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Multi-modal dissection of cell-type specific TDP-43 pathology in the motor cortex
Abstract Cytoplasmic TDP-43 pathology is a pathological sign of ALS/ALS-FTD and a converging disease event across different genotypes, phenotypes and CNS areas. To understand this process and target it therapeutically, we need to define which cell types are affected and which cell-type specific effects make them particularly vulnerable. We coupled flow-cytometry nuclear sorting and sequencing with single-nucleus multi-omic ATAC-seq and RNA-seq and spatial transcriptomics to define the transcriptional cell type of affected neurons in the post-mortem ALS/ALS-FTD motor cortex (30 ALS, 20 ALS-FTD & 32 control samples). Here, we show that mainly excitatory cortical neurons are affected by TDP-43 pathology and define the cell types that are affected the most: intratelencephalic L2-L3-LINC00507-FREM3, L3-L5-RORB-LNX2, L3-L5-RORB-ADGRL4 & L6-THEMIS-LINC00343 neurons and extratelencephalic L5-FEZF2-NTNG1 neurons. Transcriptional aberrations by TDP-43 pathology, like cryptic exon inclusion, are cell-type specific and affect distinct gene sets in each cell type, highlighting the need to address TDP-43 pathology in a cell-type specific manner.
Frontispiece: Atomic Level Fabrication of Oxychloride Interface for High‐Rate and High‐Voltage Lithium‐Ion Batteries
Outside Front Cover: Combined In‐Solution and On‐Surface Synthesis of a Fully Fused Cross‐Shaped Phthalocyanine Pentamer
Sarcopenia and fall-related outcomes in Chinese adults aged 45 years or older: a longitudinal cohort study
Dissecting the contributions to non-photochemical quenching in a land plant under fluctuating light
Abstract Photosynthetic organisms have evolved multiple non-photochemical quenching (NPQ) processes, providing photoprotection by safely dissipating excess excitation energy. These processes involve various molecular players functioning on overlapping timescales from seconds to days, making it challenging to isolate and quantify their individual kinetics. In this study, we perform whole-leaf chlorophyll fluorescence lifetime and xanthophyll concentration measurements on wild-type and various newly characterized NPQ mutants of Nicotiana benthamiana , a vascular land plant. Based on these measurements, we construct a fluorescence lifetime-based quantitative kinetic model that disentangles individual photoprotection components and, when integrated additively, accurately predicts wild-type and mutant NPQ behaviors under various light-dark regimes. Additionally, the model quantifies the per-molecule quenching effectiveness of various xanthophylls and the contributions of six quenching components (qE V , qE A, qE Z, qE L, qZ, and qI) across different genotypes. It also suggests improved overall quenching efficiency at specific VDE:ZEP:PsbS overexpression stoichiometries, aligning with previous studies and supporting translational efforts to optimize photoprotection and enhance crop yields under dynamic light environments.
Inside Back Cover: Programmable Antigen‐Specific Immunity via Self‐Adjuvanting Nanovaccines Co‐Delivering Immune Modulators (Angew. Chem. Int. Ed. 11/2026)
How leader–member exchange ambivalence influences employee feedback seeking and avoidance
Abstract Leader–member exchange ambivalence represents a critical yet underexplored factor shaping leader–employee interaction motivation. Drawing on dual-system decision theory, this study investigates how LMX ambivalence shapes employees’ feedback strategies via both intuitive and analytical processing pathways. Using hierarchical regression and Bootstrap analyses on survey data from 306 employees in China, the findings reveal that LMX ambivalence significantly increases feedback avoidance and reduces feedback-seeking behavior. Cognitive reappraisal partially mediates the relationship between LMX ambivalence and both feedback seeking and feedback avoidance, whereas emotional exhaustion partially mediates the relationship between LMX ambivalence and feedback avoidance. Moreover, the perceived organizational political climate amplifies the positive association between LMX ambivalence and emotional exhaustion, while further intensifying the negative impact of LMX ambivalence on cognitive reappraisal. These results elucidate a systematic explanatory mechanism through which LMX ambivalence undermines employees’ motivation to engage in feedback behaviors. While offering actionable insights, these findings should be interpreted in light of the specific professional and cultural context of the sample. The study provides a solid theoretical foundation for advancing research in this domain.
