Browse Articles
Discover research articles across all indexed journals
Ethics of Navigating Organ Scarcity in Heart Transplantation
Nano Eco-Scale: A scoring system for the assessment of the greenness and safety of manufactured nanomaterials for analytical and environmental applications
Abstract Manufactured nanomaterials (MNMs) have transformed analytical and environmental applications by improving efficiency and reducing resource use. However, the "nano-paradox" has raised concerns about the use and development of nanotechnology, complicating regulatory agencies’ ability to monitor MNM’s environmental impact. In this work, a novel metric tool, the Nano Eco-Scale, is proposed to assess the greenness and environmental safety of nanomaterials used in analytical and environmental applications. The framework is based on the principles of green analytical chemistry and is aligned with REACH regulations for nanomaterials, while incorporating recommendations from the Organization for Economic Co-operation and Development for standardized characterization and safety evaluation. The tool assigns penalty points to deviations from the ideal nanomaterial across four main domains: synthesis conditions, nanomaterial toxicity, exposure during use, and waste generation and disposal. The overall score is calculated as 100 minus the total penalty points. The Nano Eco-Scale score supports the evaluation and comparison of environmental impacts associated with MNM-based analytical applications such as sensing, environmental monitoring, and water treatment. This approach encourages detailed characterization, highlights potential ecotoxicity risks, and promotes safer-by-design strategies. As a screening tool, it enables rapid comparisons and helps guide the selection of safer and more sustainable options. Additionally, it facilitates systematic data collection that could support future classification approaches. The developed tool supports regulatory efforts and advances the responsible use of nanotechnology in analytical and environmental fields.
Cryogenic silicification enables nongenetic functional continuity across mammalian cell generations
Mammalian cells are intrinsically soft, with Young’s moduli typically ranging from 0.1 to 10.0 kPa depending on the organization of the F-actin cytoskeleton, rendering them highly susceptible to mechanical and environmental stresses. This inherent fragility severely constrains their manipulation and functional deployment under nonphysiological conditions. Here, we report a cryogenic dormancy–enabled silicification strategy that achieves deep integration of inorganic silica reinforcement within living mammalian cells while preserving cell viability and proliferative capacity. Transient membrane permeability during cryogenic dormancy allows intracellular accumulation of silicic acid, which subsequently undergoes protein-mediated condensation to form a conformal amorphous silica network spanning both extracellular and intracellular compartments. The resulting silica–cell hybrids, termed Silicacytes , exhibit substantially enhanced mechanical robustness and resistance to a broad range of environmental stresses. Notably, this materials-mediated reinforcement is neither permanent nor genetic in nature: silica structures are progressively partitioned during cell division, conferring a pseudoheritable enhancement that persists for two to three generations before gradually dissipating. By enabling a reversible and temporally bounded extension of cellular robustness without altering genetic identity, cryosilicification establishes a nongenetic mode of functional continuity across cell generations. This work expands the conceptual framework of material–cell interactions and provides a general strategy for transient cellular reinforcement, with implications for cell engineering, immune cell manipulation, and the development of adaptive biohybrid systems.
Stent-Free PCI: Have We Found the SELUTION?
Comparison of atmospheric cold plasma and pulsed electric fields for bioactive compound extraction and color preservation in Rosa foetida Herrm
Fly navigational responses exploit plume-specific odor motion and gradient cues
Odor cues guide animals to food and mates. Different environmental conditions can create differently patterned odor plumes, making navigation more challenging. Prior work has shown that animals turn upwind when they detect odor and cast crosswind when they lose it. Animals with bilateral olfactory sensors can also detect directional odor cues, such as odor gradient and odor motion. It remains unknown how animals use these two directional odor cues to guide crosswind navigation in odor plumes with distinct statistics. We investigated this problem theoretically and experimentally. Here, we show that these directional odor cues provide complementary information for navigation in different plume environments. We numerically analyzed experimentally generated plumes to show that odor gradient cues are more informative about crosswind directions in a smooth odor plume, while odor motion cues are more informative in a complex plume. Neural networks trained to optimize crosswind turning converged to distinctive network structures that are tuned to odor gradient cues in a smooth plume and to odor motion cues in a complex one. These trained networks improved the performance of artificial agents navigating plume environments that match the training environment. Last, we recorded Drosophila fruit flies as they navigated these odor plume environments. In the smooth plume, the gradient cue was the significant predictor of fly crosswind turning; in the complex plume, the motion cue was the significant predictor. Overall, these results demonstrate that these directional odor cues are complementary across environments and that animals exploit this relationship to navigate plumes with different statistics.
