Cell Death Signaling Platforms by Plasmodium falciparum: Implications for Eryptosis Regulation and Parasite Survival
by Lina Solís-Castillero, Ricardo Correa, Maria Fernanda Alves-Rosa and Carmenza Spadafora
Cells 2026, 15(17), 1603; https://doi.org/10.3390/cells15171603 - 3 Sep 2026
Viewed by 422
Abstract
Programmed cell death pathways in Plasmodium falciparum remain conceptually fragmented. Over decades, researchers have applied metazoan apoptotic, autophagic, and necrotic markers to this deep-branching protozoan, frequently clashing with the reality that the parasite lacks the canonical genetic machinery (such as true caspases or [...] Read more.
Programmed cell death pathways in Plasmodium falciparum remain conceptually fragmented. Over decades, researchers have applied metazoan apoptotic, autophagic, and necrotic markers to this deep-branching protozoan, frequently clashing with the reality that the parasite lacks the canonical genetic machinery (such as true caspases or death receptors) found in multicellular eukaryotes. In this work, we shift the focus from the parasite’s disputed intrinsic death machinery to the host–parasite interaction arena: the active manipulation of the host erythrocyte’s autonomous suicide program, eryptosis. The intraerythrocytic development of P. falciparum generates profound oxidative stress through hemoglobin digestion and free heme release, driving lipid peroxidation and the accumulation of reactive aldehydes such as 4-hydroxynonenal (4-HNE)—potent signaling molecules that can trigger eryptotic pathways. We integrate existing literature on membrane remodeling, protein export, and lipid raft dynamics to propose a novel Host Protein Sequestration Hypothesis. We suggest that P. falciparum evades splenic clearance by actively dismantling the host cell’s surface death signaling platforms—Clusters of Apoptotic Signaling Molecule-Enriched Rafts (CASMERs)—and pulling these host components inward. We suggest that human FAS (CD95) is internalized by the parasite and physically interacts with Plasmodium lipid-raft scaffolding proteins, preventing it from engaging FasL (CD178) that is either expressed on adjacent erythrocytes or presented within the local splenic microenvironment—an interaction that would otherwise precipitate eryptotic signaling. This perspective offers a fundamentally fresh conceptual framework for understanding malaria survival strategies and highlights a vulnerable, non-canonical therapeutic target. Full article
(This article belongs to the Section Cellular Pathology)
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19 pages, 4446 KB  
Article
Probe Cytotoxic and Oxidative Stress Effects of Nanoplastics on Caco-2 Cells: Insights from Raman Spectroscopy and Machine Learning
by Bryan Gustafson, Negar Kosari, Emily Brothersen, Morgan Mosher and Anhong Zhou
Sensors 2026, 26(17), 5375; https://doi.org/10.3390/s26175375 - 25 Aug 2026
Viewed by 417
Abstract
Nanoplastics and microplastics have become an increasing ecological and health concern due to their widespread presence in the environment and food chain. In this study, Caco-2 cells were used as an in vitro model of the human intestinal epithelium to investigate the cytotoxic [...] Read more.
Nanoplastics and microplastics have become an increasing ecological and health concern due to their widespread presence in the environment and food chain. In this study, Caco-2 cells were used as an in vitro model of the human intestinal epithelium to investigate the cytotoxic effects of polystyrene nanoparticles and microparticles of varying sizes, concentrations, and surface modification. Oxidative stress and apoptosis were evaluated following particle exposure. Raman spectroscopy, combined with machine learning analysis, was employed to detect and characterize biochemical alterations in the cells. Several peak ratios were selected to cluster data depending on size. A correlation between apoptosis and both concentration and Raman score was established highlighting its potential as a non-invasive tool to monitor nanoparticle-induced cellular damage. Resveratrol pretreatment reduced some of these harmful effects of amine-modified nanoplastics, reducing reactive oxygen species generation. This study demonstrates the potential of combining Raman spectroscopy and machine learning to assess the cytotoxic effects of micro- and nanoplastics and identifies protective strategies such as antioxidant pretreatment. Full article
(This article belongs to the Section Biosensors)
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31 pages, 10646 KB  
Article
In Silico Evaluation of Mechanobiological Parameters Under Variable Flow in Three-Dimensional Microfluidic Platforms Supporting Future Cell Migration Studies
by Juan M. Munoz, Nicole M. E. Valle, Camilla M. Liu, Arielly H. Alves, Giovana F. Pileggi, Javier B. Mamani, Mariana F. Costa, Keithy F. da Silva, Marta C. S. Galanciak, Gabriel M. Rosário, Marcelo N. P. Carreño, Mariana P. Nucci, Alejandro Sosnik and Lionel F. Gamarra
Biomedicines 2026, 14(9), 1879; https://doi.org/10.3390/biomedicines14091879 - 23 Aug 2026
Viewed by 414
Abstract
Background: Cell migration is a biological process influenced by biochemical signals and mechanical stimuli from the microenvironment. In this context, the accurate characterization of the mechanical microenvironment generated within microfluidic platforms represents an essential step for the design and interpretation of cell migration [...] Read more.
