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Dual-Stream deep learning for multimodal feature fusion and classification of balance control in elite freestyle aerial skiers

PLoS ONE Xinze Cui, Jie Gao, Pengquan Zhang et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0337296

Balance control is a key determinant of stable landing in elite freestyle aerial skiing. Rapid and precise identification of subtle differences in athletes’ balance-stability regulation is a prerequisite for targeted, evidence-based training. Conventional balance assessment typically relies on force-platform measurements of the center of pressure (COP) trajectory and subsequent time-, frequency-, and time–frequency–domain analyses. However, these indices have limited ability to capture the complex dynamics of postural control and to discriminate fine-scale differences in balance regulation among highly trained freestyle skiing aerials athletes.To address this limitation, we developed a dual-stream deep learning model that fuses time–frequency image features with COP-based statistical descriptors to classify subtle variations in balance regulation. Twenty-five elite freestyle skiing aerials athletes were recruited and performed quiet standing under two conditions: (i) bipedal stance on a stable surface with eyes open and (ii) bipedal stance on an unstable surface with eyes open. COP trajectories were recorded and their multiscale entropy computed; K-means clustering was used to stratify participants into high-, medium-, and low-stability groups. The extracted time–frequency and statistical features were then fed into the dual-stream deep learning framework for model training and validation.The proposed model achieved approximately 95% classification accuracy in distinguishing data-driven COP-based stability strata, suggesting potential utility for the sensitive assessment of balance-regulation patterns in elite freestyle skiing aerials athletes.

Correction for Sen et al., mTOR signaling governs the formation of epithelial apical projections via S6K1–RhoA and aPKC–Lgl2 axes

Proceedings of the National Academy of Sciences Jul 28, 2026 DOI: 10.1073/pnas.2622740123

Expression of Concern: Deep CNN-based detection of cardiac rhythm disorders using PPG signals from wearable devices

PLoS ONE Jul 28, 2026 DOI: 10.1371/journal.pone.0354777

Classification models for KCNQ1 variants distinguish functional and trafficking effects to enhance pathogenicity interpretation

Proceedings of the National Academy of Sciences Ana C. Chang-Gonzalez, Eric W. Bell, Carlos G. Vanoye et al. Jul 28, 2026 DOI: 10.1073/pnas.2537217123

Missense variants in the potassium channel KCNQ1 underlie most cases of congenital long QT syndrome (LQTS), one of the most common genetic arrhythmias. Variants affect protein stability, trafficking, and function, which are measurable properties that support variant interpretation. Leveraging the extensive experimental data generated by our laboratories, we developed random forest classifiers that predict seven KCNQ1 metrics: four electrophysiology and three trafficking measurements. The features for our classifiers integrate predictions from large machine learning models with protein-specific biophysical values, outperforming using either set of features alone. We applied our classifiers to interpret ClinVar variants of uncertain significance and AlphaMissense-ambiguous variants and developed global dysfunction and mistrafficking scores which distinguished benign from pathogenic variants. Global scores complemented AlphaMissense predictions, linking variants with LQTS-causing mechanisms. While effective for KCNQ1, our approach to variant prediction is generalizable to other ion channels and we recommend systematic benchmarking as done in this work to fully assess performance of future variant effect predictors.

Expression of Concern: The effects of learning experience on college students’ deep english learning: A study of the chain mediation effect of motivation and strategy

PLoS ONE Jul 28, 2026 DOI: 10.1371/journal.pone.0354764

Fluid polarity shifts initiate and amplify preferential flow in clay-rich media

Proceedings of the National Academy of Sciences Peihao Ouyang, Shijin Feng, He Chen et al. Jul 28, 2026 DOI: 10.1073/pnas.2536672123

Preferential flow governs fluid and solute transport across scales from micropores to regional watersheds, yet it is commonly attributed to static pore-structure heterogeneity. Here, we show that fluid polarity can actively reorganize pore networks and amplify preferential flow in kaolinite-rich clay media. In permeation experiments, replacing water with a low-polar hydrofluoroether triggers early breakthrough (~0.4 d) and permeability up to ~62.7× higher than predicted by standard relative permeability functions at only 18.8% low-polar saturation. Multiscale imaging and porosimetry show a transition from unimodal microporosity to connected pore-fracture bimodal architectures. Interfacial measurements indicate that low-polar fluids weaken interparticle electrostatic repulsion and thereby reorganize pore space by reducing ineffective pores and activating latent connectivity. Guided by the cross-scale mechanistic chain, we establish a one-parameter relationship linking interfacial forces to ineffective porosity and integrate it into a coupled framework that reproduces preferential path development and permeability evolution across 21 clay-rich media and 24 fluids. These findings advance a cross-scale framework for polarity-driven transport dynamics and provide a basis for incorporating fluid polarity into predictive subsurface transport models in shallow clay-rich environments.

