Browse Articles

Controlled Synthesis of Chiral β-Chloramines and Aziridines via an Organo- and Biocatalytic Cascade

Abstract Chiral organochlorides bearing C–Cl stereocenters are highly desirable motifs in synthetic and medicinal chemistry, yet their direct asymmetric synthesis from simple starting materials via biocatalysis alone remains challenging. Here, we report an integrated organo- and biocatalytic cascade that converts readily available aldehydes into enantiomerically enriched β-chloramines. Under optimized near-neutral conditions, the method delivers a broad array of β-chloramines in high yield (up to 88%) with exceptional enantioselectivity (up to >99:1 enantiomeric ratio). Notably, by simply raising the pH to 9.5, the same cascade system diverges to directly generate chiral aziridines, enabling pH-controlled access to two valuable product classes from a unified platform. The utility of this strategy is further demonstrated by preparative-scale syntheses from inexpensive commercial substrates, followed by divergent linchpin transformations to diverse chiral building blocks, including aziridines, azido amines, and acetoxy amines. Mechanistic studies provide insight into the origins of stereoselectivity and the key factors governing stereochemical outcomes.

Multimodal chatbot triage for eyelid disorders shows high accuracy and net benefit

Localized delivery of coding nucleic acids into adherent cells by in situ electroporation: integrated impedance-based monitoring allows for loss-of-function or gain-of-function screening

Abstract Coding nucleic acids (NAs) like DNA, mRNA or siRNA hold endless potential to engineer cells with respect to their genome and proteome. However, minimally invasive delivery of NAs across an intact plasma membrane into the cytosol of living cells remains a technical challenge. Electroporation creates transient pores in the plasma membrane by applying well-defined electric fields for fractions of a second allowing NA transfer across the membrane. In situ electroporation ( ISE ) applies the electric field to adherent cells growing on the surface of planar, thin-film electrodes deposited on the bottom of the culture well. This study reports on the localized delivery of plasmid DNA, mRNA, siRNA and aptamers into different mammalian cell lines by ISE . Fluorescence microscopy verified successful delivery of labeled NAs themselves (siRNA, aptamers) or expression of the proteins they encoded (DNA, mRNA). Impedance readings of the cell-covered electrodes before and after ISE allowed tracking the invasiveness of the pulse, the recovery of the cells within 30 min and the phenotypic impact of the NAs inside the cells. Loading the cells with siRNA specifically designed to knock down gene transcripts essential for survival, led to the onset of cell death within 20 h after the pulse. The combination of ISE , specific NAs and impedance-based cell monitoring paves the way for a new class of gain-of-function or loss-of-function experiments.

Temperature driven structural evolution and optical Raman and magnetic properties of Sr doped LaMnO3 nanocrystalline systems

Tissue-specific bioaccumulation of microplastics in the shallow water hydrothermal vent crab Xenograpsus testudinatus

Beyond Dealumination: Does Fluorine Reshape Zeolitic Acidity?

Abstract Fluoride-containing media have been widely adopted in the post-treatment of ZSM-5 zeolites for heterogeneous catalysis. Their effects have predominantly been discussed in terms of the well-established dealumination process. However, comparatively little attention has been paid to the influence of residual fluorine on the local chemical environment, which governs zeolitic acidity and catalytic performance. In this work, mild fluorination of ZSM-5 was achieved by controlling the ammonium fluoride (NH4F) content during hydrothermal treatment. Our findings reveal that fluorine induces significant perturbations in the acidic properties of ZSM-5, distinct from the conventional dealumination effect. To elucidate these effects at the atomic level, we employed 27Al, 19F, 27Si, and 1H solid-state magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy, which provided detailed chemical and structural insights. The correlated incorporation of fluorine within the zeolite framework leads to strong local polarization, thereby enabling the protons to exhibit Brønsted acid site (BAS)-like behavior. Comparative analysis with nonaluminum-containing silicalite-1 further confirmed the fluorine-induced acidity, as supported by two-dimensional (2D) 1H double-quantum single-quantum (DQ–SQ) MAS NMR results. Catalytic testing in the methanol-to-hydrocarbon (MTH) reaction demonstrated that such fluorinated ZSM-5 exhibits an extended catalytic lifetime along with enhanced aromatic selectivity, underscoring the pivotal electronic influence of fluorine beyond its classic role in dealumination.

