Search Results (42,762)

The integration of post-quantum digital signature (PQDS) algorithms into coherent wavelength-division multiplexing (WDM) optical networks introduces a non-negligible cryptographic overhead that fundamentally alters physical-layer performance characteristics. Unlike conventional studies that treat security and transmission independently, this work provides a cross-layer evaluation of PQDS-induced payload expansion and its direct impact on coherent optical system behavior under realistic, DSP-aligned conditions. A structured and reproducible evaluation framework is proposed to systematically analyze this interaction across multiple transmission scenarios, ranging from a single-channel QPSK baseline to a 16-channel WDM system employing both QPSK and 16QAM modulation formats. Key system parameters—including launch power, local oscillator power, bit rate, and fiber length—are jointly optimized, while performance is rigorously assessed in terms of bit error rate (BER), Q-factor, and maximum transmission reach. The results demonstrate a clear performance degradation trend driven by both spectral efficiency scaling and cryptographic payload expansion. The single-channel QPSK system achieves a maximum reach of 203 km, which decreases to 194 km in the 16-channel WDM QPSK configuration due to inter-channel interference and nonlinear effects. In contrast, the 16-channel WDM 16QAM system exhibits a significantly reduced reach of 103 km, reflecting its heightened sensitivity to noise, chromatic dispersion, and fiber nonlinearities. Furthermore, increased payload size associated with PQDS schemes is shown to exacerbate transmission impairments by extending frame duration and intensifying inter-channel interactions. These findings identify PQDS-induced overhead as a critical system-level constraint that directly governs transmission efficiency, scalability, and performance limits. The study highlights the necessity of cross-layer co-design strategies, where cryptographic mechanisms and physical-layer parameters are jointly optimized to enable efficient, reliable, and quantum-safe coherent optical communication systems. Full article

Hydroxyapatite–calcium sulfate (HACaS) bone cements have been clinically established. Combining HACaS with an antiresorptive (zoledronic acid, ZA) and osteoanabolic agent (bone morphogenic protein 2; BMP-2) may enhance the performance of HACaS bone cements in challenging indications, but it must be ensured that this does not impair their setting and mechanical properties. This study established a Vicat/Gillmore-inspired indentation protocol to quantify force-based endpoints and the setting of HACaS with biological adjuvants. HACaS was mixed with or without ZA and/or BMP-2 at 0 min and after a 2 min pre-setting phase with reduced NaCl content (lower liquid-to-powder ratio). For each time point (3–90 min), three cylindrical pellets (Ø 4 mm, height 6 mm) underwent single indentation. Setting was defined as the maximum force at needle penetration, and endpoint hardness was defined as peak force at failure. For 24 h endpoints, specimens were incubated in blood at 37 °C. One-way ANOVA with Tukey’s H post hoc test was performed per time point (n = 3; 24 h endpoints n = 5). All 2 min protocols showed accelerated setting, consistent with the initial lower liquid-to-powder ratio. ZA significantly delayed setting and remained lowest at 90 min and after 24 h in blood. Mixing sequence and vehicle composition critically influenced early mechanical properties and should be considered in the further preclinical evaluation of HACaS with osteoanabolic or antiresorptive agents. Full article

