Search Results (358)

Jujube (Ziziphus jujuba Mill.) is a widely consumed fruit in East Asia, yet its sharp-ended pits pose a high risk of gastrointestinal perforation in humans. While well-documented in human medicine, jujube pit ingestion in dogs has not previously been reported in the veterinary literature. This report describes a 15-year-old neutered male Maltese dog that presented with anorexia and lethargy five days after accidentally ingesting whole jujubes. Abdominal radiographs identified multiple intraluminal gastric foreign bodies demonstrating a distinctive, orientation-dependent sign: circular (transverse) or spindle-shaped (sagittal) opacities featuring a characteristic central longitudinal stripe. Although abdominal ultrasonography was limited in this specific case due to severe acoustic shadowing from localized gastric gas, the unique radiographic marker provided a reliable diagnostic clue before surgical confirmation. A gastrotomy was performed to successfully retrieve six intact, sharp-pointed pits, and the dog recovered uneventfully. To the authors’ knowledge, as the first report to describe the clinical progression and specific radiographic characteristics of jujube pits in a dog, this case highlights the central longitudinal stripe as a diagnostic clue. This marker facilitates the differentiation of jujube pits from other foreign bodies on plain radiographs, allowing for timely surgical intervention to prevent catastrophic complications. Full article

As emerging global environmental contaminants, organic ultraviolet absorbers (OUVAs) are widely used in personal care formulations and exhibit environmental persistence and potential bioaccumulation. Among these compounds, 2-ethylhexyl salicylate (EHS) and homosalate (HMS) are the most frequently used salicylate-type UV filters in cosmetic formulations. Although an increasing number of studies have demonstrated their environmental hazards, little is known about the molecular mechanisms underlying their cytotoxicity in mammalian systems, a fundamental knowledge gap for both human health protection and the development of more environmentally friendly consumer goods. In this study, we used mouse embryonic fibroblasts (MEFs, 3T6) and zebrafish as models to assess the toxicological phenotypes of EHS and HMS in vitro and in vivo, respectively. We found that both EHS and HMS induced cellular damage characterized by oxidative stress, disrupted intracellular calcium homeostasis, mitochondrial impairment, and DNA damage. Importantly, molecular analyses further suggested the concurrent activation of two distinct regulated cell death programs: pyroptosis, as suggested by Caspase-11-mediated GSDMD cleavage, and necroptosis, as suggested by ZBP1-RIPK3-Caspase-8-mediated MLKL phosphorylation. The in vitro data have been partially validated at the level of gene expression and in developmental toxicity in the zebrafish model, providing some in vivo phenotypic and molecular correlates. While the upstream events were experimentally verified, the causal links among them remain to be further elucidated. Taken together, this work suggested that OUVA-induced toxicity is not limited to isolated oxidative damage, but may also involve the activation of two different cell death programs. These findings provide important molecular clues to understanding the potential health and ecological risks of widely used UV filters and offer a scientific basis for their more environmentally friendly safety evaluation and regulatory management, which are crucial for advancing more sustainable chemistry and safer consumer goods. Full article

Antifungal killer toxins are cytotoxic proteins that have the potential to combat the growing threat of fungi to human health and agriculture. A lack of empirical tertiary structures has limited understanding of their mechanisms of action and their ability to target pathogens. In this study, AlphaFold and molecular dynamics simulations were used to generate tertiary structure models of all canonical Saccharomyces killer toxins and to place them in the context of historical empirical data. These models enabled the prediction of functional domains and posttranslational modifications, including proteolytic cleavage sites and disulfide bonds. They also revealed unexpected homology between Saccharomyces killer toxins, suggesting that all but K28 are likely ionophores. Structural homology to the well-studied killer toxins K1 and K2 enabled the prediction of the antifungal and immunity mechanisms of K1L, K21, K45, K74, and KHS. The understudied killer toxins Klus, KHR, and K62 were found to have homology to bacterial and plant toxins, including members of the aerolysin family and antifungal lectins. These structural similarities provide clues for the mechanisms of killer toxin carbohydrate binding, oligomerization, and membrane attack. This modeling approach will help guide the continued use of the model yeast S. cerevisiae to study killer toxins in the context of the wealth of functional data gathered in the decades since their first discovery. Full article

