Browse Articles

CD33 and clusterin interact biophysically and genetically to modulate Alzheimer risk

Abstract Mechanisms linking CD33 variants to Alzheimer Disease (AD) are poorly defined. Here, we combine structural, cellular, and genetic analyses to delineate how the CD33 M splice isoform, upregulated in carriers of CD33 risk alleles, modulates microglial function. We show that CD33 M ectodomain dimerizes, enabling binding of large multi-sialylated molecules. We demonstrate that another AD risk protein - clusterin (CLU) ± Aβ oligomers (but not ApoE) binds with nanomolar avidity to CD33 M , but not CD33 m . We show that in human monocytes CD33 M :CLU binding induces CD33 M ITIM phosphorylation, recruits SHP-1, suppresses Aβ phagocytosis, and impairs clearance of amyloid plaques. We identify a soluble CD33 M ectodomain fragment (sCD33 M ) - absent from CD33 m -expressing cells - which could contribute to the role of CD33 M in AD. Genetic analyses confirm that CD33:CLU interaction modulates amyloid burden, cognition, and disease risk. These findings define a mechanistic CLU:Aβ:CD33 M axis, highlighting CD33 M dimerization and ligand-binding sites as potential therapeutic targets.

Spatial distribution characteristics and protection strategies of National intangible cultural heritage in the Pearl river basin

Visualizing excitonic states in constructed cyclic molecular architectures by tip-enhanced photoluminescence

Ecology driven patterns of herpesvirus spread in cervids in Poland

Abstract Cervids are considered as a potential hosts for various human and animal pathogens but studies on herpesvirus infections among these species remain limited. We have used a panherpesvirus PCR to investigate herpesvirus diversity and prevalence and a BoHV-4-specific ELISA to assess exposure to BoHV-4. Among 1257 cervids tested for the herpesvirus DNA, 389 (30.9%) were positive. The prevalence was highest among fallow deer (63.9%), followed by red deer (29.8%) and roe deer (19.4%); among captive animals (42.1%) and in forest districts with low (31.2%) or medium (32.9%) forest coverage. No positive cases were found in moose. BoHV-4 specific antibodies were found in 107 out of 1179 (9.1%) tested cervids. Seroprevalence was highest among roe deer (18.7%) and in regions with the highest forest coverage (13.9%). Two gammaherpesvirus species: Fallow deer lymphotropic herpesvirus, Elk gammaherpesvirus 1; and one betaherpesvirus – Capreolus herpesvirus 1 were for the first time identified in Polish deer. Although, none of these viruses is currently considered pathogenic for cervids, the study revealed distinct ecological patterns of herpesvirus circulation among cervid species. These findings expand current knowledge of herpesvirus diversity in Polish cervids and demonstrate the value of herpesvirus surveillance for understanding pathogen transmission and wildlife–livestock interactions.

Convergent nuclear proteostasis alterations across 40S ribosomal protein deficiencies

X-DILiver: an ensemble learning framework for predicting drug-induced liver injury

Misregulation of T-box transcription factors drives BNP–NPR1 signalling underlying chronic itch

Abstract Chronic itch poses a significant clinical burden, with activation of the brain natriuretic peptide (BNP) pathway as a hallmark, though its transcriptional control remains unclear. We identify T-box transcription factor 20 (TBX20) as upregulated in skin of atopic dermatitis patients, with increased expression in NPR1 + keratinocytes. ChIP peak calling, ChIP-qPCR and dual-luciferase assays show TBX20 activates the NPR1 promoter. In mice, keratinocyte-specific TBX20 knockout (TBX20 fl/fl ; K14-Cre) reduces scratching, IL-4 and Oncostatin M levels, basophil markers, and decreases cutaneous NPR1 expression. TBX20 is also expressed in a subset of NPR1 + sensory neurons, and neuron-specific deletion similarly alleviates itch, basophil infiltration, and barrier dysfunction. RNA-seq identifies lipocalin-2 as a downstream effector of the TBX20-NPR1 axis, and its deletion reduces itch. Conversely, AAV-mediated TBX20 rescue exacerbates symptoms. Neuregulin 1 suppresses TBX20, attenuates IL-13-driven NPR1 signalling, and reduces itch. These findings define a TBX20-NPR1 axis as a critical regulator of chronic itch and skin dysfunction.

