Online reviews shape restaurant reputation, yet how price perceptions influence ratings remains unclear. This study addresses this gap by integrating prospect theory with real-world pricing data from reviews of 2,000 New York restaurants. We operationalize reference dependence using consumer-reported prices versus platform-listed reference prices. Results reveal asymmetric effects: paying above the reference price reduces ratings more than equivalent savings increase them (loss aversion), and sensitivity declines as deviations grow (diminishing sensitivity). These patterns persist after controlling for meal type and service mode and attenuate among experienced reviewers, highlighting the role of expertise. Findings suggest that online ratings may act as fairness-sensitive evaluations rather than purely neutral indicators, offering implications for price transparency and expectation management in digital hospitality platforms.
Smart tourism promises efficiency and personalization through digital technologies. But does algorithmic mediation enrich or impoverish travel experiences? Drawing on Heidegger's enframing, Foucault's governmentality, and Baudrillard's simulation theory, this conceptual paper articulates the “paradox of convenience”: technologies designed to enhance travel tend structurally to undermine conditions for meaningful experience. Three dimensions manifest this paradox—algorithmic filtering, efficiency optimization, and hyperconnectivity—each generating predictable, homogenized experiences that risk foreclosing serendipity and depth. The paper proposes three paradigm shifts: cultivation over optimization, provocation over prediction, and productive friction over seamlessness. These principles offer theoretical resources for understanding technology's ambivalent role in tourism and practical guidance for designing systems that preserve travel's transformative potential.
This paper conceptualises mobile academics as a travelling subculture characterised by shared practices, common narratives, and symbolic forms of distinction. Drawing on subcultural theory and linking it to the tourism and mobilities literatures, it moves beyond functionalist, managerialist, and constructivist approaches to examine the cultural dimensions of academic mobility through an interpretivist lens. Based on the analysis of 20 academic blogs, the study shows how academic travel functions as a performative practice through which scholars construct an “academic self” and legitimise their social position within academia, while also reproducing hierarchies and uneven participation. By reframing academic mobility as a subcultural practice, the paper offers a new lens for understanding how everyday academic routines shape differentiation and inclusion within contemporary academia.
Deoxysphingolipids (dSLs) are atypical sphingolipids that accumulate in several pathological settings, yet their impact on hematologic malignancies is poorly understood. Here, we investigate the pathways and mechanisms of deoxysphinganine (dSA) cytotoxicity in lymphoma cells and its potential as a therapeutic agent. dSA exhibited markedly greater cytotoxicity than canonical sphingoid bases in lymphoma cell lines, yet induced only cytostatic effects in normal human T cells, indicating a therapeutically exploitable window. Inhibition of ceramide synthase blocked the generation of deoxy(dihydro)ceramides, prevented mitochondrial depolarization, caspase activation, ER stress, and DNA damage, establishing CerS-dependent deoxysphingolipids as essential mediators of dSA-induced death. Mechanistically, dSA engaged a mitochondrial apoptotic pathway, with DNA damage occurring downstream of mitochondrial permeabilization and caspase activation, while PERK-driven ER stress occurred in parallel and was dispensable for cytotoxicity. Subtype-specific engagement of ER stress and DNA damage further suggests that dSL signaling is shaped by lineage context. The differential sensitivity between malignant lymphoid cells and normal T cells, together with the central role of CerS-derived deoxy(dihydro)ceramides, highlights deoxysphingolipid metabolism as a druggable vulnerability in lymphoma. These findings support further exploration of dSA-based strategies and targeted modulation of dSL synthesis as a novel therapeutic avenue for non-solid hematologic malignancies.
