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New neurons flatten social hierarchies
Abstract As complex individualized behaviors in mice arise even when genes and environment are held constant, emerging social group structures should also depend on individual behavior. Adult hippocampal neurogenesis drives individual behavior and is involved in certain social behaviors. Would thus the emergence of social structure depend on adult-born neurons? To answer this question, we co-housed cohorts of female mice with intact and genetically diminished general adult neurogenesis in a large-scale automated tracking system for three months and analyzed the development of social behaviors over time. Not only did female mice develop stable hierarchies, we also found that, despite forming a functioning mouse society, their dominance behavior increasingly diverged over time. Specifically, neurogenesis-deficient mice showcased a greater increase in hierarchical behavior throughout the experiment. Within the social behaviors, mice showed no genotype-based preference, indicating intrinsic causes for behavioral differences. In mice with intact neurogenesis, social rank was positively correlated with adult hippocampal neurogenesis. Nevertheless, neurogenesis-deficient mice occupied higher ranks in the emerging hierarchy than their wild-type cohabitants, while displaying less individualization for this trait. The observed insistence on dominance might therefore reflect inflexible social strategies. Thus, social intelligence and flexibility, enabled by adult-born neurons, promote social adaptability, egality, and flatter hierarchies.
Revisiting dopamine function in cognition through abstract decision-making
Prevalence and associated risk factors of pneumonia following surgery for geriatric osteoporotic fracture: A nationwide cross-sectional study of China
Global decline in pollination limitation of pollinator-dependent crops
Biotic pollination benefits 75% of crops, representing about 35% of global food production. Given widespread reports of pollinator decline over the last decades, crop yield losses might be expected. However, global assessments of their impact on crop yield are still missing. We analyzed temporal trends in pollination limitation (PL) and evaluated whether the use of managed pollinators and autogamy capacity reduced yield losses. We used a global dataset on the effects of pollen supplementation in pollinator-dependent crops to assess changes in PL from 1950 to present and performed a meta-analysis using 790 effect sizes across 86 crops. Our findings reveal that PL is widespread across pollinator-dependent crops, averaging 36%. However, PL has declined by 50% between 1950 and the 2010s. Crops with managed pollinators were associated with lower PL than crops without them. Importantly, fields supplemented with managed pollinators showed a steady decline in PL over time, whereas unmanaged fields showed no evidence of decline. Autogamy capacity was associated with lower PL levels. Our study highlights the importance of managed pollinators for crop production and reinforces the potential role of breeding traits aimed at increasing autogamy to reduce PL. The results suggest that current pollination management practices have become increasingly efficient in crop production systems, possibly helping to mitigate the negative impacts of wild pollinator declines. However, continued efforts to diversify pollination strategies, including the conservation of wild pollinators and the management of alternative pollinator species, can have a relevant role in ensuring long-term resilience and sustainability of global agriculture.
Impact of dietary fenugreek sprouts and β-cyclodextrin on soft goat cheese
Abstract This study investigated the combined effects of fenugreek sprout feeding and β -cyclodextrin ( β -CD) treatment on traditional soft goat cheese. Thirty-nine Hassani goats were divided into: control (C), F15 (15 g fenugreek sprouts dry/head/day), and F30 (30 g/head/day). Milk was processed with or without 0.5% β -CD. Fenugreek supplementation significantly enhanced milk production, F30 showing an approximately 60.6% increase in daily milk yield and improved fat and protein contents compared to C. In the cheese, F30 increased protein by 2.87%, while the addition of 0.5% β -CD (CF30) further increased protein by 5.0%, reduced cholesterol and triglycerides by 33.6 and 49.1%, respectively. Fenugreek supplementation improved the lipid profile, reducing total saturated fatty acids by 8.8% and increasing polyunsaturated fatty acids by 264.7% in F30. Textural analysis during storage showed hardness increasing by up to 343.8% in CF15, while springiness and cohesiveness declined. Microstructural confirmed a more homogeneous protein network in β -CD-treated samples. Sensory evaluation highlighted F15 and CF15 as the most acceptable treatments (scores of 8.8 and 8.2, respectively), whereas F30 and CF30 showed reduced acceptability. These findings demonstrated that moderate fenugreek supplementation (15 g/head/day), with or without β -CD, improved the nutritional quality, lipid profile, and structural characteristics of traditional soft goat cheese.
