Search Results (3,101)

Renal oncocytoma (RO) is a benign renal neoplasm characterized by dense accumulation of dysfunctional mitochondria possibly resulting from increased mitochondrial biogenesis and decreased mitophagy; however, the mechanisms controlling these mitochondrial changes are unclear. ROs harbor recurrent inactivating mutations in mitochondrial genes encoding the Electron Transport Chain (ETC) Complex I, and we hypothesize that Complex I loss in ROs directly impairs mitophagy. Our analysis of ROs and normal kidney (NK) tissues shows that a significant portion (8 out of 17) of ROs have mtDNA Complex I loss-of-function mutations with high variant allele frequency (>50%). ROs indeed exhibit reduced Complex I expression and activity. Analysis of the various steps of mitophagy pathway demonstrates that AMPK activation in ROs leads to induction of mitochondrial biogenesis, autophagy, and formation of autophagosomes. However, the subsequent steps involving lysosome biogenesis and function are defective, resulting in an overall inhibition of mitophagy. Inhibiting Complex I in a normal kidney cell line recapitulated the observed lysosomal and mitophagy defects. Our data suggest Complex I loss in RO results in defective mitophagy due to lysosomal loss and dysfunction. Full article

Gastric cancer (GC) is among the most common and deadliest types of cancer, with a poor prognosis primarily due to late-stage detection and the presence of cancer stem cells (CSCs). This study investigates the mechanisms regulating extracellular adenosine levels in gastric cancer stem-like cells (GCSCs) derived from the MKN-74 cell line. Our results show that GCSCs release more ATP into the extracellular medium and exhibit higher levels of CD39 expression, which enables them to hydrolyze a greater amount of ATP. Furthermore, we also found that GCSCs possess a greater capacity to hydrolyze AMP, primarily due to the activity of the CD73 protein, with no significant changes in CD73 transcripts and protein levels between GCSCs and differentiated cells. Additionally, adenosine transport is primarily mediated by members of the equilibrative nucleoside transporter (ENT) family in GCSCs, where a significant increase in the expression level of the ENT2 protein is observed compared to non-GCSCs MKN-74 cells. These findings suggest that targeting the adenosine metabolism pathway in GCSCs could be a potential therapeutic strategy for gastric cancer. Full article

Metro carriages, as enclosed transport microenvironments, have been understudied regarding pollution characteristics and health risks from ACs, especially during high-temperature summers that amplify exposure. This study applied NTS techniques for the first time across three major Chengdu metro lines, systematically identifying sixteen ACs, including hazardous species such as acetophenone, benzonitrile, and benzoic acid that are often overlooked in conventional BTEX-focused monitoring. The TAC concentration reached 41.40 ± 5.20 µg/m³, with half of the compounds exhibiting significant increases during peak commuting periods. Source apportionment using diagnostic ratios and PMF identified five major contributors: carriage material emissions (36.62%), human sources (22.50%), traffic exhaust infiltration (16.67%), organic solvents (16.55%), and industrial emissions (7.66%). Although both non-cancer (HI) and cancer (TCR) risks for all population groups were below international thresholds, summer tourists experienced higher exposure than daily commuters. Notably, child tourists showed the greatest vulnerability, with a TCR of 5.83 × 10⁻⁷, far exceeding that of commuting children (1.88 × 10⁻⁷). Benzene was the dominant contributor, accounting for over 50% of HI and 70% of TCR. This study presents the first integrated NTS and quantitative risk assessment to characterise ACs in summer metro environments, revealing a broader range of hazardous compounds beyond BTEX. It quantifies population-specific risks, highlights children’s heightened vulnerability. The findings fill critical gaps in ACs exposure and provide a scientific basis for improved air quality management and pollution mitigation strategies in urban rail transit systems. Full article

Compared to commuting, grocery shopping trips, despite their profound implications for mixed land use and transportation planning, have received limited attention in travel behavior research. Drawing upon a travel diary survey conducted in a fast-growing metropolitan region of the United States, i.e., Salt Lake County, UT, this research investigated a variety of influential factors affecting mode choices associated with grocery shopping. We analyze how built environment (BE) characteristics, measured at seven spatial scales or different ways of aggregating spatial data—including straight-line buffers, network buffers, and census units—affect travel mode decisions. Key predictors of choosing walking, biking, or transit over driving include age, household size, vehicle ownership, income, land use mix, street density, and distance to the central business district (CBD). Notably, the influence of BE factors on mode choice is sensitive to different spatial aggregation methods and locations of origins and destinations. The straight-line buffer was a good indicator for the influence of store sales amount on mode choices; the network buffer was more suitable for the household built environment factors, whereas the measurement at the census block and block group levels was more effective for store-area characteristics. These findings underscore the importance of considering both the spatial analysis method and the location (home vs. store) when modeling non-work travel. A multi-scalar approach can enhance the accuracy of travel demand models and inform more effective land use and transportation planning strategies. Full article

