Search Results (16,483)

We present a quantitative theory of contraction and expansion cycles within the Quantum Memory Matrix (QMM) cosmology. In this framework, spacetime consists of finite-capacity Hilbert cells that store quantum information. Each non-singular bounce adds a fixed increment of imprint entropy, defined as the cumulative quantum information written irreversibly into the matrix and distinct from coarse-grained thermodynamic entropy, thereby providing an intrinsic, monotonic cycle counter. By calibrating the geometry–information duality, inferring today’s cumulative imprint from CMB, BAO, chronometer, and large-scale-structure constraints, and integrating the modified Friedmann equations with imprint back-reaction, we find that the Universe has already completed $N_{\mathrm{past}}=3.6\pm 0.4$ cycles. The finite Hilbert capacity enforces an absolute ceiling: propagating the holographic write rate and accounting for instability channels implies only $N_{\mathrm{future}}=7.8\pm 1.6$ additional cycles before saturation halts further bounces. Integrating Kodama-vector proper time across all completed cycles yields a total cumulative age $t_{\mathrm{QMM}}=62.0\pm 2.5\mathrm{Gyr}$, compared to the $13.8\pm 0.2\mathrm{Gyr}$ of the current expansion usually described by $\mathrm{\Lambda }$CDM. The framework makes concrete, testable predictions: an enhanced faint-end UV luminosity function at $z\gtrsim 12$ observable with JWST, a stochastic gravitational-wave background with $f^{2/3}$ scaling in the LISA band from primordial black-hole mergers, and a nanohertz background with slope $\alpha \simeq 2/3$ accessible to pulsar-timing arrays. These signatures provide near-term opportunities to confirm, refine, or falsify the cyclical QMM chronology. Full article

Background and aims: The senescent phenotype transition of vascular smooth muscle cells (VSMCs) is a crucial risk factor for the occurrence and development of vascular diseases. Intermedin (IMD) has various protective effects on cardiovascular diseases. In this study, we aimed to explore the role and the related mechanism of IMD in the senescent phenotype transition of VSMCs of aorta in mice. Methods: The senescent phenotype transition of VSMCs was induced by angiotensin II (Ang II) administered by mini-osmotic pumps in Adm2^fl/fl and Adm2^fl/flTagCre mice. Mouse VSMCs from aorta were used in in vitro experiments. Results: The aortic mRNA level of IMD, namely Adm2, was significantly decreased in Ang II-treated mice. Senescence-associated β-galactosidase activity and protein expressions of p16 and p21 were increased in the aortas of Adm2^fl/flTagCre mice, which were further elevated in Ang II-treated Adm2^fl/flTagCre mice. In addition, Adm2 deficiency in VSMCs further increased the protein expressions of DNA damage markers including 53BP1 and γH2AX in aortas of Adm2^fl/flTagCre mice, and Ang II treatment increased their levels in aortas of Adm2^fl/flTagCre mice or in VSMCs. However, Ang II-induced increases in senescence-associated proteins and DNA damage markers could be mitigated by the administration of IMD in vitro. Mechanistically, IMD increased intracellular NAD⁺ by activating nicotinamide phosphoribosyl transferase (NAMPT), followed by enhancing poly (ADP-ribose) polymerase-1 (PARP1) activity. Inhibitors of PARP1 or NAMPT effectively blocked the beneficial role of IMD in the DNA damage of VSMCs. Conclusions: IMD alleviates DNA damage partially by activating NAMPT/PARP1, thereby inhibiting the senescent phenotype transition of VSMCs of aorta, which might shed new light on the prevention of vascular aging. Full article