Rapid Ultraoxygenated Recovery Without Preimplant Reanimation Using Older Donation After Circulatory Death Heart Donors
Combining residual U-Net and data augmentation for dense temporal segmentation of spike wave discharges in single-channel EEG
Abstract Manual annotation of spike-wave discharges (SWDs), the electrographic hallmark of absence seizures, is labor-intensive for long-term electroencephalography (EEG) monitoring studies. While machine learning approaches show promise for automated detection, they often struggle with cross-subject generalization due to high inter-individual variability in seizure morphology and signal characteristics. In this study we compare the performance of 16 machine learning classifiers on our own manually annotated dataset of 961 hours of EEG recordings from C3H/HeJ mice, including 22,637 labeled SWDs, and find that a 1D U-Net performs best. We then improve its performance by employing residual connections and data augmentation strategies combining amplitude scaling, Gaussian noise injection, and signal inversion to enhance cross-subject generalization. Our proposed model, AugUNet1D, achieves an average F1-score of 0.90 with balanced precision (0.91) and recall (0.90), representing a 29% relative improvement over the “Twin Peaks” algorithmic baseline and exceptional cross-subject performance. AugUNet1D, pretrained on our manually annotated data, along with the dataset itself, is made public for other users.
Dielectric levitation optical tweezers for powerful mesoscale biomanipulation
Optical tweezers (OT), a cornerstone of micromanipulation, are fundamentally constrained by substrate-induced adhesion and friction, limiting their application to mesoscale objects and fragile biological specimens where overcoming these resistive forces requires physiologically damaging laser powers. Here, we overcome this long-standing challenge by introducing dielectric levitation optical tweezers (DL-OT), a multiphysics platform that seamlessly integrates alternating-current dielectric levitation with optical traps. By using negative dielectrophoresis (n-DEP) to actively neutralize the normal force, DL-OT eliminates solid – solid contact and near-wall viscous drag. Crucially, we demonstrate the fundamental superiority of this active physical levitation over traditional passive antiadhesion coatings. This physical decoupling enables the smooth translation of large biological samples using low, biologically safe optical powers (~15 mW) rather than nonviable levels (>150 mW). The creation of this frictionless environment not only boosts the maximum manipulation speed of standard microtargets by 40% but also enables the stable optical transport of previously intractable mesoscale objects (100 to 260 μm), including microgears and shrimp eggs. By preventing photothermal damage and mechanical deformation, DL-OT demonstrates very good biocompatibility, significantly enhancing cell viability postmanipulation. Building upon these advantages, we demonstrate advanced on-chip biofabrication protocols through the targeted, high-precision assembly of multicellular spheroids and the safe transport of patient-derived organoids, followed by their success in situ culture. By transforming OT from a microscale tool into a mesoscale assembly platform, DL-OT paves the way for breakthroughs in tissue engineering, regenerative medicine, and the bottom – up assembly of living systems.