Background Plasma membrane proteins (PMPs) play key roles in cell signalling, adhesion, and trafficking, and are attractive therapeutic targets in cancer due to their surface accessibility. However, their typically low abundance limits detection by conventional proteomic approaches. Methods: To improve PMP detection, we employed a surface proteomics workflow combining cell surface biotinylation and affinity purification prior to LC-MS/MS analysis in cervical (SiHa) and bladder (UMUC3) cancer cell lines cultured under normoxic (21% O₂) or hypoxic (0.1% O₂) conditions. Results: In SiHa cells, 43 hypoxia-upregulated proteins were identified exclusively in the biotin-enriched fraction, including ITGB2, ITGA7, AXL, MET, JAG2, and CAV1/CAV2. In UMUC3 cells, 32 unique upregulated PMPs were detected, including CD55, ADGRB1, SLC9A1, NECTIN3, and ACTG1. These proteins were not observed in corresponding whole-cell lysates and are associated with extracellular matrix remodelling, immune modulation, and ion transport. Biotinylation enhanced the detection of membrane-associated pathways such as ECM organisation, integrin signalling, and PI3K–Akt activation. Protein–protein interaction analysis revealed links between membrane receptors and intracellular stress regulators, including mitochondrial proteins. Conclusions: These findings demonstrate that surface biotinylation improves the sensitivity and selectivity of plasma membrane proteomics under hypoxia, revealing hypoxia-responsive proteins and pathways not captured by standard whole-cell analysis. Full article

Personal Rapid Transit (PRT) and Group Rapid Transit (GRT) are classes of fully automated public transport systems, where passengers can travel in small vehicles on an interconnected, grade-separated network of guideways, non-stop, from origin to destination. PRT and GRT are considered sustainable as they are low-emission and able to attract car drivers. The parameterized cost modeling framework developed in this paper has the advantage that profitability of different PRT/GRT systems can be rapidly verified in a transparent way and in function of a variety of relevant system parameters. This framework may contribute to a more transparent, rapid, and low-cost evaluation of PRT/GRT schemes for planning and decision-making purposes. The main innovation is the introduction of the “peak hour network saturation” S: the number of vehicles in circulation during peak hour divided by the maximum number of vehicles running at line speed with minimum time headways. It is an index that aggregates the main uncertainties in the planning process, namely the demand level relative to the supply level. Furthermore, a maximum S can be estimated for a PRT/GRT project, even without a detailed demand estimation. The profit per trip is analytically derived based on S and a series of more certain parameters, such as fares, capital and maintenance costs, daily demand curve, empty vehicle share, and physical properties of the system. To demonstrate the ability of the framework to analyze profitability in function of various parameters, we apply the methods to a single vehicle PRT, a platooned PRT, and a mixed PRT/GRT. The results show that PRT services with trip length proportional fares could be profitable already for $S>0.25$. The PRT capacity, profitability, and robustness to tripled infrastructure costs can be increased by vehicle platooning or GRT service during peak hours. Full article

Background: Increasing regulatory pressure for maritime decarbonization (e.g., IMO CII, FuelEU) drives adoption of low-carbon fuels and prompts reassessment of regional ports’ competitiveness. This study aims to evaluate the economic and environmental viability of rerouting deep-sea container services to regional ports in a decarbonizing world. Methods: A scenario-based analysis is used to evaluate total costs and CO₂ emissions across the entire container shipping supply chain, incorporating deep-sea shipping, port operations, feeder services, and inland rail/road transport. The Port of Liverpool serves as the primary case study for rerouting Asia–Europe services from major ports. Results: Analysis indicates Liverpool’s competitiveness improves with shipping lines’ slow steaming, growth in hinterland shipment volume, reductions in the emission factors of alternative low-carbon fuels, and an increased modal shift to rail matching that of competitor ports (e.g., Southampton). A dual-port strategy, rerouting services to call at both Liverpool and Southampton, shows potential for both economic and environmental benefits. Conclusions: The study concludes that rerouting deep-sea services to regional ports can offer cost and emission advantages under specific operational and market conditions. Findings on factors and conditions influencing competitiveness and the dual-port strategy provide insights for shippers, ports, shipping lines, logistics agents, and policymakers navigating maritime decarbonization. Full article

