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Dual-band graphene-assisted metamaterial absorber with machine learning integration for high-sensitivity THz biosensing

SV2A PET reveals synaptic density loss in experimental autoimmune encephalomyelitis and in a pilot multiple sclerosis study

Synaptic loss is increasingly recognized as a key pathological feature in multiple sclerosis (MS), contributing to disease progression and cognitive dysfunction. Synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging has emerged as a promising tool for quantifying synaptic density in vivo. Here, we used the clinically translatable tracer [ 18 F]SynVesT-1 to comprehensively characterize synaptic density across the brain and spinal cord in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. In parallel, we performed SV2A PET in patients with MS using the first clinically implemented SV2A radiotracer, [ 11 C]UCB-J, providing cross-species validation of SV2A PET imaging as a biomarker of synaptic pathology. In EAE mice, dynamic [ 18 F]SynVesT-1 PET imaging revealed a significant global reduction in tracer uptake, with nearly 30% decrease in regional distribution volume ( V T ) across all analyzed brain regions ( P < 0.0001). Correspondingly, autoradiography (ARG) corroborated the PET findings, and additional analyses demonstrated reduced SV2A levels in the cervical and lumbar spinal cord. In a clinical PET research study, [ 11 C]UCB-J imaging in MS patients (n = 6) versus age-matched healthy controls (n = 6) showed a 16.4% reduction in global cortical SV2A binding ( P = 0.026), with significant regional reductions of 16 to 26% in several cortical and subcortical subregions. Together, these findings demonstrate that SV2A PET imaging provides a sensitive and quantitative biomarker of synaptic pathology in MS. The consistent reductions in SV2A binding observed in both preclinical and clinical research highlight the role of synaptic degeneration in MS and underscore the utility of SV2A PET imaging in MS research.

Prevalence of medication-related problems and its predictors among cancer patients in Ethiopia: A systematic review and meta-analysis

Background Preventable medication-related problems intensify the risk associated with cancer care and no data was available to represent the burden of medication-related problems among cancer patients in Ethiopia. Hence, this study was aimed to estimate the pooled prevalence of medication-related problems and identify its predictors among cancer patients treated in Ethiopia. Methods A systematic review and meta-analysis of studies retrieved from databases (Medline, EMBASE, Scopus, Cumulative Index to the Nursing and Allied Literature (CINAHL), Cochrane Library and Google Scholar) for relevant literature published before April, 2024 was made. We included observational studies conducted in Ethiopia that reported on the types, frequency, or risk factors of medication-related problems in cancer patients. Reviews, case reports, qualitative studies, and studies lacking relevant outcomes were excluded. The Newcastle-Ottawa quality assessment scale was used for quality assessment and the Egger’s regression test and the Galbraith plot were used to evaluate publication bias. The national prevalence of medication-related problems was estimated using a random-effects model meta-analysis. Moreover, subgroup analysis and meta-regression analyses were done to explore the reasons of statistical heterogeneity. The study protocol has been registered with PROSPERO under number CRD42024505218. Results A total of 15 studies comprising of 3084 cancer patients were included in this study. The adjusted pooled prevalence of medication-related problems of cancer patients who experienced at least one medication-related problem was 48% [0.48 (95% CI: 0.39–0.57; I 2  = 96%; p < 0.01)]. The study also revealed the pooled prevalence of non-adherence among the included studies to be 42% [0.42 (95% CI: 0.27–0.57; I 2  = 97%; p < 0.01)]. The presence of comorbidities (AOR = 4.47, 95% CI: 3.26–5.69), complications (AOR = 5.78, 95% CI: 3.26–8.30) and polypharmacy (AOR = 3.75, 95% CI: 2.16–5.34) were found to be predictors of developing medication-related problems. Conclusion This review found a high pooled prevalence of medication-related problems among cancer patients in Ethiopia, with predictors including comorbidities, complications and polypharmacy. About two-fifths of patients were not fully adherent to their prescribed cancer treatments. These findings highlight the need for targeted interventions to improve medication safety and adherence, and underscore the importance of future research to identify effective strategies for reducing MRPs in oncology settings.

