Search Results (394)

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

Green Stormwater Infrastructure (GSI), as a nature-based solution, has gained widespread recognition for its role in mitigating urban flood risks and enhancing resilience. Equitable spatial distribution of GSI remains a pressing challenge, critical to harmonizing urban hydrological systems and maintaining ecological balance. However, the complexity of matching GSI supply with urban demand has limited comprehensive spatial assessments. This study introduces a quantitative framework to identify priority zones for GSI deployment and to evaluate supply–demand dynamics in the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) using a coupled coordination simulation model. Clustering and proximity matrix analysis were applied to map spatial relationships across districts and to reveal underlying mismatches. Findings demonstrate significant spatial heterogeneity: over 90% of districts show imbalanced supply–demand coupling. Four spatial clusters were identified based on levels of GSI disparity. Economically advanced urban areas such as Guangzhou and Shenzhen showed high demand, while peripheral regions like Zhaoqing and Huizhou were characterized by oversupply and misaligned allocation. These results provide a systematic understanding of GSI distribution patterns, highlight priority intervention areas, and offer practical guidance for large-scale, equitable GSI planning. Full article

The gut-brain axis (GBA) represents an operant acting in a two-direction communication system between the gastrointestinal tract and the central nervous system, mediated by the enteric nervous system (ENS), vagus nerve, immune pathways, and endocrine signaling. In recent years, evidence has highlighted the pivotal role of the gut microbiota in modulating this axis, forming the microbiota-gut-brain axis (MGBA). Our review synthesizes current knowledge on the anatomical and functional substrates of gut-brain communication, focusing on interoceptive signaling, the roles of intrinsic primary afferent neurons (IPANs) and enteroendocrine cells (EECs) and the influence of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and indoles. These agents modulate neurotransmission, epithelial barrier function, and neuroimmune interactions. The vagus nerve serves as a primary pathway for afferent sensory signaling from the gut influenced indirectly by the ENS and microbiota. Dysbiosis has been associated with altered gut-brain signaling and implicated in the pathophysiology of disorders ranging from irritable bowel syndrome to mood disorders and neurodegeneration. Microbial modulation of host gene expression via epigenetic mechanisms, including microRNAs, adds another layer of complexity. The gut has a crucial role as an active sensory and signaling organ capable of influencing higher-order brain functions. Understanding the MGBA has significant implications for new therapeutic interventions targeting the microbiome to manage neurogastroenterological and even neuropsychiatric conditions. Full article

Heterozygous mutations in the GBA1 gene, encoding the enzyme glucocerebrosidase (GCase), are major risk factors for Parkinson’s Disease (PD). Ambroxol, a small chaperone originally used as a mucolytic agent, has been shown to cross the blood–brain barrier, enhance GCase activity, and reduce α-synuclein levels, making it a promising therapeutic candidate for disease-modifying effects in GBA1-associated PD (GBA1-PD). This study aimed to develop a method to quantify ambroxol levels in human plasma and cerebrospinal fluid (CSF) using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Ambroxol was determined by online solid-phase extraction (SPE), coupled with LC-MS/MS, by gradient elution on a monolithic column. Detection employed a 3200 QTRAP tandem mass spectrometer in the positive electrospray ionization mode. Calibration curves exhibited linearity across the analyzed ranges in both plasma and CSF. The recovery rate ranged from 106.7% to 113.5% in plasma and from 99.0% to 103.0% in CSF. No significant matrix effect was observed. Intra-day and inter-day precisions were below 11.8% in both matrices, and accuracy ranged from 89.9% to 103.1% in plasma and from 96.3% to 107.8% in CSF. We evaluated and confirmed the stability of the analyte in plasma and CSF across various storage conditions. The method was successfully validated according to European Medicine Agency (EMA) guidelines and its applicability was confirmed in the context of a multicenter, randomized, double-blind, placebo-controlled, phase II study, designed to monitor the ambroxol levels in the plasma and CSF of GBA1-PD. Full article

Newborn screening laboratories are increasingly adding lysosomal storage disorders (LSDs), such as Mucopolysaccharidosis I (MPS I) and Pompe disease, to their screening panels. Without newborn screening, LSDs are frequently diagnosed only after the onset of symptoms; late detection can lead to profound and irreversible organ damage and mortality. While screening of these disorders has accelerated over the past five years, there is little published information regarding the potential correlation of demographic variables (age at sample collection, birthweight, gestational age, gender, etc.) with lysosomal enzyme activity. The Missouri State Public Health Laboratory prospectively screened more than 475,000 newborns for MPS I, Pompe disease, Gaucher disease, and Fabry disease between 15 January 2013 and 15 May 2018. This report investigates trends between several demographic variables and activities of four lysosomal enzymes: α-L-iduronidase (IDUA), acid α-glucosidase (GAA), acid β-glucocerebrosidase (GBA), and acid α-galactosidase (GLA). This information provides a valuable resource to newborn screening laboratories for the implementation of screening for lysosomal storage disorders and the establishment of screening cutoffs. Full article