Background and Objectives: Hematological parameters are increasingly being investigated as readily accessible biomarkers for the diagnosis of obstructive sleep apnea syndrome (OSAS). In our study, we aimed to investigate the relationship between OSAS and albumin indices and the uric acid-to-HDL ratio (UHR). Methods: The demographic and laboratory data and AHI (apnea–hypopnea index) values of 613 patients who underwent polysomnography were obtained retrospectively from their files. Blood parameters such as white blood cells (WBCs), red blood cell distribution width (RDW), red blood cells (RBCs), hemoglobin (Hb), hematocrit (Hct), platelets (PLTs), C-reactive protein (CRP), albumin, blood urea nitrogen (BUN), and high-density lipoproteins (HDLs) were obtained from the files. Laboratory indices such as the BUN-to-albumin ratio (BAR), neutrophil-to-albumin ratio (NAR), RDW-to-albumin ratio (RAR), CRP-to-albumin ratio (CAR), and UHR were calculated. OSAS was categorized as simple snoring (SS) (control) (AHI < 5), mild (5 ≤ AHI < 15), moderate (15 ≤ AHI < 30), and severe (AHI ≥ 30). The patients were also grouped as severe (AHI ≥ 30) and non-severe (5 > AHI < 30) OSAS and compared in terms of laboratory parameters and indices. Results: Of the 613 participants, 366 (59.7%) were men, and the average age of participants was 55.22 ± 11.13 years. The biomarkers such as RBCs, Hb, Htc, CRP, BUN, creatinine, uric acid, HDLs, CAR, RAR, BAR, and UHR showed significant differences between OSAS patients and controls. WBCs, basophils, RBCs, RDW, Htc, PLTs, HDLs, uric acid, RAR, NAR, and UHR indices were significantly different between the severe OSAS and non-severe OSAS groups (p < 0.05). BAR (OR = 1.151; CI = 1.056 − 1.256; p = 0.001) and UHR (OR = 2.257; 95% CI = 1.507 − 3.382; p < 0.001) were the most important indices predicting OSAS, while RAR (OR = 1.844; CI = 1.224 − 2.778; p = 0.003) and UHR (OR = 2.203; 95% CI = 1.496 − 3.243; p < 0.001) were the strongest indices associated with severe OSAS. Conclusion: In our study, RAR, BAR, and UHR indices were closely associated with the presence and severity of OSAS. These indices can be considered low-cost, readily available methods for predicting OSAS patients. Full article

Background: Craniofrontonasal dysplasia (CFND) is an X-linked developmental disorder caused by mutations in the EFNB1 gene located on chromosome Xq13. This gene encodes ephrin-B1, a ligand for Eph receptors, which is involved in cell signaling pathways and the development of the nervous and vascular systems, as well as facial and cranial structures. Paradoxically, the syndrome manifests with greater severity in heterozygous females, whereas hemizygous males typically present with mild or no abnormalities. Methods and Results: We report the case of a late preterm female neonate with dysmorphic features at birth, who subsequently developed necrotizing enterocolitis (NEC) caused by thrombosis of the superior mesenteric artery. Extensive bowel resection led to short bowel syndrome, resulting in cholestatic liver disease, malabsorption, and growth impairment. Array-comparative genomic hybridization (a-CGH) analysis identified a ~791 Kb microduplication at Xq13.1, encompassing the EFNB1 gene, confirming the diagnosis of CFND. She was enrolled in a multidisciplinary follow-up program and, at 2 years of age, presents with marked growth and neurodevelopmental delay. Conclusions: This report describes a rare association between CFND and NEC caused by superior mesenteric artery thrombosis. To the best of our knowledge, no previously reported cases of CFND associated with thrombosis or thrombosis-related conditions, including NEC, have been identified. This is based on a literature review (2004–2025) performed using PubMed and Scopus, and limited to English-language case reports and reviews. Full article

Background/Objectives: Merkel cell carcinoma (MCC) is an uncommon but aggressive skin malignancy with a rising incidence. Limited data exist on the survival of MCC patients in Canada. This study analyzes the survival of patients diagnosed with MCC in Canada between 2000 and 2018 compared to those reported by the American Joint Committee on Cancer (AJCC) 8th edition. Risk factors included in the database were sex, age, and immunosuppression. Methods: We conducted a multicenter retrospective cohort study including patients diagnosed with stage I–IV MCC aged ≥18 from 10 Canadian university centers and three provinces. We evaluated differences in survival compared to the cohort included in the AJCC 8th edition. Results: Among 899 patients diagnosed with MCC in Canada, 327 (36.4%) had stage I, 195 (21.7%) had stage II, 305 (33.9%) had stage III, and 72 (8.0%) had stage IV at presentation. When examining risk factors, 61.1% (549) were male, 10.2% (92) were immunosuppressed, and age at diagnosis was 75 years (±11). The five-year overall survival for patients diagnosed in Canada at stage I was 56.8%, stage IIA 54.0%, stage IIB 28.0%, stage IIIA 52.7%, stage IIIB 40.2%, and stage IV 13.9%. Conclusions: Survival from MCC is low in Canada across all stages. Compared to the AJCC 8th edition, patients diagnosed with MCC in Canada have similar survival rates, except for patients diagnosed with stage IIIB, who have lower survival rates in the AJCC 8th edition. Further research is needed to improve the survival of this rare malignancy. Full article

