Search Results (8,467)

Traditional housing is a type of housing that emerged during a specific era in history, when inhabitants designed and built their own houses with the help of the entire community. In Togo, a West African country, and specifically in the urban area of Kara, traditional housing is characterized by a variety of styles due to socio-temporal changes. This study aims to analyze the dynamics of traditional housing in this urban area following these changes. The results were obtained using a methodological approach based on documentary research, interviews, field observations, GPS surveys and sketches of existing traditional buildings in the urban agglomeration of Kara. Qualitative and quantitative data were also collected. According to the methodology adopted, a total of 327 households out of a total of 24,512 were surveyed and 34 interviews were conducted. This approach reveals that the urban agglomeration of Kara has three (03) types of traditional housing depending on changes and evolution within the community. The first type, known as the original type, is characterized by round-shaped houses covered with straw and built using purely traditional methods. The second type is marked by a change in the original forms. In addition to the original round shapes, rectangular or square shapes are added, using traditional materials and techniques, with the beginning of the use of imported materials. The third type is characterized by the use of modern materials, creating a mix of shapes and materials. Full article

PRRSV poses a persistent global challenge to the swine industry due to its rapid evolution. This study aimed to characterize a novel PRRSV2 strain, HeB2023092, isolated from a suspected outbreak in China in September 2023. We performed virus isolation in porcine alveolar macrophages (PAMs), genome sequencing, phylogenetic analysis, and comprehensive genetic characterization. HeB2023092 replicated effectively in PAMs but not in Marc-145 cells. Phylogenetic analysis consistently grouped it with NADC30-like strains (L1.8). Notably, genomic analysis revealed a unique 41-amino acid deletion (478–518 aa) in Nsp2, in addition to the characteristic 111-amino acid deletion of NADC30-like strains. Significant amino acid variations were also found in the antigenic epitopes and N-glycosylation patterns of GP3 and GP5. Comprehensive recombination analysis identified three distinct recombinant regions, revealing a mosaic genome with a predominant NADC30-like backbone. The backbone incorporated genetic sequences from JXA1-like (L8.7) strains in two regions and from NADC34-like (L1.5) strains in one region. These findings highlight the continuous genetic evolution and complex epidemiology of PRRSV, underscoring the critical need for sustained surveillance and detailed characterization of circulating strains to inform effective control and vaccine development strategies. Full article

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disease that develops with age and is related to a decline in motor function. Studies suggest that the causes may be based on genetic dysfunction including PARK gene mutations and environmental factors. Methods: To explore those factors, we used multivariable logistic regression to obtain odds ratios (ORs) and adjusted ORs by using the All of Us Dataset which contains genomic, blood test, and other environmental data. Results: On Chromosome 12, there were 3709 candidate genetic polymorphisms (GPs) that are associated with PD. Of those GPs, fourteen GPs had high ORs which are similar to the OR of the PARK8 gene G2019S mutation. Of those 3709 GPs, a 2.00-fold change in OR was observed in five GPs located at bases 53,711,362 (OR = 4.86, 95% CI [1.46, 16.18]), 31,281,818 (OR = 4.37, 95% CI [1.02, 18.82]), 101,921,705 (OR = 5.38, 95% CI [1.23, 23.51]), 47,968,795 (OR = 7.82, 95% CI [1.81, 33.83]), and 112,791,809 (OR = 8.05, 95% CI [1.85, 35.05]) by calcium, Vitamin D, and alcohol intake and were statistically significant. Conclusions: The results suggest that the progression of some PD caused by certain GPs can be delayed or prevented by the environmental factors above. In February 2025, All of Us released the CT Dataset v.8 which has a 50% increase in the number of participants. Potentially, it may be possible to research more GPs and environmental factors. In future studies, we would like to explore other environmental factors and GPs on other chromosomes. It is believed that specific GPs may tailor current treatments and qualify patients for clinical trials. Additionally, genetic knowledge may help increase accuracy in clinical trials. Full article

