Search Results (402)

In this study, nanoparticles prepared by the heat-induced self-assembly of bovine serum albumin-dextran conjugates (BSA-DX) were utilized as an effective delivery system for the immunoregulatory peptide Gln-Leu-Asn-Trp-Asp (QLNWD) from Meretrix meretrix. The effects of dry-heating duration on the fabrication and characteristics of glycoprotein nanoparticles (GBA NPs) were investigated. Stable GBA NPs (110.84 nm) were obtained after 9 h of dry-heating. Depending on the addition sequence of QLNWD, the QLNWD-loaded nanoparticles were categorized into two types: pre-loading and post-loading. The two strategies were evaluated based on physicochemical characterization, colloidal stability, and RAW264.7 macrophage uptake. Results showed that upon QLNWD incorporation, both pre-loading NPs and post-loading NPs exhibited spherical morphology, with particle sizes decreasing to 105.51 nm and 94.27 nm, respectively. The encapsulation efficiency of pre-loading NPs for QLNWD was higher (87.74%), and the co-localization ability between post-loading NPs and QLNWD was stronger (Pearson’s correlation coefficient = 0.95). In vitro simulated gastrointestinal digestion experiments showed that QLNWD bioaccessibility increased to 47.5% and 42.7% for pre-loaded and post-loaded NPs, respectively. Compared to free QLNWD, NP encapsulation significantly enhanced the uptake of QLNWD by macrophages. Thus, GBA NPs, particularly those prepared by the pre-loading method, are considered promising delivery systems for marine bioactive peptides. Full article

Despite significant advances in understanding the genetics of Parkinson’s disease (PD) and Parkinsonism, the diagnostic yield remains low. Pathogenic variants of GBA1, which encodes the lysosomal enzyme β-glucocerebrosidase and causes recessive Gaucher dis-ease, are recognized as the most important genetic risk factor for PD in heterozygous carriers. This study focuses on the functional genomics of rare genetic variations in other lysosomal hydrolytic enzymes genes in patient-derived fibroblasts. We examined 49 early-onset PD patients using whole exome sequencing and in silico panel analysis based on a curated PD gene list. Two patients were found to carry the p.Asp313Tyr variant in the X-linked GLA gene (encoding GALA, typically associated with Fabry disease), and one patient carried the p.Arg419Gln variant in GLB1 (encoding β-Gal, linked to the recessive GM1 gangliosidosis and mucopolysaccharidosis type IVB). The in silico study of both variants supports a potentially damaging impact on the encoded protein function and structural destabilization. Additional candidate variants were found related to lysosomes, Golgi apparatus and neurodegeneration, suggesting a multifactorial contribution to the disease. However, none of these variants met diagnostic standards. Functional assays showed a significant decrease in GALA expression and partial retention of the enzyme in the trans-Golgi network in fibroblasts with GLA:p.Asp313Tyr, while altered Golgi morphology was observed in fibroblasts with GLB1:p.Arg419Gln. Moreover, all patients exhibited abnormalities in lysosomal morphology, altered lysosomal pH, and impaired autophagic flux. Our findings suggest that rare, heterozygous variants in lysosomal-related genes, even when individually insufficient for monogenic disease, can converge to impair lysosomal homeostasis and autophagic flux in EOPD. The underlying genetic and cellular heterogeneity among patients emphasizes the importance of combining genetic and functional approaches to better understand the mechanisms behind the EOPD, which could enhance both diagnosis and future treatments. Full article

Electromagnetic compatibility (EMC) impacts of arc discharge from medium-low speed maglev trains on the VHF Data Broadcast (VDB) link of the Ground-Based Augmentation System (GBAS) are systematically investigated. Considering that a single VDB station serves multiple runways, this study evaluates how different placements of the VDB antenna relative to runway thresholds affect its susceptibility to maglev interference. Field measurements of maglev arc radiation under various operational conditions revealed a maximum radiation field strength of 57.76 dBμV/m at 113 MHz. Laboratory experiments further identified a minimum required signal-to-interference ratio (SIR) of 26 dB for reliable VDB signal decoding. Theoretical analyses demonstrate that maintaining a separation greater than 5.73 km between the maglev arc source and runway threshold is necessary to ensure signal integrity. The findings offer practical guidance for airport planning and electromagnetic protection design. Full article

