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Rewiring an E3 ligase enhances cold resilience and phosphate use in maize
Quality of life and associated factors among naturally postmenopausal women in Arar Saudi Arabia
Use of circulating tumour DNA to prospectively guide a switch from targeted to immune therapy in BRAF mutant advanced melanoma: the randomised phase II CAcTUS trial
Abstract Checkpoint inhibitor immunotherapy (CPI) for BRAF mutant advanced melanoma first-line results in a better long-term survival compared to targeted therapy (TT), however TT induction may benefit poor prognosis groups. The parallel-arm, randomised phase II, multicentre, feasibility CAcTUS trial (Clinicaltrials.gov NCT03808441) randomised 21 patients to receive standard of care investigators choice TT or CPI, switching to the alternative upon progression ( n = 10), or commencing TT and switching to CPI upon an ≥80% reduction of BRAF variant allele frequency ( VAF) in circulating tumour DNA (ctDNA; n = 11). The study achieved its primary endpoints with 100% (95% confidence interval [CI]: 94-100%) of critical results provided within 7 days to inform a decision to switch and 100% of patients commencing TT achieving an ≥80% reduction of BRAF VAF (95% CI: 80-100%). Secondary outcomes included progression-free survival and overall survival. No new safety signals were observed for TT/CPI. Post-hoc analysis of clinical features, circulating cytokines and chemokines at ctDNA nadir following TT induction suggested a more favourable profile prior to CPI initiation. Longitudinal ctDNA dynamics revealed ctDNA provided an early signal of CPI benefit and that rechallenge with TT following CPI progression resulted in a further ctDNA response. These data support the utility of ctDNA to guide treatment decision-making within a clinically relevant timeframe to optimise treatment scheduling strategies.
In silico augmentation strategies for enhanced machine learning performance in fracture recognition
Differentiable land model reveals global environmental controls on latent ecological functions
Abstract The spatial distributions of plant functional traits observed today are living imprints of current environmental gradients and past selection, offering insight into how plants have adapted to their environments. What remains insufficiently understood is how traits combine and coordinate across environments, and whether such coordination reflects organizing principles in ecology that can improve modeling of ecosystem functional diversity and decadal-scale carbon exchange. Here we present DifferLand, a differentiable hybrid model that learns high-dimensional, coordinated environment–trait relationships directly from multi-modal satellite and in situ observations. DifferLand reveals a small number of latent axes that represent how suites of plant traits jointly shape vegetation dynamics and carbon–water fluxes, enabling the model to capture both long-term adaptation patterns and short-term responses to meteorological variability, and to outperform models that rely solely on plant functional types in spatial generalization. The spatialization network learns nonlinear interactions between plant functional attributes and environmental gradients, organizing latent ecological parameters that represent functional traits at the global scale. This latent environment–trait structure reveals large-scale patterns of ecosystem functional diversity and improves the spatial generalization of terrestrial biosphere models.
Sleep architecture differences and predictive markers of sleep perception impairment in depression
Accelerating molecular dynamics simulations using fast Ewald summation with prolates
A 3D‐Printed Scaffolded Hydrogel Microneedle Array Biosensor for Real‐Time, Continuous Monitoring
ABSTRACT Hydrogel‐based biosensors offer a promising platform for designing microneedles capable of continuously tracking biomarkers in real time. However, such biosensors have been limited by the mechanical properties of hydrated hydrogels, which are generally ineffective at penetrating the skin to access interstitial fluid (ISF). As a solution, we have developed a microneedle‐array biosensor (MAB) patch that enables continuous, reversible sensing by coupling fluorescent deoxyribonucleic acid (DNA) aptamer switches to a hydrated hydrogel mesh within a 3D‐printed scaffold. This scaffold provides essential mechanical support for skin insertion while preserving the apatmer‐hydrogel's sensing functionality in the ISF. We demonstrate this design by tuning both aptamer switch design and hydrogel mesh size to detect exogenous levels of stress hormone cortisol and the metabolite adenosine triphosphate. We subsequently incorporated our cortisol‐sensing hydrogel into the MAB scaffold and coupled this system to a custom‐designed portable optical detector. Following in vitro validation, we demonstrated the biocompatibility and in vivo utility of our system by conducting continuous, real‐time measurements of exogenous cortisol in the ISF of live rats. These results demonstrate, for the first time, submicromolar detection using a sensor‐embedded hydrogel microneedle system, highlighting the MAB platform as a versatile solution for real‐time, continuous in vivo biosensing.
Combined carcinoembryonic antigen, carbohydrate antigen 50, and neutrophil gelatinase-associated lipocalin distinguish benign and malignant pleural effusions: a Bayesian analysis
Real-time volumetric imaging of cells and molecules in deep tissues with Takoyaki ultrasound
Abstract Acoustic contrast agents and reporter genes play a critical role in allowing ultrasound to visualize blood flow, map molecules and track cellular function in optically opaque living organisms. However, many advanced agents requiring high acoustic pressures have been imaged primarily in 2D, while biological phenomena of interest unfurl in three dimensions. Here, we introduce a method for efficient, dynamic imaging of contrast agents and reporter genes in 3D using multiplexed matrix array transducers. Our “Takoyaki” pulse sequence uses the simultaneous scanning of multiple focal points to excite contrast agents with sufficient acoustic pressure for nonlinear imaging while efficiently covering 3D space. We first characterize and benchmark Takoyaki imaging performance with gas vesicle contrast agents in vitro. Then we establish utility in cellular imaging by visualizing acoustic reporter gene expression in a mouse model of glioblastoma. Finally, we demonstrate real-time volumetric imaging by tracking the dynamics of fluid motion in mouse brain ventricles during and after intraventricular contrast injection. Takoyaki imaging enables a more comprehensive understanding of biological processes by providing spatiotemporal information in 3D within the constraints of accessible multiplexed matrix-array systems.
