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Substance use disorders and addictions

A framework for assessing the trustworthiness of scientific research findings

Vigorous debate has erupted over the trustworthiness of scientific research findings in a number of domains. The question “what makes research findings trustworthy?” elicits different answers depending on whether the emphasis is on research integrity and ethics, research methods, transparency, inclusion, assessment and peer review, or scholarly communication. Each provides partial insight. We offer a systems approach that focuses on whether the research is accountable, evaluable, well-formulated, has been evaluated, controls for bias, reduces error, and whether the claims are warranted by the evidence. We tie each of these components to measurable indicators of trustworthiness for evaluating the research itself, the researchers conducting the research, and the organizations supporting the research. Our goals are to offer a framework that can be applied across methods, approaches, and disciplines and to foster innovation in development of trustworthiness indicators. Developing valid indicators will improve the conduct and assessment of research and, ultimately, public understanding and trust.

Modeling and optimizing the delamination factor in Agave americana L. biowaste fiber-reinforced biocomposite drilling: a study using RSM and ANN methods

An interpretable molecular framework for predicting cancer driver missense mutations

Missense mutations play a critical role in human disease, contributing to both inherited disorders and cancer. However, accurately predicting their functional impact—particularly for cancer driver mutations—remains a major challenge due to limited validated labels and the complex molecular basis of oncogenesis. Here, we systematically characterized over 120,000 missense variants across pathogenic, benign, driver, passenger, recurrent somatic, and common population classes, using a comprehensive set of mechanistically grounded molecular features. By assessing the statistical burden of variations, we demonstrated that these features effectively discriminate among diverse variant classes and reveal a consistent enrichment of functional sites, structural integrity, and biophysical changes in pathogenic and driver mutations. Building on these insights, we developed MutaPheno, an interpretable framework for predicting the functional consequences of missense mutations. The model integrates 34 molecular-level features, encompassing structural, functional, physicochemical, and contextual descriptors, using a random forest algorithm. Trained exclusively on pathogenic and benign variants, MutaPheno achieved strong accuracy in predicting cancer driver mutations, outperforming both cancer-specific and general pathogenicity tools, while also demonstrating superior robustness when tested on unseen proteins. Our findings highlight the shared mechanisms between pathogenic and driver mutations and emphasize the role of molecular features in improving variant interpretation. MutaPheno provides a transparent and generalizable tool that can facilitate driver discovery and the development of targeted therapies.

Computational study of carbon-doped TiO2(B) nanomaterials for improved dye-sensitized solar cells

Abstract Surface doping has emerged as a promising approach to enhance the reactivity and optoelectronic properties of titanium dioxide (TiO 2 ) and other inorganic oxide semiconductors. This strategy has significant potential to improve the efficiency and long-term stability of dye-sensitized solar cells (DSSCs). The present study employs density functional theory (DFT) calculations to investigate, for the first time, the adsorption behavior of the organometallic N719 dye on pristine and carbon-doped ultrathin TiO 2 (B) films. Initially, the interaction between the N719 dye and the pristine TiO 2 (B) (100) surface is examined, considering various molecular orientations and anchoring configurations. The adsorption energies and the resultant changes in the semiconductor’s electronic structure are determined. Subsequently, the impact of carbon doping on the preferential adsorption configurations is analyzed. The results reveal that the adsorption of the N719 dye is energetically favorable on both the pristine and C-doped TiO 2 (B) (100) surfaces. Notably, all adsorption-related properties are significantly enhanced after carbon doping, with the adsorption energy increasing by up to 300% compared to the undoped surface. This substantial increase in adsorption performance is critical for achieving highly efficient and long-lasting DSSCs.