Parkinson’s disease, associated with mutations in the GBA1 gene (GBA1-PD), is the most common genetic form of Parkinson’s disease (PD), marked by clinical heterogeneity influenced by mutation type. Extracellular vesicles (EVs), key mediators of intercellular communication, are implicated in PD pathogenesis through the transport of pathological proteins and lipids. In this study, we analyzed blood plasma-derived EVs from GBA1-PD patients carrying p.N370S and p.L444P mutations and from healthy controls using cryo-electron microscopy, lipidomics, and proteomics. EVs from GBA1-PD patients were significantly larger than those from controls, with the largest size and most multilayered vesicles observed in p.N370S carriers. Lipidomic profiling identified 237 lipid species; of these, 186 lipids were altered in p.N370S and 24 in p.L444P versus controls. Mutation carriers showed distinct lipid signatures, with p.L444P samples enriched predominantly in sphingolipids, while p.N370S carriers exhibited more extensive lipid remodeling across multiple classes, including triglycerides, cholesteryl esters, and phospholipids. Notably, Cer 23:0 was elevated across all GBA1-PD groups. Proteomic analysis revealed enrichment in pathways related to lipid transport, immune regulation, and vesicle-mediated processes. Overall, GBA1-PD patients share a distinct lipidomic EV signature, with mutation-specific patterns reflecting differing mechanisms of lysosomal dysfunction. These findings support the potential of EV profiling to unravel disease heterogeneity and identify biomarkers. Full article

This study investigates the microstructure evolution and mechanical properties of DSS2209 duplex stainless steel fabricated via cold metal transfer wire arc additive manufacturing (CMT-WAAM). The as-deposited thin-wall components exhibit significant microstructural heterogeneity along the build height due to thermal history variations. Optical microscopy, SEM-EDS, and EBSD analyses reveal distinct phase distributions: the bottom region features elongated blocky austenite with Widmanstätten austenite (WA) due to rapid substrate-induced cooling; the middle region shows equiaxed blocky austenite with reduced grain boundary austenite (GBA) and WA, attributed to interlayer thermal cycling promoting recrystallization and grain refinement (average austenite grain size: 4.16 μm); and the top region displays coarse blocky austenite from slower cooling. Secondary austenite (γ₂) forms in interlayer remelted zones with Cr depletion, impacting pitting resistance. Mechanical testing demonstrates anisotropy; horizontal specimens exhibit higher strength (UTS: 610 MPa, YS: 408 MPa) due to layer-uniform microstructures, while vertical specimens show greater ductility (elongation) facilitated by columnar grains aligned with the build direction. Hardness ranges uniformly between 225–239 HV. The study correlates process-induced thermal gradients (e.g., cooling rates, interlayer cycling) with microstructural features (recrystallization fraction, grain size, phase morphology) and performance, providing insights for optimizing WAAM of large-scale duplex stainless steel components like marine propellers. Full article

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Although genetic and environmental factors are established contributors, recent research has highlighted the critical role of the gut–brain axis (GBA) in ALS pathogenesis. The GBA is a bidirectional communication network involving neural, immune, and endocrine pathways that connect the gut microbiota with the central nervous system. Dysbiosis in ALS disrupts this axis, leading to increased intestinal permeability, neuroinflammation, and excitotoxicity. Notably, reductions in butyrate-producing bacteria, alterations in microbial metabolites, and enhanced NLRP3 inflammasome activation have been observed in patients with ALS. These changes may precede motor symptoms, suggesting a potential causative role. Interventions targeting the microbiome, such as dietary modulation, have shown promise in delaying disease onset and reducing inflammation. However, the clinical evidence remains limited. Given that gut dysbiosis may precede neurological symptoms, microbiota-targeted therapies offer a novel and potentially modifiable approach to ALS treatment. Understanding the role of GBA in ALS will open new avenues for early diagnosis and intervention. Further clinical trials are required to clarify the causal links and evaluate the efficacy of microbiome-based interventions. Understanding the brain–gut–microbiota axis in ALS could lead to new diagnostic biomarkers and therapeutic strategies. Full article