Ternary hybrid nanofluid have been revealed to possess a wide range of application disciplines reaching from biomedical engineering, detection of cancer, over or photovoltaic panels and cells, nuclear power plant engineering, to the automobile industry, smart cells and and eventually to heat exchange systems. Inspired by the recent developments in nanotechnology and in particular the high potential ability of use of such nanofluids in practical problems, this paper deals with the flow of a three phase nanofluid of MWCNT-Au/Ag nanoparticles dispersed in blood in the presence of a bidirectional stretching sheet. The model derived in this study yields a set of linked nonlinear PDEs, which are first transformed into dimensionless ODEs. From these ODEs we get a dataset with the help of MATHEMATICA environment, then solved using AI-based technique utilizing Levenberg Marquardt Feedforward Algorithm. In this work, flow characteristics under varying physical parameters have been studied and analyzed and the boundary layer phenomena has been investigated. In detail horizontal, vertical velocity profiles as well as temperature distribution are analyzed. The findings reveal that as the stretching ratio of the surface coincide with an increase the vertical velocity as the surface has thinned in this direction minimizing resistance to the fluid flow. Full article

Aging of the central nervous system (CNS) involves widespread transcriptional and structural remodeling, prominently marked by synaptic loss, impaired neurogenesis, and glial dysfunction. While age-related gene expression changes have been documented for decades, recent genome-wide next-generation sequencing studies emphasize the importance of epigenetic mechanisms—such as DNA methylation and histone modification—in shaping these profiles. Notably, these modifications are potentially reversible, making them promising targets for therapeutic intervention. However, the mechanisms by which age-associated factors, such as inflammation and oxidative stress, orchestrate these epigenetic alterations across distinct CNS cell types remain poorly understood. In this review, we propose a framework for understanding how aging and neuroinflammation are regulated by epigenetic mechanisms, contributing to brain dysfunction and disease vulnerability. Full article

In this article, we present density functional theory (DFT) calculations for $Z{n}_{(1-x)}{M}_{x}O$, where M represents one of the following substitutional metallic impurities: Ga, Cd, Cu, Pd, Ag, In, or Sn. Our study is based on the wurtzite structure of pristine ZnO. We employ the Quantum Espresso package, using a fully unconstrained implementation of the generalized gradient approximation (GGA) with an additional U correction for exchange and correlation effects. We analyze the density of states, energy gaps, and absorption spectra for these doped systems, considering the limitations of a finite-size cell approximation. Rather than focusing on precise numerical values, we highlight the following two key aspects: the location of impurity-induced electronic states and the overall trends in optical properties across the eight systems, including pristine ZnO. Our results indicate that certain dopants introduce electronic levels within the band gap, which enhance optical absorption in the visible, near-infrared, and near-ultraviolet regions. For instance, Sn-doped ZnO shows a pronounced absorption peak at ∼2.5 eV, which is in the middle of the visible spectrum. In the case of Ag and Pd impurities, they lead to increased electromagnetic radiation absorption at the near ultra-violet spectrum. This represents a promising performance for efficient solar radiation absorption, both at the Earth’s surface and in outer space. Furthermore, Ga- and In-doped ZnO present bandgaps of ∼0.9 eV, promising an interesting performance in the near infrared region. These findings suggest potential applications in solar energy harvesting and selective sensors. Full article

