Search Results (59,878)

Methamphetamine (MA) abuse, a growing global public health concern, has been linked to the emergence of neuropsychiatric effects, largely attributed to MA-induced neurotoxicity. Despite its significant impact, the precise mechanisms underlying this neurotoxicity remain poorly understood, and current therapeutic options for MA abusing patients are limited. In the present study, primary mouse neurons with 400 μM MA treatment and Nrf2 knockout C57BL/6J mice with 10 mg/kg MA treatment were used to investigate the regulatory mechanisms of Nrf2 in MA-induced cognitive impairment and neuronal apoptosis. Results revealed that Nrf2 activation occurred with in vitro and in vivo exposure to MA, with pronounced cognitive dysfunction in mice. In both primary neurons and prefrontal cortex and hippocampus tissues, MA exposure induced oxidative stress, disrupted mitochondrial dynamics (characterized by elevated Drp1 and p-Drp1 expression and reduced Mfn1 expression), enhanced mitophagy (characterized by high PINK1 and Parkin expression), and increased apoptosis. Notably, silencing or knocking out Nrf2 exacerbated MA-induced cognitive dysfunction, oxidative stress, and disruptions in mitochondrial dynamics, while further impairing mitophagy through reduced PINK1 and Parkin expression, ultimately leading to increased apoptosis. These results suggest that Nrf2 deficiency exacerbates MA-induced neuronal apoptosis and cognitive dysfunction. Consequently, Nrf2 may represent a promising therapeutic target for mitigating neurotoxic effects induced by MA. Full article

Background/Objectives: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition characterized by a complex and multifactorial genetic architecture. In this study, we report a male patient, born to non-consanguineous healthy parents, presenting with ADHD and oppositional defiant disorder (ODD). Methods: Trio-based whole-exome sequencing (WES) was performed in the proband and both parents. Variant classification was performed according to American College of Medical Genetics and Genomics (ACMG) guidelines, and the potential pathogenicity of the identified variant was further assessed through multiple in silico prediction algorithms and protein structural analyses. Results: WES identified a homozygous variant in the LNX2 gene (NM_153371.4: c.1165G>A, p.Ala389Thr), classified as a variant of uncertain significance (VUS) and supported by multiple in silico predictions. LNX2 is expressed during brain development and encodes an E3 ubiquitin ligase involved in neuronal differentiation and synaptic function. The identified variant is located within the PDZ2 domain, a functionally relevant region involved in protein–protein interactions. Although the variant is reported in population databases (gnomAD ID: rs148429804), it has not been associated with any clinical phenotype, and its presence in the homozygous state has been reported only once, remaining extremely rare and lacking clinical annotation. Structural modelling predicted localized rearrangement of the hydrogen-bonding network within the PDZ2 domain without major conformational changes. Integrative transcriptomic, and single-cell analyses further supported the biological relevance of LNX2 in neurodevelopment, highlighting its preferential association with neuronal projection-cell networks, synaptic vesicle trafficking pathways, and neuron-specific regulatory programs. Conclusion: Although the identified LNX2 variant cannot be considered causative for the patient’s phenotype and a definitive disease–gene relationship cannot be established based on a single individual, the complementary genetic, structural, and transcriptomic findings support the biological plausibility of LNX2 as a candidate gene for neurodevelopmental disorders. Additional independent patients and functional studies will be required to clarify its contribution to human disease. Full article

The number of alien species recorded in the Black Sea has increased over recent decades, raising concerns regarding their long-term ecological consequences. Among the taxa currently extending their distribution within the basin are the Pacific oyster, Magallana gigas, and the Chesapeake blue crab, Callinectes sapidus. This study presents new records of both species from the Romanian Black Sea coast obtained through citizen-reported observations. Five specimens of M. gigas collected from Constanța and Mangalia harbours were examined, together with one ovigerous female specimen of C. sapidus collected from Vadu Beach. In addition, two male C. sapidus records from Sinoe Lake were documented and validated based on photographic evidence. The finding of M. gigas in Mangalia Harbour extends the known distribution of the species along the Romanian coastline and suggests that the species is more widespread than previously documented. The occurrence of an ovigerous C. sapidus female confirms that reproduction is taking place in Romanian Black Sea waters. Morphometric measurements and reproductive traits were within the ranges reported from other Black Sea and Mediterranean populations. While none of these species can currently be regarded as invasive in Romanian coastal waters due to the absence of documented ecological impacts, the increasing frequency of records suggests that both warrant continued monitoring. The results further indicate that citizen-reported observations, when validated by specialists, can complement conventional surveys and provide valuable information on the occurrence and spread of conspicuous alien marine species, thereby supporting sustainable marine biodiversity monitoring and informed ecosystem management. Full article