Background: Cell migration is a biological process influenced by biochemical signals and mechanical stimuli from the microenvironment. In this context, the accurate characterization of the mechanical microenvironment generated within microfluidic platforms represents an essential step for the design and interpretation of cell migration studies. Understanding how hydrodynamic forces influence the mechanical microenvironment experienced by cells remains a challenge, especially in confined and biomimetic systems. Methods: In this study, a three-dimensional microfluidic device was developed in silico to characterize the effects of flow variation on mechanofluidic parameters and to provide a quantitative basis for designing future cell-migration experiments. Computational fluid dynamics simulations were performed to characterize the velocity, pressure, and wall shear stress (WSS) distributions under different inlet flow rates (0.5, 1, and 5 µL/min) and three distinct inlet/outlet configurations within the same three-dimensional geometry. Rigid hemispherical probe structures were incorporated into the model to quantify the local shear stress acting on cell-sized surfaces. Results: The results demonstrated a direct and linear relationship between the applied flow rate and the WSS, modulated by the channel geometry and the inlet and outlet configuration. Regions near micropores and lateral channels showed high WSS values, while central regions experienced less mechanical stimulation, depending on flow conditions. Comparison with WSS values and ranges associated with cellular responses reported in the literature indicated that certain operational configurations generated mechanical conditions comparable to those previously investigated in cell-based studies, including cell migration applications. Conclusions: Overall, the study highlights the importance of controlling flow conditions in microfluidic platforms and provides a quantitative basis for the development and optimization of three-dimensional microfluidic devices intended for designing future cell-migration experiments. The systematic comparison of three inlet/outlet configurations across three flow rates within the same three-dimensional geometry provides a comparative framework for identifying configuration-dependent changes in the local mechanofluidic environment, supporting the selection of operational conditions for future mechanobiological and cell-migration studies. Full article
(This article belongs to the Special Issue Innovative Approaches in In Vitro Models: From Design to Application)
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12 pages, 7150 KB  
Communication
Surface-Stress-Induced Lattice Distortion in Nanolamellar Cementite
by Marek Gocnik, Maximilian Graf, Peter Kunnas, Anna Sophie Jelinek, Daniel Marian Ogris, Ronald Schnitzer and Jozef Keckes
Materials 2026, 19(16), 3431; https://doi.org/10.3390/ma19163431 - 13 Aug 2026
Viewed by 332
Abstract
Cementite morphology is known to govern the mechanical performance of steels, yet its influence on actual crystal structure, like unit cell parameters, is not well quantified. Here, we show that cementite morphology-dependent surface stresses generate measurable lattice distortion in nanocrystalline cementite. Lamellar and [...] Read more.
