Search Results (36,449)

High-efficiency Ovum Pick-Up (OPU) and in vitro embryo production (IVP) are critical for the genetic improvement of high-value Wagyu cattle. However, oxidative stress and mitochondrial dysfunction during oocyte maturation remain major bottlenecks limiting blastocyst yield. This study investigated the role of inhibin in Wagyu oocyte competence through two independent proof-of-concept approaches. In the in vivo active immunization model, thirty Wagyu donors were immunized with a recombinant inhibin protein (INHA group), resulting in a significant increase in the number of recovered cumulus–oocyte complexes (COCs) (461 vs. 279, p < 0.05) and the proportion of high-quality oocytes compared to controls. Oocytes from the INHA group exhibited improved cytoplasmic maturation and mitochondrial function, characterized by higher membrane potential (ΔΨm, JC-1 ratio: 1.55 ± 0.06 vs. 0.83 ± 0.08, p < 0.05), elevated ATP content (2.35 ± 0.07 vs. 1.63 ± 0.03 pmol/oocyte, p < 0.05), and increased NADPH levels. Furthermore, the INHA group showed significantly reduced reactive oxygen species (ROS) accumulation and an increased GSH/GSSG ratio (8.48 ± 0.18 vs. 6.25 ± 0.09, p < 0.05), indicating restored redox homeostasis. Independently, in the in vitro anti-inhibin antibody (AIA) supplementation model, AIA supplementation during oocyte maturation significantly improved the nuclear maturation rate (92.96% ± 1.04%), blastocyst formation rate (56.63% ± 2.36%), and total cell number compared to controls (p < 0.05). Notably, AIA-derived blastocysts achieved a significantly higher pregnancy rate (78.65% ± 1.57%) following transfer. Collectively, these findings demonstrate that targeting inhibin mitigates oxidative injury and stabilizes mitochondrial bioenergetics, providing two distinct, physiology-based strategies for optimizing Wagyu oocyte yield and embryo production. Full article

Background: Predicting functional recovery after selective nerve transfer remains challenging. Intraoperative nerve action potential (NAP) recording is widely used to confirm axonal continuity in peripheral nerve surgery; however, its quantitative prognostic value in selective nerve transfer has not been clearly established. This study evaluated whether intraoperative donor fascicle NAP amplitude predicts functional recovery following selective ulnar-to-musculocutaneous nerve transfer (Oberlin procedure) for restoration of elbow flexion. Methods: This retrospective exploratory observational study included 20 patients who underwent selective ulnar-to-musculocutaneous nerve transfer (Oberlin procedure) with standardized intraoperative neurophysiological mapping and quantitative donor fascicle NAP recording. Functional outcome specific to elbow flexion was assessed at last follow-up using the Medical Research Council (MRC) grading system. Time to first electromyographic evidence of biceps reinnervation was recorded. Associations between intraoperative NAP amplitude and functional, temporal, and clinical variables were analyzed using Spearman’s rank correlation coefficient and non-parametric tests. Results: Donor NAP amplitude demonstrated substantial interindividual variability (range 60–400 µV; median 137.5 µV, IQR 87.5–200 µV). No significant associations were observed between NAP amplitude and final MRC grade (ρ = −0.103; p = 0.666), time to electromyographic reinnervation (days: ρ = −0.123; p = 0.617), patient age, or time from injury to surgery. A moderate negative correlation between NAP amplitude and lesion severity was observed but did not reach statistical significance in this small cohort (ρ = −0.419; p = 0.0659). In contrast, shorter time to electromyographic reinnervation was significantly associated with improved final functional outcome (ρ = −0.559; p = 0.013). No patient reported postoperative hand weakness. Conclusions: In this exploratory cohort, intraoperative donor NAP amplitude was not associated with time to electromyographic reinnervation or final elbow flexion strength following selective ulnar-to-musculocutaneous nerve transfer. Although intraoperative NAP mapping remains essential to confirm axonal continuity and conduction viability of the donor fascicle, NAP amplitude did not demonstrate prognostic value in this cohort and should be interpreted cautiously as an isolated predictor of functional recovery, particularly given the limited sample size and exploratory design. These findings suggest that recovery after selective nerve transfer may be influenced by broader biological determinants, including regenerative timing, rather than by isolated intraoperative amplitude metrics. Full article

