Search Results (1,011)

Nuclear lamins are the core molecular bridge linking the extracellular mechanical microenvironment to intranuclear gene regulation, and play a central regulatory role in cellular mechanosensation and mechanotransduction. Here, we systematically integrate the latest global research progress on nuclear lamins, delineating the cascade regulatory mechanism by which lamins mediate the transmission of mechanical signals across the nuclear envelope and the subsequent regulation of chromatin remodeling and epigenetic modification, with a focus on the molecular characteristics and functional specificity of distinct nuclear lamin subtypes and their interaction modes with the Linker of Nucleoskeleton and Cytoskeleton complex (LINC complex) and chromatin. Existing studies have established that nuclear lamins are mainly divided into three categories: A-type lamins (Lamin A/C), B-type lamins (Lamin B1, B2), and germ cell-specific subtypes. Among these, A-type lamins directly determine the mechanical stiffness of the nucleus and serve as the core mediators of intranuclear mechanical signal transduction. Each subtype of B-type nuclear lamins has a well-defined, non-redundant functional division: Lamin B1 and Lamin B2 indirectly maintain nuclear structural stability and regulate epigenetic status by anchoring facultative heterochromatin and constitutive heterochromatin, respectively. Notably, Lamin A/C distributed in the nucleoplasm also bears significant mechanical tension, which challenges the long-standing view that the mechanical functions of nuclear lamins are restricted to the nuclear envelope region. After mechanical force is transmitted across the nuclear envelope to nuclear lamins via the LINC complex, it can regulate the spatial conformation of chromatin and epigenetic modifications, thereby determining core cellular life activities including proliferation, differentiation, and migration. Dysregulation of this pathway is closely associated with a wide spectrum of human diseases, including cardiovascular diseases, progeria, muscular dystrophy, and neurodevelopmental disorders. Taken together, this review systematically delineates the hierarchical regulatory network of the “LINC complex–nuclear lamina–chromatin” axis, advances our understanding of the fundamental principles of cellular mechanobiology, and provides a theoretical framework for deciphering the pathological mechanisms and developing targeted therapeutic drugs for related diseases. Full article

Tartrazine (E102), a synthetic azo dye, is extensively utilized across diverse industrial sectors. Understanding the mechanisms of tartrazine degradation and identifying its breakdown products are essential for assessing its environmental fate and potential health risks. Tartrazine is studied in this work in terms of: (i) determining its concentration in a commercial food dye by use the Briggs–Rauscher (BR) oscillatory (clock) reaction as seldom-employed analytical method, (ii) examining its degradation in a highly oxidative system, such as the BR oscillatory reaction, using Raman and FTIR spectroscopy, and (iii) monitoring the degradation process in the BR system at different magnifications using optical and scanning electron microscopy (SEM). The limits of detection (LOD) and quantification (LOQ) obtained for the BR reaction were higher than those determined by UV-Vis spectroscopy. Both methods determined comparable concentrations of tartrazine in the food dye. Based on the results obtained, the reaction mechanism for tartrazine degradation in the clock reaction was proposed. The findings strongly support the BR reaction as an easily available method for determining unknown concentrations of tartrazine in commercial food dyes. Furthermore, this study highlights the potential of the BR reaction for determining microconcentrations and for the rapid degradation of commercial food dyes. Full article

