Search Results (99)

T cells play a vital role in resisting pathogen invasion and maintaining immune homeostasis. However, T cells gradually become exhausted under chronic antigenic stimulation, and this exhaustion is closely related to mitochondrial dysfunction in T cells. Mitochondria play a crucial role in the metabolic reprogramming of T cells to achieve the desired immune response. Here, we compiled the latest research on how mitochondrial metabolism determines T cell function and differentiation, with the mechanisms mainly including mitochondrial biogenesis, fission, fusion, mitophagy, and mitochondrial transfer. In addition, the alterations in mitochondrial metabolism in T-cell exhaustion were also reviewed. Furthermore, we discussed intervention strategies targeting mitochondrial metabolism to reverse T cell exhaustion in detail, including inducing PGC-1α expression, alleviating reactive oxygen species (ROS) production or hypoxia, enhancing ATP production, and utilizing mitochondrial transfer. Targeting mitochondrial metabolism in exhausted T cells may achieve the goal of reversing and preventing T cell exhaustion. Full article

Background/Objectives: Epicardial adipose tissue (EAT) is metabolically active and is in dynamic crosstalk with the surrounding cardiomyocytes, modulating their function and metabolism. Oxidative stress is a key contributor to cell death and cardiac remodeling, is a hallmark of diabetes (DM) and cardiovascular disease, such as coronary artery disease (CAD). However, little is known about these processes in EAT from patients undergoing cardiac surgery. This study investigates changes in mitochondrial dynamics, reactive oxygen species (ROS) production, and antioxidant defense levels in EAT compared to subcutaneous adipose tissue (SAT) in patients undergoing cardiac surgery, with a focus on the impact of DM and CAD. Methods: Adipose tissue biopsies were collected from 128 patients undergoing surgical cardiac intervention. Mitochondrial dynamics and oxidative stress markers were analyzed. Results: EAT exhibited increased expression of mitochondrial fusion markers [mitofusin 1 (p ≤ 0.001), mitofusin 2 (p = 0.038), and optic atrophy 1 (p ≤ 0.001)], as well as fission markers [fission 1 (p ≤ 0.001) and dynamin-related protein 1 (p ≤ 0.001)] relative to SAT. Additionally, ROS levels (dihydroethidium, p = 0.004) were elevated, while lipid peroxidation (malondialdehyde, p ≤ 0.001) was reduced in EAT compared to SAT. Reduced glutathione (GSH) levels (p ≤ 0.001) and the redox buffer ratio between reduced and oxidized glutathione (GSH/GSSG, p ≤ 0.001) were significantly increased in EAT. Interestingly, glutathione peroxidase activity (p ≤ 0.001) and the antioxidant defense markers catalase (p ≤ 0.001) and superoxide dismutase 2 (p = 0.001) were significantly reduced in EAT compared to SAT. Conclusions: The findings provide a unique molecular insight into the mitochondrial dynamics and oxidative stress profiles of EAT, highlighting potential avenues for a novel diagnostic method and therapeutic strategies for cardiac disease. Full article

The radical-mediated intramolecular translocation of cyano groups has been recognized as a useful tool for the site-selective functionalization of organic molecules. The process is believed to proceed through the addition of an in situ-generated carbon-centered radical to the nitrile triple bond, followed by the β-scission of the resulting cyclic iminyl radical intermediate to relocate the cyano group and produce a more stable carbon radical for further elaboration. Beginning in the early 1960s and continuing for the next forty years, the research in this particular area has seen a surge of growth during the past two decades with advancements in radical chemistry and photocatalysis. The present article attempts to conduct a comprehensive review of existing studies on this topic by covering the literature from 1961 to 2025. The procedures developed for the purpose are grouped and discussed in four sections according to the strategies used to generate the initial carbon radicals, which include (i) hydrogen-atom transfer (HAT), (ii) radical addition to the π system, (iii) halogen-atom transfer (XAT), and (iv) the homolytic fission of a C-C single bond. In each section, a specific emphasis will be placed on reaction conditions, substrate scopes, and mechanisms. Full article

