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Integrated framework to study genomic surveillance of selective sweeps in multivariants dynamics
Pandemics often involve complex transmission dynamics in which epidemiological surveillance is essential but not sufficient for containment, as resurgence may be driven by emerging or imported variants. Rapidly evolving pathogens produce complex disease dynamics driven by emerging variants often differing in their transmissibility, immune escape, and cross-infection. These processes influence individuals’ immune life histories, producing highly dynamic immune landscapes that modulate the emergence and dominance of novel variants. We develop an integrated modeling framework that couples multivariant mean-field epidemic modeling with a mechanistic genomic dominance model and a probabilistic surveillance model. This study examines how variant emergence timing, infectiousness advantage, and cross-infection jointly shape epidemic trajectories, immune landscapes, and genomic composition. Our results demonstrate that the dominance dynamics of cocirculating variants correspond to a selective sweep characterized by a system of multilogistic equations driven by population immunity. Moreover, we show that the detection time of newly introduced variants can be accelerated or delayed depending on their emergence conditions and the prevailing variant landscape. Finally, we demonstrate that the effectiveness of response strategies depends critically on the evolving genomic composition of the outbreak, highlighting trade-offs between surveillance sensitivity and intervention timing. We validate our framework by jointly fitting epidemiological and genomic data from the spread of the Ancestral, Alpha, Gamma, and Delta variants in the United States, Denmark, the United Kingdom, and Canada. The results provide a quantitative foundation for linking epidemic dynamics, genomic surveillance, and immune life histories, advancing the development of genomic epidemiology for multivariant outbreaks.
Postharvest delivery of Bacillus G36 metabolites formulated in AgNP modifies Salvia rosmarinus Spenn. bioactive profiles
Abstract This study explores the biological synthesis of silver nanoparticles (AgNPs) using elicitors (ML) from the beneficial bacterium Bacillus G36 and evaluates their potential to enhance bioactive compound production in postharvest rosemary ( Salvia rosmarinus Spenn.). To determine optimal synthesis conditions, different ratios of ML to AgNO3 1mM were mixed, for 24 h, evaluating a range of temperatures (28–37) and pH (5, 7, 9), with and without rosemary extracts, which were characterized by TEM, FTIR, XRD and Zpotential. Two NP were selected based on size and organic crown for biological assay on rosemary. The best conditions were a 1:1 (vv) mixture of ML and silver nitrate, pH 9, 37 °C, producing nanoparticles with an average size of 7.5 nm (S3). These small AgNPs have shown great biological activity. In contrast, adding rosemary extract (RE) to nucleation media, in order to increase reductive media potential, yielded larger particles (≈ 63.9 nm) and reduced their effectiveness. Biological assays showed that S3 AgNPs significantly increased total phenol and flavonol contents in rosemary when applied in postharvest, while ML alone did not, highlighting the better effect of elicitors when formulated in NP. Remarkably, only S3 AgNPs enhanced rosmarinic acid levels by 50%. Both S3 AgNPs and live Bacillus G36 cells also boosted diterpene (carnosic acid equivalents) concentrations. Despite effects on bioactives, only S3 and ML treatments increased the total antioxidant capacity of the extracts. Overall, the study demonstrates that biosynthesized S3 AgNPs from Bacillus G36 metabolites offer a sustainable and efficient approach to producing small, bioactive nanoparticles capable of improving and maintaining valuable phytochemicals in rosemary postharvest.
IL-17RA signaling promotes the dedifferentiation of Paneth progenitors through ADAM17 to regenerate gut epithelium post-irradiation
Control of microglial dynamics by the Arp2/3 complex and the autism- and schizophrenia-associated protein CYFIP1
Microglia use a highly complex and dynamic network of branched processes to sense and respond to their surroundings. Despite emerging evidence that microglial motility plays important roles in brain development, neurodegeneration, and neuropsychiatric disease, little is known about the intracellular machinery orchestrating microglial process dynamics. Here, we identify roles for regulators of the actin cytoskeleton in controlling microglial behavior. We show that the actin branching Arp2/3 complex is critical for maintaining microglial morphology and is required for surveillance but not chemotactic motility. Neuropsychiatric disease-associated CYFIP1, a core component of the WAVE regulatory complex linking upstream signaling pathways to activation of the Arp2/3 complex, is highly expressed in microglia but has an unknown function. We report that conditional deletion of Cyfip1 in mouse microglia reduces their morphological complexity and surveillance of the brain parenchyma, with no effect on chemotaxis. Deletion of Cyfip1 also increased microglial CD68 positive lysosome volume and engulfment of presynapses. Thus, actin remodeling by CYFIP1 and the Arp2/3 complex controls microglial dynamics and shifts microglia away from a homeostatic state with potential implications for neuropsychiatric disease.