Development and characterization of rat hindlimb ischemia models mimicking peripheral arterial disease severity

Global analysis of protein degradation reveals instability of diverse regulators in <i>Escherichia coli</i>

Regulated protein degradation underlies the timely execution of essential gene expression programs in bacteria. Here, we deployed time-resolved chemoproteomics, text mining of the PubMed and EcoCyc knowledge bases, and machine learning classification to identify proteolytic regulation in exponential and stationary phase Escherichia coli cultures. We experimentally validated the instability of diverse homeostatic and stress response regulators, including the principal cyclic-di-GMP phosphodiesterase PdeH, the N-end rule substrate chaperone ClpS, and all four A-type domain iron–sulfur cluster carriers, IscA, ErpA, NfuA, and SufA. Mutagenesis of the PdeH N-terminal extension abolished ClpXP recognition, thereby impairing stationary phase depletion of PdeH and altering macrocolony biofilm surface morphology. Unstable proteins synthesized in stationary phase such as the morphology regulator BolA, RNA polymerase ω subunit, and the biofilm regulator BssR were implicated in quiescence. Finally, machine learning–assisted substrate identification revealed Lon-mediated degradation of two opposing key regulators of surface adhesion, the RpoS antagonist FliZ and the major biofilm regulator CsgD, suggesting proteolysis may hasten transitions between motility and sessility. Together, these results highlight the role of regulated proteolysis in driving physiological adaptation for this model organism.

Strategies for updating rules driven by reinforcement learning to solve social dilemmas

This study incorporates historical performance into traditional imitation rules and proposes a moderated strategy update rule. In this framework, an individual’s temporal historical performance is calculated using the BM model. By adjusting the parameter δ , the influence of historical performance on strategy learning is determined, and the evolution of cooperation is subsequently observed. Results show that the proposed strategy update rule promotes cooperation more effectively than the traditional version, and systemic cooperation is further enhanced as δ increases. The reason why the proposed rule enhances cooperation is that it amplifies the evaluation of cooperative behavior while compressing the evaluation of defective behavior. Although establishing system objectives may hinder the diffusion of cooperative behavior, appropriate performance evaluation mechanisms can mitigate this adverse effect. Our results indicate that multidimensional evaluation can provide a theoretical basis for explaining cooperative behavior in complex environments.

The LS/CS ratio-performance relationship in DG-activated hybrid cements

A BRI1–CNGC12 phosphorylation module links hormone signaling to manganese homeostasis in plants

Manganese (Mn) toxicity in acidic or waterlogged soils severely impacts crop productivity. Although high-Mn stress triggers Ca 2+ signals that regulate Mn homeostasis, the mechanism generating these signals remains unclear. Here, we show that the cyclic nucleotide-gated channel CNGC11/12 are essential for Mn tolerance, as cngc11 / 12 mutants exhibited hypersensitivity to Mn and cngc12 mutant showed reduced Ca 2+ elevations. The brassinosteroid (BR) receptor BRI1 physically interacted with CNGC12 and phosphorylated Ser22 residue, a modification critical for channel activation. Accordingly, bri1 mutants displayed impaired Mn-induced Ca 2+ signaling and heightened Mn sensitivity. Mn stress rapidly activated BRI1 kinase, peaking within minutes, and electrophysiological assays confirmed that BRI1-mediated phosphorylation gates CNGC12-dependent Ca 2+ currents. Exogenous brassinolide treatment augmented high-Mn-induced Ca 2+ signaling, BRI1-mediated CNGC12 phosphorylation, and high-Mn tolerance. Mutations in either BRI1 or CNGC12 abolished CPK5-dependent phosphorylation of MTP8 and impaired NRAMP1 endocytosis. Our study identifies the BRI1–CNGC12 module as a key node linking BR signaling to Ca 2+ -dependent Mn detoxification, revealing how phytohormone pathways regulate ion stress adaptation.

Retraction: Combined GSTM1-Null, GSTT1-Active, GSTA1 Low-Activity and GSTP1-Variant Genotype Is Associated with Increased Risk of Clear Cell Renal Cell Carcinoma

Filtration characteristics of coconut fiber filter used in emergency rescue of dike piping

Functional recovery of the adult murine hippocampus after cryopreservation by vitrification

Cryopreserving the adult brain is challenging due to damage from ice formation, and traditional freezing methods fail to maintain neural architecture and function. Vitrification offers a promising alternative but has not been surveyed in the brain. Here, we demonstrate short-term recovery of the adult murine hippocampus after vitrification of brain slices and of the whole brain in situ. Key features of the hippocampus are preserved, including structural integrity, metabolic responsiveness, neuronal excitability, and synaptic transmission and plasticity. Notably, hippocampal long-term potentiation (LTP) was well preserved, indicating that the cellular machinery of learning and memory remains operational. These findings extend known biophysical limits for cerebral hypothermic shutdown by demonstrating recovery after complete cessation of molecular mobility in the vitreous state and thus contribute to achieving the objective of structural and functional preservation of neural tissue.