One of the fundamental goals of contemporary mobility is to optimize transport processes in urban areas. The solution in this area seems to be the implementation of the idea of sustainable transport systems based on the Smart City concept. The article presents a case study—an assessment of the possibilities of changing mobility habits based on the idea of sustainable urban transport, taking into account the criterion of energy consumption of individual means of transport. The analyses are based on a comparison of selected means of transport occurring in the urban environment according to several key parameters for the optimization and efficiency of transport processes, i.e., cost, time, travel comfort, and impact on the natural environment, while simultaneously linking them to the criterion of energy consumption of individual means of transport. The analyzed parameters currently constitute the most important group of challenges in the area of shaping and planning optimal and sustainable urban transport. The presented research was used to indicate the connections between various areas of optimization of the transport process and the energy efficiency of individual modes of transport. Analyses have shown that the least time-consuming process of urban mobility is associated with the highest level of CO₂ emissions and, at the same time, the highest level of energy efficiency. However, combining public transport with other means of transport can meet most of the transport expectations of city residents, also in terms of energy optimization. The research results presented in the article can contribute to the creation of a strategy for the development of the transport network based on the postulates of increasing the optimization and efficiency of individual means of transport in urban areas. At the same time, recognizing the criterion of energy intensity of means of transport as leading in the development of sustainable urban mobility. Thus, confirming the important role of existing transport systems in the process of shaping and planning sustainable urban mobility in accordance with the idea of Smart City. Full article

The ATP-binding cassette transporter ABCG2 plays a critical role in drug pharmacokinetics and multidrug resistance in cancer therapy. Two common nonsynonymous polymorphisms, rs2231137 (V12M) and rs2231142 (Q141K), are associated with altered ABCG2 function, drug response, and disease susceptibility. However, the functional impact of their haplotype remains poorly understood. In this study, we established Flp-In™-293 cell lines stably expressing ABCG2 (12M/141K) and systematically compared their expression and drug resistance profiles with those of cells expressing ABCG2 (12V/141Q) (WT), ABCG2 (12M/141Q), and ABCG2 (12V/141K). The mRNA of ABCG2 (12M/141K) was expressed at levels comparable to those of the other variants in cells. Cells expressing ABCG2 (12M/141K) exhibited significantly higher resistance to mitoxantrone (10.7-fold) and SN-38 (5.99-fold) than the mock cells. While ABCG2 (12M/141Q) conferred the highest resistance among the tested variants, the ABCG2 (12M/141K) haplotype showed a trend toward higher mitoxantrone resistance than the ABCG2 (12V/141Q) (WT) (p = 0.066), suggesting a haplotype-specific effect. These findings provide novel insights into haplotype-based modulation of ABCG2 function and its contribution to multidrug resistance, with potential implications for optimizing personalized chemotherapy strategies. Full article

The Barcelona Metropolitan Area (AMB) has implemented various policies to reduce car use and promote more sustainable mobility. Initiatives such as superblocks, Low Emission Zones (LEZs), and the Bicivia network aim to transform the urban model in response to environmental and congestion challenges. However, the high reliance on private vehicles for intermunicipal travel, uneven infrastructure, and social resistance to certain changes remain significant issues. This study examines the evolution of mobility patterns and assesses the effectiveness of the above policies in fostering real and sustainable change. A mixed-methods approach was adopted, which combined an exploratory factor analysis (EFA) of 2011–2024 data, trend linear regression, and a comparative international analysis. The EFA identified four key structural dimensions: traditional transport infrastructure, active mobility and bus lines, public bicycles and mixed use, and transport efficiency and punctuality. The findings reveal a clear reduction in private car use and an increase in sustainable modes of transport. This indicates that there are prospects for future transformation. Nonetheless, challenges persist in intermunicipal mobility and the public acceptance of the measures. This study provides empirical and comparative evidence and emphasizes the need for integrated metropolitan governance to achieve a resilient and sustainable urban model. Full article