Staphylococcus aureus biofilms formed on titanium surfaces are highly relevant to orthopedic implant-associated infection and remain difficult to control after maturation. This study aimed to evaluate whether ultraviolet A (UVA, 365 nm) combined with cinnamaldehyde (CA) could improve antibiofilm activity against titanium-associated S. aureus biofilms in a stage-resolved in vitro model and to examine whether the observed responses were associated with reactive oxygen species (ROS). Early stage (8 h) and 24 h biofilm models were established on total hip arthroplasty (THA)-derived titanium discs. After condition screening, 0.5 mM CA combined with 5 min UVA exposure was selected for subsequent experiments. Biofilm biomass was assessed by crystal violet staining, bacterial viability by live/dead staining and colony-forming unit (CFU) enumeration, ROS-associated fluorescence by dihydroethidium (DHE) imaging, and biofilm-associated gene expression by quantitative real-time PCR (qRT-PCR). Chondrocyte viability was also evaluated under the selected antibiofilm-effective conditions. The combined treatment showed stage-dependent antibiofilm effects, with greater biomass reduction in the 8 h biofilm model and marked impairment of bacterial viability and culturability in both models. ROS-associated fluorescence increased under combined exposure and was partially attenuated by N-acetyl-L-cysteine (NAC) in the 24 h biofilm model. In parallel, CA + UVA was associated with lower expression levels of clfA, icaA, and icaD in the 8 h biofilm model and of icaA, icaB, and icaD in the 24 h biofilm model, with partial NAC attenuation in the latter. Chondrocyte viability was lower in all treatment groups than in the untreated control, although the combined treatment did not show an obvious additional decrease compared with the single-treatment groups. These findings indicate that UVA combined with CA exerts stage-dependent antibiofilm effects in an in vitro titanium-associated S. aureus biofilm model. The observed ROS-associated responses were consistent with, but do not establish, mechanistic involvement. The current treatment setting also requires further optimization before translational applicability can be more confidently considered. Full article

Prolonged hospitalization in cardiac patients is associated with increased morbidity and healthcare resource utilization, yet early biological factors linked to extended length of stay remain insufficiently defined. This study aimed to explore an integrative framework combining oral health parameters and targeted gut microbial markers to identify factors associated with prolonged hospitalization in cardiac patients. A comparative observational design was applied, including patients with short-term hospitalization (1–4 days) and prolonged hospitalization (≥25 days). Oral health status was evaluated using a standardized dental protocol at admission and longitudinally in patients with prolonged hospitalization. Targeted qRT-PCR-based quantification of selected gut bacterial markers was performed at admission and reassessed after one and two weeks. Temporal changes were calculated relative to baseline, and multivariate logistic regression models adjusted for age, sex, and major cardiac diagnoses were used to explore associations with prolonged hospitalization. Short-term hospitalized patients (n = 27) exhibited minimal oral health variation (+2%) and stable marker profiles. In contrast, patients with prolonged hospitalization (n = 30 for oral health; n = 18 for microbial markers) showed progressive changes over time. Oral health impairment increased by 3% after one week and 16% after two weeks, while targeted microbial marker variation showed modest directional changes. Integrative models combining oral health parameters and targeted microbial markers suggested potential complementary information alongside clinical variables, within the limits of an exploratory framework and limited sample size. These findings support the relevance of multidomain clinical and biological monitoring in the early identification of patients at risk for prolonged hospitalization. Full article

Proteasome inhibitors (PIs) are central to multiple myeloma (MM) therapy; however, resistance remains a major clinical challenge, particularly in relapsed/refractory disease. To identify functional mediators of carfilzomib (CFZ) resistance, we performed complementary gain-of-function CRISPR activation and pharmacological screening approaches. These unbiased strategies converged on the E3 ubiquitin ligase MDM2 as a modulator of PI response. MDM2 transactivation enhanced MM cell survival and accelerated recovery following CFZ exposure, supporting a causal role in proteotoxic stress tolerance. Pharmacologic inhibition of MDM2 with NVP-CGM097 synergized with CFZ across multiple PI-sensitive and PI-resistant MM cell lines, irrespective of TP53 status. Mechanistically, MDM2 inhibition induced p21 upregulation, cell-cycle arrest, and reduced c-MYC expression, accompanied by impaired activation of DNA damage response mediators. Genetic silencing of MDM2 phenocopied these effects and increased CFZ sensitivity. Importantly, the combination retained efficacy in MM–stromal co-culture models and in primary patient samples, including cases harboring del(17p), while sparing normal peripheral blood mononuclear cells. Collectively, these findings identify MDM2 as a functional driver of PI resistance and support combined MDM2 and proteasome inhibition as a rational therapeutic strategy in MM, including TP53-deficient contexts. Full article

