Search Results (4,852)

Background/Objectives: Incorporating parent training into cognitive-behavioral therapy for anxious youth has not been shown to significantly improve outcomes perhaps because these interventions have not addressed potential interfering psychological barriers to implementing parenting changes and rarely offer between-session support. There is growing evidence that Acceptance and Commitment Therapy (ACT) can target these psychological barriers and generate more flexible and adaptive behavioral repertoires in parents of children with a variety of presenting challenges. Methods: Following a pilot trial of “Acceptance and Commitment Therapy for Parents of Anxious Children (ACT-PAC)” a six-week group-based intervention focused on targeting psychological barriers to parenting change using mindfulness and acceptance approaches, we collected qualitative feedback from participants in two post-treatment phases by conducting individual interviews and a focus group with participants that completed the intervention. Results: Analysis of interview responses revealed that parents found ACT principles and processes to be helpful, and many also appreciated the ACT-PAC group setting that allowed parents to recognize their experiences were shared by others and to self-disclose in a non-judgmental space. Feedback from the focus group further provides preliminary evidence that ACT-PAC is acceptable to and feasible for parent participants and suggests modifications such as involving additional caregivers, making resources more readily available, and creative structural changes that may facilitate between-session practice. Conclusions: Results suggest that the group-based intervention can be both maintained and improved for future participants. Limitations to generalizability in light of possible selection bias and the small focus group sample size are addressed. Full article

Cardiovascular disease remains the leading cause of mortality in kidney transplant recipients (KTRs). Arterial hypertension is present in a vast majority of patients after kidney transplantation, constituting the most prevalent cardiovascular comorbidity, and is a significant modifiable risk factor for other cardiovascular complications and graft loss. The 2024 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines do not address blood pressure control strategies in KTRs, and the prior 2021 KDIGO recommendations targeting values below 130/80 mmHg rely primarily on data extrapolated from non-KTR populations. This represents an existing evidence gap in the management of post-transplant hypertension. Dihydropyridine calcium channel blockers and angiotensin receptor blockers remain first-line antihypertensive medications, although most studies assessing their effectiveness in KTRs date back more than 15 years. The current treatment guidelines are based largely on limited and outdated data. Optimal selection and individualization of immunosuppressive therapy and—when feasible—its modification in some KTRs may be important in improving blood pressure control. This includes, for example, a reduction in the calcineurin inhibitor or steroid dose, as well as the use of mTOR inhibitors or belatacept. The lack of large, up-to-date randomized trials in the KTR population underscores the pressing need for further extensive research focused on this patient group. Full article

The CRISPR/Cas9 system has been widely used for gene editing in various species; however, mosaicism remains a significant challenge. This study aimed to improve gene editing efficiency and reduce mosaicism in porcine embryos by exploring double electroporation pre- and post-in vitro fertilization combined with zona pellucida (ZP) removal. We evaluated the effects of these treatments on the development and mutation rates of oocytes/zygotes edited with guide RNAs (gRNAs) targeting GGTA1, CMAH, or B4GALNT2 genes. Double electroporation significantly increased the total and biallelic mutation rates in ZP-intact zygotes but not in ZP-free zygotes edited using GGTA1-targeted gRNAs. All blastocysts from ZP-free zygotes exhibited biallelic mutations following double electroporation. For the CMAH gene, all blastocysts exhibited mutations (biallelic mutations ≥ 80%); however, double electroporation and ZP removal did not affect their mutation rates or efficiency. For the B4GALNT2 gene, double electroporation significantly increased total mutation rates in ZP-intact zygotes, whereas all blastocysts from ZP-free zygotes showed biallelic mutation. These findings suggest that double electroporation, particularly with ZP removal, may enhance gene-editing efficiency, reduce mosaicism and improve the success of genetic modifications. Full article

