Search Results (39,860)

Myostatin (Mstn), a well-characterized member of the transforming growth factor-β (TGF-β) superfamily, serves as a key negative regulator of skeletal muscle mass. Its overactivation is closely associated with the pathogenesis of various musculoskeletal and metabolic disorders. Over the past decades, inhibiting Mstn has emerged as a promising therapeutic strategy to promote muscle growth. A range of Mstn-targeted inhibitors has been developed, yielding encouraging preclinical and clinical outcomes. These include small molecules, monoclonal antibodies, peptibodies, and gene therapy-based approaches. This review summarizes the biological structure and function of Mstn, provides a comprehensive overview of recent advances in Mstn-targeted therapeutics, and offers critical insights into future directions for drug development and clinical translation. Full article

Cardiac fibrosis is a central determinant of heart failure progression and arises from pathological remodeling characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. In contrast, physiological remodeling permits adaptive cardiac growth without net fibrosis. Pregnancy represents an underexplored physiological model of reversible cardiac remodeling. In response to hemodynamic load, the maternal heart undergoes hypertrophic growth that resolves postpartum, constituting a natural paradigm of fibrosis-resistant cardiac adaptation. Pregnancy and lactation are accompanied by profound endocrine and immune reprogramming of maternal tissues. We propose that this hormonal milieu orchestrates coordinated crosstalk among endothelial cells, fibroblasts, and immune cell populations to suppress profibrotic pathways and preserve extracellular matrix homeostasis. Candidate regulators include estrogen, progesterone, prolactin family peptides, relaxin, oxytocin, and components of the renin–angiotensin–aldosterone system. During the postpartum and lactational period, prolactin and oxytocin may further promote reverse remodeling. These hormones likely act by modulating local cytokine and growth factor networks that otherwise drive fibroblast activation. By focusing on non-myocyte cardiac cells and extracellular matrix dynamics, this review positions pregnancy as a translational model to uncover endogenous anti-fibrotic mechanisms and identify novel therapeutic strategies for cardiac fibrosis. Full article

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma characterized by the t(11;14)(q13;q32) cytogenetic abnormality and cyclin D1 overexpression. We have found evidence that Forkhead box M1 (FOXM1), a transcription factor with oncogenic potential, is important in the pathogenesis of MCL. Relatively high levels of FOXM1 proteins were detectable in all six MCL cell lines examined. By immunohistochemistry, we consistently found a subset of FOXM1-positive cells in MCL tumors. Analysis of two Gene Expression Omnibus (GEO) datasets from MCL patients showed that elevated FOXM1 levels significantly correlate with a worse clinical outcome. In MCL cell lines, inhibition of FOXM1 using thiostrepton or shRNA effectively triggered apoptosis and significantly reduced cell growth. FOXM1 forms a positive feedback loop with NFκB in MCL cells. Specifically, inhibition of FOXM1 dramatically decreased the protein level/transcription activity of p65, while enforced FOXM1 expression upregulated p65 and downregulated IκBα, a key NFκB inhibitor. Conversely, curcumin-mediated NFκB inhibition decreased the protein level/DNA binding of FOXM1, while transduction of a constitutively active IKKα construct into MCL cells significantly dampened the inhibitory effects of thiostrepton. Confocal microscopy revealed that FOXM1 and p65 colocalize with each other. In conclusion, FOXM1 and NFκB work collaboratively in promoting the growth and drug resistance of MCL, and FOXM1 may be a potentially useful therapeutic target. Full article

Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including sensory deficits and functional impairment. Therefore, nerve guidance conduits (NGCs) have emerged as a promising alternative when combined with bioactive modulation strategies. In this study, we evaluated bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduits integrated with electrical stimulation (ES) at different frequencies (0, 2, 20, and 200 Hz) in a rat sciatic nerve defect model over a 4-week recovery period (n = 10 per group). Structural regeneration was assessed by morphometric analysis, electrophysiology, macrophage infiltration, CGRP immunoreactivity, retrograde Fluorogold tracing, quantitative PCR of growth factors and inflammatory cytokines, and behavioral testing. Among all stimulation paradigms, low-frequency ES at 2 Hz produced the most pronounced regenerative effects. The 2 Hz group demonstrated significantly greater axon number, axonal density, and regenerated nerve area compared with control and high-frequency groups (p < 0.05). Electrophysiological assessments revealed improved nerve conduction velocity, higher MAP amplitudes, and shorter latencies. Enhanced macrophage recruitment and elevated CGRP expression were observed, suggesting coordinated neuroimmune and neurochemical activation. Gene expression analysis indicated upregulation of neurotrophic factors and balanced inflammatory cytokine responses under low-frequency stimulation. In contrast, high-frequency stimulation (200 Hz) failed to enhance overall regeneration and showed reduced axonal metrics, suggesting possible overstimulation-associated suppression. Collectively, these findings demonstrate that BVSM-crosslinked conduits provide a stable and biocompatible regenerative scaffold, and that appropriately tuned low-frequency electrical stimulation (2 Hz) optimally enhances structural, molecular, and functional recovery. The integration of material engineering with bioelectrical modulation represents a promising strategy for next-generation bioelectronic interfaces in peripheral nerve repair. Full article