Controlling for life-history traits in vertebrates reveals that effective population size does not affect mutation rate or genome size

Why mutation rates ( μ ) and genome sizes (GS) vary among species remains a central question in evolutionary genetics. Two influential models, the drift-barrier hypothesis (DBH) and the mutational-hazard hypothesis, propose that effective population size ( N e ) shapes these traits via the efficiency of selection, predicting higher μ and larger genomes in small populations. A recent comparative analysis of vertebrates reported a significant negative correlation between N e and μ , interpreted as support for the DBH. Using phylogenetic path analysis, we reanalyze the same dataset of 55 vertebrate species spanning mammals, birds, reptiles, and fishes, in which μ was estimated from high-coverage parent–offspring trios, while explicitly controlling for six life-history traits within a causal framework that tests model-implied conditional independencies. We show that the reported N e - μ association is entirely mediated by generation time (GT), which independently influences both variables; once this “back-door” path is blocked, N e has no detectable effect on μ . Once GT is accounted for, mating system shows the largest association with μ . Parallel analyses of GS within the same validated life-history framework reveal that GS is unrelated to N e , μ , or their interaction and is decoupled from the life-history covariation that strongly structures μ . These results are robust to alternative N e estimators and causal model formulations. Together, our findings indicate that N e provides little explanatory power for variation in μ or GS across vertebrates, challenging the presumed universality of drift-limited genome evolution.

Intensity-dependent lipidomic dynamic regulation following acute swimming exercise

Abstract Exercise intensity critically determines health benefits, yet the underlying molecular mechanisms remain incompletely characterized. This study systematically compared the effects of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT) swimming on serum lipidomics. In a randomized controlled trial (ChiCTR2400089036, registered on 30/08/2024, n  = 42 healthy students), blood samples were collected at baseline, 0-, 15-, and 30-minutes post-exercise, followed by comprehensive lipidomics analysis. HIIT swimming induced 1.49- to 2.87-fold more extensive serum lipid downregulation than MICT, despite matched energy expenditure. We identified five robust intensity-dependent biomarkers: PC32:2, LPA18:2, and three 18:2-containing triacylglycerols (TAGs). Clustering analysis further revealed three distinct hierarchical patterns of lipid dynamic changes. Structurally, HIIT preferentially mobilized shorter-chain, saturated TAGs, and post-exercise lipid recovery dynamics were also intensity-dependent. The recurrent identification of linoleic acid (18:2)-enriched lipids, which negatively correlated with energy metabolites, suggests coordinated substrate channeling toward inflammatory eicosanoid pathways. These findings advance the mechanistic understanding of exercise intensity benefits and provide molecular evidence for intensity-stratified exercise prescription.

Health status monitoring of cutting arm of anchor excavator based on digital twin

Rapid evolution reveals long-range spread of SARS-CoV-2

Genomic and in vitro characterization of two lytic bacteriophages infecting multidrug-resistant Erwinia sp. strain AnSW2-5

Abstract Multidrug-resistant (MDR) Erwinia pathogens present a critical threat to global crop health and agricultural sustainability. In this study, we characterized two novel lytic bacteriophages, AnSW2-5-P-A (family Autographiviridae ) and AnSW2-5-P-K (class Caudoviricetes ), targeting the MDR Erwinia sp. strain AnSW2-5. Comparative genomics and TEM analysis revealed distinct virion architectures and confirmed the absence of lysogeny-associated genes, ensuring their safety as biocontrol agents. One-step growth assays demonstrated that P-A has a shorter latent period (~ 20 min), while P-K exhibits a significantly larger burst size (~ 110 PFU/cell). In co-culture assays, the dual-phage cocktail demonstrated a profound synergistic effect, achieving > 80% bacterial reduction ( p  < 0.05) and maintaining sustained suppression of the host for 72 h. Notably, the cocktail effectively prevented the emergence of resistant mutants, reducing the frequency of resistance ( FoR ) to below the limit of detection (< 10⁻⁸). These findings highlight the potential of using genetically diverse phage pairs with complementary lytic activities as a robust, resistance-suppressive biocontrol strategy against MDR phytopathogens.