Cementite morphology is known to govern the mechanical performance of steels, yet its influence on actual crystal structure, like unit cell parameters, is not well quantified. Here, we show that cementite morphology-dependent surface stresses generate measurable lattice distortion in nanocrystalline cementite. Lamellar and spheroidized cementite powders were extracted from a Cr-alloyed hypereutectoid steel and characterized by high-energy synchrotron X-ray diffraction combined with double-Voigt profile modeling. Despite a higher Cr content in spheroidized cementite, lamellar cementite exhibits systematically larger lattice parameters, corresponding to an average volumetric lattice strain of 6.3 ± 2.2 × 10−4. This counter-intuitive expansion is rationalized by a continuum mechanics framework that incorporates the orthorhombic elastic anisotropy of cementite and particle morphology. The model predicts the sign and magnitude of morphology-induced lattice strain, demonstrating that surface-stress effects constitute a systematic bias in diffraction-derived lattice parameters of nanostructured carbides. Full article
(This article belongs to the Section Advanced Materials Characterization)
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28 pages, 6470 KB  
Review
Plasma-Enhanced Atomic Layer Deposition of III-Nitride Thin Films and Heterostructures: Mechanisms and Applications
by Sanjie Liu, Zilong Zeng, Yongyong Cao, Zhenyi Deng, Xinjie Li, Zixin Liang, Rongjie Feng, Jiaping Long, Yu Liu, Ruifan Tang and Xinhe Zheng
Crystals 2026, 16(8), 521; https://doi.org/10.3390/cryst16080521 - 8 Aug 2026
Viewed by 425
Abstract
Group III-nitride semiconductors (GaN, AlN, InN) serve as foundational materials for modern optoelectronics, high-frequency microelectronics, and next-generation energy harvesting devices. However, traditional high-temperature epitaxy (>700 °C) introduces severe thermal stress, high dislocation densities, and fundamental incompatibility with flexible substrates or CMOS back-end-of-line (BEOL) [...] Read more.
Group III-nitride semiconductors (GaN, AlN, InN) serve as foundational materials for modern optoelectronics, high-frequency microelectronics, and next-generation energy harvesting devices. However, traditional high-temperature epitaxy (>700 °C) introduces severe thermal stress, high dislocation densities, and fundamental incompatibility with flexible substrates or CMOS back-end-of-line (BEOL) processes. Plasma-enhanced atomic layer deposition (PEALD) provides a disruptive, ultra-low thermal budget (<300 °C) pathway for atomic-scale precision growth and conformal coating. This review systematically summarizes recent frontiers in PEALD-synthesized Group III-nitrides and 2D/3D polar heterostructures. First, we dissect the microscopic nucleation kinetics, surface bond reconstruction, and impurity suppression mechanisms across diverse substrates, including Si, sapphire, quartz, metals, and flexible polymers. Next, we highlight 2D template-assisted van der Waals epitaxy on graphene and MoS2, and elucidate polarization-driven dipole interactions and band alignment engineering at 2D/3D polar interfaces (e.g., α-In2Se3, Janus MoSSe). Furthermore, we comprehensively discuss innovative applications in advanced photovoltaics (as electron transport and passivation layers in perovskite and quantum dot-sensitized solar cells), silicon-based microcavity lasers, high-electron-mobility transistors (HEMTs), and flexible multimodal sensors. Finally, key technological challenges—including the low-thermal-budget paradox, wafer-scale uniformity, and deposition throughput—are addressed alongside future perspectives in area-selective ALD and neuromorphic computing, presenting a cohesive blueprint from underlying physics to macroscopic system integration. Full article
(This article belongs to the Special Issue Advances in Wide Bandgap Semiconductor Materials)
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30 pages, 3280 KB  
Review
Helping Apo2L/TRAIL in the Battle: Synergistic Therapeutic Approaches for Cancer Therapies
by Elena Valeria Fuior, Madalina Dumitrescu, Marius Gabriel Multescu, Bianca Sanziana Daraban, Madalin Ghinea, Oana Mirancea, George E. D. Petrescu, Felix Mircea Brehar, Ana Maria Vacaru, Radu Ionita, Violeta Georgeta Bivol, Irina Florina Tudorache, Andreea Popa, Ioana Madalina Fenyo, Evangelia Zvintzou and Anca Violeta Gafencu
Int. J. Mol. Sci. 2026, 27(16), 7068; https://doi.org/10.3390/ijms27167068 - 7 Aug 2026
Viewed by 571