The application of organic residues in agriculture helps to replenish soil organic carbon (OC), improve soil fertility and biodiversity, reinforce aggregate stability, and favour water infiltration. Moreover, its application as a soil amendment alters the fate of herbicides applied to the soil. The objective here was (i) to evaluate soil quality by determining the physicochemical and biological parameters of an agricultural soil (Soil) amended with green compost (Soil + GC) over an arable pea–wheat crop rotation in a short-term experiment; and (ii) to study the dissipation and persistence of iodosulfuron-methyl-sodium applied in field plots sown with winter wheat under real field conditions. The experimental field design consisted of 24 plots (10 m²) involving 12 with control and 12 with GC-amended soils. The plots were sown with pea after GC application (~11 t ha⁻¹) in February 2023, and with winter wheat in October 2023. Iodosulfuron-methyl-sodium (Hussar^® Plus, Bayer CropScience S.L., Barcelona, Spain) was applied in post-emergence at the agronomic dose (D1 = 176 mL ha⁻¹) and double dose (D2 = 352 mL ha⁻¹). Soil samples were taken from the plots to assess the soil physicochemical and biological parameters at six sampling times after GC application, with extraction and determination of residual herbicide and metabolite (metsulfuron-methyl) concentrations. In addition, the yield and characteristics of the pea and wheat grain crops were determined. The application of GC to the soil significantly increased pH (0.5 units by July 2024) and electrical conductivity (up to 5.2 times) compared to control soil, which remained constant throughout the experiment. The OC in Soil + GC increased by 40% in July 2024 compared to control soil. Total nitrogen content increased up to 2.0 and 1.3 times during the pea–wheat growing seasons in Soil + GC compared to unamended soil. Soil dehydrogenase activity, respiration, and biomass increased by up to 1.4, 2.2 and 1.4 times, respectively, in Soil + GC compared to unamended soil over the growing seasons. The soil microbial structure, determined by phospholipid fatty acid (PLFA) analysis, recorded no significant differences between the microbial groups in both soil treatments. A non-significant increase in pea and wheat yield was observed in Soil + GC compared to unamended soil. The results revealed an increase in the residual amounts of herbicide and metabolite, being slightly more persistent, with DT₅₀ and DT₉₀ values up to 1.6 times higher, in the Soil + GC plots over time. Much higher amounts of metabolite (DT₅₀ = 24.8–29.7 days) than iodosulfuron-methyl (DT₅₀ = 5.2–8.8 days) were found in all the treatments. This may be due to wheat plants intercepting the herbicide initially at the time of application in post-emergence, the rapid dissipation of the herbicide reaching the soil, and/or the higher persistence of the metabolite compared to that of the herbicide. Overall, the soil’s physicochemical and biological properties were improved in GC-amended soil, and organic amendment increased slightly the persistence of iodosulfuron-methyl-sodium and its metabolite in the soil. Full article

Hair follicles are highly specialized mini-organs within the skin that drive the production of wool and cashmere, traits of major biological and economic importance in sheep and goats. Despite their microscopic size, hair follicles exhibit extraordinary regulatory complexity, integrating genetic programs with seasonal, endocrine, environmental, and epigenetic cues. Although transcriptional networks and signaling pathways underlying follicle morphogenesis and cycling have been extensively investigated, the post-transcriptional mechanisms that fine-tune these processes remain insufficiently understood. MicroRNAs (miRNAs) have emerged as pivotal post-transcriptional regulators that coordinate cell fate determination, lineage commitment, and tissue homeostasis. Growing evidence indicates that miRNAs play essential roles in hair follicle stem cell maintenance, proliferation, differentiation, apoptosis, and organ-level development, functioning through interconnected regulatory networks rather than isolated linear pathways. By modulating the expression of key follicle-determining genes and signaling components, miRNA-mediated regulation shapes follicle formation, cyclic regeneration, and fiber traits. In this review, we synthesize recent advances in miRNA research related to hair follicle biology, with a particular focus on wool- and cashmere-bearing mammals. We integrate findings across species to propose a systems-level framework in which miRNA networks interface with canonical signaling pathways and epigenetic mechanisms to orchestrate follicle development and regeneration. Conserved and species-specific regulatory principles are discussed to bridge fundamental follicle biology with practical applications in fiber production. Overall, this review highlights miRNAs as a critical yet previously underappreciated regulatory layer in hair follicle biology. A deeper understanding of miRNA-mediated control provides new conceptual insights into wool and cashmere development and offers a foundation for future molecular breeding and precision regulation strategies in livestock. Full article

Pluripotent stem cell (PSC) differentiation is orchestrated by intricate autocrine and paracrine signaling networks. Among these, exosomes, key components of the cellular secretome, are implicated as crucial mediators of intercellular communication via delivery of bioactive molecules, including microRNAs (miRNAs). This study investigated the role of exosomal miRNAs in stem cell differentiation using Dgcr8-deficient mouse embryonic stem cells (mESCs), which are incapable of producing mature miRNAs. Although the differentiation capacity was markedly impaired in these cells, partial restoration was observed following treatment with exosomes derived from differentiating wild-type mESCs. Exosomal miRNA uptake was confirmed, and gene ontology analysis revealed significant enrichment of pathways associated with cell fate determination, morphogenesis, and apoptosis regulation. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that exosomal miRNAs modulated multiple osteoinductive signaling cascades, notably the MAPK and TGF-β pathways, in Dgcr8-deficient cells. Apoptotic markers were also downregulated, suggesting a protective effect conferred by the exosomal cargo. Collectively, our results suggest that exosome-mediated delivery of miRNAs may represent a fundamental mechanism by which pluripotent stem cells coordinate stress responses and differentiation trajectories, providing novel insights into the regulation of embryogenesis. Full article