From Discovery to Impact in the <i>Circulation</i> Life Cycle
Semantic neighborhood-aware fuzzy clustering for balanced text categorization
Social evolution and diminished olfactory function in larval honey bees
Social evolution made larval honey bees dependent on adult colony members for feeding; they are confined to cells in waxen honeycombs and visited about 100 times per day by adult “nurse” bees. Based on organismal resource conservation theory, we predicted larvae have diminished olfactory capabilities at both the molecular and behavioral levels. Consistent with theory, larvae expressed very low levels of Orco , an essential gene for olfactory receptor (OR) function. By contrast, they showed higher expression of Ir25a, essential for other forms of sensory perception including gustation. Also consistent with theory, behavioral assays demonstrated that larvae cannot find food via olfaction, suggesting they use taste for feeding. By contrast, it is known that adult honey bees use OR-based olfaction extensively for a variety of behavioral functions, and the honey bee genome contains many OR-encoding genes. Comparative transcriptomic analyses of social and nonsocial insects suggest that this developmentally regulated suppression of olfactory function is related to social evolution, especially systems of offspring care.
Comparative Efficacy of Transfusion Strategies in Women and Men With Myocardial Infarction and Anemia: Prespecified Secondary Findings From the MINT Trial
BACKGROUND: The optimal transfusion strategy in patients with acute myocardial infarction (AMI) and anemia may be influenced by sex differences in pathophysiology and cardiovascular outcomes. The Myocardial Ischemia and Transfusion trial (MINT) randomized patients with AMI and anemia to restrictive or liberal transfusion thresholds, but sex-stratified outcomes remain undefined. The objective was to evaluate whether the clinical effect of restrictive versus liberal red blood cell transfusion strategies differs by sex in patients hospitalized with AMI and anemia. METHODS: In this prespecified secondary analysis of the MINT trial, we examined outcomes by sex and transfusion strategy. The primary outcome was 30-day composite death or MI. Secondary outcomes included heart failure, stroke, cardiac death, and 180-day mortality. Adjusted relative risks (RRs) and hazard ratios (HRs) were estimated accounting for sex differences at baseline. Interactions between sex and transfusion effects were assessed. RESULTS: There were 3504 study participants, of whom 1593 (45.4%) were women. Women received fewer transfusions on average. Primary outcome occurred in 15.7% of women and 15.7% of men and occurred in 16.5% of women and 17.1% of men in the restrictive arm, versus 14.9% and 14.2% in the liberal arm, respectively. Women had a lower mortality between 30 and 180 days (11.0% versus 13.5%; P =0.04). There were no statistically significant interactions between sex and transfusion strategy for the primary outcome (interaction P =0.60). For 30-day cardiac death, a higher RR in men was observed in the restrictive transfusion arm (RR, 2.34; 95% CI, 1.48–3.70; interaction P =0.05). CONCLUSIONS: For MINT patients with anemia and AMI, women comprised nearly half of the study population, and randomization to a restrictive or liberal transfusion strategy resulted in comparable outcomes in women and men. These findings support sex-neutral transfusion thresholds. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02981407.
Optimal control of a heat flow system via novel enhanced quadratic interpolation optimization tuned 2DOF-PID controller
Abstract This study addresses the optimal temperature regulation problem of a laboratory-scale heat flow system using a two-degree-of-freedom proportional–integral–derivative (2DOF-PID) controller tuned by a newly developed enhanced quadratic interpolation optimization (eQIO) algorithm. The main contribution lies in improving the original quadratic interpolation optimization (QIO) framework by integrating two lightweight enhancement mechanisms: a periodic parabolic local search to strengthen local exploitation and a stagnation-aware diversity recovery strategy to prevent premature convergence. The enhanced formulation preserves the deterministic interpolation-based structure of QIO while increasing convergence reliability and robustness without introducing additional algorithmic complexity. The effectiveness of eQIO is first evaluated on ten benchmark functions from the CEC-2019 test suite and compared with QIO, mountain gazelle optimization, tuned moss growth optimization, whale optimization algorithm, and superb fairy-wren optimization algorithm. Statistical results obtained from 500 independent runs indicate that eQIO consistently improves average solution quality and reduces standard deviation relative to QIO, while achieving competitive performance against population-based metaheuristic algorithms. Subsequently, eQIO is employed to tune the parameters of the 2DOF-PID controller for real-time temperature regulation experiments under step, square, and sinusoidal reference signals. The experimental results demonstrate reduced overshoot, lower steady-state error, improved tracking accuracy, and smoother control effort compared with alternative optimizer-based tuning approaches. Quantitatively, the proposed eQIO-based 2DOF-PID controller reduces the total mean absolute error (MAE) by 14.8% under step–square reference signals and by 45.8% under step–sinusoidal reference signals compared with the original QIO-based controller, while also providing smoother control action and improved tracking robustness. Overall, the proposed eQIO-driven 2DOF-PID framework establishes a computationally efficient and experimentally validated methodology for reliable thermal system control.