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers apoptosis in malignant, infected, or stressed cells while sparing normal tissues, making it an attractive therapeutic candidate. However, many tumors exhibit intrinsic or acquired resistance to TRAIL, driven by reduced DR4/DR5 surface expression, elevated decoy [...] Read more.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively triggers apoptosis in malignant, infected, or stressed cells while sparing normal tissues, making it an attractive therapeutic candidate. However, many tumors exhibit intrinsic or acquired resistance to TRAIL, driven by reduced DR4/DR5 surface expression, elevated decoy receptor levels, dysregulated DISC assembly, overexpression of c-FLIP and anti-apoptotic Bcl-2 family proteins, or activation of survival pathways such as NF-κB, PI3K/Akt, and MAPK. Moreover, TRAIL receptors can initiate non-canonical signaling pathways that promote migration, invasion, and metastasis in specific oncogenic contexts, thereby further limiting therapeutic efficacy. We aimed to integrate mechanistic insights into TRAIL biology with current therapeutic advances, providing a comprehensive framework for understanding resistance and for designing rational TRAIL-based combination strategies. We summarized the structural and signaling features of TRAIL receptors, outlined the major determinants of TRAIL sensitivity, and evaluated predictive biomarkers that may guide patient selection. In addition, we examined next-generation TRAIL agonists and targeted delivery systems developed to enhance receptor clustering, pharmacokinetics, and tumor specificity. Together, these insights highlight the therapeutic promise of mechanistically informed TRAIL combinations. A deeper understanding of resistance pathways and biomarker-guided stratification will be essential for restoring apoptotic competence and improving clinical outcomes. Full article
(This article belongs to the Special Issue Anticancer Drugs: Current Status and Future Directions)
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11 pages, 2479 KB  
Article
Cavitating Electrohydrodynamic Flow in the Vicinity of a Bio-Inspired Electrode Surface
by Jing Li, Alexander Hernandez, Beatrice Boatemaa and Xuewei Zhang
Biomimetics 2026, 11(8), 557; https://doi.org/10.3390/biomimetics11080557 - 5 Aug 2026
Viewed by 265
Abstract
Electrostrictive cavitation is a mechanism of the electrical breakdown of dielectric liquids under nanosecond pulsed high voltages and a promising way of controlled nanoscale cavity generation. To better understand electrostrictive cavitation in water, this work develops a cavitating electrohydrodynamic model to simulate the [...] Read more.
Electrostrictive cavitation is a mechanism of the electrical breakdown of dielectric liquids under nanosecond pulsed high voltages and a promising way of controlled nanoscale cavity generation. To better understand electrostrictive cavitation in water, this work develops a cavitating electrohydrodynamic model to simulate the distribution of tensile stress. Compared with the continuum electrohydrodynamic model, the tensile stress from the new model is reduced wherever cavitation has initiated. Further, an innovative electrode design concept inspired by the cell membrane is proposed, in which the electrode is hollow with a permeable enclosure, allowing liquid flow in response to a pressure difference between the interior and the outside. The simulations based on the cavitating electrohydrodynamic model suggest that this electrode design results in even lower tensile stress near the high-voltage electrode surface and holds potential to suppress cavitation and subsequent electrical breakdown. Full article
(This article belongs to the Section Biomimetic Surfaces and Interfaces)
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35 pages, 3326 KB  
Review
Coronary Calcified Nodules: From Pathological Definitions to Intravascular Imaging- and Morphology-Guided PCI
by Mateusz Lucki, Sylwia Iwańczyk, Ewa Lucka, Marek Grygier, Przemysław Mitkowski and Maciej Lesiak
Int. J. Mol. Sci. 2026, 27(15), 6999; https://doi.org/10.3390/ijms27156999 - 4 Aug 2026
Viewed by 690
Abstract
Coronary artery calcification (CAC) is a hallmark of advanced atherosclerosis and a major determinant of procedural complexity during percutaneous coronary intervention (PCI). Once considered a passive consequence of vascular degeneration, CAC is now recognized as an active, highly regulated process driven by inflammation, [...] Read more.
