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Succinate dehydrogenase (complex II of the mitochondrial respiratory chain) plays an essential role in cellular respiration in all living organisms. Its inhibition in humans leads to severe pathologies. It is targeted by succinate dehydrogenase inhibitor (SDHI) pesticides that are seeing a global rise in usage within the farming industry. Concerned about the systemic toxic effects, the use and the regulation of SDHI pesticides, the interdisciplinary Holimitox consortium, made up of sixteen French research laboratories, has been working on the subject for four years. This article is a report of the concluding meeting of the consortium, combining research programme synthesis phases and round table discussions. The Holimitox consortium emphasizes the importance of taking an interest in this family of pesticides, which are still little known yet rapidly expanding, using an integrative EcoHealth approach. This is because the challenges of public health, environmental protection, and biodiversity require a detailed understanding of food and agricultural production chains, economic issues, and the regulatory assessment procedures for these pesticides.
Authorship on academic publications is consequential for researchers in science fields. One's position in a list of authors is typically used to signal information about author contributions and status, with the first and last author positions regarded as the most prestigious and important for career advancement. Therefore, any inequities that exist in the allocation of authorship (e.g., associated with gender or geography) could affect researchers' career progression. We assessed patterns in authorship at EcoHealth Alliance, a non-profit organization that conducted One Health and conservation research. We compiled a corpus of 451 peer-reviewed journal articles published from 2011-2022, each of which had at least one EcoHealth Alliance-affiliated author, and gathered information on the gender and country affiliation of authors in first and last author positions. Within the corpus, we found that gendered male researchers and researchers with high-income country (HIC) affiliations were often in prestigious author positions. Specifically, we found that gendered male authors represented 60% of first and last authors, 65% of first and last authorships (FLAs), and 91% of highly productive authors (those with ≥ 10 FLAs). Last authorships were particularly male-dominated, with 2.7 times as many last authorships by gendered male authors as by gendered female authors. Our network analysis revealed that gendered male authors were more structurally important to the author network on average and comprised 65% of highly "powerful" authors in the network. HICs were also overrepresented in the corpus, with 72% of FLAs listing an HIC affiliation. Though our analysis was based on articles with at least one EcoHealth Alliance-affiliated author, authorship affiliations in the corpus extended to nearly 250 institutions across 43 countries, suggesting broader applicability of our findings. We conclude by offering recommendations-informed by the patterns observed in our data and based on our personal experiences as researchers-that we believe would help address the gender and geography disparities in authorship patterns we observed.
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Nutrition-sensitive ill-health is a wicked problem that has been resistant to resolution. Systems thinking and systems-based practice (SBP) offer a more relational, contextual approach but there remains the need for an integrative framework that operationalises systems thinking in a way that is transformative. Eco-nutrition addresses this gap, conceptualising food, nutrition, health and wellbeing as products of interacting biological, environmental, sociocultural, economic and political systems. A narrative review was undertaken using meta-narrative and hermeneutic approaches to synthesise the historical evolution of ecological thinking and its application to nutrition. Databases searches, citation chaining and targeted searching identified seminal and contemporary literature. Sources were selected for conceptual relevance rather than exhaustive coverage. Eco-nutrition is articulated as an interconnected systems-within-systems approach grounded in biodiversity, temporal relationality and intergenerational dynamics. It consists of three domains: biological ecologies, tangible systems and meta-contextual domains (that include system anchors, connectors, shapers and interpreters). Eco-nutrition reframes nutrition as SBP and the behavioural expression of systems literacy. The framework illustrates how misaligned systems generate biological and sociocultural consequences that manifest as eco-health disorders across economic contexts. The framework enables practitioners to work inter-sectorally, with multiple actors and across scales: recognise how structures, policies and resource flows shape eco-health outcomes; anticipate unintended consequences; identify leverage points; and build transformative ecological, social and institutional capacities. Eco-nutrition provides a coherent, integrative approach for advancing SBP in nutrition. By identifying the capabilities required for future-ready practitioners, including cultural responsiveness, reflexivity, critical and systems thinking, ethical practice, leadership and communication, it positions nutrition professionals as accountable systems stewards aligned with the realities of the Anthropocene.