To date, we and others have demonstrated that GBA1-associated Parkinson’s disease (GBA1-PD) exhibits hyperactivation of mTOR and impairment of mTOR-regulated autophagy. Our previous study showed that the degree of autophagy impairment depends on the type of GBA1 mutation in peripheral blood mononuclear cell (PBMC)-derived macrophages. Moreover, the type of GBA1 mutation (“mild”—e.g., p.N370S or “severe”—e.g., p.L444P) correlates with PD severity and may influence therapeutic response. Here, we investigated the dose-dependent effects of GCase inhibition by conduritol β-epoxide (CBE) in SH-SY5Y cells on mTOR signaling, as well as the effects of mTOR inhibition by Torin 1 on mTOR-dependent autophagy-related proteins, lysosomal morphology, and lysosomal hydrolase activities in PBMC-derived macrophages from PD patients carrying GBA1-L444P or GBA1-N370S mutations. CBE induced dose-dependent activation of mTOR signaling in SH-SY5Y, as evidenced by dose-dependent accumulation of p-RPS6 (Ser235/236). mTOR inhibition decreased Beclin-1 protein levels while increasing the LC3B-II/LC3B-I ratio, LC3B–lysosome colocalization, and lysosome number regardless of mutation type in PBMC-derived macrophages. However, Torin1 reduced p62 levels in GBA1-N370S-PD, whereas lysosomal size decreased in GBA1-L444P-PD. Interestingly, Torin 1 increased GCase activity in both patient groups. These findings suggest that mTOR inhibition restores GCase function and autophagy and may represent a potential therapeutic strategy for GBA1-PD. Full article

The skin serves as a primary defensive barrier to protect the body from environmental contaminants, infections and trauma. Unfortunately, skin barrier’s structural and functional integrity can be compromised, disrupted or impaired due to a combination of internal and external factors, making it vulnerable and often leading to a wide range of skin conditions characterized by dryness, heightened sensitivity, and increased susceptibility to damage and infections. In addition, the integrity of the skin barrier tends to deteriorate progressively with age. As people age, their skin naturally changes and can also be compromised by a plethora of factors that reduce its strength and resilience. The aging skin becomes thinner and more sensitive, coinciding with a variety of structural–functional alterations, decreased levels of natural moisturizing factor (NMF), lipid content and hydration, increased transepidermal water loss (TEWL), altered skin surface pH (pHss) and microbiome diversity. All these age-related skin integrity alterations make the skin drier, flakier, itchy, and fragile, and more susceptible to damage and breakdown, thus diminishing its ability to effectively protect, repair and heal efficiently. Identifying skin integrity issues before they progress will foster positive outcomes through effective preventive measures. Hence, it is important to understand the impact of skincare formulations on skin integrity in compromised aging skin. A well-considered, evidence-based approach to skincare can provide cleansing, moisturizing and protective benefits, while aiding the reduction in skin integrity issues like dry and itchy skin, sensitive skin, bruising, skin tears, pressure injuries (PIs), lower leg ulcers and moisture-associated skin damage (MASD). Managing skin integrity in compromised aging skin begins with gentle skin cleansing, adequate moisturization and protective barrier care to ensure the skin’s function is maximized. Full article

This case report documents the multi-season development of a 38-year-old elite F12 shot putter with macular degeneration (<10% functional vision) who improved from 13.00 m to a personal best of 14.41 m between 2021 and 2023. Athletes classified as F11–F13 compete with significant visual impairment that limits spatial feedback during rotational tasks, yet longitudinal evidence describing integrated training frameworks remains scarce. A 12-month macrocycle integrated phase-dependent velocity-based resistance training using mean concentric velocity targets (0.70–1.00 m·s⁻¹) monitored via linear position transducers with a 10% velocity loss threshold, combined with structured auditory and tactile cueing, including metronome pacing and environmental anchors. High-volume warm-ups and prehabilitation addressed a prior L4–L5 disk herniation. The athlete achieved 14.41 m at the 2023 U.S. Para Athletics Trials, with TrackMan^®-verified release velocity of 11.3 m·s⁻¹. Bench throw velocity improved by 35.4% (0.65 to 0.88 m·s⁻¹) and squat jump velocity improved by 22.9% (1.18 to 1.45 m·s⁻¹), while post-session RPE remained manageable, indicating improved neuromuscular readiness and training tolerance. No lumbar symptom recurrence occurred. This case illustrates that integrating velocity autoregulation, multisensory stabilization, and injury-informed preparation can support meaningful performance gains in visually impaired throwers and offers an applied framework for coaches working with F11–F13 athletes. Full article

