Saved Queries

Exploring the spatial correlation network (SCN) characteristics and influencing factors of the eco-efficiency of cultivated land use (ECLU) in Xinjiang’s counties is crucial for clarifying inter-regional spatial mechanisms and supporting cross-regional collaborative governance. Using a panel dataset covering 85 counties across Xinjiang, this study adopts the super-efficiency SBM model, revised gravity model, social network analysis and QAP model to quantify ECLU, and further investigate its spatial network features as well as driving mechanisms. The results showed that: (1) ECLU exhibited a fluctuating upward trend with significant regional differentiation, and northern Xinjiang performed notably better than southern Xinjiang. (2) SCN remained connected overall, but network density was low, average path length was long, and spatial transmission efficiency was relatively low. (3) Regional differences in economic levels, labor productivity, and industrial structure all had positive effects on the formation of the SCN throughout the study period. Regional differences in fiscal support for agriculture had positive effects only in 2014 and 2017, while differences in the soil and water coordination ratio had a negative effect in 2021. Future policies for sustainable cultivated land use should be differentiated and zone-specific, based on each county’s role within the correlation network, to promote coordinated improvement of ECLU across counties. Full article

(This article belongs to the Special Issue From Quantity Control to Quality Improvement: Evolving Paths of Agricultural Land Protection and Utilization)

34 pages, 2393 KB

Open AccessReview

Targeting Fungal Adaptive Networks and Emerging Molecular Targets for Next-Generation Antifungal Therapeutics

by Conrad C. Achilonu

Drugs Drug Candidates 2026, 5(3), 47; https://doi.org/10.3390/ddc5030047 (registering DOI) - 22 Aug 2026

Abstract

The global emergence of multidrug-resistant fungal pathogens, including Candida auris, Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans, and Pneumocystis jirovecii, poses a growing threat to public health, particularly among immunocompromised individuals. The limited number of available antifungal drug classes and the rapid evolution of resistance mechanisms, including target-site mutations, efflux pump activation, biofilm formation, metabolic adaptation, and stress-response signaling, have substantially reduced treatment efficacy. This review provides a comprehensive overview of current antifungal therapies, their limitations, and emerging molecular targets for next-generation antifungal drug discovery. We highlight promising targets involved in fungal cell wall biosynthesis, membrane integrity, mitochondrial metabolism, virulence regulation, and host–pathogen interactions, emphasizing their interconnected roles within adaptive resistance networks. Attention is given to small-molecule isothiazolone-based inhibitors, including phosphoglucomutase-targeting compounds, as novel candidates capable of disrupting multiple fungal survival pathways. We further discuss advances in combination therapies, anti-virulence approaches, nanotechnology-based delivery systems, and artificial intelligence-driven drug discovery pipelines that integrate multi-omics data, structural modeling, molecular docking, and virtual screening to accelerate therapeutic development. These advances support a transition from conventional single-target strategies toward systems-level, precision-guided antifungal therapies, providing a framework for overcoming multidrug resistance and improving clinical outcomes in invasive fungal infections. Full article

(This article belongs to the Special Issue Microbes and Medicines)

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22 pages, 2891 KB

Open AccessArticle

Investigation into the Energy Performance of a Pump-Turbine Under High-Load Conditions: Energy Loss and Output Power Decline

by Lingkai Zhu, Kai Liang, Yunkuan Yu, Ziwei Zhong, Zhiqiang Gong, Junshan Guo, Huixiang Chen and Kan Kan

Appl. Sci. 2026, 16(17), 8372; https://doi.org/10.3390/app16178372 (registering DOI) - 22 Aug 2026

Abstract

Pump-turbines often experience performance deterioration under high-load conditions beyond their best efficiency point, while the underlying flow mechanisms remain insufficiently understood. In this study, we investigate the relationship between internal flow structures and energy performance in a pump-turbine operating at a rated head of 202 m over a range of guide vane openings. Energy losses are evaluated using an average kinetic energy-based method and compared with an entropy production approach. A threshold-independent rigid vorticity method is adopted for vortex identification, and a streamline-based coordinate system is introduced for spatial quantification of energy loss and blade loading. The results show that hydraulic losses are mainly concentrated in the draft tube (66–75%) and runner (25–30%) under high-load conditions. A coupled vortex system formed by separation vortices and horseshoe vortices governs localized dissipation in the runner. In the draft tube, a columnar vortex rope generates strong shear layers that dominate energy loss in the cone and elbow regions. At high flow rates, negative incidence induces pressure-side separation, forming negative torque regions that reduce net runner torque and lead to output power deterioration. These findings highlight the dominant role of coupled vortex structures and pressure redistribution in performance degradation under high-load operation. Full article