Coccidiosis, caused by Eimeria species, remains a major challenge to the poultry industry. The parasite transmission relies on the environmental sporogony stage during which the parasite transforms from non-infectious to infectious oocysts. This host-independent metabolism is driven by the mannitol pathway, which operates in oocysts of Eimeria, Toxoplasma, and Cryptosporidium. Our previous in vitro study demonstrated that Piper betle L. essential oil (PBEO) exhibits anticoccidial activity through oocysticidal effects and sporulation inhibition (IC₅₀ 1.31% at 72 h). Here, we performed systematic in silico molecular docking to evaluate ten major PBEO phytochemicals against three key E. tenella mannitol pathway enzymes: mannitol-1-phosphate dehydrogenase (M1PDH), mannitol-1-phosphate phosphatase (M1Pase), and hexokinase. In hexokinase enzyme, 3-allyl-6-methoxyphenyl acetate showed the strongest binding affinity (-6.2 kcal/mol), stabilized by a conventional hydrogen bond with CYS161 and a pi-sigma interaction with Leu58. For M1Pase, β-selinene and β-caryophyllene exhibited the highest affinities (-5.9 kcal/mol each) through hydrophobic alkyl networks. Next, the M1PDH receptor, β-selinene, achieved the most favourable binding (-7.4 kcal/mol), closely followed by the bicyclic sesquiterpene derivative (-7.1 kcal/mol). PBEO constituents potentially exert anti-sporulation effects by simultaneous inhibition of multiple mannitol pathway enzymes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping and analysis (map00051) confirms that these enzymes form a non-redundant metabolic unit essential for sporulation, with no bypass reactions annotated in the parasite genome. These findings support further bio-guided isolation and development of PBEO-derived compounds as anticoccidial agents targeting the environmental stage of coccidian parasites.
The coexistence of heavy metals and antibiotics in agricultural soil poses a critical challenge to crop safety. However, the molecular mechanisms underlying their combined toxic effects in real multi-pollutant environments remain poorly understood. This study elucidated the genotoxic mechanisms underlying the effects of cadmium (Cd) and oxytetracycline (OTC) on rice (Oryza sativa L.) in the presence of copper (Cu). Results indicated that ambient Cu (50 mg/kg) significantly reduced Cd and OTC accumulation in rice roots by 86.6 % and 68.9 %, respectively. Density functional theory calculations further confirmed that this reduction stemmed from the formation of stable OTC-Cd-Cu ternary complexes. Despite the reduced uptake of Cd and OTC, Cu unexpectedly enhanced genotoxicity. Specifically, compared to the OTC-Cd group, the OTC-Cd-Cu group induced more DNA strand breaks. Further mechanistic investigations showed that Cu induced downregulation of the cell cycle regulators CYCB1 (by 20 %) and WEE1 (by 17.9 %), resulting in inhibition of G2/M transition and impaired DNA repair. Molecular dynamics simulations revealed that Cu enhanced the binding energy between DNA and OTC-Cd (-4178.17 kJ/mol), thereby destabilizing the DNA structure, as evidenced by circular dichroism analysis. Furthermore, thermodynamic parameter analysis suggested that the interaction between DNA and pollutants was an exothermic reaction. Importantly, the OTC-Cd-Cu ternary system exhibited a higher degree of impairment to DNA stability than the OTC-Cd binary system. These findings provide critical insights into the molecular basis of crop toxicity in agricultural soil and underline the urgency of comprehensive risk assessment of combined pollutants.