Forests shaped by historical human tragedies: Insights from Europe’s oldest angiosperms
A computational model of spatial politics: Hotelling-downs model as statistical physics
The Hotelling-Downs model considers parties changing policy to maximise their vote-share. Where policy position lies on a left-right axis, it describes a tendency for political parties to move towards centrist platforms. This is in contrast with widely observed political polarisation. We extend the model to two dimensions, with many parties and with single and multiple-peaked voter distribution. We find that a two party system reduces polarisation, even if voters are polarised with a bimodal distribution. By contrast, multiparty systems induce polarisation, even when most voters favour moderate position. We model the effect of turnout and activists as influences on the parties, showing that this results in more polarisation, even in a two-party system. This suggests that polarisation of parties can be driven by abstention, intra-party politics and turnout on the extremes. In the two-party case, the winning party’s positions are more moderate than the views of their supporters but better representative of the electorate as a whole. With polarisation, individual voters are better able to find a party which represents their views, but the government (winning part or coalition) is less representative of the population, even when the population has a clear consensus on all issues.
Correction: Superficial temporal artery and branches in thai cadavers: anatomical variations, ethnic considerations, and filler injection safety
ERK builds a population of short-lived nascent adhesions that produce persistent edge protrusion and cell migration
Cell migration is realized through the fast and persistent protrusion of a leading edge in the direction of movement. The actin and adhesion structures that build edge protrusions are integrated such that pro-migration signaling pathways must control both assemblies to induce protrusion. Understanding the contribution of adhesion regulation has been complicated by the inability to selectively assay the nascent adhesions that promote edge protrusion. Here, we dissect how the core RAS → RAF → MEK → ERK pathway’s control of nascent adhesions contributes to edge protrusion and cell migration by targeting an ERK FRET biosensor to adhesions and quantifying ERK’s spatial and temporal activity. We find that ERK is activated in the assembling, membrane-proximal region of nascent adhesions through adhesion scaffold paxillin, which interacts with the ERK activator MEK. Tracking nascent adhesion dynamics during cell migration showed that ERK promotes both nascent adhesion assembly and disassembly to create a population of nascent adhesions with short lifetimes. MEK inhibition is partially complemented by expression of a talin R8vvv mutant that increases the nascent adhesion population, demonstrating the significance of ERK’s adhesion regulation for edge protrusion and migration persistence. These findings suggest that when new adhesions initiate, the ERK activation level dictates adhesion assembly and disassembly rates to specifically build nascent adhesions that rapidly turn over, an adhesion population that promotes protrusion persistence and migration.
Methodological study on simultaneous detection of 6 tumor invasion and metastasis markers including MMP-9 by microfluidic chip-based magnetic particle immunofluorescence assay
Objective Conventional tumor marker detection technologies are confined to single-index sequential testing, with drawbacks like prolonged turnaround times, high sample consumption, and heavy reliance on large precision instruments. They fail to meet the needs of clinical scenarios such as point-of-care testing (POCT), primary medical institution screening, and emergency rapid assessment. This study aims to develop a multi-index simultaneous quantitative detection system, providing an efficient, convenient, and reliable technical solution for early accurate diagnosis and whole-course dynamic monitoring of tumors. Methods Leveraging the core advantages of micro fluidic chips—miniaturization, integration, and low reagent consumption—a detection platform was designed to simultaneously quantify six tumor-associated markers: matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor A (VEGF-A), soluble neural cadherin (sN-cadherin), osteoprotegerin (OPG), lysyl oxidase (LOX), and angiopoietin 2 (ANG-2). Methodological characterization included linear range verification, limit of detection (LOD) determination, precision evaluation, and specificity tests (cross-reactivity, matrix interference, and background