Obesity-associated carcinogenesis offers a model to explore the transition from metabolic dysregulation to genomic instability and carcinogenesis. Adenosine 5′-monophosphate-activated protein kinase (AMPK), the principal cellular energy sensor, coordinates adenosine triphosphate (ATP) production with metabolic demand; however, in obesity, AMPK activity is impaired, resulting in reduced ATP, elevated Adenosine Monophosphate (AMP), and cellular energy stress. Deoxyribonucleic Acid (DNA) polymerases ε (Pol ε) and δ (Pol δ) maintain replication fidelity via a 3′→5′ exonuclease proofreading activity that removes misincorporated nucleotides. Elevated AMP directly binds and selectively inhibits the exonucleases, conserving energy at the expense of genomic accuracy. As a result, replication errors escape correction and accumulate, some conferring a selective advantage and driving carcinogenic evolution. Therapeutic and lifestyle interventions that activate AMPK—including weight loss, exercise, metformin, and aspirin—restore ATP production, lower AMP, and relieve inhibition of exonuclease proofreading, thereby preserving genomic integrity and slowing mutation-driven carcinogenesis. This framework reveals two core biological principles: 1. Energy metabolism and DNAreplication fidelity are mechanistically coupled at the DNA polymerase active site. 2. The mutation rate is an adaptive metabolic phenotype, modulated by AMP levels. These concepts redefine the metabolic–genetic interface in carcinogenesis and highlight AMPK activation as a rational target for obesity-associated cancer prevention. Full article

We previously demonstrated that human herpesvirus 6A infects papillary thyroid cancer cells (BCPAP), inducing molecular changes compatible with a tumor-promoting phenotype, including increased expression of R273H mutant TP53 (mutp53), upregulation of c-Myc, and enhanced secretion of IL-6. To investigate whether and how epigenetic mechanisms contribute to these virus-induced effects, we examined the histone methyltransferase EZH2, a key regulator of chromatin repression frequently altered in cancer. HHV-6A infection reduced EZH2 expression and global H3K27me3 levels. Pharmacological inhibition of EZH2 using DS-3201 reproduced some of the molecular effects of viral infection, including increased mutp53 stability. Both viral infection and EZH2 inhibition induced delayed upregulation of SIRT1, which mediated deacetylation-dependent stabilization of mutp53 while reducing c-Myc expression. Indeed, the inhibition of SIRT1 with EX-527 reversed mutp53 accumulation but restored c-Myc expression and increased extracellular IL-6 release. This drug also reduced cell survival, suggesting that SIRT1 supports cellular adaptation to oncogenic stress triggered by EZH2 loss. Overall, our findings identify an epigenetic axis in which the HHV-6A-mediated downregulation of EZH2 induces SIRT1, regulating mutp53 stability and c-Myc expression and reshaping inflammatory signaling to maintain cell viability. These results establish a mechanistic link between viral infection, epigenetic remodeling, and oncogenic dependency. They also suggest that targeting IL-6 signaling could represent a therapeutic vulnerability in HHV-6A-associated thyroid cancer, particularly in combination with SIRT1 inhibitors. Full article

