Search Results (271)

Deoxynivalenol (DON), a trichothecene mycotoxin commonly found in cereal grains and their derived products, poses significant risks to human and animal health. In previous work, a fusion enzyme composed of the dehydrogenase DADH and the aldo-keto reductase AKR13B3 was engineered to convert DON into the non-toxic 3-epi-DON in a single step. However, the poor thermal stability of this fusion enzyme limited its industrial application. In this study, EVcouplings and the GRAPE-WEB platform were utilized to identify key amino acid residues governing the thermal stability of the fusion enzyme AKR13B3–DADH. Through single-point mutation screening and the combination of beneficial mutation sites, a triple mutant M361L/T508Y/Y603F (M1) was obtained. The half-life of M1 at 50 °C reached about 500 min, representing a 16.4-fold increase compared with the wild type, while its catalytic activity increased by 2.7-fold. The apparent melting temperature increased by approximately 4 °C. Molecular dynamics simulations verified that the improved thermostability results from reduced conformational flexibility in key regions, enhanced structural packing, and a strengthened hydrogen bond network. These results demonstrate the successful development of a thermostable DON-detoxifying fusion enzyme and provide a practical basis for its industrial application. Full article

This paper argues that the wound—psychological, ecological, and ontological—is the site where human relationality breaks down and also, paradoxically, where its restoration becomes possible. Drawing on trauma theory, Georges Bataille’s anthropology of discontinuity, and Michael Bond’s account of mortality-driven withdrawal from nature, the study shows how disrelating emerges when individuals and societies retreat from the vulnerability that connection entails. Trauma freezes relational fields; fear of death intensifies the human–nature divide; and the denial of our animality produces the ontological wound at the core of human existence. Yet this wound also marks the threshold of relation. Practices of attunement, ecological participation, and collective healing reopen the possibility of continuity—not by bypassing finitude but by inhabiting it. Read alongside Boros Ladislaus’s earth-centered vision of death as belonging, these perspectives reveal the wound as the place where connection is disclosed, where the self becomes porous, and where deeper relationality can emerge. The wound that fractures relation is also the wound that connects. Full article

The aim of the study was to synthesize nanocomposites based on cerium orthophosphate stabilized with citrate at different ratios for biomedical applications, and to evaluate its safety in different animal species. Nanocomposites were synthesized using four different initial mass ratios of Ce(NO₃)₃ × 6H₂O to citric acid: 1:5 (Ce:5CA), 1:3 (Ce:3CA), 1:1 (Ce:1CA), and 1:0.5 (Ce:0.5CA). The obtained products were characterized by a series of physicochemical methods including X-ray diffraction, transmission electron microscopy, and IR spectroscopy. Biomedical studies of the sols were performed to evaluate redox activity and their effects on the metabolism and proliferation of human fibroblasts. Safety studies were carried out in different animal species, including determination of the acute toxicity of the selected nanocomposite following application to intact skin and intragastric administration, as well as determination of subchronic toxicity using a model of acute experimental full-thickness skin wounds. According to the physicochemical studies, all synthesized nanocomposites contained nanocrystals with bimodal dimensions (width 3–10 nm, length 15–40 nm) and diffraction peaks characteristic of CePO₄. IR spectroscopy demonstrated the formation of new chemical bonds. Antioxidant activity was observed for the Ce:3CA, Ce:1CA, and Ce:0.5CA samples, being most pronounced for Ce:1–0.5CA, whose antioxidant capacity exceeded that of ascorbic acid. In contrast, Ce:5CA exhibited pro-oxidant activity at all tested concentrations. Biocompatibility with human cells was demonstrated. Ce:0.5CA was identified as the most promising candidate for biomedical applications owing to its highest regenerative and antioxidant potential and its demonstrated safety in animals following topical and intragastric administration, as well as in wound models. Histomorphological examination of the internal organs supported the safety and potential of the developed nanocomposites for skin regeneration and wound healing. Full article

