• BMI of birth cohorts rose throughout the 20th century with three structural breaks. • BMI values accelerated with the rise of the obesogenic environment in the 1950s–60s. • Evolutionary mismatch exists between the brain’s dopamine system and the obesogenic environment. • BMI increases have tapered in the late 20th century and even plateaued in the 21st century. • The obesogenic environment has likely reached a saturation point. We estimate trends in BMI values by birth cohorts (1882-2021), stratified by ethnicity and gender using nationally representative survey data on U.S.-born individuals. BMI growth accelerated among cohorts born in the 1920s as public health improvements reduced infectious disease burdens, and again among cohorts born in the 1950s and 1960s with the emergence of an increasingly obesogenic environment. An obesogenic environment is characterized by the pervasive availability and affordability of caloriedense foods, oversized restaurant portions, excessive exposure to aggressive food marketing, and high density fast-food outlets. By the late twentieth century, BMI increases tapered at historically high levels and plateaued among children in the twenty-first century, suggesting that the obesogenic environment approached saturation. These patterns indicate that weight gain reflects persistent environmental change rather than individual choices alone. Early-life exposure to these conditions is associated with higher body weight throughout adulthood, highlighting obesity as a structural and intergenerational phenomenon.

Fructose-induced prediabetes causes persistent DNA methylation changes in white adipose tissue despite metabolic normalization.

Bladder pain significantly impacts millions worldwide, severely affecting their quality of life and posing a major clinical challenge. Understanding the mechanisms underlying persistent bladder pain is critical for developing better therapeutic strategies. In this study, we investigate the effects of cyclophosphamide (CYP)-induced persistent bladder sensitization to explore the lateralized contribution of amygdala calcitonin gene-related peptide receptors (CGRP-Rs) on pain-like changes in mice. We demonstrate that CYP induces hypersensitivity lasting up to 14 days postinjury (DPI) in the urinary bladder distention assay and up to 21 DPI when assessing abdominal mechanical sensitivity. Despite persistent pain-like changes, no significant bladder histological changes were observed. Based on previous findings that CGRP signaling from the parabrachial nucleus contributes to central amygdala (CeA) lateralization, we hypothesized that CGRP-Rs play a key role in driving visceral bladder pain-related hemispherical differences. We show that inhibiting CGRP-R activity with the antagonist CGRP 8-37, in the right CeA attenuates bladder pain-like behavior, whereas left CeA inhibition sustains CYP-induced hypersensitivity. Electrophysiological recordings revealed increased firing frequency in CGRP-R-positive cells in the right CeA 7 DPI. In vivo single photon calcium imaging demonstrated increased Ca transients in CGRP-R-positive cells in the right CeA, upon the presentation of a stimulus at 0 DPI and overall at 2 DPI, further confirming the pronociceptive role of CGRP-Rs in the right CeA. Taken together, these findings provide a crucial foundation for understanding pain-induced CeA lateralization and for further studies identifying how targeting CGRP signaling could provide bladder pain relief.

Aberrant sialylation is a persistent glycosylation change in cancer that reshapes interactions within the tumour microenvironment through the display of sialylated glycans (sialoglycans) on malignant and stromal cells. Many sialoglycans engage sialic acid-binding immunoglobulin-like lectins (Siglecs), a family of receptors expressed predominantly by immune cells that frequently transmit inhibitory signals and function as glyco-immune checkpoints. Increasing evidence indicates that tumour hypersialylation suppresses myeloid and lymphoid anti-tumour activity, promotes immune evasion, and contributes to metastatic behaviour. However, both sialoglycan repertoires and Siglec expression patterns vary markedly across cancer types and disease states, suggesting strong dependence on tissue context and tumour composition. In the present review, we discuss how tissue-of-origin programmes and lineage state establish basal sialyltransferase expression and constrain the sialoglycan landscape available to tumours. We highlight emerging single-cell evidence that stromal populations, particularly cancer-associated fibroblasts, can acquire hypersialylation and actively generate immunosuppressive Siglec ligands. We also examine how transcriptional and oncogenic regulators, including SOX2, MYC, and androgen receptor signalling, reprogramme sialyltransferase expression to produce tumour-specific sialoglycan profiles. Finally, we consider how standard-of-care therapies alter both ligand availability and immune composition, thereby dynamically modifying the sialoglycan-Siglec axis during treatment and resistance. Understanding these context-dependent determinants will be critical for interpreting sialylation in cancer biology and for designing effective therapeutic strategies targeting sialoglycan-Siglec interactions.