The occurrence of marine heatwaves (MHWs) and phytoplankton blooms is accelerating under climate change, yet the frequency and drivers of their compound co-occurrence remain poorly understood. Using coastal-optimized satellite observations from 2003–2020, we mapped global compound MHW–phytoplankton bloom (MHW-PB) events across coastal large marine ecosystems and quantified their spatiotemporal trends and environmental predictors. Compound events are increasing at 4.8% yr⁻¹, driven primarily by a 6.5% yr⁻¹ rise in MHW frequency; a temporal shuffle test confirms this trend falls below random co-occurrence expectation, indicating biological suppression actively constrains compound event growth. The compound independence factor (CIF) reveals latitudinal heterogeneity: low-latitude upwelling systems show MHW–PB mutual exclusivity, while high-latitude and eutrophic coastal regions show positive co-occurrence tendency. Interpretable machine learning further shows that nutrient availability dominates bloom responses at low latitudes whereas light dominates at high latitudes, with MHW intensity exhibiting nutrient-dependent non-linear associations with bloom probability. Paradoxically, compound frequency accelerates nearly twice as fast in low latitudes (6.1% yr⁻¹) as in high latitudes (3.5% yr⁻¹), driven by rapid tropical MHW acceleration. These diverging regimes signal dual ecological risks: trophic mismatches in upwelling systems and escalating hypoxia and harmful algal bloom hazards in eutrophic coastal waters. Full article

Erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is widely used in cancer therapy; however, hepatotoxicity limits its clinical use. This study investigated the protective effects of Liv-52, a polyherbal hepatoprotective formulation, against erlotinib-induced hepatotoxicity in rats and compared its efficacy with melatonin. The animals (n = 24, Wistar albino rats) were randomly categorized into four groups: healthy (HG), erlotinib (ERG), Liv-52 + erlotinib (LEG), and melatonin + erlotinib (MEG). Liv-52 (50 mg/kg/day, orally) and melatonin (10 mg/kg/day, orally) were administered once daily for two weeks. Erlotinib (10 mg/kg, orally) was given every other day to ERG, LEG, and MEG groups for two weeks. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were measured. Hepatic malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels were analyzed. Additionally, double immunofluorescence staining was performed to evaluate apoptotic (poly[ADP-ribose] polymerase-1 [PARP-1], apoptosis-inducing factor [AIF]), inflammatory (cyclooxygenase-2 [COX-2]), and anti-inflammatory (interleukin-10 [IL-10]) biomarkers in liver tissues. Histopathological examination was also conducted to assess structural alterations. Erlotinib significantly increased MDA, ALT, AST, and LDH while decreasing tGSH, SOD, and CAT (p < 0.001). Strong immunoreactivity for PARP-1, AIF, IL-10, and COX-2, as well as severe hydropic degeneration and necrosis, was observed in ERG (p < 0.05). Both Liv-52 and melatonin significantly ameliorated biochemical, histopathological, apoptotic, and inflammatory alterations (p < 0.05). Notably, Liv-52 demonstrated superior hepatoprotective efficacy compared to melatonin. These findings indicate that Liv-52 effectively attenuates erlotinib-induced hepatotoxicity by modulating oxidative stress, inflammatory responses, and apoptotic pathways, thereby preserving liver function and structural integrity. Full article