Revealing ancient macroH2A features through in vivo analysis in the cricket <i>Gryllus bimaculatus</i>
macroH2A is one of the most atypical histone variants, being three times larger than canonical H2A due to its unique extranucleosomal macrodomain. Once thought to be vertebrate-specific, macroH2A is in fact an evolutionary ancient histone, encoded by two genes in vertebrates and a single gene in other eukaryotes. However, the absence of macroH2A in Drosophila and Caenorhabditis elegans have precluded its functional characterization beyond vertebrates. Here, we report the functional characterization of macroH2A in an invertebrate, enabled through genome editing in the cricket Gryllus bimaculatus . Endogenous tagging of the cricket macroH2A gene revealed a highly dynamic distribution of macroH2A during gametogenesis and a general association with heterochromatin. In embryos, macroH2A shows a remarkable enrichment in differentiating cells, particularly in the nervous system and muscles. Interestingly, complete gene deletion reveals that macroH2A is dispensable for viability but critical for survival after irradiation. We further show that embryos lacking the linker and macrodomain of macroH2A are equally hypersensitive to DNA damage, demonstrating that this nonhistone region safeguards genome integrity beyond vertebrates. Finally, removing the extranucleosomal domain of macroH2A unexpectedly disturbs its chromatin incorporation in a cell-type-specific manner. This study thus reveals deeply conserved features of macroH2A, shared between insects and vertebrates, but also provides insights about the regulation of its chromatin incorporation.
Incremental Prognostic Value of Subendocardial Myocardial Flow Reserve in Patients With Normal Perfusion
BACKGROUND: Although the prognostic utility of positron emission tomography (PET) myocardial flow reserve (MFR) is well established, emerging data suggest that reduced subendocardial flows also predict adverse outcomes. However, the incremental value of subendocardial MFR (MFR SE ) beyond transmural MFR (MFR TM ) remains unclear. METHODS: We studied patients in a multicenter PET registry with normal perfusion on stress/rest Rb-82 PET, excluding those with a previous history of coronary artery bypass surgery, heart transplantation, or left ventricular ejection fraction <40%. The optimal MFR SE cutoff for predicting major adverse cardiovascular events (MACEs; death, myocardial infarction [MI], revascularization, or heart failure [HF] hospitalization) was determined using Youden’s index. Patients were stratified into 3 groups: concordant-normal (MFR TM ≥2.0; MFR SE ≥2.1), discordant (low-MFR SE , normal MFR TM ), and abnormal MFR TM . Clinical outcomes were compared by MFR groups. RESULTS: Among 6603 patients (normal N=4103; discordant N=885; abnormal N=1615) the mean age was 66.3±12.4 years, and 54% were women. Compared with the concordant-normal group, patients with discordant low-MFR SE were older and more likely to have hypertension, diabetes, peripheral artery disease, and previous percutaneous coronary intervention. The median MFR TM for normal, discordant, and abnormal groups were 2.86, 2.15, and 1.72, respectively. Over a median follow-up of 4.9 years, 1661 MACE events occurred. Discordant low-MFR SE patients had a higher risk of MACE (hazard ratio [HR], 1.41; 95% CI, 1.22–1.64) and all-cause mortality (HR, 1.36; 95% CI, 1.14–1.61) compared with concordant-normal patients. The discordant group had an intermediate absolute risk of MACE, with an adjusted annualized event rate of 5.79% (95% CI, 5.10–6.49) compared with 3.99% (95% CI, 3.67–4.30; P <0.001) in the concordant-normal group and 8.35% (95% CI, 7.71–9.00; P <0.001) in the abnormal MFR TM group. CONCLUSIONS: Subendocardial MFR reveals clinically meaningful risk heterogeneity among patients with preserved transmural flow reserve, helping refine risk stratification beyond traditional PET metrics.