Metastasis remains the leading cause of cancer-related mortality and arises from ongoing interactions between malignant cells and their surrounding microenvironment. Among host factors, platelets and neutrophils have emerged as key regulators of metastatic potential. Growing evidence indicates that their coordinated activity-particularly through platelet-neutrophil aggregates（PNAs） and related mixed-cell complexes-forms an important but underrecognized pathway that promotes immune escape, vascular adaptation, and preparation of distant metastatic sites. This combination alters many critical steps in the spreading process. It includes survival within the circulation, evading the immune response, adhesion to the vessel wall and egress, and shifting target tissues. These are the result of collaborative mechanisms such as the use of soluble signaling factors, cell-cell adhesion, the NET-inflammatory response linked to coagulation, and the more persistent changes conferred by EVs and metabolism. Despite substantial progress in defining these mechanisms, important challenges limit clinical translation. Blood count-based platelet and neutrophil markers are not consistently used to assess metastatic risk across cancer types; the factors that control when and how neutrophils change functional states within tumors remain unclear; and therapeutic strategies that target platelet-neutrophil cooperation must carefully balance antimetastatic efficacy with risks such as bleeding and weakened host defense. In this review, we integrate current evidence on platelet-neutrophil-tumor interactions into a unified framework that connects biological mechanisms with clinically measurable indicators and therapeutic entry points. We examine emerging approaches to reduce metastasis supported by platelet-neutrophil interactions and NET-associated processes, consider how these strategies may complement existing cancer treatments, and emphasize the potential of combined biomarker models-such as integrating platelet measures with the neutrophil-to-lymphocyte ratio（NLR）-to improve prognostic assessment and guide future clinical validation.

Uzbekistan's cotton sector experienced a rapid increase in productivity between 2021 and 2025, during a wave of reforms that accelerated the adoption of modern cultivars and more intensive management practices. We quantified time-series trends in yield, cultivated area, technology, and economic impacts across agro-climatic zones using national production records. National average yield rose from 3.24 to 4.55 t ha-1 (+ 40.4%); total output increased by 19.3%, despite a 15.1% cut in cultivated land. Separate regression analysis suggested a two-phase fit with an inflexion around 2024, coinciding with reform measures, but formal breakpoint tests did not reach statistical significance. Over the study period, the share of planted area for advanced technologies such as RNAi- and marker-assisted selection (MAS) cultivars and imported Bt/glyphosate-tolerant (Bt/Gt) materials increased to ~ 38.51% by 2025; these technology groups achieved higher mean yields than traditional cultivars. The genotype × environment and stability analyses revealed generally consistent cultivar rankings across regions, indicating the broad adaptability of the dominant cultivars. Economic analysis also indicated that intensified systems reduced input costs and increased profitability. Taken together, these national-scale observational results document a short reform-era episode in which productivity rose despite area reduction, coinciding with rapid technology diffusion and management reform. We interpret this period as evidence of the feasibility of sustainable intensification under irrigated cotton systems, while recognising that longer time series are needed to assess persistence and long-term structural change.