Patient perceptions and preferences during a community-based telehealth care model for moderate-to-severe hypertension in rural communities in Kenya and Uganda

PLoS ONE Jason Johnson-Peretz, Andrew Mutabazi, Ambrose Byamukama et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0350915

Introduction Hypertension is a growing health concern in sub-Saharan Africa, yet access to care can be challenging, especially in rural areas. Overcoming barriers to hypertension care remains a priority. Pairing community health worker (CHW) and telehealth modalities offers one way to extend the reach of hypertension care without overburdening patients or healthcare systems in rural areas. Methods This qualitative study was nested within the SEARCH Sapphire pilot randomised controlled trial testing hypertension treatment through CHW-facilitated, clinician-driven telehealth (intervention) compared to clinic-based care (control) for adults aged ≥40 years with moderate-severe hypertension in rural western Kenya and southwestern Uganda. We conducted audio-recorded, in-depth, semi-structured interviews with purposively selected healthcare providers (clinicians and CHWs; N = 15) and participants (N = 40) between January-April 2023 to explore hypertension diagnosis and linkage to care; experiences with community hypertension care; family and work contexts; and the integration of telehealth into clinic and CHW workflows. Results Overall, participants felt satisfied with community-delivered telehealth care for hypertension. Participants noted community-based care saved on transport costs and reached those who were unwell or who lived far from clinic. Intervention arm participants felt CHWs were suitable for routine hypertension care, worked closely with clinicians, and could increase health literacy within the community. Participants desired a model with clear communication and involvement of the facility-based clinician, CHW, and participant. Providers found telehealth to be of similar quality to clinic-based care for routine hypertension treatment, though noted that clinic-based care is at times needed for more comprehensive clinical evaluation or to provide additional healthcare services. Conclusions Participants and providers indicated overall positive attitudes and receptivity to CHW-facilitated telehealth for hypertension care. CHW-delivered telehealth for community-based hypertension care offers one way to improve hypertension treatment outcomes in a manner that prioritizes patient-centeredness and maintains care quality. Trial Registration NCT04810650 Registered on 2021-03-18.

Single-cell atlas of the mouse ovary reveals molecular drivers of aging and senescence during the estropausal transition

Proceedings of the National Academy of Sciences Xifan Wang, Jiping Yang, Chen Jin et al. Jul 28, 2026 DOI: 10.1073/pnas.2600323123

Reproductive aging in mice leads to estropause, characterized by estrous cycle irregularity and eventual cessation, yet its underlying mechanism remains unclear. Here, we present a comprehensive single-cell atlas of mouse ovaries across precisely defined reproductive stages—from young (regular cycling) through the estropausal transition (regular vs. irregular cycling) to post-estropause (acyclic)—and of ovary-specific senescent cells defined by high senescence-associated β-galactosidase activity. We mapped transcriptomic dynamics of ovarian aging and characterized the molecular features of ovarian senescent cells. Our analyses revealed that during the estropausal transition, irregularly cycling ovaries exhibited accelerated aging and cellular senescence features compared with regularly cycling counterparts, including increased transcriptional noise, altered conserved aging pathways such as oxidative phosphorylation and proteostasis, hormone dysregulation in granulosa cells, and elevated expression of the senescence marker Cdkn1a and senescence-associated secretory phenotype factors. This atlas delineates the cellular and molecular hallmarks of mouse ovarian aging and ovary-specific senescent cells, providing a resource for understanding the mechanisms underlying the estropausal transition.

