Search Results (509)

Amid China’s “Manufacturing Power” push, full-chain digital restructuring in the Guangdong–Hong Kong–Macao Greater Bay Area remains hampered by mismatches among technology, organization, and environment. We therefore explored how shop floor actors perceive and shape this Technology–Organization–Environment (TOE) interplay. Semi-structured interviews with frontline operators, maintainers, and supply chain staff from GBA manufacturers were inductively coded, yielding 36 concepts, 10 categories, and 3 core TOE aggregates that were woven into a grounded model. The analysis shows that industrial internet platforms and smart equipment only create value when matched by flexible shop floor structures, cross-department data protocols, and skilled teams; otherwise, data silos, simulation–production deviations, and “buy-but-not-build” procurement stall adoption. Market pressure for customized, short-lead-time products and divergent municipal pilot policies further intensify the TOE balancing act, particularly for SMEs with weak absorptive capacity. By revealing a grassroots “technology-driven → organization-adapted → environment-adjusted” spiral that is moderated by frontline feedback, the study extends the TOE framework to micro-level, regional innovation theory and offers policy–practice levers for differentiated, cross-city manufacturing upgrading. Full article

The ongoing advance of urbanization has increased the need for accurate monitoring of urban green space (UGS). However, existing remote-sensing UGS mapping still struggles with inconsistent data quality, diverse urban forms, and limited cross-city generalization. This study focuses on China’s Guangdong-Hong Kong-Macao Greater Bay Area as its research region, establishing a fully automated UGS mapping framework based on Sentinel-2 time-series imagery and standardized OpenStreetMap (OSM) data. This process achieves UGS mapping at 10 m resolution for 16 cities within the metropolitan area through a dynamic standardized OSM tagging system, a Sentinel-2 satellite image sample generation mechanism integrating spectral and textural features, multidimensional sample quality assessment and weighting strategies, as well as balanced cross-city sampling and weighted SVM classification. The results demonstrate that this method exhibits stable performance across multiple urban environments, achieving an average overall accuracy of approximately 0.83 and an average F1 score of approximately 0.82. The highest recorded F1 score reaches 0.96, highlighting the method’s strong generalization capability under diverse urban conditions. The mapping results reveal significant disparities in UGS distribution within the Guangdong-Hong Kong-Macao Greater Bay Area, reflecting the combined effects of varying urban development patterns and ecological contexts. The unified workflow proposed in this study demonstrates strong applicability in handling heterogeneous urban structures and enhancing cross-regional comparability. It provides consistent, transparent, and reusable foundational data for regional eco-urban planning, urban green infrastructure development, and policy evaluation. Full article

Background: Female individuals with inflammatory bowel diseases (IBDs) are more likely to develop restrictive eating disorders (REDs), with both conditions appearing to share common pathophysiological pathways. We conducted a case–control study exploring eating symptomatology and interoceptive profiles in female adolescents with IBDs compared with adolescents diagnosed with REDs, in order to test the hypothesis that the two clinical populations exhibit similar interoceptive characteristics. Methods: We recruited 33 female adolescents with IBDs and 54 controls with REDs matched for age and gender. All participants completed a validated psychometric battery assessing eating disorder features (EDI-3) and interoceptive awareness (MAIA-2). Results: Twenty-seven percent of patients with IBD scored above the cut-off (>70th percentile) on the EDI-3 Eating Disorder Risk Composite (EDRC), showing an eating and interoceptive profile comparable to that of patients with REDs. The two sub-cohorts within the IBD sample differed in the ‘Not-Worrying’ and ‘Trusting’ MAIA-2 subscales, with the IBD cohort at risk of developing an ED reporting lower scores. Conclusions: Our findings indicate comparable interoceptive profiles between adolescents with IBDs who are at risk of developing EDs and patients with a confirmed diagnosis of REDs. This similarity underscores the need to further investigate the shared pathogenic mechanisms underlying these conditions, particularly the role of the gut–brain axis (GBA). Full article

