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UC-MSCs prevent cigarette smoke-induced early cellular senescence like phenotype in bronchial epithelial cells via the SIRT1/PGC-1α pathway

Abstract Chronic obstructive pulmonary disease (COPD) is an age-related chronic disease, and most of the patients are elderly. Smoking is the main pathogenic factor, and the course of disease continues to develop. Cigarette smoke exposure leads to mitochondrial dysfunction and activation of cellular senescence. Umbilical cord mesenchymal stem cells (UC-MSCs) play a significant role in mitochondrial protection, airway repair and tissue regeneration.SIRT1/PGC-1α is a key regulator of mitochondrial function and cellular senescence. Therefore, this study aims to explore whether UC-MSCs can improve cigarette smoke extract (CSE)-induced mitochondrial dysfunction and cellular senescence in bronchial epithelial cells by activating the SIRT1/PGC-1α pathway. In vitro results show that: (1) CSE induced mitochondrial dynamic imbalance, leading to mitochondrial dysfunction and ROS accumulation, which induced cellular senescence. (2) UC-MSCs activate the SIRT1/PGC-1α pathway and significantly reduce the expression of markers related to cellular senescence and improving mitochondrial function after CSE induction. (3) The SIRT1 inhibitor EX527 reversed the protective effect of UC-MSCs. This study, for the first time, reveals that UC-MSCs can improve CSE-induced mitochondrial dysfunction and cellular senescence in bronchial epithelial cells by activating the SIRT1/PGC-1α pathway. It provides a new target for COPD treatment and a strategy for slowing the progression of the disease.

Modular synthesis of trisubstituted olefins and 1,3-dienes from renewable alcohols via ligand-enabled nickel catalysis

Reply to Hojný et al.: Fusion-driven vs. fusion-negative high-grade endometrial stromal sarcoma

Progression of radial tears in L5-S1 intervertebral disc depends on location and type of movements: An in-silico study

Low back pain is a global health challenge, with disc degeneration and annular tears contributing significantly to its onset and persistence. This numerical study evaluates how degeneration and the location of radial tears jointly influence the mechanical behavior of the L5–S1 spinal unit during flexion, extension, and lateral bending. A subject‑specific finite element (FE) model employing an anisotropic hyperelastic formulation was used to simulate healthy, mild, and moderate degeneration, along with radial tears spanning 75% of the annular width at four clinically relevant locations. Quantitative stress analysis revealed pronounced movement–tear location specificity, with posterior tears exhibiting approximately 4-6x higher boundary stresses during flexion, whereas anterior tears demonstrated 1.5-2x higher stresses during extension relative to other tear locations. Posterolateral (PL) tears exhibited their highest stresses during lateral bending, with PL1 (posterior‑shifted PL tear) showing 2-3x higher values and PL2 (more lateral PL tear) reaching 3-5x higher stresses compared to sagittal motions. Degeneration shifted the dominant stress contribution in PL2 from contralateral to ipsilateral lateral bending at the tear site, concurrently amplifying stress magnitudes in flexion and extension without altering the motion-dependent vulnerability patterns associated with each tear location. These findings offer biomechanical insights into how tear location and degeneration affect tear progression and may help guide clinicians in tailoring movement‑specific conservative or interventional treatment strategies.

Hybrid deep learning framework for cardiovascular risk prediction in post-COVID-19 patients

Context-dependent interplay of Swi-Snf and Tup1-Cyc8 influences chromatin and transcription at antagonistically regulated genes

Study Protocol for “Exploring the safety and therapeutic potential of psilocybin in the treatment of anorexia nervosa in adolescents and young adults”

