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Influence of deposition conditions on ALD based Ru passivation for Cu-Cu hybrid bonding
Association of repeated high serum osmolarity with cognitive function in older Japanese adults in a KOBE study subanalysis
Abstract The relationship between serum osmolarity and cognitive function has not been fully characterized. This study aimed to examine the cross-sectional association between repeated high serum osmolarity and cognitive performance among elderly community residents. We performed a subanalysis of the Kobe Orthopedic and Biomedical Epidemiological Study, including residents aged ≥ 75 years who completed the Japanese Montreal Cognitive Assessment (MoCA-J) in 2016–2017 ( n = 127), 2018–2019 ( n = 71), and 2020 ( n = 16). Serum osmolarity was obtained from the data in the 2012–2013 survey and in the 2016–2017 survey. MoCA-J scores were dichotomized at ≤ 22 versus > 22. Multivariate logistic regression adjusted for demographic, lifestyle including daily non-alcohol drink intake, seasonal, and clinical covariates to assess associations between osmolarity status and cognitive group. Among 214 participants (mean age 76.2 ± 1.3 years; 56% female), high osmolarity (≥ 300 mOsm/L) in 2012–2013 was associated with MoCA-J ≤ 22 (OR 2.67, 95% CI 1.29–5.53, p = 0.008). A similar association emerged for 2016–2017 measurements (OR 6.12, 95% CI 1.46–25.61, p = 0.013). Participants with high serum osmolarity at both time points showed a stronger cross-sectional association with lower MoCA-J scores (OR 17.64, 95% CI = 1.8–184.83, p = 0.017). No significant association was observed between daily non-alcoholic drink (NAD) intake and either MoCA-J scores or serum osmotic pressure. Repeated high serum osmolarity was cross-sectionally associated with lower cognitive performance in Japanese community-dwelling older adults. While NAD intake showed no significant association, further research is needed to explore the potential role of serum osmolarity in cognitive health. These findings warrant confirmation in larger prospective studies.
T cell receptor specificity landscape revealed through de novo peptide design
T cells play a key role in adaptive immunity by mounting specific responses against diverse pathogens. Effective bindings between T cell receptors (TCRs) and pathogen derived peptides presented on major histocompatibility complexes (MHCs) mediate immune responses. However, predicting these interactions remains challenging due to limited functional data on T cell reactivities. Here, we introduce a computational approach to predict TCR interactions with peptides presented on MHC-I alleles, and to design immunogenic peptides for specified TCR–MHC complexes. Our method leverages HERMES, a structure-based machine learning model trained on the protein universe to predict amino acid preferences based on local structural environments. Despite no direct training on TCR-pMHC data, HERMES’s implicit physical reasoning enables us to make accurate predictions of both TCR–pMHC binding affinities and T cell activities across diverse viral and cancer epitopes, achieving up to 0.72 correlation with experimental data. Leveraging our TCR recognition model, we develop a computational protocol for de novo design of immunogenic peptides. Through experimental validation in three TCR–MHC systems, we demonstrate that our designs—with up to five substitutions from the native sequence—activate T cells at success rates of up to 50%. Last, we use our generative framework to quantify the diversity of the peptide recognition landscape for various TCR–MHC’s, offering key insights into T cell specificity. Our approach provides a platform for immunogenic peptide and neoantigen design, as well as for evaluating TCR specificity, offering a computational framework to inform design of engineered T cell therapies and vaccines.