The early-life intestinal microenvironment plays a pivotal role in shaping immune cell development. Here, we identify a colonic Wnt4-expressing stromal cell, enriched during early-life, that promotes iNKT cell proliferation via BMP-MAPK signaling. These stromal cells are spatially associated with iNKT cells and macrophages and exhibit high Bmp2 expression during the neonatal period. Depletion of BMP2 in Wnt4+ stromal cells during, but not after, this time window leads to long-lasting reductions in iNKT cells. These stromal cells are shaped by microbial signals, as germ-free and early-life antibiotic-treated mice exhibit increased Wnt4+ stromal cell abundance and elevated Bmp2 expression, with excessive iNKT cell accumulation that lasts into adulthood. These persistent changes in iNKT cells due to early-life perturbations are associated with altered susceptibility to later-life mucosal disorders. Importantly, similar stromal cells are present in fetal and neonatal human colon, and human rBMP2 promotes iNKT cell growth. Together, our findings reveal a neonatal colonic stromal niche, orchestrated by microbial cues, that regulates colonic immune homeostasis in later-life.

Exposure-scenario-dependent neurotoxicity and hepatic injury induced by complex byproducts from cured-in-place pipe materials.

ABSTRACTNeural oscillations are fundamental for encoding, filtering, and integrating sensory information, representing a core computational principle underlying perceptual experience. In particular, fluctuations in alpha (~7–13 Hz) and theta (~4–7 Hz) activity are associated with changes in cortical excitability and rhythmic modulations of perception. These oscillations are not static features but are highly plastic and can be shaped through neural entrainment, whereby brain rhythms synchronize with external rhythmic sensory stimulation. While short‐duration (~0.5–5 s) stimulation induces transient (~500 ms), localized entrainment effects, it remains unclear whether prolonged entrainment can produce persistent and spatially widespread modulations in ongoing neural activity. Here, we recorded resting‐state EEG before and after 1 min of visual rhythmic stimulation at individualized alpha (individual alpha frequency, IAF; IAF −2 Hz; IAF +2 Hz) and theta (4.5 Hz) frequencies. We assessed frequency‐specific and topographic effects by comparing alpha (7–13 Hz) and theta (3–6 Hz) power, frequency, and phase coherence before and after stimulation. Our results show that prolonged visual entrainment induces sustained increases in alpha power and phase coherence, persisting throughout the 1‐min post‐stimulation period without changes in frequency. Stimulation at IAF induced stronger modulations of intrinsic alpha oscillations than other frequencies, extending bilaterally from posterior to central and anterior regions. In contrast, theta stimulation increased phase consistency but did not induce persistent changes in theta power, suggesting no sustained modulation of endogenous theta activity. Together, these findings provide evidence that prolonged visual entrainment can induce long‐lasting and spatially distributed modulations of resting‐state alpha oscillations, particularly when stimulation is tuned to the brain's intrinsic resonant frequency. This highlights the frequency‐specific nature of neural responsiveness and the potential of rhythmic sensory stimulation to induce long‐lasting changes in large‐scale brain oscillatory networks.

Stability and structure of adaptive plant-pollinator networks under climate change.

Long-term alterations in serotonin transporter expression after adolescent fluoxetine exposure: Insights from the hippocampus and prefrontal cortex.

Alzheimer's disease is characterized by progressive cognitive decline, amyloid-β deposition, neuroinflammation, and neurodegeneration, yet effective and well-tolerated therapies remain limited. Because dysregulated myeloid responses are increasingly recognized as important drivers of disease progression, we investigated the therapeutic potential of poly(lactic-co-glycolic acid) immunomodulatory nanoparticles in the 5xFAD mouse model of amyloid-driven neurodegeneration. Poly(lactic-co-glycolic acid) immunomodulatory nanoparticles and fluorescently labeled particles displayed the expected size range and negative surface charge. After intraperitoneal administration, fluorescent particles were preferentially associated with myeloid cells in the blood, spleen, and brain, with greater uptake by brain myeloid populations in 5xFAD mice than in wild-type controls. Therapeutic treatment of 6.5-month-old 5xFAD mice, a stage at which behavioral abnormalities are already established, resulted in significant improvement in elevated plus maze behavior and a more modest improvement in Barnes maze performance. Flow cytometric analysis performed 9 weeks after the final treatment demonstrated persistent changes in brain immune composition, with the most prominent effects observed in P2RY12 + microglial populations, particularly the CD11c + subset, and comparatively limited sustained effects in CD11b + P2RY12 - myeloid cells. These changes were accompanied by reduced expression of activation- and disease-associated markers and lower pro-inflammatory cytokine production within microglial populations. Histological analysis further showed reduced cortical amyloid plaque burden, decreased CD68 immunoreactivity, and reduced neurodegeneration in treated 5xFAD mice. Together, these findings show that systemically administered poly(lactic-co-glycolic acid) immunomodulatory nanoparticles produce durable behavioral, immunological, and pathological benefits in 5xFAD mice and support further investigation of this biodegradable myeloid-targeted platform as a therapeutic strategy for Alzheimer's disease.

