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Emerging environmental contaminants increasingly accumulate in soil ecosystems, yet their chronic biological impacts on soil-dwelling organisms remain poorly understood. Here, we demonstrate that tris(2,4-ditert-butylphenyl) phosphate (AO168═O), a prevalent soil-borne contaminant formed through the oxidative transformation of the widely used plastic antioxidant (AO168), compromises nematode fitness at relatively low concentrations. Exposure of C. elegans to AO168═O induces pronounced developmental and physiological impairments, including suppressed somatic growth, delayed developmental progression, disrupted energy homeostasis, and reduced reproductive output at 400-10,000 ng/g. Transcriptomic profiling reveals a robust reprogramming of gene expression that molecularly corroborates growth and developmental restriction. Notably, longevity-regulating pathways centered on the conserved insulin/IGF-1 signaling (IIS) are consistently and significantly enriched. Integrated gene-set enrichment analyses further demonstrate that AO168═O-associated transcriptional signatures closely recapitulate established IIS- and DAF-16-regulated expression programs, which were functionally validated by pharmacological inhibition and genetic ablation. Furthermore, early-life exposure leads to persistent and long-lasting fitness deficits, such as impaired locomotor performance and a marked reduction in adult lifespan, detectable even at the lowest exposure concentration. Together, these findings identify AO168═O as a previously underrecognized factor compromising nematode fitness, providing essential laboratory-based evidence that highlights the potential vulnerability of soil biota to ubiquitous soil-borne contaminants.

Age and early life adversity (ELA) are key determinants of health, but whether they affect similar physiological mechanisms across tissues is unknown. We generated DNA methylation (DNAm) profiles across 14 tissues in 237 semi-free-ranging rhesus macaques with naturally occurring ELA. Age-associated DNAm was predominantly tissue dependent, yet tissue-specific epigenetic clocks showed that epigenetic aging was relatively consistent within individuals. ELA effects were adversity dependent, but each ELA exerted coordinated effects across tissues. Although ELA targeted many of the same loci as age, the directions of effects differed, which indicates that ELA does not uniformly increase epigenetic age. Instead, ELA leaves a coordinated, cross-tissue epigenetic signature that is distinct from-yet intertwined with-age-related differences, which advances our understanding of how early environments sculpt the molecular foundations of aging and disease.

Humic substances (HS) are increasingly investigated as natural additives to support health in humans and animals, yet their effects on honey bees remain insufficiently characterised. This study evaluated the impact of a commercial HS-based product on immunity and oxidative status of Apis mellifera. Newly emerged worker bees were kept under laboratory conditions and fed sugar syrup supplemented with 0.5% HS for seven days, while the control group received unsupplemented syrup. Effects of HS were evaluated by analysing the expression of selected immune-related genes, quantifying antimicrobial peptides (AMPs), measuring the activity of antioxidant enzymes, evaluating lipid peroxidation, and characterising hemocyte populations. HS supplementation significantly increased relative gene expression of superoxide dismutase 1 and prophenoloxidase, while expression of genes for apidaecin and defensin 1 decreased. HS supplementation significantly increased relative gene expression of superoxide dismutase 1 and prophenoloxidase, while expression of genes for apidaecin and defensin 1 decreased. Similarly, catalase enzymatic activity was significantly decreased in the HS group. No significant changes were detected in gene expression for other AMPs and relative abundance of AMPs, or other antioxidant parameters. HS supplementation significantly increased the proportion of medium granular hemocytes (p&#x2009;<&#x2009;0.05) at the expense of high granular cells (p&#x2009;<&#x2009;0.01). In conclusion, the 7-day administration of HS at 0.5% did not adversely affect bee health and modulated selected immune parameters. The biological significance of these immunomodulatory effects requires confirmation through challenge studies and field trials under natural conditions.

