Search Results (4,908)

Background/Objectives: Multisensory inputs generate a common gravity-reference frame, but just the otoliths sense the gravity vector. Graviception is frequently assessed by setting a luminous line to the subjective visual vertical (S.V.V.). Population aging and diabetes prevalence, with insufficient physical activity, imply the need to ponder these factors in clinical assessments. This study aimed to assess S.V.V. accuracy/precision in adults with/without diabetes, according to age, physical activity, and general characteristics. Methods: Participants were 262 adults without diabetes (21–80 years old (y.o.)) and 187 adults with diabetes (28–80 y.o.; matched with 187 without diabetes). All participants had no history of otology/vestibular/neurology/autoimmune/orthopedic/severe renal disease or proliferative retinopathy or traumatic injury or balance complaints. After audiology–vestibular evaluations, the International Physical Activity Questionnaire was self-administered and the S.V.V. was estimated during static and on-axis rotation conditions. Results: In participants without diabetes, S.V.V. precision but not S.V.V. accuracy decreased after the age of 50 years, with no further decrease after the age of 70 years (up to 80 y.o.); the main cofactors contributing to the variability on the S.V.V. precision were physical activity and sitting time, with inconsistent contribution from a history of COVID-19 (R = 0.44 static and 0.35 on-axis, p < 0.00001). In participants with diabetes, the major contribution to the S.V.V. precision variability was from diabetes and age (R = 0.33, static and 31 on-axis, p < 0.00001). Conclusions: Apart from aging, the sensorimotor process affected by insufficient physical activity and sedentary behavior includes vestibular decline. The complex pathophysiology of diabetes may account for the contribution from these cofactors. Full article

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two main neurodegenerative diseases and cause disability and death in patients worldwide. Neurodegeneration is characterized by a progressive loss of neuronal function and structure, causing enormous impairment in cognitive–motor function. Magnolol and honokiol are isomeric biphenyl neolignans and have exhibited neuroprotective activity in previous studies. Hence, we assessed and compared honokiol, magnolol, and mixtures of honokiol and magnolol in honokiol/magnolol molar ratios of 1:3, 1:1, and 3:1 in terms of their neurotoxicity, using the cell counting kit-8 (CCK-8) assay, and of their neuroprotective effect on intracellular reactive oxygen species (iROS) against amyloid-beta (Aβ)- and 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced neurotoxicity in SH-SY5Y cells, using the 2′,7′-dichlorodihydrofluorescein diacetate (H₂DCF-DA) assay. The results showed that honokiol (H) and magnolol (M) at 0.1 μM and the mixtures of honokiol and magnolol in H/M ratios of 1:3, 1:1, and 3:1 at 0.0001 μM exhibited a significant neuroprotective effect of reducing iROS in SH-SY5Y cells where neurotoxicity was induced by Aβ- and MPP⁺ (p-value with respect to Aβ-treated cells < 0.005 and p-value with respect to MPP⁺-treated cells < 0.0001). Moreover, magnolol and honokiol possess antioxidant properties according to computational molecular analysis with Highest Occupied Molecular Orbital (HOMO)- Lowest Unoccupied Molecular Orbital (LUMO) prediction, 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and Ferric Reducing Antioxidant Power (FRAP) assays. The mixtures of honokiol and magnolol exerted synergistic neuroprotective ability at all ratios while showing better antioxidation ability than that of pure magnolol alone but comparable to that of pure honokiol alone. Drug-likeness, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction, and toxicity profiles showed that both compounds are promising neuroprotective agents and that one of the possible targeting mechanisms is the ROS-mediated oxidative stress pathway. Additional neuronal cell lines and in vivo models are required to determine similar effects or other protective mechanisms involving the neuroprotective ability of honokiol and magnolol. Full article