Tubeless insulin pumps, introduced in France in 2016, have been associated with higher user satisfaction than tubed pumps, primarily due to reduced interference with daily tasks. Whether this translates to greater treatment persistence remains uncertain. This study evaluates persistence among people with type 1 diabetes initiating tubed or tubeless pump therapy in France. This real-world, retrospective study used data from the French National Health Data System, a comprehensive medical claims database for the entire French population from 2016 to 2021. Treatment persistence was assessed using Kaplan-Meier curves and Cox models. Changes from one pump type to another were compared across calendar years using χ2 tests. Among 1 241 624 people with insulin claims, 233 874 had type 1 diabetes. Of these, 39% (n=90 362) initiated insulin therapy during the study period; 32% started and remained on multiple daily injections (excluded), and 68% initiated pump therapy. Among pump users (n=61 251), 51% used a tubed pump, 67% a tubeless pump, and 18% initiated both types sequentially. People initiating tubeless compared with tubed pumps had higher persistence rates (unadjusted HR 0.60, 95% CI 0.58 to 0.61) and a 40% lower risk of discontinuation (p<0.0001), consistent with the adjusted model (HR 0.59, 95% CI 0.57 to 0.61). Tubeless pumps were also associated with fewer changes from one therapy to another within 12 months. Treatment changes rose for tubed pump users after tubeless pumps entered the French market. Higher persistence and lower therapy changes among tubeless pump users underscore its sustained benefit for diabetes management.

Chronic ankle instability is associated with persistent biomechanical changes including a lateral center of pressure (COP) location during stance. Gait retraining studies generally show COP location improvements. Multiple COP processing techniques are available which may impact results. Therefore, the purpose of this study is to identify the impact of processing technique on the COP location during baseline walking and in response to intervention in people with chronic ankle instability. Cohort Study. Participants with chronic ankle instability walked on an instrumented treadmill for 2minutes (baseline), completed a vibration feedback gait retraining session, and then completed a posttest treadmill trial with no feedback. The COP location was filtered using a fourth-order Butterworth filter with a 10-Hz low-pass cutoff. Processing techniques included bounding COP data within the foot: (1) relative to the border of the lateral foot in the medial-lateral plane (Straight-Plane Technique) and (2) relative to the midline of the foot which changes with foot progression angle (Foot-Progression-Angle Technique). 1D statistical parametric mapping paired ttests were completed on absolute change scores at baseline between techniques and between baseline and posttest for each of the techniques. Absolute COP change scores at baseline between processing techniques were statistically different from 5% to 44% of stance phase while walking. Baseline to posttest COP locations were statistically different from 4% to 62% of stance phase (P ≤ .01) when processed with the Straight-Plane Technique. No statistically significant difference was identified using the Foot-Progression-Angle Technique. Interpretations of COP location and COP location changes could be impacted by processing techniques with differing reference coordinate systems. New insights into processing techniques could impact interpretations of previously published work and should be considered before comparing across studies to make broad generalizations related to the COP location.