In the era of big data, the rapid proliferation of user-generated content enriched with geolocations offers new perspectives and datasets for probing the spatiotemporal dynamics of tourist mobility. Mining large-scale geospatial traces has become central to tourism geography: it reveals preferences for attractions and routes to enable intelligent recommendation, enhance visitor experience, and advance smart tourism, while also informing spatial planning, crowd management, and sustainable destination development. Using Mount Huangshan—a UNESCO World Cultural and Natural Heritage site—as a case study, we integrate GPS trajectories and geo-tagged photographs from 2017–2023. We apply a Density-Field Hotspot Detector (DF-HD), a Space–Time Cube (STC), and spatial gridding to analyze behavior from temporal, spatial, and fully spatiotemporal perspectives. Results show a characteristic “double-peak, double-trough” seasonal pattern in the number of GPS tracks, cumulative track length, and geo-tagged photos. Tourist behavior exhibits pronounced elevation dependence, with clear vertical differentiation. DF-HD efficiently delineates hierarchical hotspot areas and visitor interest zones, providing actionable evidence for demand-responsive crowd diversion. By integrating sequential time slices with geography in a 3D framework, the STC exposes dynamic spatiotemporal associations and evolutionary regularities in visitor flows, supporting real-time crowd diagnosis and optimized spatial resource allocation. Comparative findings further confirm that Huangshan’s seasonal intensity is significantly lower than previously reported, while the high agreement between trajectory density and gridded photos clarifies the multi-tier clustering of route popularity. These insights furnish a scientific basis for designing secondary tour loops, alleviating pressure on core areas, and charting an effective pathway toward internal structural optimization and sustainable development of the Mount Huangshan Scenic Area. Full article

Coastal boulder deposits (CBDs) are important geomorphic indicators of extreme wave activity, yet integrated morphometric and hydrodynamic analyses remain limited along the Moroccan Atlantic coast. This study characterizes the morphology, spatial distribution, and transport thresholds of supratidal boulders at Oued Cherrat and Mansouria, and quantifies the wave energy required for their mobilization. Between 2021 and 2025, 85 boulders were surveyed, supported by lithological analyses, GPS mapping, and pre-/post-storm photographic documentation. At Oued Cherrat, boulders ranged from 0.01 to 3.56 m³ (≤7.84 t), with solitary blocks located 30–94 m inland and larger imbricated clasts up to 150.5 m. At Mansouria, dimensions reached 22 × 20 × 3.5 m (>2032 t), positioned 5–140 m from the shoreline. Storms in January and March 2025 displaced boulders up to 4.5 m at Oued Cherrat (e.g., 6.39 t) and up to 3 m at Mansouria (e.g., 21.42 t), with new blocks deposited and megaboulders showing slight in situ rotations. Hydrodynamic modelling estimated sliding thresholds of 1.1–4.0 m/s at Oued Cherrat and 2.7–11.0 m/s at Mansouria, while rolling thresholds reached 18.23 m/s. These values confirm the dependence of transport on boulder mass, imbrications, and topography. The findings demonstrate that extreme storms can rapidly reorganize multi-tonne CBDs, while the largest megaboulders require rare, exceptionally high-energy events. Full article

Accessibility is a key dimension for sustainable transport network management and planning. However, conventional location-based accessibility measures typically rely on average travel times as the sole temporal metric, neglecting detailed travel time distributions. Consequently, these methods yield identical accessibility values for study zones with the same mean travel time but different travel time variations. To overcome this limitation, we developed a novel approach that explicitly integrates the probability density distributions of travel times, modelling the impact of travel time variability on accessibility. We applied the proposed method using GPS data collected from taxis in Harbin, China, and compared its outcomes with those from existing potential accessibility calculations. Across all 103 study zones in Harbin, the existing method underestimated the accessibility by 6–28%, with an average underestimation of 17% when benchmarked against the new method. These inaccuracies also impaired the identification of urban areas with the lowest accessibility levels, leading to the misclassification of 20% of problematic zones. The findings highlight the limitations of existing methods, which produce biassed accessibility estimations and misleading results. In contrast, the proposed travel time variability-integrated accessibility measure demonstrates greater sensitivity to actual traffic conditions, providing a more accurate and objective assessment of network performance. Full article

