Search Results (330)

Under the impact of global climate change and human activities, the occurrence of compound disasters such as cascading landslides and flash floods caused by heavy rainfall is increasing. In response to these compound disaster events, it is important to simultaneously transport emergency resources from multiple emergency rescue points to the disaster sites to promptly control the cascading development of disasters and reduce the areas affected by the disasters and associated adverse impacts. This study proposes a dynamic game model for emergency resources dispatch to comprehensively consider the evolution of the compound disaster states and the timely dispatch of emergency resources from the rescue points to the disaster site. The dynamic game model is exemplarily applied to the emergency resource dispatch for a rainstorm-induced compound disaster that occurs in the Guangdong–Hong Kong–Macao Greater Bay Area (GBA). Starting with the analysis of the characteristics of emergency resource management and the attributes of a cascading of heavy rainstorms, landslides, and flash floods, the game model simulates the dynamic game process between the “disaster state” and the “emergency resource manager” in the rescue operations. A two-stage dynamic game model can support decision-making with the objectives of minimal time cost and sufficient resource dispatch for the disaster sites. Game results show that the united emergency resource dispatch in the three GBA metropolitan areas can efficiently respond to compound disasters that occur within the GBA metropolitan area. The dynamic game model could be extended for compound disaster emergency responses with more complicated compound effects and resource constraints. Full article

Background: The gut–brain axis (GBA) is a bidirectional communication network connecting the central nervous system with the gastrointestinal (GI) tract, influencing both mental and physical health. Recent research has underscored the significant role of diet in modulating this axis, with attention to how specific dietary patterns can impact anxiety and depression, particularly when linked to disorders of gut–brain interaction (DGBIs), like intestinal bowel syndrome (IBS). Aims and Methods: This narrative review examines the effects of specific diet regimens on the GBA and its potential role in managing psychopathology, focusing on anxiety and depression, IBS, and the low-FODMAP diet. We conducted a search on PubMed and MEDLINE by combining the following key terms: “Gut–Brain Axis”, “Irritable Bowel Syndrome”, “Low FODMAP diet”, “Mediterranean Diet”, “Psychopathology”, “Anxiety and Depression”, and “Gut Microbiota”. We applied the following filters: “Clinical Trials”, “Randomized Controlled Trials”, “Reviews”, “Meta-Analyses”, and “Systematic Reviews”. In total, 59 papers were included. Results: Low-FODMAP diet, originally developed to alleviate GI symptoms in IBS, may also positively influence mental health by modulating the GBA and improving the gut microbiota (GM) composition. New insights suggest that combining the low-FODMAP diet with the Mediterranean diet could offer a synergistic effect, enhancing both GI and psychological therapeutic outcomes. Conclusions: Understanding the complex interactions between diet, the GM, and mental health opens new avenues for holistic approaches to managing psychopathology, particularly when linked to GI symptoms. Full article

The concept of symbiotic and integrated development represents the adaptive response of Macao tourism to the necessity of diversified development. It is the inevitable path for Macao tourism to achieve high-quality sustainable development. In accordance with the principles of the symbiosis theory, this paper presents an analytical framework and employs Qualitative Comparative Analysis (QCA) to examine the intricate causal processes that simultaneously influence the symbiosis integration development of Macao tourism. The results of the empirical test demonstrate that: (1) The development of Macao tourism symbiosis and integration is influenced by five factors: external policy (EP), regional integration (RI), new digital technology (DT), gaming industry (GI), and cultural element (CE); (2) There are three configuration paths for Macao’s tourism symbiosis, integration, and high-quality development, including an industrial synergy mode, innovation-leading mode, and value-sharing mode; (3) There are two configuration paths formed by the non-high-quality symbiotic integration of Macao tourism, namely, the government absence type and the market failure type; (4) RI and GI are the core conditions for the symbiotic and integrated development of Macao tourism, and there is a certain substitution relationship between EP, DT, and CE. This study advances the academic understanding of the asymmetric causal relationship between various factors and the symbiotic integration of tourism. It enhances the application of the symbiotic theory in the practise of tourism and reveals differences in the path of Macao tourism development under the combination of multiple factors. The findings provide a theoretical basis for the Macao government to optimise the tourism spatial layout and enhance tourism sustainability, build a multi-level “tourism+” symbiotic industrial structure, and establish a modern tourism governance system. Full article

