Browse Articles

Optical voltammetry of redox processes inside a nanohole with opto-iontronic microscopy

Cyclic Voltammetry (CV) is the most commonly used method in electrochemistry to characterize electrochemical reactions, usually involving macroscopic electrodes. Here, we demonstrate an optical CV technique called opto-iontronic Microscopy, which is capable of monitoring electrochemical processes at the nanoscale. By integrating optical microscopy with nanohole electrodes, we enhance sensitivity in detecting redox reactions within volumes as small as an attoliter [ ( 100 nm ) 3 ]. This technique uses electric-double-layer modulation and lock-in detection to sensitively probe ion dynamics during cyclic voltammetry in nanoholes that are under total internal reflection illumination. We applied this method to study electric double layer (dis)charging coupled to ferrocenedimethanol [Fc(MeOH) 2 ] redox reactions. Experimental results were validated against a theoretical Poisson–Nernst–Planck–Butler–Volmer model, providing insights into ion concentration changes of reaction species that contribute to the optical contrast. This work opens up opportunities for high-sensitivity, label-free analysis of electrochemical reactions in nanoconfined environments, with potential applications in pure nanocrystal growth and monitoring.

Cardiac autonomic function in bronchiectasis and age and gender-matched healthy participants: case–control study

Abstract This study aims to evaluate and compare cardiac autonomic function, specifically through heart rate variability (HRV), between individuals with bronchiectasis and their age- and gender-matched healthy counterparts. This study employed a case-control design, involving 60 participants diagnosed with bronchiectasis (cases) and a control group of healthy individuals matched by age and gender. HRV data was collected over a five-minute interval, focusing on frequency domain parameters including total power, very low frequency (VLF), low frequency (LF), high frequency (HF), and the LF/HF ratio. The bronchiectasis group exhibited a significantly elevated LF/HF ratio, indicating a shift in cardiac sympathovagal balance, relative to the control group (2.25 ± 0.39 vs. 2.05 ± 0.38; p  = 0.006). Additionally, marked differences were found in specific frequency domain parameters: LF (2.33 ± 0.55 vs. 2.55 ± 0.46; p  = 0.021) and HF (2.06 ± 0.75 vs. 2.5 ± 0.56; p  = 0.001). The results suggest a notable disturbance in cardiac autonomic regulation among individuals with bronchiectasis, compared to healthy individuals.

Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication

Emerging and reemerging viruses pose a significant threat to global health. Although direct-acting antivirals have shown success, their efficacy is limited by the rapid emergence of drug-resistant viral variants. Hence, there is an urgent need for additional broad spectrum antiviral therapeutic strategies. Here, we identify by phenotypic screening a set of stereochemically defined photoreactive small molecules (photo-stereoprobes) that stereoselectively suppress SARS-CoV-2 replication in human lung epithelial cells. Structure–activity relationship–guided chemical proteomics identified the eukaryotic translation termination factor 1 (ETF1) as a target of the photo-stereoprobes, and this interaction was recapitulated with recombinant purified ETF1. We found that the photo-stereoprobes modulate programmed ribosomal frameshifting mechanisms essential for SARS-CoV-2 infection without causing ETF1 degradation, thus distinguishing the photo-stereoprobes from other known ETF1-directed small molecules. We finally show that the photo-stereoprobes also inhibit the replication of additional viruses with noncanonical ribosomal frameshifting mechanisms. Our findings identify a mechanistically distinct class of ETF1 ligands that implicate host translation termination processes as a potential drug target for antiviral development.

Modeling metacognition and executive functions in the metacognitive wisconsin card sorting test using the neuropsychological digital-twin method

Elucidating chiral myosin–induced actin dynamics: From single-filament behavior to collective structures

The myosin superfamily encompasses over 70 classes, each with multiple subclasses, and exhibits substantial diversity in properties such as velocity, ATPase activity, duty ratio, and directionality. This functional diversity enables the specialized roles of each myosin in various organisms, organs, and cell types. Beyond these well-characterized parameters, a newly recognized property has recently come into focus: Certain myosins drive actin filaments along chiral curved trajectories. However, this newly identified property remains largely unexplored. Here, we investigated this chiral motion in vitro using Chara corallina myosin XI ( Cc XI), which drives fast clockwise (CW) movement of actin filaments. This chiral motion arises from asymmetric displacement at the filament’s leading tip, and its curvature depends on the myosin density. Surprisingly, at elevated actin concentrations, filaments exhibiting chiral curved motion undergo collective dynamics, spontaneously forming a ring-shaped structure—termed the actin chiral ring (ACR)—that exhibits persistent CW rotation. ACRs display remarkable stability, continuing to rotate at their formation site until ATP is depleted, while maintaining their structure even after rotation ceases. This stability has not been reported among reported collective motions of cytoskeletal proteins driven by various motors. Our findings demonstrate that myosins with chiral activity can autonomously organize actin filaments into stable, chiral structures through collective motion, providing insights into actin self-organization by unconventional myosins. This paradigm offers a mechanistic basis for how motor-driven molecular asymmetry can give rise to coherent structural chirality at the cellular scale—an essential step in the emergence of cell chirality and asymmetry during development.