Effect of copper rod length on the melting behavior of paraffin wax in hemispherical latent heat storage units
Abstract The inherently low thermal conductivity of phase change materials (PCMs) stills a major limitation for their use in latent heat thermal energy storage (LHTES) units, as it significantly reduces the charging procedure and decreases system responsiveness. This study presents a novel numerical examination of the isolated effect of a single vertical copper rod of varying lengths on the melting performance of RT42 paraffin wax within a hemispherical cell. Unlike previous studies that focused on fins or composite structures in other geometries, this work uniquely quantifies the impact of systematically increasing rod length (0, 10, 20, and 30 mm) on melting enhancement in hemispherical configurations. Four cases had been simulated using ANSYS Fluent 16 with enthalpy-porosity technique to obtain transient heat transfer, fluid flow, and evolution of melting front. It was shown that the copper rod boosted thermal exchange and shortened the total time of melting, and it took 300 min (no rod) to 150, 120, and 90 min when using 10, 20, and 30 mm copper rod, respectively. The highest reduction in melting time was 70 percent and the corresponding increment in the melting rate was 233 percent in the longest rod compared to the finless. Besides, the existence of the rod resulted in the existence of more homogeneous temperature distributions and stronger convective currents, which increased the overall thermal efficiency. The findings provide valuable design guidance, demonstrating that the thermal conductivity limitation of organic PCMs can be effectively overcome through simple geometric modifications using high-conductivity inserts.
Vascular smooth muscle cell state trajectories mediate molecular mechanisms of coronary disease risk
A soft electrode array with reconfigurable hydrogel interfaces for high-fidelity neurophysiological monitoring during craniotomy
Achieving accurate monitoring of electrophysiological activity from the brain cortex is critical for preventing postoperative neurological deficits during craniotomy. However, current technologies face profound challenges in enabling consistent high-quality neural signal acquisition due to complex intracranial environments (e.g., wet/fragile brain surfaces and surgical instrument interference). Here, we develop a soft electrode array with reconfigurable hydrogel interfaces for sustainable high-fidelity monitoring of electrophysiological states from the functional brain cortex throughout neurosurgical procedures. Specifically, we propose a solution-triggered reconfiguration strategy to implement the repeated disassembly/replacement of hydrogel interface layers on electrodes, ensuring consistently superior recording and stimulation properties. Furthermore, through modification with cationic hydrogel microspheres, the hydrogel interface demonstrates strengthened wet adhesion and antiswelling performances, creating robust hydrogel/brain coupling to minimize motion artifacts. In craniotomy of animal models, the electrode array maintains low impedance and high signal-to-noise ratio during repeated repositioning tests through hydrogel interface reconfiguration. In traumatic brain injury models, the electrode array can record consistent high-quality somatosensory evoked potential with dynamic tracking of potential amplitude and latency changes in sensory areas. Quantitative assessments in nerve block experiments verify that the soft electrode array can efficiently elicit motor evoked potentials in motor areas with low stimulation currents. The proposed soft electrode array represents a promising platform for sustainable high-fidelity electrophysiological monitoring. The hydrogel interface design strategy provides an effective approach for developing reconfigurable devices in biomedical applications.