Background: Language impairment is a core feature of Major Neurocognitive Disorder (MND), yet the domain-specific relationship between language functioning and everyday functional status remains insufficiently characterized. Methods: We conducted a retrospective observational study in 125 older adults diagnosed with MND according to DSM-5 criteria with mild-to-moderate cognitive impairment measured with Mini-Mental State Examination (MMSE). Language performance was assessed using semantic, phonemic verbal fluency and confrontation naming. Functional status was evaluated using basic (BADL) and instrumental activities of daily living (IADL). Ordinal logistic regression models examined associations between language domains and functional outcomes, adjusting for global cognitive status (MMSE), demographic variables, multimorbidity, and depressive symptoms. Model fit was evaluated using the Akaike Information Criterion. Results: Semantic fluency emerged as the best-performing predictor of BADL across all hierarchical models, remaining statistically significant after full adjustment for MMSE and clinical covariates (β ≈ 0.60, p < 0.05). Phonemic fluency showed the most robust association with IADL, with a stable effect across models, reaching a trend toward statistical significance in the fully adjusted analyses (β ≈ 0.22–0.27, p = 0.069). Naming ability did not influence functional outcomes. All observed associations persisted after controlling for MMSE, demographic variables, multimorbidity, and depressive symptoms. Conclusions: Language abilities showed differential associations across language domains with functional status in this sample of patients with MND. Semantic fluency was associated with basic self-care, while phonemic fluency showed a trend toward association with instrumental daily activities. These relationships remained observable after adjustment for global cognitive impairment, suggesting verbal fluency as a potentially sensitive marker of functional vulnerability. Full article

Polybrominated diphenyl ethers (PBDEs), widely used as brominated flame retardants, are known to exert persistent adverse effects on the immune systems of humans and other organisms. Previous studies have demonstrated that 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), a prevalent congener, induces apoptosis, impairs phagocytic function, and triggers aberrant immune-inflammatory reactions in RAW264.7 macrophages via the induction of elevated intracellular reactive oxygen species (ROS). However, the underlying regulatory mechanism remains unclear. The nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway is a key cellular defense system against oxidative stress. In this study, we investigated the role of the Nrf2/ARE pathway in BDE-47-induced macrophage immunotoxicity. Network toxicology analysis identified Nrf2 as a hub gene within the BDE-47-associated immunotoxicity network. Molecular docking and molecular dynamics simulations suggested a potential interaction between BDE-47 and the Keap1-Nrf2 complex, with moderate binding affinity. Experimental studies in RAW264.7 cells showed that BDE-47 exposure activated the Nrf2/ARE pathway, as evidenced by Nrf2 nuclear translocation and the differential upregulation of downstream genes (GCLC, GCLM, HO-1, NQO1, SOD1, and CAT). Importantly, Nrf2 knockdown via lentiviral shRNA or pharmacological inhibition with brusatol significantly exacerbated BDE-47-induced apoptosis and immune dysfunction, including enhanced pro-inflammatory cytokine production and impaired phagocytosis. These results demonstrate that Nrf2/ARE pathway activation represents an adaptive antioxidant response and contributes to limiting BDE-47-induced cytotoxicity and immune impairment in macrophages. Full article