Background: Variants in the GBA gene represent the most common genetic risk factor for Parkinson’s disease and are associated with a more aggressive disease course. Deep brain stimulation is an established therapy for advanced Parkinson’s disease, yet the influence of GBA status on postoperative outcomes remains incompletely defined. This review aims to summarize the clinical relevance of GBA genotyping prior to DBS and to evaluate its potential contribution to decision-making, risk stratification, and long-term management. Methods: A structured narrative review was conducted. The literature on sequencing methodology, variant interpretation, and postoperative outcomes in GBA-positive and GBA-negative patients was examined. Particular focus was placed on motor, cognitive, and neuropsychiatric outcomes, and on studies comparing trajectories across variant classes. Results: Across all study designs, patients with GBA-associated Parkinson’s disease demonstrated robust motor improvement after DBS, with outcomes comparable to those in non-carriers. Cognitive and neuropsychiatric decline occurred more rapidly in GBA carriers. Recent evidence indicates that cognitive and neuropsychiatric decline is influenced more by the genetic profile than the stimulation procedure. Variant severity appears to influence postoperative trajectories. Long-read sequencing improves detection of recombinant alleles and may refine genotype–phenotype associations. Genotyping provides additional value in counseling, expectation management, and postoperative planning. Conclusions: DBS remains an effective motor therapy for patients with GBA-associated Parkinson’s disease. Current findings indicate GBA genotyping should inform, and not limit, candidate selection. Integration of clinical, cognitive and genetic data supports more individualized management. Methodological advances in sequencing and the development of prediction models may further enhance personalized DBS planning. Full article

Megacity regions mark a transformative phase of urbanisation, in which interconnected cities undergo land-use and land-cover change (LUCC) that extends beyond administrative boundaries. However, the drivers of cross-boundary LUCC remain insufficiently examined, particularly before the top-down regional integration. The Guangdong–Hong Kong–Macao Greater Bay Area (GBA) provides a clear empirical case, having experienced cross-boundary LUCC prior to its formal designation as a megacity region in 2018. This study builds a Landsat-derived LUCC and driver dataset for the GBA. Global and local spatial autocorrelation (Moran’s I and LISA) are used to characterise spatial structure and clustering, and geographically weighted regression identifies the socio-economic and environmental determinants of built-up expansion over 1980–2018, spanning the pre-reform decade and the post-1990 land-transfer era. Findings reveal that: (1) LUCC in the GBA already exhibited a cross-border, spatially networked expansion pattern before formal regional integration policies at the national level, with built-up area growth extending beyond core cities into decentralised urban nodes. Two prominent cross-border cores and one cross-administrative core emerged, suggesting that regional integration was co-led by market forces and local governments before an institutional framework was established. (2) Although the GBA showed a clear trend towards integrated development, urban expansion was highly uneven. Such spatial disparities were mainly driven by varying socioeconomic and natural factors, including gross domestic product, population growth, real estate investment, water resource proximity, and infrastructure development. These findings enhance understanding of megacity-region dynamics and offer insights from the GBA for cross-border urbanisation and sustainable spatial governance. Full article

The intestinal microbiota, a diverse community of microorganisms residing in the human gut, recently attracted considerable attention as a contributing factor to various neurological disorders, including Alzheimer’s Disease (AD). Within the established framework of the gut–brain axis (GBA) concept, it is commonly suggested that dysbiosis, through microbial metabolites entering the brain, affect the cognitive functions in patients with AD. However, evidence for such a role of dysbiosis remains largely associative, and the complexity of the communication channels between the gut and the brain is not fully understood. Moreover, the new players of the GBA are emerging and the AD concept is constantly evolving. The objective of this narrative review is to synthesize the current evidence on the humoral, endocrine, immune, and neural communication mechanisms linking the gut and brain in AD and highlight newly discovered GBA messengers such as microRNAs, extracellular vesicles, T-cells, and the intestinal hormones, including emerging neuroprotective role for glucagon-like peptide-1 (GLP-1). Based on this knowledge, we aimed to develop a conceptual understanding of the GBA function in health and AD. We specify that, in AD, the GBA goes beyond a disrupted microbiome, but operates in conjunction with impaired intestinal secretion, motility, barrier permeability, and neuroinflammatory signaling. These factors are associated with the dysfunction of the hypothalamic–pituitary axis, altered somatic and autonomic neuronal gut regulation, and abnormal, due to memory problems, behavioral aspects of food intake. Identifying the individual profile of key molecular and cellular players contributing to an unbalanced GBA should optimize existing approaches or propose new approaches for the complex therapy of AD. Full article

The gut–brain axis (GBA) interaction is important for human health and disease prevention. Organ chips are considered a solution for GBA research. Three-dimensional (3D) cultures and microfluidics engineered in an organ chip could improve the scientific knowledge in the GBA interactions field. In this study, a novel organ chip is developed, which achieves multicellular three-dimensional cultivation by utilizing a decellularized matrix. In addition, this paper reports the rapid prototyping process of the GBA microfluidic chip in polydimethylsiloxane (PDMS) using 3D printing interconnecting poly(ethylene/vinyl acetate) (PEVA) microchannel templates. In comparison to the static culture system of the transwell model, the intestinal epithelial barrier (IEB) and blood–brain barrier (BBB) models on our chip demonstrated superior barrier function and the efflux functionality of transporters under appropriate fluidic conditions. Additionally, it is observed that butyrate protected against BBB dysfunction induced by gut-derived lipopolysaccharide (LPS) via enhancing intestinal barrier function. These results demonstrate that this multicellular, three-dimensional cultivation integrated with a fluidic shear stress simulation chip offers a promising tool for gut–brain interaction study to predict therapy of intestinal and neurological disorders. Full article