Coronary artery calcification (CAC) is a hallmark of advanced atherosclerosis and a major determinant of procedural complexity during percutaneous coronary intervention (PCI). Once considered a passive consequence of vascular degeneration, CAC is now recognized as an active, highly regulated process driven by inflammation, oxidative stress, extracellular vesicle release, osteogenic differentiation of vascular smooth muscle cells, and biomechanical remodeling. These mechanisms generate a spectrum of calcific phenotypes, ranging from microcalcifications and sheet calcium to nodular calcium and calcified nodules. Calcified nodules represent an advanced fibrocalcific plaque phenotype characterized by fractured calcific plates, luminal calcium protrusion, surface disruption, and variable thrombus formation. They can be characterized using intravascular ultrasound (IVUS), optical coherence tomography (OCT), and hybrid near-infrared spectroscopy–IVUS imaging, and are associated with coronary thrombosis, stent underexpansion, restenosis, target lesion failure, and the need for advanced calcium-modification strategies. A structured literature search of PubMed/MEDLINE, Web of Science Core Collection, and Scopus identified 83 publications published between 2020 and 2026 for inclusion in the narrative synthesis. This narrative review summarizes the biological and biomechaniclam mechanisms of coronary calcification and calcified nodule formation, compares multimodality intravascular imaging criteria, and discusses contemporary imaging-guided PCI strategies, including balloon-based modification, rotational and orbital atherectomy, excimer laser coronary atherectomy, intravascular lithotripsy, and hybrid approaches. By integrating pathobiology, intravascular imaging criteria, and lesion-specific PCI strategies, this review provides a clinically oriented framework for the assessment and management of calcified nodules. Future directions include standardized imaging definitions, prospectively validated morphology-guided treatment algorithms, and computational and artificial intelligence-assisted plaque characterization. Full article
(This article belongs to the Special Issue Advances in Pathophysiology and Treatment of Atherosclerosis)
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19 pages, 2960 KB  
Review
Cardiolipin as a Signaling Hub: Evolutionary Conservation and Programmable Platforms Coupling Mitochondrial Stress to Cell Fate
by Patrice X. Petit
Int. J. Mol. Sci. 2026, 27(15), 6868; https://doi.org/10.3390/ijms27156868 - 31 Jul 2026
Viewed by 426
Abstract
Cardiolipin (CL), a dimeric phospholipid with four acyl chains and a small polar head group, is one of the most striking examples of evolutionary continuity in cell biology. Present in the plasma membrane of α-proteobacteria and retained without fundamental modification in the inner [...] Read more.
Cardiolipin (CL), a dimeric phospholipid with four acyl chains and a small polar head group, is one of the most striking examples of evolutionary continuity in cell biology. Present in the plasma membrane of α-proteobacteria and retained without fundamental modification in the inner mitochondrial membrane (IMM) of every eukaryote examined, CL has persisted across roughly two billion years of evolution, a period over which the mitochondrion shed the great majority of its ancestral genes. This review develops, as an organizing hypothesis rather than an established fact, the proposal that CL acts as a programmable signaling hub: a lipid whose physical chemistry and membrane address allow it to nucleate distinct supramolecular platforms in response to discrete stress signals, each platform coupling a specific mitochondrial state to a defined cell fate outcome. Three CL-dependent platforms are examined, together with a fourth, emerging axis, and the evidence supporting each is explicitly graded. Platform 1, the catalytic peroxidase platform, converts the constitutive CL–cytochrome c (cyt c) structural complex into an enzymatic reaction under oxidative stress, generating oxidized CL (oxCL) species that contribute to cyt c release from the IMM; this platform is the best supported of the four. Platform 2, the receptor-like mitophagy platform, exploits NME4-dependent CL scramblase activity to translocate CL from the IMM to the outer mitochondrial membrane (OMM) surface upon membrane potential dissipation, creating an externalized “eat-me” signal recognized by LC3-II; the evidence here is moderate and largely cell-based. Platform 3, the caspase-8/BID activation platform, is proposed to assemble a CL microdomain scaffold at the OMM that recruits caspase-8, markedly accelerates BID cleavage, and couple extrinsic apoptotic signals to mitochondrial outer membrane permeabilization (MOMP); this model rests substantially on reconstituted systems and requires further validation in intact cells and in vivo. A fourth, still-debated axis links CL externalization to innate immune activation through NLRP3 recruitment, for which alternative membrane-recruitment models exist. The argument advanced here is that the conservation of CL is unlikely to be explained by its structural roles alone, although those roles are themselves sufficient to impose strong selection; disentangling structural from signaling contributions remains an open problem, and the comparative genomic work needed to do so has not yet been performed. Full article
(This article belongs to the Special Issue Oxidative Stress and Mitochondrial Dysfunction in Human Diseases)
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22 pages, 1142 KB  
Review
Refractory Celiac Disease: Nutritional Failure, Immune Dysregulation, and Lymphomagenesis
by Ioanna Aggeletopoulou, Ploutarchos Pastras, Maria Kalafateli and Christos Triantos
Nutrients 2026, 18(15), 2479; https://doi.org/10.3390/nu18152479 - 31 Jul 2026
Viewed by 810
Abstract
Refractory celiac disease (RCeD) is a rare but severe complication of celiac disease characterized by persistent or recurrent malabsorptive symptoms and villous atrophy despite a strict gluten-free diet, after exclusion of ongoing gluten exposure, alternative enteropathies, and overt lymphoma. RCeD comprises two biologically [...] Read more.