Retraction: Involvement of NF-κB in the reversal of CYP3A down-regulation induced by sea buckthorn in BCG-induced rats

PLoS ONE Jul 28, 2026 DOI: 10.1371/journal.pone.0354768

Cryo-EM reveals that <i>Escherichia coli</i> tRNA-transglycosylase can bind and act upon two tRNAs

Proceedings of the National Academy of Sciences Alexander Harjung, Ember M. Ruth, Mariusz Matyszewski et al. Jul 28, 2026 DOI: 10.1073/pnas.2601895123

Bacterial tRNA-guanine transglycosylases (TGT) are essential enzymes involved in tRNA modification, contributing to the virulence of multiple pathogens. TGT from Escherichia coli was the first protein of this family to be isolated and purified, and as such has served as a model enzyme for the biochemical characterization of TGTs. E. coli TGT is also one of the most disease-relevant TGTs, sharing high sequence identity with TGTs from several human pathogenic bacteria, including Shigella spp. and Salmonella spp. Notably, TGTs from some Shigella strains are sequence-identical to the E. coli enzyme. In addition, as a highly promiscuous enzyme, E. coli TGT has found use as an RNA-modification tool in chemical biology, enabling site-specific covalent RNA modification in vitro and in vivo. For these reasons, there has been significant interest in solving the structure of E. coli TGT. However, crystallization of E. coli TGT has proven difficult, and to date, structural insights have relied on surrogate TGT enzymes from other organisms. Here, we present the cryo-EM structure of E. coli TGT and its covalent intermediate with a full-length tRNA. Unexpectedly, the structure reveals that the E. coli TGT dimer binds and acts upon two tRNAs, which is unlike all other known TGTs. Closer analysis of the TGT–tRNA complex reveals several important interactions outside of the enzyme’s active site, that facilitate RNA binding and stabilize the conformational change of the tRNA anticodon loop. Based on these structural insights, we were able to design improved, high-affinity, TGT substrate RNA hairpins.

Experimental study of seepage-scour failure in geotextile tubes gap with damaged vertical sidewall

PLoS ONE Wen-Long Mao, Ling Zhang, Tian-Wen Wang Jul 28, 2026 DOI: 10.1371/journal.pone.0352901

Geotextile tubes, hydraulically filled with a slurry of fine silt and water, have been variously applied in hydraulic and coastal engineering fields. However, geotextile damage poses a great threat to structures made of geotextile tubes. When a water head difference exists across the tube, the soil in damaged tubes is affected by the dual actions of seepage and scour. To investigate soil failure patterns and tendencies of damaged tubes under hydraulic action, a structural apparatus and the corresponding test method were designed. Four factors considered were the radius of the damaged area ( r 0 : 0.25–2.0 cm), the grain size distribution (Sand B C u  = 3.4, Sand E C u  = 50), the scouring flow velocity ( v : 0–4 cm/s), and the hydraulic gradient. The results showed that the scouring flow exerted a limited effect on the failure mode of sand in the tubes, and that the failure process of sand in the tubes could be divided into three stages including a stable, an initial erosion, and a cyclic sand outflow stage. The hydraulic gradient at the initial erosion stage was defined as the critical gradient( j cr ), which was interactively influenced by sand gradation, damage radius, and scouring flow velocity. Under identical conditions, Sand E exhibited a higher resistance against seepage-induced failure than Sand B. In terms of stability under varying conditions, for Sand B, increasing the damage radius (tested at flow velocities of 0–4 cm/s) reduced j cr by 94%–100%, while increasing the flow velocity (tested at damage radii of 0.25–2.0 cm) reduced j cr by 60%–100%. For Sand E, the corresponding reductions were 83%–95% and 58%–88%, respectively, further confirming Sand E’s superior erosion resistance.

The circadian clock controls hepatic stellate cell activation via a BMAL1/CK1ε/REV-ERBα/transgelin signaling pathway

Proceedings of the National Academy of Sciences Manuel Johanns, Alexandre Berthier, Jimmy Vandel et al. Jul 28, 2026 DOI: 10.1073/pnas.2611767123