Sheep hemoglobin hydrolysate (SHH) has important biological antioxidant functions. However, the specific mechanism is not well understood. The aim of this study was to investigate the antioxidant activity of SHH in vivo and its potential mechanism. Eighteen Sprague Dawley rats were randomly divided into DG (gavaged with 0.9% saline), VC (gavaged with vitamin C 100 mg/kg BW) and SHH (gavaged with SHH 800 mg/kg BW) groups. The rats were given intragastric administration for 21 days. On the 22nd day, all rats were intraperitoneally injected with diquat as a challenge. The results showed that SHH treatment had no obvious effect on the growth performance and main organ index of rats after the diquat challenge. Compared to the DG group, the SHH group maintained higher serum T-AOC and GSH-Px levels after the diquat challenge. SHH significantly increased GSH-Px activity in the liver and kidney, and decreased MDA content in the kidney after the diquat challenge. SHH significantly up-regulated the gene expression of TrxR in the liver and Nrf2 in the kidney but had no significant effect on the expression of NF-κB in the kidney. Histopathological observations showed that SHH could improve the morphology of liver cells, and no obvious pathological damage was found in all organs. In conclusion, the relative decrease in oxidative stress markers observed with prophylactic SHH supplementation after diquat challenge may be mediated by the regulation of transcriptional expression of Nrf2-related redox genes. These findings demonstrate SHH’s potential as a natural antioxidant and provide promising strategies for converting low-value meat industry byproducts into functional supplements. Full article

The transition to a globalized, fabless semiconductor manufacturing model has integrated third-party foundries and external intellectual property (IP) vendors into the integrated circuit (IC) design cycle. While this collaborative system promotes innovation, it also exposes layouts to security threats. Protecting these designs is paramount; however, applying traditional encryption methodologies fundamentally alters the syntactic hierarchy of the industry-standard GDSII stream format, causing electronic design automation (EDA) tools to crash. Furthermore, a full encryption hinders modern system-on-chip (SoC) development, where different teams require access to specific modules of the design, without exposing the entire IP. To resolve this issue between collaborative layout sharing and zero-trust security, this paper presents a software implementing an encryption engine. By applying the NIST-standardized FF1 Format-Preserving Encryption (FPE) algorithm directly to the geometric data, the proposed software obfuscates sensitive spatial coordinates and structural nomenclature while maintaining the native GDSII format. The engine embeds multi-tiered cryptographic access control directly into the layout, utilizing native metadata properties. This framework allows proprietary logic to be securely compartmentalized, ensuring that interacting parties only view the specific structures they possess the clearance to decrypt. Full article

Rotational molding is a shear-free technology to produce hollow plastic parts. Rotomolded poly(lactic acid) (PLA) and its biocomposites remain in a largely amorphous state, which limits their stiffness, toughness, and thermal resistance. Post-processing thermal annealing develops crystallinity without additives, but its combined effect with natural fibers has rarely been quantified. This work evaluates annealing at 100 °C for 1 h on rotomolded PLA biocomposites reinforced with 10, 20, and 30 wt.% of agave, coir, or pine fibers. Crystallinity (DSC, XRD), density and porosity, morphology (SEM), water absorption, mechanical properties (tensile, flexural, Charpy impact, Shore D hardness), and 28-day disintegration under lab-scale composting conditions were measured for treated and untreated samples. Annealing raised the matrix crystallinity from below 21% to 41–56% and produced predominantly α crystals with a nearly constant average size of about 20 nm. The treatment improved the matrix-dominated properties for every formulation: for neat PLA, Charpy impact strength increased by 120% (28.1 to 61.7 J/m), flexural strength by 53% (61.1 to 93.4 MPa), and flexural modulus from 3264 to 4511 MPa. Tensile strength and modulus, in contrast, remained unchanged or decreased. Porosity, set by fiber content, was unaffected by annealing; at 30 wt.%, the matrix barrier nonetheless reversed, and annealed samples absorbed more water and disintegrated faster than untreated ones. Fiber content sets the balance between matrix crystallinity and the interfacial damage caused by crystallization-induced contraction. Full article