We previously demonstrated that the anti-CD33 antibody drug conjugate, gemtuzumab ozogamicin (GO) binds CD33-expressing monocytic myeloid-derived suppressor cells (M-MDSCs), is internalised, and decreases their viability. Treatment of MDSCs with GO restores T-cell proliferation in co-culture, overcomes M-MDSC suppression of CAR-T-cell proliferation, and enhances target-cell killing. GOTHAM is a phase II single arm trial. Patients with a diagnosis of solid cancer with radiological or clinical evidence of disease progression, or primary or secondary hemophagocytic lymphohistiocytosis, or macrophage activation syndrome disease relapsing/refractory to treatment at enrolment were eligible. An initial regimen of 3&#x2005;mg/m2 GO on days 1, 8, and 15 was tested, adjusted to 21-day intervals, days 1, 22, and 43. The primary outcome was the impact of GO therapy on peripheral CD33+ myeloid cells. Trial registration: ISRCTN 89158144. Using two schedules of GO, we could not convincingly demonstrate safe feasibility in patient with solid cancer because of neutropenia. However, GO reproducibly and significantly reduces circulating MDSCs. Importantly, there is consistent preliminary evidence that upon rebound the monocyte population of CD33+ cells is replaced with non-suppressive monocytes. These data support the phase Ib dose-escalation testing of GO up to 2&#x2005;mg/m2 in combination with immune checkpoint blockade and other immunotherapies in patients with solid cancer to find a dose that depletes and repolarises MDSCs without causing undue neutropenia, paving the way to using GO as an immune potentiator in this patient population.

Objective: People who use anabolic-androgenic steroids (AAS) frequently engage in polypharmacy, with evidence highlighting recurrent co-use with amphetamine-like stimulants. While the independent risks of each substance are established, little is known about their combined impact in treatment-engaged populations. This study compared people who co-use AAS with methamphetamine (AAS-M) and without (AAS-non-meth [AAS-NM]) across mental health, risk behaviors, and social determinants. Methods: Intake data were drawn from Lives Lived Well (LLW), a large Australian non-government alcohol and other drug (AOD) service provider. Clients attending any LLW service Australia-wide between 1 November 2022 and 28 February 2025 reporting past three-month AAS use on the World Health Organization Alcohol, Smoking and Substance Involvement Screening Test (WHO-ASSIST) formed the analytic sample (N&#x2009;=&#x2009;517). The sample was stratified into AAS-M (n&#x2009;=&#x2009;429) and AAS-NM (n&#x2009;=&#x2009;88) groups. Group differences in social, structural, and quality of life indicators were tested using &#x3c7;2 and independent samples t-tests. Results: Compared to the AAS-NM group, clients in the AAS-M group were significantly more likely to report trauma, psychosis, and driving under the influence, with higher impulsivity scores on negative urgency, positive urgency, and sensation seeking (&#x3c7;2 and t-tests, all p < .05; &#x3d5; = .10-.12, d = -0.29 to -0.37). They also showed greater engagement in unsafe injecting and recent overdose (&#x3c7;2, both p < .05). Social vulnerabilities were more pronounced, including elevated risks of homelessness, eviction, and recent violence (&#x3c7;2, all p &#x2264; .01; &#x3d5; = .11-.19). Finally, loneliness indicators were significantly higher among AAS-M clients (t-tests, both p < .01; d = -0.31 to -0.32). Conclusions: Co-use of AAS and methamphetamine among AOD service-engaged individuals is linked to heightened mental health concerns, risk behaviors, and social disadvantage. The findings indicate that AAS users who also use methamphetamine experience greater vulnerability than those who do not, underscoring the need for targeted responses within Australian treatment services.

This Viewpoint proposes that routine adoption of clinical artificial intelligence (AI) requires explicit alignment of payer, primary beneficiary, value metric, and life cycle accountability.

Life is a constant struggle against disorder. As we age, our ability to maintain internal order declines. In the healthy human brain, order is observable in the form of functionally segregated brain network communities that exhibit spatial consistency. These communities associate with distinct cognitive and physical functions. When mapped into the brain, they form a functional "landscape". We assessed the spatial disorder of these landscapes in older adults with a wide range of mobility using a spatial form of Shannon entropy. We found that compared to younger adults, older adults had significantly higher entropy in the sensorimotor cortex, basal ganglia, hippocampus, thalamus, and occipital lobe. Higher entropy in many of these regions was associated with worse physical function and higher body mass index in older adults. Findings suggest that spatial entropy in brain network landscapes may be a marker of declining physical function. Modifiable factors, such as losing excess weight, may help to ameliorate aging-related brain entropy increases in regions such as the sensorimotor cortex, which may in turn help to preserve physical function in older adults.