Building Information Modeling (BIM) is increasingly used to support green building design practices, yet its alignment with established green building assessment (GBA) tools remains underexamined. This study evaluates the extent to which Autodesk Revit, as a BIM tool, supports the calculation of energy-related indicators in GBA tools such as the Leadership in Energy and Environmental Design (LEED) method. A quasi-empirical, multi-method approach was employed, combining content analysis, a Revit-based simulation of a residential building, and structured evaluation by a panel of four experts. Using both subjective and objective measures, the experts assessed Revit’s effectiveness and the role of Revit’s media channels—modeling, simulation, data integration, and text documentation—in supporting and calculating LEED Energy and Atmosphere (EA) indicators. Results reveal that Revit is capable of effectively supporting 7 out of 11 LEED EA indicators. The highly supported indicators included minimum energy performance, building-level energy metering, optimized energy performance, advanced energy metering, renewable energy production, and enhanced refrigerant management while the fundamental refrigerant management indicator was evaluated as a moderately supported indicator. These highly supported indicators are core energy-related indicators; three of them are prerequisite indicators, while the remaining are credit indicators that cover 66.7% of the weight assigned for the EA indicators. The results also demonstrated that the remaining four indicators—fundamental commissioning and verification, enhanced commissioning, demand response, green power, and carbon offsets—were evaluated as poorly supported by Revit. The consistency of results across two rounds of survey, along with the expert’s consensus on 73% (8 out of 11) of the examined indicators, provides empirical validation of Rivet’s capacity to support LEED GBA. Findings also showed that modeling and simulation, followed by data integration, are the most impactful channels in supporting and calculating LEED EA criteria and requirements, with significant statistical correlation confirmed through Kendall’s Tau correlation. The findings have theoretical and practical implications for designers, green building practitioners, and BIM developers and suggest areas for further research. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder shaped by genetic factors such as LRRK2 and GBA1 mutations, as well as dietary and metabolic influences. Food-derived plasma metabolites—including caffeine, paraxanthine, trigonelline, piperine, and sitosteryl hexoside—have emerged as promising, accessible biomarkers for early detection, progression monitoring, and therapeutic targeting, yet their longitudinal behavior and genetic interactions remain insufficiently characterized. Using the Parkinson’s Progression Markers Initiative (PPMI) cohort (n = 455; 303 PD patients, 152 controls), we quantified plasma levels of these metabolites by quantitative LC-MS/MS with batch correction, examining sporadic PD and genetically defined subgroups (LRRK2-PD [PDL], GBA1-PD [PDG], dual-mutation PD [PDGL], and prodromal equivalents). Baseline one-way ANOVA showed significantly lower caffeine and paraxanthine in PDL (p = 0.0467, p = 0.0178) and PDG (p = 0.0408), reduced piperine in PDL (p = 0.0009), PDG (p = 0.0257), and prodromal LRRK2 (p = 0.0168), and elevated sitosteryl hexoside in PDG (p = 0.0184). Longitudinal regression analyses revealed that in sporadic PD, caffeine negatively correlated with MDS-UPDRS parts I (β = −2, p = 0.0475) and III (β = −7.2, p = 0.007), trigonelline declined over time and was inversely associated with part III (β = −1.7, p = 0.0069), and sitosteryl hexoside negatively correlated with parts II (β = −68.3, p = 0.042) and III (β = −74.1, p = 0.0425). In PDL, sitosteryl hexoside inversely correlated with part I (β = −54.2, p = 0.0049), while in PDGL, paraxanthine showed negative associations with part II (β = −18.5, p = 0.00327). These findings demonstrate subgroup-specific alterations in food-derived metabolites and consistent inverse associations with PD severity, supporting their potential as non-invasive biomarkers, particularly in LRRK2/GBA1 mutation carriers, and highlighting the need for longitudinal validation and dietary intervention trials to advance personalized PD management. Full article