The gut–brain axis (GBA) refers to the biochemical bidirectional communication between the central nervous system (CNS) and the gastrointestinal tract, linking brain and gut functions. It comprises a complex network of interactions involving the endocrine, immune, autonomic, and enteric nervous systems. The balance of this bidirectional pathway depends on the composition of the gut microbiome and its metabolites. While the causes of neurodegenerative diseases (NDDs) vary, the gut microbiome plays a crucial role in their development and prognosis. NDDs are often associated with an inflammation-related gut microbiome. However, restoring balance to the gut microbiome and reducing inflammation may have therapeutic benefits. In particular, introducing short-chain fatty acid-producing bacteria, key metabolites that support gut homeostasis, can help counteract the inflammatory microbiome. This strong pathological link between the gut and NDDs underscores the gut–brain axis (GBA) as a promising target for therapeutic intervention. This review, by scrutinizing the more recent original research articles published in PubMed (MEDLINE) database, emphasizes the emerging notion that GBA is an equally important pathological marker for neurological movement disorders, particularly in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease and neurotraumatic disorders such as traumatic brain injury and spinal cord injury. Additionally, the GBA presents a promising therapeutic target for managing these diseases. Full article

Carriers of Gaucher disease have an increased risk of developing Parkinson’s disease (PD). Identifying PD in its prodromal stage is crucial, as early detection before motor symptoms appear allows for potential interventions to salvage neurons and slow or prevent disease progression. At the Gaucher unit at Shaare Zedek Medical Center, we are following a large cohort of obligatory carriers of GBA1 variants (GBA1 carriers) and study ways to identify those at an increased risk for developing PD. In this study, we compared non-invasive prodromal PD tests in 164 GBA1 carriers and 49 participants with no genetic predisposition to PD (controls). The proportion of abnormal tests was compared between groups, and the risk factors for having abnormal tests (at least one or ≥20%) were studied. There were no differences between GBA1 carriers and controls in the frequency of abnormalities, having at least one abnormal test or having ≥20% abnormal tests. Having ≥20% of abnormal tests was associated mainly with age. Principal component analysis identified distinct cognitive, motor, and non-motor dysfunction patterns in GBA1 carriers compared to controls, with cognition in GBA1 carriers more closely linked to motor dysfunction and less influenced by mood and sleep, while in controls, executive function was tied to emotional state and fatigue. Younger carriers outperformed older ones in motor and some cognitive tasks. Those with a family history of PD showed worse cognitive scores than participants with no family history. Sex-based analysis revealed males obtained higher scores in most of the cognition subtests of the NeuroTrax test, whereas it was females in motor and other cognitive domains, mainly in the group of GBA1 carriers. A longitudinal follow-up of GBA1 carriers is ongoing to understand PD progression in GBA1 carriers with the aim of offering targeted intervention for those at higher risk. Full article

Newborn bloodspot screening for one or more lysosomal storage disorders (NBS-LSD) is currently performed by many public health NBS laboratories globally. The screening tests measure activities of selected lysosomal enzymes on dried blood spot (DBS) specimens collected from newborns by the heel stick method Because these assays measure enzyme activity, the quantitative results are dependent on the particular analytical method. DBS quality control (DBS QC) materials with assay-specific certified values that span the relevant range from typical to LSD-affected newborns are an important component of quality assurance in NBS laboratories. The Newborn Screening Quality Assurance Program (NSQAP) at the U.S. Centers for Disease Control and Prevention (CDC) provides public health NBS laboratories with DBS QC sets for NBS-LSD comprising four admixtures of pooled umbilical cord blood and a base pool made from leukodepleted peripheral blood and heat-inactivated serum. To evaluate the suitability of these materials for use with digital microfluidics fluorometry (DMF) assays which can currently measure the activity of four enzymes (acid α-galactosidase (GLA); acid β-glucocerebrosidase (GBA); acid α-glucosidase (GAA); and iduronidase (IDUA)), CDC collaborated with the Newborn Screening Unit at the Missouri State Public Health Laboratory (MSPHL). Using MSPHL criteria, we found that the certified results from each of two DBS QC lots collectively spanned the range from typical (screen negative) to enzyme deficient (screen positive) newborn DBS levels for each of the four lysosomal enzymes measured. The range included borderline results that would require repeat screening of the newborn under the MSPHL protocol. We conclude that these DBS QC preparations are suitable for use as external quality control materials for DMF assays used to detect LSDs in newborns. Full article

Understanding the historical peak situation and the rules for CO₂ emissions from buildings helps to formulate reasonable building mitigation strategies, accelerating the achievement of the Chinese government’s carbon peak goal. As developed regions, cities in the Guangdong–Hong Kong–Macao Great Bay Area (GBA) provide valuable reference cases. This study quantified the historical building CO₂ emissions of GBA cities and analyzed the contribution of driving factors using the Kaya identity and logarithmic mean Divisia index. Furthermore, we assessed the historical peak situation using the MK trend test method and discussed the reasons behind the inter-city difference in the peak situation shown by the environmental Kuznets curve. The results indicate that the building-related CO₂ emissions of the GBA will slowly increase to 96.90 Mt CO₂ by 2020 and that P&C buildings accounted for a larger proportion of emissions. Emission factors and population made the largest positive and negative contributions, respectively, to this total. At the city level, Guangzhou, Shenzhen, and Hong Kong ranked as the top three sources of building CO₂ emissions. Hong Kong peaked, Dongguan and Macao plateaued, and other cities maintained either slow or quick growth. CO₂ emissions unit area, per capita building CO₂ emissions, and building CO₂ emissions reached a peak in that order. This study provides a valuable reference for formulating a city-level path showing building CO₂ emissions peaks. Full article