The accurate extraction of urban residential space (URS) is of great significance for recognizing the spatial structure of urban function, understanding the complex urban operating system, and scientific allocation and management of urban resources. The traditional URS identification process is generally conducted through statistical analysis or a manual field survey. Currently, there are also superpixel segmentation and wavelet transform (WT) processes to extract urban spatial information, but these methods have shortcomings in extraction efficiency and accuracy. The superpixel wavelet fusion (SWF) method proposed in this paper is a convenient method to extract URS by integrating multi-source data such as Point of Interest (POI) data, Nighttime Light (NTL) data, LandScan (LDS) data, and High-resolution Image (HRI) data. This method fully considers the distribution law of image information in HRI and imparts the spatial information of URS into the WT so as to obtain the recognition results of URS based on multi-source data fusion under the perception of spatial structure. The steps of this study are as follows: Firstly, the SLIC algorithm is used to segment HRI in the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) urban agglomeration. Then, the discrete cosine wavelet transform (DCWT) is applied to POI–NTL, POI–LDS, and POI–NTL–LDS data sets, and the SWF is carried out based on different superpixel scale perspectives. Finally, the OSTU adaptive threshold algorithm is used to extract URS. The results show that the extraction accuracy of the NLT–POI data set is 81.52%, that of the LDS–POI data set is 77.70%, and that of the NLT–LDS–POI data set is 90.40%. The method proposed in this paper not only improves the accuracy of the extraction of URS, but also has good practical value for the optimal layout of residential space and regional planning of urban agglomerations. Full article

Urban vitality, which indicates the development level of a city and the quality of life of its residents, is a complex subject in urban research due to its diverse assessment methods and intricate impact mechanisms. This study uses multisource data to evaluate the urban vitality of the Guangdong–Hong Kong–Macao Greater Bay Area (GBA) across social, economic, cultural, and environmental dimensions. It analyzes the spatial distribution characteristics of urban vitality and examines the relationships between urban vitality and land use at both regional and city scales. The results indicate that the urban vitality in the GBA generally exhibits a spatial distribution pattern of a high central density and a low peripheral spread, where built-up areas and cropland emerge as key influencing factors. Cities with different developmental backgrounds have unique relationships between land use and urban vitality. In high-vitality cities, the role of the built-up area diminishes, and natural ecosystems, such as wetlands, enhance vitality. In contrast, in low-vitality cities, built-up areas boost urban vitality, and agriculture-related land types exert a lower negative or even positive effect. This research contributes to the understanding of the spatial structures of urban vitality related to land use at different scales and offers insights for urban planners, builders, and development managers in formulating targeted urban vitality enhancement strategies at the regional collaborative and city levels. Full article

The human GBA1 gene encodes lysosomal acid β-glucocerebrosidase, whose activity is deficient in Gaucher disease (GD). In Drosophila, there are two GBA1 orthologs, Gba1a and Gba1b, and Gba1b is the bona fide GCase encoding gene. Several fly lines with different deletions in the Gba1b were studied in the past. However, since most GD-associated GBA1 mutations are point mutations, we created missense mutations homologous to the two most common GD mutations: the mild N370S mutation (D415S in Drosophila) and the severe L444P mutation (L494P in Drosophila), using the CRISPR-Cas9 technology. Flies homozygous for the D415S mutation (dubbed D370S hereafter) presented low GCase activity and substrate accumulation, which led to lysosomal defects, activation of the Unfolded Protein Response (UPR), inflammation/neuroinflammation, and neurodegeneration along with earlier death compared to control flies. Surprisingly, the L494P (called L444P hereafter) flies presented higher GCase activity with fewer lysosomal defects and milder disease in comparison to that presented by the D370S homozygous flies. Treatment with ambroxol had a limited effect on all homozygous fly lines tested. Overall, our results underscore the differences between the fly and human GCase enzymes, as evidenced by the distinct phenotypic outcomes of mutations in flies compared to those observed in human GD patients. Full article