Genuine learning biases persist after accounting for temporally decreasing learning rates: Insight from fitting six datasets

Pan centromeric FISH enhances precision in radiation biodosimetry

Abstract Accurate biodosimetry is critical for assessing radiation exposure in radiological emergencies, occupational monitoring, and clinical management, where precise dose estimation informs life-saving decisions and regulatory compliance. Current gold-standard cytogenetic methods face limitations in sensitivity and reproducibility, especially at low doses (< 0.5 Gy) (practical limitations at low doses, including very low dicentric yields, higher statistical noise, and greater scoring uncertainty as aberration frequencies near background levels). This study presents a systematic comparison of pan-centromeric fluorescence in situ hybridization (pan-cent-FISH) and Giemsa staining for detecting dicentric (DC) and ring (R) chromosomes following 60 Co-γ irradiation (0–3 Gy). Analysis of more than 15,000 metaphases per technique revealed enhanced sensitivity of pan-cent-FISH technique, demonstrating a 1.72-fold higher linear coefficient and enhanced (1.13-fold) quadratic coefficient (β), indicating improved sensitivity across both low and high dose ranges. Blind validation with eight samples showed pan-cent-FISH achieved ~ 2-fold greater accuracy, with mean absolute differences of 0.0538 Gy (vs. 0.1105 Gy for Giemsa) and average relative errors of 7.13% (vs. 15.35% for Giemsa). At low doses (0.1 Gy), pan-cent-FISH maintained 9.0% error, while Giemsa exceeded acceptable limits (21.0% error). The standardized fluorescence detection used for the technique eliminated morphological ambiguities, reducing false negatives by ~ 40% and improving first-pass accuracy.

Identification of a stylet-secreted effector protein family as a core component of root-knot nematode feeding tubes

Proteins secreted from a mouth stylet of sedentary plant-parasitic root-knot nematodes self-polymerize to form a unique feeding tube structure within host cells modified into giant feeding cells by the nematode. Feeding tubes have essential functions as they complex with the host endomembrane system for nutrient uptake to sustain parasitism. Despite their significance, they remain one of the least understood aspects of nematode parasitism of plants. Their small size and location within giant-cells deeply embedded within galls encasing adult females has prohibited studies to isolate and discern their molecular composition. Here, we developed a protocol for the isolation and semipurification of root-knot nematode feeding tubes from giant-cell cytoplasm of several host plant species to provide a unique view of these structures at the light and scanning electron microscopy level revealing previously undescribed features of their structure. Our methods allowed for the isolation and solubilization of sufficient quantities of enriched feeding tubes enabling a comparative proteome analysis across host species that identified proteins with an increased likelihood to function in feeding tube formation. A comparison across root-knot nematode species further narrowed candidates to a conserved class of secretory proteins that specifically localized within secretory granules of the dorsal gland of adult females and in feeding tubes formed within host cell cytoplasm to unequivocally demonstrate these proteins as core components of feeding tubes. Our finding gives scientists a look into the protein composition of feeding tubes opening the door to a better understanding of their structure and function in nematode parasitism.

Enhanced kinetic performance and stability of catalase immobilized on epoxy-functionalized kaolinite

Abstract The immobilization of catalase onto stable, reusable supports is crucial for efficient peroxide-based biocatalytic applications. In this study, catalase was immobilized for the first time onto epoxy-functionalized kaolinite particles prepared via surface silanization with (3-glycidyloxypropyl)trimethoxysilane. Structural and surface characterizations confirmed successful organosilane grafting while preserving the layered kaolinite framework. The modified support exhibited rapid enzyme uptake and a high immobilization capacity of approximately 300 mg g −1 . Kinetic analysis showed a substantial decrease in K m from 57.3 mM (free catalase) to 21.6 mM after immobilization, indicating enhanced substrate affinity. In contrast, V max decreased due to diffusion limitations typical of heterogeneous systems. Despite this, catalytic efficiency increased nearly 1.8-fold. Moreover, immobilized catalase demonstrated significantly improved operational reusability and long-term storage stability compared to the free enzyme. These results highlight silanized kaolinite as a robust, low-cost, and efficient mineral-based support for catalase immobilization, with strong potential for environmental and industrial biocatalytic applications.