Background: Pes planus is a common foot deformity that may lead to both structural and functional consequences. This alteration in foot morphology has been associated with changes in neurosensory mechanisms such as proprioception and balance. This study aims to evaluate proprioception and balance parameters in young adults with pes planus by comparing them with healthy individuals. Methods: This case–control study, which had a quantitative and cross-sectional design, included a total of 90 volunteer university students aged 18–30. The presence of pes planus was assessed using the Navicular Drop Test. Proprioception assessment was performed using a digital goniometer to measure active and passive joint position sense, while balance assessment was performed using the Y Balance Test. Results: The groups were similar in terms of demographic and anthropometric characteristics (p > 0.05). In the proprioception assessment, a significant difference was observed in active joint position sense scores in individuals with pes planus (p = 0.032). In contrast, no significant difference was found between the two groups in terms of passive joint position sense (p = 0.769). According to the Y Balance Test results, no difference was observed in the anterior and posteromedial directions (p = 0.690 and p = 0.806). At the same time, the balance performance of individuals with pes planus was significantly lower in the posterolateral direction (p = 0.045). Conclusions: Young individuals with flexible pes planus showed differences in active joint position sense and balance performance in the posterolateral direction. This situation shows that pes planus may be associated with not only structural but also neurosensory functions. The findings highlight the importance of planning protective interventions early. In the future, there is a need for longitudinal studies conducted with larger and more heterogeneous samples, including rigid type pes planus. Full article

The sheep Y chromosome encodes genes essential for testicular development and spermatogenesis, yet their transcriptional dynamics across developmental and pathological states remain largely uncharacterized. Here, we profiled Y-linked gene expression using RNA-seq datasets from Hu sheep testes across postnatal development (0, 3, 6, 12 months) and from divergent testicular (large, normal, small, cryptorchid) and epididymal (large, small) weights. Developmental trajectory analysis of 134 expressed Y-linked genes revealed three distinct patterns: progressive activation from birth to sexual maturity (dominated by multicopy families ZNF280BY, HSFY, PRAMEY, TSPY3), progressive decrease, and stage-specific expression. Differential expression identified 41 Y-linked genes consistently downregulated in small, cryptorchid, and pre-pubertal testes compared with normal or large mature testes. Hierarchical clustering showed that 6-month-old small testes transcriptionally clustered with cryptorchid testes, not with immature or normal testes. In the epididymis, only one Y-linked gene was differentially expressed between large and small groups. Among X–Y gametolog pairs, most showed positive expression correlations in testes, whereas DDX3X/DDX3Y exhibited a significant negative correlation (ρ = −0.450, p = 0.0185); strikingly, this pair reversed to a positive correlation in the epididymis (ρ = 0.607, p = 3.29 × 10⁻⁵). In conclusion, Y-linked transcriptional profiles distinguish testicular pathology from normal maturation, and DDX3X/DDX3Y regulation is strictly tissue-specific. Full article

Background: Distinguishing genuine kinase–substrate motifs from background noise is a growing challenge, as mass spectrometry (MS)-based global phosphoproteomics identifies a rapidly expanding set of phosphorylation sites. One of the major limitations is selecting an appropriate background model that systematically controls both technical and biological sources of bias. Although using the entire proteome as a background in a FASTA format considers the overall amino acid composition, it is still prone to biases from protein abundance and the uneven distribution of sequence space (particularly around low-abundance proteins). By contrast, internal background methods can control experiment-specific detection biases, but they may not fully capture residue-specific compositions or general trends in phosphorylation. Methods: I develop a Dual-Background Enrichment (DBE) framework with a position-specific enrichment (PSE) strategy, which involves analyzing motif enrichment against two distinct background models: (1) A residue-heterogeneous internal background composed of phospho-motifs centered on the residue; e.g., phosphoserine (pS) motifs are tested relative to the pool of all detected phosphothreonine (pT) and phosphotyrosine (pY) motifs from the same experiment. (2) A FASTA background that includes all S, T, and Y residues in the UniProtKB proteome sequences. Results: Motifs are classified as high confidence if they meet statistical significance (q ≤ 0.05, fold enrichment > 1.5) against both background models. Conclusion: By applying the DBE strategy to a large-scale phosphoproteomics dataset, we distinguish motifs driven by amino acid composition (enriched in FASTA background only) from those reflecting kinase substrate specificity (enriched in both backgrounds). This dual-reference approach reduces false positives arising from sequence composition bias and enriches high-confidence candidate kinase recognition motifs. Full article