Mitochondrial reactive oxygen species (ROS) play a central role in cardiac ischemia/reperfusion injury, heart failure, and arrhythmogenesis, while also serving essential signaling functions under physiological conditions. Among the eleven identified mitochondrial ROS-producing sites, complexes I and III are considered the major contributors, particularly under conditions of impaired electron flow. However, much of the existing knowledge comes from rodent models or cultured cells and is often assumed to apply to humans. Here, ROS production from complexes I and III was measured directly in human myocardial and skeletal muscle biopsies and compared with corresponding rat tissues under identical experimental conditions. Hydrogen peroxide generation was quantified using Amplex UltraRed, with simultaneous monitoring of mitochondrial respiration using a Clark-type oxygen electrode. Across all examined mechanisms—reverse and forward electron transport at complex I and the ubiquinol oxidation site of complex III, rat tissues produced more ROS than human tissues, consistent with their higher respiratory rates. However, the dominant ROS-producing sites differed: in rats, complex III was the primary source, whereas in human tissues the highest ROS production occurred during reverse electron transport at complex I. When normalized to respiration, human tissues showed relatively greater ROS generation at complex I but markedly lower production at complex III. These direct measurements of mitochondrial ROS production in human myocardium provide new insight into cardiac redox physiology and may explain the limited clinical translation of cardioprotective strategies targeting mitochondrial ROS production, such as interventions aimed at modulating reperfusion injury or preconditioning. Full article

Dietary antioxidants and phytochemicals are believed to support cognitive health, but evidence on composite dietary indices remains limited. This cross-sectional study of 1845 community-dwelling older adults in China investigated the associations of the composite dietary antioxidant index (CDAI) and dietary phytochemical index (DPI) with cognitive function and mild cognitive impairment (MCI). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA; Beijing version). MCI was diagnosed through a two-stage procedure: MoCA-based preliminary screening (with education-stratified cutoffs: 13/14 for illiterate, 19/20 for 1–6 years, 24/25 for ≥7 years) followed by neurologist confirmation. CDAI was calculated as the sum of the standardized intakes of six antioxidants (selenium, zinc, carotenoids, vitamin A, vitamin C, vitamin E); DPI was defined as the percentage of the total energy intake from phytochemical-rich foods (fruits, vegetables excluding potatoes, legumes including soy products, nuts, seeds, and whole grains). Multivariable linear regression, logistic regression, and receiver operating characteristic (ROC) curve analyses were performed. The basal metabolic rate (BMR) and systemic immune-inflammation index (SII; platelets × neutrophils/lymphocytes) were tested as potential statistical mediators. Each one-unit increase in CDAI was associated with a 0.068-point higher MoCA score (95% CI: 0.012–0.123), and each one-unit increase in DPI was associated with a 0.029-point higher MoCA score (95% CI: 0.008–0.050). BMR and SII partially mediated the association between CDAI and MoCA score, but temporal ordering remains unclear due to the cross-sectional design. When both CDAI and DPI were in the highest quartile, participants had a 46.3% lower risk of MCI compared with those with both indices in the lowest quartile (OR = 0.537, 95% CI: 0.308–0.935). A predictive model incorporating CDAI, inflammatory markers, and red blood cell parameters showed moderate discriminatory ability in this study sample (apparent AUC = 0.731, bootstrap-corrected AUC = 0.728). These findings suggest that a higher combined dietary antioxidant and phytochemical intake may be jointly associated with better cognitive function, although the cross-sectional design precludes causal inference. Full article

Functional foods enriched with bioactive compounds have attracted increasing attention for their potential to improve metabolic health and reduce the risk of chronic diseases. White tea, a minimally processed tea rich in polyphenols and antioxidant constituents, may exert beneficial effects on obesity-related metabolic disturbances through multiple molecular pathways. In this study, we investigated the effects of white tea in a high-fat diet-induced obesity model in rats, with particular emphasis on metabolic regulation and adipokine signaling. Body weight, lipid profile, glucose homeostasis, insulin resistance-related parameters, and circulating levels of apelin and irisin were evaluated. High-fat diet feeding impaired metabolic balance and altered obesity-associated biochemical parameters, whereas white tea administration ameliorated several of these changes. White tea was associated with improvements in body weight gain and selected metabolic parameters, together with modulation of adipokine-related markers. These findings suggest that white tea may function as a bioactive-rich functional food with beneficial effects on pathways involved in obesity and metabolic homeostasis. Our results support the potential contribution of white tea-derived compounds to nutrition-based strategies for the prevention and management of obesity. Full article