A silent Kv channel subunit shapes PV neuron action potential waveform and short-term synaptic plasticity during high-frequency firing

Fast-spiking parvalbumin-positive (PV) neurons provide precisely timed, context-dependent inhibition within cortical circuits. PV neuron firing properties are specialized among cortical neurons, suggesting that they express a unique complement of ion channels. Here, we show that the PV-specific silent voltage-gated potassium (Kv) channel subunit Kv6.4 (encoded by Kcng4 ) modulates both intrinsic and synaptic properties of cortical PV neurons. Kv6.4 does not form functional channels on its own but, as shown in prior work, assembles with Kv2 subunits to create heterotetrameric channel complexes, effectively reducing Kv2-mediated delayed rectifier current. We find that Kcng4 expression is enriched within a distinct Pvalb -expressing subclass in primary somatosensory (S1) and motor (M1) cortex and emerges during postnatal development. In PV neurons, Kv6.4 loss reduces action potential (AP) height and width, hyperpolarizes the threshold and interspike potential, and accelerates AP upstroke particularly during repetitive firing. Kv6.4 loss, potentially due to the changes in AP waveform, also alters GABA release and paired-pulse depression at synapses made by PV onto pyramidal (PYR) neurons. The effects of Kv6.4 loss are amplified during high-frequency firing, within the physiological range of fast-spiking PV neurons, likely due to altered repolarization dynamics that accumulate across successive APs. These findings are thus consistent with the function of Kv6.4 in modifying Kv2-mediated delayed rectifier currents. Hence, Kv6.4 tunes the temporal precision of PV inhibitory output, a feature that may be critical for stable excitation–inhibition ratios and adaptive circuit function underlying learning and behavior.

Controlling sodium silicate sol-gel transition time through encapsulation of hydrochloric acid using tunable polymeric microcapsules

Nuclear speckles are regulatory hubs for viral and host mRNA expression during HSV-1 infection

Herpes simplex virus type 1 (HSV-1) infection remodels the host nucleus, marginalizing chromatin and forming viral replication compartments (VRCs). Nuclear speckles, nuclear bodies enriched in RNA-processing factors, reposition around VRCs and undergo structural changes. While viral mRNAs are transcribed in VRCs and host transcription is largely suppressed, the nuclear routes used by viral and upregulated host transcripts and their relationship with nuclear bodies remain unclear. We show that immediate-early (IE) viral transcripts uniquely accumulate in nuclear speckles prior to export, unlike early or late transcripts, revealing a selective nuclear speckle-dependent pathway. Similarly, host mRNAs upregulated during infection traffic into nuclear speckles after transcription. Moreover, nuclear speckles are structurally remodeled, marked by the long non-coding RNA (lncRNA) MALAT1 removal and increased dynamics of the nuclear speckle core protein SRRM2. Finally, we found that blocking mRNA export causes IE transcripts to accumulate in nuclear speckles and that nuclear speckle disassembly severely impairs IE mRNA export, preventing downstream viral gene expression. These findings establish nuclear speckles as dynamic regulatory hubs that selectively facilitate the processing and export of IE viral mRNAs during HSV-1 infection.

Robust broadband adaptive beamforming for planar arrays with tunable nulls in high-dynamic scenario

Grazer exclusion is associated with higher fast-cycling carbon pools but lower slow-cycling mineral-associated carbon across grasslands

The removal of livestock grazers from historically grazed grasslands is widely proposed as a key strategy for the enhancement of soil organic carbon (SOC) for climate mitigation. Yet, accurate assessments of how grazer exclusion impacts SOC pools of differing stability are lacking, with most studies focusing on total SOC rather than the distribution of SOC within fast and more stable, slow-cycling pools. Here, we used 12 historically grazed grassland sites along an 800 km south–north gradient across the United Kingdom to test how particulate (POC) and mineral-associated organic carbon (MAOC) pools were linked to long-term (>10 y) exclusion of large domesticated grazers. We found that grazer exclusion was associated with relatively higher fast-cycling C pools, including plant and litter C, and to a lesser extent POC, but lower more stable, slow-cycling MAOC pools compared to grazed controls. Grazer exclusion was also associated with a marked shift in vegetation composition, with greater cover of ericoid mycorrhizal (ErM) shrubs over arbuscular mycorrhizal (AM) graminoids. This vegetation shift likely played a dual role in regulating SOC, contributing to higher POC via both the input of recalcitrant litter and by the enhancement of soil moisture and lower MAOC due to priming and decreased mineral protection of SOC. Our findings provide evidence that while the exclusion of grazers tends to favor fast-cycling C pools, it coincides with lower SOC persistence, potentially increasing the vulnerability of grassland SOC stocks to future climate change.

A scalable hybrid framework for boosting customer experience and operational efficiency in e-commerce