Background Anorexia nervosa (AN) is a severe psychiatric disorder with high morbidity, mortality, and relapse rates, most commonly emerging during adolescence. Despite specialized psychological and nutritional treatments, outcomes remain suboptimal, with high rates of relapse and chronicity. Psilocybin has been investigated with preliminary efficacy in other psychiatric conditions characterized by rigidity and treatment resistance, but clinical evidence in AN—particularly in adolescents—is limited. Objective The psiAN study aims to evaluate the safety, tolerability, and feasibility of psilocybin therapy combined with psychological support in adolescents and young adults with relapsing AN, while exploring clinical, experiential, and neurobiological correlates of change. Methods A phase IIa, open-label, randomized controlled trial enrolling individuals aged 16–35 years with DSM-5 AN and a history of relapse. Participants are randomized to receive either two administrations of psilocybin (25 mg) with manualized psychological support plus treatment as usual (TAU), or TAU alone. Primary outcomes focus on safety and tolerability, assessed through adverse events, psychiatric monitoring, and medical parameters measured from first dosing to primary endpoint. Secondary outcomes include change in eating disorder symptom severity, relapse composite measures, mood, well-being, personality traits from baseline to primary endpoint with follow-up to 12 months. Functional magnetic resonance imaging (fMRI) and peripheral brain-derived neurotrophic factor are included as exploratory mechanistic measures. fMRI will evaluate pre- to post-intervention changes in structural and functional connectivity and task-related responses during a simplified Monetary Incentive Delay task (MIDT) and a Calorie-Cue Task (CCT). ClinicalTrials.gov Identifier: NCT07169747. Ethics and dissemination The study follows Good Clinical Practice (GCP), the Declaration of Helsinki, and EU Clinical Trials Regulation requirements, with staged inclusion of adolescents (16–17-year-olds) after a safety board review of adult data (18–35-year-olds). This protocol was prepared with reference to the SPIRIT 2025 guidelines (Chan et al., 2025) to enhance transparency and inform future trials.

Effect of EPS geofoam inclusion parameters on the structural performance of rigid box culverts under induced trench installation

Abstract Buried rigid box culverts are widely used in transportation and water structures and are often constructed beneath high embankments. Due to the stiffness contrast between the rigid structure and surrounding backfill soil, the soil column directly above the culvert experiences smaller settlement than adjacent soil columns, which may result in stress concentration and increased vertical pressure on the culvert. The induced trench installation (ITI) method was introduced to mitigate this problem by adopting a compressible inclusion above the structure to initiate positive soil arching and redistribute the loads away from the culvert. This study investigates the influence of expanded polystyrene (EPS) geofoam inclusion parameters on the structural behavior of buried rigid box culverts through a series of experimental tests. Eleven reduced-scale laboratory model tests were conducted, including one reference test without EPS and ten tests incorporating EPS inclusions with varying densities, thicknesses, widths, and installation locations. Static surface loading ranging from 20 to 140 kPa was applied using a rigid footing system, while vertical pressures within the backfill were monitored using miniature pressure sensors installed above and beside the culvert. The results show that EPS inclusion significantly alters the load transfer mechanism within the backfill and promotes the development of positive soil arching. Among the investigated parameters, EPS thickness had the most pronounced influence on stress reduction, increasing the pressure reduction efficiency from approximately 50% to about 70% as the thickness increased from 2.5 cm to 10 cm. A lower EPS density also slightly enhanced stress reduction due to its higher compressibility. The findings demonstrate that properly configured EPS geofoam inclusions can effectively reduce vertical stresses acting on buried rigid culverts and improve their structural performance under embankment loading conditions.

Peripheral editing of polyols to chiral alkanes

Modeling diurnal Temperature-Rainfall relationships under multicollinearity using PLS-SEM: A case study of Ghana

Rainfall variability in tropical climates is influenced by interacting thermal processes, yet maximum (TMAX) and minimum (TMIN) temperatures are often highly collinear, complicating the estimation of their distinct relationships with precipitation. This study applies Partial Least Squares Structural Equation Modeling (PLS-SEM) to long-term station-based climate data from Ghana (1981–2020; N = 252 station × calendar month observations) to examine structural associations among TMAX, TMIN, and rainfall (RAIN), including differences between coastal and inland regimes. The model represents a simplified component of the broader hydroclimatic system. The results indicate a statistically significant negative association between TMAX and rainfall ( β  = −0.454, p < 0.001) and a positive association between TMIN and rainfall ( β  = 0.166, p < 0.001). The relationship between TMAX and TMIN is positive but not statistically significant ( β  = 0.152, p = 0.053). Mediation analysis does not support a significant indirect pathway from TMAX to rainfall via TMIN ( β  = 0.025, p = 0.076). The model explains 21.1% of rainfall variance. Multi-group analysis reveals spatial heterogeneity, with a stronger negative TMAX-rainfall association inland ( β  = −0.721) than along the coast ( β  = −0.427), and a stronger TMAX-TMIN association in coastal regions ( β  = 0.753 vs. 0.337). The findings suggest that TMAX and TMIN exhibit distinct statistical relationships with rainfall that vary across climatic regimes. However, given the limited variables and observational design, the results should be interpreted as structural associations rather than definitive physical mechanisms. The study demonstrates the utility of PLS-SEM for handling multicollinearity and interdependent relationships in climate data while highlighting the need to incorporate additional atmospheric variables to improve explanatory depth.