Heterogeneity in lysosomal dynamics and metabolic functions along the kidney proximal tubule
Pharyngeal electrical stimulation for postextubation dysphagia after stroke: a randomized trial on hospitalization costs from a health insurance perspective
Abstract Dysphagia is a frequent and serious complication after stroke, associated with pneumonia, malnutrition, prolonged intensive care unit stay, and higher healthcare costs. Pharyngeal electrical stimulation (PES) is a novel therapy that may support recovery from postextubation dysphagia. This study assessed the cost-effectiveness of PES in stroke patients from a health insurance perspective. We performed a secondary analysis of a randomized controlled trial including 60 stroke patients with postextubation dysphagia, randomized to PES ( n = 30) or sham stimulation ( n = 30). Sham treatment involved identical device placement without stimulation. Acute hospital costs were estimated per patient using the 2025 German Diagnosis-Related Groups (DRG) reimbursement system. Mean costs were compared between groups with a one-sided t-test, and distributions were explored with boxplots. Mean DRG costs per patient were €22,392.89 (SD = €14,980.84) in the sham group and €18,127.20 (SD = €7,828.65) in the PES group. The difference was not statistically significant ( p = 0.087). However, three outliers with costs >€50,593 occurred in the sham group, compared with none in the PES group (maximum €35,257.49). Although the difference in mean hospitalization costs between groups was not statistically significant, extreme high-cost outliers occurred only in the sham group in this pilot sample. This observation is exploratory and hypothesis-generating and requires confirmation in larger, adequately powered health-economic studies before firm conclusions regarding cost-effectiveness can be drawn.
Unbiased recording and identification of thymic cellular interactomes using synthetic Notch receptors
Abstract Cellular interactions between thymocytes and other immune and stromal thymic cells play a key role in T cell maturation and homeostasis. Previous efforts delineating the cellular interactomes that support T cell development have mostly relied on imaging techniques, genetic deletion of essential molecular factors and bone marrow chimeras. Here, using synthetic NOTCH receptors we took a direct and unbiased genetic approach to fluorescently label cells in physical contact with CD4 + and CD4 + CD8 + thymocytes in vivo in mice. Prospective isolation and transcriptional characterization at single-cell level of the interacting cells exposed the thymic cellular interactome that supports these T cells and how ageing erodes these interactions. Cellular interactors included, among others, dendritic cells, B cells, IL-17 + γδ T cells, fibroblast subsets and thymic epithelial cells. Ligand-receptor pair analyses highlighted signals involved in survival, differentiation and antigen presentation. Our work provides a new means to study thymic cellular interactions.
Logistics equipment condition monitoring and prediction based on digital twin and machine learning
The association of physical activity with urological cancer risk: a systematic review and meta-analysis
Spatially distributed wettability characterization in porous media
Learning turbulent flows with generative models for super resolution and sparse flow reconstruction
Effects of unilateral step training along with rhythmic auditory stimulation on balance and postural stability in stroke patients
Lightweight hybrid neural network with physics consistency regularization for lithium-ion battery state of health estimation
Prescription‑dose stratification improves deep learning‑based VMAT dose prediction in locally advanced NSCLC
Abstract Volumetric-modulated arc therapy (VMAT) planning for locally advanced non-small cell lung cancer (NSCLC) is an iterative and planner-dependent process that often requires multiple optimization cycles to balance target coverage and organ‑at‑risk (OAR) sparing. Deep‑learning dose prediction can accelerate planning by providing patient‑specific reference dose distributions, but the impact of prescription‑dose mixing during model training remains unclear. This study evaluated whether prescription‑stratified models improve VMAT dose prediction performance. Seventy-two NSCLC VMAT cases were recalculated to 50, 54, and 60 Gy and split into training, validation, and test sets (42/10/20 cases). Four models with identical 3D U-Net architecture were developed: three single-prescription models (50/54/60 Gy) and one mixed-prescription model (50 + 60 Gy). Performance was assessed using mean absolute error (MAE) for planning target volume (PTV) and OAR dose metrics. Single-prescription models reproduced PTV coverage (D 95% and D 99% ) with MAEs < 4 Gy and hot-spot (D 2cc and D 5cc ) errors < 1 Gy, while mean dose errors for lungs and heart were ≤ 2.3 Gy. The mixed-prescription model showed larger errors: PTV hot-spot MAE rose to 11.3 Gy, and spinal cord maximum-dose errors reached 5–6 Gy, although most other OAR metrics changed modestly. Voxel‑wise difference maps revealed local deviations of a few Gy in low-dose lung regions and near steep gradients. These findings indicate that prescription‑dose stratification improves clinically relevant prediction metrics and support deep‑learning dose prediction as a planning decision‑support and optimization‑guidance tool.