Although critical to the labor force, organizational research rarely considers the perspectives of Black women generally and individual differences in cultural identity specifically. Simultaneously, although cultural psychologists have linked individual differences in race and gender socialization, termed the Strong Black Woman (SBW) schema, to mental health outcomes, it has not been tested in work contexts. Finally, research using the Strong Black Woman Cultural Construct Scale has largely analyzed this multidimensional construct unidimensionally, potentially obscuring subdimensions' unique effects on health and work outcomes (i.e., affect regulation, caretaking, and self-reliance). The current work addresses these empirical gaps. Two studies using cross-sectional and multiwave designs tested relations between the SBW schema and burnout (ntotal = 343; age range = 18-69). Black women workers completed measures of the SBW schema and burnout. In Study 2, measurements were separated by 1 week. In Study 1, we refined the Strong Black Woman Cultural Construct Scale (SBWCCS-9) to improve subscale validity and validated the factor structure in Study 2. The multidimensional approach had the best predictive validity, accounting for approximately three times as much variance in burnout and revealing discrete costs and benefits of the SBW schema. Whereas affect regulation and caretaking were positively associated with burnout, self-reliance negatively predicted burnout. Black women's cultural identity plays a key role in organizational life and is best conceptualized as multidimensional. Affect regulation and caretaking contributed to burnout, whereas self-reliance offered protective benefits. The SBW schema acts as a double-edged sword in Black women's work lives. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

Stereotactic body radiotherapy (SBRT), most commonly delivered in 5 fractions, is an established treatment option for patients with localized prostate cancer. While efforts to further reduce treatment to fewer than 5 fractions are ongoing, the efficacy and tolerability of single high-dose SBRT remain to be established. To determine in men with localized prostate cancer whether a single-fraction SBRT can be a valid treatment option in terms of biochemical disease control and safety. This multicenter, single-arm, prospective, phase 1/2 nonrandomized clinical trial included men with localized prostate cancer at low or intermediate risk, with International Society of Urological Pathology grade group 1 or 2, and without significant tumor in the transitional zone. Participants were recruited between 2017 and 2022 in 5 academic centers in Europe and the US. Data were analyzed between February and May 2026. Participants were treated with a 19-Gy single-fraction prostate SBRT with urethra-sparing and intrafraction motion control. The primary end point was biochemical relapse-free survival (bRFS) at 3 years (expected value of 96% included in the 95% CI). Secondary end points included occurrence of genitourinary (GU), gastrointestinal (GI), and sexual adverse events (AEs) and quality of life (QOL) assessment. Among the 45 patients recruited (median age, 72 [range, 60-82] years), 43 were treated per protocol. After a median follow-up of 55.3 (IQR, 49.9-60.7) months, the estimated 3-year bRFS was 92.9% (95% CI, 85.4%-100%), meeting the primary end point. At 3 years, grade 2 GU and GI AEs were observed in 4 (9.8%) and 2 (4.9%) participants, respectively, with only a grade-3 proctitis observed in 1 patient at month 12. Grade 2 or higher erectile dysfunction increased from 9 of 42 patients (21.4%) at baseline to 15 of 39 (38.4%) at 3 years. A significant minimally clinically important change in Expanded Prostate Cancer Index Composite scores was observed in 6 (14%) and 12 (28%) participants for GU and sexual scores, respectively. The impact in GI bother scores was minimal. In this multicenter phase 1/2 trial, a single-fraction 19-Gy urethra-sparing SBRT met the primary end point, achieving a 3-year bRFS of 92.9%, with grade 2 GU and GI AEs remaining below 10% and 5%, respectively, at 3 years. Longer follow-up is warranted to assess long-term disease control. ClinicalTrials.gov Identifier: NCT03294889.