In practical array signal processing applications, direction-of-arrival (DOA) estimation often suffers from degraded accuracy under low signal-to-noise ratio (SNR) and limited snapshot conditions. To address these challenges, we propose an off-grid DOA estimation method based on Fast Variational Bayesian Inference (OGFVBI). Within the variational Bayesian framework, we design a fixed-point criterion rooted in root-finding theory to accelerate the convergence of hyperparameter learning. We further introduce a grid fission and adaptive refinement strategy to dynamically adjust the sparse representation, effectively alleviating grid mismatch issues in traditional off-grid approaches. To address frequency dispersion in wideband signals, we develop an improved subspace focusing technique that transforms multi-frequency data into an equivalent narrowband model, enhancing compatibility with subspace DOA estimators. We demonstrate through simulations that OGFVBI achieves high estimation accuracy and resolution while significantly reducing computational time. Specifically, our method achieves more than 37.6% reduction in RMSE and at least 28.5% runtime improvement compared to other methods under low SNR and limited snapshot scenarios, indicating strong potential for real-time and resource-constrained applications. Full article

Oocyte maturation represents a fundamental biological process in bovine reproduction, establishing the physiological basis for fertilization and early embryonic development while critically determining the propagation of improved varieties and breeding efficiency. The roles of MQC in reproduction have gained substantial scientific attention. The proper maturation of oocytes fundamentally depends on adequate mitochondrial functionality. However, the intrinsic regulatory mechanisms governing MQC during bovine oocyte maturation remain incompletely characterized. Here, we discuss the most recent progress on the molecular mechanisms and roles of mitochondrial fission/fusion, biogenesis, and mitophagy in MQC. Building upon the mechanistic foundations of MQC in bovine oocyte maturation, this review identifies key mitochondrial-targeted supplements with potential applications in enhancing oocyte quality. Furthermore, we evaluate epigenetic influences on mitochondrial regulatory networks through mitochondrial–nuclear communication. Finally, we discuss the challenges in elucidating mitochondrial quality control mechanisms during oocyte maturation and propose corresponding strategies to address these obstacles. Integrating mechanistic insights, this review proposes strategies to enhance in vitro culture systems and identify oocyte quality markers, providing valuable insights for optimizing in vitro production (IVP) of bovine embryos and enhancing reproductive efficiency. Full article

Cisplatin (Cis) is a widely used chemotherapy drug, but its nephrotoxicity limits its clinical application. Acute kidney injury (AKI) is a common complication, restricting long-term use. This study investigates the mechanisms of cisplatin-induced AKI and explores potential therapeutic targets. C57BL/6J mice were intraperitoneally injected with 20 mg/kg cisplatin to establish an AKI model. Serum creatinine, urea nitrogen, and tubular injury biomarkers (NGAL, KIM-1) progressively increased, indicating kidney dysfunction. Mitochondrial ATP levels significantly decreased, along with reduced mitochondrial fission and fusion, suggesting mitochondrial dysfunction. Increased oxidases and reduced antioxidants indicated redox imbalance, and metabolic reprogramming was observed, with lipid deposition, impaired fatty acid oxidation (FAO), and enhanced glycolysis in proximal tubular epithelial cells (PTECs). Nuclear factor erythroid 2-related factor 2 (NRF2) is a key transcriptional regulator of redox homeostasis and mitochondrial function. We found NRF2 levels increased early in AKI, followed by a decrease in vivo and in vitro, suggesting activation in the stress response. Nfe2l2 knockout mice showed aggravated kidney injury, characterized by worsened kidney function and histopathological damage. Mechanistically, Nfe2l2 knockout resulted in redox imbalance, reduced ATP synthesis, mitochondrial dysfunction and metabolic dysregulation. Furthermore, we activated NRF2 using dimethyl fumarate (DMF), observing a reduction in kidney damage and lipid deposition in mice. In conclusion, activating NRF2-dependent antioxidant pathways plays a crucial role in protecting against cisplatin-induced AKI. NRF2 may serve as a potential target for developing therapeutic strategies to prevent cisplatin nephrotoxicity. Full article

In neurons, mitochondria generate energy through ATP production, thereby sustaining the high energy demands of the central nervous system (CNS). Mitochondrial dysfunction within the CNS was implicated in the pathogenesis and progression of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and multiple sclerosis, often involving altered mitochondrial dynamics like fragmentation and functional impairment. Accordingly, mitochondrial targeting represents an alternative therapeutic strategy for the treatment of these disorders. Current standard drug treatments present limitations due to adverse effects associated with their chronic use. Therefore, in recent years, nutraceuticals, natural compounds exhibiting diverse biological activities, have garnered significant attention for their potential to treat these diseases. It has been shown that these compounds represent safe and easily available sources for the development of innovative therapeutics, and by modulating mitochondrial function, nutraceuticals offer a promising approach to address neurodegenerative pathologies. We referred to approximately 200 articles published between 2020 and 2025, identified through a focused search across PubMed, Google Scholar, and Scopus using keywords such as “nutraceutical,” “mitochondrial dysfunction,” and “neurodegenerative diseases. The purpose of this review is to examine how mitochondrial dysfunction contributes to the genesis and progression of neurodegenerative diseases. Also, we discuss recent advances in mitochondrial targeting using nutraceuticals, focusing on their mechanisms of action related to mitochondrial biogenesis, fusion, fission, bioenergetics, oxidative stress, calcium homeostasis, membrane potential, and mitochondrial DNA stability. Full article