Biocompatible 3D hierarchical flower-like iron-doped silver nanostructures as a platform for in vitro and in vivo drug delivery

FcγRIIB functions as an IgG transporter in the mammary gland

In mammals, passive acquisition of maternal immunoglobulins is essential for neonatal immune development and defense against infections. IgG, a central mediator of humoral immunity, is maternally transferred via distinct mechanisms depending on placental structure in placental mammals. In humans (hemochorial placenta), IgG is prenatally transported across the placenta, whereas in large domestic animals such as pigs and cows (epitheliochorial/connective chorionic placenta), IgG is exclusively transferred postnatally via colostrum and absorbed in the neonatal intestine. Rodents (allantoic chorionic placenta) employ both pathways. Critically, IgG must traverse multiple tissue barriers-including the placenta, mammary gland, and neonatal intestine-to reach the circulation of newborns. While FcRn is known to facilitate IgG transport in the placenta and neonatal intestine, the mechanisms underlying IgG secretion into milk remain unclear. Here, we identify FcγRIIB as the key transporter mediating maternal IgG transfer across the mammary gland in mammals. Using constitutive and conditional knockout mice, we demonstrate that FcγRIIB deficiency impairs mammary IgG transfer, whereas its overexpression enhances milk IgG levels. Strikingly, in pigs, FcγRIIB is highly upregulated in mammary tissue prepartum, and its disruption abolishes IgG accumulation in colostrum. Our work opens avenues for improving neonatal immunity through targeted modulation of FcγRIIB-mediated IgG transport.

The adaptive nature of the foam proteome produced by Mahanarva spectabilis (Hemiptera: Cercopidae) when infesting forage grasses with different levels of antibiosis-type resistance

Abstract The spittlebug Mahanarva spectabilis (Distant, 1909) (Hemiptera: Cercopidae) produces a stable extracellular foam during its nymphal stage, which plays a critical role in survival and host plant interactions. In this study, we present the first comprehensive proteomic characterization of foam secreted by M. spectabilis nymphs, using a shotgun LC–MS/MS approach. We analyzed the foam produced by nymphs feeding on four forage cultivars showing different levels of antibiosis-type resistance against M. spectabilis , as follows: Cenchrus purpureus cv. Pioneiro (moderately resistant) and cv. Roxo de Botucatu (susceptible); Urochloa brizantha cv. Marandu (resistant), and Urochloa decumbens cv. Basilisk (susceptible). A total of 196 proteins were identified, including a substantial fraction of unannotated proteins with high abundance, suggesting specialized foam-specific functions. Functional annotation revealed enrichment in hydrolases, oxidoreductases, and binding proteins, highlighting potential roles in microbial regulation, stress response, and structural maintenance. Comparative analysis revealed consistent up-regulation of cytoskeletal and metabolic proteins in resistant/moderately resistant hosts, alongside repression of proteins related to carbohydrate and lipid metabolism. Multivariate and GO-based analyses confirmed host genotype-dependent modulation of foam composition. The findings demonstrate that higher levels of resistance to M. spectabilis are associated with two key strategies: (1) the suppression of metabolic pathways, likely limiting nutrient availability to the insect, and (2) the activation of defence-related proteins, such as antioxidant enzymes, which enhance the plant’s ability to cope with stress. These findings underscore the dynamic and adaptive nature of the foam proteome, reflecting both environmental and physiological constraints. Our results provide new insights into the molecular basis of foam function and its relevance for insect survival, offering promising avenues for the development of novel strategies targeting foam-mediated defence mechanisms.