Osteoarthritis (OA) is primarily a degenerative disease triggered by joint inflammation and oxidative stress. While Aster glehni is an edible and traditionally medicinal herb, the beneficial effect of A. glehni on OA progression remains unknown. This study aimed to investigate the effect of A. glehni extract (AGE) and its primary biological compound—3,5-dicaffeoylquinic acid (3,5-DCQA)—on inflammation and oxidative stress in chondrocytes. AGE effectively inhibited the expression of interleukin (IL)-6, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-1, and MMP-13 in chondrocytes stimulated by IL-1β for 24 h. In contrast, 3,5-DCQA did not inhibit IL-6, COX-2, and MMP expressions under the same conditions. However, when chondrocytes were stimulated by IL-1β for a short duration (6 h), 3,5-DCQA suppressed IL-6, COX-2, and MMP expressions. The inhibition of IL-6, COX-2, and MMP expressions by AGE was associated with the p38 kinase and nuclear factor-κB signaling pathways, but not ERK and JNK signaling pathways. Furthermore, AGE prevented cell apoptosis and reduced intracellular reactive oxygen species levels in chondrocytes induced by hydrogen peroxide (H₂ O₂). AGE restored the decreased superoxide dismutase 1 and catalase mRNA expressions caused by H₂ O₂. Collectively, AGE may protect against cartilage deterioration by inhibiting inflammation and oxidative stress, making it a promising therapeutic agent for alleviating OA. Full article

Senescence is a dynamic, multifaceted process implicated in tissue aging, organ dysfunction, and intricately associated with numerous chronic diseases. As senescent cells accumulate, they drive inflammation, fibrosis, and metabolic disruption through the senescence-associated secretory phenotype (SASP). Despite its clinical relevance, senescence remains challenging to detect non-invasively due to its heterogeneous nature and the lack of universal biomarkers. Recent advances in the development of specific imaging probes for positron emission tomography (PET) enable in vivo visualization of senescence-associated pathways across key organs, such as the lung, heart, kidney, and metabolic processes. For instance, [¹⁸F]FPyGal, a β-galactosidase-targeted tracer, has demonstrated selective accumulation in senescent cells in both preclinical and early clinical studies, while FAP-targeted radioligands are emerging as tools for imaging fibrotic remodeling in the lung, liver, kidney, and myocardium. This review examines a new generation of PET radioligands targeting hallmark features of senescence, with the potential to track and measure the process, the ability to be translated into clinical interventions for early diagnosis, and longitudinal monitoring of senescence-driven pathologies. By integrating organ-specific imaging biomarkers with molecular insights, PET probes are poised to transform our ability to manage and treat age-related diseases through personalized approaches. Full article

Cellular senescence, a state of stable cell cycle arrest accompanied by a complex senescence-associated secretory phenotype (SASP), is a fundamental biological process implicated as a key driver of lung aging and lung age-related diseases (LARDs). This review provides a comprehensive overview of the rapidly evolving field of senotyping based on cellular heterogeneity in lung development and aging in health and disease. It also delves into the molecular mechanisms driving senescence and SASP production, highlighting pathways such as p53/p21, p16^INK4a/RB, mTOR, and p38 MAPK as therapeutic targets. The involvement of various novel SASP proteins, such as GDP15, cytokines/chemokines, growth factors, and DNA damage response proteins. We further highlight the effectiveness of senotherapeutics in mitigating the detrimental effects of senescent cell (SnC) accumulation within the lungs. It also outlines two main therapeutic approaches: senolytics, which selectively trigger apoptosis in SnCs, and senomorphics (also known as senostatics), which mitigate the detrimental effects of the SASP without necessarily removing the senescent cells. Various classes of senolytic and senomorphic drugs are currently in clinical trials including natural products (e.g., quercetin, fisetin, resveratrol) and repurposed drugs (e.g., dasatinib, navitoclax, metformin, rapamycin) that has demonstrated therapeutic promise in improving tissue function, alleviating LARDs, and extending health span. We discuss the future of these strategies in lung research and further elaborate upon the usability of novel approaches including HSP90 inhibitors, senolytic CAR-T cells, Antibody drug conjugate and galactose-modified prodrugs in influencing the field of personalized medicine in future. Overall, this comprehensive review highlights the progress made so far and the challenges faced in the field of cellular senescence including SnC heterogeneity, states of senescence, senotyping, immunosenescence, drug delivery, target specificity, long-term safety, and the need for robust cell-based biomarkers. Future perspectives, such as advanced delivery systems, and combination therapies, are considered critical for translating the potential of senotherapeutics into effective clinical applications for age-related pulmonary diseases/conditions. Full article