The Use of Botulinum Toxin Type A in Esophageal Atresia Management: a Randomized, Controlled, Investigator-blinded Feasibility and Exploratory Trial in Piglets

Abstract Anastomotic strictures and leaks are severe complications following esophageal atresia (EA) repair. We hypothesized that esophageal injections of botulinum toxin type A (BTX-A) could mitigate these complications through muscle relaxation. This randomized, controlled, blinded animal trial evaluated the feasibility and safety of a long- and short-gap porcine EA model. Furthermore, the effect of BTX-A as a surgical adjunct on anastomotic outcomes were exploratory assessed. Twenty-four animals received BTX-A or saline pre- or intraoperative to a three- or one-centimeter esophageal resection and primary anastomosis. The primary feasibility endpoint was animal completion rate at postoperative day 14, while stricture severity was the primary exploratory outcome. Secondary exploratory outcomes were anastomotic leakage frequency, and biomechanical and histological characteristics. Animal completion rate was 62.5% (15/24). There was no difference in stricture severity between the intervention and control groups (Esophageal Anastomotic Stricture Index 0.41 [IQR 0.26–0.55] versus 0.35 [IQR 0.27–0.58]; p  = 0.73). One animal in the control group suffered an anastomotic leak. Biomechanical properties and anastomotic healing did not differ. While the procedure was technically feasible, refinement is necessary to reduce attrition rate and establish a safe model for long-term evaluation. More studies are needed to determine whether BTX-A can provide a reduction in anastomotic complications.

Propagating slow-mode shocks discovered in dynamical solar flare loops

Data-driven classification and design of bioactive cellulose acetate electrospun films for active food packaging

The development of bio-based food packaging materials is increasingly important for reducing reliance on petroleum-based plastics. For practical packaging use, these materials must also achieve suitable mechanical performance, including strength, flexibility, and stiffness. This study reports the fabrication of bioactive cellulose acetate (CA) films containing aloe vera gel (AG) and lemongrass essential oil (EO) using electrospinning, aimed at developing mechanically robust films with potential relevance to active food packaging applications. Mechanical performance was systematically assessed across 11 formulations generated by a Latin Hypercube Design. Tensile strength (TS), elongation at break (EAB), and Young’s modulus (YM) were measured, and response surface methodology was employed to model the effects of CA, AG, and EO, including their interactions. CA emerged as the primary determinant, improving TS and YM but reducing EAB at higher concentrations. AG functioned as a natural plasticizer, enhancing flexibility while lowering stiffness, whereas EO showed conditional effects, providing limited plasticization at low concentrations and reduced mechanical integrity when combined with elevated CA or AG concentrations. Trade-offs between the measured properties emphasized the role of interactions rather than single components. Films were subsequently classified into flexible, balanced, and rigid categories based on the experimental thresholds, linking formulations with potential packaging applications and providing a basis for rational design of biodegradable packaging materials.

Retraction Note: Graphene-based LSPR sensors enable polarization-independent detection of CEA antigens

Distinct and compensatory roles of STAG1 and STAG2 in post-mitotic genome refolding

Shared decision-making in pediatric physical therapy: A qualitative study among adolescents, parents, and physical therapists

Objective Shared Decision Making (SDM) is a collaborative process between patients and clinicians. A structured approach for SDM in pediatric physical therapy is lacking. This two-phase study aimed to 1) explore how and when to apply SDM in pediatric physical therapy in primary healthcare, and to identify barriers and facilitators influencing its use, and 2) adapt an SDM model for use in pediatric physical therapy and propose strategies for implementation. Methods The study consisted of two phases. In Phase 1, six focus groups were conducted, two per participant group: adolescents (12-18y, n = 11), parents of children (4-18y, n = 9), and pediatric physical therapists (n = 6). A qualitative survey among 46 pediatric physical therapists validated focus group results. An inductive analysis explored how and when SDM should be applied, and a deductive analysis identified barriers and facilitators by linking codes to Consolidated Framework for Implementation Research (CFIR) domains. In Phase 2, the research team integrated results into an existing goal-based SDM-model, and implementation strategies were selected using the CFIR-Expert Recommendations for Implementing Change tool. Results SDM can begin at intake and goal setting, with ongoing, individualized involvement of children and parents throughout therapy. When comparing therapy options, treatment frequency, duration, homework, expectations, and possibilities at home can be discussed. Barriers included time constraints and the challenge of balancing multiple perspectives, while facilitators were the possibility to adapt SDM conversations per family and a supportive practice culture. A goal-based SDM-model was adapted for pediatric physical therapy. Implementation strategies identified were professional training, use of SDM tools, sufficient contact with parents, time to learn SDM, a supportive team culture, and empowering parents and children. Discussion This study provides guidelines for implementing SDM in pediatric physical therapy in primary care. A multifaceted implementation approach, guided by this study’s implementation strategies, may enhance SDM integration into clinical practice.