Ensemble and temporal feature-based framework for rainfall classification in Bangladesh

Accurate rainfall classification is essential for Bangladesh, where monsoon variability strongly influences agriculture, water resource management, and disaster preparedness. This study proposes a robust machine learning framework for rainfall intensity classification at the daily temporal scale and nationwide spatial coverage , using over 543,839 daily weather records collected from 35 meteorological stations across several decades from a publicly available national meteorological dataset. The dataset includes rainfall, temperature, humidity, and sunshine duration, which were preprocessed and categorized into four intensity levels: No Rain, Light Rain, Moderate Rain, and Very Heavy Rain. Various models were evaluated, including Random Forest, Decision Trees, Gradient Boosting, K-Nearest Neighbors, Naïve Bayes, Extreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LightGBM), and Categorical Boosting (CatBoost), along with deep learning architectures such as Artificial Neural Network (ANN), Deep Neural Network (DNN), One-Dimensional Convolutional Neural Network (1D-CNN), Long Short-Term Memory (LSTM), and Bidirectional LSTM (Bi-LSTM). Random Forest achieved the highest accuracy (77.37%), while Bi-LSTM performed best among deep learning models (76.97%). To address class imbalance, we adopted class weighting in the final models; SMOTE was explored as an ablation and then excluded due to poorer generalization. Model interpretability using Local Interpretable Model-Agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP) consistently identified humidity and sunshine as the most influential predictors, with SHAP further revealing strong interactions between lagged humidity and temperature. The framework‘s reliable classification of rainfall intensities supports data-driven irrigation scheduling, early flood warnings, and climate-resilient agricultural and disaster management planning in Bangladesh.

Mechanism of action of Astragalus membranaceus for treating diabetic foot ulcers based on single-cell RNA sequencing data and network pharmacology

METTL3-mediated N6-methyladenosine modification of <i>Dnajb1</i> modulates cardiomyocyte ferroptosis during myocardial infarction

Myocardial infarction (MI) affects millions of individuals worldwide, with ferroptosis recognized as a pivotal regulated cell death pathway in this context. N6-methyladenosine (m6A), the most prevalent mRNA modification, is essential in modulating RNA splicing, export, stability, and translation during MI progression. Nonetheless, the involvement of m6A modification in cardiomyocyte ferroptosis has yet to be elucidated. This study aimed to elucidate the regulatory mechanisms of m6A modification in cardiomyocyte ferroptosis by conducting an integrated analysis of methylated RNA immunoprecipitation-sequencing and RNA-sequencing data obtained from myocardial tissues of MI mice, to identify promising therapeutic strategies for MI. We demonstrated that the differentially m6A-modified DnaJ heat shock protein family member B1 ( Dnajb1 ) gene suppressed ferroptosis during the pathological process of MI. DNAJB1 overexpression protected against hypoxia-induced cardiomyocyte ferroptosis by suppressing pro-ferroptotic effectors. Mechanistically, methyltransferase-like 3 (METTL3) bound to Dnajb1 , enhancing its m6A modification and diminishing mRNA stability, while insulin-like growth factor 2 mRNA-binding protein 3 competes for binding and increases mRNA stability. DNAJB1 prevented hypoxia-induced glutathione depletion and lipid peroxidation by inhibiting glutathione peroxidase 4 degradation via the autophagic-lysosomal pathway. In vivo, DNAJB1 overexpression improved heart function, reduced infarct size and fibrosis, and lowered plasma malondialdehyde levels in MI mice, whereas METTL3 co-overexpression counteracted these cardioprotective effects. Overall, this study uncovers a METTL3/ Dnajb1 pathway in cardiomyocyte ferroptosis during MI. METTL3 modifies Dnajb1 through m6A, destabilizing its mRNA and weakening glutathione peroxidase 4-dependent antioxidant defense, thus promoting ferroptosis. These insights into epitranscriptomic regulation of cell death highlight potential therapeutic targets to prevent ferroptosis-related cardiac damage.

