Browse Articles

High-risk pregnancy prediction using Taguchi-optimized machine learning methods and TOPSIS-based model selection

A mechanism for substrate quality control in outer membrane protein assembly

The assembly of β-barrel proteins into the outer membrane (OM) of Gram-negative bacteria is catalyzed by the β-barrel assembly machine (Bam) complex, which consists of two essential proteins, the BamA β-barrel and the lipoprotein BamD, and three nonessential lipoproteins BamBCE. While it is well established that BamD serves an essential role in regulating the activity of BamA, the physiological reasons underpinning the need for BamD-mediated regulation of β-barrel assembly are unclear. Here, we demonstrate that BamD-mediated regulation of BamA functions as a mechanism of substrate quality control that ensures the efficient assembly of β-barrel proteins into the OM. Through the use of substrate C-terminal fragments and multiple alleles of bamA and bamD that prevent effective regulation of BamA by BamD, we show that BamD activity is necessary to prevent the accumulation of defective β-barrel substrates on BamA. Notably, these bamAD alleles all confer resistance to the Bam complex inhibitor MRL-494 in a manner that correlates with the degree to which BamD activity is bypassed, suggesting that MRL-494 inhibits β-barrel assembly by disrupting BamD-mediated conformational changes in BamA. We further show that BamD activity functions to prevent the uptake of toxic small molecules across the OM through a mechanism that functionally overlaps with that of the substrate quality control protein Skp. Collectively, these results not only establish that BamD, like Skp, functions to ensure proper quality control of β-barrel substrates but also demonstrate the importance of substrate quality control functions in maintaining the integrity of the OM permeability barrier.

Global tastes, local choices: Strontium isotope and concentration evidence for changing dietary input in Roman Nijmegen, the Netherlands

This study investigates dietary practices and local interaction in Roman and pre-Roman Nijmegen, the Netherlands, through strontium isotope ratios (⁸⁷Sr/⁸⁶Sr) and concentration measurements on cremated human remains from rural, urban, and military contexts, which primarily reflect the geological provenance of dietary strontium. Located along the Lower Rhine borderlands, Nijmegen formed a key node within the Batavian region, where local communities intersected with imperial networks. The results reveal isotopic contrasts between site types: urban and military groups tend to display higher strontium concentrations, possibly consistent with greater engagement with salt-preserved and salt-rich foods, while in the northern contexts relatively stable concentrations alongside a narrowing of isotope ratios may suggest continuity in dietary practices, potentially including earlier traditions of salt consumption. These patterns indicate that dietary change was not uniform, but shaped by the interaction between emerging imperial foodways and pre-existing local practices. Rather than reflecting simple differences in access, the isotopic evidence points to varied and context-dependent forms of engagement with Roman provisioning systems.

Data-driven prediction of micro-piled raft load–settlement using machine learning and Monte Carlo simulation

Abstract This study investigates the load–settlement behavior of micro-piled raft foundations in clay, focusing on key factors such as raft and micro-pile geometry and critical soil properties. A comprehensive dataset comprising 480 experimental records. sourced from both small-scale laboratory and large-scale field tests. was used to evaluate the predictive capabilities of six supervised machine learning algorithms: Gaussian process regression ( GPR ), extreme gradient boosting ( XGBoost ), gradient boosting machine ( GBM ), random forest ( RF ), K-nearest neighbors ( KNN ), and support vector regression ( SVR ). Each model was optimized using Bayesian optimization with 5-fold cross-validation to ensure robust performance. Model evaluation was conducted using statistical metrics, visual diagnostics (predicted-versus-actual plots), Regression error characteristics curves, score analysis, and hyperparameter tuning. Among the tested models, GPR demonstrated superior accuracy and generalization, effectively capturing the nonlinear soil–structure interaction typical of micro-piled raft foundations. Probabilistic analysis using Monte Carlo simulations, incorporating realistic variability in geometric and geotechnical input parameters, further validated the model’s robustness. The close agreement between predicted and experimental load–settlement responses, along with consistently narrow 95% confidence intervals, confirms the reliability of GPR . These findings position GPR as a highly promising approach for practical geotechnical design applications. Future research should focus on expanding dataset diversity, improving parameter independence, and applying advanced tuning techniques to further enhance model reliability and applicability to full-scale foundation systems.

