Browse Articles

Biosynthesis of pyomelanin from methanol with engineered Komagataella phaffii and its characterizations

N6-methyladenosine modification of FZR1 mRNA positively regulates antiviral innate immunity by targeting the MAVS–TRAF3/6 axis

Activation of retinoic acid-inducible gene-I-like receptors (RLRs) is important for type I interferon (IFN-I) production and antiviral innate immunity initiation. However, the epigenetic mechanisms that regulate RLR signaling remain poorly understood and require further investigation. Here, we demonstrate that Fizzy-related protein 1 (FZR1), which is essential for mitotic exit and G1/S transition, potentiates antiviral innate immune responses against RNA viruses. Mechanistically, vesicular stomatitis virus infection increases N6-methyladenosine (m 6 A) modification of FZR1 mRNA, which enhances FZR1 translation and elevates intracellular FZR1 protein levels. Upregulated FZR1 attenuates mitochondrial antiviral-signaling protein (MAVS) binding to 6-Phosphofructo-2-Kinase/Fructose-2, 6-Biphosphatase 3, a glycolytic rate-limiting enzyme, thereby promoting MAVS aggregation. Furthermore, FZR1 facilitates tumor necrosis factor receptor-associated factor 3/6 (TRAF3/6) autoubiquitination independently of the anaphase-promoting complex/cyclosome, subsequently activating interferon regulatory factor 3 and P65 of nuclear factor κB to drive the production of IFN-I and proinflammatory cytokines. Consequently, FZR1 deficiency impairs antiviral responses and increases viral titer in vitro and in vivo. Pharmacological inhibition of FZR1 significantly attenuates MAVS activation and TRAF3/6 ubiquitination, thereby abolishing FZR1-mediated antiviral immunity both in vitro and in vivo. Collectively, these findings reveal a molecular mechanism by which m 6 A modification of FZR1 activates the MAVS–TRAF3/6 signaling axis to potentiate IFN-I-dependent antiviral innate immunity.

Thermal and dielectric performance of transformer oil-based nanofluid with fullerene C60 nanoparticles

Bidirectional regulation of social memory by two distinct types of GABAergic neurons in the lateral septum

Electrostatically driven pattern formation in mixed charged–neutral multicomponent elastic membranes

Multicomponent crystalline and amorphous elastic shells exhibit heterogeneous surface patterns that provide distinctive functionalities in cellular environments. Such patterning typically arises from the competition between short-range attractive and long-range repulsive interactions in membranes. Here, we demonstrate that the intrinsic competition between electrostatic repulsion and elastic deformation is sufficient to drive spontaneous surface patterning in elastic shells, requiring no additional attractive interactions. Using numerical simulations, we demonstrate pattern formation in mechanically homogeneous membranes with heterogeneous surface charge composition across different topologies, including spheres, discs, and flat periodic membranes. We also examine patterns in crystalline and amorphous shells of coassembled charged and neutral components with different bending rigidities. At low charge fraction, discrete charged surface domains form. At intermediate charge fraction, the competition between electrostatics and elasticity leads to elongated domains (rods) of the charged component, which results in lamellar patterns at nearly equal fraction of the charged and neutral components. At high charge fraction, nanodomains of the neutral component form. Amorphous shells exhibit similar progressions but with disordered structures rather than ordered lamellar patterns. These pattern morphologies are observed in both the closed shells and flat membranes. As salt concentration increases, all patterns coarsen due to the screening of electrostatic interactions.

Quantum-enhanced privacy aggregation for healthcare monitoring in wireless body area networks

Multimodal imaging reveals a lysosomal drug reservoir that drives heterogeneous distribution of PARP inhibitors

Abstract For all drugs, effective target engagement requires sufficient intracellular concentrations of drug to be reached, but whether tumour heterogeneity impacts drug distribution and efficacy is poorly studied. Poly (ADP-ribose) polymerase (PARP) inhibitors have transformed treatment opportunities for women with high-grade serous ovarian carcinoma, but resistance remains a clinical hurdle in this highly heterogeneous tumour type. Here, we present a patient-derived explant multi-modal imaging pipeline, which demonstrates that cell-intrinsic PARP inhibitor accumulation is highly variable, both between patients and within tumours. Spatial transcriptomics reveals enrichment of apoptotic and lysosomal signatures in high-drug regions. Rucaparib, an intrinsically fluorescent PARP inhibitor, accumulates heterogeneously at the single-cell level, with rucaparib-high cells demonstrating increased drug response relative to rucaparib-low. Mechanistically, lysosomal sequestration creates a rucaparib reservoir that determines drug levels in the nucleus. Perturbation of lysosomal content alters intracellular levels of weak base PARP inhibitors rucaparib and niraparib, but not olaparib. Together these data suggest that lysosomes act as a reservoir for a subset of PARP inhibitor drugs to improve drug response.