Reparative macrophage polarization and macrophage-derived reactive oxygen species (ROS) are required for ischemia-induced revascularization in peripheral artery disease (PAD). Our previous study showed that mitochondrial fission protein dynamin-related protein 1 (DRP1) promotes reparative polarization and metabolic reprogramming in macrophages and post-ischemic neovascularization. However, the redox-dependent mechanism governing DRP1 activation in this context remains elusive. Here, using a mouse hindlimb ischemia (HLI) model of PAD, we identify cysteine sulfenylation (CysOH) of DRP1 as a critical redox modification induced in ischemic bone marrow (BM)-derived cells. BM chimeric mice reconstituted with CRISPR/Cas9-generated “redox-dead” DRP1-C631A knock-in mutant (Drp1^C/A) BM exhibited markedly reduced limb perfusion recovery and CD31⁺ capillary density in ischemic muscles following HLI. These defects were associated with enhanced Ly6G⁺ neutrophil accumulation, pro-inflammatory F4/80⁺CD80⁺ M1-like macrophages and reduced anti-inflammatory F4/80⁺CD206⁺ M2-like macrophages in ischemic muscle. Mechanistically, using an in vitro PAD model, hypoxia serum starvation (HSS) rapidly induced NADPH oxidase 2-dependent cytosolic ROS production and DRP1-CysOH formation in wild-type macrophages. In contrast, Drp1^C/A macrophages failed to undergo DRP1-CysOH-dependent mitochondrial fission under HSS, resulting in aberrant metabolic reprogramming characterized by enhanced glycolysis and mitochondrial ROS, pro-inflammatory p-NF-κB and M1-genes, and suppressed anti-inflammatory p-AMPK, efferocytosis and M2-genes. Thus, our findings establish DRP1 sulfenylation as a previously unrecognized redox-sensing mechanism that links ischemia-induced ROS to reparative macrophage reprogramming and revascularization, identifying a novel therapeutic target for PAD. Full article

Post-Quantum Cryptography (PQC) migration to National Institute of Standards and Technology (NIST) Federal Information Processing Standards (FIPS) 203, 204, and 205 under the National Security Agency (NSA) Commercial National Security Algorithm Suite (CNSA) 2.0 is a multi-year, multi-domain transformation across cloud, enterprise, embedded, operational technology (OT), tactical, and national-security systems. Anthropic’s Claude Mythos Preview (April 2026) introduces artificial intelligence (AI)-accelerated cybersecurity capabilities that intersect this migration directly, performing autonomous reasoning against previously unknown vulnerabilities in production software—a qualitative departure from signature-based and static and dynamic application security testing (SAST/DAST) tooling. Drawing on federal guidance from NIST, NSA, the Office of Management and Budget (OMB), and the Cybersecurity and Infrastructure Security Agency (CISA), and on independent analyses from the Centre for Emerging Technology and Security (CETaS) and the UK AI Security Institute, we present a lifecycle and architecture analysis of how Mythos-class models alter PQC migration timelines, risk surfaces, lifecycle dependencies, and architectural constraints. Modeling Mythos as both accelerator and destabilizer, we derive an analytic projection of a compressed two-to-four-year migration window for highest-exposure systems, against traditional baselines of five-to-ten years for small organizations and twelve-to-fifteen-plus years for large enterprises. The compression collapses human-labor bottlenecks in discovery, planning, and code modification, not cryptography itself. We propose a lifecycle-aligned migration model, an updated cost model, and governance requirements for frontier-model access. The binding constraint shifts domain-conditionally: defender capacity at adversary tempo governs software-analytical phases, while non-compressible external cadence governs embedded and regulated domains. Full article

Regenerative medicine integrates interdisciplinary approaches towards restoring the function of diseased organs. This study examined alterations that occurred in the liver under a high-fat diet (HFD) with the development of obesity and fatty liver, and changes in metabolic homeostasis and glucose levels, in mice. HFD nutrition causes hyperglycemia, leading to the formation and accumulation of advanced glycation end-products (AGEs) promoting protein post-translational modifications (PTMs) and introducing crosslinking in the extracellular matrix (ECM). Using histological and gene expression analyses, we detected an increase in adiposity, as well as in ECM protein deposition in the liver. Further, decellularization of the liver yielded the isolated ECM organ scaffold, allowing us to analyze the chemical modification in proteins by various imaging methods combined with spectroscopy. The measurements of intrinsic protein fluorescence are consistent with increased AGE-associated levels. SEM allows for the visualization of ECM fiber thickening as a result of protein crosslinking. Using cathodoluminescence, a label-free imaging method, we confirmed the protein modifications. The combination of innovative technologies highlights the ECM structural alterations associated with impaired glucose regulation and liver adiposity. These findings provide novel views on liver-scaffold ECM structure under metabolic diseases that will play a significant role in accelerating the understanding of effective regenerative therapies. Full article