Background: Multidrug resistance (MDR), primarily driven by P-glycoprotein (P-gp)-mediated drug efflux, presents a significant challenge in cancer therapy, contributing to chemotherapy failure and poor patient outcomes. Objectives: In this study, we explored the potential of manidipine (MA), a clinically approved calcium channel blocker, to reverse P-gp-mediated MDR through modulation of calcium signaling via nuclear factor of activated T cells 2 (NFAT2). Methods: Paclitaxel (PTX) resistance ABCB1-overexpressing cancer in vitro and in vivo were used for evualting the anti-MDR effects of MA, as well as the underlying mechanism with siRNA of NFAT2. Results: We found that MA at non-toxic concentrations (0.6–5.4 μM) significantly sensitize drug-resistant colorectal (HCT-8/T) and non-small cell lung (A549/T) cells to PTX, reducing its IC₅₀ by up to 1328-fold in vitro models. Mechanistically, MA inhibited P-gp efflux activity without altering its expression, as shown by an increased intracellular accumulation of doxorubicin and Flutax-2 (2.3- and 3.1-fold, respectively) and dose-dependent modulation of ATPase activity (EC₅₀ = 4.16 μM). Notably, MA reduced intracellular calcium levels (52% reduction, p < 0.001) and downregulated NFAT2, an oncogene overexpressed in resistant cells. In vivo, MA (3.5 mg/kg) synergizes with PTX to inhibit tumor growth by 68% (p < 0.001) in A549/T xenograft model, without an observable decrease in weight. Conclusions: In sum, all these results position MA as a novel NFAT2 inhibitor to overcome P-gp-mediated MDR via modulating calcium signaling, which points to further investigation for its clinical applications. Full article

This study investigated the protective effects of Gardenia jasminoides Ellis polysaccharides (GP) on lipopolysaccharide (LPS)-induced immunosuppression and oxidative stress in mice and explored how GP modulates macrophage polarization through the TLR4/NF-κB signaling axis. The results showed that GP notably restored thymus and spleen indices in LPS-treated mice, markedly decreased the serum concentrations of malondialdehyde, and enhanced superoxide dismutase activity and total antioxidant capacity. In RAW 264.7 macrophage cultures, GP displayed immunostimulatory effects by improving phagocytic activity, promoting NO synthesis, and enhancing the secretion of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. These effects were observed in cells not pretreated with TAK-242 or PDTC; however, they were not observed in cells pretreated with these inhibitors. At 300 µg/mL concentration, GP markedly enhanced the transcriptional levels of iNOS and cytokine genes. Protein analysis revealed significant upregulation of TLR4, MyD88, TRAF6, NF-κB RelA/p65, and phosphorylated p65. Fluorescence imaging confirmed the nuclear translocation of p65. Collectively, these findings indicated that GP reversed systemic immunosuppression and oxidative stress, offering foundational insights for developing natural immune regulators. The observed immunomodulatory properties of GP are likely mediated through the TLR4/NF-κB signaling pathway. Full article

Objectives: SailGP is an international professional mixed-sex sailing competition, which uses F50 foiling catamarans capable of reaching speeds up to ~100 km/h. This seminal study assesses injuries and illnesses observed by male and female sailors during trainings and competitions in SailGP’s third season. This study aims to assess injury and illness incidence, comparing results with other professional sailing events and high-performance sports. In addition, injury and illness risk factors (sex and position) will be explored with the goal to reduce morbidity for future seasons. Materials and Methods: This retrospective cohort design analysed medical records of male and female sailors during SailGP’s third season (April 2022 to May 2023). Risk factors assessed included sailor sex, sailor position (helm, strategist, grinder, flight controller and wing trimmer), sailing venue, wind speed and mechanism of injury/nature of illness. International Olympic Committee reporting guidelines on injuries and illnesses were followed, including the STROBE-SIIS checklist. Confidence intervals were set at 95%, statistical tests were two-sided and p-values < 0.05 were considered statistically significant. Results: A total of 40 on-water injuries were reported in 32 athletes. Injury incidence was greater during competitions than trainings, with strategists and then grinders being the most frequently injured positions. Competition injury incidence was 32.6 per 1000 h and 6.42 injuries per 365 days. Training injury incidence was 2.62 injuries per 1000 h and 3.82 injuries per 365 days. Knee, ankle, hand and head injuries were most prevalent, with three concussions observed during trainings and competitions (two female and one male). Direct impacts and falls during manoeuvres caused most injuries. Overall injury incidence (IRR = 2.69 [95% CI 1.41–5.16]), risk of training injuries (RR = 3.75 [95% CI 1.59–8.83], p = 0.001), risk of competition injuries (RR = 1.79 [95% CI 0.65–4.90], p = 0.25) and overall concussion risk (RR = 10.04 [95% CI 0.91–110.46], p = 0.02) were greater in females. Ten sailors accounted for 17 illnesses. Females had a 3.33 increase in training and competition illnesses (IRR = 3.33 [95% CI 0.94–11.81]). Conclusions: Competition injury incidence was higher than previous reported sailing studies. Knee injuries were most prevalent and direct impacts caused most injuries. Female sailors reported a higher injury and illness incidence. These results may guide injury prevention efforts and the development of an IOC-equivalent consensus statement. Future studies should examine time loss. Full article

