Browse Articles

Vahan Samvedak: a comprehensive real-time college bus tracking and safety system

SpatialCOC: an integrative framework for spatial continuous mapping and cross-omics correction in spatial multi-omics data

Abstract Integrating spatial multi-omics data presents significant challenges, particularly in uncovering the spatial patterns of cells and deciphering the real regulatory mechanisms among various omics. These insights are critical for harnessing the full potential of each modality while minimizing the impact of biotechnological biases that will lead to unstable results. Here, we introduce SpatialCOC, a framework that treats spatial information as prior knowledge to learn omics-specific spatial distributions, then discovering nonlinear correlations among modalities. The effectiveness and robustness of SpatialCOC are validated using real-world datasets, encompassing diverse tissue sections analyzed with multiple experimental techniques. Compared to existing methods, SpatialCOC excels in identifying region-specific continuous spatial domains and maintains batch-consistency across trajectory inferences. By providing a novel perspective on the interplay between spatial information and multi-omics modalities, SpatialCOC offers a flexible approach that can accommodate modality data of arbitrary dimensions.

The tip of the iceberg: Profiling cooling agents using computational approaches to inform tobacco regulatory science

Cooling agents (chemicals added to impart a cooling sensation) in tobacco products are receiving increased attention due to their use as menthol substitutes. However, detailed information on their chemical structures, physico-chemical properties, cooling activity, and human and ecotoxicity potential has not been compiled. Our goal was to profile cooling agents that could be used as menthol substitutes in tobacco products, along with descriptions of their cooling properties and estimated toxicological effects. First, we compiled a library of 228 cooling agents, including 180 unique two-dimensional (2-D) chemical structures based on a review of multiple public data sources (literature, invention patents, and public databases). The library includes chemicals with a “cool” and/or “mint” flavor profile as designated by the Flavor and Extract Manufacturers Association (FEMA), chemicals reported to activate the cation channel transient receptor potential melastatin 8 (TRPM8) receptor, and/or chemicals with reported subjective perceived sensory cooling. Second, we classified the cooling agents into three main chemical skeletons using similar structural motifs and estimated their physico-chemical properties related to cooling attributes using Schrödinger Canvas software, including log octanol-water partition coefficient (LogKow), vapor pressure, and electrotopological state index. Third, to investigate the cooling agents’ similarity to each other and to menthol, we applied an unsupervised machine learning algorithm (Knowledge Discovery by Accuracy Maximization [KODAMA]) and hierarchical clustering techniques and identified six clusters. Fourth, we compiled available perceived cooling intensity data. Fifth, we used models based on experimental and predicted data (EPA’s web-based Hazard Comparison Module [HCM]) to estimate human health toxicity and ecotoxicity. Some cooling agents are associated with genotoxicity, developmental toxicity, skin irritation, and eye irritation, and pose toxicity to fish, algae, and invertebrates. Using this surveillance approach will help inform future tobacco regulatory decisions and policies by profiling chemicals used as cooling agents in tobacco products and those that pose potential health hazard concerns.

The striking history of safety matches

A privacy-preserving cloud storage framework with hybrid encryption, homomorphic keyword search, and blockchain-based integrity verification

Atomistic characterization of the maturation mechanisms in the HIV-1 capsid domain

Abstract During HIV-1 maturation, capsid proteins (CA) are proteolytically cleaved from the immature Gag lattice and undergo conformational transitions in which the amino-terminal and carboxy-terminal domains rearrange into mature conformations prior to assembling into fullerene complexes. Little is known, however, of the structural transitions and energetic principles governing this transformation. Here, we reveal the dynamical mechanisms of CA maturation using all-atom and enhanced sampling simulations. Free energy calculations demonstrate that immature CA is intrinsically unstable as a monomer and rapidly converts into a mature form that is consistent with x-ray crystallographic and cryo-electron microscopy structures. Analysis of the minimum free energy pathway indicates that conformational change in CA proceeds through stepwise, ratcheting transitions, and we identify a metastable intermediate distinct from the immature and mature endpoints. Energy decomposition analysis uncovers the interdomain residue-residue interactions, particularly charged contacts, that stabilize the mature state. These results reveal the interactions and molecular mechanisms that drive the conformational changes required for HIV-1 capsid domain maturation.