China has committed to carbon neutrality by 2060 by necessitating a comprehensive transformation of its building sector, particularly in rapidly urbanizing areas such as the Greater Bay Area (GBA), where subtropical climates, urban heat island effects, and extreme weather events present distinct challenges for achieving carbon reduction objectives through green building practices. The goal of this study is to establish an analysis method for green building success in the GBA’s subtropical environment, paying attention to the challenging goals of reducing carbon and making buildings more climate-resilient. Research techniques involved performing building energy simulations with EnergyPlus and DesignBuilder, applying LightGBM models for machine learning, using case studies from 32 buildings in Shenzhen, Hong Kong and Guangzhou and carrying out an evaluation of the policy using a PEI. Energy usage in green buildings was 45.3% less than in conventional structures, with Energy Use Intensity ranging from 65.1 to 72.4 kWh/m²/year, while traditional buildings used between 118.5 and 124.2 kWh/m²/year. Also, the carbon footprint during the life cycle of buildings was decreased by 38.4% and they became more resilient to typhoons, giving residents 72.4 h of power during storms, while conventional buildings gave only 8.3 h. HVAC system efficiency was the leading factor, accounting for 24.3% of the difference in energy performance. A detailed approach is developed for optimizing subtropical green buildings, based on unique design features and helpful policy ideas to promote carbon neutrality in swiftly growing metropolitan areas around the world. Full article

Background: Genetic factors pertinent to Parkinson’s disease (PD) might predispose an individual to post-traumatic stress disorder (PTSD). Humans who are heterozygous for the glucocerebrosidase 1 (GBA) L444P Gaucher mutation have an increased PD risk and elevated levels of alpha synuclein (aSyn). Mice that are heterozygous for the GBA mutation and express aSyn with the A53T mutation show elevated anxiety levels at 20 months of age compared to those expressing only A53T. Objective: This study aims to assess whether A53T and A53T-L444P affect the risk of developing PTSD phenotypes and whether sex and age modulate this risk. Methods: Young (5.1 ± 0.2 months) and older (11.3 ± 0.2 months) A53T and GBA L444P female and male mice were tested for fear learning and memory extinction in the contextual fear conditioning and passive avoidance paradigms. Subsequently, the mice were tested for measures of activity and anxiety in the open field and for depressive-like behavior in the forced swim test. Results: In the contextual fear memory extinction paradigm, only young A53T female mice showed contextual fear memory extinction, while older A53T female mice showed increased activity levels over subsequent days. In the passive avoidance memory paradigm, no mice showed extinction of passive avoidance memory. When the frequency of entering the more anxiety-provoking center of the open field was analyzed, a test history x sex x age interaction was observed. In the forced swim test, test history affected the depressive-like behavior in mice trained; there was more depressive-like behavior in mice trained in the contextual fear memory extinction paradigm than in mice trained in the passive avoidance memory extinction paradigm. Moreover, there was an effect of age with more depressive-like behavior in older than in younger mice, and an effect of genotype with more depressive-like behavior in A53T-L444P compared to A53T mice. When cortical phosphorylated tau (pS 199) levels were analyzed, there was an effects of genotype, a sex x age interaction, and ant age x test history interaction. Conclusions: A53T and A53T-L444P affect the risk of developing PTSD phenotypes. Fear extinction test history, genotype, and age affect depressive-like behavior and tau pathology. Full article

Dark skies, a vital natural and cultural resource, have been increasingly threatened by light pollution due to rapid urbanization, leading to ecological degradation and biodiversity loss. As a key strategy for sustainable regional development, dark sky parks (DSPs) not only preserve nocturnal environments but also enhance livability by balancing urban expansion and ecological conservation. This study develops a novel framework for evaluating DSP suitability, integrating ecological and socio-economic dimensions, including the resource base (e.g., nighttime light levels, meteorological conditions, and air quality) and development conditions (e.g., population density, transportation accessibility, and tourism infrastructure). Using the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) as a case study, we employ Delphi expert consultation, GIS spatial analysis, and multi-criteria decision-making to identify optimal DSP locations and prioritize conservation zones. Our key findings reveal the following: (1) spatial heterogeneity in suitability, with high-potential zones being concentrated in the GBA’s northeastern, central–western, and southern regions; (2) ecosystem advantages of forests, wetlands, and high-elevation areas for minimizing light pollution; (3) coastal and island regions as ideal DSP sites due to the low light interference and high ecotourism potential. By bridging environmental assessments and spatial planning, this study provides a replicable model for DSP site selection, offering policymakers actionable insights to integrate dark sky preservation into sustainable urban–regional development strategies. Our results underscore the importance of DSPs in fostering ecological resilience, nighttime tourism, and regional livability, contributing to the broader discourse on sustainable landscape planning in high-urbanization contexts. Full article