Tsukamurella species are rare environmental aerobic actinomycetes that are increasingly recognized as opportunistic human pathogens, particularly among immunocompromised patients and those with indwelling medical devices. This review aims to summarize the clinical spectrum, diagnostic methodologies, patterns of antimicrobial resistance, and treatment outcomes associated with human Tsukamurella infections. A narrative review of published case reports, case series, and microbiological studies was conducted, emphasizing clinical manifestations, laboratory identification, antimicrobial susceptibility, and therapeutic interventions. The available evidence indicates that catheter-related bloodstream infections are the most frequently reported presentations; however, pulmonary, ocular, cutaneous, endocardial, central nervous system, peritoneal, and prosthetic joint infections have also been documented. Diagnosis remains challenging, as Tsukamurella can be misidentified by conventional methods; precise identification often necessitates advanced techniques such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and 16S ribosomal ribonucleic acid (16S rRNA) gene sequencing. Successful management typically involves prolonged targeted antimicrobial therapy and the removal of infected devices. In conclusion, Tsukamurella is an under-recognized pathogen, and standardized diagnostic and susceptibility-testing protocols, along with larger clinical studies, are essential to enhance patient management.
Calcitonin gene-related peptide (CGRP) is traditionally recognized as a key mediator of nociception and vasodilation. However, it also functions as a context-dependent immune "double agent," capable of both restraining inflammation and driving pathological responses. Here we discuss CGRP multifaceted roles in innate and adaptive immunity, inflammation, resolution, infection, autoimmunity, and cancer. In the innate immune response, CGRP predominantly exerts anti-inflammatory and tolerogenic effects on macrophages, mast cells, neutrophils, ILC2s, and NK cells, yet can promote pro-inflammatory signalling in acute high-DAMP (damage associated molecular patterns) settings. In adaptive immunity, it generally suppresses Th1 responses and induces CD8+ T cell exhaustion in chronic conditions, while paradoxically enhancing Th1 differentiation during acute viral infections. Aberrant TRPV1-CGRP signalling exacerbates IL-23/IL-17-driven pathology in psoriasis and experimental autoimmune encephalomyelitis, whereas CGRP depletion in severe systemic infections such as sepsis impairs neuro-immune protection. In the tumour microenvironment, tumours hijack sensory nerves to release CGRP, suppressing anti-tumour immunity, and directly stimulating cancer cell growth. This review highlights the potential of repurposing clinically approved anti-CGRP monoclonal antibodies-currently used for migraine-for conditions where elevated or dysregulated CGRP signalling drives pathology, while emphasizing the need for context-aware targeting to preserve physiological homeostasis.
Environmental microorganisms are sensitive indicators of aquatic ecosystem disturbance, yet their links with river eco-health remain poorly understood. We investigated water quality, bacterial and fungal communities and socioeconomic factors across source, suburban and urban sections of the Minjiang River. Water quality and microbial diversity exhibited clear spatial gradients consistent with agricultural, industrial and residential activities. Proteobacteria dominated urban bacterial communities, Actinobacteria prevailed in suburban areas and Armatimonadetes were associated with intensive human activities. Fungal assemblages also showed spatial differentiation, with Chytridiomycota dominating upstream, Ascomycota midstream and Basidiomycota downstream. At the genus level, CL500-29 marine group and hgcI-clade were enriched upstream, whereas Limnohabitans and Flavobacterium dominated downstream; Septoria prevailed upstream, while Mycosphaerella, Didymella and Ampelomyces were more abundant downstream. Multivariate analyses (PCA, RDA, Mantel tests) identified TP, TN and DO as key drivers of bacterial communities, while COD, BOD5 and DO primarily shape fungal distributions. Socioeconomic factors, including GDP per capita and population density, also contributed significantly. Predicted functional profiles based on OTUs showed spatial differences in microbial metabolic potential. This study provides a preliminary spatial analysis linking water quality, human activities and microbial communities in an urban river system.