Photosynthesis, the main energy source for life on Earth, confronts escalating challenges of high-light–high-temperature stress (HLHT). Our previous study identified a mutation in ATP synthase, F₁-α-C252Y, that significantly enhances the HLHT tolerance of Synechococcus elongatus PCC 7942 (Sye7942), although the underlying mechanism remains obscure. In this study, we found that this mutation led to elevated levels of the b subunit of F_o, F₁ subunits, and the ATP synthase within cells, without affecting ATP synthetic activity, indicating improved intracellular ATP synthesis activity. Additionally, the mutation altered the transcriptome of Sye7942, impacting the expression of genes involved in crucial processes, such as the electron transport chain, carbon fixation, and regulatory factors, which are crucial for cyanobacteria’s adaptation to stresses. Correspondingly, the mutant exhibited enhanced photosynthesis, accelerated growth, and increased glycogen under HLHT conditions, showing improved adaptation. The higher intracellular ATP synthesis activity, along with enhanced photosynthetic activity, suggests increased ATP production in the mutant under HLHT. Enhancing ATP production and remodeling the cellular transcriptome appear to be key strategies employed by the C252Y mutation for Sye7942 acclimating to HLHT. These findings provide valuable insights for enhancing photosynthetic efficiency and stress resilience in cyanobacteria and other photosynthetic organisms facing HLHT challenges. Full article

Azo dyes demonstrate dose-dependent carcinogenic and mutagenic effects in exposed cells. Among remediation approaches, microbial adsorption is the most sustainable and environmentally friendly method for eliminating azo dyes. A novel Aspergillus terreus silica composite was developed as a sustainable adsorbent for crystal violet dye (CVD) removal. The fungal strain was isolated from dye wastewater and was genetically identified by 18S rRNA gene sequencing. Dried mycelia of A. terreus (PX920301) were combined with SiO₂ (1:1 w/w) through iterative hydration-drying cycles, yielding a composite characterized by FTIR analyses. Removal CVD %, adsorption capacity, and CVD residual were calculated, and the adsorption process was optimized using Box–Behnken design (four factors, 25 runs). The biosafety of the composite was assessed for phytotoxicity and microbial toxicity. The composite was also applied to real dyes wastewater collected from the bacteriological laboratory. Aspergillus terreus-silica composite showed the highest CVD removal percentage by 85.4%, adsorption capacity (qe) 121.1 mg/L, and lowest CVD residual by 7.26 mg/L, followed by the dried active mycelia (DA-mycelia) with CVD removal 40.23%, adsorption capacity (qe) 57.05 mg/L, and CVD residual by 29.73 mg/L. Optimization data cleared that the maximum experimental values of CVD removal (%) was 99.59% (predicted value 100%) obtained in run number (4) using initial CVD concentration (200 mg/L), pH (8), adsorbent composite weight (0.1 g), and contact time (48 h). Biosafety evaluation demonstrated negligible phytotoxicity against Triticum aestivum seedlings post-treatment, with restored germination and growth comparable to controls. Microbial toxicity assays via well-diffusion to seven microbial isolates confirmed no toxic activities against the tested bacteria, yeast, and fungi, underscoring the composite’s environmental safety. The composite could decolorize the real dye wastewater of laboratories by 95.37%. In conclusion, A. terreus mycelial-silica composite offers a cost-effective, sustainable, and eco-friendly alternative solution for dye bioremediation. Full article

Welded joints are widely recognized as the most critical point in structures made of armour steels due to pronounced thermal effects, microstructural heterogeneity, and the degradation of mechanical and fatigue properties. This study investigates the mechanical properties and fatigue crack growth resistance of a welded joint produced on SA 500 armour steel, with the aim of preserving the properties of the base material as much as possible. To achieve this, a welding procedure incorporating a high-strength filler wire and optimized welding parameters was applied. Hardness and tensile testing was conducted to evaluate the extent of property degradation caused by welding. The results demonstrate that the applied welding process effectively limited the reduction in hardness and tensile strength, achieving values reasonably close to those of the base material. In addition, fatigue crack growth behaviour was investigated in accordance with ASTM E647, using both the Paris law and the McEvily law. The obtained fatigue crack growth curves and threshold stress intensity factor (ΔK_th) values indicate the nearly identical fatigue behaviour of the base material and the heat-affected zone, confirming the successful preservation of base material fatigue behaviour in the thermally affected zone. Moreover, the weld metal exhibited superior resistance to fatigue crack initiation and growth. Overall, the results confirm that the proposed welding approach provides favourable mechanical and fatigue performance for welded joints in armour steel applications. Full article