Immune cells employ intermittent integrin-mediated traction forces for 3D migration

To reach targets outside the bloodstream, immune cells can extravasate and migrate through connective tissue. During tissue infiltration, immune cells migrate in an amoeboid fashion, characterized by weak matrix adhesions and low traction forces, that allows them to achieve high migration speeds of up to 10 µm/min. How immune cells reconcile amoeboid migration with the need to overcome steric hindrance in dense matrices is currently not understood. Here we show that NK92 (natural killer) cells can switch from their default amoeboid migration mode to a contractile, mesenchymal-like migration mode when moving through fibrous human amniotic membrane (HAM) tissue. We subsequently study immune cell migration in reconstituted 3D collagen networks with known mechanical properties and pore sizes and apply time-lapse confocal reflection microscopy to obtain simultaneous measurements of migration speed, directional persistence, and cell contractility. We find that NK92 cells exert substantial acto-myosin driven, integrin-mediated contractile forces of up to 100 nN on the extracellular matrix during short contractile phases. This burst-like contractile behavior is also found in primary B, T, NK cells, neutrophils, and monocytes, and is tightly related to the fraction of cells that become stuck in narrow pores of the surrounding matrix. Our results demonstrate that steric hindrance guides the rapid regulation of integrin-mediated adhesion to the ECM in a large number of immune cell subtypes.

Effect of optimized germination on nutritional functional and phytochemical characteristics of green gram

Abstract Germination is an effective bioprocessing strategy for enhancing the nutritional quality and functional potential of legumes. This study systematically evaluated the effects of controlled germination on the nutritional, functional, phytochemical, antioxidant, and sensory characteristics of ten elite green gram ( Vigna radiata L.) cultures, with the objective of identifying genotypes suitable for sprout-based functional food applications. Germination was conducted for 8, 12, 16, and 20 h, and optimization was achieved based on overall sensory acceptability (OSA) score using a nine-point hedonic scale. The highest sensory acceptability scores, ranging from 6.01 to 8.60, were observed at 8 - 12 h of germination, whereas extended germination significantly reduced acceptability due to the development of bitterness. Compared with non-germinated samples, optimally germinated green gram cultures exhibited significant improvements in nutritional composition, including increased crude protein content from 17.38 – 24.81 to 20.12 - 26.32 g 100 g⁻ 1 and crude fiber from 9.86 - 13.82 to 11.36 - 16.42 g 100 g⁻ 1 . Ash content also increased marginally following germination. Vitamin C, which was absent in raw grains, was synthesized during germination and reached levels of approximately 55.04 to 85.48 mg 100 g⁻ 1 . In contrast, anti-nutritional factors were substantially reduced, with tannin content decreasing from 320 - 458 to 65 - 97 mg tannic acid equivalent 100 g⁻ 1 and phytic acid from about 754 - 906 to 102 - 175 mg 100 g⁻ 1 . Germination significantly enhanced phytochemical composition and antioxidant capacity, as evidenced by increased total phenolic and flavonoid contents and higher DPPH radical scavenging activity, which increased from 23.78 - 32.41% in raw grains to 35.47 - 40.59% in germinated samples. Functional properties, including water and oil absorption capacities, were also significantly improved following germination. Overall, this study presents a novel comparative screening of elite green gram cultures and establishes optimized germination as a practical and scalable approach for developing green gram sprouts in both fresh and dry forms in salads, weaning/supplementary foods, nutrient-dense convenience foods, etc., for improved nutrition.

Single-cell spatial map of cis-regulatory elements for disease-related genes in the macaque cortex

Predicting individual incubation of opioid craving by whole-brain functional connectivity