Traditional methods for screening high-melanin-yielding Auricularia heimuer strains are time-consuming and environmentally unfriendly. To address this issue, fifteen A. heimuer strains were used to determine the mycelial biomass, absorbance at 500 nm, CIE L*a*b* colorimetric values, and melanin yield of the fermentation broth. Pearson correlation analysis was performed to clarify the correlations among these indicators, and a regression equation was fitted to establish a rapid screening method. A total of 84 A. heimuer strains were used to verify this method, of which one high-melanin-yielding strain was obtained. The structural characterization and in vitro antioxidant activities of A. heimuer melanin (AHM) were determined. The results showed that the melanin yields of fifteen A. heimuer strains were extremely significantly positively correlated with absorbance at 500 nm (r = 0.880, p < 0.01). The fitted linear regression equation was Y = 0.0246X + 0.00094 (R² = 0.8756, p < 0.01). When 84 tested strains were investigated with this method, 8 strains (53.33%) exhibited relative differences below 10%, which is consistent with the satisfactory accuracy of the absorbance-based screening method. Finally, a high-melanin-yielding strain HMCC50028 was obtained, with a melanin yield of 0.0540 g/100 mL. The results of UV-Vis spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM) of AHM indicated that the melanin exhibited structural characteristics consistent with fungal melanins, belonging to the natural melanin family. In vitro assays demonstrated that AHM possessed excellent superoxide anion radical scavenging activity and ferric reducing power. Full article

Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger downstream of G protein-coupled receptors (GPCRs) and a central regulator of cellular signaling. Genetically encoded exchange proteins directly activated by cAMP (Epac)-based Förster resonance energy transfer (FRET) biosensors enable real-time monitoring of cAMP dynamics in living cells, but commonly used cyan/yellow FRET pairs require short-wavelength excitation, limiting compatibility with multiplex imaging and blue-light optogenetic tools such as bacterial photoactivated adenylyl cyclases (bPACs). Here, we engineered and systematically characterized four red-shifted Epac-based single-chain FRET cAMP sensors combining yellow or orange FRET donors with red fluorescent FRET acceptors. Using ratiometric live-cell imaging, we quantified stimulus-evoked FRET responses and identified Epac_red4 as the best-performing variant, showing an approximately 55% decrease in normalized FRET after forskolin stimulation. Epac_red4 also reliably detected G_i/o-mediated decreases in cAMP following μ-opioid receptor activation. Brief 405 nm light pulses induced graded and reversible cAMP elevations using the low dark-activity variant bPAC-F198Y. Furthermore, Epac_red4 enabled analysis of cAMP recovery kinetics during phosphodiesterase inhibition and multiplex imaging of cAMP and intracellular Ca²⁺ using Fura-2 with minimal spectral and pH-related interference under physiological imaging conditions. Together, Epac_red4 represents a robust red-shifted cAMP sensor for optogenetic and multiplex signaling studies. Full article

Background/Objectives. Neurofilament light chain (NfL) is a biomarker of axonal injury with prognostic value in acute ischemic stroke and a promising surrogate outcome marker. This study evaluated whether serum NfL concentrations in ischemic stroke were modified by varying degrees of renal function. Methods. In this prospective, single-center observational study, patients aged 18–80 y admitted to the IRCCS Mondino Foundation—Stroke Unit between May 2022 and August 2024 were enrolled. Inclusion criteria were: radiologically confirmed ischemic stroke within 24 h of onset, NIHSS ≥ 1 at admission, pre-stroke mRS < 2, no other neurological comorbidities, and eGFR > 30 mL/min/1.73 m². Serum creatinine was measured on admission, and eGFR was calculated using the CKD-EPI equation. Serum NfL was measured by Ella™ immunoassay at T0 (≤24 h), T1 (5 ± 3 d), and T2 (7 ± 3 d). Factors associated with serum NfL concentrations were assessed using linear mixed-effects models, and prognostic associations were evaluated by multivariate logistic regression. Results. Ninety-seven patients were included (median age 68.3 y; 39.2% female). Higher NfL levels were independently associated with lower eGFR (−2.4% per mL/min/1.73 m² increase; 95% CI −3.2% to −1.6%; p < 0.001), and higher NIHSS at admission (+3.5% per point; 95% CI 0.7% to 6.4%; p = 0.014). Time from stroke onset was also associated with NfL (p < 0.001). Among patients with 3-month follow-up and T2 measurement (n = 62), the main effects of log10-transformed NfL at T2 and eGFR were not independently associated with unfavorable outcomes. However, a significant log10 NfL × eGFR interaction was observed (OR 0.22; 95% CI 0.07–0.73; p = 0.014), indicating that the prognostic association of NfL varied according to renal function. Conclusions. Renal function affects serum NfL after ischemic stroke and appears to modify its prognostic association with 3-month outcomes. Full article