Liver fibrosis is a progressive and life-threatening condition with no effective targeted treatments. Growing evidence indicates a two-way relationship between circadian rhythm and fibrogenesis, although the specific molecular signaling pathways involved are still not well understood. The molecular clock, which governs circadian rhythms, regulates metabolic and cellular functions, and its pharmacological manipulation has shown potential as a therapy for organ fibrosis. Although the liver’s molecular clock appeared resilient to the progression of chronic liver disease in humans from steatosis to fibrosis, detectable changes in the daily amplitude of clock genes were observed in a cohort of people living with obesity. We found a clock-controlled signaling pathway that drives hepatic stellate cell (HSC) activation, a key initiating event in fibrosis progression. Interfering with this pathway, either by disrupting the core regulator CLOCK:BMAL1 or activating the nuclear receptors REV-ERBs, significantly reduced HSC activation. We also identified transgelin as the downstream effector of clock-regulated HSC contractility, a characteristic of HSC activation. Transgelin is regulated indirectly by a BMAL1-CK1ε signaling pathway and directly by REV-ERBα. Our findings identify a hitherto undescribed mechanism that links the molecular clock to HSC activation and cell contractile function, which is relevant to human fibrotic diseases. This pathway provides several entry points for drugs to target and disrupt primary fibrogenic signaling. By connecting clock biology to the cellular processes that cause fibrosis, our work also offers a mechanistic basis for chronotherapeutic strategies against chronic liver disease.

Motivational regulations for exercise in Brazilian outpatients with bipolar disorder: An analysis based on the self-regulation theory

PLoS ONE Fernanda Castro Monteiro, Carlos Linhares Veloso Filho, Thaís de Almeida Britto et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0354264

Despite the well-known physical activity (PA) benefits for physical and mental health, bipolar patients seem to be insufficiently active and often encounter challenges in participating in and adhering to programs involving PA. The present study aimed to assess the motivational regulation for exercise in bipolar disorder patients. This cross-sectional study utilizes objective (accelerometers) measures to assess PA. The Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAM-D) were used to assess mania and depressive symptoms. The Behavioral Regulation in Exercise Questionnaire – 3 (BREQ-3) was used to assess the motivators for exercise. The sample was composed of 43 patients with bipolar disorder (81.5% female, mean age = 47 years; SD = 10.4). Sufficiently actives patients according to accelerometer moderate-vigorous physical activity (MVPA) were significantly more intrinsically regulated than those insufficiently actives (p = 0.002). The linear regression model showed that intrinsic regulation predicted 20% of the variability for accelerometer MVPA (p = 0.004). Notable contrasts were observed in integrated regulation. When asked whether they consider exercise as a part of their identity, 27.6% of the insufficiently active patients selected “Very true for me.” Meanwhile this view was endorsed by 57.1% of sufficiently active. Similarly, 50% of the active group reported that exercise is a fundamental part of who they are compared with 31% of the insufficiently active group. Our findings suggest that more autonomous forms of motivation, particularly integrated and intrinsic regulation, were associated with higher levels of PA among individuals with BD, whereas less active participants tended to present higher depressive symptomatology and lower motivational quality.

Observed rapid adjustment of the atmospheric boundary layer to submesoscale sea surface temperature fronts

Proceedings of the National Academy of Sciences Igor Uchoa, Jacob O. Wenegrat, Alex Kinsella et al. Jul 28, 2026 DOI: 10.1073/pnas.2605662123

Current understanding of the role of ocean variability in air–sea exchange is constrained to large and mesoscale dynamics. Oceanic fronts and filaments with horizontal spatial scales of order 0.1 to 10 km—denoted submesoscale—are challenging to observe due to their fast-evolving flow and small spatiotemporal scales of variability. Observations investigating the air–sea fluxes at the submesoscale have shown substantial fluxes of heat, moisture, and momentum, affecting the structure of the overlying atmosphere. Here, modulations of the turbulent atmospheric boundary layer driven by ocean temperature anomalies are investigated using submesoscale-resolving ship and airborne measurements, providing in situ evidence of the atmospheric response to ocean submesoscale temperature variability. Observations suggest near-surface turbulent mixing driven by strong air–sea fluxes of heat and momentum, modifying the vertical structure of the planetary boundary layer. Linear regression coefficients between wind speed and sea surface temperature anomalies reveal a response similar in magnitude to that seen at larger scales, with an integrated change of 0.23 m s −1 °C −1 , but occurring over smaller length-scales, implying sharper gradients. Lagged correlations and scaling analysis imply a combined influence of horizontal advection and vertical turbulent mixing of momentum in the atmosphere, previously only described by numerical simulations. Observed cross-frontal wind divergences over the lower 200 m suggest coherent circulations with vertical velocities of order 1 cm s −1 . These observations confirm the rapid adjustment of the marine boundary layer to submesoscale ocean temperature variability and the importance of submesoscale-driven air–sea fluxes in changing the properties of the lower atmosphere, processes not resolved in most forecasting and prediction models.