The capacity utilization of all-solid-state sulfur cathodes reveals a significant disparity between material and electrode levels due to the high proportion of inactive components required for electro-ionic transport. While the all-electrochem-active (AEA) electrode concept seeks to bridge this gap, fully realizing the energy-density potential of sulfur-based cathodes remains challenging. Here, we report a new strategy for co-modulating the redox of the transition-metal cation/sulfur anion to unlock the potential of the sulfur-based electrode. By carefully adjusting the coordination between S anions and Ti cations, we constructed the AEA electrode with S-anion (TiSx, x > 2)/Ti-cation (amorphous TiS2) co-redox, where TiSx activates the redox activity of sulfur-rich phases with narrower bandgaps through the reversible cleavage and recombination of S-S bonds, thereby enhancing the capacity utilization of anion-redox in the electrode level, and amorphous TiS2 serves as an electrochemically active matrix facilitating mixed ionic-electronic conduction. This design eliminates inactive components and enables synergistic anion-cation redox chemistry. Consequently, this designed cathode achieves an unprecedented electrode-level energy density of 1829&#xa0;Wh/kg, sustains an areal capacity of 11.6 mAh/cm2, and exhibits long-term stability over 10&#xa0;000 h. Device-level demonstrations validate this synergistic approach as an effective design principle for realizing high-energy-density, long-life all-solid-state battery cathodes under practical conditions.

Periodontal diseases are among the most prevalent noncommunicable diseases (NCDs) worldwide, with advanced stage contributing to disability, impaired nutrition, frailty, and reduced quality of life. Despite this burden, periodontal care remains weakly integrated into global NCD strategies, limiting public health advocacy and healthy aging. We conducted a conceptual and policy-oriented analysis to identify opportunities for repositioning periodontal care as a public health function. Key domains examined included (a) preventive healthcare through the common risk factor approach; (b) case identification and diagnosis designed to serve both clinical care and population surveillance; (c) de-implementation of care with limited incremental benefit at scale, including the role of payment incentives in shaping utilization. To evaluate long-term affordability, projected global periodontal healthcare expenditure through 2050 was modeled using a cohort-based Monte Carlo simulation, comparing current utilization patterns, expansion to 80% population coverage, and an alternative capitation-informed scenario. Reorienting periodontal care toward proactive, cost-effective prevention and integrating case identification within primary care and NCD platforms offer greater potential for equitable population health gains than simply expanding procedure-intensive treatments. Risk-stratified care pathways based on patient-important outcomes, combined with de-implementation of low-value practices, can preserve oral function while reducing avoidable service volume and costs. Expenditure modeling indicates that achieving high coverage under prevailing fee-for-service delivery would substantially increase global financial burden, whereas a capitation-informed scenario reduced projected expenditure by 30% at the same coverage level, suggesting alternative incentives could expand access with less cost escalation, including in low- and middle-income settings worldwide. Aligning periodontal care with public health principles-prioritizing prevention, value, and equity over treatment volume-is a paradigm shift essential for achieving sustainable improvements in population health, healthy aging, and long-term health-system affordability.

Rates of adolescent psychiatric hospitalization have increased significantly over the last decade. Despite heightened risk for life-threatening behavior and readmission in the year following hospitalization, mental health service use has varied. Parental burden and youth externalizing behavior have been associated with service use in community samples, with most research focused on children and their parents. The present study explored longitudinal relations between parental burden, externalizing symptoms, and mental health service use in a high-risk clinical adolescent sample in the year following hospitalization. The sample included 252 mothers with an adolescent recently discharged from psychiatric hospitalization. Mothers completed measures of parental burden (Child and Adolescent Impact Assessment), youth externalizing symptoms (Achenbach Child Behavior Checklist), and youth mental health service use (Child and Adolescent Services Assessment) at 1 (M1), 3 (M3), 6 (M6), and 12 (M12) months following adolescent discharge from psychiatric hospitalization. Bidirectional relations between variables were examined with a cross-lagged autoregressive model. Controlling for baseline levels, greater externalizing symptoms were positively associated with parental burden and negatively associated with recommended use of individual psychotherapy over time. Recommended use of youth individual psychotherapy at M3 predicted lower externalizing symptoms at M6. No other longitudinal relations were found. Findings enhance our understanding of the experience of adolescents and families and inform service use patterns during the posthospitalization period. Recommendations for discharge practices and postdischarge care are discussed. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