Background/Objective: Niclosamide exhibits considerable potential for the treatment of drug-resistant cancers. However, its poor aqueous solubility substantially limits its oral bioavailability and therapeutic efficacy. To overcome this limitation, we developed a novel pharmaceutical supramolecular crystalline phase comprising niclosamide and nafamostat. Methods: In this study, we developed a niclosamide–nafamostat pharmaceutical supramolecular crystalline phase using a conventional solvent evaporation technique. Comprehensive solid-state characterization was carried out using X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). In vitro drug transport kinetics and barrier transport efficiency were evaluated across artificial transpermeable membranes using a diffusion cell setup. In vitro anticancer efficacy was systematically screened against human lung, breast, and pancreatic cancer cell lines. Finally, in vivo translation was established using female NOD/SCID mice tumor-bearing animal models; therapeutic efficacy and total tumor burden were evaluated. Results: Niclosamide–nafamostat cocrystal (NNC) was found to form a distinct crystalline phase, with characterization results supporting a unique crystal lattice stabilized through strong intermolecular hydrogen-bonding interactions and exhibiting high thermal purity. Crucially, the supramolecular crystalline phase considerably enhances membrane transport, yielding superior cumulative permeation and enhanced apparent permeability (Papp) values compared to those of pure niclosamide. In vitro evaluation across multiple cancer cell lines demonstrated a tenfold increase in antiproliferative potency compared to the parent compounds. Furthermore, in vivo studies revealed a twofold increase in tumor growth inhibition and a tenfold reduction in total tumor burden (p < 0.05). Conclusions: These findings demonstrate that the NNC supramolecular crystalline phase platform successfully optimizes membrane permeability and antitumor efficacy, highlighting its potential for treating advanced cancers. Full article

Animal-assisted interventions (AAIs) for children with developmental disabilities (DD) have traditionally focused on dogs and horses, with less research on cat-centered AAIs. However, many potential AAI participants prefer, or only have access to, cats. The current Randomized Control Trial (RCT) study evaluated a novel Cat-Assisted Training (CAT) intervention designed to promote healthy behaviors in children, while also strengthening child–cat bonds. Participants included 36 children with DD (ages 8–17 years) and their family cats. Participating pairs were randomly assigned to either the CAT intervention (experimental) group or the waitlist control group. Feasibility was supported by 100% session attendance, a 94.4% post-intervention retention rate, and an 81% average homework completion rate. Participants in the CAT group reported increases in health-promoting activities, such as walking with their cat (p = 0.008), and demonstrated a significant increase in cat care responsibility (p = 0.039). Cats showed an immediate increase in sociability toward their child (p = 0.036), and a higher rate of secure attachment to their child partner at the one-year follow-up compared to baseline (p = 0.031). Overall, this initial study suggests that the CAT intervention represents a promising AAI model, providing empirical support that cats can be active and successful AAI partners for children with DD. Full article

A growing body of empirical study recognises a tendency for users to form (para)social bonds with Large Language Models, even when users know explicitly that these systems lack interiority or personhood. This contribution argues that such attachments arise from evolved human capacities to attribute being, moral status and, in some ways, ‘soul’ to nonhuman others—and that this capacity now operates without the belief-systems that have historically mediated it. When users encounter helpful, patient, emotionally available behaviour in conversational agents, they project the interior states that would produce those behaviours in themselves: authentic interiority and phenomenal consciousness. Humans have been making such assessments throughout our cultural history, developing ontologies and theologies for managing our relations with nonhuman, mythic and spiritual others. By contrast, modernity has disenchanted its landscapes, dismantling these cultural models even as the ‘ensouling architecture’ of our social and semiotic cognition remained unchanged. Contemporary users thus encounter machine others through the same neurocognitive lens as their ancestors did with spirits and animals on enchanted, animate landscapes, but without the mediation of culture, norm and taboos which place a premium on appropriate conduct, reciprocity and moderation. The resulting condition—a ‘Turing Animism’—leads users to ‘feel soul’ where there is only simulacrum. Full article