Background: Targeted therapies directed against oncogenic drivers have substantially improved outcomes for patients with epidermal growth factor receptor (EGFR)-mutant and anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Despite high initial response rates, most patients ultimately develop acquired resistance to tyrosine kinase inhibitors (TKIs), reflecting complex biological adaptations under therapeutic pressure. Methods: This narrative review synthesizes experimental, translational, and clinical studies examining how environmental and occupational respiratory exposures may influence resistance mechanisms in EGFR- and ALK-driven NSCLC. The review emphasizes exposure-associated signaling plasticity, inflammatory microenvironmental modulation, metabolic reprogramming, and pharmacokinetic alterations. Results: Recent evidence suggests that respiratory exposures, including cigarette smoke, air pollution, diesel exhaust, and occupational inhalational toxicants, can modulate oncogenic signaling networks relevant to resistance to targeted therapies. These mechanisms include aberrant EGFR activation, bypass signaling through the mesenchymal–epithelial transition receptor (MET) and SRC pathways, epithelial–mesenchymal transition (EMT), adaptive kinome remodeling, and exposure-associated inflammatory signaling, all of which may influence tumor evolution and therapeutic response. Conclusions: This review introduces a novel exposome-driven conceptual framework integrating environmental exposures with signaling plasticity and resistance evolution in oncogene-driven NSCLC. These findings support the concept that the respiratory exposome may represent an underrecognized modifier of targeted therapy response. Incorporating structured exposure assessment into precision oncology approaches may refine risk stratification and inform exposure-aware therapeutic strategies. Full article

Background: Quantitative genetic analysis of image- or video-derived phenotypes is increasingly being performed for a wide range of traits. Pig body weight values estimated by a conventional approach or a computer vision system can be considered two different measurements of the same trait but with different sources of phenotyping error. Previous studies have shown that trait measurement error, defined as the difference between manually collected phenotypes and image-derived phenotypes, can be influenced by genetics, suggesting that the error is systematic rather than random and is more likely to lead to misleading quantitative genetic analysis results. Therefore, we investigated the effect of trait measurement error on the genetic analysis of pig body weight (BW). Results: Calibrated scale-based and image-based BW showed high coefficients of determination and goodness of fit. Genomic heritability estimates for scale-based and image-based BW were mostly identical across growth periods. Genomic heritability estimates for trait measurement error were consistently negligible, regardless of the choice of computer vision algorithm. In addition, genome-wide association analysis revealed no overlap between the top markers identified for scale-based BW and those associated with trait measurement error. Overall, the deep learning-based regressions outperformed the adaptive thresholding segmentation methods. Conclusion: This study showed that manually measured scale-based and image-based BW phenotypes yielded the same quantitative genetic results. We found no evidence that BW trait measurement error could be influenced, at least in part, by genetic factors. This suggests that trait measurement error in pig BW does not contain systematic errors that could bias downstream genetic analysis. Full article

The field of nanoparticle-based biotechnology has undergone substantial advancement, characterized by progress in targeted drug delivery systems, the development of innovative diagnostic and imaging platforms, the expanded adoption of environmentally sustainable (“green”) synthesis approaches, and an increasing emphasis on the integration of emerging technologies such as artificial intelligence and nanorobotics. Conventional nanoparticle synthesis often involves toxic reducing agents; however, recent advances promote eco-friendly green synthesis methods utilizing biological systems such as bacteria, fungi, algae, yeast, plants, and actinomycetes. These biological approaches are safe, sustainable, cost-effective, and capable of producing highly stable Nanoparticles (NPs). The interaction of nanomaterials with biological systems is crucial for developing intracellular and subcellular drug delivery technologies with minimal toxicity, governed by nano–bio interface mechanisms such as cellular translocation, surface wrapping, embedding, and internal attachment. Key factors influencing NP behavior include morphology, size, surface area, surface charge, and ligand chemistry. Magnetic nanoparticles, particularly iron-based forms, exhibit unique superparamagnetic properties that are strongly influenced by particle size, as explained by the Néel relaxation mechanism, in which thermal energy induces flipping of magnetic moments. Nanoparticles demonstrate diverse modes of action, including antimicrobial activity, reactive oxygen species (ROS)-induced cytotoxicity, genotoxicity, and plant growth promotion. NP performance and biological effects are strongly dependent on their size, shape, dosage, and concentration. This critical review article aims to elucidate evolution, classification, preparation methods, and multifaceted applications of nanoparticles Full article

