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Growth-Coupled Assembly of Hydrogen-Bonded Organic Framework Membranes on Cell Surfaces
Real-world effectiveness and clinical predictors of response to first-generation TTR silencers in variant ATTR amyloidosis with polyneuropathy
Abstract Transthyretin (TTR) gene-silencing therapies have transformed the management of variant transthyretin amyloidosis with polyneuropathy (ATTRv-PN). However, real-world evidence on effectiveness, safety and durability is limited. We conducted a multicenter retrospective study across ten Spanish referral hospitals including 98 genetically confirmed ATTRv-PN amyloidosis patients treated with patisiran (n = 81) or inotersen (n = 17). Patients were classified as total, partial, or non-responders according to clinical evolution and Neuropathy Impairment Score (NIS). Baseline clinical, neurophysiological (CMAP, SNAP, ESC), and biochemical parameters were analyzed. Longitudinal NIS changes, treatment persistence, and safety were assessed. Total responders had higher baseline CMAP amplitudes (p = 0.045), while baseline neurophysiological measures showed modest discriminatory capacity overall, with electrochemical skin conductance providing the strongest signal. Baseline renal function differed across groups (eGFR, p = 0.022), but the direction of this association was not consistent with improved response. Compared with inotersen, patisiran showed a higher total response rate (59.3% vs. 23.5%), slower NIS progression (median + 0.31 vs. +4.00 points/year; p = 0.011), and greater treatment persistence (log-rank p = 0.0005). No discontinuations due to adverse events occurred with patisiran, versus 41.2% with inotersen. ESC showed the highest predictive value (AUC 0.681 overall; 0.783 in the patisiran subgroup), while baseline NIS was less informative. In routine practice, patisiran was associated with more favourable effectiveness and tolerability compared to inotersen. Baseline neurological preservation, particularly motor and small-fiber measures, may help identify patients more likely to benefit from treatment. However, these findings should be interpreted with caution due to the limited sample-size and the observational nature of the study.
Topological Control of Dual Protonic–Electronic Conduction in Metal–Organic Frameworks
Interpretable reinforcement learning with structured policies for prescriptive supply chain analytics
Photocatalytic Controlled Halodefluorination of Perfluoroalkyl Compounds Using <i>N</i> -Arylphenothiazines
Polarity-resolved Ziziphus fruit extracts as multifunctional leads: GC-MS and UHPLC-MS/MS profiling, MIC-based bioactivity, and MD/MM/GBSA support
Proton-Gated Torsional Spring for Molecular Energy Storage
Fuel consumption prediction of driverless trucks in Open-pit mines based on deep Siamese Transformer network model
Topologically Programmed Dual-Channel Covalent Organic Frameworks Decouple Gas and Ion Fluxes for Acidic CO <sub>2</sub> Electroreduction
Sleep duration among medical students and its association with bronchial asthma, anxiety, and depression
Correlating Interfacial Li <b> <sup>+</sup> </b> Exchange Rate with Reversible Cycling of Lithium Metal Anodes
Synaptic Ca2+ channels and neurexins are linked through direct and indirect binding complexes
Abstract Rapid release of neurotransmitters from presynaptic boutons is essential for brain function and is triggered by Ca 2+ influx through voltage-gated calcium channels (VGCCs), which consist of an α1 pore-forming subunit, intracellular β subunits, and mostly extracellular α2δ auxiliary subunits. Neurexins (Nrxn) regulate neurotransmission and presynaptic Ca 2+ influx, but the physical interactions with VGCC subunits remain unknown. Here, we examined these interactions in recombinant VGCC-Nrxn complexes using a nanobody-based co-precipitation system. We found that the α2δ-1 and α2δ-3 variants bind to the α1 pore-forming subunits of Ca V 2.1- and Ca V 2.2-type VGCCs with distinct preferences, whereas Nrxn1α and Nrxn1β do not directly interact with α1. Since Nrxn1α binds both α2δ variants but Nrxn1α/α2δ complexes do not include α1, mobile α2δ subunits may dynamically toggle between Nrxn1α and the Ca V core. Additionally, Nrxn1α associates with α1 subunits independently of α2δ through the intracellular scaffold protein Mint2, which enhances Nrxn1α/α2δ complex formation by inhibiting full glycosylation of α2δ. Extracellularly shorter Nrxn1β cannot bind α2δ but can indirectly associate with Ca V 2 α1 pore-forming subunits via either Mint2 or CASK proteins. Therefore, our findings reveal distinct molecular complexes through which αNrxn and βNrxn variants interact with VGCC subunits to regulate presynaptic Ca 2+ influx. (196 words)
Correction to “Peptide-Mimicking Poly(2-oxazoline)s Possessing Potent Antifungal Activity and BBB Penetrating Property to Treat Invasive Infections and Meningitis”
Determinants of willingness-to-pay for genomic sequencing in hong kong: psycho-socio-economic factors and healthcare engagement from a contingent valuation study
Arylboron Tetraphenylethylene-Analog AIEgens Enabling Reversible Closed-Shell/Open-Shell Switching
Integrated biosorption and bioreduction of hexavalent chromium using Fusarium species under optimized process parameters
Abstract Fungal biosorption and bioreduction of hexavalent chromium (Cr(VI)) provide a sustainable and cost-effective alternative to traditional physicochemical methods by utilizing microbial enzymatic pathways for detoxification. Fusarium verticillioides and Fusarium oxysporum were isolated and tested for their ability to remove Cr(VI) from aqueous solutions. Biomass and filtrate obtained after growth of F. verticillioides at pH 2 showed a maximum Cr(VI) removal achieving 77% and 79% removal, respectively.While biomass and filtrates obtained after growth of F. oxysporum at pH4 showed the optimal Cr(VI) removal (69%) for biomass and (97%) for filtrate, respectively. Increasing inoculum size up to 38 × 10 8 CFU enhanced Cr(VI) reduction efficiency, but removal decreased with higher Cr(VI) concentrations, with no removal observed at 60 mg/l. Removal efficiency also increased significantly with incubation time up to five days. Scanning electron microscopy revealed structural changes in fungal biomass associated with biosorption and reduction of Cr(VI) to the less toxic Cr(III), supported by detection of chromate reductase activity in fungal exo- and endo-filtrates as well as membrane debris. Atomic absorption spectroscopy indicated that F. verticillioides and F. oxysporum converted approximately 95% and 78% of Cr(VI) to Cr(III), respectively, suggesting these fungi offer eco-friendly bioremediation strategies by combining cell-wall biosorption with enzymatic bioreduction mechanisms to transform toxic chromium into less harmful forms.