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Protective potential of tween 80-functionalized chitosan-selenium nanoparticles containing quercetin against cisplatin neurotoxicity in PC12 cells: an in vitro and network pharmacology study

RETRACTED: Ph-triazole as a therapeutic agent for pancreatic cancer: Synthesis, in silico, and in vitro evaluation

The current study investigated the therapeutic potential of Ph-triazole in silico and in vitro against pancreatic cancer. Common targets between Ph-triazole and pancreatic cancer, notably P53 protein, were identified using the venny 2.1.0 tool and imported into the String database to construct the protein-protein network. Box plot revealed that the most prominent hub gene TP53 is strongly up-regulated in pancreatic tumor tissues (N = 179) compared to normal tissue samples (N = 171), and stage plots confirmed that its upregulation is found during all four stages of the disease. Survival analysis of the pancreatic cancer patients revealed a strong correlation between TP53 gene overexpression and low overall survival and disease-free survival. Molecular docking showed that Ph-triazole exhibits a strong binding affinity for P53 protein. In vitro data also confirmed the anti-proliferative effect of Ph-triazole in pancreatic cancer cell models. Therefore, Ph-triazole can act as an anti-proliferative agent for pancreatic cancer and needs to be investigated further by in vivo studies.

Personalized CRISPR knock-in cytokine gene therapy to remodel the tumor microenvironment and enhance CAR T cell therapy in solid tumors

Abstract The immunosuppressive tumour microenvironment (TME) remains a central barrier to effective immunotherapy in solid tumours. We present a gene-therapeutic strategy that enables localized remodelling of the TME via tumour-intrinsic cytokine expression. Central to this approach is CancerPAM, a multi-omics bioinformatics pipeline that identifies and ranks patient-specific, tumour-exclusive CRISPR-Cas9 knock-in sites with high specificity and integration efficiency. Using neuroblastoma as a model, CancerPAM analysis of tumour sequencing data identifies optimal knock-in sites for pro-inflammatory cytokines (CXCL10, CXCL11, IFNG), and CancerPAM rankings correlate strongly with target-site specificity and knock-in efficiency, validating its predictive performance. CRISPR-mediated CXCL10 knock-in enhances CAR T cell infiltration and antitumour efficacy in vitro and in vivo, including humanized CD34⁺ HuNOG mice, where CXCL10-expressing tumours show stronger immune infiltration and prolonged tumour control within a reconstituted human immune microenvironment. Our findings establish a framework for safe and effective CRISPR-based cytokine delivery, integrating localized TME remodelling with cellular immunotherapies to enhance CAR T cells and other treatments in immune-refractory solid tumours.

Volcanic forcing of the Lomagundi–Jatuli carbon isotope excursion

The Lomagundi–Jatuli Event (LJE), Earth’s most pronounced and prolonged positive carbon isotope excursion, followed the Great Oxidation Event and remains enigmatic in origin. We present a Pb–Pb isochron age of 2,194 ± 5 Ma for black shales from the Francevillian FB Formation, Gabon—an LJE type locality—coinciding with the emplacement of the Large Igneous Province that gave rise to the extensive Birimian–Eburnean orogenic segment. This orogeny produced very large volumes of juvenile crust in the form of oceanic plateau basalts that were eventually reworked through subduction and collisions. These processes released substantial volcanic CO 2 into the ocean–atmosphere system, disrupting the carbon and oxygen cycles for 100 to 200 My. Volcanic outgassing likely outpaced alkalinity production from weathering, leading to an increase in the δ 13 C of sedimentary carbonates. Reanalysis of global δ 13 C–δ 18 O datasets reveals a previously unrecognized dual bimodality, attributed here to episodic volcanic degassing and subsequent oceanic carbonate saturation. Weathering of emergent crust enhanced nutrient fluxes, driving primary productivity and organic carbon burial. We further propose that volcanic CO 2 emissions modulated the Dole Effect by shifting the balance between terrestrial and marine photosynthetic oxygen production, altering atmospheric oxygen isotope ratios independently of climate. These processes collectively drove the δ 13 C excursion of the LJE and may have fostered conditions conducive for early eukaryotic evolution.