The price of safety and convenience: Urban shoppers’ willingness to pay for hygienic market stalls and minimal processing of leafy vegetables in Kenya

The safety of fresh food is a serious concern across sub-Saharan Africa. Stronger incentives are needed to stimulate market retailers to adopt more hygienic practices and to drive improvements in fresh produce market infrastructure. A price premium for safe produce could incentivize retailers to do this, but it is unknown if shoppers would accept a higher price. The objective of this study was to evaluate the demand for safer vegetables among urban consumers in Africa. The Becker–DeGroot–Marschak (BDM) method was used to conduct a non-hypothetical experimental auction with 417 randomly selected shoppers in five fresh produce markets in Kisumu, Kenya. Shoppers chose between two bundles of mixed African leafy vegetables: (1) whole, unpackaged, and (2) minimally processed vegetables – washed, plucked, and packaged; and two food safety conditions: (3) conventional handling practices in a traditional stall, and (4) hygienic handling in an improved stall based on government guidelines. The results show that shoppers are willing to pay about 24% more for whole vegetables from clean stalls and about 26% more for minimally processed vegetables. Plucked vegetables pose a higher food safety risk than whole vegetables, but wealthier, time-constrained shoppers opt for them for convenience. These findings indicate that urban shoppers in Kenya attach value to the safety of fresh produce. Retailers can command higher prices by enhancing stall hygiene, but external support will be needed to upgrade retail market infrastructure.

Long-term random sampling confirms high-use areas and indicates declining abundance of juvenile smalltooth sawfish (Pristis pectinata) in Charlotte Harbor, Florida

Abstract We evaluated 13 years of fishery-independent small juvenile (&lt; 1.86 m stretch total length) endangered smalltooth sawfish sampling data from southwest Florida’s Charlotte Harbor estuarine system. From 2010 through 2022, within the sampling domain, estimated abundance declined, with an annual average across all seasons of 34 ± 11 individuals (range: 15–69). High-use areas were spatiotemporally stable and associated with well-oxygenated (dissolved oxygen &gt; 7 mg/L), warm (25–33 °C), and brackish (salinity 5–27) waters between 5 and 15 km upriver along natural shorelines with concentrations of mangroves in both riverine nurseries. Adult female abundance, back-calculated from expected brood size (48 ± 16, range: 26–144) and stable age distribution (87 ± 30, range: 39–211), was low. Our findings of a significant declining trend in relative abundance of small juveniles and limited numbers of adult females are concerning considering ongoing threats from commercial shrimp trawl bycatch, destruction of nursery habitats, and major recent mortality events. Our model facilitates estimation of the number of individuals potentially exposed to harmful anthropogenic activities and identifies perennial high-use areas as priorities for permanent protection from habitat alterations and loss to promote recovery of the endangered smalltooth sawfish population in this unique estuarine system.

Cooperation and the evolution of bacterial niche breadth

Bacteria exhibit varying niche breadths, with generalists thriving in diverse environments and specialists confined to specific habitats. Although genes for cooperative traits have been suggested to influence niche breadth evolution, their precise role remains unclear. We used a combination of phylogeny-based comparative methods to test causal hypotheses about the directionality of the relationship between genes for cooperation and bacterial niche breadth evolution across 25,785 species. Our results revealed 1) a positive correlation between the proportion of genes for cooperation and niche breadth; 2) genes for cooperation influenced niche breadth evolution, with a decreased proportion of such genes promoting niche contraction as the predominant evolutionary direction; and 3) genes for cooperation experience more frequent gain and loss within species rather than across species. These findings suggest a role of bacterial cooperation in influencing niche breadth evolution and maintaining the ecological versatility of bacteria. While our results are consistent with a simple relationship under the hypotheses tested, more complex causal scenarios are possible, including the role of factors that influence both cooperation and niche breadth.