interference). Consistency with clinical gold-standard methods was assessed via correlation analysis, Kappa test, and Bland-Altman analysis. Diagnostic efficacy was evaluated using ROC curve analysis, and detection timeliness was improved by optimizing the “two-reaction and two-washing” core process. Results All six markers exhibited excellent analytical performance: the coefficients of determination (R²) of their dose-response curves ranged from 0.9968 to 0.9993, with linear ranges of 0.012–16,000 pg/mL (VEGF-A, OPG, ANG-2) and 0.016–9,600 ng/mL (MMP-9, sN-cadherin, LOX), and limits of detection (LODs) of 0.012–0.019 pg/mL (or equivalent ng/mL units). Precision was outstanding: intra-batch relative standard deviations (RSDs) were 2.51%–5.12% for low-concentration samples and 0.88%–4.14% for high-concentration samples, while inter-batch RSDs, chip repeatability RSDs, and storage stability RSDs were all ≤ 6.76%, meeting the clinical threshold standard of ≤10%. Specificity verification showed that both cross-reactivity rates and interference rates were significant non-specific binding or matrix interference observed. Compared with the gold standard, the coefficient of determination (R²) was > 0.95, the Kappa coefficient was 0.8–1.0 (excellent agreement), and over 90% of sample deviations fell within the 95% confidence interval (CI). The area under the receiver operating characteristic curve (AUC) ranged from 0.9546 to 0.9882, with both detection sensitivity and specificity reaching 93%–98%. The detection system shortened the total detection time to 24 minutes, required only microliter-scale sample consumption, and was 5–8 times faster than enzyme-linked immunosorbent assay (ELISA)/chemiluminescence immunoassay. Conclusion The microfluidic chip system integrates high sensitivity, precision, specificity, rapidity, and miniaturization, achieving high equivalence with traditional methods. It breaks through conventional limitations, meeting clinical needs for early screening, dynamic monitoring, and large-scale surveillance, with significant clinical transformation and industrialization prospects. Future optimization will involve multi-center validation, panel expansion, and AI integration to support personalized tumor care.
APASA: adaptive selection of informative peritumoral regions for improved automated cancer lesion analysis
Tuning reductase activity in monoterpene indole alkaloid biosynthesis
Monoterpene indole alkaloids encompass a diverse class of plant natural products. Many of these valuable compounds, including the anticancer medicines vinblastine and vincristine ( Catharanthus roseus ) and the antiaddiction treatment ibogaine ( Tabernanthe iboga ) utilize a common biosynthetic intermediate, 19 E -geissoschizine, which is produced by the medium-chain dehydrogenase/reductase geissoschizine synthase (GS). Herein, we report facilitator of geissoschizine synthase (FoGS), a protein that improves formation of 19 E -geissoschizine by acting in combination with GS. The identification of a FoGS ortholog that works with GS to produce 19 Z -geissoschizine shows how this protein also enables control over product stereochemistry. We demonstrate that FoGS and GS interact to form a stable heterodimer and through mutagenesis identify FoGS residues that contribute to the combined activity of FoGS and GS. This work highlights the involvement of proteins in metabolic pathways that, when assayed alone, appear nonessential, but nevertheless increase the efficiency or specificity of a given metabolic step.
TNFR2 is expressed by a discrete subset of epidermal T cells with an IL-17 gene signature during psoriasis
Psoriasis is a chronic skin disease that results in scaly patches and affects 2–3% of people worldwide. Therapeutic treatment targets the TNF-α/IL-17 axis to disrupt keratinocyte hyperproliferation and inflammation. While more is known about the role of dermal αß and γδ T cells in IL-17 production, less is understood about the role of resident epidermal T cells. Here, we examine how TNF-α modulates epidermal γδ T cell activation and function. We show that a subset of activated epidermal γδ T cells expresses TNFR2 with or without TNFR1. Stimulation with TNF-α induces epidermal γδ T cells to produce IL-17 family cytokines and chemokines. Epidermal γδ T cells do not require TNFR1 or 2 for development or homing to the skin. Instead, TNFR2 plays roles in epidermal γδ T cell function skewing them toward a Tγδ17 phenotype during psoriasis. Investigation of the mechanisms by which TNF-α associated inflammation impacts epidermal γδ T cell function may help identify new cellular targets for immunotherapy or mark them as early regulators of skin inflammation.
