Browse Articles

Development of eco-friendly activated carbon from olive pits for the adsorption of tartrazine with isotherm kinetic and thermodynamic studies

Probing the binding stability of organic UV filters to human SLC transporters using AlphaFold and molecular dynamics simulations

Abstract The ubiquitous presence of organic ultraviolet filters (UVFs) in environmental and human, driven by their heavy usage in personal care formulations, has raised significant concern. Despite this, the transmembrane transport mechanisms of UVFs—key to understanding cutaneous absorption and organ-specific toxicity—remain poorly defined. To bridge this gap, this study coupled molecular docking with molecular dynamics (MD) simulations to systematically screen the interactions between various UVFs and solute carrier (SLC) transporters. Through the analysis of 23,970 complex pairs, we identified distinct binding behaviors. Specifically, Tris-biphenyl triazine (TBPT) and Diethylhexyl butamido triazone (DBT) formed highly stable complexes with SLC22A31 and SLC29A4, respectively, exhibiting strong binding affinities (− 10.8 and − 9.8 kcal/mol). Over 200 ns simulations, these complexes maintained ligand Root Mean Square Deviation (RMSD) values below 5 Å. Crucially, per-residue interaction profiling revealed that this persistent stability is governed by high-occupancy (> 80%) hydrophobic anchors, which form rigid “hydrophobic traps” around the lipophilic UVFs. Conversely, the Pentyl 4-(dimethylamino) benzoate (APABA) and TMEM163 complex demonstrated weak interaction (− 3.9 kcal/mol) with significant structural instability, indicated by progressive ligand escape and RMSD values exceeding 15 Å. These findings elucidate how specific UVF-SLC interactions, driven by local hydrophobic complementarity, may facilitate localized toxicological effects, offering a novel computational framework for assessing the transmembrane health risks associated with organic UVFs exposure.

Synchronous stability analysis and enhancement method for grid connected inverters in weak grids

Adaptive cruise control for electric vehicles using hybrid-mode MPC

Abstract The rapid transition towards electromobility urges a concurrent focus on safety and intelligent vehicle control. In this regard, Advanced Driver Assistance Systems (ADAS) are paramount, playing a critical role in mitigating human error and enhancing road and passenger safety. However, challenges remain in the robust formulation and integration of such control systems, particularly considering the difficulty in modeling sophisticated architectures and the power synergy paths of hybrid/electric drivelines. This paper presents a comprehensive, novel methodology that utilizes a single-platform solution for model parameters tuning and online optimization of the control layers within an Adaptive Cruise Control (ACC) system for Electric Vehicles (EVs). To this aim, an intelligent Model Predictive Control (MPC) is developed, based on decentralized control modes for cruising, spacing, and braking. A unified prediction model is implemented to provide look-ahead estimation of the driving situation based on real-time measurements. The efficacy of the model prediction and control mode swapping was investigated through experimental testing of a real EV on a chassis dynamometer, with an emulated lead vehicle detected by an on-board LiDAR sensor. The single-platform, featuring updated model parameters and optimized control gains, demonstrated an ability to maintain speed-tracing and precise spacing when exposed to different disruptive scenarios. The per-mode tracking accuracy achieved 98% in cruise control, 87.8% in spacing control, and 55.0% in braking mode under coasting-only constraints. The proposed work thus offers a significant, unified solution to handle the complex challenges of driveline modeling and control system design, mitigating computational and technical difficulties.

Transcriptome signature for host directed antiviral reprogramming by Nimba & Triphala in macrophage Dengue virus infection models

Study on the stability enhancement mechanism of a high-speed axial compressor under paired swirl distortion

Abstract Serpentine and buried air intake configurations are widely employed in modern fighter aircraft, which induces significant swirl distortion at the inlet and adversely affects compressor operational stability. This study investigates the instability mechanism and stability enhancement technology for high-speed axial compressors under paired swirl, employing combined numerical simulation and experimental verification. Research indicates that compressor stall is primarily caused by expansion of the tip leakage vortex and flow blockage from the forward migration. Casing treatment efficiently alleviates flow blockage by suppressing the formation and development of the tip leakage vortex, which not only improves the stall margin but also restructuring the radial flow pattern to improve the total pressure ratio, thereby facilitating more stable performance in high-speed compressors. In simulations and experiments, casing treatment increased the stall margin by 52.66% and 50.40%, respectively, while the peak efficiency saw only minor reductions of 0.05 and 0.13 percentage points, respectively.