Background: The combination of conventional drugs and inhibitors of signaling molecules is an effective strategy to increase cancer treatment efficacy and reduce drug doses to protect against their cytotoxic effects. Our research has shown the cisplatin concentration-dependent shift in the role of MAP kinase JNK from antiapoptotic to proapoptotic in non-small cell lung cancer A549 cells. Cell death/survival signaling molecules, tumor suppressor p53 and pro-survival protein kinase AKT were detected to be differently regulated by JNK inhibition at low vs. high cisplatin concentrations. Here, we further investigated the phenomenon and potential mechanisms of combined JNK inhibition and cisplatin treatment. Methods: Cell death in vitro was evaluated by MTT and Western blot assays after combined cisplatin and specific inhibitor treatment; two-way ANOVA was used for analysis. Results: JNK is differently involved in determining cellular sensitivity to different DNA-damaging drugs. There is no universal cell death induction mechanism originating from DNA damage through the involvement of JNK. The outcome of JNK inhibition also depends on the cell type. We found that there is an unusual reciprocal interaction between p53 and AKT in cisplatin-treated A549 cells, where p53 inhibits AKT, while AKT activates p53. In the case of cisplatin + JNK inhibitor SP600125, DNA damage and reactive oxygen species (ROS) contribute to cell death regulation in different ways. ROS exert opposite roles on cell fate-determining molecules p53 and AKT, and ROS act on p53 and AKT in opposite directions at low vs. high concentrations of cisplatin, combined or not with JNK inhibition. The differentially activated p53 in response to ROS (at low versus high concentrations of cisplatin, combined with JNK inhibitor) may be a molecular switch in the role of JNK from antiapoptotic to neutral/proapoptotic, and an executor of cell death. ROS is a possible threshold regulator that, together with an as-yet-unidentified factor, can differentially regulate p53. As a result, AKT phosphorylation and function are altered. The findings emphasize the importance of assessing the role of drug concentration when combining them with JNK inhibition when monitoring therapeutic efficacy and toxicity issues in personalized cancer treatment. Full article

Novel therapeutic strategies are required to protect the heart from acute ischaemia-reperfusion injury (IRI) and improve outcomes in patients with acute myocardial infarction (AMI). Mitochondria play a critical role in determining cardiomyocyte fate following acute IRI, with genetic and pharmacological inhibition of Drp1-mediated mitochondrial fission limiting cardiomyocyte death. We investigated the role of the mitochondrial Drp1 receptors, MiD49 and MiD51, as novel targets for cardioprotection. In cardiac cell lines subjected to simulated IRI, dual genetic knockdown of both MiD49 and MiD51 reduced cell death, inhibited mitochondrial fission, prevented mitochondrial permeability transition pore opening, and attenuated mitochondrial calcium overload compared with wild-type cells. However, individual knockdown of either MiD49 or MiD51 did not induce mitochondrial elongation or inhibit MPTP opening. Whole-body genetic ablation of MiD49 in adult mice modestly altered mitochondrial morphology but did not affect myocardial infarct size or cardiac function following AMI. Together with the in vitro protection seen with dual MiD49/51 knockdown, these findings suggest that MiD49 deficiency alone is insufficient and that coordinated inhibition of MiD49 and MiD51 may be required for cardioprotection. Full article

The escalating accumulation of pharmaceutical micropollutants in global water systems represents a significant challenge to current circular economy frameworks, highlighting a critical gap in the management of environmental persistence. Although advanced remediation technologies are often proposed to mitigate this crisis, their engineering optimization is frequently compromised by a reliance on empirical approximations rather than precise physicochemical constants. Addressing this fundamental deficit, this study executes a rigorous determination of mass transfer properties for two ubiquitous contaminants: Butylparaben and Triclosan. Utilizing a high-precision electrolytic conductance method under infinite dilution, we investigated transport dynamics across varying temperature gradients (305.15–319.15 K). Experimental data were subjected to advanced mathematical modeling, where the Modified Robinson–Stokes (MRS) quadratic model significantly outperformed classical linear approaches ($R^2>0.98$), accurately capturing non-ideal solute–solvent interactions. The derived limiting molar conductivities facilitated the calculation of infinite dilution diffusion coefficients via the Nernst–Haskell equation, yielding values of $0.99\times {10}^{-8}$ m²/s for Butylparaben and $0.98\times {10}^{-8}$ m²/s for Triclosan. Furthermore, Stokes–Einstein analysis quantified the hydrodynamic radii, elucidating the steric mechanisms governing the sluggish migration of bulky chlorinated ethers compared to single-ring esters. These precise transport parameters are not merely theoretical values; they are essential inputs for developing accurate computational fate models and designing regenerable separation processes, thereby providing the hard physics required to engineer solutions for the perpetual pollution era. Full article