OptoRibo-seq for spatiotemporally resolved mapping of the local protein translatome

Localized protein translation occurs in numerous subcellular compartments and regulates diverse biological processes by rapidly changing protein compositions in response to subcellular needs. Existing assays for subcellular local translation either require physical isolation, which is prone to contamination and loss of material, or imaging-based readout, which is often hampered with low throughput. In this study, we report the development of the optoRibo-seq method that features photoactivatable enzyme-mediated proximity labeling of ribosomes in genetically specified subcellular locations. We demonstrate the spatial specificity of optoRibo-seq at the endoplasmic reticulum (ER) membrane, with a temporal resolution of 1 min. In cells undergoing chemically induced ER stress, optoRibo-seq allowed mapping of the dynamic changes in the ER-proximal translatome, identifying transcripts involved in protein folding and targeting. Our strategy provides a general platform for spatiotemporally resolved profiling of subcellular protein translation.

Study on stability analysis of soil nail reinforced slopes under loading based on the discrete element method

Soil nailing is widely used to improve slope stability, yet the mechanical response of soil-nailed slopes subjected to surcharge loading remains insufficiently understood, particularly at the mesoscopic level. In this study, the discrete element method (DEM) was employed to investigate the progressive failure process, macroscopic stability, and micromechanical behaviors of a soil-nailed slope subjected to point loading and distributed linear loading with varying magnitudes and loading widths. The numerical results show that surcharge loading significantly reduces slope stability and increases deformation. Under point loading, the safety factor decreases continuously with increasing load magnitude and the deformation remains highly localized. Under linear loading, the safety factor decreases sharply as the loading width increases from 0 to approximately 1.5–2.0 m, and then tends to stabilize, whereas displacement continues to increase monotonically. Micromechanical analyses indicate that surcharge loading promotes rapid accumulation of elastic strain energy, intensifies particle rotation, and increases stress heterogeneity within the slope. Load distribution also strongly affects the force transfer mechanism in the reinforcement system: narrow loads are mainly resisted by upper nails, while wide distributed loads mobilize deeper nails and shift the stabilizing effect to lower reinforcement layers. The results suggest that surcharge loads near the slope crest should be carefully controlled, and that sufficient setback distance is important for limiting stress transmission into the active failure zone. These findings provide insight into the failure mechanism of soil-nailed slopes under surcharge loading and offer practical guidance for reinforcement design.

Predicting differential ratings of perceived exertion (dRPE) in youth soccer using decision tree models

A redox- and proton-coupled inner membrane transporter mediates copper import to the bacterial cytoplasm

Copper homeostasis in bacteria requires tightly regulated import systems to balance copper’s essential redox functions with its inherent cytotoxicity; yet, the mechanisms of cytoplasmic copper uptake remain poorly understood. In particular, the widespread CopD family of transmembrane proteins has been linked genetically to cytoplasmic copper import, but has not been mechanistically characterized. Here, using in vivo uptake assays, proteoliposome-based, real-time copper translocation kinetic measurements, and spectroscopic and electrochemical analyses, we demonstrate that CopD from the methanotroph Methylosinus trichosporium OB3b functions as a Cu + /H + symporter and a Cu 2+ reductase. Real-time transport measurements reveal transporter-mediated saturable transport with micromolar Cu + affinity and rapid translocation rates consistent with facilitated diffusion or potential secondary active transport, and pH-sensitive fluorescence assays establish obligatory proton cotransport coupled to Cu + translocation. Three conserved residues, two histidines and a tryptophan, predicted to reside in the periplasmic and transmembrane regions, respectively, were identified as critical determinants of copper uptake, with likely roles in substrate coordination and gating. Notably, CopD contains a C-terminal periplasmic cytochrome c domain with a complex electron paramagnetic resonance spectrum dominated by a low-spin, six-coordinate heme with a midpoint potential of 138 ± 5 mV. Spectroscopic and electrochemical data show that this heme can reduce Cu 2+ to Cu + , both in solution and when copper is bound to the cognate M. trichosporium OB3b periplasmic chaperone CopC. These findings support a model in which CopD couples periplasmic Cu 2+ reduction to Cu + /H + symport across the inner membrane, establishing a new paradigm for bacterial copper import and metal transporter function.