Circulating tRF-Gly-GCC as a biomarker for colorectal cancer and Crohn’s disease activity

Abstract Distinguishing intestinal inflammation from colorectal cancer remains challenging using non-invasive biomarkers. tRNA-derived fragments have been implicated in cancer, but their role in Crohn’s disease activity and their ability to differentiate inflammatory from malignant intestinal conditions remain unclear. This study evaluated circulating tRF-Gly-GCC in patients with active Crohn’s disease ( n  = 20), inactive Crohn’s disease ( n  = 20), colorectal cancer ( n  = 24), and healthy controls ( n  = 21). Serum tRF-Gly-GCC expression levels showed a directional increase across disease states, from controls to inactive Crohn’s disease, active disease, and colorectal cancer. A Jonckheere–Terpstra test formally confirmed a significant monotonic increase (z = 7.896, p  < 0.001). The marker distinguished colorectal cancer from controls with high sensitivity (95.8%) and specificity (95.2%), and differentiated colorectal cancer from Crohn’s disease with sensitivity of 95.8% and specificity of 80.0%. It also distinguished active from inactive Crohn’s disease with 90% sensitivity and 90% specificity. In Crohn’s disease, tRF-Gly-GCC correlated with disease activity indices but not with fecal calprotectin. These findings suggest that circulating tRF-Gly-GCC reflects intestinal inflammatory activity and may serve as a non-invasive biomarker for disease assessment and differentiation between inflammatory and malignant conditions.

Convergence and divergence of DNA methylation and gene expression patterns in neopolyploid Arabidopsis kamchatica

Abstract Polyploidization is a key evolutionary force in plants, but the reasons behind its prevalence remain unclear. While the potential ecological benefits of established polyploids are well studied, little is known about the short-term genomic and epigenetic responses immediately after polyploidization, which are crucial for successful speciation. In this study, we assemble the genomes of the two progenitors of Arabidopsis kamchatica ( A. halleri and A. lyrata ) and examine the epigenome of synthetic and natural tetraploids of A. kamchatica to investigate the combined effect of allopolyploidization and environment on DNA methylation changes. We find the most significant methylation changes at allopolyploidization, followed by smaller changes in subsequent generations. Offspring grown under different conditions show divergent patterns, suggesting environmental effects, while their methylation patterns converge toward those of natural tetraploids over generations. Our findings highlight two key epigenetic changes post-polyploidization: convergence toward established polyploids and divergence driven by environmental factors.

Expression of Concern: Differential microRNA profiling of the Marshallese population in Arkansas reveals a higher association with chronic diseases

Applying large language models to spam detection in the Kazakh low-resource language setting

Abstract In this paper, we test the efficacy of multilingual transformer-based large language models for spam classification tasks on the low-resource Kazakh language. Due to the lack of sufficient labeled data for spam emails written in the Kazakh language, we evaluate the ability of modern multilingual models for generalized tasks, especially the gains obtainable through supervised learning. In this analysis, we test a range of popular models such as bert-base-multilingual-cased, distilbert-base-multilingual-cased, and xlm-roberta for spam detection that are either trained for zero-shot tasks or through parameter-efficient supervised learning using LoRA. The experimental findings show that the zero-shot accuracy of multilingual LLMs is inconsistent, especially for the less common spam class, where the models tend to lack the ability to generalize because of the underrepresented Kazakh corpus. Yet, the models achieve considerable accuracy after being trained on a labeled corpus, where all models achieve accuracy above 0.99, especially XLM-R, which achieves a macro-F1 value of 0.99 and substantially reduces false negatives. A closer examination of these misclassified instances shows that common linguistic patterns, such as marketing necessities, financial jargon, or the conversational tone, play a significant role in their misclassification. The experimental results indicate that a limited amount of annotated instances for the Kazakh language, leveraging the efficiency of LoRA-based fine-tuning, can be effectively combined to improve the multilingual models’ performance even on security-related tasks.