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Electrostatic properties of disordered regions control transcription factor search and pioneer activity
A role for condensin-mediator interaction in mitotic chromosome organization
Decoding phantom limb movements from intraneural recordings
Abstract Limb loss causes severe sensorimotor deficits and often necessitates prosthetic devices, particularly in lower-limb amputees. Although direct neural recording from residual nerves offers a biomimetic route for prosthetic control, low signal amplitudes and challenges in nerve interfacing have limited adoption. Intraneural multichannel electrodes provide a potential solution by enabling access to motor signals from muscles lost after amputation. Here, we report intraneural recordings from two transfemoral amputees using transversal intrafascicular multichannel electrodes implanted in distal branches of the sciatic nerve. We identified multiunit activity associated with volitional phantom movements of the knee, ankle, and toes, exhibiting joint- and direction-specific modulation distributed across electrodes. A Spiking Neural Network–based decoder outperformed conventional methods in predicting attempted movements, with further gains achieved by integrating intraneural and intermuscular signals. Motor and sensory maps showed minimal overlap, indicating early segregation within the sciatic nerve. These findings pave the way for bidirectional, neurally-controlled prosthetic systems.
Dual spillover of carbon monoxide and hydrogen initiates tandem urea electrosynthesis
Particulate matter (PM2.5 and PM10) prediction using fourier series decomposition in combination with LSTM and SVM
Combined bacteriophage and antibiotic therapy for refractory peritoneal dialysis-related peritonitis caused by Klebsiella pneumoniae
Higher-order aberrations and visual outcomes of a new refractive extended depth-of-focus intraocular lens with a target of slight myopia
Myoferlin is a component of late-stage vRNP trafficking vesicles for enveloped RNA viruses
Abstract The Rab11 endosomal recycling pathway is exploited by important respiratory RNA viruses such as IAV and RSV, aiding viral egress from the apical surface of polarized epithelial cells. Late in infection, Rab11-containing vesicles specifically transport viral ribonucleoprotein (vRNP) complexes towards the cell surface before packaging and budding. Rather than employing traditional Rab11-positive recycling endosomes, virus-infected cells generate remodelled Rab11-containing vesicles, as observed during IAV infection. Besides Rab11, no other conserved host co-factors have been identified among these various vRNP trafficking vesicles. Here we discover and confirm myoferlin’s association with IAV vRNPs in the cytoplasm and colocalisation with Rab11 during late stages of infection. We also find that this role is conserved in late-stage vRNP trafficking of other viruses, including RSV and SeV. Myoferlin likely recruits the EHD family of proteins, which are involved in endosomal biogenesis, to these unique vRNP trafficking endosomes, highlighting myoferlin’s pivotal role in viral replication.
A cross-sectional study on associated factors of Chinese herbal medicine use in middle-aged and older adults with dyslipidaemia
Discovery of antimicrobial peptides targeting Acinetobacter baumannii via a pre-trained and fine-tuned few-shot learning-based pipeline
Feasibility of multisource CBCT for improving the predictability of dental implant primary stability compared to conventional CBCT
Cryo-EM structures of bacteriophage T4 portal-neck assembly intermediates reveal a viral genome retention mechanism
The spectral power distribution prediction of LED light source based on Gaussian mathematical model and improved residual network
Antiparallel stacking of Csu pili drives Acinetobacter baumannii 3D biofilm assembly
Abstract Many Gram-negative nosocomial pathogens rely on adhesive filaments, known as archaic chaperone-usher pili, to establish stress- and drug-resistant, multi-layered biofilms. Here, we uncover the mechanism by which these pili build three-dimensional (3D) biofilm architectures. In situ analyses of Acinetobacter baumannii biofilms using electron microscopy (EM) reveal an extensive network of ultrathin, flat stacks of archaic Csu pili interconnecting bacterial cells in 3D space. Cryo-EM structures of a single native pilus, pilus pairs, and two types of multi-pilus stacks show that the pili pack into antiparallel sheets, with their rods connected laterally by junctions at their zigzag corners. This antiparallel arrangement ensures that contacts form primarily between pili from interacting cells rather than pili from the same cell. With a remarkably short helical repeat, archaic chaperone-usher pili spontaneously establish a high density of junctions that determines the biofilm’s 3D architecture. Our findings may help develop new therapies against multidrug-resistant bacterial infections by targeting pilus-pilus interactions.
Synergistic and distinct effects of expansive posture and nasal breathing on psychological and physiological self-regulation in adolescents
Abstract Adolescents are vulnerable to anxiety and low self-efficacy due to heightened emotional reactivity and immature regulatory systems. Embodied interventions, such as posture adjustment and controlled breathing, have shown promise for enhancing psychological self-regulation, but their synergistic effects in adolescents remain unclear. This study examined the immediate and sustained effects of expansive posture, nasal breathing, and their combination on self-efficacy, anxiety, and autonomic nervous system (ANS) activity in adolescents aged 15–18 years. Participants completed the Trier Social Stress Test, received one of four interventions, and were assessed with self-report questionnaires (General Self-Efficacy Scale; State–Trait Anxiety Inventory-6; n = 138) and continuous electrodermal activity (EDA; n = 62) recorded during the intervention and a subsequent Stroop task. Results showed that expansive posture—alone or combined with nasal breathing—significantly increased self-efficacy, while all three active interventions reduced anxiety compared with controls. Physiological analyses revealed distinct patterns of ANS modulation: nasal breathing alone yielded more stable EDA profiles with lower variability—consistent with enhanced autonomic flexibility in HRV studies—while the combined intervention produced larger autonomic fluctuations, suggesting compensatory responses. These findings highlight the complementary benefits of posture and breathing strategies and support a phased “activate–then–stabilize” approach to adolescent self-regulation.