A natural assumption in evolutionary biology is that to coevolve, species must interact with each other and should therefore co-occur. However, many evolutionary dynamics may be mediated by migratory or vector-borne agents, raising the possibility of coevolutionary interactions between allopatric species. In mimicry theory, a recurring assumption is that all species participating in a mimicry system must be sympatric, because predators must encounter both model and mimic/co-mimic to confuse between them. While it has been suggested that mimicry may occur between allopatric species through the mediation of migratory predators, this possibility has remained largely unexplored, theoretically and empirically. To explore this question, we used computer simulations that model the population dynamics of two populations of unprofitable aposematic prey connected by migratory predators. Each population in the simulation is affected by both local predators, which do not migrate and are therefore not directly affected by the foreign signal, and by migratory predators, which are affected by the signals in both populations. Our results demonstrate that migratory predators may drive the evolution of mimicry between allopatric species in a wide range of ecological scenarios, and that this phenomenon may be constrained by selective pressure from local predators. Furthermore, we suggest that migratory agents may facilitate not only mimicry, but a wide range of hitherto unappreciated coevolutionary interactions between allopatric species. In light of this perspective, we identify and discuss potential case studies of mimicry and other forms of coevolution occurring between allopatric species, including host-pathogen and herbivore-plant arms races.

The lamprey occupies a pivotal position for elucidating vertebrate brain evolution. Using spatial transcriptomics and single-nucleus RNA sequencing, we generated a three-dimensional molecular atlas of the lamprey brain, identifying 209 distinct cell clusters across 14 regions. Cross-species comparisons revealed broad conservation of regional spatial architecture, defining an ancestral organizational blueprint. Within this conserved framework, however, marked lineage-specific divergence emerged. We observed extensive neuronal specialization across vertebrate lineages, accompanied by regulatory shifts associated with spatial reorganization and functional diversification of neuronal populations. Additionally, our results suggest that a cerebellum-like architecture predates the jawed vertebrate cerebellum. Together, these findings identified constraints on neural organization and detected cellular innovations driving evolutionary diversification.

Preeclampsia (PE) is a complication during pregnancy characterized by hypertension, organ damage, and systemic inflammation. Increasing evidence suggests that the gut microbiome may play a role in the pathophysiology of PE. However, previous studies on the gut microbiome have generally overlooked the distinction between subgroups of PE, although clinical manifestations may differ. Also, most studies have not used deep sequencing techniques. Therefore, this study aimed to explore further potential differences in gut dysbiosis in different PE subgroups compared to controls using shotgun metagenomics. We studied the bacterial gut microbiome using shotgun metagenomic sequencing in 37 pregnant patients in the third trimester from a Swedish cohort, separating patients according to subtype (healthy controls N&#x2009;=&#x2009;21, late-onset PE N&#x2009;=&#x2009;8, early-onset PE N&#x2009;=&#x2009;8). Differential relative abundances and alpha diversity were evaluated using Wilcoxon rank sum test, and beta diversity was evaluated using PERMANOVA. Multiple linear regression was used to study associations between gut microbiome composition differences and clinical parameters. Late-onset PE and early-onset PE were both associated with significantly different beta diversity compared to controls. Differences remained significant after adjusting for age, and were not affected by gestational age, BMI or parity. Alpha diversity was lower in late-onset PE compared to controls. While no significant differences in taxonomic abundances were seen after correcting for multiple testing, several interesting leads were identified, including a higher abundance of genus Blautia in late-onset PE, and lower abundance of Coprococcus catus and unclassified Lachnospiraceae in early-onset PE. Functional analysis did not reveal any significant differences after false discovery rate (FDR) correction. In conclusion, our results showed subgroup-specific gut microbiome differences in PE with more pronounced associations in late-onset PE, despite limited power due to the observational design and small cohort. Accordingly, our results highlight the importance of subgroup analysis when studying PE.

AbstractMany invasive species establish uniquely, or with particular success, in disturbed ecosystems. We propose that for an invasive species, ecosystem disturbance may thus constitute an adaptive strategy of niche construction. Accordingly, a species' propensity to induce large-scale ecosystem change is likely to increase not only its expected damage as an invasive species but also its success as one. We suggest that this perspective, focusing on ecosystem-disturbing feedback mechanisms driven by invasive species, may be instrumental in understanding and predicting invasive species' dynamics. It complements the common view, which focuses on the effects of invasion dynamics and the respective ecosystem changes on the native species and which typically views these changes as collateral consequences of the invasion. Our perspective highlights invasives-driven ecosystem alterations as potential drivers of the invasion, and it emphasizes the potential importance of indirect benefits to the invasive that are brought about by the ecosystem disturbance and its cascading effects.