Interlinked relationship between e-cigarette use and physical activity behaviour among Malaysian university students who use e-cigarettes: A cross-sectional study

PLoS ONE Chrisminder Dain, Lei Hum Wee, Yin How Wong et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0354336

Introduction E-cigarette (EC) use is increasing among young adults in Malaysia. However, evidence on how EC-related behaviours and perceived physical activity barriers are associated with physical activity participation remains limited. This study examined the associations between EC-related behaviours and perceived physical activity barriers with physical activity status among Malaysian university students who use EC. Methods A cross-sectional online survey was conducted between December 2023 and July 2024 across six Malaysian universities. Of 660 respondents, 564 met the age and International Physical Activity Questionnaire (IPAQ) criteria and were included in the analysis. Physical activity was classified as active and inactive. Exposures included EC use frequency, dual use, nicotine content, nicotine dependence, EC knowledge, motivations and perceptions for EC use, EC-related side effects, and perceived physical activity barrier items across personal, social and physical domains. Associations were analysed using chi-square tests and binary logistic regression, with odds ratios (ORs) and 95% confidence intervals. Results Overall, 64.9% were classified as active. At the crude level, EC use frequency, nicotine content, and dual-use status were associated with physical activity. However, these variables were not retained in the multivariable model due to multicollinearity. Nicotine dependence emerged as one of the strongest behavioural correlates of physical inactivity, with higher dependence associated with greater odds of physical inactivity. Perceived barriers to physical activity, particularly personal and social barriers, demonstrated the strongest and most consistent associations, with substantially higher odds of inactivity across barrier levels. EC knowledge and perception variables were not independently associated after adjustment, although item-level patterns were observed. Reported EC related symptoms were mainly gastrointestinal, respiratory, and neurological but were not analysed in relation to physical activity. Conclusion Physical activity among Malaysian university students who use EC is more consistently associated with nicotine dependence and perceived barriers, than with sociodemographic or knowledge variables. These findings suggest that interventions may benefit from addressing behavioural dependence and contextual constraints. Given the cross-sectional design, these results should be interpreted as hypothesis-generating. Implications Physical activity among university students who use EC appears more closely associated with nicotine dependence and perceived barriers than with knowledge or sociodemographic factors. While some EC use patterns showed crude associations, nicotine dependence emerged as one of the strongest behavioural correlates of physical inactivity. Lower perceived barriers, particularly personal and social, were consistently linked to higher activity participation. These findings suggest that intervention strategies may benefit from addressing behavioural dependence alongside reducing personal and social barriers to physical activity, particularly factors related to motivation, self-confidence, and competing demands. Integrating accessible, context-specific physical activity opportunities within EC cessation or harm-reduction programmes may enhance engagement and promote healthier lifestyle behaviours among young adults.

The ARHGAP32 isoform PX-RICS is specifically targeted to inhibitory synapses by binding to gephyrin

Proceedings of the National Academy of Sciences Guanhua Bai, Ruifeng Huang, Yinmiao Lian et al. Jul 28, 2026 DOI: 10.1073/pnas.2601488123

Precise regulation of excitatory–inhibitory balance is critical for neural circuit function, and its disruption underlies neurodevelopmental disorders such as autism spectrum disorder (ASD) and epilepsy. PX-RICS, a major ARHGAP32 splice variant enriched at inhibitory synapses, has been linked to cognitive dysfunctions; however, the molecular basis of its synaptic targeting and function remains unknown. Here, we identify gephyrin as the primary synaptic anchor for PX-RICS and determine the 2.2 Å crystal structure of their complex. Our structural analysis reveals that the N-terminal gephyrin-binding region (GBR) engages gephyrin E-domain through conserved hydrophobic interactions, explaining the isoform-specific targeting of PX-RICS (but not RICS) to inhibitory synapses. This binding interface overlaps with the neurotransmitter receptor binding site on gephyrin, suggesting a competitive yet dynamic interaction landscape among these inhibitory synaptic proteins. Arhgap32 ΔGBR mice exhibit key features of ARHGAP32 -related disorders, including impaired social novelty recognition and increased seizure susceptibility, indicating that gephyrin-mediated anchoring is critical for PX-RICS to function in inhibitory synapses.