Mapping targetable sites on the human surfaceome for the design of novel binders

The human cell surfaceome, integral to cell communication and disease mechanisms, presents a prime target for therapeutic intervention. De novo protein binder design against these cell surface proteins offers a promising yet underexplored strategy for drug development. However, the vast search space and limited data on natural or competitive binders have historically limited experimental success. In this study, we systematically analyzed the entire human surfaceome, identifying approximately 4,500 targetable sites and introducing potential binding seeds for initiating protein design applications. To validate these seeds, we implemented two experimental approaches (protein scaffolding and peptide cyclization) on three representative targets (FGFR2, IFNAR2, and HER3). Our results revealed a high success rate, showing that seeds provide valuable starting points for binder design against our identified targetable sites, as well as the need for constant improvements of computational protein design pipelines utilizing machine learning and physics-based methods. Additionally, we present SURFACE-Bind, an interactive database offering open access to all generated data. The high-throughput computational design methods and target-specific binder seeds established here pave the way for a new generation of targeted therapeutics for the human surfaceome.

Estimating chemical oxygen demand in municipal landfill leachate using multilayer perceptron artificial neural networks based on seasonal monitoring data

Medullary and C3–C4 propriospinal pathways underlying mammalian forelimb movement control

Classic models associate goal-directed upper limb movements with cortical motor areas and balance control with the brainstem. However, recent rodent studies suggest that medullary regions and local spinal circuits also contribute to forelimb execution, leaving it uncertain if these findings apply to humans. Critically, the dynamic interactions among medullary motor regions, intersegmental spinal networks, and cortical sensorimotor areas during hand movement control remain poorly understood. Here, through functional MRI (fMRI) studies in humans and mice during forelimb movement tasks, we reveal topographically organized corticomedullary networks, comprising the lateral rostral medulla (Lat-RM) and caudal medulla (CauM), that regulate forelimb movement. In mice, the corticomedullary coupling in both CauM and Lat-RM increased systematically along a ventro-medio-dorsal gradient, with the strongest links to primary motor and premotor cortices. In humans, higher‐order sensorimotor regions drove the strongest connectivity with CauM and Lat-RM, while the more medially located medial rostral medulla remained weakly engaged. Furthermore, simultaneous brain-spinal fMRI revealed distinct functional territories within the human C3–C4 cervical spinal cord, with ventral regions exhibiting strong connectivity to the medulla and dorsal regions to lower cervical segments. Together, our findings identify a conserved corticomedullary network underlying forelimb movement control across species, while also uncovering variation in cortical involvement. They indicate the presence of an indirect pathway involving both the reticulospinal pathway and the C3–C4 propriospinal system, which contributes to fine hand motor control in the mammalian brain.

Comprehensive evaluation of sound absorption property in dual-layer porous concrete pavement

The seeds of the future are in the present: A blind exploration of metastable states

In this work, we present a type of molecular dynamics simulation that aims at finding, in a blind way, metastable states. Using only data coming from an initial unbiased simulation, and with the help of an appropriately defined loss function, we compute a bias that favors sampling yet unexplored configurational space regions, encouraging the system to leave the initial basin. In our work, we take advantage of what is normally thought to be a defect, namely the difficulty of neural networks to generalize. Contrary to most other enhanced sampling methods, which need previous knowledge of the reactive process, we are able to explore in a blind way metastable states, overcoming otherwise insuperable kinetic bottlenecks. We illustrate the workings of the method with a number of instructive examples.

‌Application of XGBoost and logistic regression in predicting 90 days mortality for elderly severe acute renal failure patients

OsKAT1 is a short Shaker potassium channel involved in root-to-shoot potassium translocation and contributes to rice grain yield

Shaker potassium channels play essential roles in K + uptake and distribution in plants. Studies on Shaker channels in Arabidopsis have provided a paradigmatic framework, but the rice genome encodes an additional member, OsKAT1, whose function remians poorly defined. OsKAT1-type channels are characterized by an innately short cytosolic C terminus, forming a unique clade of monocot-specific short Shakers that is prevalent in Poaceae species. In rice, OsKAT1 is predominantly expressed in the root stele. Disruption of OsKAT1 (KO mutation) leads to a significant reduction in K + secretion into the xylem sap delivered to the shoot. Patch-clamp experiments on root stele protoplasts of WT and KO plants indicate that OsKAT1 functions as an inward channel. Functional analyses in Xenopus oocytes reveal that despite activating at weakly negative voltages, OsKAT1 is intrinsically incapable of mediating substantial outward currents—a property attributed to its truncated C terminus. Together with outward K + channel activity, this feature enables stelar cells to remain significantly permeable to K + around the K + equilibrium potential. When expressed in Arabidopsis , OsKAT1 contributes to K + transport in the xylem sap, but only in wild-type plants that express SKOR, a Shaker channel specialized for this role. These results demonstrate that OsKAT1 constitutes a component of K + translocation to shoots and shed light on the energization and regulation underlying this function. Moreover, OsKAT1 is shown to improve rice adaptation to environmental conditions and enhance grain yield under field conditions through its facilitating root-to-shoot ion translocation.