Whether the fecal metabolome differs according to intensive low-density lipoprotein cholesterol (LDL-C) target achievement among statin-treated patients is unclear. In this cross-sectional study, 124 statin-treated adults with chronic disease were stratified by fasting LDL-C into a target-achieved group (< 70 mg/dL, n = 52) and a target-not-achieved group (≥ 70 mg/dL, n = 72). Stool samples were profiled by untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry, and multivariable models adjusted for age, sex, chronic kidney disease, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were used to identify metabolites independently associated with target achievement. Statin dose, treatment duration and glucose-lowering therapy were also compared between the groups. Paired 16S rRNA gene sequencing data available for a subset (n = 86) were used for integrative correlation and network analyses. Partial least-squares discriminant analysis showed separation between the two groups. Eight annotated metabolites-glutamine, glutamate, phenylalanine, N-acetyl-L-phenylalanine, L-methionine, N-acetyl-L-methionine, lysine, and N-methyl-D-aspartic acid, predominantly amino acids and their derivatives-were present at lower fecal levels in participants who achieved the LDL-C target. Metabolite set enrichment analysis implicated amino acid and nitrogen metabolism, and multiomics network analysis identified an Anaerotruncus-centered amino acid module with high degree centrality. In conclusion, LDL-C target achievement under statin therapy was associated with a coherent "low fecal amino acid" signature and an Anaerotruncus-linked microbe-metabolite hub. These findings suggest that intestinal nutrient handling and gut microbial amino acid metabolism may contribute to variability in LDL-C response, and they warrant prospective mechanistic evaluation.
Metabolic dysfunction-associated liver disease (MASLD) arises from the accumulation of triglycerides within the liver. MASLD can advance to metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and hepatocellular carcinoma. Monoacylglycerol acyltransferase 2 (MOGAT2) is essential for triglyceride synthesis and plays a significant role in regulating lipid metabolism. Here, we demonstrate the ability of a new human MOGAT 2 inhibitor, VB-85387, to inhibit the development of MASLD/MASH and further define its effects on the key metabolic pathways that progress MASH development. MASLD/MASH was induced using a methionine, choline-deficient diet (LMCD) or by streptozotocin treatment combined with high fat diet feeding (STAM-HFD). VB-85387 significantly mitigated the severity of MASLD and reduced signs of MASH in mice subjected to these two distinct diets. VB-85387-treated mice exhibited decreased fibrosis, evidenced by reduced hepatic triglyceride concentrations, hydroxyproline levels, and collagen deposition. NAS scores were consistently lower in VB-85387-treated mice across both models. VB-85387-treated mice showed induced PPARα signaling and reduced SREBP transcription, demonstrating a likely role for VB-85387 in regulating lipogenesis and fatty acid β-oxidation. STAM-HFD treated mice showed lower NF-κBp65 activation, which was associated with lower TNFα expression. IL-1β and IFNβ levels were also both reduced, suggesting VB-85387 can reduce pro-inflammatory pattern recognition receptor signaling. In addition, treatment suppressed IL-4/IL-6-dependent JAK activation. Overall, VB-85387 inhibited MASLD development by reducing liver triglyceride levels, fibrosis, and meta-inflammatory signaling. VB-85387 was as effective or superior to the MOGAT2 inhibitor phase I clinical trial drug BMS-963272 in reducing MASLD and fibrosis. VB-85387 has considerable potential for developing therapeutics targeting MASLD/MASH.
Glioma represents one of the most aggressive tumors in the central nervous system, with clinical management facing significant challenges including high recurrence rates and therapeutic resistance. Ferroptosis, an iron-dependent form of cell death, holds potential for glioma treatment, yet tumor cells frequently develop evasion mechanisms. This study elucidates the molecular mechanisms by which hypoxic microenvironment confers ferroptosis resistance in glioma cells, focusing on the pivotal role of the HIF-1α/SREBP1 signaling axis and its downstream effectors FASN and SCD1. Our experimental results demonstrate that hypoxic conditions significantly upregulate HIF-1α expression and confer resistance to RSL3-induced ferroptosis. Mechanistic studies reveal that HIF-1α promotes SREBP1 activation, which subsequently upregulates FASN and SCD1 expression to suppress lipid peroxidation.Furthermore, the HIF-1α-specific inhibitor PX-478 effectively reverses hypoxia-induced ferroptosis resistance and significantly enhances tumor cell sensitivity to ferroptosis inducers. In vivo experiments confirm the potent antitumor effects of PX-478 combined with RSL3. This study systematically elucidates the role of the HIF-1α-SREBP1-FASN/SCD1 signaling axis in ferroptosis regulation in glioma, providing important theoretical foundations and experimental support for developing HIF-1α-targeted ferroptosis therapies.