Very short-term production prediction for photovoltaic plants using Temporal Convolutional Networks

PLoS ONE Loukas Samaras, Elena García-Barriocanal, Miguel-Angel Sicilia et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0354512

Very short-term forecasting of solar photovoltaic energy production at national scale is challenging due to the high variability and spatial aggregation of generation across large territories. This paper evaluates Temporal Convolutional Networks (TCN) — a deep learning architecture based on causal and dilated convolutions — for nowcasting national-level solar production at one-hour and fifteen-minute horizons, using data from Spain sourced from the European Network of Transmission System Operators for Electricity. Multivariate models augmented with past weather observations (solar irradiance and sun height) are compared against linear regression baselines. Results demonstrate that the multivariate TCN substantially outperforms linear regression at the one-hour horizon, and achieves consistent improvement at the fifteen-minute horizon. The relative contribution of architecture and weather features is resolution-dependent: at hourly granularity, the TCN architecture itself provides the dominant gain, while at the fifteen-minute scale the inclusion of weather covariates becomes the primary driver of accuracy, reflecting the greater atmospheric variability at finer temporal scales. A key finding is that past-only weather inputs are sufficient for accurate nowcasting, eliminating the need for future meteorological forecasts as model inputs. The results support the practical applicability of TCN-based models for national-level solar energy integration and provide a data-driven feature-selection criterion for similar renewable energy forecasting tasks.

H <sub>2</sub> S-mediated protein persulfidation regulates redox metabolic flux underlying salt-stress resilience in rice

Proceedings of the National Academy of Sciences Zhengyao Lin, Mingjian Zhou, Xiaoyun Ma et al. Jul 28, 2026 DOI: 10.1073/pnas.2608150123

Hydrogen sulfide (H 2 S) functions as a gaseous signaling molecule in plant stress responses through the persulfidation of protein cysteine (Cys) residues. A comprehensive, Cys site-specific map of the plant persulfidome has been lacking, despite its importance for achieving a systems-level understanding of the biological roles of Cys persulfidation. Using a state-of-the-art N -ethylmaleimide-biotin-based proteomics strategy, we generate a dynamic map of 1,691 persulfidated Cys sites in the rice ( Oryza sativa ) leaf proteome. Our results reveal a global dynamic changes in protein persulfidation during prolonged salt stress, with notable impacts on proteins involved in metal-dependent catalysis, redox metabolism, and the pentose phosphate pathway (PPP). Based on these patterns, we investigated the functional relevance of persulfidation within the nonoxidative PPP. H 2 S-mediated persulfidation decreased the activity of the representative nonoxidative PPP enzyme ribose-5-phosphate isomerase, leading to increased NADPH production and subsequent activation of NADPH-dependent redox enzymes, including monodehydroascorbate reductase (MDHAR) isoforms of the ascorbate-glutathione (AsA-GSH) cycle. Persulfidation protected MDHAR3/5 from oxidative inhibition and degradation, thereby sustaining AsA-GSH cycle capacity and supporting reactive oxygen species scavenging. This site-specific persulfidome provides a valuable resource for exploring plant redox regulation, and our functional analyses offer mechanistic insight into how H 2 S-dependent protein persulfidation modulates redox metabolic fluxes to bolster NADPH availability and maintain redox homeostasis during salt-stress adaptation.