Background: Cryopreservation of hematopoietic stem cells (HSCs) at −80 °C using uncontrolled-rate freezing is frequently employed in resource-constrained settings, yet concerns remain regarding long-term viability and clinical efficacy. Reliable post-thaw assessment is essential to ensure graft quality and engraftment success. Methods: This single-center, retrospective study evaluated 72 cryopreserved stem cell products from 25 patients stored at −80 °C for a median of 868 days. Viability was assessed using both acridine orange (AO) staining and 7-AAD (7-aminoactinomycin D) flow cytometry at three time points: collection (T0), pre-infusion (T1), and delayed post-thaw evaluation (T2). Associations between viability loss, storage duration, and clinical engraftment outcomes were analyzed. Results: Median post-thaw viability remained high (94.8%) despite a moderate time-dependent decline (~1.02% per 100 days; R² = 0.283, p < 0.001). Mean viability loss at T2 was 9.2% (AO) and 6.6% (flow cytometry). AO demonstrated greater sensitivity to delayed degradation, with a significant difference between methods (p < 0.001). Engraftment kinetics were preserved in most patients, with neutrophil and platelet recovery primarily influenced by disease type rather than product integrity. Notably, storage duration and donor age were not significantly associated with engraftment outcomes or CD34⁺ cell dose. Conclusion: Long-term cryopreservation at −80 °C maintains HSC viability sufficient for durable engraftment, despite gradual decline. While transplant outcomes are primarily dictated by disease biology and remission status, AO staining provides enhanced sensitivity for detecting delayed cellular damage. Notably, our viability-loss model offers a practical framework for predicting product quality, potentially supporting graft selection and clinical decision-making in real-world, resource-constrained transplant settings. Full article

Despite the health concerns regarding alcohol and its link to cancer, moderate consumption of red wine has been associated with healthy aging and longevity, defined as up to one drink per day for women and two drinks per day for men (approximately 142 mL or 5 oz per drink). Previous research has revealed the health benefits of red wine, particularly in relation to cardiovascular disease. However, the influence of genetic factors on these benefits remains to be elucidated. In this study, we explored genes linked to red wine and created a curated gene set that intersects with those related to centenarians, which are markers of exceptional longevity. By analyzing literature from over 190 databases, we identified and validated a curated list of 43 genes associated with red wine and centenarians. We conducted gene set enrichment analysis as well as enrichment analysis of diseases and their tissue distributions. The results suggest that these genes play a crucial role in stress response and apoptosis, which are essential for cell survival and renewal. Additionally, these genes were enriched in pathways associated with smooth muscle cell proliferation, neuroinflammation, nucleotide excision repair, and lipoprotein metabolism (false discovery rate, FDR < 3 × 10⁻⁷). Gene set enrichment analysis indicated significant tissue distribution in the gastrointestinal, cardiovascular, and respiratory systems. Furthermore, the disease–gene enrichment analysis pointed to associations with diseases related to tissues and organs, including cardiovascular disease (heart disease and stroke), type 2 diabetes, gastrointestinal diseases and metabolic diseases, immune diseases, and cancer (FDR < 9.37 × 10⁻⁶); notably, cardiovascular diseases, diabetes, and cancer are leading causes of death, suggesting that these genes may be protective against those diseases. Our review of the literature indicates that individuals who do not currently drink alcohol should not be encouraged to start. However, we propose that moderate consumption of red wine, especially for middle-aged to older adults after 40 years old, can provide significant health benefits due to its components and the positive effects of hormesis. Although further research is necessary to uncover additional genes, this study provides the first genetic overview of the health benefits of red wine, emphasizing its potential in supporting healthy aging and longevity. Full article