In the context of rapid urbanization, traditional villages in the Weibei Loess Plateau gully region are facing compounded pressures from social structure disruption and physical space reconstruction. It is urgent to deeply analyze the influence mechanism of social relations on spatial adaptability. This study attempts to construct an analytical framework that couples social relationships with village spatial development. With Tangjia Village in the gully region of the Weibei Loess Plateau as an example, the study integrated various data sources such as satellite imagery, interviews, and policy documents. Through social network analysis and an improved cascade failure model, the spatial adaptation processes and characteristics based on changes in kinship, occupational ties, and geographical networks were explored. The findings indicate that (1) before 2001, kinship networks led to the formation of a monocentric settlement structure. From 2001 to 2011, occupational ties fostered the differentiation of industrial and residential zones. After 2011, geographical networks drove the multifunctional integration of space. (2) Clan-based settlement zones (consisting of 80 kinship nodes) and core cultural tourism facilities are key units in maintaining spatial adaptability. The research reveals the impact mechanism of social network fission on spatial function reorganization and proposes adaptive planning strategies, aiming to provide theoretical and practical value for the coordinated governance of society and space in traditional villages. Full article

(1) Background: Generation IV supercritical water-cooled reactors (SCWRs), including small modular reactor (SCW-SMR) variants, are pivotal in nuclear technology. Operating at 300–500 °C and 25 MPa, these reactors require detailed understanding of radiation chemistry and transient species to optimize water chemistry, reduce corrosion, and enhance safety. Boron, widely used as a neutron absorber, plays a significant role in reactor performance and safety. This study focuses on the yields of radiolytic species in subcritical and supercritical water exposed to ⁴He and ⁷Li recoil ions from the ¹⁰B(n,α)⁷Li fission reaction in SCWR/SCW-SMR environments. (2) Methods: We use Monte Carlo track chemistry simulations to calculate yields (G values) of primary radicals (e⁻_aq, H^•, and ^•OH) and molecular species (H₂ and H₂O₂) from water radiolysis by α-particles and Li³⁺ recoils across 1 picosecond to 0.1 millisecond timescales. (3) Results: Simulations show substantially lower radical yields, notably e⁻_aq and ^•OH, alongside higher molecular product yields compared to low linear energy transfer (LET) radiation, underscoring the high-LET nature of ¹⁰B(n,α)⁷Li recoil nuclei. Key changes include elevated G(^•OH) and G(H₂), and a decrease in G(H^•), primarily driven during the homogeneous chemical stage of radiolysis by the reaction H^• + H₂O → ^•OH + H₂. This reaction significantly contributes to H₂ production, potentially reducing the need for added hydrogen in coolant water to mitigate oxidizing species. In supercritical conditions, low G(H₂O₂) suggests that H₂O₂ is unlikely to be a major contributor to material oxidation. (4) Conclusions: The ¹⁰B(n,α)⁷Li reaction’s yield estimates could significantly impact coolant chemistry strategies in SCWRs and SCW-SMRs. Understanding radiolytic behavior in these conditions aids in refining reactor models and coolant chemistry to minimize corrosion and radiolytic damage. Future experiments are needed to validate these predictions. Full article