Mitochondrial derived peptide humanin improved semen quality, semen freezability, antioxidant status and in-vitro fertility in crossbred bull

A neuron–astrocyte signaling axis in the ACC sustains diabetic neuropathic pain

Can ferric-oxyl excited states explain elongated iron-oxygen bonds in heme peroxidase catalytic intermediates?

Abstract The use of X-ray structures to determine and interpret the ferryl iron-oxygen bond order in molecular oxygen-activating heme enzymes has, in the past, been controversial. This has mainly stemmed from the susceptibility of ferryl species to X-ray-induced electronic state changes. In this work we establishe using time-resolved serial femtosecond X-ray crystallography (tr-SFX) on a dye-decolourising peroxidase that the ferryl intermediate species (Compounds I and II) captured following in situ mixing of microcrystals with H 2 O 2 have single, rather than the double bond character expected. X-ray emission validated tr-SFX data with quantum refinement, time-dependent-DFT calculations and QM/MM geometry optimizations together support the concept that the single iron-oxygen bond character is not an indication of ferryl reduction or a protonated form (Fe IV -OH) but is instead attributed to the existence of accessible excited states possessing ferric-oxyl (Fe III –O •– ) character. Such states offer insight into the nature of ferryl heme.

AI-enabled cybersecurity framework for future 5G wireless infrastructures

Abstract The deployment of fifth-generation (5G) wireless networks is transforming digital connectivity through ultra-low latency, high data rates, and massive device support. However, enabling technologies such as network slicing, virtualization, edge computing, and dense Internet of Things (IoT) integration significantly expand the attack surface, necessitating advanced cybersecurity strategies. This study proposes a comprehensive multi-layered cybersecurity framework tailored for 5G infrastructures. The framework incorporates device-level trust validation, secure network slice configuration and isolation, dynamic policy enforcement at the orchestration layer, and AI-driven threat detection to provide end-to-end protection across the 5G architecture. Unlike traditional reactive security models, the proposed approach adopts security-by-design principles to proactively mitigate threats. The framework’s effectiveness is evaluated through extensive simulations and benchmarking against established standards, including the NIST Zero Trust Architecture and 3GPP TS 33.501. Results demonstrate a threat detection rate of up to 97.6%, low-latency performance under high-load and adversarial conditions, and scalable operation with large-scale device connectivity. Despite these results, challenges remain in ensuring consistent policy enforcement across distributed edge nodes, achieving interoperability among heterogeneous devices, and balancing performance with stringent security requirements. The study concludes by highlighting future research directions, including quantum-resilient cryptography and self-healing, AI-enhanced security mechanisms, to address evolving threats in future 6G networks.

RHOA controls oncogenic B cell receptor signaling in aggressive lymphoma

Diffuse large B cell lymphoma (DLBCL) is characterized by a variety of specific genetic alterations that impact signaling pathway dependencies and therapeutic outcomes. Among the recurrently mutated genes, we identified RHOA , a member of the small GTPase family, as a selective dependency in DLBCL. Here, we show that RHOA function is essential for the survival of ABC DLBCL cells because it sustains oncogenic B cell receptor (BCR) signaling through maintaining a signaling-permissive conformation of the cortical actin network. This enables the formation of active BCR microclusters at the cell surface, ultimately resulting in constitutive, BCR-driven NF-κB survival signaling. Moreover, we found that RHOA controlled endocytosis of the BCR and thereby the assembly of the endolysosomal My–T–BCR multiprotein complex, a central activator of NF-κB consisting of MYD88, Toll-like receptor 9, and the internalized BCR. The recurrent DLBCL-associated RHOA R5W mutation rendered RHOA constitutively active in its GTP-bound state and changed the conformation of the actin network from primarily filamentous actin to globular actin. This altered actin state led to an increase in BCR microcluster formation, amplification of NF-κB signaling, and resistance to inhibitors targeting chronic active BCR signaling. Hence, our study establishes RHOA and its mutant isoforms as critical regulators of oncogenic BCR signaling in DLBCL.