A high risk of relapse triggered by craving during abstinence remains a main challenge in opioid addiction treatment. Multiple brain regions have been implicated in opioid craving, but the brain-wide neural mechanisms underlying this process remain poorly understood. Using resting-state fMRI and connectome-based predictive modeling, we identified a whole-brain connectome that predicted the time-dependent increases (incubation) in oxycodone craving in individual rats after voluntary abstinence induced by exposure to an electric barrier. Incubation of oxycodone craving was operationally defined as the increase in nonreinforced lever pressing during relapse tests from early (day 1) to late (day 15) abstinence (incubation score). We found that changes in whole-brain functional connectivity during abstinence, but not during oxycodone self-administration, predicted the incubation score. Greater decreases in functional connectivity were associated with higher incubation scores. The predictive connectome involved complex interactions across multiple brain systems, including frontal-striatal, frontal-insula, insula-striatal, and hippocampal and sensorimotor circuits. To test causality of the predictive connectome, we examined the effect of pharmacological inactivation of dorsomedial striatum (DMS), which significantly decreased oxycodone seeking after electric barrier-induced abstinence. DMS inactivation increased connectivity strength within the predictive connectome, supporting a causal role of this connectome in incubation of oxycodone craving. The predictive connectome did not predict food-reward seeking after electric barrier-induced abstinence, indicating specificity to oxycodone craving. Our findings identify a brain-wide connectome marker that predicts individual differences in the incubation of opioid craving and provide potential targets for developing personalized interventions and monitoring therapeutic outcomes in opioid addiction treatment.

Genomic identification and complete mitochondrial recovery of a Late Holocene porcupine (Erethizon dorsatum) mummy from Yukon permafrost

Abstract We identified a 3000-year-old specimen from the Traditional Territory of the Tr’ondëk Hwëch’in in central Yukon Territory, Canada as the first known mummified remains of an ancient North American porcupine (Erethizon dorsatum) , known as “Ts’ey” in the Hän language, using genetic analysis and metagenomic validation. Our analysis of the sample yielded the first-ever complete ancient mitochondrial genome for (E. dorsatum) and only the second full mitogenome for the species. Its Holocene age is considerably younger than the Pleistocene megafauna typically recovered in the Yukon permafrost, demonstrating the potential for these deposits to preserve specimens from interglacial periods. Crucially, this finding confirms the presence of porcupines in the region 3000 years ago, in line with the hypothesis that this species only dispersed into Yukon and Alaska following the establishment of boreal forests after the Last Glacial Period.

Oligomerization-competent PIF4 drives thermomorphogenesis through functional redundancy in transactivation and DNA binding

Coexpression among eastern oyster host and microbiome genes suggests coordinated regulation of calcifying fluid chemistry

Marine animals that build shells, such as oysters, carefully regulate the chemistry of their internal calcifying fluids, but the molecular mechanisms behind this control, as well as whether microbes play a role in calcification, are poorly understood. To better understand oysters’ molecular mechanisms and the role of their calcifying-fluid microbes, we conducted experiments that simulated a tidal cycle, measured calcifying fluid pH and total dissolved inorganic carbon, and characterized host and microbial gene expression via transcriptomics. These experiments showed that calcifying fluid pH remained relatively stable throughout tidal pH fluctuations, with corresponding increases in oyster transcripts for ion transport and acid–base regulation. These data provide direct evidence that tidal fluctuations drive rapid changes in oyster calcifying fluid chemistry. Most surprisingly, increases in microbial transcripts related to nitrogen and sulfur cycling correlated to higher calcifying fluid DIC, and coexpression network analysis revealed patterns of gene expression that linked oyster immune and neural pathways to microbial redox processes, providing molecular evidence of potential host modulation of microbial metabolism. Together, these results reveal that oysters actively regulate their calcifying fluid pH over short timescales, and the endemic microbiome metabolic responses can yield metabolites that influence calcifying fluid pH, alkalinity, and ultimately calcification. These data offer a perspective on oyster physiological capacity and, most importantly, the potential role of microbes in oyster calcification. In light of ongoing changes in ocean pH and temperature, oysters provide a model for studying animal–microbial responses to environmental acidification and how their interactions may shape biomineralization.

Modular 4WD agricultural robot for cutting, collection, and precision seeding: design and simulation-based evaluation

Abstract This paper presents a four-wheel differential-drive (4WD) autonomous platform that consolidates grass cutting, collection, leaf crushing, and precision seeding through modular, quick-release toolheads. A vertically stacked two-unit architecture separates the drive/blower subsystem in a steel-framed base from a high-capacity collection chamber; transparent panels aid inspection and service. System specifications are formalized, and operating energy budgets are modelled to predict runtimes across cutting (≈ 1.2 h), crushing (≈ 2.0 h), and seeding (≈ 8.0 h) modes. Coverage-path algorithms (zigzag, spiral, concentric) are simulated, with results confirming that the boustrophedon pattern achieves complete rectangular coverage with minimal redundancy. Robustness simulations quantify debris deflection (> 95% rejection), slope climb limits (≈ 25° at < 20% slip), and stone-ingestion probability (≈ 10%), validating operational resilience. Finite-element analysis of the steel and aluminum chassis demonstrates high safety factors (> 15) with negligible stress or deformation under representative static loads. Beyond robotic functions, composting pathways for collected biomass are outlined to close the loop on sustainability. While dynamic load events and hardware validation are deferred to future work, the results indicate that the proposed modular 4WD platform integrates cutting, collection, and seed delivery with serviceability, structural robustness, and environmental benefit, making it a promising candidate for campus and small-scale agricultural automation.