Computational fluid dynamics analysis of middle ear pressure dynamics: Evidence for efficient pressure equalization during partial eustachian tube opening

Background Eustachian tube (ET) dysfunction is associated with middle ear pathologies; however, the quantitative relationship between ET opening and pressure equalization remains insufficiently characterized. Computational fluid dynamics (CFD) offers a robust tool for analyzing middle ear pressure dynamics, particularly in elucidating pressure equilibrium mechanisms under partial ET opening conditions. Objective This study aimed to investigate pressure dynamics in the tympanic cavity, mastoid antrum, and air cells during ET opening using CFD, to compare pressure distributions between full and partial openings, and to determine whether partial opening can achieve equilibration equivalent to full opening. Methods Eight normal temporal bones were reconstructed from high-resolution computed tomography scans of four healthy adults. ET openings were simulated at 10%, 30%, 50%, and 100% patency using CFD, and results were validated against in vivo Tubomanometry data. Pressure variations in the tympanic cavity, mastoid antrum, and air cells were monitored throughout the process. Mesh independence was verified to ensure reliability, and statistical analyses were conducted using SPSS 27.0, with P  &lt; 0.05 considered significant. Results CFD simulations revealed distinct pressure dynamics within the ET–middle ear system. Airflow velocity peaked at the narrow isthmus, generating a localized pressure drop. Effective middle ear pressure equilibration—across the tympanic cavity, antrum, and mastoid air cells—was achieved with partial ET opening in most cases: 30% opening sufficed for full equilibration in two ears, while 50% opening achieved complete equilibration in six. This equivalence to full patency was consistently observed during pressurization, stabilization, and depressurization phases. Conclusion Effective middle ear pressure equilibration can be achieved with partial ET opening (50%) in most cases (75% of ears). These findings provide valuable insight into middle ear physiology and its response under pathological conditions, offering a theoretical basis for optimizing the management of ET dysfunction.

Plasma lipids connecting olfaction with cognition and physical function

Abstract Olfactory deficit is an early sign of neurodegenerative diseases, such as Alzheimer’s disease (AD), and is related to age-related cognitive and physical function decline. However, underlying biological processes are not fully understood. Identifying shared lipid metabolites may shed some light. In 656 Baltimore Longitudinal Study of Aging participants (mean age:70.5 years), we examined associations of plasma lipids with olfaction, cognitive impairment (including AD), cognition, and physical function, after adjusting for demographics. Plasma lipid metabolites, assayed via FIA- and LC-mass spectrometry, were analyzed as 6 lipid classes. Odor identification was measured via the 16-item Sniffin’ Sticks. Cognition was measured via a neuropsychological battery. Physical function measures included gait speed, chair stands, and balance. Very long-chain and long-chain sphingomyelins and glycosylceramides were positively associated with olfaction, select cognitive measures (Trail Making Test-Part A, Digit Symbol Substitution Test, Purdue Pegboard Test), and physical function. Sphingomyelins were also associated with memory (California Verbal Learning Test immediate recall) and cognitive impairment (all p  &lt; 0.05). Only very long-chain sphingomyelins and glycosylceramides affected associations between olfaction and outcome measures (Δβ:10-25.9%). Plasma sphingomyelins and glycosylceramides, especially those with very long-chain carbons, may at least in part explain the relationship between olfaction and functional outcomes. Future omics studies may provide additional mechanistic insights.

The dynamic response of the bacterial flagellar motor to its direct intracellular input signal

The bacterial flagellar motor drives bacterial swimming and chemotaxis by rotating helical flagellar filaments. When Escherichia coli navigates chemical gradients, the motor switches from counterclockwise (CCW) during forward swimming to clockwise (CW) during direction-changing tumbles. The motor responds indirectly to extracellular chemosensory input to membrane-bound chemoreceptors using an intervening intracellular signaling pathway. How the motor responds to its direct input signal—the diffusible messenger phosphorylated CheY (CheY-P)—remains poorly understood. Steady-state motor measurements have been modeled as an allosteric switch between CCW/CW states that depends on mean CheY-P levels. Allosteric models have suggested that as many as 20 CheY-P molecules can be bound to the motor when it switches rotational direction. But steady-state models cannot predict the sensitivity of the motor to dynamic changes in CheY-P that essentially modulate chemotactic behavior. We present an optogenetic reagent that precisely controls the direct dynamical input signal to the motor. We designed a “caged” molecule, Opto-CheY, that is transiently activated by photon absorption. We find that activation and binding of one to three additional CheY-P molecules is sufficient to switch the motor from the CCW to CW state. The sensitivity of the motor to small changes in CheY-P occupancy helps resolve a long-standing paradox about the high sensitivity of the chemotactic response to external sensory input. Optogenetic biochemistry by light-activated uncaging of signal molecules is a new strategy to dissect information-processing in the living cell.