Understanding human–nature–animal relationships is central to conservation and visitor management, yet these relationships are commonly studied through language-based surveys that may exclude participants across age groups and diverse cultural or educational backgrounds. This limitation highlights the need for more inclusive and experience-sensitive approaches capable of capturing relational meanings beyond verbal expression. This study adopts a visual participatory approach in which volunteer tourists were invited to draw circles representing themselves in relation to images of a giant panda, nature, and a pet. Extending the visual idea of Schultz’s Inclusion of Nature in Self in the Connection to Nature Index, more than 1000 tourists at the Chengdu Research Base of Giant Panda Breeding produced over 3000 drawings. These drawings were systematically coded along three dimensions—circle size, orientation, and spatial relationship—and analyzed using multinomial logistic regression and non-parametric tests. The results reveal consistent yet differentiated patterns of visual representation. Participants most frequently expressed relationships with nature and pets through enclosing circles, suggesting spatial inclusion, whereas relationships with the giant panda were more often represented through separate but proximal positioning, indicating a more mediated or observational mode of connection. Demographic factors, including age, residence, and visitation stage, significantly influenced drawing configurations, supporting the interpretation of connection as a context-sensitive and dynamic process rather than a fixed individual trait. Associations between drawing dimensions and self-reported pro-environmental orientation and momentary well-being were observed, although these relationships should be interpreted cautiously given the use of brief, context-specific indicators. Overall, the findings demonstrate that participatory drawing can function as both a research instrument and an engagement tool, enabling diverse visitor groups—including children—to express relational understandings of nature and wildlife. For conservation practice, such visual methods offer a scalable and low-barrier approach to visitor engagement, with potential applications in environmental education, interpretation design, and the assessment of human–animal relationships in situ. Full article

Understanding how individuals decide to adopt shelter dogs remains a significant challenge within animal welfare research, as existing studies identify correlates of adoption outcomes without explaining the underlying decision process. This hypothesis introduces a conceptual framework that synthesizes empirical findings from dog adoption studies with interdisciplinary theories to explain how adoption decisions emerge. Using a signal-to-noise perspective, the framework conceptualizes early bond formation between a potential adopter and a dog as a valuation signal that competes with uncertainty arising throughout the process. The functional model describes the adoption process as a lifecycle involving search, visitation, interaction, and decision phases, during which potential adopters seek information, evaluate available dogs, and form perceptions of compatibility. Interdisciplinary decision models, including Prospect Theory and the Diffusion Decision Model, are integrated to explain how information is framed, evaluated, and accumulated until a decision is reached. Empirical findings from human–dog interaction research are used to support the hypothesis that potential adopters evaluate companionship potential based on early bond formation associated with human–dog interactions. The framework offers a broad perspective on how adoption decisions may occur and establishes a theoretical foundation to guide future hypothesis development, measurement, and experimental research in companion animal adoption. Full article

Animal-assisted services (AAS) involve providers working in partnership with specially trained animals to deliver therapeutic, educational, and supportive benefits that promote human well-being. Although research shows dog-assisted AAS benefits recipients, little is known about handlers’ motivations and how this work impacts handlers and their dogs. This study explores why individuals engage in AAS with their dogs and the relational benefits and challenges involved. A convenience sample of adult AAS handlers was recruited through various organizations via newsletters and social media. Participants (N = 247), predominantly older, white, and highly educated women, responded to three open-ended survey questions. Data were analyzed using reflexive thematic analysis, which revealed several interconnected themes. Handlers described profound joy, pride, and purpose derived from sharing their dogs with others, and an enhanced capacity to support recipients. Participants reported using AAS to augment professional roles, to pay forward acts of kindness, and to enrich their dogs through social interaction. While overwhelmingly meaningful, this work also involves challenges, underscoring the need for organizational support for AAS teams. Training programs should equip handlers to recognize signs of animal stress, navigate demanding contexts, and engage in proactive conversations about rest, retirement, and loss. Normalizing these experiences may promote handler well-being and sustain ethical, relationship-centered AAS practice. Full article

