Pandey N et al. · Jul 1, 2026
Background and aims Increasing reports of plastic accumulation in human tissue have raised concerns about potential adverse health outcomes. Evidence of negative effects of nanoplastics is heterogeneous and provides limited insights into the underlying pathogenic toxicity mechanisms in humans. Methods In the present study, carboxylate-modified fluorescently labelled polystyrene nanoparticles (PS NPs) were used to investigate uptake and cytotoxicity in three different hepatic models of varying complexity, including HepG2 cells, IHH cells, and human precision-cut liver slices (hPCLS). Results The results show model- and dose-dependent effects on hepatocytes. 74.2% ± 13.4% of the IHH cells showed PS NPs uptake at 0.1 μg/mL, which is considerably lower than the estimated plastic concentration in human blood (1.8-4.7 μg/mL). The viability of IHH cells decreased to 10.6% ± 9.1% after exposure to 100 μg/mL for 48 h. Early signs of hepatic injury were found in hPCLS at high concentrations. No changes were observed in the redox state and mitochondrial respiratory parameters of HepG2 cells after exposure. Conclusion The PS NPs exposure experiments show uptake across all three hepatic models and toxic effects in IHH cells and hPCLS. Overall, the study highlights the need for physiologically relevant human tissue models to understand the impact of nanoplastic pollution on human health.
Environmental Science
Atzori S et al. · Jul 1, 2026
Backgrounds and aims Ultrasound-based spleen stiffness measurement (SSM) is a valid non-invasive tool to assess portal hypertension (PH) in chronic liver disease. Whereas the role of the respiratory phase during liver stiffness measurements is established, no study has specifically addressed how respiration influences SSM by transient elastography. Aims To evaluate the influence of respiration on SSM assessed with FibroScan 630 (Echosens, Paris, France). Methods Eighty-three patients with chronic liver disease of different aetiologies underwent SSM using vibration-controlled transient elastography (VCTE). Results SSM acquired during a normal respiratory cycle showed better diagnostic accuracy than measurements obtained during breath-hold after deep inspiration (AUROC 0.835 [95% CI 0.743-0.928] vs. 0.798 [95% CI 0.697-0.899]). Conclusion SSM by VCTE should be performed during quiet breathing, as it showed good diagnostic accuracy for predicting the presence of oesophageal varices (OV) in patients with chronic liver disease.
Medicine
Wiering L et al. · Jul 1, 2026
Metabolic dysfunction-associated steatotic liver disease (MASLD), a major public health concern, is influenced by an interplay of genetic, environmental, and lifestyle factors, with socioeconomic factors functioning as important upstream determinants whose roles remain not yet fully understood. This review synthesizes current evidence on how different indicators of socioeconomic status as well as related social determinants of health-income, poverty, food insecurity, health insurance, education, migration, and composite indices-relate to MASLD prevalence, severity, and outcomes across different world regions. Several studies associate these socioeconomic factors with an increased risk of MASLD, illustrating the disease's link with socioeconomic disadvantages. However, socioeconomic factors often lose or attenuate their independent association with MASLD once key downstream determinants-such as diet quality, physical inactivity, and metabolic comorbidities-are considered, supporting a model in which socioeconomic factors mainly shape exposure to metabolic and behavioural risk factors rather than exerting a direct causal effect. Among the factors examined, education and food insecurity demonstrate the most consistent independent associations with MASLD. Notably, the direction of socioeconomic gradients appears to differ by regional income level, with lower SES associated with higher MASLD burden in high-income countries but an inverse pattern in several middle-income settings. Evidence remains largely limited to the United States, Europe, and a small number of Asian cohorts, underscoring the need for more geographically diverse research. This review highlights the association of different socioeconomic factors with MASLD, while also revealing the need for more detailed studies which systematically disentangle individual and area-level social determinants of health, model mediating pathways and incorporate underrepresented regions and paediatric populations. A deeper understanding of how socioeconomic factors and downstream mediators jointly drive MASLD could inform targeted clinical strategies and multi-level policies aimed at mitigating the social gradient in MASLD.
Medicine
Fortis HO et al. · Jul 1, 2026
Endurance competition preparation involves complex psychological, logistical, and sociocultural factors. This study investigated the pre-race nutrition practices of female endurance athletes, by applying a newly developed extended Theory of Planned Behaviour, including behavioural execution to the framework to capture real-world influences (ETPB-X). Using a convergent mixed-methods design, 27 female triathletes competing at the 2024 IRONMAN World Championships completed questionnaires, 48-h food diaries, and semi-structured interviews before and after the race. Quantitative data (n = 23) were analysed for energy and macronutrient intake, whereas qualitative data were thematically coded using the conceptual ETPB-X framework, incorporating attitudes, subjective norms, perceived behavioural control (PBC), utilitarian drivers, and behavioural execution. Only 26% (6/23) of athletes achieved carbohydrate loading guidelines (8-12 g·kg -1 body mass (BM)·day -1 ), with an overall mean intake of 6.4 ± 2.1 g·kg -1 BM. Higher carbohydrate intake correlated with faster finish times (r = -0.50, p = 0.035), whereas fibre intake was positively associated with gastrointestinal (GI) symptom severity (r = 0.85, p < 0.001). Qualitative findings revealed that adherence to diet plans was influenced by PBC, travel logistics, emotional regulation, and athlete identity. This study provides a novel application of the ETPB-X framework to pre-race nutrition in female endurance athletes. Athletes often under-achieve carbohydrate loading targets despite awareness, with success determined as much by psychosocial and contextual factors as by knowledge. Practically, enhancing PBC, improving planning/preparation, and delivering clear goal-aligned education may bridge the intention-behaviour gap. Integrating behavioural frameworks into performance nutrition offers a pathway towards more effective athlete-centred interventions.