This work is devoted to the investigation of dielectric permittivity which is influenced by electronic, ionic, and dipolar polarization mechanisms, contributing to the material’s capacity to store electrical energy. In this study, an extended dataset of 86 polymers was analyzed, and two quantitative structure–property relationship (QSPR) models were developed to predict dielectric permittivity. From an initial set of 1273 descriptors, the most relevant ones were selected using a genetic algorithm, and machine learning models were built using the Gradient Boosting Regressor (GBR). In contrast to Multiple Linear Regression (MLR)- and Partial Least Squares (PLS)-based models, the gradient boosting models excel in handling nonlinear relationships and multicollinearity, iteratively optimizing decision trees to improve accuracy without overfitting. The developed GBR models showed high R² coefficients of 0.938 and 0.822, for the training and test sets, respectively. An Accumulated Local Effect (ALE) technique was applied to assess the relationship between the selected descriptors—eight for the GB_A model and six for the GB_B model, and their impact on target property. ALE analysis revealed that descriptors such as TDB09m had a strong positive effect on permittivity, while MLOGP2 showed a negative effect. These results highlight the effectiveness of the GBR approach in predicting the dielectric properties of polymers, offering improved accuracy and interpretability. Full article

Background/Objectives: Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset neurodevelopmental disorder, characterized by difficulty maintaining attention, impulsivity, and hyperactivity. While the cause of this disorder is still unclear, recent studies have stated that heredity is important in the development of ADHD. This is linked to a few comorbidities, including depression, criminal behavior, and anxiety. Although genetic factors influence ADHD symptoms, there are also non-genetic factors, one of which is oxidative stress (OS), which plays a role in the pathogenesis and symptoms of ADHD. This review aims to explore the role of OS in ADHD and its connection to antioxidant enzyme levels, as well as the gut–brain axis (GBA), focusing on diet and its influence on ADHD symptoms, particularly in adults with comorbid conditions. Methods: The literature search included the main available databases (e.g., Science Direct, PubMed, and Google Scholar). Articles in the English language were taken into consideration and our screening was conducted based on several words such as “ADHD”, “oxidative stress”, “diet”, “gut–brain axis”, and “gut microbiota.” The review focused on studies examining the link between oxidative stress and ADHD, the role of the gut–brain axis, and the potential impact of dietary interventions. Results: Oxidative stress plays a critical role in the development and manifestation of ADHD symptoms. Studies have shown that individuals with ADHD exhibit reduced levels of key antioxidant enzymes, including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD), as well as a diminished total antioxidant status (TOS) compared to healthy controls. Additionally, there is evidence of a close bidirectional interaction between the nervous system and gut microbiota, mediated by the gut–brain axis. This relationship suggests that dietary interventions targeting gut health may influence ADHD symptoms and related comorbidities. Conclusions: Oxidative stress and the gut–brain axis are key factors in the pathogenesis of ADHD, particularly in adults with comorbid conditions. A better understanding of these mechanisms could lead to more targeted treatments, including dietary interventions, to mitigate ADHD symptoms. Further research is required to explore the therapeutic potential of modulating oxidative stress and gut microbiota in the management of ADHD. Full article

Amongst women and gender diverse (WGD) populations experiencing homelessness in Canada, one of the most vulnerable and understudied subgroups are those who are pregnant. A key barrier to accessing housing for this population are policies that lead to siloed sector work and complicated and inaccessible services. Frequent relocation and fragmented access to essential prenatal and postnatal support are the result. Experiences of homelessness for WGD people are distinct from that of cisgender men; the former tend to experience ‘hidden homelessness’ and are more likely to rely on relational, precarious, and sometimes dangerous housing options. The homelessness sector, its policies, and services tend to be cis-male-centric because of the greater visibility of homelessness in cis-men and fail to meet pregnant WGD people’s needs. This paper describes the findings from a one-day symposium that was held in Toronto, Canada, in June 2023 that aimed to address the siloed approach to housing provision for pregnant WGD people experiencing homelessness. A key focus was to understand how to incorporate a gendered and intersectional discourse into practice and policy. Adopting a gender-based analysis plus (GBA+) approach within policymaking can help illuminate and address why certain groups of WGD people are disproportionately affected by homelessness, including Indigenous Peoples, recent immigrants, racialized people, and those experiencing intimate partner violence, poverty, and substance use. Full article