13 pages, 15636 KB

Open AccessFeature PaperArticle

Prediction of Suitable Habitats for the Critically Endangered Species Araucaria angustifolia Under Climate Change

by Na He, Lianrong Hu, Zhixiao Zhang, Ling Liu, Jinping Shao and Jing Pang

Diversity 2026, 18(9), 503; https://doi.org/10.3390/d18090503 (registering DOI) - 22 Aug 2026

Abstract

Araucaria angustifolia (Bertol.) Kuntze, a critically endangered tree species, plays an irreplaceable ecological role in its native habitats. Under global climate change, identifying the drivers governing its geographic distribution and assessing climate-related threats can provide scientific guidance for the long-term conservation and habitat restoration of this species. In this study, a total of 287 valid occurrence records from 27 countries were compiled. Combined with 14 screened environmental variables, an optimized Maximum Entropy (MaxEnt) model was used to predict the potential suitable habitats of A. angustifolia under historical climate conditions (1970–2000), as well as under low-emission (SSP126) and high-emission (SSP585) scenarios for the future periods of 2050, 2070, and 2090. Under historical climatic conditions, the average training AUC value from 10 replicate model runs was 0.979, indicating excellent and reliable model performance. Globally, the species has 1.91 × 10⁶ km² of moderately suitable habitat and 0.95 × 10⁶ km² of highly suitable habitat, with a total suitable habitat area of 2.86 × 10⁶ km², accounting for only 1.92% of the global terrestrial area. Mean annual temperature (bio1), mean temperature of the coldest quarter (bio11), and annual temperature range (bio7) are the dominant environmental variables shaping the distribution of A. angustifolia, followed by annual precipitation (bio12). Under future climate scenarios, the overall suitable habitats of A. angustifolia exhibit a slight contracting trend, whereas their spatial distribution patterns remain relatively stable. Full article

(This article belongs to the Special Issue Plant Adaptation and Survival Under Global Environmental Change)

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15 pages, 2278 KB

Open AccessArticle

Machine Learning-Driven Drug Repositioning Identifies Putative IRAK4 Inhibitors Through Structure-Based Computational Evaluation

by Hyewon Na, Juwon Park and Jiwon Choi

Curr. Issues Mol. Biol. 2026, 48(9), 855; https://doi.org/10.3390/cimb48090855 (registering DOI) - 22 Aug 2026

Abstract

Interleukin-1 receptor-associated kinase 4 (IRAK4) is one of the IRAK family proteins and plays an important role in the regulation of innate and inflammatory responses. In particular, IRAK4 acts as a key regulator of the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling pathways and has attracted attention as a therapeutic target for immune and inflammatory diseases. In this study, an integrated computational approach combining machine learning, molecular docking, and molecular dynamics simulations was applied to identify putative IRAK4 inhibitor candidates. Bioactivity data of IRAK4 were obtained from the ChEMBL and PubChem databases and evaluated for multiple binary classification models. The optimized XGBoost model based on ECFP4 and PubChem fingerprints achieved an ROC-AUC of 0.996 and an average precision (AP) of 0.991 on the independent test set. After that, 20 candidate compounds with high predictive probability score were finally selected through subsequent screening of the DrugBank database. Among them, DB12168 (MK-0557), DB15040 (TP-271), and DB18152 (Zilurgisertib) exhibited favorable binding free energies and stable complex formation with IRAK4 through molecular dynamics simulations and MM-PBSA calculations. Overall, these results demonstrate that approaches incorporating machine learning and structure-based computational analysis can be useful for discovering and prioritizing potential IRAK4 inhibitor candidates. Full article

(This article belongs to the Special Issue Novel Drugs and Natural Products Discovery—2nd Edition)

20 pages, 5451 KB

Open AccessArticle

Asymmetric Connectivity Between Redox-Active Tyrosines and Reaction-Center Chlorophylls in Photosystem II

by Shalini Yadav and Dimitrios A. Pantazis

Plants 2026, 15(17), 2557; https://doi.org/10.3390/plants15172557 (registering DOI) - 22 Aug 2026