Bisphenol A exposure in myasthenia gravis: Potential targets and mechanisms revealed by network toxicology and molecular dynamics

PLoS ONE Shupeng Wu, Yaoqi Wu, Li Zhang et al. Jul 28, 2026 DOI: 10.1371/journal.pone.0354138

Background Myasthenia gravis (MG) is a B-cell-mediated autoimmune disease characterized by impaired neuromuscular transmission. Although genetic predisposition and thymic abnormalities are well recognized, they cannot fully explain the increasing incidence and regional heterogeneity of MG, highlighting the potential contribution of environmental factors. Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, exhibits estrogenic activity, immunomodulatory effects, and mitochondrial toxicity, and has been implicated in multiple autoimmune disorders. However, the potential role of BPA in MG pathogenesis remains largely unexplored. Methods BPA-related targets and MG-associated genes were collected from public databases, and overlapping targets were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and pathways of the overlapping targets. Candidate targets were screened using four machine-learning algorithms, including least absolute shrinkage and selection operator (LASSO) regression, support vector machine-recursive feature elimination (SVM-RFE), random forest (RF), and extreme gradient boosting (XGBoost). Differential expression and diagnostic performance were validated using the Gene Expression Omnibus (GEO) dataset GSE85452. Immune infiltration was assessed using CIBERSORT. Molecular docking and molecular dynamics (MD) simulations were conducted to evaluate the potential binding stability and interaction modes between BPA and key target proteins. In addition, C2C12 myoblasts were treated with different concentrations of BPA for 24 h, and cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Based on the cell viability results, 50 μM BPA was selected for quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses of key genes. Results A total of 225 overlapping targets were identified between BPA exposure-related targets and MG-associated genes. Enrichment analyses showed that these targets were mainly associated with ion transport, membrane potential regulation, muscle system processes, immune signaling, apoptosis, endocrine resistance, and AGE–RAGE signaling pathways.Four machine-learning algorithms identified cholinergic receptor nicotinic beta 1 subunit (CHRNB1), KRAS proto-oncogene, GTPase (KRAS), phosphomannomutase 2 (PMM2), and toll-like receptor 4 (TLR4) as candidate targets. Validation in the GSE85452 dataset showed that CHRNB1, PMM2, and TLR4 were significantly upregulated in MG samples compared with control samples, whereas KRAS showed no significant difference. receiver operating characteristic (ROC) analysis further demonstrated that CHRNB1, PMM2, and TLR4 had good diagnostic performance, with area under the ROC curve (AUC) values of 0.827, 0.856, and 0.821,respectively. Immune infiltration analysis revealed altered immune cell infiltration patterns and associations between key targets and specific immune cell subsets. Molecular docking predicted favorable binding of BPA to CHRNB1, PMM2, and TLR4, with binding energies of −7.4, −5.7, and −5.8 kcal/mol, respectively. MD simulations further supported the potential stability of these BPA-target complexes. In vitro experiments showed that BPA reduced C2C12 cell viability in a concentration-dependent manner. qRT-PCR validation showed that treatment with 50 μM BPA significantly upregulated Chrnb1 expression, while downregulating Pmm2 and Tlr4 expression.Western blot analysis further confirmed that BPA exposure significantly decreased the protein expression of TLR4 and PMM2, while increasing that of CHRNB1 in C2C12 cells. Conclusions This study provides integrated computational and experimental evidence that BPA exposure may be associated with MG-related molecular alterations. BPA may affect MG-related biological processes through the regulation of ion transport, neuromuscular signaling, immune activation, and glycosylation-related metabolism. CHRNB1, PMM2, and TLR4 may serve as potential molecular links between BPA exposure and MG-related pathological processes.

Children’s books about scientists convey demotivating messages

Proceedings of the National Academy of Sciences Jessica R. Gladstone, Gabrielle Applebaum, Andrei Cimpian Jul 28, 2026 DOI: 10.1073/pnas.2612021123

Biographies of scientists are widely used to spark children’s interest and broaden participation in science. In telling the stories of successful scientists, these books convey implicit “recipes for success”—yet no study has systematically examined whether these recipes align with what motivation research recommends. Here, we provide the first large-scale analysis of motivational messages in children’s science biographies (422 best-selling books, 1,355 protagonists). Four main findings emerged. First, scientific ability was portrayed equally often as fixed and as malleable, a pattern unlikely to support motivation. Second, interest in science was overwhelmingly portrayed as fixed: Most scientists were said to be captivated by science from a young age. Third, scientists in physics, engineering, and computer science were portrayed as more reliant on fixed ability than scientists in other fields. Fourth, biographies of female scientists disproportionately emphasized effort even after adjusting for the obstacles they faced, consistent with stereotypes attributing women’s success to hard work over talent. These findings suggest that well-intentioned efforts to diversify science through role model exposure in children’s science biographies may fall short.