BACKGROUND:Lipoprotein(a) [Lp(a)] reflects inherited atherothrombotic risk, whereas the C-reactive protein-triglyceride-glucose index (CTI) integrates systemic inflammation, triglyceride-related lipid disturbance, and glucose-related metabolic stress. Their individual and joint association with angiographic coronary lesion burden in acute coronary syndrome (ACS) remain incompletely defined. We examined whether CTI complements Lp(a) in characterizing coronary lesion burden in ACS. MATERIALS AND METHODS:This retrospective, single-center study included 2,836 consecutive patients with ACS who underwent coronary angiography. Coronary lesion burden was assessed using continuous Gensini score, a high Gensini score, and multivessel disease (MVD). Multivariable regression, restricted cubic spline analyses, CTI-stratified analyses, incremental receiver operating characteristic analyses, and internally validated machine-learning analyses with SHAP interpretation were performed. RESULTS:Higher Lp(a) and CTI level were both associated with greater coronary lesion burden. Compared with Lp(a) <75 nmol/L, Lp(a) ≥175 nmol/L was associated with high Gensini score (OR, 1.51 [95% CI, 1.17-1.96]) and MVD (OR, 1.69 [95% CI, 1.27-2.26]). Each 1-SD increase in CTI was associated with high Gensini score (OR, 1.47 [95% CI, 1.35-1.60]) and MVD (OR, 1.18 [95% CI, 1.08-1.28]). Among inflammatory-lipid indices, CTI showed the most consistent associations and provided the largest numerical incremental discrimination beyond Lp(a). The associaton between ver high Lp(a) and coronary lesion burden was more pronounced at higher CTI levels, particular for MVD. Machine-learning analyses further supported the relevance of both CTI and Lp(a). CONCLUSIONS:In patients with ACS, higher Lp(a) and CTI level were associated with greater angiographic coronary lesion burden. CTI may complement Lp(a) by capturing inflammatory-metabolic status, supporting their joint assessment for more refined characterization of lesion-burden risk in ACS.
Lipoprotein metabolism is significantly different between mice and humans thus making it difficult to model disorders of human lipid metabolism in transgenic mice. Systemic lipoprotein metabolism is predominantly governed by hepatocytes, and mice with humanized livers display human-like lipid profiles. Here we report a highly efficient method to knock out genes in human hepatocytes while retaining their ability to repopulate immune deficient rodents. As proof-of-principle Fah deficient, immune compromised mice were repopulated with Apolipoprotein B (APOB) knockout human hepatocytes. Mice humanized with knockout cells recapitulated typical features of human hypobetalipoproteinemia. We conclude that at least some human lipid metabolism disorders can be modeled in liver chimeric mice using human knockout hepatocytes.
This study investigates the neural correlates of tourism immersion in augmented reality environments using EEG data and machine-learning-based neural decoding. The results identify the alpha, beta, and gamma frequency bands as key potential predictors of immersion, with decoding accuracies of 73.24%, 70.13%, and 70.83%, respectively. Alpha- and beta-band activity may be associated with attentional processes during immersion, whereas gamma-band activity may reflect conscious awareness and emotional processing. The study also identifies immersion-relevant patterns in the prefrontal, central, and parietal regions, which may be associated with emotion regulation, multisensory integration, and the sense of presence. These neural indicators contribute to understanding the neural processes underlying tourists' immersive experiences and provide practical implications for the development and evaluation of future immersive technologies.