Objectives: The objective of magnetisation transfer imaging (MTI) is to quantitatively assess myelin integrity in the cervical spinal cord (CSC) using MRI technology. The magnetisation transfer ratio (MTR) has been extensively studied as a prospective biomarker for identifying microstructural alterations in both healthy and diseased tissue. This systematic review aims to assess the repeatability and reproducibility of MTI-derived MTR studies in human CSC. Methods: A systematic search was performed in PubMed, Scopus, and Web of Science to identify studies evaluating the reliability of MTI, specifically MTR. Studies that met the criteria presented statistical metrics including intraclass correlation coefficient (ICC), coefficient of variation (CV%), or Bland–Altman (BA) analysis. Only peer-reviewed articles in English were included. The review adhered to PRISMA 2020 guidelines, and methodological quality was evaluated using the Quality Assessment with Diverse Studies (QuADS) tool. Results: Thirty studies were identified; following screening, six studies satisfied the inclusion requirements. These investigations assessed the reliability and reproducibility of MTR in both healthy individuals and patients with cervical myelopathy throughout spinal levels C1–C7. The ICC values exhibited considerable variability, spanning from poor agreement to about 0.90%, depending on the region of interest. The CV% values varied from 1.3% to 6.1% in non-healthy populations and from 0.5% to 12.7% in healthy groups. The BA analysis indicated no systematic bias, characterised by relatively minimal mean differences. A quantitative meta-analysis was not conducted due to methodological differences in each study. QuADS ratings demonstrated moderate to high methodological quality (77–96%). Conclusions: MTR exhibits generally low ICC values over different ROIs in most of the included studies and high to medium reproducibility for the evaluation of CSC. Nonetheless, diversity in acquisition procedures, statistical reporting and ROI selection continues to be a significant limitation of our study for not reporting the meta-analysis. Full article

Inflammatory and oxidative stress within the pancreatic islet microenvironment can alter insulin-derived peptides and generate neoepitopes that may reshape autoreactive T cell recognition in type 1 diabetes (T1D). One such modification, C19S, represents a cysteine-to-serine substitution at position 19 of the insulin B-chain and has recently been identified among human leukocyte antigen class II (HLA-II)-associated insulin neoepitopes recognized by autoreactive CD4+ T cells. Although the biological relevance of C19S has been determined, the molecular features that may distinguish C19S-specific T cell receptor (TCR) engagement from native insulin recognition remain incompletely defined. Here, we used comparative protein–protein docking, molecular dynamics (MD) simulations, interface-contact analysis, conformational landscape analysis, and binding-energy calculations to examine TCR engagement of human leukocyte antigen DQ8 (HLA-DQ8) presenting either native insulin peptide or the corresponding C19S insulin peptide. Initial modeling indicated that both peptide-HLA-DQ8 complexes were compatible with TCR-bound ternary complex formation. However, the C19S-containing complex was predicted to exhibit altered peptide-centered dynamics, changes in peptide backbone presentation, and reorganization of both TCR-peptide and TCR-HLA-DQ8 contacts. Comparative molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) and molecular mechanics generalized Born surface area (MM/GBSA) analyses further suggested a distinct calculated energetic profile under the applied modeling conditions for the C19S-containing complex, with residue-level decomposition localizing energetic differences to selected interface hotspots. Together, these findings provide a molecular framework for generating hypotheses about how C19S may reshape the HLA-DQ8-presented insulin recognition surface, with implications for future experimental studies of autoreactive CD4+ T cell recognition and antigen-specific tolerogenic strategies in T1D. Full article

Building materials and their spatial distribution play a significant role in determining the outcomes of human-caused and natural disasters in urban and peri-urban areas. However, building-level data on building and roofing materials are scarce. Here, we explore the feasibility and performance of a Convolutional Neural Network (CNN) model using spectrally transformed high-resolution multispectral imagery to map roofprints (i.e., classifying and delineating roofing materials at the building footprint-level) in Washington, District of Columbia (D.C.) and Denver, CO, United States. To generate consistent training data, we integrate geospatial vector data of individual building footprints with real estate industry-derived building-level roofing material data to create labeled image data from Planet SuperDove imagery. We compare the CNN classifier to a pixel-based machine learning (ML) model to demonstrate the capability of our roofprints mapping approach. With F1-scores ranging from 0.56 to 0.95 for the most common roof material classes, the CNN model outperformed the pixel-based ML classifier by 15% and 17% in Washington, D.C., and Denver, respectively. Results demonstrate within-domain robustness for the studied metropolitan areas, which are characterized by differing building densities, roof morphologies, and material patterns. While cross-region transferability was not evaluated, our findings provide a controlled comparison of pixel-based and context-aware approaches for rooftop material mapping and highlight the importance of hierarchical representations that integrate spectral information with roof texture, edge characteristics, spatial arrangement, and neighborhood context for improving classification performance. Accurately mapping building materials has the potential to advance urban planning and environmental policies, including assessments of heat exposure, energy demand, as well as hazard risk and community resilience. Full article