Organizing adult attachment in alternative ways: A qualitative assessment of schemas antithetical to the secure base script

How adults make meaning of their childhood experiences with caregivers plays a central role in how they anticipate support, manage distress, and interpret relationships. To understand how adults conceptualize these attachment relationships, the Adult Attachment Interview (AAI) probes for childhood memories of general relationships, day-to-day interactions, and instances of loss, threat, and separation. Across these narratives, the AAI captures expectations of whether caregivers are perceived as an available source of support in times of distress, and whether they serve as a secure base from which to seek comfort and explore the world. Developing a coding system for secure base script knowledge, based on the AAI (AAIsbs), Waters, and Facompré also identified alternative, schema-like representations that seemed to conflict with the secure base script. Before exploring empirical questions regarding these alternative schemas, the present study undertook a qualitative systematic examination of their content in a large, risk-diverse corpus of interviews from 14 studies. Conducting a thematic analysis, 1,592 AAIs were examined by seven trained coders. This resulted in the identification of three novel themes (Favoritism, Incompetent, and Restrictive), the amendment of three existing schemas (Caregiver Source of Distress, Harsh and Threatening Parenting, and Self-Involved), and the replication of evidence for existing schemas. Together, the diversity and thematic coherence of alternative schemas underscore how relational expectations may be organized around vigilance, distress, or self-reliance, rather than comfort and support. This study contributes to theory-building on relational representations by expanding our understanding of how caregiving relationships are cognitively structured under conditions of relational adversity.

Hybrid topic classification approach integrating TF-IDF, BiGRU, and modified builder optimization algorithm (MBOA)

Transcription start site heterogeneity controls MDA5 sensing of unspliced HIV-1 RNAs

Heterogenous transcription start site (TSS) usage dictates the 5′ leader structure and function of unspliced HIV-1 RNAs (usRNA). We and others have previously reported that expression and Rev/CRM1-mediated nuclear export of HIV-1 usRNA in macrophages activates MDA5, MAVS, and innate immune signaling cascades. In this study, we reveal that MDA5 sensing of viral usRNA is largely determined by TSS and cytoplasmic RNA function in macrophages. We show that HIV-1 usRNAs ( cap 1G) that are preferentially destined for dimerization and viral genome packaging are specifically targeted by MDA5, while efficiently translated ( cap 3G) usRNAs are immunologically silent. Using mutant viruses which generate usRNA with altered 5′ leader structure, or inclusion of a retroviral constitutive transport element which drives mRNA-like NXF1-dependent nuclear export of viral usRNA, we show that transcription initiation site and nuclear export pathway choice are major determinants of both HIV-1 usRNA immunogenicity and cytoplasmic function. In total, we identify innate immune response modulation as a consequence of the well-conserved heterogenous TSS usage among ancestral and extant HIV-1 isolates in humans, and shed light on how MDA5 discriminates between self and non-self RNAs.

The electrical characteristics of Nanosheet FET within the quasi-ballistic transport: Role of scattering and temperature variation

The article highlights the effects of quasi-ballistic and diffusive transport on electron mobility, band gap, and electrostatic behavior in scaled Nanosheet FETs. It also provides comprehensive physical insight into the effects of different scattering mechanisms on the gate-length scaling process (from 16 nm to 6 nm) and their impact on performance metrics. The temperature is modeled from 220 K to 450 K to analyze its effect on electron mobility and the lateral electric field profile. It is observed that defects, such as oxygen vacancies, affect the work function of the gate stack region and induce scattering mechanisms at the oxide interface, thereby enhancing band-to-band and trap-assisted tunneling of electrons. Increased temperature in the device causes significant phonon scattering, resulting in approximately a 45% drop in the mobility, with a standard deviation of 328.7 cm²/V·s. The higher phonon and surface-scattering rates at elevated temperatures modify the band gap profiles, leading to a reduction of 48–72 meV in the band gap. Due to the reduced scattering and lower contact-poly pitch, the highest drive current is achieved at a 6 nm gate length in the quasi-ballistic and diffusive transport regimes. Gate-length scaling suffers from increased scattering rates and higher tunneling probabilities, leading to higher leakage current and a reduced I ON /I OFF ratio. Scattering mechanisms introduce resistance in the channel region, resulting in a drop in mobility. The electrostatic profiles and mobilities are mapped along the channel to comprehend the device operation at the scaled node.