The distinctive bitter profile of Castanopsis fissa honey (LSZH) has not yet been clearly characterized at the chemical and molecular levels. Based on the LSZH samples (n = 6), this study investigated bitterness-associated compounds and their potential receptor interactions by integrating sensory evaluation, machine learning, untargeted metabolomics, electronic tongue analysis, targeted UPLC-QQQ-MS/MS quantification, and molecular docking. A Random Forest model combined with untargeted metabolomics screened 71 candidate bitter compounds, among which alkaloid-related metabolites were prominently represented. Electronic tongue analysis showed that several compounds exhibited higher bitterness-related sensor responses than quinine under the tested conditions. Targeted UPLC-QQQ-MS/MS analysis identified and quantified five key compounds, among which kynurenic acid was the most abundant, reaching approximately 4500 ppm (mg/kg). Molecular docking suggested that these compounds could favorably interact with the human bitter taste receptor TAS2R46, with binding affinities ranging from −5.4 to −6.5 kcal/mol, mainly through hydrogen bonding, hydrophobic interactions, and π-related interactions. Overall, this study provides chemical evidence and mechanistic clues for understanding the bitterness of LSZH and offers an integrated analytical framework for screening bitterness-associated compounds in complex food systems. Full article

Background/Objectives: High-altitude pulmonary edema (HAPE) remains a serious condition with limited preventive options. This study evaluated the prophylactic protective effects of nebulized human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUC-MSC-EVs) in a rat model of hypobaric hypoxia-induced lung injury and explored potential mechanistic clues, with a focus on oxidative stress and TEK/Tie2 signaling. Methods: Rats were exposed to hypobaric hypoxia (47 kPa; 9.7% O₂) for 72 h and received prophylactic nebulized hUC-MSC-EVs (300 μg/rat). Lung injury was evaluated by histopathology, wet-to-dry ratio, and bronchoalveolar lavage fluid (BALF) protein concentration. Invasive pulmonary function indices were measured using a forced oscillation system. BALF cytokines (TNF-α, IL-6, and IL-10), reactive oxygen species (ROS), and TEK/Tie2 expression in lung tissue were assessed. In addition, transcriptome sequencing (RNA-seq) was performed to characterize global transcriptional changes. N-acetylcysteine (NAC), a classical antioxidant, was included as an auxiliary mechanistic intervention to assess the association of ROS with TEK/Tie2 changes. Results: Compared with hypoxia controls, prophylactic nebulized hUC-MSC-EVs reduced histopathological injury, pulmonary edema, and barrier leakage, and improved pulmonary function indices. hUC-MSC-EV intervention also attenuated inflammatory responses in BALF, with decreased TNF-α and IL-6 and increased IL-10. Hypobaric hypoxia increased ROS accumulation and decreased TEK/Tie2 expression, whereas nebulized hUC-MSC-EVs reduced ROS and partially preserved TEK/Tie2 expression. NAC pretreatment similarly reduced ROS and was accompanied by Tie2 preservation. Conclusions: Prophylactic nebulized hUC-MSC-EVs mitigated hypobaric hypoxia-induced lung injury, accompanied by reduced oxidative stress, improved vascular barrier integrity, and preservation of TEK/Tie2 expression. These findings support nebulized hUC-MSC-EVs as a potential lung-targeted prophylactic strategy for hypobaric hypoxia-induced lung injury and suggest that ROS imbalance may be associated with Tie2 preservation. Full article