Various pathologic conditions can cause oral mucosal changes. However, data regarding the prevalence and sociodemographic distribution of oral mucosal changes are insufficient. The 6th German Oral Health Study (DMS • 6) not only provides cross-sectional analyses of oral mucosal changes but also longitudinal analyses after a 9-year follow-up. For cross-sectional analysis, data from 797 younger seniors (65- to 74-year-olds) from the DMS • 6 cross-sectional component were employed. Longitudinal analysis was performed on data from the DMS • 6 senior cohort including 373 participants from 2014 (baseline) who were reexamined in 2023 (follow-up). The most frequent oral mucosal changes were documented based on the DMS V protocol. Each lesion was photographed and verified by two independent experts, and no other diagnostic tests were performed. Among younger seniors, the overall prevalence of oral mucosal changes was 13.3%. Furthermore, the prevalence of leukoplakia was 4.3%. These rates are consistent with those previously reported. Regarding gender distribution, men were affected more frequently than women. Longitudinal analysis revealed that the majority (68%) of oral mucosal changes detected at baseline were not detected at follow-up. However, three participants showed persistent prosthesis-related changes. Approximately 10% of those who were healthy at baseline presented one or more incident oral mucosal changes over the observation period. In detail, 2.8% developed new serious lesions (carcinomas and leukoplakias). The progression of oral lichen planus and smoker's keratosis could not be determined because individuals with these findings in previous studies were no longer part of the longitudinal sample. Documentation of malignant lesions plays an important role in research and for those affected. However, non-malignant lesions, such as leukoplakia, oral lichen planus, and smoker's keratosis should also be documented in epidemiologic studies, particularly their risk of degeneration and correlation with tobacco consumption. (Quintessence Int 2026;57(Suppl):S76-S81; doi: 10.3290/j.qi.b6955533).

Cardiopulmonary bypass (CPB) is an essential technique for cardiac surgery but significantly increases the risk of perioperative neurological complications. Electroencephalography (EEG) enables real-time monitoring of brain function and provides sensitive biomarkers for early detection of cerebral injury. However, a systematic synthesis of how CPB-related physiological, pharmacological, and technical factors influence EEG signals, and how these insights can be integrated into clinical decision-making, is still lacking. To systematically review the effects of temperature management, mean arterial pressure (MAP), hemodilution, anesthetic agents, embolization, and systemic inflammatory response during CPB on EEG parameters (including frequency bands, Bispectral Index (BIS), quantitative EEG metrics such as burst suppression ratio (BSR), spectral edge frequency (SEF), etc.), and to evaluate the associations between EEG changes and postoperative delirium (POD) and stroke. Following the PRISMA 2020 guidelines, we searched PubMed, Web of Science, and related databases for original English-language articles published between February 1974 and September 2025. adult patients (≥18 years) undergoing cardiac surgery with CPB and intraoperative EEG monitoring (raw or processed). reviews, case reports, animal studies, pediatric populations, and articles with inaccessible full texts. Two reviewers independently screened the literature and extracted data; a narrative synthesis was performed. Fifty-one studies were included. (1) Hypothermia: BIS decreases linearly with temperature (≈1.12 units/°C); electrocerebral silence occurs during deep hypothermic circulatory arrest; EEG recovery dynamics during rewarming predict POD. (2) MAP and cerebral perfusion: The rate of MAP decline (≥0.66 mmHg/s) is a stronger predictor of EEG abnormalities than the absolute MAP value; under fixed pump flow, some patients exhibit coexisting cerebral overperfusion and metabolic suppression. (3) Hemodilution: Maintaining hemoglobin ≥9.4 g/dL prevents EEG slowing; a drop below 9.2 g/dL significantly increases the risk of slowing. A ≥10% decrease in regional cerebral oxygen saturation (rSO2) is associated with a 1.5-fold increased risk of burst suppression. (4) Anesthetic agents: Propofol maintains flow-metabolism coupling, and BSR reflects deep anesthesia better than BIS; sevoflurane and isoflurane impair autoregulation and suppress EEG. (5) Embolization and inflammation: EEG epileptiform discharges increase the risk of POD five-fold; a decrease in LIR predicts stroke (AUC 0.771) and POD (AUC 0.779); persistent EEG changes increase the risk of POD 2.65-fold. CPB-related factors affect EEG signals through distinct mechanisms, and specific EEG patterns (slowing, burst suppression, asymmetry, epileptiform discharges) are significantly associated with postoperative neurological complications. Multimodal monitoring (EEG + cerebral oximetry + hemodynamics) with clear intervention thresholds facilitates individualized brain protection. Future interventional studies using real-time EEG feedback are needed to confirm improvements in long-term neurological outcomes.