A segmentation network for enhancing autonomous driving scene understanding using skip connection and adaptive weighting
Real-world safety assessment of tamsulosin based on adverse event analysis from the FAERS database
Exploring bacteria–surface interactions with a fluorescent membrane tension probe
Understanding how bacteria interact with surfaces is critical for advancing applications in biofilm and biofouling prevention, biomaterial development, or biosensing. However, the biophysical mechanisms underlying these interactions remain poorly characterized, and novel microscopy strategies are needed to specifically address the biointerface. In this study, we employ fluorescence lifetime imaging microscopy (FLIM) with the tension reporter Flipper-TR to investigate membrane tension in live bacteria interacting with various surfaces. We show that Flipper-TR stains both Gram-positive and Gram-negative bacterial membranes, exhibiting fluorescence lifetimes shorter than those in eukaryotic cells, with slight variations between bacterial types and likely reflecting differences in membrane composition. Flipper-TR displays lifetime variations along the vertical axis of bacterial cells, suggesting spatial differences in membrane tension influenced by cell wall architecture. Our results further demonstrate that Flipper-TR is responsive to the nature of bacterial interactions with surfaces. By comparing bacterial immobilization on surfaces with different coatings, we show that Flipper-TR can sensitively distinguish differences in membrane tension arising from distinct adhesion mechanisms. Additionally, Flipper-TR detects changes in membrane tension when bacteria are exposed to engineered nanostructured substrates. Overall, this work expands the toolbox to study the mechanical aspects of bacterial–material interactions and contributes to providing design rules for novel materials that influence bacterial behavior.
Development of a prediction model for student teaching satisfaction based on 10 machine learning algorithms
Endoplasmic reticulum stress and oxidative imbalance is the missing link in fibromyalgia pathophysiology
A generalizable deep learning framework for structure-based protein–ligand affinity ranking
Rapid and accurate estimation of protein–ligand binding affinities is crucial for early-stage drug discovery, yet hindered by a trade-off between the accuracy of gold-standard physics-based methods and the speed of simpler empirical scoring functions. Machine learning (ML) promised to bridge this gap, but its potential is unrealized due to limited model generalizability. Current ML models often fail when predicting affinities for novel proteins or chemical series unseen during training. We hypothesize that this failure stems from a competition within these models during training, where the learning of spurious correlations from structural motifs prevalent in the training data competes with the learning of transferable, physicochemical principles governing molecular interaction. Here, we introduce COnvolutional Representation of Distance-dependent Interactions with Attention Learning (CORDIAL), a deep learning framework designed with an inductive bias toward learning the distance-dependent physicochemical interaction signatures between proteins and ligands, explicitly avoiding direct parameterization of their chemical structures. This interaction-only approach proves effective. Through leave-superfamily-out validation that simulates encounters with novel protein families, we demonstrate that CORDIAL maintains predictive performance and calibration. This contrasts with diverse contemporary ML models, whose predictive ability is degraded under these conditions. Our results highlight the value of encoding appropriate task-specific physicochemical principles into ML architectures and offer a validated strategy for developing generalizable models for structure-based drug discovery.
Leveraging RegNet and CBAM for precise detection of honey adulteration using thermal image analysis
The regulation of placental pericyte function through transforming growth factor β-1 signalling
Ubiquitin-mediated degradation restricts spatiotemporal accumulation of the cytoplasmic male sterility protein WA352 to anthers in rice
Cytoplasmic male sterility (CMS) is caused by mitochondrial genes that are constitutively expressed in plant tissues, although the encoded proteins preferentially accumulate in anthers. The mechanisms regulating CMS protein accumulation remain unclear. Here, we explored this process using wild-abortive CMS (CMS-WA) rice ( Oryza sativa ). We show that WA352, the causal protein of CMS-WA, is degraded by the ubiquitin–proteasome system (UPS). Structural analysis and protein truncation assays revealed that the N terminus of WA352 is critical for its anchoring to the inner mitochondrial membrane and its UPS-mediated degradation. Functional complementation confirmed that WA352 151–352 , lacking the N-terminal domain, accumulates constitutively in vegetative tissues, causing a reactive oxygen species burst and retarding rice growth. We further identified three mitochondrion-localized F-box proteins that participate in WA352 ubiquitination and degradation. Our findings demonstrate that UPS-mediated regulation restricts WA352 accumulation to anthers, allowing it to specifically disrupt anther development, thus helping to explain the male-specific effects of CMS genes in plants.