Abstract

Photosystem II (PSII) contains several cofactors involved in light harvesting, charge separation, electron transfer, and catalysis. The initial charge separation in the reaction center of PSII creates the strongest known redox-cofactor oxidant in biology, a cationic radical distributed over a “special pair” of chlorophyll molecules (P680^•+). Two redox-active tyrosines, Y_Z and Y_D, located at opposite sides of the special pair, are the principal residues that reduce this cationic radical. Y_Z, in turn, oxidizes the manganese cluster of the oxygen-evolving complex to drive water oxidation, whereas Y_D forms a stable radical facilitated by local water translocation. The details of this asymmetry and the role of nearby protein residues in mediating branch-specific electron/hole-transfer pathways remain incompletely understood. Here, we investigate pathways for electron transfer (ET) from Y_Z and Y_D to P680^•+ and identify specific residues that are likely responsible for mediating ET. Graph-based analysis predicts aromatic residue-assisted pathways on both branches but also reveals a distinct tryptophan (D2-Trp191) that connects Y_D with P680^•+, whereas the corresponding D1-side position is occupied by a non-aromatic D2-Ile192. This suggests a possible role of this tryptophan as an ET mediator, thereby differentiating the nature of electronic connectivity between Y_Z/Y_D and the reaction center. Residue conservation analysis indicates retention of D2-Trp191 across various organisms. Molecular dynamics show that the predicted donor–mediator and mediator–acceptor contacts remain structurally persistent over the simulation, while QM/MM calculations show appreciable spin-density localization capacity, providing strong computational support for an ET mediator role of D2-Trp191. Together, these results suggest that ET between the redox-active tyrosines and the reaction-center chlorophylls occurs via distinct mechanisms—direct vs. mediated—with D2-Trp191 being a D2-specific mediator for the branch-selective electron/hole-transfer connectivity in PSII. Full article

(This article belongs to the Special Issue Multidisciplinary Perspectives on Photosynthesis: Integrating Experimental and Theoretical Approaches)

20 pages, 3720 KB

Open AccessFeature PaperArticle

Influence of Au Nanoparticle Concentration on H₂ Production over SrTiO₃ Perovskite: Role of Metal–Semiconductor Charge Separation

by Carlos D. Constantino-Robles, Rufino Nava, Juan C. Durán-Álvarez, Carlos M. Cortés-Romero, Jorge Domingo Mendiola-Santibáñez and María De Los Ángeles Cuán-Hernández

Catalysts 2026, 16(9), 753; https://doi.org/10.3390/catal16090753 (registering DOI) - 22 Aug 2026

Abstract

The development of efficient photocatalysts for hydrogen production is a key challenge for sustainable energy technologies. In this study, strontium titanate (SrTiO

_{3}

) was synthesized via a citrate-assisted sol-gel method and subsequently modified by deposition-precipitation using nominal HAuCl

_{4}

precursor concentrations of [...] Read more.

The development of efficient photocatalysts for hydrogen production is a key challenge for sustainable energy technologies. In this study, strontium titanate (SrTiO

_{3}

) was synthesized via a citrate-assisted sol-gel method and subsequently modified by deposition-precipitation using nominal HAuCl

_{4}

precursor concentrations of 1.0, 1.5, and 2.0 mM. The resulting materials were characterized by XRD, Raman spectroscopy, UV-Vis diffuse reflectance spectroscopy, SEM with EDS, and X-ray fluorescence (XRF). Au incorporation did not produce detectable changes in the SrTiO

_{3}

crystalline phase or its optical band gap, which remained at 3.19–3.20 eV. The additional absorption band centered near 550 nm was consistent with the localized surface plasmon resonance of metallic Au nanoparticles. Microscopy indicated increasing surface coverage and aggregation at the highest nominal precursor concentration. Under irradiation with a low-pressure Hg lamp, all Au-containing materials presented substantially greater H

_{2}

evolution than pristine SrTiO

_{3}

, whereas the comparatively small differences among the Au-modified samples indicated an apparent activity plateau across the evaluated concentration range. Because the Au-associated absorption band near 550 nm lies outside the main 254 nm emission of the lamp and the SrTiO

_{3}

band gap remained mostly unchanged, the enhanced H

_{2}

evolution is consistent with improved interfacial charge separation in the Au/SrTiO

_{3}

system. A Schottky-junction-mediated pathway is proposed based on the observed activity trends and the electronic properties reported for Au/SrTiO