Conventional applications of the CLUE-S model rely on a static driver assumption, using driver data and their associated coefficients from a base year to simulate land-use patterns for a future target year—an approach that implicitly assumes temporally invariant human–land relationships. To address this limitation, this study introduces and compares two simulation models: the Baseline-Driven Pattern (BDP), which follows the conventional protocol by employing base-year drivers to project future land use, and the Target-Driven Pattern (TDP), which instead utilizes driver data and coefficients that correspond synchronously to the target year, thereby capturing the dynamic evolution of driving mechanisms over time. In terms of implementation, the TDP involves updated driver datasets and regression coefficients, enabling a more accurate spatial allocation of land-use demand. Comparative experimental results from Xiamen in China demonstrate that the TDP achieves higher simulation accuracy than the BDP simulation, with notably greater sensitivity to dynamic factors such as transportation infrastructure and policy boundaries. For study periods 1989–2000 and 2000–2010, the accuracy of TDP simulation for all land-use types surpasses that of BDP simulation. As time progresses, the advantage of TDP simulation over BDP simulation becomes more pronounced, resulting in a significant improvement in the simulation accuracy. These findings confirm that the temporal alignment between driver data and the simulation period is a critical determinant of CLUE-S simulation accuracy. This methodological refinement holds significant implications for model-based land-use planning: it allows simulation procedures to explicitly incorporate future driver conditions articulated in planning documents. Moreover, it equips decision makers with a more realistic simulation tool for evaluating the land-use consequences of alternative planning interventions in scenario-based analyses. Full article

Land use change has direct human impacts and profoundly alters the structure and function of terrestrial ecosystems. Numerous studies have explored land use change dynamics in the context of socio-economics, often overlooking the influence of climate change on the potential suitability of land use. To address this gap, we propose an integrated framework combining CLUE-S and MaxEnt models to analyze how land use in Tai’an City, Shandong Province, China, responds to future socio-economic and climate change scenarios. The CLUE-S model, based on land demand, and the MaxEnt model, based on suitability assessment, can effectively explore the trends of land change under the influence of human activities and global warming. This study maps the spatial distributions of land use under socio-economic development and four climate change pathways. Overall, the AUC values of the CLUE-S model were all greater than 0.7, and those of the MaxEnt model were all greater than 0.5, indicating that the results of both are relatively reliable. Our study reveals that, within the baseline development (BL) scenario, cultivated land, forest land, grassland, and unused land are projected to decrease between 2020 and 2040. Conversely, the expansion of water bodies and built land will keep growing. In addition, climate change is expected to enhance the suitability of cultivated land between 2020 and 2040, while reducing that of forest land, grassland, unused land, and built land, with only minimal effects on water bodies. Finally, our framework projected that the most widespread priority areas are cultivated land, followed by forest, grassland, water, built land, and unused land. These priority areas are largely determined by human activities, while the influence of climate change is relatively small. Our research framework has broad applicability to the other regions. Considering the MaxEnt model within the framework is beneficial for excluding unsuitable distribution areas of land use types in the CLUE-S model, which will provide new insights for the sustainable use of land resources. Full article

Against the backdrop of rapid modernization and tightening agricultural resource constraints, coordinating urbanization and grain production is a key challenge for China. Using panel data from 30 Chinese provinces from 2004 to 2023, this study applies the coupling coordination degree (CCD) model and a panel vector autoregression model to examine the spatiotemporal coupling characteristics and interaction mechanisms among new-type urbanization (NTU), cultivated land use efficiency (CLUE), and food security (FS). The results show that these three systems have gradually evolved toward coordinated development, with major grain-producing regions consistently leading and entering a moderate coordination stage earlier than other regions. Spatially, CCD exhibits significant positive spatial autocorrelation, characterized by stable “High–High” agglomeration in Northeast China and “Low–Low” agglomeration in southern provinces. Dynamic analysis indicates that system fluctuations are mainly driven by internal inertia, while inter-system interactions are also significant; NTU promotes CLUE, and CLUE and FS exhibit bidirectional causality with complex feedback effects. This study argues for promoting urban–rural factor mobility, advancing green and technology-enabled land use, implementing region-specific development strategies, and establishing a “human–land–grain” early-warning mechanism to safeguard food security during urban expansion. Full article

This article reviews key data in the context of the Strait of Gibraltar from the Iberian perspective: a region of significant importance that boasts the highest concentration of rock art sites containing prehistoric paintings and engravings spanning the full spectrum of human rock art, from its inception to the recent historic period. This area is of exceptional value for investigating the replacement of hunter–gatherer–fisher groups by tribal community societies over time, as well as the transition from Neanderthals to Homo sapiens on both sides of the Strait. Current understanding of this resource is analysed and the main threats to it are addressed alongside possible solutions. Full article