Background: Uveal melanoma is the most common intraocular malignancy in adults with a poor prognosis. Although local therapies are effective, treatment options for advanced disease remain limited. Combination strategies using chemotherapeutic agents and natural compounds, such as quercetin, are in focus for their potential to enhance antitumor efficiency and overcome resistance. Methods: The effects of doxorubicin, quercetin, and their combination were investigated in uveal melanoma cell lines. Cell viability was determined by an MTT assay, and apoptosis and cell cycle distribution by flow cytometry. Invasion assays were performed to evaluate metastatic potential, while modifications in signaling pathways were analyzed by Western blotting and qPCR. Results: Both doxorubicin and quercetin significantly reduced cell viability and induced apoptotic and necrotic cell death. The combination treatment demonstrated additional inhibitory effects in both cell lines, shown by increased SubG1 populations, reduced invasive capacity, and modulation of signaling pathways. Cell cycle analysis indicated treatment-induced growth inhibition. Notably, pathway modifications varied between cell lines, suggesting heterogeneous responses. Conclusions: Quercetin may potentiate certain antitumor effects of doxorubicin in uveal melanoma, particularly by reducing post-treatment invasiveness and modulating certain PI3K/AKT pathway-related proteins. These results support the possibility of quercetin-based combination therapies, although further molecular and in vivo studies are required. Full article

Background/Objectives: Telewellness programs can expand access to exercise and social opportunities for older adults, especially those with mobility disabilities. The TechSAge Tele Tai Chi clinical trial assessed whether the Tai Chi for Arthritis and Fall Prevention program was feasible and acceptable when delivered in a virtual format for adults aging with mobility disabilities, and examined pre-to-post changes in two primary outcomes: physical activity and social connectedness. Methods: The TechSAge Tele Tai Chi study was a single-arm clinical trial. Sixty community-dwelling adults (60–77 years of age; M = 69.2, SD = 4.8) with self-identified long-term mobility disability (≥10 years) joined the virtual classes from home twice a week for 8 weeks. Participants exercised along with pre-recorded video lessons and engaged in guided social discussion. Assessments at baseline, post-intervention, and 1-month follow-up were analyzed with linear mixed models. Results: Leisure physical activity (PASIPD) increased significantly, with back-transformed marginal means rising from 14.2 MET h/wk at baseline to 28.7 MET h/wk post-intervention (p < 0.001). The Social Participation subscale of social connectedness also increased from baseline to post-intervention (p = 0.014); the overall social-connectedness composite did not change significantly. The virtual translation was feasible with high intervention fidelity and adherence, and participants reported high acceptability, satisfaction, enjoyment, and intention to continue. Conclusions: Adults aging with mobility disabilities can safely and successfully participate in virtual group tai chi with appropriate modifications and technology support. Full article

Dengue is an arboviral disease of global significance caused by Orthoflavivirus denguei (DENV), which has four antigenically distinct serotypes. The envelope (E) protein plays a critical role in viral entry and eliciting immune responses. This study aimed to compare the biochemical and immunological properties of the E protein across the four DENV serotypes using in silico approaches. E protein reference sequences were retrieved from RefSeq and analyzed with various bioinformatics tools. Sequence alignment revealed identities ranging from 63.08% to 77.69%. Biochemical analysis showed minimal variation in molecular weight and isoelectric point; however, the net charge of DENV-3 E protein was notably lower. Secondary structure predictions indicated a predominance of alpha-helices in DENVs-1/2, while DENVs-3/4 featured more beta-sheets. Post-translational modification analysis revealed mostly casein kinase II phosphorylation sites across all serotypes, with DENV-4 uniquely presenting also tyrosine kinase sites. Amino acids W231/D341 in DENV-1, Q86 in DENVs-2/4, and D87/D339 in DENV-3 showed maximum antigenicity scores in B cell recognition, while the human leukocyte antigen (HLA) alleles B*08:01/B*39:01 and DRB4*01:01, recognized by T cells, presented the highest number of predicted epitopes for the different DENV serotypes. Conservation analysis showed that the major antigenic regions highlighted in this study are highly conserved among contemporary DENV isolates despite the genetic variability observed within each serotype. These findings suggest that subtle structural differences in the E protein may contribute to distinct immunogenic profiles, highlighting candidate regions for future investigation. Full article