Potential utility of postmortem CT-based classification as a practical pre-autopsy assessment tool for hepatic steatosis

Abstract This study aimed to establish postmortem computed tomography (PMCT)-specific Hounsfield unit (HU) criteria and developed an HU-based assessment tool for pre-autopsy triage of hepatic steatosis. Overall, 166 deceased individuals underwent whole-body PMCT followed by autopsy with liver histopathology. Hepatic attenuation was measured as a volumetric mean HU of the entire liver and as a four-point mean HU. No significant difference was noted between the volumetric and four-point mean HU ( p  = 0.183). However, the four-point mean HU differed significantly across histological steatosis grades ( p  < 0.001) and decreased with increasing severity, although the difference between mild and moderate steatosis was non-significant ( p  = 0.981). Receiver operating characteristic analysis indicated an optimal cutoff of 42.59 HU (sensitivity 60.7%, specificity 86.1%), from which three HU-based categories were defined (≥ 44.5 HU: normal; 42.0–44.4 HU: borderline; <42.0 HU: suspected steatosis). In the validation cohort ( n  = 104), the tool achieved an accuracy of 0.865, sensitivity of 0.756, specificity of 0.949, precision of 0.919, and F1-score of 0.829. This three-category PMCT HU-based classification system provides a practical tool for the triage of hepatic steatosis. The high specificity and precision support its use as a rule-in aid to prioritize suspected steatosis cases and improve autopsy workflow efficiency.

Wind turbine proximity and health: Longitudinal evidence from US households

Rapid growth of wind energy plays a key role in global efforts to reduce carbon emissions, yet public concerns persist about its potential health effects, particularly through noise exposure. While some studies and media reports suggest that wind turbines may contribute to sleep disturbances, anxiety, and even suicide, existing evidence remains limited and inconclusive. This study combines geolocated data on turbines from the US Wind Turbine Database with longitudinal survey data on over 120,000 households (2011–2023) and consumer purchasing records to assess whether proximity to wind turbines affects mental and physical health. We examine a wide range of outcomes, including depression, anxiety, sleep disorders, headaches, and use of sleep aids and painkillers. Comparing households before and after nearby turbine installations, we find no detectable adverse health effects from turbine exposure at typical exposure distances. While we cannot rule out small effects, our CIs exclude moderate-to-large impacts, suggesting that fears about substantial health impacts are not borne out in population-level data. Other disamenities such as noise, shadow flicker, and visual intrusion may still affect quality of life even absent measurable health impacts.

The interaction between rumination and job embeddedness among trainee nurses during internship: A multicenter longitudinal study

Objective To explore the developmental trajectory of rumination and job embeddedness among college trainee nurses and examine the predictive relationship between them, with the aim of providing a theoretical basis for improving trainee nurses’ job embeddedness. Design A longitudinal study. Methods A total of 405 nursing interns from 12 colleges and universities in China were selected as the survey subjects. They were tracked using the Ruminative Responses Scale (RRS) and the Global Job Embeddedness Items (GJEI) at three time points: T1 (initial stage of internship, 1–2 months), T2 (middle stage of internship, 5–6 months), and T3 (completion of internship, 9–10 months). A cross-lagged model was constructed to analyze the causal relationship between the two variables. Results A total of 382 valid questionnaires were collected, yielding an effective response rate of 94.32%. In analyzing the overall trend from T1 to T3, rumination significantly decreased from a baseline of (44.79 ± 5.28) to (41.61 ± 5.27) (F = 47.360, P < 0.001). Concurrently, the score of job embeddedness increased significantly from (22.42 ± 4.89) to (25.48 ± 4.60) (F = 25.690, P < 0.001). The level of rumination at a previous time point negatively predicted job embeddedness at the subsequent point (β = −0.403, P < 0.01; β = −0.411, P < 0.001), and job embeddedness at a previous time point negatively predicted rumination at the next point on average (β = −0.397, P < 0.001; β = −0.385, P < 0.001). At the initial level, rumination can predict job embeddedness negatively (β = 0.433, P = 0.002), the initial level of rumination can predict the development speed of job embeddedness negatively (β = 0.395, P = 0.005), and the development speed of rumination can positively predict the development speed of job embeddedness (β = 0.450, P < 0.001). Conclusion practice trainee nurses rumination is on the decline, job embeddedness is on the rise. Educators and clinical instructors should assess and monitor rumination levels in trainee nurses and strategically leverage the dynamic relationship between rumination and job embeddedness to enhance the latter during clinical training.