Gestational Diabetes Mellitus (GDM) is the most common metabolic complication of pregnancy, affecting approximately 14% of pregnancies globally. Despite the frequent normalization of glycemic parameters immediately after delivery, GDM is an important precursor of subsequent chronic disease, increasing the risk of type 2 diabetes (T2DM). Current international guidelines suggest just a strictly observational approach during the immediate puerperium, recommending metabolic screening only between 6 and 12 weeks postpartum. This has contributed to the creation of a therapeutic “orphan window” where women receive no specific metabolic support, leaving their metabolic status unassessed and unmanaged. We postulate that the immediate postpartum period represents a critical window of “metabolic plasticity” where the abrupt cessation of placental hormones offers a unique opportunity to restore insulin sensitivity and promote “beta-cell rest” before the onset of irreversible dysfunction. Consequently, this narrative review and perspective examines the epidemiological urgency of the GDM-to-T2DM transition and provides a biological rationale for early pharmacological or nutraceutical intervention. Specifically, we discuss the limitations of metformin and present the hypothesis of myo-inositol combined with alpha-lactalbumin as a safe, lactation-compatible “bridging therapy” to preserve beta-cell function, improve compliance, and modify the natural history of diabetes in this high-risk population, highlighting that this theoretical proposal requires validation through future clinical trials. Full article

Mitophagy serves as an essential quality control mechanism that maintains mitochondrial homeostasis through selective autophagic clearance of damaged organelles. Vascular dementia (VD) has been increasingly associated with mitophagy dysregulation in recent studies. However, the precise molecular mechanisms underlying mitophagy’s involvement in VD pathogenesis remain poorly characterized. To elucidate the role of mitophagy in VD, we systematically examined the expression of key mitophagy pathways in hippocampal neurons of bilateral common carotid artery occlusion (BCCAO) rats and in oxygen–glucose deprivation (OGD)-treated HT22 cells. Intriguingly, under autophagy-deficient conditions, both BNIP3 and BNIP3L were markedly downregulated, whereas FUNDC1 expression increased; PINK1/Parkin levels remained unaltered. To further dissect the functional contributions of BNIP3 and BNIP3L, we administered the mitochondrial fission inhibitor Mdivi-1 to BCCAO model rats. Histopathological analysis revealed pronounced neuronal damage and apoptosis in the hippocampal region, which was further exacerbated upon Mdivi-1 treatment. In vitro, BNIP3 silencing significantly compromised cell viability, elevated reactive oxygen species (ROS) accumulation, disrupted mitochondrial membrane potential (ΔΨm), suppressed mitophagy, and increased apoptotic rates. Conversely, BNIP3 overexpression reversed these detrimental effects. Notably, treatment with the autophagy inhibitor 3-methyladenine (3-MA) diminished LC3B-Tomm20 colocalization and intensified apoptosis, reinforcing the critical role of BNIP3-mediated mitophagy in neuronal survival. Similarly, BNIP3L overexpression enhanced cell viability, attenuated ROS production, restored ΔΨm, and mitigated apoptosis, while 3-MA treatment again impaired mitophagic flux and worsened cell death. Collectively, these findings underscore the critical and distinct roles of BNIP3 and BNIP3L in maintaining mitochondrial homeostasis and neuronal survival under ischemic conditions. Full article

Cochlear implantation (CI) effectively restores hearing across the whole lifespan but may be followed by vestibular complaints, especially in adult recipients. The aim of this narrative review is to provide a comprehensive characterization of vestibular complaints after CI in adults, collecting clinical and instrumental data, as well as discussing the risk factors for their development. From data reported in the literature, we defined five recurring clinical presentations of postoperative vestibular disturbances (phenotypes): acute postoperative vestibular syndrome, benign paroxysmal positional vertigo (BPPV), delayed Ménière-like vertigo attributable to secondary endolymphatic hydrops, chronic postoperative disequilibrium, and stimulation-linked vertigo. According to the different pathogeneses underlying each presentation, the management of postoperative vestibular complaints should be phenotype-guided, including short-course vestibular suppressants and early mobilisation for acute presentations; canalith repositioning for BPPV; empiric therapy for hydropic-like episodes; and vestibular rehabilitation when imbalance is persistent, programming changes for stimulation-linked symptoms. Alongside this phenotype-driven approach, subjective symptoms are common across cohorts but are usually transient and persistent disability is uncommon. Furthermore, instrumental data across the studies indicate that objective abnormalities cluster in otolith and low-frequency canal measures: Cervical, ocular VEMP, and caloric responses are more often impaired than high-frequency canal function on vHIT, confirming histopathological studies showing preferential saccular involvement during the insertion of the electrode array. The risk of postoperative vestibular complaints not only appears to be modulated more by patient-related factors, especially pre-existing vestibular loss, but also by the aetiology of deafness, or age, rather than by device characteristics; atraumatic surgical approaches may further reduce this risk. This review emphasizes that future research on vestibular complaints after CI should adopt standardized phenotypes when evaluating symptoms, objective vestibular function, falls, and quality of life. Additionally, it should correlate these outcomes with hypothetical risk factors and detailed surgical reports. 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