The transition to low-emission road transport in Europe depends not only on the growth of plug-in electric vehicle (PEV) uptake, but also on the timely expansion of publicly accessible charging infrastructure. This article provides a descriptive and diagnostic assessment of the relationship between electrification dynamics and public charging infrastructure development in Europe. The analysis combines a long-run descriptive window (2015–2024, with 2025 treated separately as a scenario observation) and a core diagnostic window (2020–2024) for which a consistent proxy of potential infrastructure strain—plug-in vehicles per public recharging point (VPP)—is available. The results show a strong increase in PEV share in new registrations, from 1.0% in 2015 to 20.92% in 2024, while the number of public recharging points rose from 67,064 to 900,000 over the same period. In the core sample, VPP declined from 15.24 in 2020 to 13.92 in 2024, which is consistent with a catch-up phase in infrastructure deployment after 2021. At the same time, the short-window relationship between PEV share, infrastructure scale and average CO₂ emissions of newly registered cars remains weak and unstable, indicating the role of additional structural factors. The article contributes a transparent, replicable indicator-based framework for describing infrastructure strain in aggregate European data. In policy terms, the findings support a shift from simple point-count targets toward functionally and spatially differentiated infrastructure planning, including interoperability, power structure, and accessibility in underserved areas. Full article

This study evaluated the effects of a commercially produced, ready-to-use probiotic supplement, dominated by lactic acid bacteria, on the growth performance and selected health indicators of salmon (Salmo salar L.) fry, parr, and presmolts reared for restocking purposes. The results indicated a stage-specific response to probiotic application. In salmon fry, short-term immersion baths were associated with reduced juvenile mortality and improved tolerance to fluctuations in temperature and dissolved oxygen. In parr, immersion treatments were linked to improved growth performance, condition factor, and a lower incidence of gill-cover necrosis compared to the Control group. In presmolts, short-term dietary supplementation with probiotics was associated with increased growth rates relative to Controls. Probiotic application was associated with changes in bacterial isolates and, in some groups, lower antimicrobial resistance (AMR) indices, particularly after 14 days of immersion treatment. Probiotic supplementation was associated with improved growth and increased tolerance to environmental stressors, indicating its potential to support fish welfare and sustainable aquaculture. Full article

In ovarian cancer, reactive oxygen species (ROS) are both toxic byproducts and mediators of signaling and stress adaptation, such that the same “ROS change” can suppress or promote tumors in vivo. Here, we integratively summarize how ROS modulation reshapes tumor growth, metastasis, and treatment response in ovarian cancer, based on 22 original in vivo-containing studies that were selected from a five-database search of papers published from January 1990 to December 2025. On the antitumor axis, ROS amplification in xenograft models is accompanied by reduced tumor burden and increased markers of cell death, and can operate through diverse death programs beyond apoptosis, including pyroptosis and ferroptosis. ROS-based anticancer effects may vary depending on whether cytoprotective autophagy is co-induced. For example, in models treated with daphnetin, ROS-dependent cell death occurs together with induction of cytoprotective autophagy and the anticancer effect is strengthened when an autophagy inhibitor is added. In a therapeutic context, autophagy may thus function as an adaptive response in tumor cells to partially buffer ROS-induced stress. Conversely, on the pro-tumor axis, ROS can serve as an upstream signal driving inflammatory and metastatic processes. In a peritoneal metastasis model, GPX1 inhibition-induced ROS elevation was linked to increased metastatic burden. In the context of drug resistance, platinum resistance is proposed to be an adaptive state shaped not by the absolute level of ROS alone, but by integrated ROS-sensing and buffering circuits, the DNA damage response (DDR), and NF-κB networks. In vivo, AMPK–ROS axis activation through ACLY inhibition or resetting of drug responsiveness can be connected to tumor suppression and increased sensitivity. Furthermore, ROS modulation is not limited to tumor cell-intrinsic targets: it can also be linked to therapeutic response reprogramming at the tumor microenvironment (TME) level, such as via regulation of acidity/ROS conditions and coupling to macrophage polarization in immunocompetent syngeneic models. Taken together, these lines of in vivo evidence indicate that, in ovarian cancer, ROS should not be interpreted in a binary “increase/decrease” manner, but rather in terms of redox-buffering capacity, the engaged signaling axes (cell death, DDR, metastasis/inflammation), and interactions with TME factors. Full article