Biochemistry, Genetics and Molecular Biology
Marinko S et al. · Jul 1, 2026
Introduction Many patients do not benefit from cardiac resynchronization therapy (CRT) with current guideline parameters. The objective of this study was to examine the relationship between left ventricular activation time (LVAT) from the standard 12-lead surface electrocardiogram (ECG) and clinical outcome from CRT. Methods A retrospective study was performed on patients receiving CRT implants at a large-volume tertiary care center. Digital ECGs were collected pre- and post-implant. LVAT was defined as the time from QRS onset to maximum deflection in lead V6. The primary combined endpoint was heart failure hospitalization or all-cause mortality. Results The study group comprised 415 patients (median age [Q1-Q3] of 72.8 years [65.1-78.7], 77.3% male, median baseline LVEF 27.5% [22-30], and 43.1% with ischemic heart failure etiology) who were followed for up to 7.6 years (median 2.8). LVAT was measured pre-implant (median 78 ms [66-98]) and post-implant (median 88 ms [74-106]). In Kaplan-Meier analysis, a longer pre-implant LVAT was associated with a reduced risk of reaching the primary endpoint in patients with LBBB (log-rank p = 0.046). Post-implant LVAT was not associated with clinical outcome. Conclusion Our results show that a longer baseline LVAT is associated with a lower risk of heart failure hospitalization and all-cause mortality. This relationship was of borderline significance in multivariable analysis. Prospective trials would be useful to further explore the potential role of pre-implant LVAT in patient selection for CRT.
Medicine
Soendenbroe C. · Jul 1, 2026
Muscle fibre denervation describes the loss of effective neural input from a motor neuron to one or more muscle fibres. In ageing, denervation is increasingly recognised as an important contributor to progressive declines in muscle strength and functional capacity, yet it remains heterogeneous and difficult to define in humans. This ambiguity reflects both biological complexity and current methodological limitations. The purpose of the present review is to synthesise current human evidence for muscle fibre denervation in ageing, clarify key conceptual distinctions, and evaluate methodological approaches used to assess denervation in humans. Muscle fibre denervation can occur through structural disconnection of the motor neuron from the fibre or through functional impairment of neuromuscular transmission. Evidence for denervation in ageing is derived from histological, molecular, electrophysiological, and circulating biomarker approaches, each capturing distinct and only partially overlapping aspects of neuromuscular integrity. Importantly, no single measure provides a comprehensive assessment of denervation. Experimental models of disuse in humans reveal a functional denervation phenotype, characterised by molecular and electrophysiological changes that partially resemble those observed with ageing. Physical activity appears to mitigate against aspects of muscle fibre denervation; however, the mechanisms underlying these effects remain incompletely understood. Collectively, the available evidence indicates that denervation in ageing is a multifaceted and dynamic process that requires multimodal, longitudinal approaches to define, detect, and ultimately target denervation-related mechanisms to preserve neuromuscular function across the human lifespan.
Biochemistry, Genetics and Molecular Biology
Yuan Q et al. · Jun 24, 2026
Objective Adenosquamous carcinoma (ASC) of the lung, containing both adenocarcinoma (AC) and squamous cell carcinoma (SCC) components, is associated with aggressive behavior and poor prognosis. Due to overlapping imaging features with AC and SCC, its preoperative diagnosis remains challenging. This study aimed to compare CT and pathological characteristics among ASC, AC, and SCC; identify key differentiators. Methods This retrospective study included 27 patients with pathologically confirmed ASC who underwent surgical resection from November 2018 to January 2025. Forty cases each of AC and SCC, matched for age, sex, and smoking history, were selected for comparison. Clinical, radiological, and pathological features were analyzed. Variables with statistical significance (P Results Compared with SCC, ASC lesions were more peripheral and associated with higher distance ratios (DR), pleural retraction, spiculation, and lymph node metastasis (LNM). Compared with AC, ASC tumors were larger, more often solid, and exhibited lobulation, bronchial cutoff sign, and advanced staging. Among the evaluated analyses, the combined pathology-imaging approach showed the highest discriminatory performance, with AUCs of 0.909 (ASC vs SCC) and 0.900 (ASC vs AC). LNM and DR were more strongly associated with ASC relative to SCC, whereas larger tumor size, ill-defined margins, and advanced stage were more strongly associated with ASC relative to AC. Conclusion Certain CT imaging features, especially DR and LNM, were associated with ASC and may provide useful information for preoperative radiological assessment and subtype stratification.