Attosecond shaping of multi-electron pulses in a home-built 37-keV beamline

Decomposition-Enhanced Network for financial time series forecasting

Therapeutic potential of Echinocactus grusonii and its associated endophytic fungus Aspergillus oryzae in neuroprotection: in vitro and in silico investigations

Abstract The Golden Barrel Cactus ( Echinocactus grusonii , syn. Kroenleinia grusonii ), native to Mexico, is well known in horticulture but remains insufficiently studied with respect to its chemical composition. This study examined the chemical profile and neuroprotective potential of Echinocactus grusonii spines and its endophytic fungus, Aspergillus oryzae . The spines contained markedly higher levels of phenolics (293 mg gallic acid/g DW extract), flavonoids (132 mg quercetin/g DW extract), and alkaloids (14.5 mg atropine/g DW extract) compared to the stem. Untargeted metabolomics (UPLC-HRMS/MS) tentatively identified 27 metabolites in the spines and 14 in the fungal extract. Both extracts exhibited potent, dose-dependent inhibition of acetylcholinesterase (AChE) and β -secretase (BACE-1). The spines extract showed IC₅₀ values of 0.362 µg/mL (AChE) and 0.425 µg/mL (BACE-1), while the fungal extract was more effective against AChE (IC₅₀ = 0.255 µg/mL). In silico docking was performed for all identified compounds, and molecular dynamics simulation of the top-scoring candidates demonstrated stable interactions with the target enzymes. These findings highlight the spines of Echinocactus grusonii and their associated endophytes as promising dual-target neuroprotective sources for the management of neurodegenerative disorders.

A hybrid ConvNeXt-ViT framework with differential evolution optimization for breast cancer classification

Abstract Breast cancer, a leading cause of mortality among women worldwide, necessitates early detection through mammography. Yet, automated classification remains challenging due to class imbalance, limited datasets, and the need for both local and global feature extraction. While convolutional neural networks (CNNs) excel in local feature extraction for mammogram classification, they struggle with long-range contextual dependencies. Conversely, transformer-based models capture global relationships effectively but require large datasets and substantial computational resources, limiting their applicability in medical imaging. To overcome these limitations, we propose DEViTNeXt, a new hybrid framework that synergistically combines ConvNeXt’s convolutional efficiency with Vision Transformer (ViT) attention-based global modeling, enhanced by Differential Evolution (DE) optimization. The framework employs comprehensive preprocessing (Gaussian filtering, CLAHE enhancement) and a hybrid augmentation pipeline that integrates GAN-based synthesis of malignant cases with geometric transformations. Dual-branch feature extraction leverages ConvNeXt for hierarchical local features and ViT for global contextual relationships, with Multi-Head Attention (MHA) refinement dynamically emphasizing diagnostic regions in both branches. A DE-optimized MHA fusion layer adaptively integrates complementary. A composite loss function (Weighted Cross-Entropy + Focal Loss) addresses class imbalance while focusing on complex malignant cases. Extensive experiments on the CBIS-DDSM and MIAS datasets demonstrate DEViTNeXt’s superiority, achieving 99.63% accuracy, 99.45% sensitivity, and 99.55% specificity on CBIS-DDSM under binary (Benign vs. Malignant) classification, and 98.50% accuracy on MIAS (3-class), outperforming state-of-the-art methods.

Subjective persistent dizziness handicap and psychological factors in vestibular schwannoma patients: a cross-sectional study

Abstract Persistent dizziness is a frequent and disabling symptom after retrosigmoid microsurgery for vestibular schwannoma (VS), negatively affecting quality of life. While vestibular outcomes are well studied, the contribution of psychological factors to persistent dizziness remains insufficiently understood. This cross-sectional study included 93 patients with VS, of whom 80.6% reported postoperative dizziness. Psychological factors were assessed using validated self-report questionnaires covering premorbid mental health conditions, personality traits, somatization, anxiety, depression, and psychological distress. Dizziness-related impairment was quantified using the Dizziness Handicap Inventory (DHI). Associations were examined using Spearman correlations with bootstrap resampling, followed by multivariable linear regression to identify independent predictors of dizziness handicap. Dizziness handicap was robustly associated with vestibular symptom burden, somatization, anxiety, and psychological distress. Higher anxiety and somatization scores were consistently related to greater dizziness-related impairment, particularly in emotional and functional domains. Higher scores on the GBI Social Support subscale, reflecting surgery-related changes in the need for and reliance on social support rather than baseline social support resources, were associated with greater dizziness handicap and independently predicted higher DHI scores. Personality traits showed heterogeneous associations; conscientiousness was positively associated with physical dizziness handicap and showed a trend-level association with overall handicap, potentially reflecting increased symptom monitoring or health awareness. Given the cross-sectional design and absence of objective vestibular testing, causal relationships cannot be established. Persistent dizziness after VS surgery likely reflects multifactorial mechanisms involving vestibular, psychological, and functional contributors. Future longitudinal studies integrating comprehensive neuro-otological assessments are needed to clarify temporal relationships and underlying mechanisms.