Fungicide contamination is an increasing global environmental concern, due to the harm they may pose to non-target organisms, their contribution to antimicrobial resistance, and the potential risks to human health when drinking water (DW) sources are impacted. Many fungicides used in agriculture are chiral and may exist as racemates, or a combination of diastereoisomers and/or enantiomers. Since enantiomers can differ in environmental fate, distribution, and toxicity, enantioselective analysis of chiral fungicides is crucial. The aim of this study was to develop and validate an analytical method for the determination of azole chiral and achiral fungicides in DW using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS). Chromatographic separation of one achiral fungicide and five chiral fungicides was achieved using a polysaccharide chromatographic column under reverse elution mode. The validated method demonstrated high sensitivity with method detection limits (MDL) below 0.86 ng L⁻¹ and was successfully applied to 13 DW samples collected from various supply networks across Portugal. Seven out of the 15 targeted analytes were found at trace concentrations (>MDL). Fluconazole was the most frequently detected (~87% of the samples). The hazard quotients (HQs) for individual compounds for each individual fungicide (sum of the enantiomers for those chiral) and the hazard index (HI, sum of the individual HQ values) were calculated in each DW sample, indicating no significant health risks to consumers, since it is well below 0.1 for all compounds. Full article

According to the World Health Organization (WHO), substance dependence and mental health disorders, such as anxiety, depression, post-traumatic stress disorder (PTSD), insomnia, bipolar disorder, and schizophrenia, affect >360 million people worldwide. As a result the increasing use of psychoactive pharmaceuticals, including non-benzodiazepines (also referred to as Z-drugs), has been observed. The COVID-19 pandemic has also had an additional significant negative effect on people’s mental health. Among the aforementioned mental health disorders, chronic insomnia is reported to affect approximately 10% of the adult population. Z-drugs are frequently used in the treatment of insomnia due to their rapid onset of action. They are metabolized in the human organism, but noticeable amounts of the original compound are released to the environment via household wastewater. The extensive use of these pharmaceuticals has led to growing concern about the occurrence of their residues in the environment. Unfortunately, the information on the analytical methods for determining Z-drugs, their main metabolites and transformation products in the environment, efficiency of their removal in wastewater treatment plants, their fate, their presence in environmental matrices, and their ecotoxicological effects is limited. This review paper focuses on summarizing data on these topics. To the best of our knowledge, such a comprehensive review has not yet been published. Full article

During aging, bone marrow stromal (a.k.a. mesenchymal stem) cells (BMSCs) shift their lineage commitment away from osteogenesis and towards adipogenesis, resulting in bone loss and marrow fat accumulation. We previously reported that during osteogenesis, BMSCs activate mitochondrial oxidative phosphorylation (OXPHOS) at least in part by downregulating cyclophilin D (CypD) expression and, consequently, mitochondrial permeability transition pore (MPTP) activity. We also reported that in contrast, during adipogenesis, BMSCs upregulate CypD and MPTP, activate glycolysis and inhibit OXPHOS. To further study the role of CypD in BMSC bioenergetics, adipogenesis and bone marrow fat accumulation, we used CypD loss-of-function (LOF) or gain-of-function (GOF) models in osteo-adipoprogenitors in vitro and in vivo. We found that CypD LOF and GOF are associated with impaired and enhanced BMSC adipogenesis, respectively, both in vitro and in ectopic bone grafts in vivo. In addition, bioenergetic profiling and metabolomic analyses show evidence of corresponding metabolic reprogramming in CypD LOF and GOF cells. In summary, our study demonstrates the role of CypD-regulated mitochondrial metabolism during BMSC adipogenesis, facilitating the understanding of stem cell fate determination and the molecular mechanism of age-related bone loss as well as bone marrow fat accumulation. Full article