Gaucher disease (GD) is an autosomal recessive disorder caused by the deficient activity of the lysosomal enzyme glucocerebrosidase (GCase). Although enzyme replacement therapy (ERT) remains the standard of care for non-neuropathic GD patients, its high cost significantly limits accessibility. To enhance production efficiency, we developed a lentiviral system encoding a codon-optimized GCase gene driven by the human elongation factor 1a (hEF1α) promoter for stable production in human cell lines. A functional lentiviral vector, LV_EF1α_GBA_Opt, was generated at a titer of 7.88 × 10⁸ LV particles/mL as determined by qPCR. Six transduction cycles were performed at a multiplicity of infection of 30–50. The transduced heterogeneous human cell population showed GCase-specific activity of 307.5 ± 53.49 nmol/mg protein/h, which represents a 3.21-fold increase compared to wild-type 293FT cells (95.58 ± 16.5 nmol/mg protein/h). Following single-cell cloning, two clones showed specific activity of 763.8 ± 135.1 and 752.0 ± 152.1 nmol/mg/h (clones 15 and 16, respectively). These results show that codon optimization, a lentiviral delivery system, and clonal selection together enable the establishment of stable human cell lines capable of producing high levels of biologically active, synthetic recombinant GCase in vitro. Further studies are warranted for the functional validation in GD patient-derived fibroblasts and animal models. Full article

The gut–brain axis (GBA) represents a complex bidirectional communication network that links the gut microbiota (GM) and the central nervous system (CNS). Recent research has revealed that neurosteroids (NSs) play crucial roles in modulating neuroinflammatory responses and promoting neuroprotection. Meanwhile, GM alterations have been associated with various neuroinflammatory and neurodegenerative conditions, such as multiple sclerosis, Alzheimer’s disease, and amyotrophic lateral sclerosis. This review aims to provide a comprehensive overview of the intricate interactions between NS, GM, and neuroinflammation. We discuss how NS and metabolites can influence neuroinflammatory pathways through immune, metabolic, and neuronal mechanisms. Additionally, we explore how GM modulation can impact neurosteroidogenesis, highlighting potential therapeutic strategies that include probiotics, neuroactive metabolites, and targeted interventions. Understanding these interactions may pave the way for innovative treatment approaches for neuroinflammatory and neurodegenerative diseases, promoting a more integrated view of brain health and disease management. Full article

The rapid growth of construction and demolition waste (CDW) presents significant challenges to sustainable urban development, particularly in densely populated regions, such as the Guangdong–Hong Kong–Macao Greater Bay Area (GBA). Despite substantial disparities in CDW management (CDWM) performance across cities, the key influencing factors and effective strategies remain underexplored, limiting the development of localized and evidence-based CDWM solutions. Therefore, this study formulated three hypotheses concerning the relationships among CDWM performance, city attributes, and governance capacity to identify the key determinants of CDWM outcomes. These hypotheses were tested using clustering and correlation analysis based on data from 11 GBA cities. The study identified three distinct city clusters based on CDW recycling, reuse, and landfill rates. Institutional support and recycling capacity were key determinants shaping CDWM performance. CDW governance capacity acted as a mediator between city attributes and performance outcomes. In addition, the study examined effective strategies and institutional measures adopted by successful GBA cities. By highlighting the importance of institutional and capacity-related factors, this research offers novel empirical insights into CDW governance in rapidly urbanizing contexts. Full article

Intermittent fasting (IF) is emerging as a heterogeneous neurometabolic intervention with the possibility of changing the course of neurodegenerative diseases. Through the modulation of the gut–brain axis (GBA), cellular bioenergetics (or metabolic) reprogramming, and involvement in preserved stress adaptation pathways, IF influences a range of physiological mechanisms, including mitobiogenesis, autophagy, circadian rhythm alignment, and neuroinflammation. This review critically synthesises current preclinical and early clinical evidence illustrating IF’s capability to supplement synaptic plasticity and integrity, reduce toxic proteins (proteotoxic) burden, and rehabilitate glial and immune homeostasis across models of Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. The key players behind these effects are bioactive metabolites such as short-chain fatty acids (SCFA) and β-hydroxybutyrate (BHB), and molecular mediators such as brain-derived neurotrophic factor (BDNF). We feature the therapeutic pertinence of IF-induced changes in gut microbiota composition, immune response, and mitochondrial dynamics, and we discuss emerging approaches for merging IF into precision medicine frameworks. Crucial challenges include individual variability, protocol optimisation, safety in cognitively vulnerable populations, and the need for biomarker-guided, ethically grounded clinical trials. Finally, we propose IF as a scalable and flexible intervention that, when personalised and integrated with other modalities, may reframe neurodegeneration from a model of irreversible decline to one of modifiable resilience. Full article