Interactions between the chemical compounds contained in mouthwashes and the components of dental composites may significantly influence their functional properties. The study investigated the effect of mouthwashes on the mechanical properties and color stability of a restorative nanocomposite. Twelve mouthwashes characterized by different chemical compositions were selected and distilled water was used as a control. Composite specimens were conditioned for 24 h, 48 h, and 72 h. Changes in microhardness (HV), compressive strength (CS) and diametral tensile strength (DTS) were evaluated. In addition, color changes were analyzed using spectrophotometric measurements. The results demonstrated a significant decrease in both HV and CS after exposure to mouthwashes, depending on their composition and immersion time. DTS values remained stable. Color changes were statistically significant; however, the values observed remained within clinically acceptable limits from an esthetic standpoint. The loss of mechanical properties was generally most pronounced during the initial period of contact between the mouthwashes and the tested material, which should be considered as unfavorable. The influence of ethanol molecules on mechanical properties was not stronger than that of many ethanol-free solutions. The frequently suggested correlation between changes in composite material hardness and the pH values of mouthwashes was not confirmed. Full article

Low-light image enhancement (LLIE) remains challenging due to severe degradation of high-frequency structures and semantic ambiguity under extreme darkness. Although existing methods achieve satisfactory brightness recovery, they often suffer from structural inconsistency and semantic drift, as diverse scenes are typically processed with uniform enhancement strategies or static text prompts. To address these issues, we propose a Multi-Modal Structural and Semantic-Adaptive Network (MSSA-Net) under a structure-anchored paradigm. First, we design a Multi-Scale Self-Refinement Block (MSRB) to enhance degraded visible representations through multi-scale feature extraction and progressive refinement. Meanwhile, a pseudo-infrared structural prior derived from the input image is introduced to provide noise-insensitive geometric cues. These cues are extracted via a Structure-Guided Cross-Attention (SGCA) module to produce structure-dominant features. The refined visible features and structural features are then adaptively integrated through an adaptive residual fusion (ARF) module to achieve balanced restoration. Furthermore, we develop a Large Multi-modal Model (LMM)-Driven Scene-Adaptive Attention mechanism that generates instance-aware scene tags from a coarse preview and injects semantic embeddings into visual features. Extensive experiments demonstrate that MSSA-Net improves structural fidelity, brightness recovery, and semantic naturalness across multiple benchmarks. Full article