Titanium dioxide nanoparticles (TiO₂ NPs) are incorporated into automotive coatings to enhance durability, corrosion, UV resistance, and, in some formulations, photocatalytic self-cleaning. While the toxicology of pristine TiO₂ is well studied, the behavior of TiO₂ NPs embedded in polymer matrices and subjected to real-world aging, maintenance, and removal remains poorly characterized. This narrative review synthesizes 24 publications spanning the lifecycle of TiO₂ nano-enabled automotive coatings, from synthesis and formulation through application, in-service weathering, repair, refinishing, and end-of-life environmental fate. Upstream properties, such as coating functionality and performance, have been examined as determinants of later-life release, exposure, and fate. Across studies, dispersion state, interfacial compatibility, and surface modification—together with transformations such as agglomeration, photocatalysis, weathering, and eco-corona formation—shape particle stability, release, exposure relevance, and toxicological risk. Evidence indicates that sanding and accelerated weathering predominantly generate matrix-associated, polymer-fragment-dominated aerosols rather than pristine TiO₂ NPs, while NP-specific exposure measurements during spray application remain limited. Hazard data suggest matrix embedding may attenuate, but does not eliminate, biological responses relative to pure particles. Wastewater treatment plants and biosolids have been shown to act as sinks with potential for soil accumulation following sludge application. Regulatory frameworks rarely account for aging, transformation, and release, stressing the need for synchronized testing of aged materials and nano-specific exposure metrics to support safer-by-design coatings and risk governance. Full article

Sepsis remains a leading global health challenge, characterized by high mortality and a persistent lack of disease-modifying therapies. Despite decades of investment, therapeutic progress has been constrained by reductionist strategies that target isolated pathogenic components. This perspective argues that these failures reflect a fundamental mischaracterization of sepsis—not as a disorder of discrete pathways, but as the collapse of complex biological systems in which normally coordinated processes become desynchronized. We identify the intermediate filament protein vimentin as a determinant of system fate governing the transition from adaptive host defense to pathological breakdown. Acting as a context-dependent network integrator and signal amplifier, vimentin coordinates antagonistic cellular programs by integrating biochemical and biophysical cues across immune, vascular, and metabolic systems. Under physiological stress, this coordination enables the orderly activation and resolution of inflammatory and suppressive responses required for pathogen control and restoration of homeostasis. In sepsis, persistent or excessive insults drive vimentin-mediated overactivation, uncoupling these programs and propagating systems-level instability that culminates in organ dysfunction. By integrating mechanistic, preclinical, and emerging clinical evidence, this perspective proposes vimentin modulation as a clinically translatable, systems-oriented strategy aimed at realigning host response networks to address the dynamic, opposing pathologies of sepsis that have eluded current therapies. Full article

During the early pupal stage in butterflies, the peripheral portion of wing tissue undergoes apoptosis to finalize adult wing morphology, and wing color patterns are determined coordinately. We hypothesized that the development of wing morphology and color patterns may involve NADPH oxidase (NOX). To test this hypothesis, we treated pupae of the blue pansy butterfly Junonia orithya with NOX inhibitors. When VAS2870, isuzinaxib, or diphenyleneiodonium chloride (DPI) in dimethyl sulfoxide (DMSO) was topically applied to the pupal wing tissue via the sandwich method, wing morphology and color pattern elements, including eyespots, parafocal elements, submarginal bands, and marginal bands, were severely deformed as if the marginal area were surgically removed. The topical application of DMSO alone mildly deformed and enlarged eyespots without affecting other color patterns and wing morphology. When systemically injected into pupae, VAS2870 increased eyespots in males but decreased eyespots in females, likely due to the sexual dimorphism of this species. These results suggest that NOX and probably hydrogen peroxide play important roles in wing morphogenesis and color pattern fate determination in butterfly wings. Sexually dimorphic eyespot size in this species may also be explained by the sexually differential activities of NOX. Full article

Skeletal muscle regeneration declines with age despite the persistence of satellite cells (muscle stem cells, MuSCs), suggesting that regenerative impairment reflects functional dysregulation rather than MuSC depletion. Increasing evidence identifies early MuSC activation during the immediate post-injury period as a stress-sensitive, rate-limiting transition that is particularly vulnerable in aged muscle. Aged MuSCs exhibit elevated stress responses and reduced membrane remodeling capacity, accompanied by weakened activation-associated transcriptional induction. In contrast, proliferative and differentiation programs remain largely intact once activation is successfully initiated. These findings underscore that impaired coordination during early activation contributes to long-term regenerative decline in aging. Within this framework, MG53 (tripartite motif–containing protein 72, TRIM72), a muscle-enriched TRIM family E3 ubiquitin ligase originally identified as a mediator of sarcolemmal membrane repair, may also function as a stress-responsive regulator that stabilizes the early activation environment. Rather than directly determining cell fate, MG53 is proposed to facilitate activation by mitigating stress-associated membrane disruption and maintaining programmatic coordination under age-related physiological constraints. Most mechanistic evidence derives from rodent models, and direct validation in human aging muscle remains limited. These observations suggest that targeting early activation, rather than simply increasing proliferation, may better preserve regenerative capacity in aging skeletal muscle. Full article