The rise in antimicrobial resistance and heavy metal contamination poses major risks to human health and the environment. This study reports the green synthesis of silver nanoparticles (AgNPs) using a polar extract of Geranium wallichianum D. Don ex Sweet. to evaluate antibacterial activity and Hg2+-sensing. This is the first reported use of G. wallichianum as a dual reducing and stabilizing agent, enabling a rapid sunlight-assisted synthesis completed within 15 min. Characterization confirmed successful formation of AgNPs: UV-Vis spectroscopy monitored stability, FT-IR verified functional group interactions, PXRD confirmed the crystalline phase, SEM revealed an average particle size of 26 nm, and hydrodynamic size and zeta potential were 39 nm and - 28 mV, respectively. Antibacterial activity was assessed using 30 µg/mL AgNPs, 30 µg/mL erythromycin as a positive control, 30 µg/mL plant extract, and DI water as a negative control. All tests were conducted in triplicate and analyzed using one-way ANOVA (p < 0.05). The biogenic AgNPs exhibited strong antibacterial activity against Staphylococcus epidermidis (20 mm ZOI), Klebsiella pneumoniae (18 mm ZOI), and Escherichia coli (19 mm ZOI). The MIC and MBC values ranged from 15 to 30 µg/mL, confirming the dose-dependent antibacterial potency. Additionally, AgNPs showed excellent colorimetric response toward Hg2+, with a linear detection range of 1-100 µM and a limit of detection (LOD) of 6.68 µM. The sensor demonstrated high selectivity and practical applicability in real-water samples. Overall, the unique sunlight-driven synthesis strategy, coupled with the strong antibacterial potential and exceptional Hg2+ selectivity, underscores the novelty and sustainability of G. wallichianum-mediated AgNPs as a versatile nanoplatform for biomedical and environmental applications.
Atherosclerosis is caused by inflammatory processes that alter the permeability of arterial wall cells and leucocyte recruitment, leading to oxidation of low-density lipoproteins in the artery. The use of dietary polyphenols as antioxidants seems promising. Herein, molecular docking-based screening was initially used to predict the interactions of epicatechin and hydroxytyrosol on multiple cytokines that can trigger atherosclerosis development. Computational results show that epicatechin and hydroxytyrosol interact with the cytokines, namely, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, monocyte chemoattractant protein 1 (MCP-1), granulocyte-macrophage colony-stimulating factor, leukocyte differentiation antigen CD36, and oxidized low-density lipoprotein receptor-1. Cytotoxicity of both the bioactive compounds to human monocytic THP-1 macrophages was evaluated by lactate dehydrogenase and crystal violet assays. ROS activity evaluation was done for the phytocompounds followed by monocyte migration assay for MCP-1. The expression levels of selected biomarkers were further assessed by quantitative polymerase chain reaction. Inhibition of these atherosclerotic biomarkers may limit the atherogenic effect. Notably, these two polyphenols at a concentration of 0-125 µg/mL for 24 h showed no cytotoxicity on THP-1 macrophages and exhibited decreased ROS production and MCP-1 levels. The genes implicated in the early stages of inflammation are potential therapeutic targets to effectively reduce atherogenesis and prevent CVD. The interaction between the selected cytokines and the two natural compounds indicates their potential ability to inhibit the inflammation in vitro and exhibit anti-atherogenic effects. Hence, epicatechin and hydroxytyrosol possess significant anti-atherosclerotic effects and, in combination, could contribute positively to the treatment of atherosclerosis.
Coal mining activities can alter soil heavy-metal accumulation and risk patterns. To identify pollution characteristics, sources, and ecological and health risks, 88 surface soil samples from Tongchuan Town, Ordos City, were analyzed using enrichment factor, potential ecological risk index, positive matrix factorization, soil physicochemical analysis, and Monte Carlo-based health risk assessment. Heavy-metal concentrations were generally low and regional pollution risk was controllable, although Cd exceeded the agricultural soil risk screening value at some sites. Cd and Hg showed local enrichment and dominated ecological risk, with over 60% of sites at moderate or higher risk. Industrial-traffic sources contributed the most (44.09%), followed by natural sources (34.06%), coal-related emission-atmospheric deposition (16.35%), and mining disturbance-agricultural inputs (5.50%). Soils were strongly alkaline, with low organic matter and nitrogen and potassium deficiencies. Health risks were acceptable; oral ingestion was dominant, Cr and As were key contributors, and children were more sensitive.