Visualizing the breakdown of the quantum anomalous Hall effect

The creation of topologically nontrivial matter across electronic, mechanical, cold-atom, and photonic platforms is advancing rapidly, yet understanding the breakdown of topological protection remains a major challenge. In this work, we use magnetic imaging combined with global electrical transport measurements to visualize the current-induced breakdown of the quantum anomalous Hall effect (QAHE) in a magnetically doped topological insulator. We find that dissipation emerges at localized hot spots near electrical contacts, where an abrupt change in Hall angle leads to significant distortions of the current density. Using changes in the local magnetization as a proxy for electron temperature, we directly observe that the electrons are driven out of equilibrium with the lattice at the hot spots and throughout the device in the breakdown regime. By characterizing energy relaxation processes in our device, we show that the breakdown of quantization is governed entirely by electron heating, and that a vanishing thermal relaxation strength at millikelvin temperatures limits the robustness of the QAHE. Our findings provide a framework for diagnosing energy relaxation in topological materials and will guide realizing robust topological protection in magnetic topological insulators.

Deterministic statistical patterns preceding ice shocks revealed by ice deformation measurements

A synthetic ERFVII-dependent circuit in yeast sheds light on the regulation of early hypoxic responses of plants

Plants face hypoxic conditions either chronically, as particular tissues are characterized by fluctuating or stable low oxygen levels, or acutely, when flooded. In vascular plants, transcriptional adaptive responses to hypoxia are rapidly mounted by Ethylene Response Factors VII (ERFVIIs), regulated by Plant Cysteine Oxidases (PCOs) through the cysteine branch of the N-degron pathway (Cys-NDP) for oxygen sensing. However, this relatively simple regulatory circuit, consisting of both constitutively expressed as well as hypoxia-inducible ERFVIIs and PCOs, interacts with diverse signaling cues and pathways invoked by hypoxia. To understand the share of the PCO-mediated oxygen sensing mechanism in the production of hypoxia responses, we insulated the PCO/ERFVII circuit from Arabidopsis thaliana and adapted it to Saccharomyces cerevisiae . Using a reporter gene to monitor the output of the circuit allowed us to compare the speed and amplitude of response to hypoxia in the engineered yeast and the source organism. Hypoxia triggered ERFVII stabilization both in Arabidopsis and yeast, leading to a similarly fast transcriptional response that was however larger in plants. A simple hypoxia-inducible feedback loop improved the amplitude of response in yeast, demonstrating the importance of this regulation in the endogenous PCO/ERFVII circuit. Finally, computational modeling of the yeast circuit enabled us to identify promoter competition and presence of hypoxia-inducible PCOs as key parameters that shape early hypoxia responses in plant cells.

Multi-dimensional deep learning–based segmentation and volumetric assessment of sphenoid sinus fluid on postmortem CT in drowning cases

Macrophage–glia interactions regulate immune damage to enteric neurons during West Nile virus infection

Functional gastrointestinal (GI) tract disorders affect a substantial proportion of the global population and are often preceded by intestinal infections that cause injury to enteric neurons and glia through unrestrained immune responses. However, the mechanisms that limit infection-induced inflammation and protect the enteric nervous system remain poorly understood. Here, we defined such neuron–glia–macrophage interactions after West Nile virus (WNV) infection; this model neurotropic virus causes GI tract dysmotility in mice via injury of enteric neurons through a T cell–mediated cytolytic mechanism. In response to WNV infection, RNA sequencing analysis showed that resident muscularis macrophages upregulate antiviral, proinflammatory, and immunomodulatory genes. Whereas pharmacological depletion of resident macrophages did not affect the viral burden in the GI tract, it instead reshaped the enteric glial response to WNV, resulting in excessive production of T cell and neutrophil chemoattractants. The amplified recruitment of these immune cell types worsened enteric neuronal injury. Together, our findings identify resident muscularis macrophages as key regulators of glia-driven inflammation during enteric viral infection and reveal their role in protecting enteric neurons from immune-mediated damage.