Experimental evaluation of the thermal performance of a parallel microchannel cooling system for thermal management of multicore processors under low computational loads
Distinct cell type–specific mechanisms underlie cognitive dysfunction during persistent integrated stress response activation
Persistent activation of the integrated stress response (ISR) is a central driver of cognitive decline in both neurodevelopmental and neurodegenerative disorders. However, the cell type–specific mechanisms underlying these deficits remain poorly understood. By integrating single-cell RNA-seq and single-cell assay for transposase-accessible chromatin sequencing, we generated a brain ISR atlas using Ppp1r15b R658C mice, a clinically relevant model of intellectual disability characterized by selective and persistent ISR activation. We find that distinct brain cell types differentially engage transcriptional and chromatin remodeling programs. Notably, selective deletion of the major ISR downstream effector ATF4 in GABAergic neurons, but not in glutamatergic neurons, exacerbates ISR-mediated cognitive decline in Ppp1r15b R658C mice, demonstrating that different neuronal subtypes rely on distinct ISR effectors. We define a molecular single-cell signature of persistent ISR activation that serves as a metric of ISR-mediated cellular vulnerability and as a biomarker for cognitive dysfunction across human cognitive disorders. These findings demonstrate that cell type–specific responses drive cognitive dysfunction during persistent ISR activation.
SIRT5 Ameliorates Cardiac Fibrosis via PCK2 Desuccinylation-Mediated Metabolic Reprogramming in Cardiac Fibroblasts
BACKGROUND: SIRT5 (sirtuin 5) is a member of the sirtuin family known to regulate cardiac metabolism, aging, and function. However, its role in cardiac fibroblast (CFB) metabolism, activation, and fibrosis remains elusive. METHODS: Expression changes of SIRT5 in CFBs from cardiac tissue of human and mouse with heart failure were determined. The functional role of SIRT5 in cardiac fibrosis was evaluated through CFB-specific knockout and overexpression of Sirt5 in mice. The involvement of succinylation of lysine 489 (Lys489) on PCK2 (phosphoenolpyruvate carboxykinase 2) in SIRT5-mediated regulation of cardiac fibrosis was assessed by introducing the Lys489-to-arginine mutation of PCK2 in Sirt5 -deficient CFBs and in CFB-specific Sirt5 knockout mice. RESULTS: SIRT5 expression was markedly reduced in CFBs from humans and mice with heart failure and showed a negative correlation with cardiac fibrosis severity. Loss of Sirt5 in CFBs exacerbated left ventricular dysfunction, cardiac hypertrophy, and cardiac fibrosis in mice subjected to transverse aortic constriction, whereas overexpression of Sirt5 in CFBs significantly attenuated these pathological changes. Sirt5 deficiency promoted CFB activation by driving a metabolic shift from oxidative phosphorylation to glycolysis. Mechanistically, Sirt5 deficiency increased the succinylation of PCK2 at Lys489, a key enzyme linking glycolysis and the tricarboxylic acid cycle, which consequently inhibited this enzyme activity in CFBs. Importantly, this specific modification at the Lys489 mutation that prevents succinylation effectively reversed both the metabolic reprogramming and the hyperactivation of CFBs induced by Sirt5 knockout. In vivo , introducing the Pck2 K489R mutation fully rescued the exacerbated cardiac fibrosis and dysfunction observed in Sirt5 -deficient mice after transverse aortic constriction. CONCLUSIONS: By desuccinylating PCK2 at Lys489, SIRT5 prevents the metabolic reprogramming and subsequent activation of CFBs, protecting against cardiac fibrosis.