Human motivation is governed by a long-memory cognitive process in which the depth of temporal integration—how far into the past the system draws upon accumulated experience—is not fixed, but dynamically compressed under cognitive stress. Despite extensive empirical evidence that acute stress impairs working memory and narrows temporal integration in decision-making, no existing mathematical framework has formally coupled the memory depth of the governing operator to a physiologically grounded stress indicator. To address this gap, we propose a stress-adaptive variable-order fractional model for motivational intensity $M\left(t\right)$, in which the Caputo fractional order $\alpha \left(t\right)$ varies inversely with an aggregated stress indicator $\sigma \left(t\right)$ through the Hill-type coupling $\alpha \left(t\right)={\alpha }_{min}+({\alpha }_{max}-{\alpha }_{min})C/(C+\sigma \left(t\right))$, thereby encoding the empirically documented shift from deep integrative to shallow heuristic processing as cognitive load increases. Rather than deriving the model by algebraic manipulation of a differential equation, we formulate it directly as a causally consistent type-III Volterra integral equation, in which the memory kernel is evaluated at the history time s, ensuring that the weight assigned to each past state reflects the memory depth that was physiologically active when that state was experienced. Well-posedness is established rigorously via the Banach fixed-point theorem with explicit contraction constants, uniform boundedness and non-negativity of solutions are derived through the fractional Gronwall inequality, and numerical solutions are computed using an Adams–Bashforth–Moulton predictor–corrector scheme adapted to the variable-order kernel. Five numerical experiments demonstrate that stress-induced variation in $\alpha \left(t\right)$ produces qualitatively richer dynamics compared with the tested constant-order baselines: the proposed model achieves a steeper peak decline rate (0.48 versus 0.19–0.45), a larger burnout gap (3.15 versus 1.92–2.81), and faster recovery to ninety percent of peak motivation (4.2 versus 3.9–7.3 time units), while the empirically observed numerical convergence approaches $O\left(h^2\right)$ for sufficiently small step sizes. The framework offers a principled phenomenological substrate for memory-adaptive cognitive modelling, with direct implications for stress-aware intelligent tutoring systems that are capable of inferring $\alpha \left(t\right)$ in real time from biometric signals such as heart rate variability or galvanic skin response, and adjusting instructional complexity accordingly. Empirical calibration against learning-analytics and psychophysiological datasets, together with stochastic extensions for probabilistic burnout-risk prediction, are identified as immediate priorities for future research. Full article

Background: The recombinant zoster vaccine (RZV) has been shown to reduce the risk of dementia and delay cognitive decline. However, economic evaluations in populations with mild cognitive impairment (MCI), particularly those incorporating cognitive outcomes, remain unavailable. This study evaluated the cost-effectiveness of RZV vaccination at age 50 among Chinese adults with MCI. Methods: A decision tree–Markov model was developed from a societal perspective to assess the lifetime cost-effectiveness of RZV (Shingrix, GSK) in a cohort of 1 million immunocompetent Chinese adults with MCI receiving vaccination at the age of 50. The primary outcome was the incremental cost-effectiveness ratio (ICER), while secondary outcomes included cases averted and the number needed to vaccinate (NNV) to prevent one case of herpes zoster (HZ), postherpetic neuralgia (PHN), and dementia. A willingness-to-pay (WTP) threshold equivalent to the 2024 Chinese gross domestic product (GDP) per capita (13,121 USD) was applied. Sensitivity analyses were conducted to test the robustness of the results. Results: Over a lifetime horizon, RZV vaccination was estimated to avert 54.64% of HZ cases, 97.58% of PHN cases, and 12.28% of dementia cases compared with no vaccination, resulting in an additional 2.23 million quality-adjusted life years (QALYs) gained. The ICER was 4216.99 USD/QALY, remaining well below the WTP threshold. The corresponding NNVs were 6.25 for HZ, 24.03 for PHN, and 280.82 for dementia progression. Conclusions: RZV vaccination is cost-effective for Chinese adults aged 50 years with MCI, providing substantial health gains through reductions in both HZ burden and dementia progression. Full article