Assessment of hemagglutinin-inhibition activity following influenza vaccination during the 2022–2023, 2023–2024, and 2024–2025 seasons

Seasonal influenza vaccines are available in multiple formulations including egg-based inactivated standard-dose, cell-based inactivated, recombinant, and live-attenuated. However, vaccine effectiveness and antibody responses vary by vaccine type, recipient age, and prior influenza exposures. Both age and repeated annual vaccination can modulate immune outcomes through antigenic differences between historical and updated vaccine formulations. In this three-season (2022–2023–2024–2025) study, 1,328 participants aged 9–89 years received one of six vaccine types (Fluzone standard dose (SD) or high dose (HD), Fluad, Flucelvax, Flublok, Flumist). Collected serum samples were tested for hemagglutination inhibition (HAI) activity against vaccine strains and historical circulating strains before vaccination and day 28 post-vaccination. Seroprotection and seroconversion rates were analyzed by age group and vaccine platform. Repeated vaccination across consecutive seasons was associated with reduced HAI boosting to current vaccine strains in some participants, although vaccination broadly increased antibody titers to prior strains (back-boosting) and maintained high seroprotection rates from year to year. Participants ≥65 years had lower post-vaccination HAI titers compared to younger adults and had rapid waning of HAI titers than vaccinated younger adults, yet elderly participants with HAI titers <1:40 had higher seroconversion rates following vaccination, which may in part reflect lower baseline titers in this group allowing a ≥ 4-fold rise to meet the seroconversion definition with Fluzone HD or Fluad adjuvanted vaccines compared to younger vaccinated participants. Over the three seasons, younger adult participants vaccinated with Flublok had higher HAI titers than participants vaccinated with Fluzone SD against H1N1 and H3N2 strains. In contrast, post-vaccination HAI titers in elderly participants were comparable between Fluzone HD and Fluad recipients for each vaccine component, including influenza A and B strains. Participants vaccinated with Flumist had low or no measurable serum HAI activity. Overall, the elicitation of vaccine induced immune responses is strongly influenced by vaccine formulation, age and immune history of the participant.

Dietary pollen and carbohydrate sources influence longevity, physiology, and gut microbiota in honey bee (Apis mellifera)

Abstract The Western honey bee ( Apis mellifera ) is essential for crop pollination and ecosystem stability and production for beekeepers as well, yet rising colony losses are a major concern. Poor nutrition is a key stressor, prompting beekeepers to supplement carbohydrates and proteins during nectar and pollen shortages. This study was conducted under controlled laboratory cage conditions to evaluate the interaction effects of two carbohydrate sources, regular corn syrup (rich in maltose) and sucrose syrup; and three pollen types (rapeseed, kiwi, and mixed pollen) on honey bee longevity and physiological performance. Bees fed corn syrup lived longer and developed larger hypopharyngeal glands (HPG) than those fed sucrose syrup. Among pollen treatments, mixed pollen produced the most favorable outcomes, including increased survival, larger HPG acini, and higher vitellogenin levels. The combination of corn syrup and mixed pollen (CS–MP) yielded the longest lifespan, and lowest food consumption, indicating improved nutritional efficiency. Gut microbiota composition varied with diet: RP and KP diets showed higher relative abundances of Sondgrassella and Gilliamella compared with MP whereas the mixed pollen diet promoted a higher relative abundance of Lactobacillus . These results demonstrate that optimizing carbohydrate and pollen combinations can significantly enhance honey bee health, longevity, and colony resilience, providing practical insights for nutritional management in apiculture.

Clonal biases dictate availability of colonic cancer driver mutations for transformation

Abstract Aged normal tissues harbour cancer mutations predisposing to transformation. However, how different pro-oncogenic events in the human colon compare in frequency, behaviour and subsequent transformation risk remains unclear. Here, we analyse mutation hotspot regions in five colorectal cancer genes ( APC , KRAS , TP53 , FBXW7 and CTNNB1 ) using targeted sequencing of 76,800 normal colonic glands from 56 patients. We show that cancer-driving mutations are present in all genes in histologically normal tissue. Reconstruction of clone dynamics reveals that FBXW7 R465C mutations preferentially become fixed within the tissue, whereas KRAS G12 mutations strongly promote expansion. Modelling mutation order indicates that early loss of both APC copies increasingly favours an APC -first pathway with age, while KRAS activation is equally likely to initiate events in younger individuals. Spatial transcriptomics highlights phenotypic heterogeneity among KRAS mutant clones, with mixed lineage presentation observed only in a subset, a state linked to elevated transformation risk in other organs.