_{3}

interfaces, rather than to a plasmonic or band-gap-tuning effect. The selected STO/Au 2.0 mM material retained approximately 97% of its initial apparent H

_{2}

evolution rate after three consecutive cycles, indicating favorable short-term activity retention. Overall, this comparatively simple synthesis route provides a practical baseline for investigating the influence of nominal Au precursor concentration on H

_{2}

evolution over SrTiO

_{3}

. Full article

(This article belongs to the Special Issue 15th Anniversary of Catalysts: Recent Advances in Catalytic Reaction Engineering)

18 pages, 6196 KB

Open AccessArticle

Divergent Expression and Stress Responsiveness of mitfa and mitfb in Congjiang Golden-Backed Crucian Carp

by Sheng Zeng, Jinli Hu, Qinglan Zhou, Feng Chen, Ning Qin, Zhou Zhou and Xianbo Zhang

Fishes 2026, 11(9), 494; https://doi.org/10.3390/fishes11090494 (registering DOI) - 22 Aug 2026

Abstract

The microphthalmia-associated transcription factor (Mitf) family is central to melanocyte biology. Teleosts possess two mitf paralogs, mitfa and mitfb, yet their functional divergence remains incompletely understood. Here, we characterized the coding sequences, phylogeny, tissue distribution, developmental expression, cellular localization, and stress responsiveness of mitfa and mitfb in Congjiang natural mutant crucian carp (NMCC). Both genes encoded proteins containing the characteristic bHLH-ZIP domain. Phylogenetic analysis revealed that teleost mitfb clustered with the tetrapod mitf clade, indicating closer evolutionary affinity than mitfa. mitfa was predominantly expressed in skin and eyes, whereas mitfb showed broad tissue distribution. Both paralogs were constitutively expressed in skin across developmental stages; mitfa levels remained consistently lower than mitfb. Both transcripts were localized to melanocyte-containing regions of the skin. Transcriptomic analysis following high temperature (34 °C), UV radiation, and combined stress (48 h) revealed that mitfa was significantly upregulated by thermal stress, while mitfb showed no significant changes. Profiling of DNA damage response pathways uncovered extensive, stress-specific transcriptional remodeling. High temperature broadly suppressed apoptotic genes while upregulating tsc2, gadd45b, and cdip1; UV triggered widespread apoptotic gene activation. Combined stress elicited a hybrid signature. Notably, robust DNA Damage Response pathway remodeling contrasted with muted mitf responses, suggesting that DNA Damage Response-to-pigmentation signaling may operate predominantly at post-transcriptional levels. These findings reveal a substantial regulatory divergence between mitfa and mitfb, with mitfa maintaining a conserved melanogenic role while mitfb has been co-opted for broader functions in non-pigmentary tissues. The differential stress responses of the two paralogs further provide new insights into tissue-specific genotoxic stress signaling and melanogenic regulation in teleosts. Full article

(This article belongs to the Special Issue Genetics and Breeding of Fishes)

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30 pages, 2859 KB

Open AccessReview

Recent Advances in Solid-State Hydrogen Storage Based on Metal Hydrides and Nanoporous Carbon Materials

by Bakhytzhan Lesbayev, Moldir Auyelkhankyzy, Gaukhar Ustayeva, Nurgali Rakhymzhan, Aidos Tolynbekov, Ayazhan Zhamash and Meruyert Nazhipkyzy

Nanomaterials 2026, 16(17), 1049; https://doi.org/10.3390/nano16171049 (registering DOI) - 22 Aug 2026

Abstract

Hydrogen is considered one of the most promising energy carriers for sustainable and carbon-neutral energy systems. However, the large-scale deployment of hydrogen technologies is limited by the lack of efficient, safe, and cost-effective hydrogen storage methods. This review examines current hydrogen storage technologies and the physical and chemical mechanisms underlying hydrogen adsorption. Traditional storage approaches, including compressed gas and liquid hydrogen, are briefly analyzed with respect to their advantages, limitations, safety concerns, and energy requirements. Special focus is given to solid-state hydrogen storage systems based on metal hydrides, which offer high storage capacities and enhanced operational safety. Recent advances in intermetallic hydrides, magnesium-based materials and complex hydrides are discussed, along with challenges related to thermodynamic stability, sorption kinetics, thermal management, and cycling durability. This review also highlights recent developments in nanoporous carbon materials and the role of the hydrogen spillover mechanism in improving adsorption performance. Experimental studies reporting hydrogen adsorption capacities above 7 wt.% and up to 11.2 wt.% are analyzed. Based on the reviewed literature, key research directions are identified for optimizing the adsorption properties of advanced materials and accelerating the development of efficient and sustainable hydrogen storage technologies for future energy applications. Full article