Introduction: Chronic dermatological diseases that appear in adolescence, such as acne vulgaris, atopic dermatitis, alopecia areata and psoriasis vulgaris, not only cause physical symptoms but also significantly affect young people’s quality of life, mental state, self-esteem and social relationships. Social media, especially information spread by influencers, significantly influences adolescents’ body image, health-related attitudes and even the quality of the physician-patient relationship. The aim of our study was to explore the relationships between dermatology-related quality of life, media use, health values, body image and self-esteem among adolescents with chronic dermatological diseases. Methods: In our cross-sectional, quantitative study, we used validated questionnaires (DLQI, EQ-5D-5L, IRVS, Attitude Scale, STAI-Y2, SWLS-H, Rosenberg Scale, BAT), which we supplemented with a media consumption questionnaire of our own design. Structured data collection took place between October 2024 and March 2025, with the participation of 208 adolescents aged 11–18. Data analysis was performed using SPSS 26.0 (Spearman’s correlation, Mann–Whitney test). Differences were considered significant at p < 0.05. Ethical approval: BM/22429-1/2024. Results: Acne vulgaris was the most common diagnosis (65%), followed by atopic dermatitis (22%) and psoriasis (11%). Over a quarter of the adolescents (27%) followed influencers who provided skincare advice. The mean daily screen time was 4.5 h, with 3.7 h on smartphones. A longer screen time was significantly correlated with poorer dermatological quality of life. Greater dermatology-related quality of life impairment (higher DLQI scores) was associated with poorer general quality of life (EQ-5D-5L). Following skincare-related influencers was significantly associated with dermatology-related quality of life and anxiety. Conversely, stronger health values were significantly linked to more favourable health behaviors. Conclusions: In this sample, greater dermatology-related quality-of-life impairment was associated with poorer psychosocial outcomes. Longer screen time was associated with poorer dermatology-related quality of life and less favourable psychosocial outcomes. The novelty of our study lies in the use of a self-developed media consumption questionnaire, which is suitable for the complex mapping of psychological and quality-of-life factors in adolescents. Full article

Fibrosis is a common extracellular matrix pathology characterized by increased scarring, representing a critical checkpoint toward cirrhosis and hepatocellular carcinoma. Its onset involves coordinated interplay among hepatocytes, Kupffer, and hepatic stellate cells (HSCs). Extracellular ATP and its derivates act as crucial damage-associated molecular patterns when released by injured liver cells, binding to specific purinergic receptors (P2X, P2Y, and P1) to establish an autocrine–paracrine signaling loop. The hepatic fibrotic response underlies the activation of ATP receptors that generate second messengers and cationic conductance. In parallel, extracellular nucleotidases hydrolyze ATP towards less phosphorylated intermediates and adenosine. This review focuses on the role of P2X and P2Y receptors in liver injury. The P2X7 receptor regulates the NLRP3 inflammasome in Kupffer cells and HSCs, while the P2X4 receptor is upregulated in myofibroblasts, modulating migration and matrix synthesis. Among P2Y receptors, P2Y2 drives inflammation and steatosis but promotes HIF-1α-mediated DNA repair. The P2Y6 receptor promotes alcohol-induced injury but restrains metabolic-dysfunction-associated steatohepatitis. P2Y2 and P2Y4 receptors maintain biliary homeostasis in cholangiocytes, whereas the P2Y1 receptor preserves HSC quiescence by blocking YAP translocation. Finally, UDP-glucose–P2Y14 induces HSC activation. Targeting these specific purinergic receptors or ecto-nucleotidases represents a promising pharmacological frontier against hepatic fibrosis. Full article