Study of memory-dependent dynamics of a predator–prey model with hyperbolic mortality

Regulatory rewiring of <i>Dand5</i> drove left–right organizer heterotopy and organ asymmetry evolution in chordates

Heterotopy—the spatial relocation of developmental processes—is a key mechanism driving morphological innovation, yet its underlying regulatory basis remains poorly understood. In chordates, the left–right (L–R) organizer shifted from the anterior domain as represented by amphioxus to the posterior end in vertebrates, accompanied by a coordinated relocation of the entire L–R gene regulatory network (GRN), including Dand5 and its downstream genes Nodal , Lefty, and Pitx . Here, we dissect the regulation of Dand5 in amphioxus and compare it with vertebrates. We show that L–R asymmetry of amphioxus Dand5 is established transcriptionally and not posttranscriptionally as in vertebrates. Its transcription is directly activated by Hedgehog signaling and repressed by Wnt signaling, independent of vertebrate-specific inputs from Brachyury, and Notch and Wnt signaling. However, key elements required for postregulation of vertebrate Dand5 asymmetry, including the responsiveness of its 3’-untranslated region (UTR) to Bicc1-mediated RNA repression and Bicc1 expression in embryonic posterior end, seem already present in amphioxus. Our study therefore provides empirical evidence that repurposed regulatory sequences can drive heterotopy of developmental GRNs, offering a mechanistic explanation for the evolutionary shift of the LR signaling center and a foundation for exploring the diversification of LR organs across chordates.

Size–curvature constraint in the closing motion of Venus flytrap leaves

Among carnivorous plants, the Venus flytrap ( Dionaea muscipula ) is known for its rapid (&lt;1 s) trap closure. Although buckling instability, hydrostatic pressure, and hydroelastic coupling have all been proposed to be involved, the nature of this process and the relationship between trap size and curvature remain elusive. Here, we monitored the closure of Venus flytraps and performed micro – CT scanning and 3D reconstruction, revealing that increasing angular velocity was correlated with higher values of a non-dimensional shape index. Based on these experimental data, we constructed a geometric model of the trap that takes leaf orientation into account. We found that leaf curvature is dependent on leaf size, a relationship we denote as a size – curvature constraint. We further propose a curvature design derived from differential deformations of a two-layer model of the leaf, which could be a powerful tool to control the curvatures of soft and bending surface structures in the field of biomimetics.

FrogPCSP: a propeptide cleavage site predictor for frog antimicrobial peptides

Molecular insight into the interplay among heterogeneous plasmacytes and microenvironment cells and their clinical relevance in myeloma

Multiple myeloma (MM) develops with the acquisition of genetic abnormalities in plasmacytes and changes in microenvironment cells (MECs). Despite the progress in understanding MM disease mechanism through omics studies, the genomic/transcriptomic profiling remains limited in Chinese MM patients. Here, we collected 277 newly diagnosed MM (NDMM) patients in the Shanghai MM Omics (SMMO) project. Analysis of 267 cases with whole-genome/whole-exome sequencing and RNA sequencing (RNA-seq) identified three genetic groups (MY, HRD, and MS/CD). Using single-cell RNA sequencing (scRNA-seq), we investigated 59 NDMM subjects from SMMO, 20 relapsed cases from public database and 30 normal controls. Eight subpopulations of plasmacytes from NDMM (mSP1–mSP8) were defined, each showing unique signatures while forming a differentiation trajectory. The mSP2 is worth noting due to its high proliferative property. Regarding MECs, we found T cell subsets including T-helpers, Tregs, and cytotoxic T cells all in dysfunctional status and increased myeloid-derived suppressor cells such as macrophages mainly in M2 polarization, both constituting a milieu in favor of MM cell growth and immune escape. Furthermore, we scrutinized the crosstalk between MM cells and MECs and that among distinct MECs. A dynamic, comprehensive MM pathogenesis network was revealed, with a number of ligand–receptor pairs. Importantly, the mSP2 signature can be projected to the MM cell RNA-seq data of 235 patients to generate a Score100 with prognostic value in SMMO. Via multivariate analysis of the International Staging System, Consensus Genomic Staging, and Score100, we propose a practical MM stratification model for evaluating aggressive myeloma.