The climate crisis is not only an environmental issue but also a growing challenge to biopsychosocial well-being. This study examined the association between climate crisis awareness and mental health-related indicators, specifically eco-anxiety and depressive symptoms, among healthcare professionals. This cross-sectional study was conducted between June and September 2023 using an online survey in Türkiye. A total of 301 healthcare professionals-including physicians, psychologists, nurses, and allied health personnel-participated using snowball (non-probability) sampling. Data were collected using a sociodemographic questionnaire, the Beck Depression Inventory (BDI), the Ecological Awareness and Consciousness Scale (EACS), and the Eco-Anxiety Scale (EAS). The EACS was adapted from an existing instrument and applied for exploratory purposes. Statistical analyses were conducted using SPSS 25.0, employing nonparametric tests (Mann-Whitney U and Spearman's correlation). Results showed that 71.4% of participants were female and 28.6% were male, with a mean professional experience of 10.96 ± 6.9 years. Most participants (87%) reported being informed about climate change, primarily through media sources. Climate crisis awareness was positively correlated with eco-anxiety (r = 0.339, P < 0.001), and eco-anxiety was positively associated with depressive symptom severity (r = 0.482, P < 0.001). In secondary analyses, male participants reported higher levels of eco-anxiety and depressive symptoms than females (P < 0.01). These findings highlight the psychological correlates associated with climate crisis awareness among healthcare professionals and underscore the importance of integrating mental health support and resilience-building strategies into climate-related education and awareness initiatives. Given the cross-sectional design, the findings reflect associations rather than causal effects.
The innate-adaptive immune interface is a decisive control point determining whether therapeutic interventions induce durable protection, antitumor immunity, inflammatory, or immune tolerance. Many immunotherapies fail in translation because immunity is often treated as a single-output system rather than a spatially and temporally organized network shaped by tissue context, antigen-presenting cell fate, biomolecular conditioning, and metabolic state. This review introduces the immunoscape framework as a nanobiotechnology-oriented model for linking immune-state mapping with controllable translational variables, including delivery route, release kinetics, first-contact immune cells, lymphatic routing, biomolecular corona identity, antigen-presenting cell fate, and safety-gate assessment. Unlike systems immunology, which primarily describes immune networks, or conventional immune engineering, which often focuses on selected payloads, targets, or platforms, the immunoscape framework provides a design layer for predicting context-dependent immune outcomes. We discuss two converging strategies for reprogramming this interface: natural biologics, including beta-glucans, polyphenols, microbial metabolites, and extracellular vesicles; and smart nanomaterials, including lipid nanoparticles, biomimetic vesicles, lymph node-targeted platforms, and stimulus-responsive nanoarchitectures. We further propose translational design rules to guide clinically realistic immune-reprogramming nanomedicines for cancer, infectious, inflammatory, and regenerative applications.
Bats are a diverse order of mammals that play an important role in ecosystem services. Numerous recent studies have focused on bats' role in the emergence and transmission of zoonotic pathogens, particularly viruses, but relatively fewer studies have investigated antimicrobial resistance in bacteria harbored by bats. Here, we estimate the prevalence and antibiotic profiling of Staphylococcus (S.) aureus in oral and rectal samples from bats in Northern Pakistan and assess factors associated with carriage of these bacteria by bats. Two hundred individual bats of five species: Pipistrellus javanicus (n = 17), Pipistrellus pipistrellus (n = 10), Rhinopoma microphyllum (n = 48), Rousettus leschenaultii (n = 124), and Scotophilus kuhlii (n = 1) were captured for non-lethal collection of samples to isolate S. aureus. Bats sampled were collected from two different provinces of Pakistan, specifically Khyber Pakhtunkhwa and Punjab, in August 2018 and from Sheikhupura Fort in October 2019. Bats were sampled from three sites: a natural cave, a man-made castle, and an animal shed, in Khyber Pakhtunkhwa and Punjab provinces. Out of 400 samples, 58 swabs were positive for S. aureus, including 34 rectal and 24 oral swabs. Prevalence of S. aureus carriage varied significantly among species (0-100%), with Rousettus leschenaultii exhibiting the highest prevalence. In addition, prevalence varied significantly among habitats but not between sex, age class, or reproductive status. S. aureus isolates showed resistance to tetracycline, gentamicin, and erythromycin and carried resistant genes such as TetK, TetM, ermA, and aacA-D. In this context, it is imperative to prioritize initiatives aimed at educating local communities about reducing exposure to antibiotic-resistant bacteria disseminated by bats and concurrently fostering awareness regarding the critical role bats play in our ecosystem.