Proteomic analysis reveals selenium-induced metabolic alterations in forest-grown ginseng
Built-in electric field engineering in Co2N0.67/CoP heterostructures for glycerol electrooxidation-assisted hydrogen production
Single-cell analyses identify independent aging processes that compete to determine cellular fate in budding yeast
Phenotypic heterogeneity is prevalent during aging, yet its underlying molecular drivers remain poorly understood. In budding yeast, two distinct aging trajectories, characterized by either ribosomal DNA (rDNA) instability or mitochondrial decline, have been proposed to be mutually exclusive. Here, we systematically dissect the heterogeneity among aging yeast cells by combining single-cell transcriptomics with longitudinal fluorescence microscopy. Our data reveal distinct transcriptional responses that emerge in aging cells, highlighted by loss of rDNA silencing, a hypoxia response, and the environmental stress response (ESR). Contrary to expectation, we establish that ESR induction is not caused by rDNA instability but is instead a consequence of an early decline in mitochondrial membrane potential. However, the ESR is merely a biomarker of this decline and not itself a determinant of lifespan. While rDNA instability and mitochondrial dysfunction are anticorrelated as terminal phenotypes, we find that they are not necessarily mutually exclusive and can instead proceed concurrently within individual cells. Targeted genetic perturbations that are specific for one pathway do not impinge on the other, which is in contradiction to the idea of mutual inhibition between the two. We therefore propose a “competing hazards model”, where independent aging processes progress in parallel, and the observed mode of death is determined by which process first reaches a catastrophic failure point. Our work untangles the causal links between several aging pathways and provides a framework for understanding how distinct aging trajectories emerge from independent molecular events.
Comparison of serum 25-hydroxyvitamin D levels between patients with multiple chemical sensitivity and healthy controls: A case–control study
Abstract Vitamin D deficiency has been associated with a range of neurological and allergic conditions. Whether such an association exists in multiple chemical sensitivity (MCS) has not been clarified. This study aimed to compare serum 25-hydroxyvitamin D (25[OH]D) concentrations between patients with MCS and healthy controls. We conducted a case–control study including 80 patients with physician-diagnosed MCS and 5,518 controls. Serum 25(OH)D concentrations were compared using a general linear model with bias-corrected and accelerated bootstrap resampling (1,000 iterations), adjusting for age, sex, season of blood collection, smoking status, body mass index, alcohol intake, and physical activity. Vitamin D deficiency (< 20 ng/mL) was highly prevalent in both groups (78.8% in MCS vs. 75.3% in controls). Median serum 25(OH)D concentrations did not differ significantly between groups (14.6 vs. 15.6 ng/mL, p = 0.622). Adjusted analyses confirmed no statistically significant difference (adjusted difference = 1.07 ng/mL, 95% CI: −0.18 to 2.46, p = 0.119). Despite the high prevalence of vitamin D deficiency, patients with MCS did not differ significantly from controls in serum 25(OH)D concentrations. Although serum 25(OH)D concentrations did not differ significantly between groups, the findings do not exclude a mechanistic role of vitamin D. Local dysregulation of vitamin D receptor signaling or tissue-specific activation may contribute to neuroimmune sensitization in MCS, highlighting the need for system-level investigations.
A shared speed encoding model for running and backing away behaviours in segregated neural circuits
Abstract How neuronal firing within a circuit encodes behavioural intensity, like running speed, is largely unknown. Projections from temporal association cortex (TeA) and superior colliculus (SC) to dorsal periaqueductal grey (dPAG) circuit can both trigger running behaviour. Using in vivo loose-patch recordings with circuit manipulations in mice, we quantified a firing - speed relationship and established its encoding model. Here, we report two behavioural patterns induced by circuit activation: backing away and rebound running. Mechanistically, dPAG CaMKIIα neurons receiving inputs from either TeA or SC, function as distinct “behavioural units”, controlling two “unit behaviours” of running and backing away, respectively. The unidirectional inhibition from the backing away unit to the running unit is mediated by somatostatin (SOM) neurons in dPAG, enabling transitions among four behavioural states: running, backing away, stopping, and rebound running. Both running and backing away behaviours follow a unified motor encoding model, quantified by a single-phase association equation.