A requirement-driven framework for cloud service provider selection using AHP, QFD, and TOPSIS

Confidence-guided cryo-EM map optimisation with LocScale-2.0

Abstract Cryogenic sample electron microscopy (cryo-EM) maps often display uneven quality, with high-resolution features coexisting alongside weak or poorly ordered regions. Such variation complicates structural interpretation, especially for heterogeneous macromolecular assemblies. Here, we present LocScale-2.0, a context-aware map optimisation framework that operates without prior knowledge of molecular structure or composition. By leveraging general expectations of electron scattering by biological macromolecules, it enhances local detail and connectivity while preserving weak but biologically relevant structural context. We further introduce LocScale-FEM, a Bayesian approximate deep-learning approach that emulates this optimisation to generate feature-enhanced maps. LocScaleFEM provides voxel-wise confidence scores that give a statistically grounded measure of reliability, are sensitive to local phase error in the feature-enhanced map, and highlight regions where interpretation warrants caution. Selected examples illustrate how confidence-guided map optimisation can aid biological interpretation and increase objectivity in cryo-EM density analysis.

Artificial intelligence powered decoding of Plasmodium falciparum sporozoite motility patterns

Mid-IR light modulators enabled by dynamically tunable ultra-high-Q silicon membrane metasurfaces

Abstract Metasurfaces enable subwavelength control of free-space light for applications in sensing, nonlinear optics, and quantum photonics. However, their practical deployment is hindered by two key limitations: a tradeoff between low- Q resonances and weak amplitude contrast, and their predominantly static nature allowing only passive functionalities. These challenges are particularly severe in the mid-infrared (mid-IR), where the scarcity of low-loss materials constrains performance and scalability. Here, we demonstrate actively tunable single-crystalline silicon membrane metasurfaces combining high- Q resonances, strong amplitude contrast, and wafer-scale manufacturability. Our platform achieves record-high measured Q -factors up to 3000 in the mid-IR and supports two dynamic modulation schemes: electro-thermal tuning via Joule heating with  >50% modulation depth at CMOS-compatible voltages and speeds up to 14.5 kHz, and ultrafast all-optical modulation via carrier generation in silicon with nanosecond response times and estimated sub-GHz rates. These results establish silicon membrane metasurfaces as a scalable platform for active mid-IR photonics.

Aqueous Cascade Synthesis of Robust Dual‐Linkage Covalent Organic Frameworks for Efficient Hydrogen and Oxygen Evolution at an Industrial‐Level Current Density

ABSTRACT One‐step integration of robust dual linkages into a covalent organic framework (COF) in H 2 O remains a significant challenge. Herein, we report an aqueous‐phase synthesis strategy for constructing crystalline COFs containing both propenone and meta ‐pyridyl linkages via a one‐pot cascade reaction. This approach ingeniously combines reversible aldol condensation with irreversible Chichibabin pyridine synthesis, leveraging the intermediate role of chalcone units to promote error corrections for crystallization. The resulting dual‐linkage COFs (termed PYP‐1, ‐2, ‐3) exhibit well‐defined crystalline structures. When evaluated as metal‐free electrocatalysts, PYP‐3 delivers superior performance, achieving a low overpotential of 46 mV for the hydrogen evolution reaction (HER) at 10 mA cm −2 and outstanding durability for the oxygen evolution reaction (OER) exceeding 600 h at an industrial current density of 500 mA cm −2 . In situ FTIR spectra and density functional theory calculations reveal that the high‐density pyridinic nitrogen sites function as intramolecular proton relays, facilitating concerted proton‐coupled electron transfer and optimizing intermediate adsorption via donor‐acceptor interactions. This work establishes a green and versatile platform for constructing dual‐linkage COFs and highlights their potential as advanced electrocatalysts for sustainable energy conversion.

Nonlinear association between cockcroft-gault creatinine clearance and all-cause mortality in critically ill cerebrovascular disease patients: a retrospective cohort study

Single-nucleus analysis of the adult human olfactory epithelium uncovers shared neurogenesis programs with the brain

Microenvironment Engineering as a Design Principle for Suppressing Catalyst Metal Loss

ABSTRACT Stability losses in platinum electrocatalysts arise from dissolution, redeposition, and restructuring processes that are strongly shaped by the catalyst microenvironment. Yet the degree to which ionomer chemistry and support porosity jointly govern the true platinum mass balance remains unresolved. Here, by integrating operando ICP‐MS with an ion‑exchange approach that quantifies platinum species retained within the ionomer, we distinguish apparent dissolution from actual metal loss across model polycrystalline platinum and supported nanoparticles. We find that direct ionomer‐platinum contact enhances intrinsic dissolution while simultaneously trapping dissolved platinum ions, leading to a pronounced mismatch between measured and actual platinum loss. Extending this framework to porous and nonporous carbon supports reveals that pore‐confinement fundamentally alters degradation pathways, promoting local redeposition and suppressing net metal loss. Our results show that managing ionomer access and nanoscale transport within the catalyst microenvironment is a key practical factor in improving electrocatalyst durability.