The gaze information channel paradigm models fixation sequences as a first-order Markov chain and quantifies gaze behaviour through Shannon entropy and mutual information (MI), where $I(X;Y)$ measures the reduction in uncertainty about the next fixation state given the current one. This paper extends the framework by introducing two new channels: the saccade amplitude channel, which discretises saccade angular distance into three categories (short, medium, long) with a four-category variant also analysed, and the pupil diameter channel, which discretises fixation-period pupil size into three categories. Both are applied to 10 observers viewing 12 Van Gogh paintings. The amplitude channel shows that observer-driven variation exceeds stimulus-driven variation. The pupil channel yields the highest $I(X;Y)$ among the two new channels ($0.489\pm 0.209$ bits per participant), consistent with the slow dynamics of pupil responses. Goodness-of-fit tests confirm significantly non-random sequential structure in both channels ($p<0.01$) for all pooled matrices. A simultaneous cross-channel association analysis across all five channels finds that 19 of 20 pairwise Spearman correlations are non-significant; the single nominally significant result (pupil–duration, $\rho =+0.697$, $p=0.025$) does not survive Bonferroni correction and is not robust to outlier removal. Two theoretical observations are presented: an upper bound on conditional entropy in terms of transition persistence (Proposition 1), and a refinement monotonicity result showing that finer discretisation cannot decrease channel MI (Remark 2). An exploratory comparison with five computational aesthetics measures finds a nominally significant negative correlation between pupil $I(X;Y)$ and Bense’s palette redundancy ($\rho =-0.692$, $p=0.013$, uncorrected), suggesting that diverse colour palettes are associated with stronger sequential pupil dynamics; permutation entropy and statistical complexity show no association with any channel. Full article

We introduce and study several conditions related to the factorization problem of composite numbers. For this purpose, we employ cyclotomic polynomials, Sylvester resultants, and the Fermat equation. For instance, we show that for $m\in \mathbb{N}$ and distinct primes p and q with p not dividing m, the existence of a solution to the Fermat equation $X^p+Y^p=Z^p$ in positive characteristic q such that $X+Y\ne Z$ and $X,Y$ and Z are m-th roots of unity implies the factorization of a composite natural number N that is a multiple of $pq$ at the cost of $O\left(\varphi \left(m\right)[m^3+m^2{(logN)}^2]M(\lfloor {log}_{2}N\rfloor +1)\right)$, where $\varphi$ is the Euler’s function and M is the multiplication time function for $\mathbb{Z}$. We also show that such solutions do not exist for many semiprime integers N, provided that m is required to have a fixed polynomial upper bound in $logN$. Full article

Sensor-based process monitoring often involves both process variables and quality-related variables. These variables are usually used together to detect faults and to evaluate their effects on process quality or performance. However, most existing monitoring methods still rely on squared reconstruction residuals. This treatment assumes a fixed residual structure and may be insufficient for nonlinear industrial processes. In practice, residual variances may vary with operating conditions. Residuals from different variables may also be correlated. To address this problem, this paper proposes a probabilistic residual modeling method for process–quality fault detection. The method retains the latent-variable structure of deep variational canonical correlation analysis. It further introduces conditional residual distributions for the process side and the quality side. These distributions are parameterized by the latent operating state inferred from sensor measurements. Residual negative log-likelihoods are then used as monitoring statistics. In this way, residual abnormality is evaluated under the current operating condition. The proposed method is verified on a three-phase flow facility and a continuous stirred tank reactor process. Compared with PLS, CCA, DCCA, and DVCCA, the proposed method improves the detection of process-side disturbances and provides clearer separation between process-related and quality-related abnormal responses. Quantitatively, in the TPFF air line blockage case, the process-side statistic $J_x$ achieved an FDR of 82.02% with an FAR of 1.52%, compared with an FDR of 52.02% obtained by the corresponding DVCCA statistic $SP{E}_x$. In the TPFF open direct bypass case, $J_x$ and $J_y$ achieved FDRs of 90.87% and 91.07%, respectively, with FARs of 0.00%. In the CSTR coolant-temperature sensor-bias case, $J_x$ achieved an FDR of 88.29% with an FAR of 0.00%, while $J_y$ remained below its control limit, supporting process–quality fault discrimination. Full article