Refractory celiac disease (RCeD) is a rare but severe complication of celiac disease characterized by persistent or recurrent malabsorptive symptoms and villous atrophy despite a strict gluten-free diet, after exclusion of ongoing gluten exposure, alternative enteropathies, and overt lymphoma. RCeD comprises two biologically distinct entities. RCeD-I is associated with phenotypically normal, polyclonal intraepithelial lymphocytes and generally reflects persistent gluten-independent mucosal inflammation with a relatively favorable prognosis. RCeD-II is defined by expansion of aberrant clonal intraepithelial lymphocytes lacking normal surface T-cell markers and is increasingly regarded as a low-grade intraepithelial lymphoma or in situ lymphomatous disorder, with substantial risk of progression to enteropathy-associated T-cell lymphoma (EATL). Mechanistic studies identify epithelial stress, IL-15-driven IEL survival, stromal and innate immune amplification, and cytotoxic epithelial injury as central drivers of refractory mucosal damage. In RCeD-II, aberrant IELs acquire a hybrid T/NK-like phenotype, persist through anti-apoptotic IL-15/JAK–STAT signaling, and induce enterocyte killing, while molecular alterations involving JAK1, STAT3, JAK/STAT regulators, NF-κB signaling, epigenetic regulators, and chromosomal abnormalities support stepwise lymphomagenesis. Recent single-cell multiomic studies further reveal genetically altered intestinal lymphocyte clones and intratumoral heterogeneity across the RCeD-II–EATL continuum. From a nutritional immunology perspective, RCeD illustrates a setting in which removal of the initiating dietary antigen is insufficient to restore mucosal immune homeostasis. This review summarizes the pathogenic processes that distinguish RCeD-I from RCeD-II and link failed mucosal recovery after gluten withdrawal to persistent immune-mediated epithelial injury, aberrant IEL expansion, clonal evolution, and lymphoma progression. Full article
(This article belongs to the Special Issue Nutrition and Immune Modulation in Autoimmune Diseases)
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40 pages, 17882 KB  
Article
Long-Term Climate Variability and Photovoltaic Energy Potential for Sustainable Hospital Infrastructure in Türkiye: A Multi-Method Assessment
by Youssef Kassem, Hüseyin Gökçekuş and Dündar Arif Ekinci
Energies 2026, 19(15), 3589; https://doi.org/10.3390/en19153589 - 30 Jul 2026
Viewed by 552
Abstract
The main objective of the current study is to assess the techno-economic feasibility, climate change adaptability, and sustainability of photovoltaic energy systems in six large hospitals in Turkey (Adana, Başakşehir, Bursa, Elazig, Gaziantep, and Yozgat) to achieve United Nations recommendations as Sustainable Development [...] Read more.