(This article belongs to the Topic Advanced Materials in Chemical Engineering)

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23 pages, 3181 KB

Open AccessArticle

Silencing of Kinesin Light Chain 1 Suppresses Aggressive Phenotypes in Cholangiocarcinoma Cells Through Transcriptomic Alterations

by Thanakrit Rattanaarchanai, Phonprapavee Tantimetta, Phanthipha Runsaeng, Sompop Saeheng and Sumalee Obchoei

Int. J. Mol. Sci. 2026, 27(17), 7525; https://doi.org/10.3390/ijms27177525 (registering DOI) - 22 Aug 2026

Abstract

Cholangiocarcinoma (CCA) is an aggressive malignancy with limited treatment options and poor clinical outcomes. Kinesin light chain 1 (KLC1), a component of the kinesin-1 motor complex involved in intracellular transport, has been implicated in cancer biology; however, its role in CCA remains unclear. This study investigated the functional role and molecular alterations associated with KLC1 silencing in CCA. Analysis of publicly available datasets showed that KLC1 mRNA expression was significantly elevated in CCA tissues, and immunohistochemical images from the Human Protein Atlas demonstrated stronger KLC1 protein expression in tumor tissues. siRNA-mediated KLC1 knockdown markedly suppressed cell proliferation, migration, and invasion in KKU-213A and KKU-055 cells and altered the expression of epithelial–mesenchymal transition-associated proteins. Transcriptomic profiling identified 2074 differentially expressed genes following KLC1 knockdown. Functional enrichment analyses revealed significant alterations in cytoskeleton-associated processes and mitogen-activated protein kinase (MAPK) signaling. Protein–protein interaction network analysis identified interconnected gene networks associated with these pathways. Selected differentially expressed genes were validated by RT–qPCR, supporting the transcriptomic findings. Collectively, these results suggest that KLC1 contributes to aggressive phenotypes in CCA cells and is associated with transcriptomic alterations involving cytoskeletal regulation and MAPK signaling, highlighting KLC1 as a potential contributor to CCA progression and warranting further investigation. Full article

(This article belongs to the Section Molecular Oncology)

22 pages, 2085 KB

Open AccessArticle

Integrative Physiological, Transcriptomic, and Functional Analysis Reveals a Positive Contribution of TaCDPK22-5A to Drought Adaptation in Wheat

by Bo Liu, Yu Li, Huina Li, Kexin Niu, Hongliang Wang and Luxian Liu

Genes 2026, 17(9), 985; https://doi.org/10.3390/genes17090985 (registering DOI) - 22 Aug 2026

Abstract

Background: Drought tolerance in wheat is a complex trait controlled by multiple regulatory networks, among which calcium-dependent protein kinases (CDPKs) act as important components linking stress perception with downstream cellular responses. However, the functional contribution of individual CDPK members to drought adaptation in wheat remains largely unclear. This study aimed to identify and functionally characterize drought-responsive CDPK genes associated with differential drought responses in wheat. Methods: Two wheat lines derived from the same breeding background exhibiting contrasting drought adaption, 23B1 and 23B39, were subjected to PEG6000-induced osmotic stress. Growth traits, osmotic adjustment-related metabolites, membrane damage indicators, and antioxidant enzyme activity were evaluated. Transcriptomic analysis was performed at early drought-response stages, followed by differential expression analysis, functional enrichment, CDPK family screening, and qRT-PCR validation. The role of TaCDPK22-5A was further investigated using barley stripe mosaic virus (BSMV)-mediated virus-induced gene silencing (VIGS). Results: The drought-responsive line 23B1 maintained stronger growth, accumulated higher levels of proline and soluble sugars, exhibited enhanced peroxidase activity, and showed reduced membrane lipid peroxidation compared with 23B39. Transcriptome analysis revealed extensive transcriptional reprogramming under drought stress, with differentially expressed genes mainly associated with metabolic adjustment, transport regulation, secondary metabolism, and stress-responsive pathways. Among the identified CDPK members, TaCDPK22-5A showed a strong drought-responsive expression pattern in the line exhibiting stronger drought tolerance (23B1). Virus-induced gene silencing of TaCDPK22-5A significantly impaired drought tolerance, resulting in reduced growth, biomass accumulation, and chlorophyll retention under drought conditions. Conclusions: These findings demonstrate that TaCDPK22-5A contributes positively to drought adaptation in wheat and highlight CDPK-mediated calcium signaling as an important regulatory component of drought responses. The identified gene provides a potential target for improving drought resilience in wheat breeding. Full article