Chronic kidney disease (CKD) involves uremic toxin-driven tubular injury and systemic vascular dysfunction, in which mitochondrial impairment and apoptotic cell loss contribute to progressive tissue deterioration. Accordingly, a targeted EV platform is required to enable efficient miRNA delivery to the toxin-stressed tubular–endothelial compartment. Based on our previous study showing that melatonin restores miR-4516 levels under CKD-related stress, we directly loaded miR-4516 into engineered extracellular vesicles (EVs) to evaluate its effects on mitochondrial function and cell survival. Here, we engineered EVs with a G3-C12/RGD surface modification and established a miR-4516 loading strategy to enhance delivery to kidney proximal tubule cells and vascular endothelial cells. miR-4516 loading increased EV-associated miR-4516 levels without major changes in particle size distribution, and EV identity was supported by CD9 and CD81 expression. Confocal microscopy and flow cytometry demonstrated increased cellular uptake of miR-4516-loaded G3-C12/RGD-EVs compared with control EVs in TH1 proximal tubule cells and HUVECs. Under indoxyl sulfate stress, engineered EV treatment restored intracellular miR-4516 and improved mitochondrial function, as indicated by recovery of respiratory Complex I and Complex IV activities and improved Seahorse bioenergetic parameters (OCR/ECAR, basal and maximal respiration, ATP-linked respiration, and spare respiratory capacity). Annexin V staining further indicated reduced toxin-induced apoptosis. In an adenine diet-induced CKD mouse model, intravenous administration of miR-4516-loaded G3-C12/RGD-EVs improved urinary albumin-to-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine. These findings indicate that miR-4516-loaded, targeting-engineered EVs may mitigate uremic toxin-associated mitochondrial dysfunction and renal impairment in CKD. Full article

Background and Objectives: Pro-inflammatory diet and high-fat diet (HFD) often coexist in real-world, but their combined impact on the gut–liver axis and potential nutritional countermeasures remain insufficiently studied. This study aimed to evaluate a pro-inflammatory–high-fat composite dietary pattern on the intestine and liver in the population, and to further evaluate the protective potential of astaxanthin (ATX) in complementary experimental systems. Methods: Data from the NHANES 2005–2010 were used to construct four composite exposure groups based on the dietary inflammation index (DII) and energy from fat. Survey-weighted regression analyses were performed to examine associations with systemic inflammation and liver injury. Interaction and C-reactive protein (CRP)-mediated effect analyses were conducted. Fifty SD rats were randomly divided into control group, model group induced by HFD combined with inflammatory factors, and low-, medium-, and high-dose Haematococcus pluvialis (HP) intervention groups. Serum lipids, liver enzymes, liver and colon pathology, and inflammatory and oxidative markers were measured in rats. In an in vitro organ-on-chip barrier model, the effect of ATX was observed when colonic barrier damage was induced using palmitic acid and lipopolysaccharides. Results: The high DII combined with HFD showed the largest increases in CRP, liver enzymes, and fatty liver index. A synergistic interaction was observed between DII and HFD, with CRP mediating approximately 20% of the effect. In rat model, HP-derived ATX improved the lipid profile, attenuated hepatic steatosis and oxidative damage, and reduced colonic pro-inflammatory cytokines, while restoration of tight junction proteins was limited. In colon organoid model, ATX showed limited efficacy in improving inflammation and barrier function. Conclusions: The pro-inflammatory–high-fat dietary pattern synergistically exacerbates gut–liver dysfunction. HP-derived ATX alleviates metabolic and inflammation-induced enterohepatic comorbidity, but its effect on repairing barrier structure is limited. Full article

The automatic reading recognition of digital instruments is crucial for achieving metering automation and intelligent inspection. However, in non-standardized industrial environments, the masking effect caused by the coupling of non-uniform low-light conditions and the reflective surfaces of instrument panels severely degrades the displayed information, significantly limiting the recognition performance. Conventional image processing methods, while aiming to restore the imaging quality of instrument panels through low-light enhancement, inevitably introduce overexposure and indiscriminately amplify background noise during this process. To address the two key challenges of illumination recovery and noise suppression in the process of restoring panel image quality under non-uniform low-light conditions, this paper proposes a coarse-to-fine cascaded perception framework (CFCP). First, a lightweight YOLOv10 detector is employed to coarsely localize the meter reading region under non-uniform illumination conditions. Second, an Adaptive Illumination Correction Module (AICM) is designed to decouple and correct the illumination component at the pixel level, effectively restoring details in dark areas. Then, an Illumination-invariant Feature Perception Module (IFPM) is embedded at the feature level to dynamically perceive illumination-invariant features and filter out noise interference. Finally, the refined detection results are fed into a lightweight sequence recognition network to obtain the final meter readings. Experiments on a self-built industrial digital instrument dataset show that the proposed method achieves 93.2% recognition accuracy, with 17.1 ms latency and only 7.9 M parameters. Full article