Deciphering the molecular impact of ALDH5A1 missense variants in succinic semialdehyde dehydrogenase deficiency through combined in vitro and in silico approaches

Meta-analytic evidence for distinct neural correlates of conditioned versus verbally induced placebo analgesia

Abstract Placebo analgesia demonstrates that belief and expectation can significantly alter pain, even without active treatment. Placebo analgesia can be induced through verbal suggestion, classical conditioning, or their combination, though the role of conditioned neural responses above and beyond effects of verbal instructions remains unclear. We conduct a systematic meta-analysis of individual participant data from 16 within-participant placebo neuroimaging studies ( n  = 409), employing univariate and multivariate analyses to identify shared and distinct mechanisms of placebo analgesia induced by suggestions alone versus suggestions combined with conditioning. Both techniques increase activity during pain in the dorsolateral prefrontal and inferior parietal cortices and decrease activation in the insula, putamen, and primary sensory areas. Adding conditioning enhances engagement of regions associated with context representation and pain modulation (e.g., dorsolateral/dorsomedial prefrontal cortices) and decreases in nociceptive regions (e.g., primary sensory and insular areas). Conditioning also strengthens the negative association between analgesia and nociceptive activity, as quantified by the Neurologic Pain Signature. Combining conditioning with instructions yields greater placebo analgesia, mediated by increased ventromedial prefrontal and dorsal caudate activity, alongside decreased sensory-nociceptive and cerebellar activity. These findings suggest the two strategies rely on partially distinct mechanisms in the brain.

Harnessing Photons for Trifold Output: Chromic, Luminescent, and Mechanical Transformations in a Smart Material

ABSTRACT By leveraging the dual photochemical activity of vinylpyridinium building blocks, the concurrent [2+2] photocycloaddition and photoinduced electron transfer are integrated within coordination polymer frameworks to achieve triple photoresponses, simultaneously generating photochromism, fluorescence modulation, and photomechanical actuation within a single crystalline system. The efficient photocycloaddition occurs in the interpenetrated framework despite the criss‐crossed olefin arrangement, resulting in rapid stress accumulation and release that manifests as explosive photosalient behavior alongside optical switching. The framework‐dependent ligand conformations produce distinct fluorescence readouts, allowing the progress of the cycloaddition to be monitored optically. When embedded in poly(vinyl alcohol) matrices, the crystal‐level micro‐strain is amplified into programmable macroscopic motions including straightening, crawling, and gathering under single‐wavelength irradiation. This work provides a design strategy for integrating multiple photoresponses into a single material, contributing to programmable light‐driven actuators and adaptive devices.

Dynamic analysis of high speed railway box girders using a moving load finite element model

Internalized components of membrane attack complexes disrupt proteostasis and acquire alarmin-like properties

Abstract Immune effects of membrane attack complexes (MAC) have been widely attributed to their abilities to cause cell death. Here, we show that the MAC component, C9, forms non-cytolytic aggregates with pro-inflammatory effects. Intracellular aggregates of C9 are detected within inflamed tissues of patients in association with endothelial cell (EC) activation but not increased cell death. We identify NUMBL as a Rab35 effector that directly binds surface-bound C9 to promote C9 internalization and entry into the endolysosomal pathway. Within acidified endolysosomes, C9 forms insoluble aggregates that are targeted for degradative aggrephagy in a process that activates NF-κB. For C9 aggrephagy to occur, ZFYVE21, a Rab5 effector, complexes with RNF34 to bridge C9 aggregates to LC3B+ aggresome membranes. We detect C9 aggregates in vivo, and we show that a ZFYVE21-RNF34 signaling axis is required for C9 aggrephagy and NF-κB -dependent EC activation in three separate mouse models. Mice with conditional loss of ZFYVE21 in ECs show reduced aggregraphy, resulting in attenuated systemic inflammation and reduced tissue injury following skin transplantation. Our data show that the C9 component of MACs forms intracellular aggregates with alarmin-like properties.