Browse Articles

Discrete Immolative Guanidinium Transporters deliver mRNA to specific organs and red blood cells

Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease

Aberrant pace of cortical neuron development in brain organoids from patients with 22q11.2 deletion syndrome-associated schizophrenia

Bringing the museum into the hospital to promote cultural wellness in patients undergoing haemodialysis through a virtual reality tour

Tumor control and immune activation through palliative irradiation and ATR inhibition, PATRIOT Part C: a phase Ib trial

Deep-learning model for embryo selection using time-lapse imaging of matched high-quality embryos

A randomized, double-blind, placebo-controlled trial of niclosamide nanohybrid for the treatment of patients with mild to moderate COVID-19

Abstract Effective and reliable treatments for SARS-CoV-2 infections are a key part of global COVID-19 management. Based on vitro studies, niclosamide has been considered as a potential drug candidate for SARS-CoV-2, but its clinical development has been limited due to poor solubility and bioavailability. Here we report results from a randomized, double-blind, placebo-controlled clinical trial involving 300 patients (Clinical Trial Registration Number: KCT0007307) that assessed the efficacy and safety of the niclosamide nanohybrid CP-COV03 at two different doses. Oral CP-COV03 was well tolerated, with no serious adverse events reported in any treatment group. The primary endpoints demonstrated that CP-COV03 significantly alleviated all 12 FDA-recommended COVID-19 symptoms, with symptom improvement sustained for more than 48 h. Additionally, CP-COV03 reduced SARS-CoV-2 viral load by 56.7% within 16 h of the initial dose compared to baseline. Secondary endpoints, including time to sustained symptom resolution, time to return to usual health, and reduction in hospitalization risk, also showed favorable results in the CP-COV03 group compared to placebo. These findings indicate that CP-COV03 is a safe and effective therapeutic option for the treatment of mild to moderate COVID-19 and represents a promising advancement in the repurposing of niclosamide through nanohybrid engineering.

Skin burns after high-intensity focused ultrasound ablation: a retrospective control study

Intestinal CD4−CD8αβ−TCRαβ+ T cells function as tolerogenic antigen presenting cells in mice

Trends in surgical indications and causative diagnoses in enucleation from 2007 to 2022

Abstract To evaluate surgical indications and causative underlying diseases in patients undergoing enucleation in a tertiary eye unit. Retrospective analysis of all enucleations performed at the University Eye Hospital of LMU Munich from January 2007 to December 2022. 491 eyes of 491 patients were enucleated in this period; 237 right and 254 left eyes. 59.3% (291) of patients were male, while 40.7% (200) were female. The median patient age at enucleation was 59 years (range 2–99, IQR 43–72). The four most common surgical indications were painful blind eye (318, 64.8%), malignancy (139, 28.3%), disfiguring blind eye (14, 2.9%) and treatment-refractory perforated corneal ulcer (13, 2.6%). There was only one indication for enucleation due to acute trauma (1, 0.2%). Information on causative diagnosis was available from 2013 to 2022 (257). The most common causative diagnoses leading to enucleation were choroidal melanoma (107, 41.6%), status post (s/p) trauma (65, 25.3%), and s/p retinal detachment (17, 6.6%). The annual enucleation count showed a decline from 2007 to 2022. Regarding indications for enucleation there is a negative trend for “painful blind eye” and “malignant tumor”. Our study demonstrates a decrease in the annual number of enucleations between 2007 and 2022. While the causative diagnoses remained unchanged over the last ten years, there was a negative trend in surgical indications due to malignant tumors and painful blind eyes. Only one enucleation was performed due to acute trauma.

A multicellular self-organized probiotic platform for oral delivery enhances intestinal colonization

State estimation of voltage and frequency stability in solar wind integrated grids using multiple filtering techniques

Abstract The increasing integration of solar and wind energy into modern power grids introduces challenges in maintaining voltage and frequency stability due to their intermittent and uncertain nature. This study evaluates the performance of three advanced state observers: extended Kalman filter (EKF), unscented Kalman filter (UKF), and cubature Kalman filter (CKF) for real-time monitoring and stability assessment in solar and wind-integrated grids (SAWIG). The analysis focuses on estimation accuracy, convergence speed, and classification performance under varying phasor measurement unit (PMU) sampling rates. Simulation results reveal that the CKF achieves the lowest root mean square error (RMSE) of 0.005 at a 10 Hz sampling rate, outperforming the UKF (0.007) and EKF (0.010). In terms of dynamic performance, CKF stabilizes within 0.1 s, while UKF and EKF require 0.2 and 0.4 s, respectively. Classification evaluation shows that CKF achieves the highest accuracy of 99.5%, with precision, recall, and F1-score of 99.2, 99.3, and 99.4%, respectively. In contrast, UKF reports values of 98.8, 98.5, 98.7, and 98.6%, while EKF records 97.6, 96.9, 97.1, and 97.3%. Confusion matrix analysis further confirms a classification accuracy of 95% for CKF. These results demonstrate its robustness, speed, and precision in ensuring reliable state estimation for voltage and frequency stability in renewable-integrated smart grids.