Seed aging is a major constraint for plant establishment in arid and semi-arid ecosystems, where poor seed vigor directly limits species persistence and restoration success. Desert species are particularly vulnerable to storage- and stress-induced deterioration, yet practical strategies to recover germination capacity in aged seeds remain limited. This study aimed to quantify aging-induced losses in germination performance and to evaluate whether exogenous gibberellic acid (GA₃) can partially restore seed vigor through physiological, biochemical, and hormonal regulation. Fresh seeds (FS), naturally aged (NA), and artificially aged (AA) seeds of four desert species (Salsola affinis C.A.Mey., Trigonella arcuata C.A.Mey., Ceratocarpus arenarius L., and Alyssum desertorum Stapf) were exposed to graded GA₃ concentrations (0–500 mg L⁻¹). Germination indices (GP, GR, GI, VI), antioxidant enzymes (SOD, POD, CAT), lipid peroxidation (MDA), phytohormones (IAA, ABA, cytokinins), and multivariate trait relationships were assessed. Without GA₃, NA reduced germination potential by 22.8–33.6%, while AA caused more severe losses of 42.4–67.8%, depending on species. Germination rate declined by 15.7–32.5% under NA and 36.4–65.2% under AA. GA₃ application improved all germination indices up to 200 mg L⁻¹ (GA200), which increased GP by 22.8–32.0% and vitality index by 17.0–28.5% compared with GA₀, whereas GA500 showed diminishing returns. Aging suppressed antioxidant enzymes by 15–20% (NA) and 30–45% (AA) and increased MDA by up to 50%, while GA200 enhanced SOD, POD, and CAT and reduced MDA by 8–18%. Aging also reduced IAA and cytokinins (~28–50%) and increased ABA (27.7–77.4%), with GA200 partially restoring hormonal balance. In conclusion, GA₃ at an optimal dose (200 mg L⁻¹) partially reverses aging-induced physiological and hormonal constraints, improving germination and vigor, although recovery remains limited under advanced deterioration. Full article

Two-pore domain potassium (K₂P) channels are the most recently identified family of potassium channels. They are regarded as the largest group of background “leak” channels, encoded by 15 mammalian KCNK genes, and divided into six subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). These channels have a role in stabilizing the resting membrane potential. Their widespread presence in the heart and vasculature supports cellular homeostasis by regulating cardiac rhythm, vascular tone, and protection against ischemic stress. The TASK, TWIK, and TREK subfamilies are the most abundantly expressed K₂P channel subfamilies in the cardiovascular system, and dysregulation of specific members has been strongly linked to the development of major cardiovascular diseases. Mutations in TASK-1 have been identified in patients with pulmonary arterial hypertension, providing human genetic evidence linking K₂P dysfunction to pulmonary vascular disease. While alterations in other K₂P channels, such as TREK-1, have been demonstrated in preclinical studies where reduced channel activity is associated with ischemia–reperfusion injury and promotes cardiac arrhythmias. Growing evidence suggests that K₂P channels could serve as promising therapeutic targets, with pharmacological activation of TASK-1 and TREK-1, for instance, that might help restore vascular tone, reduce remodeling, and offer cardioprotection. Their unique leak-channel properties enable the development of highly selective treatments. This review addresses the molecular biology, physiological roles, and disease relevance of K₂P channels in the cardiovascular and pulmonary systems, emphasizing their potential as targets for innovative therapies in cardiovascular diseases. Full article