Medicine
Sapkota S et al. · Jun 24, 2026
Crown rust, caused by the fungal pathogen Puccinia coronata f. sp. avenae (Pca), is a destructive foliar disease of oat. Use of host resistance is the preferred method of disease management. However, frequent emergence of new Pca races has hindered crown rust management in oat. Identification and deployment of non-race-specific genetic resistance will aid oat breeding efforts to develop germplasm with durable crown rust resistance. To map and characterize crown rust resistance, a recombinant inbred line (RIL) population was developed from a cross between LA07065_SBSBSB_32-2 and CDC Dancer and evaluated for crown rust reaction in four field environments for two years. The RIL population was genotyped using the oat 6K Infinium iSelect single nucleotide polymorphism (SNP) array and a total of 956 polymorphic SNP markers were used to construct the linkage map. Quantitative trait loci (QTL) mapping detected a total of six QTL on chromosomes 2D, 4A, 7A, 7C, and 7D influencing crown rust resistance. Two of these QTL were validated using genotype-phenotype association analysis in an independent set of oat lines. The identified QTL demonstrated additive effects on crown rust resistance within the RIL population. A major QTL on chromosome 7C, QPca-ars-7C, was detected consistently across environments and explained up to 16.54% of the phenotypic variation. Markers linked to QPca-ars-7C, and other QTL detected in this study have the potential to be used in marker-assisted selection for crown rust resistance.
Agricultural and Biological Sciences
Shearer JJ et al. · Jun 23, 2026
Background Heart failure (HF) is a complex syndrome with high mortality. Proteomics risk scores have shown promise in predicting mortality beyond guideline-recommended clinical tools. It is crucial to understand how risk scores generated by different methods and populations perform, and whether they highlight the same protein targets relevant to outcomes. Methods To examine whether the study design impacts proteomics scores designed to predict mortality in HF, we evaluated three published risk scores that used the SomaScan assay to measure plasma proteins in a community cohort, clinical trial, and registry. Each score was assessed in the aforementioned community cohort and Cox models examined the association of a 1-standard deviation increase in score with mortality, with and without adjustment for clinical covariates. Performance of each risk score to predict 5-year mortality risk was assessed using calibration plots and time-dependent area under the curve and compared with a clinical model. Results Risk scores were similarly distributed and moderately correlated (Pearson correlation coefficient = 0.59-0.76). A 1-standard deviation increase in each risk score was associated with an increased risk of all-cause mortality: community cohort (HR = 2.70, 95% CI: 2.50-2.91); clinical trial (HR = 1.76, 95% CI: 1.65-1.88); registry (HR = 1.70, 95% CI: 1.6-1.81). Risk remained after adjustment for clinical covariates, although slightly attenuated, and similar across different ejection fraction categories. All risk scores showed strong calibration across the risk levels, alone, with an average expected over observed ratio ranging between 0.96-1.56. Seven proteins were included in at least two risk scores, with renin being included in all three. Conclusions All three proteomics risk scores improved risk stratification in HF patients beyond guideline recommended clinical tools, independent of study design and ejection fraction. These results demonstrate that proteomics risk scores can enhance risk stratification across the HF syndrome, even when derived from different methods and populations.
Chemistry
de Boer RJ et al. · Jun 22, 2026
Patients infected with life-threatening multi-drug resistant (MDR) bacteria have been treated with cocktails of bacteriophages. This is a complicated form of personalized medicine as the phages given to a patient have to be selected beforehand on the basis of their lytic capacity of the infecting bacteria. Because bacteria rapidly become resistant, the evolution of resistance to a diverse cocktail of phages is a complicated dynamical process, during which competing bacterial strains replace one another by accumulating several resistance mechanisms, each of which may involve a fitness cost. As a consequence, it is typically not known why a particular phage therapy succeeded or failed, and how one can optimize the composition of the cocktails to maximize the rate of success. To improve upon this, we extend an existing in vivo-calibrated mouse model into a novel mathematical model for the human situation, and include multiple phages infecting multiple bacterial strains, differing in their resistance to each of the phages. We adjust several parameter estimates of the bacterial model to the human situation, and use the model to describe a successful case of phage therapy involving several cocktails, each containing several phages. In the model, treatment success crucially depended on pretreatment resistance levels, and on the diversity and the timing of the cocktails. Once an appropriate cocktail is found, it is less important to further optimize the infection rates of the phages. Resistant bacterial strains expand rapidly when sensitive strains decline, and the higher the infectivity of the phages, the faster resistant strains expand. Because resistance evolves rapidly, it is best to provide a diverse set of phages right from the start of therapy, i.e., to hit hard and early, and create a high genetic barrier to bacterial resistance.
Environmental Science