Jingling Granules alleviate atherosclerosis through activating autophagy and inhibiting human umbilical vein endothelial cells apoptosis

Ultraslow oscillations as a temporal scaffold for coordinating episodic memories

Abstract The entorhinal–hippocampal circuit plays a central role in episodic memory, yet the contribution of the medial entorhinal cortex (MEC) ultraslow (< 0.01 Hz) oscillation remains poorly understood. Here, we develop a biologically inspired computational oscillation-coordinated replay model integrating MEC-like ultraslow oscillations with entorhinal grid–hippocampal place cell interactions and injected replay-like sequential activity. In the model, replay-like events were probabilistically triggered and temporally aligned to an imposed ultraslow oscillatory scaffold. We compared this condition to a baseline lacking both oscillatory modulation and replay-like structure. Under these conditions, recall accuracy and coding overlap were higher when replay-like dynamics were coordinated by the oscillatory scaffold. The present results demonstrate that oscillatory structure can enhance the temporal organization and effectiveness of replay-like dynamics. These findings provide a proof-of-concept framework for understanding how ultraslow fluctuations may contribute to memory processes by coordinating, rather than generating, replay activity, and enabling testable predictions for models in which replay emerges endogenously.

Concentrations of bisphenol A and selected bisphenol analogues in urban reservoirs in different seasonal conditions

Correction: Oncogenic HPV types identified in Paleolithic and Chalcolithic human genome sequencing data from Ust’-Ishim and Ötzi

RSS-enabled hybrid-modulation 19-level switched-capacitor inverter with ninefold voltage boost inductorless soft-charging low device count and minimized LDP

Prevalence and factors associated with pain in patients undergoing dialysis: a nationwide multicenter cross-sectional study

Assessing land use and carbon stock dynamics coupled with the PLUS-InVEST-OMGD model: a multi-scenario simulation in Sichuan Province, China

Bis-Tetrazine Fluorogenic (Silicon)-Rhodamine Dyes for Live-Cell Labeling

Abstract Fluorogenic click dyes are valuable tools for biorthogonal labeling, enabling real-time visualization of biomolecules and cellular processes in their native environments. However, achieving efficient quenching and high fluorescence turn-on within a single dye scaffold remains a significant challenge. Herein, we report a class of fluorogenic click dyes based on a structural modification of (silicon)-rhodamines at the amino groups of the xanthene scaffold, resulting in a particularly short linker and a highly optimized quenched state. This modification enables the synthesis of both mono- and bis-functional derivatives. The monofunctional dyes are fully compatible with established click-labeling strategies and display exceptional fluorogenic responses, with fluorescence enhancements of up to 2 orders of magnitude. Notably, the bis-functional derivatives are fluorogenic dyes that exhibit fluorescence turn-on ratios approaching 3 orders of magnitude upon biorthogonal reaction, making them particularly suitable for live-cell applications. We show that the short bis-linker has high potential for anisotropy measurements that can report on protein size and dynamics. We further demonstrate the unique utility of these bis-functional dyes for peptide cyclization, enhancing cellular uptake while enabling real-time visualization. Together, this work introduces a versatile dye class that substantially expands the scope of click chemistry and will advance applications in live-cell imaging as well as studies of protein structure and dynamics.

Preclinical characterization and early development of R835, a novel, selective dual IRAK1 and IRAK4 inhibitor

Abstract Interleukin-1 receptor associated kinase (IRAK)1 and IRAK4 are serine/threonine kinases critical for downstream signaling of most toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs), leading to proinflammatory cytokine production and activation of innate immune and inflammatory responses. Herein, we describe the preclinical characterization and early clinical development of R835, a potent, selective dual inhibitor of IRAK1/IRAK4 and the active metabolite of the prodrug R289, which is currently undergoing clinical evaluation in relapsed/refractory lower-risk myelodysplastic syndrome (LR-MDS). In multiple cell types and in orally dosed mice, R835 potently and selectively inhibited TLR- and IL-1R-dependent proinflammatory cytokine production. In a randomized, placebo-controlled, double-blind, phase 1, first-in-human study in 82 healthy participants, R835 was well tolerated with a favorable pharmacokinetic profile and markedly inhibited lipopolysaccharide-induced cytokine release (TNF, IL-6, IL-8, MIP1α, and MIP1β) compared with placebo, mirroring preclinical data. Taken together, these initial findings indicate that R835 may represent a novel therapeutic for inflammatory diseases.