(This article belongs to the Special Issue Abiotic Stress in Crop: Molecular Genetics and Genomics)

17 pages, 317 KB

Open AccessArticle

Don’t Believe the Hype: Methodological Approaches for Applying LLM-Assisted Content Analysis to Reported Speech in Journalism

by Jessy de Cooker

Journal. Media 2026, 7(3), 173; https://doi.org/10.3390/journalmedia7030173 (registering DOI) - 22 Aug 2026

Abstract

To better understand how journalists represent sources, it is necessary to systematically study the use of reported speech in news coverage. This paper presents a method for LLM-assisted content analysis to identify and classify reported speech in Dutch newspapers automatically. The study evaluates a three-step procedure utilising role-based instructions to prompt the model as a professional journalist. First, a codebook for identifying citation structures and source types was developed with LLM support and then manually verified. Second, inter-coder reliability between human coders and the LLM was assessed on a representative sample of Dutch news articles using a human-in-the-loop validation approach. Third, the prompt-engineered LLM was used to code a large corpus spanning seven decades (1950–2024). Manual verification of 16,689 citations shows a weighted F1-score of 0.75, which aligns with recent benchmarks for high-capacity models performing complex journalistic coding. While human oversight remains the benchmark for reliability, due to issues such as repeated citations that were given as examples in the used prompts and representational bias, LLM-based systems perform sufficiently well for large-scale analyses of journalistic source use. The paper concludes that hybrid human–AI workflows provide a practical bridge between traditional rule-based approaches and new generative models, offering scalable and cost-effective methods for studying source representation in journalism. Full article

30 pages, 2610 KB

Open AccessReview

The Role of Transcriptional and Atypical Cyclin-Dependent Protein Kinases in Melanoma

by Jonatan Kaszubski, Maciej Gagat, Agata Wawrzyniak and Agnieszka Żuryń

Cancers 2026, 18(17), 2726; https://doi.org/10.3390/cancers18172726 (registering DOI) - 22 Aug 2026

Abstract

Melanoma, a skin cancer with the highest mortality rate, poses a significant medical challenge. Despite the revolution in the treatment of this cancer brought about by the development of immunotherapy and targeted therapies using BRAF/MEK inhibitors, the complex mutation profile and the development of drug resistance compel researchers to seek new solutions. Cyclin-dependent kinases (CDKs), a group of enzymes regulating fundamental processes in every eukaryotic cell, are generating significant interest in the context of potential targeted therapies for melanoma. The best-studied CDKs, responsible for controlling specific phases of the cell-cycle, have been extensively described in the literature, and their inhibition is increasingly used as a treatment for various cancers. However, in addition to the classic cell-cycle CDKs, CDKs regulating transcription can also be distinguished. Other family members responsible for tissue-specific processes are commonly referred to as atypical or untypical CDKs. These include CDK5, which plays a critical role in the nervous system. In recent years, a growing body of research has focused on the role of transcriptional and atypical CDKs in the progression of cancers, including melanoma. However, their precise function remains unclear. This paper will provide an overview of the role of CDKs, other than cell cycle CDKs, in melanoma development and provide a comprehensive understanding of their potential use in future targeted therapies. The advantages and disadvantages of inhibiting these kinases in melanoma therapy will be discussed, as well as the synergies with various molecular pathways analyzed to date. Full article

(This article belongs to the Special Issue Cell Cycle Dysregulation in Cancers)

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28 pages, 4024 KB

Open AccessReview

Piezo1 as a Key Mechanosensitive Ion Channel Linking Mechanical Overload to Mitochondrial Dysfunction, Mitophagy, and Immunometabolic Dysregulation in Osteoarthritis

by Hechmi Toumi, Ahmad Almhdie-Imjabbar and Eric Lespessailles

Cells 2026, 15(17), 1511; https://doi.org/10.3390/cells15171511 (registering DOI) - 22 Aug 2026