Industry associations increasingly promote sustainability in tourism by acting as intermediaries between regulators and industry, sharing insights, disseminating knowledge, and supporting voluntary frameworks and good-practice mechanisms. Yet their influence on member behaviour remains uneven and difficult to explain. This study examines how sustainability interventions delivered by an industry association shape member responses under voluntary conditions. Using a realist evaluation of the European Tourism Association (ETOA), the study develops the concept of bounded principal–agent relationships to explain why association influence is structurally constrained, negotiated, and sometimes inverted. Findings show that members engage symbolically, selectively, or autonomously, with high-performing members using associations for strategic legitimisation rather than guidance. Absorptive capacity conditions engagement depth but does not imply progression.
Combination is an effective way to improve tourism demand interval forecasting accuracy. However, determining which models to combine and identifying optimal combination weights remain challenging. This study proposes a novel two-stage multi-objective intelligent combination strategy for combined interval forecasts of tourism demand. The technique strengthens interactions among individual forecast intervals while adaptively selecting the optimal model subset for combination purposes, and balances interval coverage and interval width to overcome the drawbacks of traditional interval forecasting methods. Empirical results show that the proposed intelligent combination strategy produces more accurate forecast intervals compared to benchmark models. These findings offer insights for improving tourism interval forecasting and facilitating operational decisions.
High-altitude polycythemia (HAPC) remains prevalent among Tibetans despite genetic adaptations, including EPAS1/HIF2A. Excessive erythrocytosis elevates blood viscosity and increases cardiopulmonary risk, yet erythrocyte metabolic and membrane-lipid mechanisms of HAPC and of therapeutic erythrocytapheresis (TE) remain incompletely defined. We conducted integrated metabolomic and lipidomic profiling of washed erythrocytes from HAPC patients and non-HAPC (NHAPC), and from HAPC patients after TE. Relative to NHAPC, HAPC showed coordinated erythrocyte remodeling spanning amino acid and purine metabolism together with membrane phospholipid and lipid structure (unsaturation and chain length) changes. The disease contrast was multiomic, whereas the acute post-TE contrast was lipid dominant, consistent with apheresis acting primarily through erythrocyte removal. K-means stratification revealed clinically meaningful TE response heterogeneity, but erythrocyte omics did not define stable responder subtypes. These findings point to erythrocyte membrane lipids as a persistent molecular feature of HAPC and of the acute TE response.
Clinically, acute kidney injury (AKI) is one of the most frequent complications of Naja atra (N. atra) envenomation, primarily attributed to snake venom phospholipase A2 (SVPLA2). Although the SVPLA2 inhibitor varespladib shows great therapeutic promise, the underlying mechanisms remain incompletely understood. Herein, we integrated multi-omics and molecular biology approaches to investigate the critical role of SVPLA2 in N. atra venom-induced AKI, as evidenced by pharmacological inhibition with varespladib. Proteomic profiling identified HRAS and CCND1 as key mediators of SVPLA2-induced nephrotoxicity. Mechanistically, SVPLA2 disrupts lipid raft integrity, impairing HRAS palmitoylation-dependent plasma membrane localization and GTPase activity. This defect suppresses phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling, causing apoptosis and cell cycle arrest in renal tubular epithelial cells, enforced activation of PI3K-AKT signaling effectively rescued cells from injury. Beyond direct cytotoxicity, SVPLA2 profoundly remodels the renal immune microenvironment. SVPLA2 enhances glycolysis by upregulating hexokinase 2 (HK2) while suppressing fatty acid oxidation through downregulation of carnitine palmitoyltransferase IA, thereby metabolically driving M1 polarization. This metabolic shift impairs macrophage efferocytosis and sustains inflammatory injury. HK2 knockdown reverses these effects in macrophages. Taken together, this study reveals a dual epithelial-immune mechanism by which SVPLA2 activity critically contributes to N. atra venom-induced AKI, as evidenced by pharmacological inhibition with varespladib. These findings highlight PI3K-AKT signaling and HK2 as potential therapeutic targets for N. atra-triggered AKI. Supplementary key words.