In this manuscript, a novel presenilin-2 (PSEN2) mutation, Val226Ala, was found in a 59-year-old Korean patient who exhibited rapid progressive memory dysfunction and hallucinations six months prior to her first visit to the hospital. Her Magnetic Resonance Imaging (MRI) showed brain atrophy, and both amyloid positron emission tomography (PET) and multimer detection system-oligomeric amyloid-beta (Aβ) results were positive. The patient was diagnosed with early onset Alzheimer’s disease. The whole-exome analysis revealed a new PSEN2 Val226Ala mutation with heterozygosity in the 5th transmembrane domain of the PSEN2 protein near the lumen region. Analyses of the structural prediction suggested structural changes in the helix, specifically a loss of a hydrogen bond between Val226 and Gln229, which may lead to elevated helix motion. Multiple PSEN2 mutations were reported in PSEN2 transmembrane-5 (TM5), such as Tyr231Cys, Ile235Phe, Ala237Val, Leu238Phe, Leu238Pro, and Met239Thr, highlighting the dynamic importance of the 5th transmembrane domain of PSEN2. Mutations in TM5 may alter the access tunnel of the Aβ substrate in the membrane to the gamma-secretase active site, indicating a possible influence on enzyme function that increases Aβ production. Interestingly, the current patient with the Val226Ala mutation presented with a combination of hallucinations and memory dysfunction. Although the causal mechanisms of hallucinations in AD remain unclear, it is possible that PSEN2 interacts with other disease risk factors, including Notch Receptor 3 (NOTCH3) or Glucosylceramidase Beta-1 (GBA) variants, enhancing the occurrence of hallucinations. In conclusion, the direct or indirect role of PSEN2 Val226Ala in AD onset cannot be ruled out. Full article

With emerging genetic association studies, new genes and pathways are revealed as causative factors in the development of Parkinson’s disease (PD). However, many of these PD genes are poorly characterized in terms of their function, subcellular localization, and interaction with other components in cellular pathways. This represents a major obstacle towards a better understanding of the molecular causes of PD, with deeper molecular studies often hindered by a lack of high-quality, validated antibodies for detecting the corresponding proteins of interest. In this study, we leveraged the nanoluciferase-derived LgBiT-HiBiT system by generating a cohort of tagged PD genes in both induced pluripotent stem cells (iPSCs) and iPSC-derived neuronal cells. To promote luminescence signals within cells, a master iPSC line was generated, in which LgBiT expression is under the control of a doxycycline-inducible promoter. LgBiT could bind to HiBiT when present either alone or when tagged onto different PD-associated proteins encoded by the genes GBA1, GPNMB, LRRK2, PINK1, PRKN, SNCA, VPS13C, and VPS35. Several HiBiT-tagged proteins could already generate luminescence in iPSCs in response to the doxycycline induction of LgBiT, with the enzyme glucosylceramidase beta 1 (GCase), encoded by GBA1, being one such example. Moreover, the GCase chaperone ambroxol elicited an increase in the luminescence signal in HiBiT-tagged GBA1 cells, correlating with an increase in the levels of GCase in dopaminergic cells. Taken together, we have developed and validated a Doxycycline-inducible luminescence system to serve as a sensitive assay for the quantification, localization, and activity of HiBiT-tagged PD-associated proteins with reliable sensitivity and efficiency. Full article

Parkinson’s disease (PD) is a multifactorial, chronic, and progressive neurodegenerative disorder inducing movement alterations as a result of the loss of dopaminergic (DAergic) neurons of the pars compacta in the substantia nigra and protein aggregates of alpha synuclein (α-Syn). Although its etiopathology agent has not yet been clearly established, environmental and genetic factors have been suggested as the major contributors to the disease. Mutations in the glucosidase beta acid 1 (GBA1) gene, which encodes the lysosomal glucosylceramidase (GCase) enzyme, are one of the major genetic risks for PD. We found that the GBA1 K198E fibroblasts but not WT fibroblasts showed reduced catalytic activity of heterozygous mutant GCase by −70% but its expression levels increased by 3.68-fold; increased the acidification of autophagy vacuoles (e.g., autophagosomes, lysosomes, and autolysosomes) by +1600%; augmented the expression of autophagosome protein Beclin-1 (+133%) and LC3-II (+750%), and lysosomal–autophagosome fusion protein LAMP-2 (+107%); increased the accumulation of lysosomes (+400%); decreased the mitochondrial membrane potential (∆Ψm) by −19% but the expression of Parkin protein remained unperturbed; increased the oxidized DJ-1Cys106-SOH by +900%, as evidence of oxidative stress; increased phosphorylated LRRK2 at Ser935 (+1050%) along with phosphorylated α-synuclein (α-Syn) at pathological residue Ser129 (+1200%); increased the executer apoptotic protein caspase 3 (cleaved caspase 3) by +733%. Although exposure of WT fibroblasts to environmental neutoxin rotenone (ROT, 1 μM) exacerbated the autophagy–lysosomal system, oxidative stress, and apoptosis markers, ROT moderately increased those markers in GBA1 K198E fibroblasts. We concluded that the K198E mutation endogenously primes skin fibroblasts toward autophagy dysfunction, OS, and apoptosis. Our findings suggest that the GBA1 K198E fibroblasts are biochemically and molecularly equivalent to the response of WT GBA1 fibroblasts exposed to ROT. Full article