Determinants of knowledge, attitudes and childbirth experiences related to obstetric violence among women who delivered in the public health facilities of Jimma Zone Southwest Ethiopia: A cross sectional study design

Background The World Health Organization recognizes every woman has the right to respectful and dignified care during childbirth. However, a significant number of women experienced obstetric violence (OV) acts or omissions causing harm, violating rights, or undermining autonomy, remains prevalent globally, including in Ethiopia where women’s knowledge gaps and unfavorable attitudes perpetuate it due to limited rights awareness and cultural norms. In southwest Ethiopia, evidence on women’s knowledge, attitudes, childbirth experience related to OV, and their determinants among facility-based deliveries is scarce. This study thus investigates these factors among mothers delivering in public health facilities. Method An institutional-based retrospective cross-sectional study was conducted among 402 women in public hospitals of the Jimma zone from August 12 to October 12, 2022. A simple random sampling technique was used to select the study subjects for structured, pre-tested face-to-face exit interviews. Data were entered into Epi-Data version 3.1 and exported to SPSS version 23 for analysis. Then, factors that showed significant associations in a bivariable linear regression model were added to multivariable linear regression models. Variables that had a P-value of < 0.05 in the multivariable model were considered statistically significant. Finaly, the results were presented using texts, tables and graphs. Results The present study showed that more than two-thirds of women had a knowledge about universal rights during childbirth with a mean score of 14.89 ± 6.76, 68). About two out of three participants had unfavorable attitude towards childbirth experience (mean 33.55 ± 4.91, 66%) and experienced OV (mean 67.09 ± 11.79, 64%) during labor and childbirth. Women living in urban areas (β = −4.69, 95% CI: −6.41, −2.96), those with antenatal care (ANC) contacts (β = −9.65, 95% CI: −11.18, −8.11), who gave birth at night (β = 4.06, 95% CI: 2.42, 5.70), and without obstetric complications (β = −8.07, 95% CI: −9.98, −6.16) showed significant associations with obstetric violence. ANC contacts (β = 3.23, 95% CI: 2.02, 4.45) and companion utilization (β = 4.87, 95% CI: 2.14, 7.59) positively associated with women’s knowledge levels. Absence of obstetric complications (β = −3.06, 95% CI: −4.00, −2.11), urban residence (β = −1.89, 95% CI: (−2.86, −1.01) and ANC contacts (β = −3.36, 95% CI: −4.13, −2.59) were associated with unfavorable attitudes toward childbirth experience related to obstetric violence. Conclusion The study revealed that more than two-thirds of participants had relatively lower knowledge of childbirth rights. Likewise, approximately two-thirds held unfavorable attitudes and experienced obstetric violence (OV). The most commonly reported forms OV were non-dignified care, non-consented care, and physical abuse. Sociodemographic factors (residence, maternal occupation) and maternal factors (ANC contacts, obstetric complications, companion utilization) associated with women’s knowledge, attitudes, and childbirth experience related to OV. To mitigate the challenges, prioritize comprehensive training for providers on respectful and dignified care, alongside women’s education to foster rights awareness and self-advocacy. Enhance ANC access, companion policies, and targeted strategies for high-risk groups (e.g., rural residents, certain occupations) to create supportive childbirth environments.

AI agents replicate human social dynamics in days

Influence mechanism of pre-oxidation on the secondary oxidation characteristics of coal: insights from TG-DSC-FTIR analysis

Unlocking the ionic transport dynamics modulated by concentration artifacts of Li(Na)-ion batteries via operando optical fiber spectroscopy

Methylviologen resistance in loss-of-function mutants of the polyamine transporter gene OsLAT5

TALENs and CRISPR/Cas have become routine tools for genome editing. During stable plant transformation, genes coding for editing enzymes, e.g., Cas9, guide RNAs (gRNA), and selectable or screenable markers are integrated into the nuclear genome. Identification of successful transformants relies on selectable or screenable markers, typically genes providing resistance to herbicides or antibiotics. Selectable markers use a substantial portion of the T-DNA, hence reducing transfer efficiency by limiting the effective number of TALENs or guide/pegRNAs that can be used. Marker genes are frequently subject to gene silencing. Here, we generated loss-of-function mutations in PUT/LAT-type polyamine transporter family genes to confer resistance to methylviologen (MV) in rice. As proof of concept, CRISPR/Cas9 constructs with gRNAs were generated to target three close homologs, namely OsLAT1 , OsLAT5 , and OsLAT7 . Loss of OsLAT5 (also known as OsPUT3 or OsPAR1 ) function was sufficient to confer resistance to MV in rice seeds, seedlings and calli. Loss-of-function alleles generated by editing of LAT5 can serve as a selectable marker at the seed germination stage. We discuss the potential utility of rice lat5 loss of function variants as selectable markers for genome editing.