As critical ecosystems, coastal zones necessitate the identification of their ecosystem service values, trade-off/synergy patterns, spatiotemporal evolution, and driving factors to inform scientific decision-making for sustainable ecosystem management. This study selected the coastal zone of the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) as the research region. By incorporating land-use types such as mangroves, tidal flats, and aquaculture areas, we analyzed land-use changes in 1990, 2000, 2010, and 2020. The InVEST model was employed to quantify six key ecosystem services (ESs): annual water yield, urban stormwater retention, urban flood risk mitigation, soil conservation, coastal blue carbon storage, and habitat quality, while spatial correlations among them were examined. Furthermore, Spearman’s rank correlation coefficient was used to assess trade-offs and synergies between ecosystem services, and redundancy analysis (RDA) combined with the geographically and temporally weighted regression (GTWR) model were applied to identify driving factors and their spatial heterogeneity. The results indicate that: (1) Cultivated land, forest land, impervious surfaces, and water bodies exhibited the most significant changes over the 30-year period; (2) Synergies predominated among most ecosystem services, whereas habitat quality showed trade-offs with others; (3) Among natural drivers, the normalized difference vegetation index (NDVI, positive effect) and evapotranspiration were critical factors. The proportion of impervious surfaces served as a key land-use change driver, and the nighttime light index emerged as a primary socioeconomic factor (negative effect). The impacts of drivers on ecosystem services displayed notable spatial heterogeneity. These findings provide scientific support for managing the supply-demand balance of coastal ecosystem services, rational land development, and sustainable development. Full article

Background/Objectives: Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of misfolded alpha-synuclein protein in the brain. Mutations in the glucocerebrosidase 1 (GBA1) gene have been identified as a significant genetic risk factor for both PD and DLB. GBA1 encodes for the lysosomal enzyme glucocerebrosidase, which is responsible for the breakdown of glucosylceramide (GC). Deficiencies in glucocerebrosidase activity lead to the accumulation of glucosylceramide within lysosomes, contributing to lysosomal dysfunction and impaired protein degradation. The aim of this narrative review is to update the underlying mechanisms by which GBA1 mutations contribute to the pathogenesis of PD and DLB. Methods: A comprehensive literature search was conducted across four major electronic databases (PubMed, Web of Science (Core Collection), Scopus, and Embase) from inception to 8 November 2025. The initial search identified approximately 1650 articles in total, with the number of hits from each database being as follows: PubMed (~450), Web of Science (~380), Scopus (~520), and Embase (~300). Results: The mechanism by which mutations in the GBA1 gene contribute to PD involves both loss-of- function and gain-of-function pathways, which are not mutually exclusive. Typically, GBA1 mutations lead to a loss of function by reducing the activity of the GCase enzyme, impairing the autophagy- lysosomal pathway and leading to α-synuclein accumulation. However, some mutant forms (GBA1L444P) of the GCase enzyme can also acquire a toxic gain of function, contributing to α-synuclein aggregation through mechanisms like endoplasmic reticulum stress and misfolding. While Venglustat effectively reduced GC levels, a key marker associated with GBA1-PD, the lack of clinical improvement led to the discontinuation of its development for this indication. Conclusions: GBA1-mediated lysosomal and lipid dysregulation represents a key pathogenic axis in PD and DLB. Understanding these mechanisms provides crucial insight into disease progression and highlights emerging therapeutic strategies—such as pharmacological chaperones, substrate reduction therapies, and gene-targeted approaches—aimed at restoring GCase function and lysosomal homeostasis to slow or prevent neurodegeneration. Full article

The Guangdong–Hong Kong–Macao Greater Bay Area (GBA) is a key economic region in China facing increasing pressure to balance socioeconomic development with environmental protection and energy conservation. This study examines the interrelationships among energy consumption, air pollutants (PM_2.5, NO₂, and SO₂), and carbon dioxide (CO₂) emissions in the GBA from 2000 to 2020. Using spatial correlation matrices and temporo-spatial decoupling analysis, we assess spatial patterns, temporal dynamics, and interactions among these factors. Results show that the GBA has made significant progress in reducing air pollution and carbon emissions. Notably, since 2013, concentrations of PM_2.5, NO₂, and SO₂ have decoupled markedly from energy consumption, reflecting effective pollution control measures. Although CO₂ emissions have decreased more gradually, the trend remains positive, indicating steady advances in carbon management. These findings underscore the need for continued optimization of the energy structure to achieve coordinated control of energy use, air quality, and carbon emissions—essential for promoting sustainable, high-quality development in the region. Full article