We synthesized the current evidence from the literature and conducted a 2 × 3 factorial experiment to quantify the impact of thermocycling on the Vickers microhardness (HV) of dental CAD/CAM materials: VITA ENAMIC (VE, polymer-infiltrated ceramic network) and CERASMART (CS, nanofilled resin-matrix). Sixty polished specimens (n = 10 per Material × Cycles cell; 12 × 2 × 2 mm) were thermocycled at 5–55 °C (0, 10,000, 20,000 cycles; 30 s dwell, ≈10 s transfer) and tested as HV0.3/10 (300 gf, 10 s; five indentations/specimen with standard spacing). Assumptions regarding the model residuals were met (Shapiro–Wilk W ≈ 0.98, p ≈ 0.36; Levene F(5,54) ≈ 1.12, p ≈ 0.36), so a two-way ANOVA (Type II) with Tukey’s HSD post hoc (α = 0.05) was applied. VE maintained consistently higher HV than CS at all cycle levels and showed a smaller drop from baseline: VE (mean ± SD): 200.2 ± 10.8 (0), 192.4 ± 13.9 (10,000), and 196.7 ± 9.3 (20,000); CS: 60.8 ± 6.1 (0), 53.4 ± 4.7 (10,000), and 62.1 ± 3.8 (20,000). ANOVA revealed significant main effects from the material (η²p = 0.972) and cycles (η²p = 0.316), plus a Material × Cycles interaction (η²p = 0.201). Results: Thermocycling produced material-dependent changes in microhardness. Relative to baseline, VE varied by −3.9% (10,000) and −1.7% (20,000), while CS varied by −12.2% (10,000) and +2.1% (20,000); from 10,000→20,000 cycles, microhardness recovered by +2.2% (VE) and +16.3% (CS). Pairwise comparisons were consistent with these trends (CS decreased at 10,000 vs. 0 and recovered at 20,000; VE only showed a modest change). Conclusions: Thermocycling effects were material-dependent, with smaller losses and better retention in VE (PICN) than in CS. These results align with the literature (resin-matrix/hybrids are more sensitive to thermal aging; polished finishes mitigate losses). While HV is only one facet of performance, the superior retention observed in PICN under thermal challenge suggests the improved preservation of superficial integrity; standardized reporting of aging parameters and integration with wear, fatigue, and adhesion outcomes are recommended to inform indications and longevity. Full article

Introduction: Primary glomerulopathies are immune-driven kidney diseases. IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) are prevalent entities with a risk of chronic progression. Immune checkpoints, such as PD-1/PD-L1, CTLA-4/CD86, and CD200R/CD200, regulate activation and tolerance in T, B, and NK cells, and also exist in soluble forms, reflecting systemic immune balance. Objective: To compare immune checkpoint profiles in IgAN and MPGN versus healthy volunteers (HV) through surface expression, soluble serum levels, and PBMC transcripts, with attention to sex-related differences and diagnostic value assessed by ROC curves. Materials and Methods: Ninety age-matched subjects were studied: IgAN (n = 30), MPGN (n = 30), HV (n = 30). Flow cytometry evaluated checkpoint expression on CD4+/CD8+ T cells, CD19+ B cells, and NK cells. ELISA quantified sPD-1, sPD-L1, sCTLA-4, sCD86, sCD200, sCD200R; PBMC transcript levels were assessed. Group comparisons, sex stratification, and ROC analyses were performed. Results: Lymphocyte distributions were preserved, but IgAN patients showed anemia and impaired renal function, while MPGN patients had greater proteinuria and dyslipidemia. GN patients displayed increased PD-1/PD-L1 and CD200R/CD200, with reduced CTLA-4/CD86, compared to HV. Serum analysis revealed elevated sPD-1, sPD-L1, sCD200, sCD200R and decreased sCTLA-4, sCD86. PBMC transcripts paralleled these trends, with PD-1/PD-L1 mainly increased in MPGN. Sex had minimal impact. ROC analyses showed strong GN vs. HV discrimination by CD19⁺CTLA-4⁺, PD-1/PD-L1, and CD200/CD200R, but limited ability to separate IgAN from MPGN. Conclusions: IgAN and MPGN share a sex-independent checkpoint signature: PD-1/PD-L1 and CD200R/CD200 upregulation with CTLA-4/CD86 downregulation. CD19⁺, CTLA-4⁺, and soluble PD-1/PD-L1/CD200(R) emerge as promising biomarkers requiring further validation. Full article