The Ministry of Land, Infrastructure, and Transport conducted a demonstration project targeting pilot areas to commercialize drone delivery services in urban areas and to present a standard model. In this study, flight data on drone delivery routes in Ulju and drone hovering in Yeosu were collected and analyzed for flight safety. Since there are no domestic or international regulations on the stability of drone flight, we were given the task of analyzing whether drone path flight should be maintained within a 10 m error range from the planned path line by the Korea Transportation Safety Authority and whether hovering works while satisfying the left and right radius errors and altitude errors within 3 m. Accordingly, the drone flight path data analyzed in Ulju met the criteria of up to 1.07%, and the hovering data analyzed in Yeosu met the criteria of less than 3% for the entire section data. Therefore, the drone flight stability evaluation analyzed in this paper is considered to have been passed. Based on the results of this study, is the data are expected to serve as a cornerstone for establishing guidelines for drone delivery flight data analysis regulations. Full article

This study details how 3-(naphthalen-2-yl)-1-phenylprop-2-en-1-one (3NPEO) behaves in terms of photophysics when exposed to different solvents. The solvatochromic effect study reveals significant polarity shifts in the excited states of the 3NPEO compound, likely due to an intramolecular proton transfer mechanism. Measurements of dipole moments provide insight into their resonance structures in both ground and excited states. Electrochemical analysis revealed a reversible redox process, indicating a favorable charge transport potential. HOMO and LUMO energies of the compound were computed via oxidation and reduction potential standards. 3NPEO exhibits optimal one-photon and two-photon absorption characteristics, validating its suitability for visible wavelength laser applications in photonic devices. Furthermore, molecular docking and dynamics simulations demonstrated strong interactions between 3NPEO and the progesterone receptor enzyme, supported by structure–activity relationship (SAR) analyses. In vitro cytotoxicity assays on the MDAMB-231 breast cancer cell line showed moderate tumor cell inhibitory activity. Apoptosis studies confirmed the induction of both early and late apoptosis. These findings suggest that 3NPEO holds promise as a potential anticancer agent targeting the progesterone receptor in breast cancer cells. Overall, the findings highlight the substantial influence of solvent polarity on the photophysical properties and the design of more effective and stable therapeutic agents. Full article

Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article

Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown and under intense investigation. Localization to the hippocampus can now be explained by anatomical features of the blood vessels supplying this region. Blood supply and hence oxygen delivery to the area are jeopardized by poor flow through narrowed arteries. In genomic and metabolomic studies, the respiratory chain and mitochondrial pathways which generate ATP were leading pathways associated with AD. This review explores the notion that ATP depletion resulting from hippocampal hypoperfusion has a prime role in initiating damage. Sections cover sensing of ATP depletion and protective responses, vulnerable processes with very heavy ATP consumption (the malate shuttle, the glutamate/glutamine/GABA (γ-aminobutyric acid) cycle, and axonal transport), phospholipid disturbances and peroxidation by reactive oxygen species, hippocampal perfusion and the effects of hypertension, chronic hypoxia, and arterial vasospasm, and an overview of recent relevant genomic studies. The findings demonstrate strong scientific arguments for the proposal with increasing supportive evidence. These lines of enquiry should be pursued. Full article

RNA-seq analysis of the highly differentiated human retinal pigment epithelial (RPE) cell-line ARPE-19, cultured on transwells for ≥4 months, yielded 44,909 genes showing 83.35% alignment with the human reference genome. These included mRNA transcripts of RPE-specific genes and those involved in retinopathies. Monolayers were fed photoreceptor outer segments (POS), designed to be synchronously internalised, mimicking homeostatic RPE activity. Cells were subsequently fixed at 4, 6, 24 and 48 h when POS were previously shown to maximally co-localise with Rab5, Rab7, LAMP/lysosomes and LC3b/autophagic compartments. A comprehensive analysis of differentially expressed genes involved in proteolysis revealed a pattern of gene orchestration consistent with POS breakdown in the autophagy-lysosomal pathway. At 4 h, these included elevated upstream signalling events promoting early stages of cargo transport and endosome maturation compared to RPE without POS exposure. This transcriptional landscape altered from 6 h, transitioning to promoting cargo degradation in autolysosomes by 24–48 h. Longitudinal scrutiny of mRNA transcripts revealed nuanced differences even within linked gene networks. POS exposure also initiated transcriptional upregulation in ubiquitin proteasome and chaperone-mediated systems within 4–6 h, providing evidence of cross-talk with other proteolytic processes. These findings show detailed evidence of transcriptome-level responses to cargo trafficking and processing in RPE cells. Full article