Environmental variation can induce phenotypic changes through adaptation of populations and acclimation of individuals. While genetic adaptation creates persistent change within a population via allele frequency shifts, reversible plastic phenotypes can be inherited through non-genetic mechanisms, independent of DNA sequence change. Most transgenerational plasticity studies in animals examine generations where embryonic or germline exposure to environmental cues cannot be definitively excluded. Empirical evidence for persistence definitively beyond this critical threshold in animals remains scarce, particularly for morphological defenses induced by vertebrate predators. We measured phenotypic effects of vertebrate predator exposure in the clonally reproducing water flea, Daphnia lumholtzi, isolating environmental effects from genetic variation. We exposed the G0 generation to fish conditioned media, then measured morphological defenses in definitively unexposed G3, G4, and G5 generations, characterizing the temporal dynamics of non-genetic inheritance. Predator-induced morphologies persisted through G4 before receding in G5, demonstrating that non-genetic effects extend well beyond the embryonically exposed G1 and germ cell exposed G2 generations. This provides rare empirical evidence for transgenerational plasticity lasting through G4, without confounding genetic variation. We also examined ontogenetic patterns of somatic and defensive trait development, revealing trait-specific temporal dynamics in transgenerational effect expression and decay. These results highlight how current and ancestral environments interact to determine phenotypic variation across generations and underscore the ecological significance of non-genetic inheritance in natural populations, particularly for understanding population responses to environmental change and predator reintroduction.

The de Winter electrocardiographic (ECG) pattern is considered an ST-elevation myocardial infarction (STEMI) equivalent and is most commonly associated with acute proximal left anterior descending (LAD) occlusion. However, de Winter-like anterior ST-T morphology may occur without complete LAD occlusion and may coexist with multivessel coronary artery disease; therefore, ECG-angiography correlation is essential. A 60-year-old male with type 2 diabetes presented with 2h of exertional chest discomfort accompanied by dizziness, diaphoresis, and fatigue. Initial ECG showed inferior ST-segment elevation (II, III, aVF) with concomitant de Winter-like changes in the precordial leads (V2-V6). Based on the inferior STEMI criteria, emergent coronary angiography was recommended, but the patient declined immediate percutaneous coronary intervention and received conservative medical therapy. Delayed angiography on day 4 demonstrated near-total mid-right coronary artery (RCA) occlusion (culprit lesion) and severe proximal LAD stenosis without complete occlusion. PCI with stent implantation was successfully performed in the RCA. The patient remained haemodynamically stable and was discharged with a plan for staged LAD revascularisation after clinical stabilisation, although no definitive intervention timing was documented during 1-month follow-up. At follow-up, clinical recovery was favourable, with persistent ECG changes and mildly impaired left ventricular diastolic function. This case demonstrates that de Winter-like anterior ECG morphology may coexist with inferior STEMI in multivessel coronary artery disease. Such morphology should not be interpreted in isolation as evidence of LAD occlusion, but integrated with angiographic findings and the overall ischaemic context. When inferior STEMI criteria are present, standard emergent reperfusion pathways should be prioritised irrespective of concurrent anterior ST-T morphology.

Environmental time-activity patterns from 2019 to 2025: changing patterns of exposure to different environments depend on work status and job type.

A rare case of breakthrough tick-borne encephalitis in early adolescence after vaccination with four doses of TBE vaccine.