Genotype-by-environment interactions and seed yield stability of narrow-leaf lupin sweet varieties (Lupinus angustifolius L.) based on AMMI and GGE biplot analyses
Smart event-triggered MINFLUX microscopy to catch and follow rare events
Abstract MINFLUX microscopy allows characterization of molecular organization and dynamics with single nanometer spatial resolution and sub-hundred microseconds temporal resolution. However, acquisition times often span minutes to hours as a single fluorophore is measured at a time. Studying live cellular processes therefore requires careful consideration of where and when to apply it, hence manual control limits its potential applications. To overcome acquisition speed, initiation, and data throughput limitations, we present event-triggered MINFLUX: a smart microscopy method using confocal monitoring with real-time image analysis, and applying MINFLUX exactly where and when deemed necessary. The method is controlled through a custom-written open-source Python framework automatically controlling a commercial MINFLUX microscope. We investigate molecular membrane dynamics and organization in 2D and 3D during cellular events: lipid dynamics at caveolae; membrane topography during dynamin-mediated endocytosis; and membrane fluidity and topography during HIV-1 budding site formation. Rapid event detection and minimal regions of interest provides data that would be unfeasible or impossible to acquire through manual microscope control.
Integrated torrefaction-anaerobic digestion of bamboo waste for enhanced energy recovery: process optimization, product characterization, and techno-economic evaluation
Abstract This study evaluates an integrated valorization pathway for bamboo waste that combines torrefaction and anaerobic digestion (AD) to recover energy from both solid and liquid process streams within a circular economy framework. Specifically, a dual-stream valorization approach is developed to maximize energy recovery from both bio-coal and torrefaction condensate. Bamboo’s high lignin content (24–27 wt%), low ash content (< 3 wt%), and favorable volatile composition enable enhanced thermochemical upgrading and subsequent biochemical energy recovery. Torrefaction at 290 °C for 60 min increased the higher heating value (HHV) of bio-coal from 17.6 $$\:\pm\:$$ 0.4 MJ/kg to 25.4 $$\:\pm\:$$ 1.5 MJ/kg, accompanied by ~ 66% reduction in volatile matter and significant lignin enrichment, resulting in improved fuel quality. The aqueous condensate, typically underutilized, containing biodegradable organic acids with low inhibitor concentrations achieved a biomethane potential of 493 $$\:\pm\:$$ 1.7 mL-CH 4 /g-VS during AD, indicating its suitability as a secondary energy source under the tested conditions. The integrated process delivers a net energy recovery of approximately 21 GJ/ton, which is higher than rice husk and rice straw evaluated under identical optimized operating conditions, highlighting feedstock-dependent performance differences under similar conditions. A techno-economic assessment of a 50,000 t/y integrated torrefaction-AD pilot plant facility in India indicated economic feasibility with an internal rate of return (IRR) of 15.8% and a payback period of 6.5 years. Notably, the economic analysis is directly based on experimentally derived mass and energy balances, enhancing its practical relevance. By enabling near-complete utilization of bamboo residues, the proposed pathway supports the development of decentralized biorefineries, sustainable resource use, circular economy principles, and UN Sustainable Development Goals (SDGs) 7, 12, and 13.
Filamin–ETV4/5 acts as mechanosensor–mechanotransducer axis that drives cell competition-mediated elimination of transformed cells
Experimental evolution reveals genomic signatures of variety-specific selection of Cercospora beticola in Germany
Abstract Cercospora leaf spot, caused by Cercospora beticola , is the most destructive foliar disease of sugar beet. Management has relied heavily on fungicides, but widespread fungicide resistance emphasized the need for resistant varieties. To assess how varietal resistance shapes C. beticola populations, we conducted a 3-year field experiment at four locations in Germany using sugar beet varieties ranging from susceptible to highly resistant. Infected leaves were collected separately per variety and location to serve as inoculum for the following year, maintaining variety- and location-specific pathogen populations under controlled selective conditions. A total of 900 isolates were subjected to whole-genome sequencing and population genetic analyses. Isolates collected in 2022 showed extensive admixture among locations. Equal mating-type ratios were observed in some populations but skewed in others, suggesting that sexual reproduction may occur locally. Location-specific re-inoculation preserved population continuity but did not produce detectable local adaptation. By contrast, the population was affected to some extent by variety-specific re-inoculation. Populations from one highly resistant variety formed two divergent lineages with reduced diversity and altered allele frequency spectra, consistent with host-driven selection. Genome scans identified 26 candidate genes, including two putative effectors, associated with adaptation to the highly resistant variety. These findings demonstrate rapid C. beticola adaptation to resistant varieties, highlighting the role of host-driven selection in resistance management.