Conventional pavement in aging communities requires renovation in alignment with global carbon reduction initiatives. This study, centered on upgrading facilities in Guangdong, Hong Kong, and the Macao Greater Bay Area (GBA), utilized the Energy Expert platform to assess the carbon footprint of permeable pavement using life cycle assessment (LCA). The results revealed that the total carbon emission of the 64,065 m² permeable pavement was 7066.21 tCO₂eq. The carbon emission contribution, from highest to lowest, was the production phase, maintenance phase, end-of-life phase, and construction phase. Notably, transportation alone constituted a substantial portion, amounting to 30.15% of total carbon emissions. Compared to traditional pavements, permeable pavement showcased substantial potential for carbon reduction, primarily during the use phase, by enhancing groundwater recharge and mitigating the urban heat island effect, which is critical in reducing the carbon footprint. The estimated total carbon reduction was 853.10 tCO₂eq. Sensitivity analysis highlighted diesel energy use in the maintenance phase (51.20%), transportation of cement raw materials in the production phase (45.80%), and transportation of graded gravel for disposal in the end-of-life phase (3.00%) as key factors. Our findings suggest that adopting specific carbon reduction measures, such as substituting gangue for cement binder, transitioning to manual sweeping, and recycling all discarded materials can achieve notable reductions in the respective phases. These findings contribute to a deeper understanding of the role of permeable pavement in reducing carbon emissions, providing insights for the renovation of aging communities. Full article

Neurosteroids are pleiotropic molecules involved in various neurodegenerative diseases with neuroinflammation. We assessed neurosteroids’ serum levels in a cohort of Parkinson’s Disease (PD) patients with heterozygous glucocerebrosidase (GBA) mutations (GBA-PD) compared with matched cohorts of consecutive non-mutated PD (NM-PD) patients and healthy subjects with (GBA-HC) and without (NM-HC) GBA mutations. A consecutive cohort of GBA-PD was paired for age, sex, disease duration, Hoehn and Yahr stage, and comorbidities with a cohort of consecutive NM-PD. Two cohorts of GBA-HC and HC were also considered. Clinical assessment included the Movement Disorder Society revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Montreal Cognitive Assessment (MoCA). Serum samples were processed and analyzed by liquid chromatography coupled with the triple quadrupole mass spectrometry. Twenty-two GBA-PD (males: 11, age: 63.68), 22 NM-PD (males: 11, age: 63.05), 14 GBA-HC (males: 8; age: 49.36), and 15 HC (males: 4; age: 60.60) were studied. Compared to NM-PD, GBA-PD showed more hallucinations and psychosis (p < 0.05, Fisher’s exact test) and higher MDS-UPDRS part-II (p < 0.05). Most of the serum neurosteroids were reduced in both GBA-PD and NM-PD compared to the respective control cohorts, except for 5α-dihydroprogesterone. Allopregnanolone was the only neurosteroid significantly lower (p < 0.01, Dunn’s test) in NM-PD compared to GBA-PD patients. Only in GBA-PD, allopregnanolone, and pregnanolone levels correlated (Spearman) with a more severe MDS-UPDRS part-III. Allopregnanolone levels also negatively correlated with MoCA scores, and pregnanolone levels correlated with more pronounced bradykinesia. This pilot study provides the first observation of changes in neurosteroid peripheral levels in GBA-PD. The involvement of the observed changes in the development of neuropsychological and motor symptoms of GBA-PD deserves further attention. Full article

Aggregation of α-synuclein (αSyn) and its accumulation as Lewy bodies play a central role in the pathogenesis of Parkinson’s disease (PD). However, the mechanism by which αSyn aggregates in the brain remains unclear. Biochemical studies have demonstrated that αSyn interacts with lipids, and these interactions affect the aggregation process of αSyn. Furthermore, genetic studies have identified mutations in lipid metabolism-associated genes such as glucocerebrosidase 1 (GBA1) and synaptojanin 1 (SYNJ1) in sporadic and familial forms of PD, respectively. In this review, we focus on the role of lipids in triggering αSyn aggregation in the pathogenesis of PD and propose the possibility of modulating the interaction of lipids with αSyn as a potential therapy for PD. Full article