Mitochondrial dysfunction is a pivotal driver in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and congenital anomalies of the kidney and urinary tract (CAKUT). The kidneys, second only to the heart in mitochondrial density, rely on oxidative phosphorylation to meet the high ATP demands of solute reabsorption and filtration. Disrupted mitochondrial dynamics, such as excessive fission mediated by Drp1, exacerbate tubular apoptosis and inflammation in AKI models like ischemia–reperfusion injury. In CKD, persistent mitochondrial dysfunction drives oxidative stress, fibrosis, and metabolic reprogramming, with epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs) regulating genes critical for mitochondrial homeostasis, such as PMPCB and TFAM. Epigenetic dysregulation also impacts mitochondrial–ER crosstalk, influencing calcium signaling and autophagy in renal pathology. Mitophagy, the selective clearance of damaged mitochondria, plays a dual role in kidney disease. While PINK1/Parkin-mediated mitophagy protects against cisplatin-induced AKI by preventing mitochondrial fragmentation and apoptosis, its dysregulation contributes to fibrosis and CKD progression. For instance, macrophage-specific loss of mitophagy regulators like MFN2 amplifies ROS production and fibrotic responses. Conversely, BNIP3/NIX-dependent mitophagy attenuates contrast-induced AKI by suppressing NLRP3 inflammasome activation. In diabetic nephropathy, impaired mitophagy correlates with declining eGFR and interstitial fibrosis, highlighting its diagnostic and therapeutic potential. Emerging therapeutic strategies target mitochondrial dysfunction through antioxidants (e.g., MitoQ, SS-31), mitophagy inducers (e.g., COPT nanoparticles), and mitochondrial transplantation, which mitigates AKI by restoring bioenergetics and modulating inflammatory pathways. Nanotechnology-enhanced drug delivery systems, such as curcumin-loaded nanoparticles, improve renal targeting and reduce oxidative stress. Epigenetic interventions, including PPAR-α agonists and KLF4 modulators, show promise in reversing metabolic reprogramming and fibrosis. These advances underscore mitochondria as central hubs in renal pathophysiology. Tailored interventions—ranging from Drp1 inhibition to mitochondrial transplantation—hold transformative potential to mitigate kidney injury and improve clinical outcomes. Additionally, dietary interventions and novel regulators such as adenogens are emerging as promising strategies to modulate mitochondrial function and attenuate kidney disease progression. Future research should address the gaps in understanding the role of mitophagy in CAKUT and optimize targeted delivery systems for precision therapies. Full article

This study presents a comprehensive uncertainty and sensitivity analysis of the effective neutron multiplication factor ($k_{\mathrm{eff}}$) in a large-scale sodium-cooled fast reactor (SFR) modeled after the European Sodium Fast Reactor. Utilizing the Serpent Monte Carlo code and the ENDF/B-VII.1 cross-section library, this research investigates the impact of cross-section perturbations in key isotopes (²³⁵U, ²³⁸U, and ²³⁹Pu for both mixed oxide (MOX) and metal fuels. Particular focus is placed on the capture, fission, and inelastic scattering reactions, as well as the effects of fuel temperature on reactivity through Doppler broadening. The findings reveal that reactivity in MOX fuel is highly sensitive to the fission cross sections of fissile isotopes (²³⁹Pu and ²³⁸U, while capture and inelastic scattering reactions in fertile isotopes such as ²³⁸U play a significant role in reducing reactivity, enhancing neutron economy. Additionally, this study highlights that metal fuel configurations generally achieve a higher ($k_{\mathrm{eff}}$) compared to MOX, attributed to their higher fissile atom density and favorable thermal properties. These results underscore the importance of accurate nuclear data libraries to minimize uncertainties in criticality evaluations, and they provide a foundation for optimizing fuel compositions and refining reactor control strategies. The insights gained from this analysis can contribute to the development of safer and more efficient next-generation SFR designs, ultimately improving operational margins and reactor performance. Full article

The canonical model of vertebrate sex chromosome evolution predicts a one-way trend toward degradation. However, most sex chromosomes in lower vertebrates are homomorphic. Recent progress in studies of sex determination has resulted in the discovery of more than 30 master sex determination (MSD) genes, most of which are from teleost fish. An analysis of MSD gene acquisition, recombination suppression, and sex chromosome-specific sequences revealed correlations in the modes of MSD gene acquisition and the evolution of sex chromosomes. Sex chromosomes remain homomorphic with MSD genes acquired by simple mutations, gene duplications, allelic variations, or neofunctionalization; in contrast, they become heteromorphic with MSD genes acquired by chromosomal inversion, fusion, and fission. There is no recombination suppression with sex chromosomes carrying MSD genes gained through simple mutations. In contrast, there is extensive recombination suppression with sex chromosomes carrying MSD genes gained through chromosome inversion. There is limited recombination suppression with sex chromosomes carrying MSD genes gained through transposition or translocation. We propose a cause–effect model that predicts sex chromosome evolution as a consequence of the acquisition modes of MSD genes, which explains the evolution of sex chromosomes in various vertebrates. A key factor determining the trend of sex chromosome evolution is whether non-homologous regions are created during the acquisition of MSD genes. Chromosome inversion creates inversely homologous but directly non-homologous sequences, which lead to recombination suppression but retain recombination potential. Over time, recurrent recombination in the inverted regions leads to the formation of strata and may cause the degradation of sex chromosomes. Depending on the nature of deletions in the inverted regions, sex chromosomes may evolve with dosage compensation, or the selective retention of haplo-insufficient genes may be used as an alternative strategy. Full article