The main objective of the current study is to assess the techno-economic feasibility, climate change adaptability, and sustainability of photovoltaic energy systems in six large hospitals in Turkey (Adana, Başakşehir, Bursa, Elazig, Gaziantep, and Yozgat) to achieve United Nations recommendations as Sustainable Development Goal 7 (affordable and clean energy) and Sustainable Development Goal 13 (climate action). This study aims to determine the impact of long-term climate change on the availability of photovoltaic (PV) energy resources. To achieve this goal, this research was conducted through a multi-step approach combining (1) the detection of long-term climate trends using linear regression on the TerraClimate database, (2) the spatial analysis of photovoltaic solar energy potential using high-resolution satellite imagery (Google Maps) for roof suitability and parking areas, (3) the estimation of photovoltaic electricity generation and the calculation of the capacity factor, (4) the application of the Response Surface Methodology (RSM) based on NASA Giovanni data to model the nonlinear reciprocal relationships between precipitation (R), aerosol optical thickness (AOT), photovoltaic solar energy production, and (5) the techno-economic analysis using the Levelized energy cost (LCOE), payback period, and CO2 emission reductions. The results show statistically consistent warming trends across all sites with trends for Tmax ranging from +0.0205 to +0.0268 °C/year and for Tmin from +0.0208 to +0.0300 °C/year. The temperature of PV cells increases at a rate of +0.0197 °C/year and the wind speed decreases by −0.0031 to −0.0149 m/s/year, which indicates a reduction in convective cooling. Solar radiation, on the other hand, is relatively constant with small trends ranging from +0.0002 to +0.0566 W/m2/year, and confirms the consistent solar resource availability. Seasonal PV resource potential varies from ~70–95 W/m2 in winter to 290–310 W/m2 in summer. Furthermore, the installed PV capacities are between 6 MW (Yozgat) and 47 MW (Başakşehir) with capacity factors of 17.0–19.7% and payback periods of 4.31–4.88 years. RSM models have high explanatory power (R2 = 0.57–0.74) with AOT as the most important negative driver of PV performance. Consequently, the results show that while the solar resource of Türkiye is stable and highly exploitable, PV efficiency is increasingly determined by climate-induced thermal stress and reduced wind cooling. The study highlights the economic viability, environmental advantages, and strategic relevance of PV systems at hospitals for resilient, low-carbon healthcare infrastructure in future climate scenarios. Full article
(This article belongs to the Topic Building Energy and Environment, 3rd Edition)
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Review
Bacterial Sentience Is Determined by the Stochastic, Chaotic, and Deterministic Behavior of Cytoplasmic Particles
by Leon M. T. Dicks, Carolina Pohl and Alfred Botha
Curr. Issues Mol. Biol. 2026, 48(8), 777; https://doi.org/10.3390/cimb48080777 - 30 Jul 2026
Viewed by 316
Abstract
Bacteria are constantly exposed to stress, which intensifies as cells age, nutrients are depleted, and metabolite levels change. As metabolic activity increases, the cytoplasm transitions from a glass-like to a more fluid state, supporting the stochastic (spontaneous) and chaotic (nonlinear and unpredictable) movement [...] Read more.
Bacteria are constantly exposed to stress, which intensifies as cells age, nutrients are depleted, and metabolite levels change. As metabolic activity increases, the cytoplasm transitions from a glass-like to a more fluid state, supporting the stochastic (spontaneous) and chaotic (nonlinear and unpredictable) movement of particles. The rate at which suspended particles or those in vacuole-like “cages” move depends on the cytoplasm’s energized and fluidic state. Cells respond to stochastic and chaotic behavior by regulating gene transcription, translation, and post-translational modifications. These stochastic and chaotic reactions generate a liquid–liquid phase separation (LLPS), causing particles to separate. This produces a dynamic force that drives cytoplasmic “turnover”. Internal and external physicochemical changes are monitored by chemoreceptors on the cell surface and embedded in the cell membrane, which activate transcriptional regulators to control gene expression, modulate enzymatic fluctuations, and regulate post-translational modifications. Sentience may also arise from the quantum-like behavior of ions, electrons, neutrons, and protons (tunneling and entanglement) and from hyperstructures that drive complex enzymatic reactions. This is, however, a highly debated topic. We argue that bacteria are conscious and do not rely solely on phosphorylation states, as in two-component systems (TCSs), but also on other cytoplasmic dynamics. We provide several examples to support the argument. It is, however, important to note that bacterial consciousness cannot be compared to that of higher life forms with a central nervous system. We refer to bacteria’s awareness of their environment as sentience and define bacterial sentience as the ability to respond to external stimuli and to reactions within a dynamic cytoplasm, thereby transferring signals either directly or via signal transduction pathways to turn gene expression on or off. We also point out that stochastic/chaotic randomness keeps the cytoplasm in a permanently dynamic, flexible, and stochastic state, safeguarding the cell against sudden, unpredictable environmental changes. Full article
(This article belongs to the Special Issue Latest Review Papers in Molecular Biology 2026)
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