This article considers traditional Inuit beliefs and practices as expressed through human–animal relationality, examining the physical and spiritual significance of qimmiit (sled dogs), and how qimmiit functioned as co-travellers with humans across physical and spiritual realms of existence. Drawing on ethnographic and missionary narrative sources, it explores Inuit–Qimmiit relationality as central to survival in the pre-modern period. Consulted sources include the writings of explorer–ethnographer Knud Rasmussen, Church of England missionary Edmund James Peck, anthropologist Franz Boas, explorer–author Peter Freuchen, and Oblate missionary Pierre Henry (Kajualuk). These accounts, despite Euro-centric and Christian biases, provide distinct yet overlapping experiences with sled dogs and understandings of Inuit traditions and worldviews. Read comparatively, these ethnographic texts reveal how qimmiit were essential to mobility and spiritual–social order. The article draws on the Qikiqtani Truth Commission to contextualize the harm and suffering caused by the loss of qimmiit during the dog killings of the 1950s to 1970s. The song “Travel Without Me,” from the Animal Kinship Project and written to commemorate qimmiit in the aftermath of the sled dog slaughter, provides a narrative framework structured around kinship and travel, foregrounding Inuit understandings of shared journeys across human and canine existence and framing Inuit–Qimmiit relations as enduring bonds that traverse both physical life and afterlife. Within Inuit religious cosmologies, relationships between humans and qimmiit extend beyond practical cooperation to encompass shared spiritual existence, relational obligation, and continuity of soul across physical and metaphysical worlds. Ethnographic accounts recorded by Rasmussen, Peck, Boas, Freuchen and Henry describe dogs not merely as working animals but as ensouled beings who participate in travel, naming practices, shamanic mediation, cosmogonic and afterlife narratives. Read through a religious studies lens, these sources reveal a cosmological framework in which mobility and survival are embedded within sacred relational structures linking human and animal life. This article examines Inuit–Qimmiit kinship as a form of physical–spiritual relationality, arguing that dogs function as co-travellers whose relational position across embodied and cosmological domains illuminates Inuit understandings of personhood, cosmological balance, and the continuity of life beyond death. Full article

Well-founded animal models of maternal separation show that early postnatal separation from the mother represents a massive stress factor for the offspring, with far-reaching negative effects on their physical and behavioural development. However, studies also show that the effects of maternal separation can be at least mitigated by appropriate physical attention. In this case report, we document the successful rehabilitation of a single orphaned male harbour seal pup by attempting to substitute natural maternal attention with intensive human attention. The pup underwent excellent physical development and displayed a close bond with its carers, characterised by intensive physical contact and suckling on a carer’s hand. However, during the final rehabilitation phase in a large outdoor enclosure, the pup increasingly reduced its affiliation to its carers. After its release, long-term observations over four years documented its hunting success, corresponding optimal physical development, and successful integration into existing wild seal groups. At the age of four, the now sub-adult seal displayed socio-sexual behaviour that is typical for this age and maintained a close bond with a wild female seal for months. The report shows that the rehabilitation of orphaned seals is possible by substituting maternal care with human care, resulting in neither a fixation on humans nor modifying species-specific behaviour. Thus, the pup’s chances of survival and potential reproduction in the wild were not jeopardised by this method of rehabilitation. Full article

Goat (Capra hircus) welfare is an important issue in any farming system. The aim of the study was a comprehensive analysis of the impact of environmental factors and farming practices on the welfare of goats, with particular attention to physical, behavioural, and emotional aspects. It includes a review of the up-to-date literature on the effects of environmental conditions including air temperature, air humidity, space, feeding systems, social relationships (mother–offspring, human–animal, animal–animal), zootechnical procedures (dehorning, castration, hoof trimming) and welfare assessment methods. It compares the AWIN, Anzuino, Muri and Leite protocols for assessing goat welfare and their application in the Five Domain Model. Goat welfare is strongly influenced by their environment, nutrition and socialisation: heat stress and confined space cause physiological disorders, decreased immunity and increased aggressive behaviour and a monotonous diet leads to frustration and reduced cognitive activity, whereas positive early contact with humans reduces anxiety and maintaining the mother–kid bond supports the social development of young goats. Furthermore, significant improvements in welfare and stress reduction can be achieved by providing anaesthesia and painkillers where necessary to minimise pain and enriching the environment with items that support natural behaviour, such as platforms, brushes and items for cognitive tasks. In general, the keeper should take a holistic approach, combining environmental optimisation, humane husbandry practices and regular monitoring using validated assessment protocols to improve welfare. These measures are both an ethical obligation and a prerequisite for animal health and production efficiency. Nevertheless, there is a need for further research focussing on the development of non-invasive assessment methods and innovative forms of environmental enrichment. Full article