Multi-objective optimization of urban blue-green space configuration using NSGA-II for enhanced ecosystem services
Oxytocin modulates the neurocomputational mechanisms engaged in learning rank relationships in social networks
Indirect evidence from preclinical and neuropharmacological studies suggests that oxytocin may attenuate social dominance relationships and modulate social memory. In humans, oxytocin may also modulate self- versus other-oriented reward learning and in-group/out-group decisions differently. Although the neural bases of learning social hierarchy by observation have been identified for linear hierarchies (a 1 < a 2 < a n ), the brain mechanisms engaged in learning more complex rank relationships (i.e. <, =, >) in social networks remain unknown. Here, we investigated the modulatory role of oxytocin on the neurocomputational mechanisms engaged when learning ranks in social networks and when making transitive inferences based on social memory retrieval. Participants learned rank relationships between members of two social networks, one in which they were embedded and the other not. During a subsequent test phase, they inferred rank relationships between pairs of members not encountered before. During training, oxytocin (vs. placebo) improved choice accuracy regarding rank relationship between pairs of members for other-oriented network and increased activity of the ventromedial prefrontal cortex. During the test phase, oxytocin modulated the balance between self/other social memory, boosting performance and amygdala responses for memory retrieval concerning social networks in which participants were not embedded. These findings demonstrate that oxytocin modulates the brain computations needed to learn and retrieve rank relationships in social networks in a manner that depends upon reference-frame.
Reporting quality of qualitative health studies published by Peruvian authors: A scoping review
Qualitative research offers valuable insights into complex social and behavioral processes in the health sciences; however, its contribution depends on the quality and transparency of reporting. This scoping review aimed to describe the methodological characteristics and reporting quality of qualitative studies published by Peruvian authors between 2022 and 2025. Following Prisma-scr guidelines, a systematic search was conducted in SCOPUS, and reporting quality was assessed using the Standards for Reporting Qualitative Research (SRQR) tool. A total of 147 qualitative studies were included. Most were published in English (49.0%), had a median of five authors; 71.4% had a first author affiliated with a Peruvian institution, and 58.5% involved exclusively Peruvian authors. Studies were mainly conducted in Lima (50.3%). Ethics committee approval was not reported in 24.5% of studies, and 40.8% did not provide an ethics approval code. Adherence to SRQR items was highest for abstracts (95.9%), study purpose (95.2%), and presentation of findings (93.9%), whereas reporting of title elements (31.3%), qualitative approach (49.0%), and researcher reflexivity (37.4%) was limited. Publication in Spanish and Peruvian first authorship were associated with lower SRQR scores, whereas a higher number of authors and international collaboration were associated with higher scores. Overall, qualitative studies published by Peruvian authors showed variable reporting quality, with important methodological and ethical aspects frequently under reported, highlighting the need to strengthen reporting practices, particularly for core qualitative components.
Two-way tuning of the decidual natural killer cells and recurrent pregnancy loss
ModBind <sub>dG</sub> : A simulation-based absolute predictor of free energy of binding based on population reweighting
Recently, we described ModBind, a powerful simulation-based predictor of ligand off-rates and binding free energy. Here, we describe an update to the method—ModBind dG —that allows for the prediction of absolute free energies of binding. ModBind dG is a two-state model for predicting free energy of binding through population-based reweighting of accelerated sampling. We demonstrate theoretically and in practice that ModBind dG can accurately predict the absolute binding free energies of small molecules binding to relevant protein targets. Additionally, we show performance enhancements to the method where ModBind dG can predict up to 2,000× more compounds per day compared to state-of-the-art free energy methods. We show that the method can make accurate predictions on validation datasets as well as active drug discovery programs in our own pipeline. Furthermore, we describe the utility of ModBind dG in a prospective virtual screen that enabled the discovery of multiple chemotypes for a previously “undruggable” protein target. ModBind dG represents an opportunity to significantly impact computational drug discovery, making rigorous physics-based screening of hundreds of thousands to millions of compounds accessible to the entire pharmaceutical community.