RETRACTED ARTICLE: AI-optimized GRU-based self-attention model for predictive diabetes staging in IoT healthcare 5.0

Effects of a 12-week dance program with two weekly frequency protocols on fine motor competence and balance in preschool children: A randomized controlled trial

This study examined the effects of structured dance programs on motor competence in preschool children. In a 12-week randomized controlled trial, 80 children were randomly assigned to two dance intervention groups (EG1: 2 × 35 min/week; EG2: 3 × 25 min/week) or a control group (CG) following the standard physical education curriculum. Fine motor skills, fine motor integration, and balance were assessed using the Bruininks–Oseretsky Test of Motor Proficiency, administered both before and after the intervention. Significant improvements were observed in EG1 for fine motor precision (p < 0.001), fine motor integration (p = 0.022), and static balance (standing on one leg on a balance beam with eyes open; p < 0.001). EG2 showed significant gains in dynamic balance (walking forward on a line; p < 0.001). Both dance programs enhanced preschoolers’ motor competence compared to the control, with higher session volume producing superior outcomes. These results support integrating structured dance sessions into preschool curricula to effectively enhance motor competence, offering a practical strategy to promote physical development in early childhood.

Bidentate mixed-ligand strategy in dinuclear gold photoredox catalysis

S-cone-specific circuitry in the outer plexiform layer of a cone-dominant mammal

In the vertebrate retina, short wavelength-sensitive S-cones and their downstream interneurons play unique roles in both image forming and non-image-forming vision. Due to their conserved relative rarity in the retina and the high density of rods found in many model species, S-cone circuitry is challenging to examine in detail. Here, we combine electrophysiology, high-quality 3D electron microscopy reconstruction, and electroretinography to characterize in fine detail the S-cone selective circuitry in the outer plexiform layer (OPL) of the cone-dominant retina of the thirteen-lined ground squirrel (13-LGS). The 13-LGS retina has no S-OFF bipolar cell, and both horizontal cell types show distinct S-cone preferences. Signal processing in the 13-LGS OPL appears to have evolved for separate channels that independently modulate synaptic sensitivity of S- and M-cone networks.

Prediction of drug approvals in oncology using explainable artificial intelligence

Elemental composition of vaping and smoking aerosols: Influence of liquid type and tank conditions

This study compares the elemental composition of aerosols produced by e-cigarettes and traditional cigarettes using Energy Dispersive Spectroscopy (EDS). Both homemade and store-bought e-liquids were tested under various tank conditions (full, half, and empty), and emissions were collected using nitrocellulose membranes and coil cotton. Additional measurements were performed on unheated e-liquids, cigarette filters, unused cotton, and membranes to assess background contamination. Key elements identified included chromium (Cr), aluminum (Al), sodium (Na), sulfur (S), chlorine (Cl), and copper (Cu). Homemade e-liquids showed significantly higher Cr and Al concentrations, especially under partial tank conditions, suggesting intensified coil degradation. Store-bought e-liquids demonstrated more stable emission profiles. Traditional cigarette smoke contained fewer trace metals but exhibited different elemental patterns. Supplementary viscosity and thermal analyses revealed that homemade liquids degrade more rapidly under heat, which may enhance metal leaching from coils. These findings underscore the influence of liquid composition and device conditions on emission profiles, emphasizing the need for quality control in e-liquid production and further toxicological evaluation of e-cigarette use.