Oasis regions in arid northwestern China represent critical interfaces for watershed ecological security and rural sustainable development. However, under escalating resource constraints and intensifying human–land conflicts, the disorderly expansion of rural settlements has increasingly constrained high-quality territorial development. Liangzhou District, located in the transitional zone of the upper Heihe River Basin at the eastern end of the Hexi Corridor, provides a representative case for examining the spatial evolution of rural settlements in oasis environments. Using multi-temporal land-use data from 2000 to 2023, this study integrates landscape pattern metrics, kernel density estimation, and nearest-neighbor analysis to characterize the spatiotemporal evolution of rural settlements. The Markov–CLUE-S model is further applied to simulate land-use changes under three scenarios for 2035: natural development, new urbanization, and ecological protection. Results indicate that the number of rural settlement patches increased from 1598 to 3009, while their total area expanded from 10,321.83 hm² to 20,828.34 hm², demonstrating a sustained expansion trend and a transition from scattered distribution to increasingly clustered patterns along urban centers and major transportation corridors. Scenario simulations suggest that rural settlement areas will decline by 5.27 km², 12.13 km², and 11.68 km² under the three respective scenarios, predominantly converting to cropland, grassland, and urban construction land. Model validation yields a Kappa coefficient of 0.88, confirming high simulation accuracy. This study develops an integrated “pattern evolution–driving mechanism–scenario response” analytical framework for rural settlement dynamics in arid oasis regions, highlighting the combined influences of environmental constraints and socio-economic drivers. The findings provide a scientific basis for rural spatial optimization and watershed-scale territorial governance in arid regions. Full article

Due to their extensive common-sense knowledge and linguistic understanding, large language models (LLMs) have demonstrated remarkable capabilities in text comprehension and logical reasoning for natural language processing tasks. Traditional prompt-based learning methods, which rely on contextual pattern matching, have proven to be effective in extracting knowledge from LLMs. However, these approaches are constrained by training data pattern matching, overlook reasoning processes, and consequently suffer from suboptimal prompt performance and limited interpretability. Moreover, considering that the intermediate steps generated by single-chain reasoning may not effectively assist LLMs in identifying the sentiment polarity of aspect terms, and that multiple reasoning paths often exist for complex reasoning tasks to reach correct conclusions, this paper proposes a Multi-Chain Thought Prompt Learning framework (MT-CPL). Starting from fundamental concepts, this method simulates human multi-path reasoning patterns to progressively construct comprehensive thought processes and deeply explore sentiment cues. Based on syntactic structures and the semantic logic of text, the framework incorporates four distinct perspectives of text comprehension: hierarchical reading, experiential reading, keyword-based reading, and analogical reading. It establishes a multi-chain prompt template and employs voting mechanisms to select correct reasoning path outcomes. The MT-CPL approach aims to guide LLMs in mining multi-dimensional textual information from different perspectives, gradually uncovering hidden contextual sentiment clues, while mitigating issues caused by irrelevant sentiment cues in intermediate reasoning steps. By decomposing main tasks incrementally, the method achieves progressive reasoning, effectively reduces the difficulty of direct analysis, and further enhances model interpretability through the integration of inherent common-sense knowledge. Full article

In this segment of the Palliative Care Unit case series, we introduce a patient with a long history of oncological treatments for recurrent breast cancer. After active treatments and a global control of the neoplasm, disease progression made the patient access different lines of chemotherapies, even asking for them in anticipation of a few advantages in the balance between benefits and risks. When the patient decided to permanently discontinue chemotherapy, she felt she had disrupted her values. Also, as a reaction to breaking bad news without estimating alternative paths, she considered her deteriorating condition as the sole criterion for assisted dying in another country. Could this be a self-consistent choice for this patient, so determined to find and pursue possibilities in treatment previously? Should this clue respond precisely to the patient’s needs? This contribution’s objective is to debate possibilities of patient self-determination and dignity at the end of life by integrating psychological support, palliative care, and legal–ethical awareness. This case study presents multidisciplinary team work through some key turning points. This team work was carried out in a national context that is currently inconclusive regarding assisted suicide, since active euthanasia is illegal. At the same time, the national Constitutional Court (242/2019) recently opened the possibility of eventual medically assisted suicide under certain circumstances. In this case, health professionals considered this context and tried to delve deeply into respecting the patient’s identity in order to determine when and if the exceptional circumstances were met. This case highlights the ethical sense of end-of-life accompaniment, which when conducted by physicians, nurses, and psychologists together can lead to effective support and allow patients to maintain their identity and to express themselves respecting not only their fears but also their vision of themselves as human beings. A first key turning point was, for instance, taking into account the patient’s history and values, and a subsequent one was supporting the patient in exploring healthcare services and related end-of-life support. In a further key turning point, the patient was helped in engaging with physicians in order to understand types of continuous care, as well as the timing and expected results of sedation. Finally, she chose a healthcare service where she could spend the end of her life in fulfillment of her values. Overall, this case report illustrates how integrating psychological support, palliative care, and legal–ethical awareness can promote patient self-determination and dignity at the end of life. Full article