Heterogeneous multicopy of blaCTX-M variants on the same plasmid enhances evolutionary adaptability in clinical Klebsiella pneumoniae
Abstract Pathogenic bacteria continually evolve under antimicrobial pressure through acquired resistance genes, making it crucial to understand their evolutionary strategies. We identify a clinical Klebsiella pneumoniae isolate resistant to ceftazidime/avibactam (CZA), harboring heterogeneous multicopy bla CTX-M , among which a bla CTX-M-249 variant mediates CZA resistance. Both bla CTX-M-249 and its closely related allele bla CTX-M-65 are dominant within the clonal population and are located at two loci on the same plasmid, with their proportions shifting under antibiotic pressure. Using experimental and mathematical models, we demonstrate that the heterogeneous arrangement of bla CTX-M variants on the same plasmid confers greater stability and competitive advantage than that across separate plasmids, particularly during drug switching. Re-analysis of large genomic datasets supports the universality of this phenomenon. Our findings reveal an evolutionary strategy in which β-lactamase genes, through multicopy heterogeneity on a single plasmid, ensure stable inheritance of resistance and enhance bacterial adaptability under fluctuating clinical antibiotic pressures.
A generative AI-driven cybersecurity framework for small and medium enterprises software development: an ANN-ISM approach
Analysis of the transcriptomic and metabolomic landscape of prostate cancer with different anatomical origins using snFLARE-seq and mxFRIZNGRND
Abstract Prostate cancer cells of different anatomical locations display remarkable heterogeneity. This poses a challenge to the clinical relevance of pre-clinical models and the efficacy of contemporary therapeutic approaches. Here we develop the snFLARE-seq and mxFRIZNGRND methodologies to directly investigate the transcriptomic and metabolomic landscape of prostate cancer patients utilizing formalin-fixed paraffin-embedded (FFPE) specimens. A retrospective analysis reveals the clinical disparities of prostate cancer from peripheral zone (PZ), transition zone (TZ), and across PZ and TZ. The snFLARE-seq, refined for enhanced single-nucleus sequencing, unveils distinct cell type distributions and signaling pathways between PZ and TZ samples. Hormone therapy substantially affects cancer cells and microenvironment, leading to a polarized feature of epithelial cells and a subverted immune microenvironment. With improvements in metabolite extraction, mxFRIZNGRND reveals unique metabolic features of prostate cancer from different origins. The metabolomic results indicate that PZ cancer cells are in a metabolic-dormant status, which are probably awaken by hormone therapy. Integrative analysis of results from snFLARE-seq, mxFRIZNGRND, and TCGA database uncovers four metabolic pathways and related genes associated with disease aggressiveness. Our work could accelerate investigations on disease heterogeneity and evolution in real-world clinical settings, stimulating patient-specific precision healthcare solutions.
Using colored dissolved organic matter fluorescence to trace Pacific-derived water in the Eastern Canadian Arctic
Hepatocytes functionally reprogrammed by KIAA1199-high colorectal cancer cells favour the accumulation of pro-metastatic Egr1+ neutrophils
Abstract Colorectal cancer liver metastasis (CRLM) is a leading cause of mortality, driven by poorly defined molecular interactions within the hepatic niche. Here, we identify a distinct population of pro-metastatic Early Growth Response 1 (Egr1) + neutrophils that accumulate in the pre-metastatic liver. Mechanistically, we show that KIAA1199-high cancer cells secrete granulin-rich extracellular vesicles, which are internalized by hepatocytes. This uptake triggers a subset of functionally reprogrammed hepatocytes, characterized by a profound metabolic reprogramming and the suppression of peroxisome proliferator-activated receptor gamma (PPARγ) signaling, leading to increased secretion of Serum Amyloid A2 (SAA2). Hepatocyte-derived SAA2 subsequently activates Formyl Peptide Receptor 2 (FPR2) on neutrophils, stabilizing Egr1-driven transcriptional program via the PI3K-AKT pathway to enhance neutrophil survival and pro-angiogenic activity. These Egr1 + neutrophils co-localize with reprogrammed hepatocytes at the tumor-liver interface, where they promote vascular remodeling to facilitate metastatic colonization. Pharmacological restoration of PPARγ or FPR2 inhibition abrogate CRLM in preclinical models in female mice. Furthermore, a combined KIAA1199-SAA2 signature predicts liver metastasis risk in patients. Our findings delineate a KIAA1199-PPARγ/SAA2-Egr1 axis orchestrating the pre-metastatic niche and propose metabolic normalization as a preventative strategy for liver metastasis.