Mitochondria are central hubs of antiviral immunity and cellular metabolism, yet the links between SARS-CoV-2–induced mitochondrial remodeling, antiviral gene regulation, and post-translational control remain incompletely understood. Here, we investigated mitochondrial–immune remodeling in SARS-CoV-2–infected lung-derived LC-HK2 cells at 48 and 96 h post-infection using confocal and high-content imaging, colocalization analysis, CellProfiler quantification, RT-qPCR, proteomics, cytokine profiling, and conditioned-medium analysis. Infection induced a time-dependent mitochondrial phenotype. At 48 hpi, cells displayed early mitochondrial stress and fission-associated signatures, including increased DRP1, transient upregulation of mitochondrial respiratory genes, and reduced MFN1/2. At 96 hpi, mitochondria shifted toward elongated perinuclear networks, accompanied by increased fusion/biogenesis markers and partial ISG15–MFN2 colocalization, indicating a spatial association between ISG15-related antiviral/stress responses and mitochondrial remodeling. Antiviral and ISG-related transcripts were consistently upregulated, but IFN-α2 secretion remained limited, suggesting partial uncoupling between antiviral transcriptional activation and downstream interferon output. SUMO2/3 was dynamically modulated and showed time-dependent colocalization with mitochondrial dynamics proteins and MAVS. Together, these data support a coordinated mitochondrial–immune regulatory axis involving mitochondrial remodeling, ISG15-associated responses, and SUMO-dependent regulation during SARS-CoV-2 infection. Full article

Background/Objectives: Vascular diseases remain a leading cause of global mortality, yet the dietary and lifestyle factors that contribute to them are not fully understood in Central Anatolian populations. This study aimed to quantify the dietary and lifestyle predictors of vascular disease status in a case–control cohort from a tertiary care setting in Yozgat province. Methods: A total of 1452 adults were enrolled from Yozgat Bozok University Research Hospital: Cardiovascular Surgery (CVS; cases, n = 720) and Primary Care (PC; controls, n = 732). All participants completed a 43-item questionnaire on diet, lifestyle, and sociodemographic characteristics. Binary logistic regression was used to identify independent predictors of case status, with age, sex, education, and income being included in the model. Results: Chronic comorbidities were present in 33.9% of the control group and 80.3% of the case group. Use of olive oil was most strongly associated with control status (odds ratio [OR] = 0.17; 95% confidence interval [CI]: 0.11–0.27), followed by use of butter (OR = 0.25). Paradoxically, fast food (OR = 0.24) and junk food (OR = 0.31) consumption were more frequent among controls. The use of sunflower oil (OR = 2.30), diabetes (OR = 5.22), and elevated serum ferritin (OR = 1.04 per 10 ng/mL) independently predicted a higher likelihood of being in the case group. The model explained 54.8% of the variance (Nagelkerke R² = 0.548). Conclusions: The apparently higher prevalence of unhealthy dietary behaviours among controls is most plausibly attributed to post-diagnosis dietary modification among cases (an ‘illness effect’), underscoring the window for intervention before disease onset. As this case–control design precludes causal inference, these associations are hypothesis-generating. Promoting olive oil and reducing sunflower oil represent practical, culturally feasible dietary targets for cardiovascular risk counselling in Central Anatolia, pending prospective confirmation. Full article

This work reports the colloidal synthesis of Nd-containing mixed-halide perovskite quantum dots described as CsPb(Nd)Br_3−γCl_γ, followed by post-synthetic surface modification with an acid-activated amino-functional siloxane. This notation is used deliberately because the available FE-SEM, DLS, EDX, and optical data confirm the formation of an Nd-containing mixed-halide colloidal perovskite system, but do not provide direct crystallographic proof of substitutional Nd³⁺ incorporation at the Pb²⁺ B-site. The obtained dispersions show stable blue emission with a maximum at about 458 nm, a photoluminescence quantum yield of about 56%, an essentially invariant emission maximum when the excitation wavelength is varied from 300 to 390 nm, and monoexponential decay kinetics with a characteristic lifetime of 6.67 ± 0.97 ns. Field-emission scanning electron microscopy combined with morphometric analysis of at least 150 particles indicates a nanoscale size distribution with an average equivalent diameter of 8.8 nm, a median of 7.3 nm, and 93.25% of particles smaller than 25 nm. Dynamic light scattering confirms a narrow hydrodynamic size distribution in the 7–9 nm range and a low polydispersity index. Elemental mapping by EDX confirms the co-presence of Cs, Pb, Br, Cl, and Nd in the analyzed particles. The observed blue shift is discussed in terms of the combined effect of chloride incorporation, nanoscale size, possible Nd-related perturbation of the local electronic/defect structure, and reduced non-radiative losses after surface passivation. No definitive crystallographic assignment of Nd to a specific lattice site is claimed; the composition is therefore treated as nominal, and the structural interpretation remains provisional pending XRD/XPS or related studies. Full article