Shared human-machine control of an intelligent bionic hand improves grasping and decreases cognitive burden for transradial amputees

Genome of venomous caterpillar <i>Doratifera vulnerans</i> reveals recruitment of immune peptides and their adaptation as pain-inducing toxins

Gene duplication followed by adaptation to new selection pressures has been proposed to be of central importance in the evolution of venom toxins. Coupling high-quality genome data with quantitative bioactivity readouts can be used to understand how venom toxins evolved, but such studies are rare. Here, we report a near chromosomal-level genome assembly for Doratifera vulnerans (Lepidoptera: Limacodidae), which is venomous in the larval stage. We identify 115 gene loci that produce the polypeptide toxins in venom, including numerous multigene families as well as single-copy genes. Previously described membrane-permeabilizing peptides that cause pain are shown to be encoded by a gene cluster on chromosome 7 that also encodes multiple members of the cecropin family, which are insect innate immunity peptides. These data reveal the origin of defensive toxins from immune peptides followed by strong sequence divergence driven by positive selection pressures. Dv13, which is present as a trace component in the venom, and which has sequence features conserved with canonical cecropin A, potently inhibited the growth of Gram-negative bacteria and fungi, but only weakly permeabilized the membranes of mammalian neurons with EC 50 values &gt;100 µM. In contrast, peptides Dv11 and Dv12 are abundant in the venom, have sequence features divergent from Dv13, and potently disrupt mammalian neuronal membranes with EC 50 values as low as 190 nM, but have reduced antimicrobial activity. These data provide evidence for the adaptation of innate immune peptides as specialized defensive venom toxins and provide a natural experiment informing the structure–activity relationships of cecropin family peptides.

Development and validation of a novel prediction model for hypertensive disorders of pregnancy based on maternal cardiovascular function and placental blood flow metrics at 22 to 24 gestational weeks using machine learning

Abstract Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal and perinatal morbidity worldwide, and current screening strategies have limited predictive value in low-risk populations especially for late-onset HDP. This study aimed to develop and internally validate an interpretable machine-learning model for predicting HDP using noninvasive parameters of maternal systemic hemodynamics, endothelial function, and utero-placental and feto-placental blood flow measured in mid-pregnancy. In this cross-sectional cohort, 577 normotensive women underwent impedance cardiography and Doppler ultrasonography at 22 + 0 to 23 + 6 weeks’ gestation. The incidence of HDP was 16.6% (96/577) most (87.5%) occurring at term (≥ 37 weeks), including 73 cases of gestational hypertension (12.6%) and 23 cases of pre-eclampsia (4.0%). An optimized predictive model with seven physiological features was developed using Extreme Gradient Boosting (XGBoost). Hyperparameters were optimized using stratified 10-fold cross-validation maximizing average Precision Recall Area Under the Curve (PR–AUC), and the decision threshold was selected by maximizing the geometric mean of sensitivity and specificity on a separate validation set. On an independent test set ( n  = 58; 10 HDP), the model achieved an Area Under the Receiver Operating Curve (ROC–AUC) of 0.82 (95% CI 0.65–0.95) and a PR–AUC of 0.57 (95% CI 0.26–0.84). At the optimized operating point, sensitivity was 70% (95% CI 0.40–1.00), specificity 79% (95% CI 0.67–0.90), precision 41% (95% CI 0.18–0.65), and negative predictive value 93% (95% CI 0.84–1.00). This interpretable, non-invasive mid-gestation model demonstrates strong discrimination and excellent negative predictive value, supporting its integration into routine second-trimester screening for risk stratification without reliance on biochemical markers.