Lithosyntrophy: Obligate syntrophy in a phosphite-oxidizing, methanogenic culture
The anaerobic conversion of organic matter to methane and carbon dioxide typically relies on obligate syntrophic interactions between bacteria and methanogenic archaea, where interspecies electron transfer enables thermodynamically constrained reactions to proceed near equilibrium. Syntrophs often couple the oxidation of fermentation products such as fatty acids and alcohols to the reduction of protons to form hydrogen (H 2 ). These reactions can only proceed if low H 2 concentrations are maintained by H 2 -consuming syntrophic partners. Here, we describe “lithosyntrophy,” a mode of syntrophic interaction in which electrons that drive hydrogenotrophic methanogenesis originate from an inorganic compound rather than from the canonical organic substrates. Candidatus Phosphitivorax anaerolimi Phox-21 oxidizes phosphite (HPO 3 2− , oxidation state +3) to phosphate coupled to hydrogenogenesis in an obligate energetic dependency on a hydrogenotrophic methanogen, Methanoculleus sp. Physiology experiments, thermodynamic calculations, genomic annotation, and metaproteomics analysis collectively revealed a mechanism for syntrophic phosphite oxidation in Phox-21. In this pathway, electrons derived from phosphite drive H 2 production via an electron-confurcating hydrogenase. Unlike previously characterized acetogenic phosphite oxidizers, Phox-21 is a mixotroph that assimilates acetate to form biomass. Lithosyntrophic phosphite oxidizers may play important roles both in transferring reducing equivalents as well as biologically available phosphorus to other members of their surrounding microbial communities, establishing a previously unrecognized metabolic and biogeochemical link between the phosphorus and carbon redox cycles in anoxic ecosystems.
Potential impact of nicorandil on the pharmacodynamics of anti-angiogenic agents
All-optical logic processing unit using Kerr nonlinearity of MXene
FDA must regulate stem cell therapies to mitigate risks to patients and the public
Multi-model forecasting of $$\text {NO}_{2}$$ and $$\text {O}_{3}$$ in Abu Dhabi: benefits of correlation-based feature augmentation
Permeable nanoreactor eye drop for enzymatic cascade-mediated treatment for acute retinal injury model mimicking geographic atrophy
Phase separation of DDHD2 remodels lipid metabolism to dictate treatment sensitivity in luminal breast cancer
Luminal breast cancer is characterized by a persistent risk of recurrence and dysregulated lipid metabolism. However, the role of phase separation, a novel mechanism for the spatial compartmentalization of proteins, in lipid remodeling within the context of breast cancer remains largely unexplored. Utilizing the multiomics data from our large breast cancer cohort (n = 773), we revealed that aberrant lipid metabolism negatively impacts the prognosis of patients with luminal breast cancer. Furthermore, we deciphered that the copy number alteration-driven cis -regulation of DDHD domain containing 2 (DDHD2) is correlated with lipid remodeling in luminal breast cancer. Mechanistically, DDHD2 forms biomolecular condensates through phase separation upon AKT1-mediated phosphorylation, which enhances its lipase activity, reduces the abundance of proferroptotic lipids, and consequently decreases ferroptosis susceptibility. Therapeutically, the DDHD2 inhibitor KLH45 remarkably enhances ferroptosis sensitivity to restrict luminal breast cancer progression, and its combination with ferroptosis inducers further improves the efficacy of endocrine therapy. Collectively, our findings reveal a key role of DDHD2 condensates in lipid reprogramming and propose an innovative therapeutic strategy for luminal breast cancer.
Artificial intelligence integrated WeChat social media adoption for collaborative learning engagement among university students
Abstract Artificial intelligence (AI) has transformed social media into a powerful tool for educational learning engagements. WeChat, a Chinese social media platform, is extensively used by students for academic learning, collaboration, and information acquisition. However, research on the adoption of AI-integrated social media for learning engagement remains limited, especially in the Chinese context. Based on the traditional Technology Acceptance Model (TAM), this study proposes an AI-Integrated Social Media Adoption (AISMA) model for learning engagement by integrating the core TAM constructs—perceived usefulness (PU) and perceived ease of use (PEOU), with the external factors of collaborative learning, social support, resource sharing, and facilitating conditions to investigate their influence on students’ intention to adopt AI-integrated WeChat for learning engagement. Data from Chinese university students were analyzed using structural equation modeling (SEM) via Smart-PLS 4. The results confirm that collaborative learning, social support, and resource sharing are significant direct drivers of AI-integrated social media adoption. Furthermore, facilitating conditions significantly influence both PU and PEOU and also directly drive adoption intention. A key finding from the moderating analysis is that PEOU significantly amplifies the effects of all three external factors (collaborative learning, social support, and resource sharing) on adoption intention. While PU significantly strengthens the relationship for social support and resource sharing, it does not moderate the link between collaborative learning and adoption intention. The study concludes by discussing the theoretical contributions and practical implications for educators and platform developers.