β-agonists are prohibited antibiotics that have raised concerns due to their illegal use in the livestock industry, posing potential toxicity risks to human health. For ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) analysis of β-agonists, effective sample pretreatment is a crucial and challenging process that dictates the overall reliability and sensitivity of the method. Thus, this study developed a reliable method utilizing dispersive solid-phase extraction (d-SPE) with NH₂-UiO-66 as a superior adsorbent, coupled with UPLC-MS/MS, to extract and quantify β-agonists in environmental water, swine urine, and milk. The synthesized NH₂-UiO-66 exhibited outstanding adsorption capacities (146.06–358.00 mg/g) towards the target analytes. The optimized method demonstrated excellent performance: low matrix effects (−13.10–15.30%), wide linearity (0.1–50 μg/L), low limits of detection (0.04–0.09 μg/L), and satisfactory recoveries (81.48–106.67%) with good precision (intra-day RSDs 1.51–6.24%; inter-day RSDs 2.06–10.96%). Adsorption mechanism studies revealed that the extraction process, which followed the Langmuir isotherm and pseudo-second-order kinetic models, was driven primarily by electrostatic interactions, π-π stacking, and hydrogen bonding. Moreover, the material could be reused up to 10 times, with satisfactory recoveries of 81.30% to 116.10%. The proposed NH₂-UiO-66-d-SPE-UPLC-MS/MS protocol is generic and provides a robust and practical solution for monitoring trace β-agonists in animal-derived foods and environmental samples, ensuring food safety and environmental health. Full article

Background: The peptidyl–prolyl cis–trans isomerase PIN1 regulates multiple oncogenic and tumor-suppressive pathways and is frequently overexpressed in human cancers. Although pharmacological inhibition of PIN1 has shown antitumor potential, existing PIN1-targeting degraders lack systematic structure–activity relationship (SAR) analyses and display inconsistent cellular efficacy, leaving the therapeutic relevance of PIN1 degradation unclear. Methods: Two series of PIN1-targeting PROTACs were designed using the covalent inhibitor sulfopin as the PIN1 binder and ligands for either cereblon (CRBN) or von Hippel–Lindau (VHL). Systematic SAR studies focused on linker structure and jointing atom composition. PIN1 degradation was assessed by Western blotting in multiple cancer cell lines, and further investigated through a series of computational and mechanistic experiments. Antitumor efficacy and safety were evaluated in an MCF-7 xenograft mouse model with preliminary pharmacokinetic analysis. Results: SAR analysis revealed that short, linear linkers and reduced hydrogen bond donor content markedly enhanced PIN1 degradation, whereas VHL-recruiting PROTACs showed inferior cellular activity. These studies identified PC2, a CRBN-recruiting PROTAC, as a lead compound. PC2 selectively induced ubiquitin–proteasome-dependent PIN1 degradation with minimal global proteomic or transcriptomic perturbation. Despite modest antiproliferative effects in vitro, PC2 significantly suppressed tumor growth in vivo without observable toxicity and achieved effective intratumoral PIN1 degradation. Conclusions: This study defines SAR-guided design principles for PIN1-targeting PROTACs and demonstrates that selective PIN1 degradation can produce robust antitumor activity in vivo. PC2 represents the first PIN1 degrader validated in animal models and supports targeted PIN1 degradation as a viable anticancer strategy. Full article

Orthodontic treatment with fixed appliances increases the risk of enamel demineralization and biofilm accumulation around brackets and other devices. Conventional orthodontic bonding materials provide adequate mechanical retention but limited bioactive protection. This narrative review summarizes current in vitro, in vivo, and clinical evidence on nanoparticles (NPs) incorporated into orthodontic adhesives and cements, focusing on antimicrobial and remineralizing effects, mechanical performance, potential clinical relevance, and safety. Electronic searches of PubMed, Science Direct and Google Scholar identified laboratory, animal, and human studies evaluating NP-modified orthodontic bonding systems. Most available data derive from in vitro experiments, which consistently show that silver, zinc oxide, titanium dioxide, calcium phosphate-based particles, and related nanoparticles can inhibit cariogenic biofilms, reduce enamel demineralization surrogates, and, in many formulations, maintain clinically acceptable shear bond strength while enabling fluoride or calcium/phosphate ion release. A smaller number of in vivo and short-term clinical studies suggest reduced plaque accumulation and fewer or less severe white-spot lesions when nanoparticle-containing materials are used, although study designs and outcome measures are heterogeneous. Overall, NP-enhanced orthodontic bonding materials appear promising for combining mechanical durability with biological protection. However, the current level of evidence is limited by the predominance of in vitro data, small sample sizes, and short follow-up in clinical studies. Well-designed, long-term clinical trials with standardized outcomes are required before routine clinical adoption can be recommended. Full article