Designing ethical souvenirs to sustain the cultural integrity of Dunhuang heritage

Mass-produced tourism souvenirs often dilute the cultural integrity of heritage sites, yet the mechanisms by which design philosophy and ethics sustain authenticity remain underexplored. This study investigates how designers’ philosophical stances and ethical practices shape authentic Dunhuang souvenirs. Adopting a qualitative single-case design, the investigation used purposive sampling to recruit 11 participants (eight designers and three cultural experts). Data from in-depth semi-structured interviews, non-participant observations, and document review were analysed via reflexive thematic analysis conducted concurrently with data collection. Three interlinked themes emerged: (1) design principles and philosophy, (2) ethical considerations, and (3) design implementation, coalescing into the Ethical Design for Cultural Integrity (EDCI) framework. The EDCI explains how authenticity and market relevance can be co-achieved by coupling value-laden design reasoning with procedural safeguards in production. Practical guidance includes: pre-brief checklists identifying non-negotiable cultural elements; embedded ethics procedures across decision points; and feedback-rich implementation cycles that preserve core motifs while meeting manufacturability and price envelopes. The study’s originality lies in integrating philosophy, ethics, and implementation into a single process view of heritage product design and in operationalising ethics as procedural governance rather than declarative intent, offering a replicable pathway for culturally responsible souvenir development.

Extremely cold ocean temperatures in iron formation brine pools of snowball Earth

Abstract For the severe low-latitude “snowball Earth” glaciations, glacial deposits occurring on all continents is well-established. However, cold, salty, ice-covered oceans—a salient prediction of snowball Earth—is difficult to establish geologically. Here we demonstrate that anomalously high iron isotope values (δ 56 Fe) of snowball iron formation—never observed in earlier anoxic Archaean oceans—can be attributed to additional temperature-dependent fractionation in extremely cold brine pools in the snowball ocean. Experiments and modeled fractionations relevant to the precipitation of iron formation demonstrate temperature-dependent δ 56 Fe fractionation, where colder temperatures correspond with more positive δ 56 Fe. Assuming the ~ 0.9‰ differential in δ 56 Fe values of snowball iron formation in excess of those preceding the Great Oxidation Event is due to temperature-dependent fractionation, we calculate that the temperature of the iron formation brine pools was –15 ± 7°C. Such cold snowball brine pools, colder than those in Antarctic margins today, represent Earth’s coldest recorded ocean temperatures.

What does drive temporal variation in population size in mammalian species?

PatternFusion: a hybrid model for pattern recognition in time-series data using ensemble learning

Where to flee? Preferences for host communities among displaced people in Congo

Previous research has explored host communities’ attitudes toward displaced individuals, but much less is known about what displaced people seek in a host community. Understanding both perspectives is key to fostering successful local integration. We address this gap through a randomized conjoint experiment in which nearly 2,000 respondents in the Kasai region of the Democratic Republic of Congo - internally displaced persons (IDPs), returned IDPs, repatriated refugees, and members of the host community - evaluated hypothetical host communities, imagining where they would prefer to settle if forced to flee. Results indicate that, beyond safety, respondents prioritize job opportunities while also valuing social networks and political participation. Preferences are largely similar across groups. The findings suggest that the promotion of economic opportunities and inclusive governance are among the most effective strategies to create conditions conducive to local integration.

Platelet-bioengineered hiPSC-sEVs achieve targeted repair of fibrotic sinoatrial node in preclinical SND models

Control of renal calcium permeability via a tight junctional claudin switch

Tight junctions seal the paracellular space between epithelial cells, with their claudin (CLDN) composition dictating epithelial permeability properties. In kidney thick ascending limbs, calcium is reabsorbed paracellularly through a meshwork of CLDN16 and CLDN19 polymers. CLDN14 is strongly upregulated by high blood calcium, restricts this paracellular calcium flux, and is linked to kidney stone disease. How CLDN14 controls paracellular calcium flux and structurally incorporates into this complex junction is unknown. Using confocal and super-resolution microscopy, we show that CLDN14 preferentially associates with CLDN19, thereby gradually replacing CLDN16 in the CLDN19 copolymer in vitro and in mice in vivo. The claudin switch depends on CLDN14 polymerization and occurs on a timescale of days via a pathway independent of dynamin-mediated endocytosis. Our findings reveal a mechanism of tight junction regulation, demonstrating how dynamic claudin remodeling within this complex structure controls renal calcium excretion and contributes to kidney stone pathogenesis.