METTL9 sustains vertebrate neural development primarily via non-catalytic functions

Abstract METTL9 is an enzyme catalysing N1-methylation of histidine residues (1MH) within eukaryotic proteins. Given its high expression in vertebrate nervous system and its potential association with neurodevelopmental delay, we dissected Mettl9 role during neural development. We generated three distinct mouse embryonic stem cell lines: a complete Mettl9 knock-out (KO), an inducible METTL9 Degron and a line endogenously expressing a catalytically inactive protein, and assessed their ability to undergo neural differentiation. In parallel, we down-regulated mettl9 in Xenopus laevis embryos and characterised their neural development. Our multi-omics data indicate that METTL9 exerts a conserved role in sustaining vertebrate neurogenesis. This is largely independent of its catalytic activity and occurs through modulation of the secretory pathway. METTL9 interacts with key regulators of cellular transport, endocytosis and Golgi integrity; moreover, in Mettl9 KO cells Golgi becomes fragmented. Overall, we demonstrate a developmental function of Mettl9 and link it to a 1MH-independent pathway, namely, the maintenance of the secretory system, which is essential throughout neural development.

Modelling and algorithms of highway transportation network in urban agglomerations

Nanoscale cuticle mass density variations influenced by pigmentation in butterfly wing scales

Momentum-locked spin between topological and defect states in 1D patterns on bilayer graphene

Abstract Gating Bernal bilayer graphene breaks the inversion symmetry so that the stacking AB/BA boundaries within the gap reveal topologically protected states. In this study, we theoretically investigate arrays where the AB and BA domains are periodically patterned with experimentally identified defect lines. In the calculations we consider electron-electron interaction effects using density functional theory. Our findings reveal the existence of topological states within a gap induced by the patterning without an applied gate voltage. Furthermore, with an applied gate potential, the defect lines introduce spin-polarized states pinned within the gap and exhibit ferromagnetically coupled states. Importantly, we observe a hybridization of magnetic and topological states near the valleys that form conducting channels characterized by spin-momentum locking. The effect persists even with slight n-doping and gate voltage; however, the progressively pinned n-doped defect states induce spin polarization in the topological and valley states. Additionally, the two-dimensional bands under doping conditions exhibit nesting across the Fermi surface, allowing for modulation of charge densities along the lines which are nearly commensurate with the underlying graphene-defect lines. These quasi-one-dimensional patterns in bilayer graphene show a new kind of spin-conducting channels with novel characteristics common to both spintronics and valleytronics.

March5-mediated Trim28 degradation preserves islet β-cell function in mice

Spectrophotometric investigation of cocarboxylase interaction with pyridoxine hydrochloride and their interactional properties

Cryo-EM captures early intermediate steps in dynein activation by LIS1

Abstract Cytoplasmic dynein-1 (dynein) is an essential molecular motor in eukaryotic cells. Dynein primarily exists in an autoinhibited Phi state and requires conformational changes to assemble with its cofactors and form active transport complexes. LIS1, a key dynein regulator, enhances dynein activation and assembly. Using cryo-EM and a human dynein-LIS1 sample incubated with ATP, we map the conformational landscape of dynein activation by LIS1 and identify an early intermediate state that we propose precedes the previously identified dynein-LIS1 Chi state. Mutations that disrupt this species, which we termed “Pre-Chi”, lead to motility defects in vitro, emphasizing its functional importance. Together, our findings provide insights into how LIS1 relieves dynein autoinhibition during the activation pathway.

Performance evaluation of enhanced deep learning classifiers for person identification and gender classification

Abstract Person authentication using periocular images is a prominent research domain. Although the biometric identification systems have advanced, the existing approaches still struggle with accuracy, overfitting issues and computational efficiency, especially when utilizing periocular images for person identification and gender classification. In order to overcome these limitations, this paper proposes an enhanced deep learning classifier (EDLC) paradigm to recognize a person based on the periocular region within a face. A novel Hexagon-shaped ROI extraction is performed in the localization phase to extract the periocular ROIs. Following that, the feature extraction mechanism is accomplished utilizing the Laplacian transform. Finally, three distinct custom EDLCs are employed, such as dilated axial attention convolutional neural network, self-spectral attention-based relational transformer net, parameterized hypercomplex convolutional Siamese network for classification. Further, an adaptive coati optimization algorithm is used to adjust the hyperparameters of the classification models. The efficacy of the model is assessed concerning different outcome indicators. It is also compared with the recent competitive models. For person identification, the SSA-RTNet has achieved a maximum accuracy of 99.8% and 99.67% using the UBIPr and UFPR datasets respectively. Similarly, for gender classification, an accuracy of 98.4% and 99.68% using SSA-RTNet was obtained for the UBIPr and UFPR datasets. As a result, it is perceived that a considerable improvement was observed using the enhanced models.