We aimed to investigate the therapeutic effects of alpha-pinene (α-pinene), a major component of phytoncide, in in vitro and in vivo models of mild traumatic brain injury (mTBI), raising the possibility of treating mTBI, a condition currently lacking adequate therapies. An in vitro model was established using SH-SY5Y cells and a cell injury controller, and was treated with α-pinene (0.5 g/mL). An in vivo model was induced by a stereotaxic impactor in male C57BL/6J mice and treated with α-pinene intravenously (50 mg/kg and 100 mg/kg) for 3 days post-injury. Histopathological and immunohistochemical comparisons were conducted alongside cognitive function tests to evaluate -pinene treatment. In vitro analysis showed that alpha-pinene treatment significantly increased TUNEL-positive cells. Elevated NOX4 and p22phox mRNA expressions and a high Bax/Bcl-2 protein expression ratio were noted following alpha-pinene treatment. mTBI mice treated with alpha-pinene exhibited a notable decrease in brain water content with fewer FJB-positive neurons and lower protein expression of Bax and Bcl-2 compared to untreated mTBI mice. Immunofluorescence staining for NOX4 and GFAP-positive or Iba-1-positive cells demonstrated that the increased oxidative stress and astrogliosis or activated microglia triggered by mTBI were alleviated after alpha-pinene treatment. Cognitive function testing revealed a general improvement in mTBI mice treated with alpha-pinene, with statistical significance observed in the NOR test. Alpha-pinene appears to be beneficial for neuroprotection and enhancing cognitive function in the early phases of mTBI. Full article

Background/Objectives: Dynamic balance during the Y-Balance Test (YBT) relies on coordinated multi-joint control of the lower extremity. Although hip muscle strength is considered important for YBT performance, the relative contribution of individual hip muscle groups remains insufficiently understood. This study aimed to examine the associations between isometric hip abduction, external rotation, and extension strength and YBT performance in healthy adults. Methods: In this cross-sectional study, 104 healthy adults underwent assessment of isometric hip abduction, external rotation, and extension strength using strap-stabilized handheld dynamometry. Hip extension strength was measured in the prone position with the knee flexed to 90°. Strength values were normalized and expressed as joint torque (Nm/kg). YBT performance was assessed in the anterior, posteromedial, and posterolateral directions and as a composite score. Associations were examined using Pearson correlation coefficients. To account for the dependency of bilateral measurements, a linear mixed model (LMM) was used to evaluate the collective and independent contribution of hip strength components to YBT performance, with sex, age, and BMI included as covariates. Results: All hip strength measures showed significant positive correlations with YBT performance (r = 0.19–0.49, p < 0.05). Hip extension strength demonstrated the strongest associations, particularly with posterolateral reach (r = 0.49). After adjustment for demographic covariates, sex was the strongest predictor of YBT performance across all directions (β = 7.8–8.9, p < 0.001), with males achieving higher scores than females. Hip extension and abduction strength were significant predictors of posterolateral reach (p < 0.05), whereas no hip strength variable independently predicted anterior reach or composite score after adjustment for demographic factors. No significant differences in YBT performance were observed between limbs. Conclusions: Sex was the strongest predictor of YBT performance in healthy adults. Hip extension and abduction strength were independently associated with posterolateral reach performance after controlling for demographic factors, suggesting that the association between hip muscle strength and dynamic balance may be direction-specific. These findings highlight the importance of accounting for sex when interpreting the relationship between hip strength and YBT performance. Full article