Acquired Immunodeficiency Syndrome (AIDS) is caused by Human Immunodeficiency Virus (HIV), and continues to be responsible for a substantial number of deaths worldwide each year. Development of a robust and efficient HIV-1 vaccine remains a critical priority. Structural analysis of viral proteins provides a foundational approach to designing peptide-based immunogenic vaccines. In the current experiment, we used computational prediction approaches alongside molecular docking and molecular dynamics (MD) simulations to identify potential epitopes within gp120 and Nef proteins. The selected co-epitopes were fused with the HBsAg-binding protein (SBP), a 344-amino acid protein previously identified in our laboratory through screening of a human liver cDNA expression library against HBsAg, to facilitate efficient delivery to and uptake by dendritic cells (DCs), thereby enhancing antigen (Ag) presentation. Flexible linkers are used to connect B cells, Helper T Lymphocytes (HTLs), and Cytotoxic T Lymphocytes (CTLs) in a sequential manner. The assembled vaccine construct comprises 757 amino acids, corresponding to a recombinant protein of 83.64 kDa molecular weight. Structural analysis through docking studies, MD simulations, and 3D structure validation revealed that the designed protein exhibits high structural stability and potential for interaction with Toll-like receptors (TLRs). These findings support the vaccine’s ability to enhance cellular and humoral feedback, including the stimulation of T and B cells and induction of antibody (Ab) production. The results underscore the promise of this in silico designed co-epitope vaccine as a viable candidate for HIV-1 prevention and suggest that such constructs may serve as effective immunogens in future HIV-1 vaccine strategies. Full article

Immune checkpoint inhibitors (ICIs), including PD-L1 inhibitors, have been approved by the FDA for the treatment of cancers; however, only a small number of cancer patients benefit from these ICIs. Furthermore, the development of drug resistance to this type of treatment is often inevitable. The mechanisms of resistance to PD-L1 inhibitors can be attributed, in part, to an incomplete understanding of the regulation of PD-L1 protein expression. In this study, we identified the role of the E3 ligase GP78, also known as the Autocrine Motility Factor Receptor (AMFR), in the regulation of PD-L1 protein levels. We show that GP78 physically interacts with PD-L1, which is confirmed by IP and Western blotting and is supported by molecular modelling using AlphaFold2. Our modeling studies predict that the interface amino acids of the Ig1 domain of PD-L1 interact with the RING domain and a β-hairpin preceding the CUE domain of GP78. The crystal structure of the PD-1/PD-L1 complex reveals that the interaction with PD-1 is mediated by the Ig1 domain of PD-L1. Furthermore, proteasomal degradation of PD-L1 has been observed via GP78-mediated K48-linked ubiquitination, indicating a key regulatory role for GP78 in the downregulation of PD-L1. Because GP78 expression is inversely correlated with PD-L1 levels in cancer, these findings may have clinical implications for predicting tumor immune evasion and patient response to PD-1/PD-L1 blockade therapies. Taken together, these findings identify a previously unknown mechanism by which GP78 targets PD-L1 for ubiquitination and subsequent degradation in cancer cells, and suggest that blocking the interaction between PD-L1 and PD-1 by an E3 ligase is a novel strategy to improve immunotherapies for cancer patients. Full article

Outdoor substations present complex conditions such as uneven terrain, strong illumination variations, and frequent occlusions, which pose significant challenges for autonomous robotic inspection. To address these issues, we develop an embedded inspection robot that integrates attention-enhanced semantic segmentation with GPS-assisted navigation for reliable operation. A lightweight DeepLabV3+ model is improved with ECA-SimAM and CBAM attention modules and further extended with a GPS-guided attention component that incorporates coarse location priors to refine feature focus and improve boundary recognition under challenging lighting and occlusion. The segmentation outputs are used to generate real-time road masks and navigation lines via center-of-mass and least-squares fitting, while RTK-GPS provides global positioning and triggers waypoint-based behaviors such as turning and stopping. Experimental results show that the proposed method achieves 85.26% mean IoU and 89.45% mean pixel accuracy, outperforming U-Net, PSPNet, HRNet, and standard DeepLabV3+. Deployed on an embedded platform and validated in real substations, the system demonstrates both robustness and scalability for practical infrastructure inspection tasks. Full article