We examine the bias- and temperature-dependent direct current, radio frequency, and equivalent-circuit characteristics of a 150 nm AlGaN/GaN/SiC high-electron-mobility transistor (HEMT) for high-frequency applications. DC and S-parameter measurements on the wafer were conducted under various gate-bias settings within a varying thermal condition (−40 °C to 150 °C). The findings suggest a distinct decrease in drain current and transconductance with rising temperature, mostly attributed to heightened carrier dispersion and self-heating effects. At V_ds = 15 V, the I_ds decreases from 247.63 mA at −40 °C to 142.94 mA at 150 °C. The maximum transconductance decreases from approximately 56.5 mS to 31.5 mS. The assessed thermal resistance varies from 6.3 °C·mm/W to 11 °C·mm/W, signifying an increasing thermal limitation at elevated temperatures. The device has a point at which the temperature coefficient is zero at V_gs = −7.0 V, where the threshold-voltage shift and mobility degradation counterbalance one another. Small signal investigation indicates that f_t decreases from approximately 53 GHz to 39 GHz, whereas f_max declines from 107 GHz to 74 GHz within this temperature range. The derived equivalent-circuit characteristics demonstrate the temperature sensitivity of intrinsic capacitances, resistances, transconductance, and delay components, but extrinsic capacitances and inductances exhibit comparatively lower temperature sensitivity. The measured and modeled S-parameters are in strong agreement, hence validating the extraction methodology. The findings may serve as valuable guidance for bias optimization and thermally conscious RF circuit design with GaN HEMT technology. Full article

A cascade impactor equipped with microparticle surface acoustic wave sensors along with a surface cleaning system is an innovative system developed by our team to measure particles and monitor air quality. The system has been proven to function properly under various particle concentrations. Nevertheless, long exposure times and heavily polluted media impose a limitation on cascade impactors, known as surface saturation. This problem affects the sensitivity of our sensors, which tends to degrade with particles fouling the surface. To overcome this issue, a surface cleaning system that uses a Rayleigh wave-actuated water droplet has been implemented and tested. Rayleigh waves were generated on an innovative SAW chip, thus exciting the droplet using Radio-Frequency power. NaCl solutions and SiC particles were considered. The optimal droplet size was determined along with the required Radio-Frequency power. Experiments showed that the SAW-driven droplet successfully displaced the collected particles outside of the sensing zone, irrespective of their nature, without affecting the sensor’s performance. The results found in this study provide further improvements to our particle measuring system, advancing it towards an autonomous self-regenerating prototype. Full article

The COVID-19 pandemic has led to a rise in residential office utilisation. As a result, it has become increasingly important to configure workspaces and design dwellings to ensure adequate indoor environmental quality. Currently, UK industry best practice largely focuses on rationalising the window-to-wall ratio (WWR) for dwellings. However, there is an increased regulatory stringency on new build glazing thermal performance, without much regard to achieving adequate daylighting. This paper looks into enhancing daylighting sufficiency within newly constructed UK housing to meet the daylight availability requirements of the British Standard—BS EN 17037:2018+A1:2021—whilst simultaneously ensuring daylighting sufficiency, thermal comfort, and sustainability. A quantitative methodology was adopted using DesignBuilder through a calibrated daylighting simulation in association with thermal modelling for a typical semi-detached house in the UK. The performance of five glazing solutions with varying WWR was assessed against BS EN 17037:2018+A1:2021. The WWR of all glazing types was increased from an initial WWR of 15.26% until daylighting sufficiency was realised. The findings show that the house attained inadequate daylighting with the initial WWR of 15.26%, as 77% of frequently occupied spaces achieved an illuminance of 100 lx for 50% of the daylight hours and 300 lx for 42% of the frequently occupied space for 50% of the daylight hours, which failed to comply with the standard. Thus, a larger WWR of 25% is required for the house to comply with the current daylighting standard with the existing glazing type. However, a change of glazing type would enable compliance at a lower 20% WWR. In this study, a refinement strategy was conceived to review a combination of key parameters for refining the glazing selection. However, it was found that no compliant daylighting refinement strategy could be realised without an increase of 3.66 °C to the peak operative temperature. This paper, however, highlights the significance of fenestration selection beyond thermal performance, demonstrating the importance of other design variables such as daylight transmittance, solar heat gain coefficient, glazing heat losses, and peak operative temperatures. Full article