Abstract

Osteoarthritis (OA) is increasingly recognized as a mechanically driven whole-joint disease in which abnormal mechanotransduction initiates a cascade of mitochondrial dysfunction, chronic inflammation, and progressive cartilage degeneration. Among the mechanosensitive molecules identified to date, Piezo1 has emerged as a key mechanosensitive regulator linking pathological mechanical loading to intracellular calcium signaling and downstream cellular responses. Growing evidence indicates that persistent Piezo1 activation promotes mitochondrial calcium overload, excessive reactive oxygen species production, ATP depletion, mitochondrial membrane depolarization, and impaired mitophagy, ultimately amplifying chondrocyte dysfunction and extracellular matrix degradation. In parallel, mitochondrial damage triggers immunometabolic reprogramming through activation of the cGAS–STING pathway and the NLRP3 inflammasome. It also promotes pro-inflammatory cytokines, including interleukin-1β, tumor necrosis factor-α, and interleukin-6. Together, these responses may contribute to a self-perpetuating cycle of inflammation and tissue destruction. This review provides a comprehensive synthesis of recent advances regarding the role of Piezo1 in OA, focusing on the mechanistic links between mechanotransduction, mitochondrial dysfunction, mitophagy, and immunometabolic dysregulation. We further discuss the contribution of mitochondrial quality-control pathways, including PINK1/Parkin-, BNIP3-, and FUNDC1-mediated mitophagy, as well as alterations in mitochondrial dynamics involving DRP1, MFN1, MFN2, and OPA1. Emerging experimental models are discussed as valuable tools for accelerating therapeutic discovery. Finally, we critically evaluate current therapeutic strategies targeting the Piezo1–mitochondria axis, including mechanosensitive channel modulation, mitochondrial protection, mitophagy enhancement, gene therapy, biomaterial-assisted delivery, and nanomedicine. Collectively, current evidence supports the Piezo1–mitochondria–immune axis as an important mechanistic framework contributing to OA pathogenesis and as a potential therapeutic target. Integrating mechanobiology, mitochondrial medicine, and precision-engineered experimental models may facilitate the development of next-generation disease-modifying therapies capable of slowing or preventing osteoarthritis progression. Full article

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19 pages, 15025 KB

Open AccessArticle

Dose-Dependent Alterations in Lung Immune Subpopulations in Influenza a Virus Infection

by Tatiana Betáková, Miriam Mladá, Karin Donátová and Jana Jakubíková

Int. J. Mol. Sci. 2026, 27(17), 7522; https://doi.org/10.3390/ijms27177522 (registering DOI) - 22 Aug 2026

Abstract

This study aimed to characterize the modulation in immune cell subpopulations in murine lungs following influenza A virus (IAV) infection, assessing the effects of infectious dose, viral adaptation, and NS1 expression. Immune cell subsets were profiled by surface receptor expression using multiparametric flow cytometry with a 10-antibody immunophenotyping panel. Neutrophils expressing Ly-6G were significantly increased in the lungs following lethal-dose infection with IAV, independently of NS1 expression; in contrast, lethal-dose infection with all viruses reduced CD163⁺ and F4/80⁺ neutrophil subpopulations. Lethal-dose infection increased pulmonary CD68⁺ macrophages while decreasing CD163⁺, CD193⁺, and F4/80⁺ macrophage subsets, as well as F4/80⁺ myeloid cells, by day 3 post-infection; these reductions were independent of NS1 expression and infectious dose. Following lethal-dose IAV infection, NK cells exhibited upregulation of IL-23R⁺ and IL-12Rβ2⁺ subsets, while the CD193⁺ NK subpopulation was decreased on day 3 post-infection. Profiling of NKT cells revealed an expansion of the IL-12Rβ2⁺ NKT subset on day 3 post-infection. Adaptive immune profiling of lung CD4⁺ T cells revealed a selective increase in Th1-like cells (IL-12Rβ2⁺ CD4⁺) after WSN infection, a marked reduction in Th2-like cells (CD193⁺ CD4⁺) following infection with IAV regardless of NS1 status or dose, and an expansion of CD4⁺NK1.1⁺ cells only after lethal-dose infection. Immune cell subset frequencies were comparable between infections with NS1-expressing and wild-type viruses; NS1 expression did not alter subset composition, whereas the infection dose modulated their abundance. These findings expand our understanding of the subpopulation of immune cells and their possible role in influenza virus pathogenesis. Full article

(This article belongs to the Special Issue Immune Response in Animals)

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