Background/Objectives: X-linked hypohidrotic ectodermal dysplasia (XLHED) is a rare monogenic disorder characterized by hypohidrosis, hypotrichosis, and hypodontia, caused primarily by pathogenic variants in the EDA gene. XLHED predominantly affects males due to its X-linked recessive inheritance, while female carriers may exhibit variable phenotypes due to random X-inactivation. Early diagnosis is critical for timely counseling and emerging therapeutic interventions. We report a rare prenatal diagnosis of XLHED in dizygotic dichorionic male twins during a dichorionic diamniotic pregnancy. At 24 weeks’ gestation, ultrasonographic anomalies—facial dysmorphisms, oligodontia, and hypoechogenic skin—raised suspicion for ectodermal dysplasia. Methods: Non-invasive prenatal test and targeted next-generation sequencing (NGS) of Cell-free DNA identified an hemizygous EDA deletion (c.612_629del; p.Ile205_Gly210del) with 52% variant allele frequency. Results: This in-frame deletion affects a highly conserved region in the TNF homology domain of ectodysplasin-A1, likely compromising protein function. The variant was confirmed in both fetuses via genetic analysis on amniotic fluid and in the heterozygous state in the mother, consistent with X-linked recessive inheritance. Family history revealed a maternal uncle with XLHED. Additional heterozygous variants were also identified in CPT2, GBA1, GJB2, and SMN1 genes. Following comprehensive genetic counseling, the mother opted for abortion. Conclusions: This case underscores the value of applying advanced genomic technologies—cfDNA-based NGS—for prenatal diagnosis of rare genetic disorders. The identification of apathogenic EDA variant expands the mutational spectrum of XLHED and supports early diagnosis for informed reproductive decisions and potential access to emerging prenatal therapies. Broader application of such technologies may improve outcomes in future pregnancies at risk for monogenic disorders. Full article

Gaucher disease (GD), caused by biallelic pathogenic variants in GBA1, has evolved from being understood as a macrophage-restricted lysosomal disorder to a multisystem condition involving neuroinflammation, immune dysregulation, and cell-type-specific lipid toxicity. This expanded view has driven a parallel progression in GD mouse model development. Early chemically induced and germline knockout models provided foundational insights but were limited by perinatal lethality or incomplete phenotypic fidelity. Subsequent generations of conditional, inducible, and lineage-specific models enabled dissection of visceral and neuronopathic manifestations and clarified the contributions of macrophages, B cells, neurons, microglia, osteoblasts, and endothelial cells to disease pathogenesis. More recent humanized immune and gene-edited platforms, together with multi-omics integration, now allow modeling of genotype-specific biology and therapeutic response with greater translational precision. In this review, we synthesize the evolution of GD mouse models across these eras, evaluate their strengths and limitations, and highlight species-specific challenges including differences in lipid metabolism, immune architecture, and the absence of the GBAP1 pseudogene in mice that influence interpretation and clinical translation. We outline emerging strategies for incorporating patient-derived mutations, modifier pathways, and clinically meaningful endpoints into future models. Our aim is to provide a coherent framework that bridges murine and human GD biology and supports the development of more predictive platforms to accelerate mechanistic discovery, biomarker development, and therapeutic innovation across all subtypes of GD. Full article

Background/Objective: Genetic factors contribute significantly to Parkinson’s disease (PD), especially in cases with early onset or positive family history. However, previous investigations of the genetic landscape in PD populations were mainly based on targeted genotyping. The aim of this study was to investigate the prevalence of pathogenic variants in known PD-associated genes in a series of Swedish PD patients. Methods: We performed whole-exome sequencing on 285 PD probands from southern Sweden. Our series was enriched for patients with early disease onset or positive family history. We focused on 44 genes previously linked to PD. Results: We identified a CHCHD2 p.(Phe84LeufsTer6) frameshift variant in two unrelated patients and report the first PD case of Swedish ancestry carrying the VPS35 p.(Asp620Asn) variant. Additionally, in one patient each, we found an SNCA duplication, an SNCA p.(Ala53Thr) variant, and a LRRK2 p.(Gly2019Ser) variant. Thus, only 2.1% (n = 6) of patients in this series had Mendelian monogenic PD forms. In addition, forty-three patients carried variants in GBA1, including T369M, which may lack disease-association in our population (n = 12); E326K (n = 22), which is classified as a PD risk variant; as well as N370S (n = 3), R329H (n = 3), S107L (n = 1), and L444P (n = 1), with one patient harboring both T369M and E326K. Pathogenic variants in ARSA, ATP7B, and PRKN genes were also detected in heterozygote form, but their role in PD remains uncertain. Conclusions: Monogenic forms of PD are rare in southern Sweden, even among the familial and early-onset PD patients that were overrepresented in our study. Our findings highlight the genetic diversity in Swedish PD patients and identify key variants for further functional and clinical studies. Full article