Growing attention has recently been devoted to the role of sound environments in the preservation of cultural heritage. Within this framework, the acoustic history of the Teatro Nuovo in Turin is investigated through virtual reconstructions of its principal architectural configurations, and buildings referring to architecture, built for acoustic purposes and used for sound-related activities, are considered places where acoustic heritage exists. For this reason, this paper aims to find out the acoustic heritage of the Teatro Nuovo in Turin, Italy, through a simulated reconstruction of its sound field evolution, before the last theatre’s recent closing. Acoustics of both the first realization in 1936 and the altered one in 1950 are analyzed, considering geometrical and material characteristics over time. Reverberation Time, RT, Clarity, C₈₀, Strength, G, Definition, D50, and lateral fraction, JFL, are considered, comparing the two scenarios, according to the Just Noticeable Difference, JND. The evaluation to use the space as a multipurpose auditorium follows. Conclusions underline that the second configuration was much more suitable both for speech activities and opera, with the Reverberation Time reducing from 1.78 to 1.24 s, and C80 and D50 increasing, but the multipurpose capability of the hall fair remaining. Acoustic suggestions for further restoration processes are indicated. Full article

Background/Objectives: Whole exome sequencing (WES) has emerged as a clinically valuable second-tier test following abnormal biochemical newborn screening (NBS). However, population-specific data on diagnostic yield, secondary findings (SFs), and exome-wide carrier burden remain scarce in East Asian neonates, particularly since the release of the ACMG SF v3.3 gene list. We aimed to characterize these metrics in a Taiwanese neonatal cohort. Methods: We retrospectively analyzed 118 consecutive neonates referred to Taipei Veterans General Hospital between August 2021 and August 2022 following abnormal biochemical NBS. WES was performed on the Illumina NovaSeq 6000 platform; variants were classified per the 2015 ACMG/AMP framework and re-evaluated under ACMG SF v3.3. Referral categories comprised lysosomal storage diseases (n = 61), amino acid disorders (n = 38), fatty acid oxidation disorders (n = 13), and organic acid disorders (n = 6). Results: Fifty neonates (42.4%) received confirmed molecular diagnoses and 45 (38.1%) were carriers (combined molecular resolution 80.5%). Five participants (4.2%) harbored pathogenic/likely pathogenic variants in ACMG SF v3.3 genes (TTN, LDLR, PTEN, RYR1, TP53). Incidental findings occurred in 51.7%, and at least one recessive-carrier variant was detected in 99.2% (mean 4.15 per individual; median 4). The Taiwanese-specific c.639+919G>A cardiac Fabry variant accounted for 24/25 confirmed male Fabry cases, and the p.Gly576Ser pseudodeficiency allele confounded all suspected Pompe cases. Conclusions: Second-tier WES substantially improves diagnostic precision, discriminating confirmed diagnoses from carrier, pseudodeficiency, and biochemical false-positive states. The high carrier burden and incidental-finding rate underscore the importance of comprehensive pre- and post-test genetic counseling in East Asian neonatal genomic programs. Full article

Sargassum muticum is an invasive brown macroalga that has rapidly expanded along the Moroccan Atlantic coast, posing ecological challenges while representing an abundant marine biomass with potential biotechnological value. This study investigated the biochemical composition and metabolic properties of Moroccan S. muticum through compositional analysis, in vivo metabolic evaluation, and molecular docking. Proximate analysis revealed a carbohydrate-rich composition with moderate protein content, together with photosynthetic pigments and nutritionally relevant minerals. In a cafeteria diet-induced rat model, dietary supplementation with S. muticum significantly attenuated body weight gain, improved adiposity-related indices, reduced serum total cholesterol, triglycerides, LDL cholesterol, and C-reactive protein levels, and increased HDL cholesterol. To obtain mechanistic insight, molecular docking analysis was performed using representative phlorotannins reported from Sargassum species. Among the compounds evaluated, dieckol showed the highest docking scores toward key metabolic targets, including AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma. Although these in silico findings do not demonstrate biological activation, they provide preliminary mechanistic support for the observed in vivo effects. Overall, the results highlight the potential of S. muticum for sustainable valorization as a functional marine bioresource. Full article