Dynamin-related protein 1 (Drp1) is essential for mitochondrial dynamics in skeletal muscle, particularly in regulating fission, mitophagy, and maintaining mitochondrial function. Exercise is crucial for sustaining muscle function, promoting mitochondrial adaptations that enhance energy metabolism and oxidative capacity in skeletal muscle. In this Review, we discuss the role of Drp1 in exercise-induced mitochondrial adaptations and its potential implications for skeletal muscle health. We first address the evidence that Drp1 activity must be maintained within a narrow physiological range. Both Drp1 deficiency and overabundance provoke muscle atrophy and dysfunction, establishing a Goldilocks principle for mitochondrial fission. We then examine the multi-layered post-translational modification code that governs Drp1 activity, including canonical phosphorylation, redox-sensing modifications, and the receptor selectivity model that may specify distinct fission programs. A three-stage model of exercise-induced mitochondrial adaptation is presented, describing how Drp1 activity is temporally orchestrated from acute fragmentation through short-term remodeling to long-term network optimization, and how these morphological transitions govern substrate metabolism and determine exercise performance. The pathological consequences of Drp1 dysregulation are examined in metabolic disease, where Drp1 is chronically hyperactivated, and in aging, where Drp1 activity is deficient. Finally, we analyze the ROS-Drp1 signaling axis as the mechanistic basis for the bidirectional regulation of Drp1 by exercise. Moderate exercise-induced ROS production activates Nrf2 and AMPK signaling, which suppress excessive fission in metabolic disease while restoring insufficient fission in aging, thereby moving Drp1 activity toward the physiological Goldilocks zone in both contexts. This context-dependent, bidirectional regulation distinguishes exercise from pharmacological inhibitors and identifies the ROS-Drp1 axis as a therapeutic target for conditions at opposite ends of the Drp1 activity continuum, such as sarcopenia and type 2 diabetes. Full article

Glioblastoma (GB) remains one of the most therapy-resistant solid tumors, characterized by profound metabolic plasticity, intratumoral heterogeneity, and a highly immunosuppressive microenvironment. While immunotherapies such as chimeric antigen receptor T (CAR-T) cells have shown promise in hematological malignancies, their efficacy in GB has been limited. Emerging evidence suggests that tumor-specific metabolic dependencies and post-translational modifications (PTMs) may represent exploitable vulnerabilities. This review discusses disulfidptosis, a recently described form of regulated cell death driven by disulfide stress under conditions of limited reducing capacity, as a context-dependent metabolic–redox vulnerability in GB. We further discuss how altered protein glycosylation and glycocalyx architecture in glioblastoma regulate cell survival, death signaling, and immune recognition. Particular emphasis is placed on the glycosylation of surface antigens targeted by CAR-T cells, including EGFR/EGFRvIII, IL-13Rα2, mesothelin, B7-H3, HER2, and GD2, and on how glycan-dependent epitope accessibility may limit therapeutic efficacy. Finally, we distinguish disulfidptosis, whose direct relevance to CAR-T-cell responses remains to be established, from glycosylation and glycocalyx remodeling as more direct determinants of target–antigen accessibility and immune recognition. Therapeutic strategies addressing these vulnerabilities may provide rational opportunities to improve CAR-T-based and combinatorial therapies for GB. Full article

Transfer RNAs (tRNAs) are chemically matured decoding molecules that are central to protein synthesis. Their post-transcriptional modifications, especially those in the anticodon stem-loop (ASL), shape local RNA structure, codon recognition and translational fidelity at the tRNA-mRNA decoding interface. 2′-O-methylation (Nm) is a conserved ribose modification installed at selected ASL positions, particularly positions 32 and 34, by the modular Trm7/FTSJ1 methyltransferase system. Rather than directly changing base-pairing identity, these marks help prepare the decoder for efficient translation and function within an interconnected 32–34–37 modification network, best illustrated by tRNA^Phe. Loss of Trm7/FTSJ1-mediated Nm may impair selected codon–tRNA decoding pairs; in yeast, Trm7 deficiency is additionally associated with GAAC activation and phenotypes consistent with reduced functional tRNA^Phe availability. In humans, mutations in FTSJ1 are associated with nonsyndromic X-linked intellectual disability (NSXLID), suggesting that disruption of tRNA chemical maturation can affect neuronal translation programs. In this review, we integrate anticodon-loop modifications at positions 32, 34, and 37 into a decoder-centered framework and compare the conserved enzymatic logic of yeast Trm7 and human FTSJ1 with their divergent substrate repertoires. By synthesizing structural, biochemical, genetic, and translational evidence, we distinguish established mechanisms from working models and unresolved questions concerning tRNA modification hierarchies and neuronal vulnerability. Full article