Dissolved oxygen (DO) is a fundamental water quality parameter that directly determines aquaculture productivity. China contributes 57% of the global aquaculture production, with the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) serving as a key contributor. However, this region faces significant environmental challenges due to increasing intensive stocking densities and outdated management practices, while also grappling with the systematic monitoring limitations of large-scale operations. To address these challenges, in this study, a random forest-based model was developed for DO concentration retrieval (R² = 0.82) using Landsat 8/9 OLI imagery. The Lindeman, Merenda, and Gold (LMG) algorithm was applied to field data collected from four cities—Foshan, Hong Kong, Huizhou, and Zhongshan—to identify key environmental drivers to the changes in DO concentration in these cities. This study also employed satellite imagery from multiple periods to analyze the spatiotemporal distribution and trends of DO concentrations over the past decade, aiming to enhance understanding of DO variability. The results indicate that the average DO concentration in fishponds across the GBA was 7.44 mg/L with a statistically insignificant upward trend. Spatially, the DO levels remained slightly lower than those in other waters. The primary environmental factor influencing DO variations was the pH levels, while the relationship between natural factors such as the temperature and DO concentration was significantly hidden by aquaculture management practices. The further analysis of fishpond water quality parameters across land uses revealed that fishponds with lower DO concentrations (7.293 mg/L) are often located in areas with intensive human intervention, particularly in highly urbanized regions. The approach proposed in this study provides an operational method for large-scale DO monitoring in aquaculture systems, enabling the qualification of anthropogenic influences on water quality dynamics. It also offers scalable solutions for the development of adaptive management strategies, thereby supporting the sustainable management of aquaculture environments. Full article

Background: The gut–brain axis (GBA) has been demonstrated to be involved in normal neurodevelopment, with its dysfunction potentially contributing to the onset of mental disorders. In this systematic review and meta-analysis, we aimed to examine the relationship between levels of specific biomarkers of intestinal permeability or inflammation and scores of depressive symptoms or suicidality. Methods: All studies investigating the link between depressive symptoms and/or suicidality and biomarkers associated with intestinal permeability or inflammation were included. Studies providing data for comparisons between two groups—depressive or suicidal patients vs. healthy controls, or suicidal vs. non-suicidal patients—were included in the meta-analysis. Studies examining the correlation between depressive symptoms and biomarker levels were also included into the review. Data were independently extracted and reviewed by multiple observers. A random-effects model was employed for the analysis, and Hedge’s g was pooled for the effect size. Heterogeneity was assessed using the I² index. Results: Twenty-two studies provided data for inclusion in the meta-analysis, while nineteen studies investigated the correlation between depressive symptoms and biomarker levels. For depressive symptoms, when compared to the controls, patients showed significantly increased levels of intestinal fatty acid-binding protein (I-FABP) (ES = 0.36; 95% CI = 0.11 to 0.61; p = 0.004; I² = 71.61%), zonulin (ES = 0.69; 95% CI = 0.02 to 1.36; p = 0.044; I² = 92.12%), antibodies against bacterial endotoxins (ES = 0.75; 95% CI = 0.54 to 0.98; p < 0.001; I² = 0.00%), and sCD14 (ES = 0.11; 95% CI = 0.01 to 0.21; p = 0.038; I² = 10.28%). No significant differences were found between the patients and controls in levels of LPS-binding protein (LBP) and alpha-1 antitrypsin (A-1-AT). For suicidality, four studies were identified for quantitative analysis, three of which focused on I-FABP. No significant differences in I-FABP levels were observed between suicidal patients and the controls (ES = 0.24; 95% CI = −0.30 to 0.79; p = 0.378; I² = 86.44%). Studies investigating the correlation between depressive symptoms and levels of intestinal permeability and inflammation biomarkers did not provide conclusive results. Conclusions: A significant difference was observed between patients with depressive symptoms and controls for biomarkers of intestinal permeability (zonulin, which regulates tight junctions), inflammatory response to bacterial endotoxins (antibodies to endotoxins and sCD14—a soluble form of the CD14 protein that modulates inflammation triggered by lipopolysaccharides), and acute intestinal epithelial damage (I-FABP, released upon enterocyte injury). Studies investigating suicidality and related biomarkers were limited in number and scope, preventing definitive conclusions. Overall, these findings suggest that biomarkers of gut permeability represent a promising area for further investigation in both psychiatric and forensic pathology. They may have practical applications, such as supporting diagnostic and therapeutic decision-making in clinical settings and providing pathologists with additional information to help determine the manner of death in forensic investigations. Full article