Pancreatic lipase is the major enzyme responsible for breaking down dietary triglycerides in the intestines. A previous report suggested that intestinal angiopoietin-like 4 (ANGPTL4) might serve as an endogenous inhibitor of pancreatic lipase and thus regulate fat absorption. As ANGPTL4 expression is reportedly induced by high-fat-diet feeding, we hypothesized that induction of ANGPTL4 by a high-fat diet would lead to an increased inhibition of pancreatic lipase, less breakdown of dietary triglycerides, and ultimately a reduced rate of postprandial triglyceride absorption. To test this hypothesis, we generated intestinal epithelial cell-specific ANGPTL4 knockout mice, fed them diets with varying levels of fat, and measured postprandial triglyceride absorption and intestinal triglyceride lipase activity. As we hypothesized, we found that chronic high-fat feeding reduced the rate of postprandial triglyceride absorption in mice. However, this regulation of postprandial triglyceride absorption appeared to be largely independent of ANGPTL4, as similar decreases were observed in both wild-type and intestinal epithelial cell-specific ANGPTL4 knockout mice. We conclude that there is mechanism by which chronic high-fat feeding reduces the rate of secretion of dietary triglycerides into the circulation, but that this mechanism does not require intestinal ANGPTL4.
Tourism design faces the challenge of addressing vulnerability produced when tourists with disability, chronic illness, cognitive, psychosocial, sensory, or age-related access needs encounter service, environmental, informational, and attitudinal barriers. We adapted simulated empathy theory to model situated access experience and address the limits of traditional approaches, including externalism and projection. Using mediated narrative netnography of 21 public travel stories, we introduce a five-phase Simulated Empathy Design Framework: Contextual Immersion, Empathic Modeling, Inferential Alignment, Adaptive Implementation, and Experiential Accountability. Emphasizing phenomenological grounding, inferential humility, and temporal adaptability, the framework supports inclusive travel. It advances vulnerability-centered design toward experiential responsibility by foregrounding dignity and participation. The conceptually grounded and analytically illustrated framework offers a foundation for research, with netnography providing disciplined illustration.
Weight rebound remains the core challenge in the long-term management of obesity. Although current mechanistic understanding mainly focuses on physiological adaptations, the role of biomechanical factors remains largely unexplored. This study aims to investigate the contribution of lysyl oxidase (LOX)-mediated adipose tissue (AT) stiffening to the process of weight rebound. Our clinical analysis first established a correlation among obesity, elevated AT stiffness, and higher LOX levels. We then demonstrated that the weight rebound model mice displayed accelerated lipid accumulation and worsened metabolic functions. Importantly, AT stiffness dynamically increased during obesity, failed to normalize after weight loss due to persistent fibrosis, and reached its highest level during the regain stage. LOX expression followed an identical temporal pattern, showing a strong positive correlation with tissue stiffness. Mechanistically, mimicking a high-stiffness microenvironment in vitro promoted adipocyte differentiation and lipid accumulation in a LOX-dependent manner. Crucially, pharmacological inhibition of LOX in vivo significantly attenuated the rate of weight rebound. Our findings provide supportive evidence that LOX-mediated AT stiffening creates a pro-adipogenic mechanical microenvironment that contributes to accelerated weight rebound and metabolic deterioration, highlighting the LOX-stiffness axis as a potential therapeutic target for preventing weight rebound.
This research note introduces a sensory framework that highlights heat as a key embodied and ethical aspect of tourist practicestravel and points to new directions in studying experiences of and practices in the heat. The framework is introduced in response to an era of global heating, where rising heatwaves increasingly affect popular destinations and, tourists turn toward cooler alternatives