Cross-species metabolic characterization of eutylone and mechanism-based inhibition of CYP2D6 and CYP2B6 with drug interaction implications

Immune-induced TCR-like antibodies regulate specific T cell response in mice

Abstract Antigen-specific regulation of T cell response is crucial for limiting hyperimmune response. However, the molecular mechanisms governing specific immune regulation remain unclear. In this study, we discover that antibodies specific to the antigen peptide-MHC class II complex are produced during helper T cell responses to various antigens, including hen egg lysozyme and proteolipid protein peptide. These antibodies specifically inhibit T cell receptor (TCR) recognition of MHC class II molecules presenting specific antigen peptide. We term these antibodies ‘immune-induced TCR-like antibodies’ or iTabs. Immunization with peptides containing flanking residues induces iTabs whereas immunization with peptides lacking flanking residues does not. Furthermore, we show that immunization with iTab-inducible peptide or iTab treatment suppress autoimmune disease development in a mouse model of experimental autoimmune encephalomyelitis. Thus, our findings provide a strategy for suppressing antigen-specific helper T cell responses using specific peptides, potentially controlling autoimmune diseases.

A comparative study of organoid-derived and cell line-derived intestinal epithelial models

Background In vitro intestinal epithelial models are being developed for studying gut physiology, barrier function, and drug transport. There are two major in vitro models which are currently used: cell line-derived monolayers (such as Caco-2/HT29 cocultures) and primary cell monolayers derived from human intestinal organoids. Aim To conduct a side by side comparison of organoid-derived and cell line-derived intestinal epithelial monolayers, assessing their morphological features, barrier performance, and secretome under similar culture conditions. Methods Human duodenum-derived organoids and Caco-2/HT29 cocultures (9:1 ratio) were seeded onto Transwell inserts and were harvested at the same time for comparative analysis. Barrier function was assessed by transepithelial electrical resistance (TEER) and Lucifer Yellow permeability. Structural characterization was performed using immunofluorescence microscopy, scanning and transmission electron microscopy. Secretion of growth factors and chemokines was quantified on apical and basal sides via multiplex assays. Results Both models formed intact epithelial barriers with robust tight junctions and displayed appropriate apical-basolateral polarization, confirmed by the presence of microvilli. However, the organoid-derived model exhibited occasional villus-like protrusions and ultrastructural crypt-like invaginations, homogenous secretion of Mucin 2 over the surface, and release of epithelial growth factor whereas the cell line model exhibited longer and more densely packed microvilli and higher apical secretion of vascular endothelial growth factor. The barrier properties were comparable except that the organoid model had decreased permeability (Lucifer Yellow). Conclusions This study highlights key structural, functional, and molecular similarities and differences that influence the physiological relevance and application scope of each model. It enables educated decision making when choosing the best model for a particular “Context of Use” weighing the pros and cons between experimental convenience and physiological relevance.

Stop the ‘space race’: space exploration must be a shared human endeavour

New large pterosaur tracks from Korea and their implications on terrestrial behavior

2040 greenhouse gas reduction targets and energy transitions in line with the EU Green Deal

Abstract The European Green Deal aims to guide the European Union towards achieving net-zero greenhouse gas emissions by implementing a comprehensive set of policy initiatives and legislation. While emission reduction targets and policies up to 2030 are mostly implemented, it is of high priority for EU legislation to spell out the further transformation to climate neutrality by defining interim policy targets for 2040. To provide information for this target-setting process, we use an integrated energy-economy-climate model with high sector detail to explore pathways to achieve climate neutrality in the EU under uncertainty about key energy system developments. Results suggest that emission reductions of 86% (sensitivity range: 80% to 93%) by 2040 relative to 1990 are consistent with a cost-efficient distribution of mitigation efforts over time, substantially exceeding the 78%-level implied by a linear interpolation between the 2030 and 2050 targets. Additionally, we identify a 7-fold (sensitivity range: 4–8-fold) upscaling of electricity generation from wind and solar, a 49% (sensitivity range: 45–59%) share of electricity in final energy supply and an upscaling of carbon capture and storage (CCS) to 188 Mt CO2/yr (sensitivity range: 56–257) as crucial transformation milestones for 2040.