Human motion exhibits high-dimensional and stochastic characteristics, posing significant challenges for modeling and prediction. Existing approaches typically employ coupled spatiotemporal frameworks to generate future poses. However, the intrinsic nonlinearity of joint interactions over time, compounded by high-dimensional noise, often obscures meaningful motion features. Notably, while adjacent joints demonstrate strong spatial correlations, their temporal trajectories frequently remain independent, adding further complexity to modeling efforts. To address these issues, we propose a novel framework for human motion prediction via the decoupled spatiotemporal clue (DSC), which explicitly disentangles and models spatial and temporal dependencies. Specifically, DSC comprises two core components: (i) a spatiotemporal decoupling module that dynamically identifies critical joints and their hierarchical relationships using graph attention combined with separable convolutions for efficient motion decomposition; and (ii) a pose generation module that integrates local motion denoising with global dynamics modeling through a spatiotemporal transformer that independently processes spatial and temporal correlations. Experiments on the widely used human motion datasets H3.6M and AMASS demonstrate the superiority of DSC, which achieves 13% average improvement in long-term prediction over state-of-the-art methods. Full article

Landslides are among the most damaging natural hazards, posing significant threats to human lives and infrastructures, especially in mountainous regions such as the Central Apennines (Italy). This study focuses on the Mt. Marsicano catchment (2245 m a.s.l.), characterized by peculiar morphometric features and geomorphological constraints that highlight the possibility of potential landslide scenarios. The methodological approach led to the identification of potential landslide propagation patterns. The RAMMS::DEBRIS FLOW module was used to model two potential landslide scenarios: a debris flow-like movement with a volume of 2.03 × 10⁴ m³ and a rock avalanche-like movement with a volume of 1.2 × 10⁶ m³. Findings from the latter scenario suggested river obstruction and potential lake formation upstream. Triggering mechanisms were partially explored, linking the debris flow scenario to heavy rainfall events (>50 mm/day) and the rock avalanche scenario to earthquakes with Mw > 5.0. Despite the absence of occurred landslides for back-calculation analysis and modeling based on geomorphic evidence rather than calibrating to a specific local past event, the study provides preliminary clues about the combination between morphometric analysis and geomorphological constraints in hypothesizing potential landslide scenarios. It provides a foundation for anticipating future landslide impacts in mountainous areas with limited historical data, offering valuable geomorphological insights for preventive hazard assessment and mitigation strategies in similar environments. Full article

The family Flaviviridae is divided into flaviviruses, hepaciviruses and pestiviruses. Its members infect a wide range of organisms, from insects to humans, and share a similar genome organization where proteins require sequential cleavage from a single translated polyprotein. Despite decades of study, the structures of some non-structural (NS) membrane proteins, or details of their protein–protein interactions (PPIs), are still unclear. Since AlphaFold (AF) can be used to predict interactions between protein domains using Predicted Alignment Error (PAE) score plots, we hypothesized that AF-predicted interactions between domains of complete viral polyproteins can represent PPIs if these interactions are retained once the different proteins are sequentially cleaved. We complemented this approach using AF predictions involving all independent separate protein sequences, instead of using a single polyprotein. We found that most of these PPIs have already been reported experimentally, which validates the use of AF in this context, but not all of these PPIs have been characterized from a structural perspective. Thus, we propose that AF provides testable hypotheses regarding residues involved in these PPIs, and that comparison of the three genera in this family may provide much needed clues to the function of these proteins during the viral life cycle. Full article