The delamination of building facades creates a critical demand for inorganic adhesive mortars with high long-term adhesion. Geopolymer (GP) represents an eco-friendly alternative to Portland cement (PC). However, the effect of polymer additives, commonly used in cement-based adhesive mortars, on GP mortar remains insufficiently studied. This study examines the effects of hydroxypropyl methylcellulose (HPMC) and vinyl acetate-ethylene (VAE) polymer on the workability, mechanical properties, durability, and microstructure of GP mortar. Results show that an optimal HPMC content (0.4 wt%) improves the fluidity, compressive strength, and adhesive strength of GP mortar, approximately 6%, 16%, and 20%, respectively. These enhancements are attributed to the incorporation of uniformly distributed microbubbles in the mortar matrix. Beyond this optimal content, however, HPMC impairs flowability and adhesion due to its thickening effect. In contrast, VAE addition significantly enhanced adhesive strength by approximately 28%, albeit at the cost of a 17% reduction in compressive strength, resulting from the retardation of the alkali activation process. This gain in adhesion is associated with the formation of a continuous polymer film that establishes both physical interlocking and chemical bonding with the GP matrix. Furthermore, HPMC improved the durability of the GP mortar, while VAE did not contribute to this aspect. These insights offer valuable guidance for designing high-performance GP-based adhesive mortars suitable for building applications. Full article

Background/Objectives: Neurological and psychiatric disorders share overlapping mechanisms, such as oxidative stress, neuroinflammation, and neurotransmitter imbalance. In this context, multitarget natural molecules have gained attention. 1-nitro-2-phenylethane (1N2PE), a major constituent of Aniba canelilla essential oil, is known for its antioxidant, anti-inflammatory, and anticholinesterase effects, yet its neuropharmacological profile remains poorly understood. Methods: This study integrated in silico predictions and in vivo behavioral assays to characterize 1N2PE. Results: Pharmacokinetic analyses indicated favorable drug-like properties, with high gastrointestinal absorption, blood–brain barrier penetration, and no P-gp substrate profile. Molecular docking and dynamics revealed stable interactions with dopamine transporter (DAT, ΔG = −26.26 kcal/mol), prostaglandin-H synthase-1 (PGHS-1, ΔG = −20.27 kcal/mol), serotonin transporter (SERT, ΔG = −18.20 kcal/mol), and acetylcholinesterase (AChE, ΔG = −16.58 kcal/mol). In vivo, using a scopolamine-induced impairment model, 1N2PE significantly improved spatial memory and cognition in the Morris water maze. Treated animals reduced the distance to the target zone by ~40% compared with scopolamine-only rats (p < 0.01), normalized latency during training, and exhibited 30% less immobility (p < 0.05), indicating antidepressant-like effects. Moreover, 1N2PE attenuated anxiety-like thigmotaxis, restoring exploratory patterns (p < 0.0001). Conclusions: Together, these findings highlight 1N2PE as a multitarget candidate for cognitive and psychiatric disorders, combining favorable pharmacokinetic properties with preclinical efficacy, warranting further biochemical and translational investigations. Full article

Microviscosity and lipid order are the main parameters characterizing the phase states of the membrane. Variations in microviscosity and lipid composition in a living cell may indicate serious disturbances, including various kinds of stress. In this work, the effect of hyperosmotic stress on the microviscosity of mitochondrial membranes was investigated, using potato (Solanum tuberosum L.) tuber mitochondria. The microviscosity of mitochondrial membranes isolated from check and stressed (9 days at 34–36 °C) tubers was estimated by determining the generalized polarization (GP) values using a Laurdan fluorescent probe in confocal microscopy studies. It was revealed that the GP distribution in mitochondria isolated from stressed tubers contained new component-characterizing membrane domains with an increased lipid order compared to the rest of the membrane. We have mapped the microviscosity of mitochondrial membranes for the first time and observed the dynamics of the membrane microviscosity of an individual mitochondrion. The hyperosmotic stress significantly influences the functional state of potato mitochondria, decreasing the substrate oxidation rate and respiratory control coefficient but increasing MitoTracker Orange fluorescence. Under hyperosmotic stress, the microviscosity of mitochondrial membranes changes, and membrane domains with increased lipid order are formed. The revealed changes open up prospects for further research on the participation of raft-like microdomains of mitochondria in plant resistance to stress factors. Full article