Prediction of delirium in trauma patients using interpretable machine learning

Human placental extract ameliorates methotrexate-induced nephrotoxicity in albino rats: ultrastructural, biochemical and biophysical studies

Abstract Methotrexate (MTX) is a well-known medication for the treatment of different cancer types and autoimmune diseases. The current study target was to measure the capability of human placental extract (HPE) to ameliorate the nephrotoxicity induced by MTX in male albino rats. In the present study, rats were distributed into four groups; a control group (each rat was intraperitoneally injected with 0.5 ml of 0.9% NaCl daily for five days), HPE-treated group (HPE, 10.08 mg/Kg b.w/day, was subcutaneously injected for two weeks), MTX-treated group (MTX, 5 mg/Kg b.w/day, was intraperitoneally injected for five days) and MTX and HPE-treated group (Both MTX and HPE were injected to rats at the same time with the same doses, duration and injection routes in MTX and HPE groups). During the experimental period, clinical observations and body weights of rats were recorded. Rats were dissected after twenty-four hours from the last dose of each group, blood samples were collected for relative blood viscosity measurements and kidneys were also collected for biochemical, ultrastructural and dielectric properties (dielectric constant, dielectric loss and conductivity) investigations. MTX treatment resulted in a highly significant decrease in rat body weights, a highly significant decrease in glutathione (GSH) level and catalase (CAT) activity, a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and a highly significant increase in the malondialdehyde (MDA) level and relative blood viscosity compared to the control group. Besides, obvious ultrastructural changes and pronounced decrease in the dielectric properties of kidney tissues were noticed. While HPE treatment with MTX improved body weight, biochemical, ultrastructural and biophysical changes comparing to the MTX group. Human placental extract can reduce MTX-induced nephrotoxicity in rats through boosting oxidative stress/anti-oxidant balance as it is rich with essential elements.

Weber’s Law in walking: sensory scaling is observed in multi-sensory, dynamic tasks

Abstract Behavioral flexibility requires adequate sensitivity to external stimuli to maintain optimal motor performance under evolving task demands. Empirical evidence shows sensitivity scaling follows Weber’s Law, which states that sensory stimulus perception is scaled by background sensory context magnitude. However, Weber’s Law has been assessed only in uni-sensory static tasks, and whether this principle extends to multi-sensory, dynamic motor tasks remains an open question. We assessed somatosensory perception of relative leg motion (i.e., speed differences between legs) in healthy young adults, hypothesizing that sensitivity to leg speed differences would follow Weber’s Law. We estimated participants’ sensitivity to speed differences (sensory stimuli) using two-alternative forced choice (2AFC) tasks. Participants walked at speeds representing distinct sensory contexts: slow (low-intensity), comfortable (medium-intensity), and fast (high-intensity). All groups compared their assigned testing speed against a common reference speed. We found that sensitivity to speed differences was consistent with Weber-like scaling at both slow and fast non-habitual walking speeds, but deviated near comfortable speed. Moreover, a drift-diffusion model using only reaction times reproduced the sensitivity scaling with walking speed, indicating that the model’s evidence accumulation process can account for speed-dependent changes in perceptual sensitivity in multi-sensory, dynamic motor tasks.

Aberrant Phase Separation of Endothelial MAML1 Causes Congenital Heart Disease by Suppressing Notch Activity

BACKGROUND: Congenital heart disease (CHD), the most common birth defect and a leading cause of infant mortality, is frequently linked to dysregulated Notch signaling. However, the role of the Notch transcriptional coactivator Mastermind-like 1 (MAML1) in CHD pathogenesis and the underlying molecular mechanism remain unclear. METHODS: We investigated the role of MAML1 in CHD by focusing on a patient-derived Q401K mutation with a knock-in mouse model and an endocardium-specific Maml1 knockout mouse model, complemented by CRISPR-edited human heart organoids. Cardiac phenotypes were assessed by echocardiography and histological analysis. The underlying molecular mechanisms were dissected through biochemical assays, microscopy to analyze liquid-liquid phase separation (LLPS), and mass spectrometry to identify posttranslational modifications and the upstream kinase of MAML1. RESULTS: In a clinical cohort of patients with CHD, we identified rare missense variants of MAML1 associated with ventricular septal defects. Modeling a patient-derived variant (Q401K) was sufficient to recapitulate key ventricular septal defect–related phenotypes in both knock-in mice and human heart organoids. To confirm the tissue-specific pathogenicity, we showed that endocardium-specific knockout of MAML1 in mice and MAML1 deletion in human heart organoids caused similar septal and valvular defects by disrupting Notch-driven endocardial-to-mesenchymal transition. Mechanistically, we discovered that MAML1 activity depends on LLPS, which forms nuclear condensates, required for efficient interaction with the NOTCH1 intracellular domain and activation of downstream transcriptional targets. Crucially, patient-derived pathogenic variants, including Q401K, function as charge-altering mutations within the intrinsically disordered region 2, a core region for MAML1 LLPS, pathologically abrogating LLPS to downregulate Notch signaling. Furthermore, we identified a regulatory axis in which PKN2 phosphorylates MAML1 at Ser314, which destabilizes MAML1 condensates and consequently attenuates Notch transcriptional output. CONCLUSIONS: These findings support MAML1 as a candidate gene for CHD and identify MAML1 LLPS as a critical biophysical determinant of Notch transcriptional output in endocardial cells. The electrostatic integrity of MAML1 condensates is essential for proper regulation of Notch signaling during cardiac morphogenesis. Dysregulation of this state, whether through CHD-associated charge-altering variants or aberrant PKN2-mediated phosphorylation, impairs Notch signaling and disrupts endocardial-to-mesenchymal transition, thereby establishing a converged molecular mechanism underlying congenital cardiac malformations.