Hydroxytyrosol (HT), a principal bioactive phytochemical abundant in Mediterranean dietary sources, has emerged as a molecule of significant scientific interest owing to its multifaceted health-promoting properties. Accumulating evidence suggests that HT’s therapeutic potential in metabolic disorders extends beyond conventional antioxidant capacity to encompass mitochondrial regulatory networks. This review synthesizes contemporary evidence from our systematic investigations and the existing literature to delineate HT’s comprehensive modulatory effects on mitochondrial homeostasis. We systematically summarized the impact of HT on mitochondrial dynamics (fusion/fission equilibrium), biogenesis and energy metabolism, mitophagy, inter-organellar communication with the endoplasmic reticulum, and microbiota–mitochondria crosstalk. Through this multidimensional analysis, we established HT as a mitochondrial homeostasis modulator with potential therapeutic applications in metabolic syndrome (MetS) and its related pathologies including type 2 diabetes mellitus, obesity-related metabolic dysfunction, dyslipidemia, non-alcoholic steatohepatitis, and hypertension-related complications. Moreover, we further discussed translational challenges in HT research, emphasizing the imperative for direct target identification, mitochondrial-targeted delivery system development, and combinatorial therapeutic strategies. Collectively, this review provides a mechanistic framework for advancing HT research and accelerating its clinical implementation in MetS and its related diseases. Full article

Mitochondrial dynamics, governed by fusion and fission, are crucial for maintaining cellular homeostasis, energy production, and stress adaptation. MFN2 and OPA1, key regulators of mitochondrial fusion, play essential roles beyond their structural functions, influencing bioenergetics, intracellular signaling, and quality control mechanisms such as mitophagy. Disruptions in these processes, often caused by MFN2 or OPA1 mutations, are linked to neurodegenerative diseases like Charcot-Marie-Tooth disease type 2A (CMT2A) and autosomal dominant optic atrophy (ADOA). This review explores the molecular mechanisms underlying mitochondrial fusion, the impact of MFN2 and OPA1 dysfunction on oxidative phosphorylation and autophagy, and their role in disease progression. Additionally, we discuss the divergent cellular responses to MFN2 and OPA1 mutations, particularly in terms of proliferation, senescence, and metabolic signaling. Finally, we highlight emerging therapeutic strategies to restore mitochondrial integrity, including mTOR modulation and autophagy-targeted approaches, with potential implications for neurodegenerative disorders. Full article

Vemurafenib is a BRAF (rapidly accelerated fibrosarcoma B-type)-targeted therapy used to treat patients with advanced, unresectable melanoma. It inhibits the MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathway and tumor proliferation in BRAF^V600E-mutated melanoma cells. Resistance to vemurafenib has been reported in melanoma patients due to secondary NRAS (neuroblastoma RAS viral oncogene homolog) mutations, which lead to paradoxical MAPK pathway activation and tumor proliferation. However, the impact of this paradoxical activation on mitochondrial dynamics and function in NRAS-mutated melanoma is unclear. Here, we investigated the effects of vemurafenib on NRAS^Q61R-mutated melanoma cells, focusing on mitochondrial dynamics and function. As expected, vemurafenib did not exhibit cytotoxicity in SK-MEL-147 NRAS^Q61R-mutated melanoma cells, even after 72 h of incubation. However, it significantly enhanced the MAPK/ERK signaling through paradoxical activation, accompanied by decreased expression of mitochondrial fusion proteins and activation of the fission protein DRP1 (dynamin-related protein 1), leading to small, rounded mitochondrial morphology. These observations were corroborated by transcriptome data obtained from NRAS-mutated melanoma patients, showing MFN1 (mitofusin 1) and OPA1 (optic atrophy 1) downregulation and DNM1L (DRP1 gene) upregulation. Interestingly, inhibition of mitochondrial fission with mdivi-1 or modulation of oxidative phosphorylation via respiratory chain inhibition or uncoupling significantly sensitized NRAS^Q61R-mutated melanoma cells to vemurafenib. Despite vemurafenib’s low cytotoxicity in NRAS-mutated melanoma, targeting mitochondrial dynamics and/or oxidative phosphorylation may offer a promising strategy for combined therapy. Full article