Success rate and associated factors of conservative management of adhesive small bowel obstruction at Dessie comprehensive specialized hospital, Northeast Ethiopia
Genetic variability and association of chickpea germplasms (Cicer arietinum L.) for nutritional profiles grown in northern Ethiopia
Linking the production of reactive oxygen species to the expression of antimicrobial peptides through aquaporin in an arthropod
In arthropods, bacterial infection activates dual oxidase 2 (Duox2) to produce extracellular reactive oxygen species (ROS), while stimulating the expression of antimicrobial peptides (AMPs) through immune deficiency (Imd)/Relish pathway. Although both strategies contribute significantly to antibacterial immunity, the Duox2/ROS system and Relish/AMPs pathway are generally considered separate branches. In the present study, we report that these two branches are connected by an aquaporin 4 (Aqp4) in a crustacean, the red swamp crayfish Procambarus clarkii . Aqp4 is found to be critical for the crayfish antibacterial response. The significance of Aqp4 is achieved by transporting extracellular ROS into the intracellular compartment after bacterial infection. The increase in intracellular ROS levels, mediated by the c-Jun N-terminal kinase, promotes the nuclear translocation and thereby the transcriptional activity of FoxO. As the key transcription factor of Relish, FoxO regulates the upregulation of Relish and ultimately the expression of Relish-targeting AMPs. By linking ROS production to AMP expression, the sequential ROS/Aqp4/FoxO/Relish/AMPs axis makes a relatively significant, yet previously unnoticed, contribution to the antibacterial response. Therefore, this study reveals the intriguing association between ROS production and AMP expression, the two central antibacterial strategies and provides insights into the regulatory mechanisms of arthropod immunity.
Preliminary effectiveness and feasibility of ASHA-led mobile health intervention for diabetes care in Indian primary health care settings
Abstract Diabetes management in resource-limited settings faces challenges in screening, guideline-based treatment, and healthcare access. The IMPACT Diabetes study evaluated a community-based, technology-enabled task-shifting intervention for diabetes care in India. A cluster randomized controlled trial was conducted in 16 villages/peri-urban areas across 8 primary health centers (PHCs) in two states in India. Accredited Social Health Activists (ASHAs) screened 1,785 community participants, identifying 418 individuals with diabetes. The intervention group received nine months of CDSS-supported care delivered by ASHAs under physician supervision, while the control group received usual care. The primary outcome was the proportion of participants achieving ≥ 0·5% reduction in glycated haemoglobin (HbA1c) from baseline. Secondary outcomes included healthcare utilization and medication adherence. A significantly higher proportion of intervention participants achieved HbA1c reduction ≥ 0·5% compared to the control group (21.8% vs. 10.3%, p < 0.05). Intervention participants had more frequent physician visits (85·0% vs. 29·8%), higher glucose-lowering medication adherence (63·0% vs. 43·1%, p < 0·05), and better engagement with diabetes management practices. Qualitative findings demonstrated that the intervention was acceptable and feasible for patients, ASHAs, and physicians, empowering ASHAs in chronic disease care. This study demonstrates that task-shifting and digital health tools can improve diabetes outcomes in low-resource settings. Future research should explore long-term sustainability and cost-effectiveness.
Paroxetine suppresses 27-hydroxycholesterol-induced responses in THP-1 human monocytic cells by regulating the AKT/mTORC1 pathway
Parkinsonism disrupts the balance between excitatory and inhibitory activity within the primary motor cortex during movement
Parkinson’s disease (PD) has been associated with alterations in neuronal activity in the basal ganglia-thalamocortical (BGTC) network. Previous studies have suggested that cortical disinhibition is a feature of PD, but there has been little direct evidence of the changes in cortical neuronal spiking activity to support this hypothesis. To test the hypothesis that activity in the motor cortex is enhanced in PD, we investigated the effects of parkinsonism on movement-related neuronal activity in the primary motor cortex (M1). Microelectrode arrays were chronically implanted in M1 of two nonhuman primates and populations of cells were collected before and after the induction of parkinsonism using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In both animals, we found that during the reaching task in the parkinsonian state, the proportion of M1 neurons that were activated (excited) during movement were increased, while those that were suppressed (inhibited) decreased. These data support the concept that dopaminergic loss in parkinsonism promotes a loss of inhibition in the motor cortex, leading to overactivity in M1 and a disruption in spatial-temporal processing of information within the BGTC circuit that contributes to the motor dysfunction observed in PD.