&#x3b2;-Thalassemia major typically manifests between six months and two years of age. It is characterized by chronic anemia, and a range of multisystemic complications lead to increased morbidity and disease burden. It has a significant influence on patients' mental and social health, making a biopsychosocial approach necessary for all encompassing therapy. This study examines how biopsychosocial, biochemical variables and genetic variants, namely the PDE7B gene SNP rs2327669, is associated with &#x3b2;-thalassemia major. Analysis of 400 patients and 400 controls, ages 2 to 18 years, was conducted with an emphasis on psychosocial aspects using a standardized questionnaire developed with the assistance of a psychiatrist and previously published studies to assess the psychological burden, biochemical indicators through biochemical analysis and genotyping with the help of Tetra ARMS-PCR. The findings presented here demonstrate the association between &#x3b2;-thalassemia major's biopsychosocial, biochemical aspects and genetic predispositions. A significant association between the rs2327669 and clinical indicators, were found by SNP genotyping with significance value&#x2009;<&#x2009;0.05. In personality characteristics and SNP genotyping association it was found, neuroticism and introversion were associated to the GG mutant genotype, whereas conscientiousness and compassion were associated to the CC and CG genotype (p-value&#x2009;<&#x2009;0.005). Through this study it was observed that, the PDE7B rs2327669 polymorphism is significantly associated with selected biochemical and psychosocial parameters in &#x3b2;-thalassemia major patients. Larger cohort studies are necessary in the future, so it could lead toward focused therapies that tackle physiological & biopsychosocial issues, enhancing the clinical results and quality of life for &#x3b2;-thalassemia major patients.

Eggs are natural and multifunctional bioresources, and their components are widely applied in the food, biomedical, functional, and environmental fields. Most studies have focused on the chemical properties or functional characteristics of individual components, and a systematic understanding that connects molecular structure, material performance, and cross-disciplinary applications is lacking. This review comprehensively synthesized existing studies, covering inorganic constituents (e.g., eggshell minerals), natural fibers (e.g., eggshell membrane), and protein and lipid structural features, determining their roles in functional regulation, interfacial activity, network formation, and material properties. Advancements in egg-based composite systems, including protein-polysaccharide networks, egg yolk lipid-based nanocarriers, eggshell-eggshell membrane composites, and protein-keratin crosslinked systems, are highlighted. The effects of the conditions of preparation, composite strategies, and interfacial modulation on the microstructure, rheology, film-forming ability, and stability were critically discussed. Future perspectives were proposed, emphasizing multicomponent synergistic design, cross-phase interface engineering, and the development of egg-based smart materials. This framework provides a systematic reference for using eggs in high-performance food systems, biomedical applications, and functional composite materials.

TL1A and its receptor DR3 are key regulators of mucosal immune responses, but their role in periodontal disease is unknown. Herein, we investigated whether TL1A/DR3 signaling contributes to mucosal immune amplification and tissue-destructive inflammation in periodontitis using SAMP1/YitFc (SAMP) mice, which develop spontaneous ileitis and periodontal disease. DR3 deficiency markedly attenuated alveolar bone loss and improved periodontal architecture, restoring a phenotype comparable to healthy AKR (parental) controls. Gingival tissues from wild-type SAMP mice exhibited increased expression of both Tnfsf15 (encoding TL1A) and Tnfrsf25 (encoding DR3), with both positively correlating with disease severity. This was accompanied by elevated levels of IL-17, TNF-&#x3b1;, and IL-1&#x3b2;, and by increased numbers of CD4+ T helper cells and neutrophils. Conversely, SAMPxDR3-/- mice exhibited reduced inflammatory cytokine production and immune cell accumulation. These findings support a model in which the TL1A/DR3 axis is associated with amplification of mucosal immune responses in periodontal disease, linking effector T cell activation, increased cytokine production, and recruitment of innate immune cells. Altogether, our data identify the TL1A/DR3 cytokine-receptor pair as a potential regulator of inflammatory circuits that drive periodontal pathology. Blocking this pathway may provide a therapeutic modality for patients affected by chronic periodontitis.