Microplastics (MPs) and nanoplastics (NPs) are pervasive and persistent environmental pollutants raising growing concerns regarding their potential hazards to human respiratory health. This review systematically summarizes current epidemiological evidence and experimental findings concerning the respiratory toxicity of MPs and NPs. Exposure to these particles is associated with various pulmonary disorders, including pneumonia, chronic obstructive pulmonary disease, asthma, and other pathological lung injury. At the molecular level, MP- and NP-induced toxicity primarily involves oxidative stress, leading to mitochondrial dysfunction and endoplasmic reticulum stress. This oxidative damage triggers diverse forms of cell death, such as apoptosis, pyroptosis, ferroptosis, and autophagy. Furthermore, MPs and NPs induce pulmonary inflammation, disrupt the integrity of the alveolar-capillary barrier, promote pulmonary fibrosis, and cause DNA damage, mainly via oxidative stress pathways. This review also identifies critical directions for future research on the respiratory toxicity of MPs and NPs. Overall, this review highlights the respiratory health risks associated with MPs and NPs, emphasizing mechanisms involving oxidative stress, inflammation, and fibrosis, and underscores the urgent need for further investigation. It provides essential toxicological evidence and insights that could inform the development of effective protective strategies.
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Here, we explore the operational challenges of One Health-related research that focuses on disease ecology, emphasizing the need to understand bridging disciplines of ecology and epidemiology. While epidemiology considers the distribution and determinants of health in populations, ecology situates biological processes of interacting organisms within broader environmental and evolutionary contexts. Disease ecology emerges as a discipline, highlighting hosts-pathogens-environment interactions and bridging gaps between epidemiology and ecology. We discuss persistent barriers to the advance of disease ecology, such as disciplinary siloes, differing methodologies, and lack of incentives that continue to hinder collaboration despite increasing awareness of the importance of disease ecology research. Integration offers benefits for epidemiology and ecology: improved understanding of prediction uncertainty, stronger evidence, and more impactful applications across veterinary and public health, and biological conservation. We list priority pathways in cross-training and high-level implementation approaches to advance disease ecology and realize the aspirational goals of One Health.
Ecosystem health and human well-being are closely interlinked components of socio-ecological systems, playing a critical role in achieving regional sustainability. We examine the coupling relationship between ecosystem health and human well-being across 228 counties in the middle reaches of the Yellow River Basin-an area facing intense resource and environmental pressure. The main findings are as follows: (1) from 2000 to 2020, ecosystem health in the study area gradually improved, with the average index increasing by 13.61%, mainly driven by enhancements in ecosystem vitality and ecosystem services. However, significant spatial disparities remain, with a pronounced polarization between counties. (2) Over the same period, human well-being increased by 132.29%, but regional inequality also intensified, as indicated by a 31.91% increase in the coefficient of variation. (3) Granger causality tests indicate a bidirectional predictive relationship, significant at the 1% level for one direction and at the 5% level for the other. Impulse response analysis suggests that both systems exhibit self-reinforcing mechanisms, with the magnitude of self-response gradually declining over time. Although ecological improvement and social development may have potential positive mutual influences, these cross-effects were not found to be statistically significant. Spatial analysis shows significant positive spatial autocorrelation within each system, yet a significant negative spatial correlation between them, with dominant cluster types characterized by "high human well-being-low ecosystem health" (distributed in urban agglomerations) and "low human well-being-high ecosystem health" (distributed in mountainous ecological areas) spatial patterns. These findings provide empirical evidence for integrated socio-ecological governance and offer scientific support for coordinated development strategies in large river basin regions.