Longitudinal analysis of CYFRA 21-1 levels in patients with pulmonary nodules: Differential trajectories between benign and malignant cases
Background CYFRA 21−1, a cytokeratin-19 fragment, is a validated serum biomarker for non-small cell lung cancer (NSCLC). However, most studies rely on single time-point measurements, limiting its specificity in differentiating malignancy from benign pulmonary conditions. Inspired by the clinical utility of serial PSA measurements in prostate cancer, we investigated whether longitudinal trends in CYFRA 21−1 could enhance diagnostic and monitoring capabilities in patients with pulmonary nodules. Methods and Findings We analyzed 132 patients with pulmonary nodules from the Vanderbilt Thoracic Biorepository. For the primary analysis, patients who underwent treatment prior to biomarker assessment were excluded, resulting in an untreated cohort of 121 patients (91 benign and 30 malignant nodules). CYFRA 21−1 levels were measured serially using electrochemiluminescence assays. Longitudinal trends were assessed using linear mixed-effects models to estimate biomarker trajectories. Primary analyses compared benign vs. malignant nodules using longitudinal modeling of log-transformed CYFRA 21−1 values. At baseline, CYFRA 21−1 levels were significantly higher in malignant versus benign nodules. Longitudinal mixed-effects modeling did not demonstrate statistically significant differences in trajectories between benign and malignant nodules. Benign nodules showed a small positive trend in log(CYFRA 21−1) whereas malignant nodules showed greater longitudinal variability. The magnitude of change assessed using the absolute slope of log(CYFRA 21−1) was significantly greater in malignant nodules compared with benign nodules (p < 0.05). Exploratory diagnostic analysis showed that baseline log(CYFRA 21−1) achieved and AUC of 0.68 (95% CI 0.56-0.79) with sensitivity 0.63 and specificity 0.71. The absolute slope of log(CYFRA 21−1) yielded an AUC of 0.67 (95% CI 0.48-0.87) with sensitivity 0.39 and specificity 0.97. Conclusions CYFRA 21−1 exhibits substantial within-patient variability over time, with trajectories that reflect disease state and treatment. These findings suggest that longitudinal monitoring of CYFRA 21−1 may provide additional information beyond single time-point measurements in the evaluation of pulmonary nodules. Further studies in large prospective cohorts are warranted to validate these findings before clinical implementation.
Heavy metals in mining and agricultural ecotone: vertical distribution, ecological risks, and health implications
Abstract Heavy metal contamination in the mining–agriculture ecotones is influenced by lithogenic enrichment, industrial emissions, and agricultural inputs. Currently, knowledge of the vertical patterns and risk pathways in these environments is insufficient. In this study, paired soil profiles from mining and smelting areas of the manganese triangle (Xiushan, Chongqing, China) were analyzed to assess their physicochemical properties, metal concentrations, and ecological and health risks. The pH value was higher in the smelting soils (6.4–6.8) than in the mining soils (5.9–6.1). This similar trend was also observed in As and Pb, whereas contrary trend appeared in Zn and Cu. By contrast, Mn, Fe, Cr, Co, Sb, Se, and S concentrations remained stable across profiles, which indicated they had strong lithogenic controls. Pollution indices identified Sb (single-factor pollution index: < 9.15) and Cd (single-factor pollution index: 3.44–3.76) as dominant pollutants. The potential ecological risk index attributed 43.0% of the ecological risk in mining soils to Cd and 38.1% of the risk in smelting soils to Sb. Ecological risk classifications indicated moderate risks for smelting soils across depths, while mining soils exhibited greater variability with localized high-risk zones. In a human health risk assessment, the dominant contributors to carcinogenic and noncarcinogenic risks were ingestion (> 95%) and dermal contact (73%–80%), respectively, and inhalation had a negligible contribution. These results show mining- and smelting-derived metals have distinct vertical geochemical behaviors, which provides a mechanistic basis for targeted risk management in mining–agriculture ecotones.