Is it time to ‘cap and trade’ credits for research-funding proposals?

Optimal FOPID controller design for an AVR system using a Chaotic-Enhanced Phototropic Growth Algorithm (C-PGA)

Patient-derived lymphoma spheroids reveal predictive markers of glofitamab resistance in relapsed/refractory B-NHL

Abstract Bispecific antibodies (bsAbs) such as glofitamab represent a promising therapeutic approach for relapsed/refractory B-cell non-Hodgkin lymphoma (R/R B-NHL), but resistance mechanisms remain poorly understood. This study aimed to identify predictive markers of bsAb resistance based on the response of 3-dimensional patient-derived lymphoma spheroids (PDLS) established from 39 R/R B-NHL samples. PDLS were treated with glofitamab for 3 days, and B-cell depletion was quantified to assess the ex vivo treatment response. Comprehensive immune profiling was performed on patient samples using multiparametric flow cytometry, single-cell RNA sequencing, codetection by indexing spatial proteomics, and functional assays. High responders to glofitamab possessed CD8+ T cells with consistently higher cytotoxic and activation signatures across effector differentiation states, whereas low responders showed enrichment of exhausted CD8+ T cells with enhanced expression of exhaustion markers (T-cell immunoglobulin and ITIM domain [TIGIT], LAG3, and PD1). Furthermore, low responders exhibited elevated functional CD4+ T follicular helper (Tfh) cells in close proximity to malignant B cells, thus promoting their survival through interleukin-21 and C-X-C motif chemokine ligand 13 signaling pathways. Analysis of pretreatment RNA-sequencing data from 48 patients with R/R B-NHL confirmed that high Tfh cell abundance is associated with poor glofitamab response. In PDLS, anti-TIGIT cotreatment enhanced glofitamab efficacy in low responders, and Tfh cell depletion experiments confirmed that reducing Tfh cell activity increased B-cell depletion. Together, these findings identify CD8+ T-cell exhaustion and functionally activated Tfh cells as key factors associated with glofitamab resistance in R/R B-NHL. This work supports their potential use as predictive biomarkers for selecting patients with higher probability of response and provides a foundation for future combination therapeutic strategies.

Better diagnostics could have limited this Ebola outbreak

Enhanced response of extreme compound events to cumulative CO2 emissions

White blood cell count to platelet ratio (WBC/PLT) is associated with adverse lipid parameters and lower antioxidants intake in patients with NAFLD

Another “one stone hit two birds” candidate in chronic GVHD

Health information needs of women with gestational diabetes mellitus: a qualitative study

Clonal tracing of blood stem cells across mouse and human lifespans

Abstract For over 60 years, blood researchers have been counting clones with every tool at their disposal. Inspired by phage and fly geneticists, Till and McCulloch irradiated mice to induce chromosomal aberrations. Using this labeling strategy, they demonstrated that different types of blood cells shared the same mutation in every spleen colony, thereby proving the existence of hematopoietic stem cells. Since their breakthrough, technological advances have enabled researchers to quantify hematopoiesis at single-cell resolution in increasingly complex samples across both mice and humans. With these modern sophisticated lineage-tracing methods, our foundational understanding of the blood system is being reshaped. For instance, we now interpret hematopoietic architecture as arising from stem and progenitor cells of diverse developmental origins, each with distinct fate biases encoded by unique regulatory states. Interacting with this regulatory layer, genetic mutations and epimutations arise, expanding clonally and becoming pervasive with age. Together, clonal heterogeneity and age-driven clonal selection may underlie the perplexing diversity of therapy responses in cancer and beyond. As these paradigm-shifting insights gain traction, clonal tracing is being adopted across dozens of biological and clinical studies. Here, we review the modern toolbox of clonal tracking technologies, with a focus on next-generation sequencing-based approaches, and provide a practical guide for matching specific research questions with optimal experimental strategies.

Power imbalances in adviser–student relationships need safeguarding