Browse Articles

Bioactive glass nanoparticles induce intrinsic p53-dependent apoptosis and promote genomic instability via ROS overproduction and mitochondrial depolarization in triple-negative breast cancer cells

Abstract Triple-negative breast cancer (TNBC) is among the most aggressive breast cancer subtypes, characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression. The lack of these molecular targets, combined with the limitations of current treatment, particularly chemotherapy, which suffers from poor tumor selectivity, systemic toxicity, rapid development of resistance, and high recurrence rates, underscores the urgent need for innovative therapeutic strategies. Nanoparticle-based therapies have emerged as promising alternatives to overcome these challenges. Bioactive glass nanoparticles (BGNps), in particular, are recognized for their biocompatibility and multifunctional biological activity, yet their anticancer potential against TNBC remains fully unexplored. This study therefore aimed to investigate the therapeutic efficacy and molecular mechanisms of BGNps in highly aggressive triple-negative MDA-MB-231 breast cancer cells. Cells were treated with two-fold increasing concentrations of BGNps (7.8–1000 µg/ml), and cytotoxicity was assessed using the MTT assay. Genomic DNA integrity was evaluated using the alkaline comet assay, while oxidative stress and mitochondrial function were measured with 2′,7′-dichlorodihydrofluorescein diacetate (2′,7′-DCFH-DA) and Rhodamine-123 staining, respectively. Apoptotic induction was further examined using DAPI nuclear staining and chromatin diffusion assays, and transcriptional regulation of apoptosis- and mitochondria-related genes was analyzed by qRT-PCR. The results of MTT assay demonstrated that BGNps exerted potent, concentration-dependent cytotoxicity in MDA-MB-231 cells, with an IC50 value of 184.3 µg/ml. Treatment with BGNps at the IC50 concentration induced excessive reactive oxygen species (ROS) generation, severe mitochondrial membrane depolarization, extensive genomic DNA damage, and pronounced apoptotic cell death in MDA-MB-231 cancer cells. These effects were associated with marked upregulation of p53 and concurrent downregulation of anti-apoptotic Bcl-2 and mitochondrial ND3 genes, amplifying oxidative stress and mitochondrial dysfunction. In conclusion, BGNps display strong potential as a novel nanotherapeutic for TNBC, offering an effective alternative to conventional chemotherapy. Their multi-step mechanism; encompassing ROS induction, mitochondrial disruption, and apoptosis activation, highlights their promise in overcoming the intrinsic resistance and therapeutic limitations of this highly aggressive breast cancer subtype.

Gene duplication, horizontal gene transfer, and trait trade-offs drive evolution of postfire resource acquisition in pyrophilous fungi

Wildfires significantly alter soil carbon (C) and nitrogen (N), reducing microbial richness and biomass, while selecting for “fire-loving” pyrophilous microbes that drive postfire nutrient cycling. However, the genomic strategies and functional trade-offs (balancing gains in one trait with costs in another) underlying the traits that enable pyrophilous microbes to survive and thrive postfire are virtually unknown. We hypothesized that pyrophilous fungi employ specialized genomic adaptations for C and N cycling, with evolutionary trade-offs between traits governing aromatic C degradation, N acquisition pathways, and rapid growth. To test these hypotheses, we performed complementary comparative genomics, transcriptomics after pyrogenic organic matter amendment, and growth rate bioassays for 18 pyrophilous fungi from five Ascomycota (Eurotiales, Pleosporales, Sordariales, Coniochaetales, and Pezizales) and three Basidiomycota (Agaricales, Holtermanniales, and Geminibasidiales) orders isolated from burned soils. We found a dramatic trait trade-off between fast growth and number of genes responsible for aromatic C degradation, implying burned environments select for metabolically costly genes despite their evolutionary cost. We used the comparative genomics framework to evaluate genomic signatures of evolution and found that either gene duplication and somatic mutation, or recombination via sexual reproduction, were the primary drivers of fungal genomic variation in aromatic C degradation and N acquisition genes. Finally, we identified cross-kingdom bacterial to fungal horizontal gene transfer (HGT) as a secondary strategy producing novel aromatic C degradation genes. Overall, we found that trait trade-offs and genome evolutionary strategies are key drivers that may predict the persistence and contribution of pyrophilous fungi to global C and N cycling.

Defining expansions and perturbations to the RNA polymerase III transcriptome and epitranscriptome by modified direct RNA nanopore sequencing

Abstract RNA polymerase III (Pol III) transcribes cytosolic transfer RNAs (tRNAs) and other non-coding RNAs (ncRNAs) essential to cellular function. However, many aspects of Pol III transcription and processing, including RNA modifications, remain poorly understood, mainly due to a lack of available sensitive and systematic methods for their analysis. Here, we present DRAP3R (Direct Read and Analysis of Polymerase III transcribed RNAs), a modified nanopore direct RNA sequencing approach and analysis framework that enables the specific and sensitive capture of pre-mature Pol III transcribed RNAs. Applying DRAP3R to distinct cell types, we identify previously unconfirmed tRNA genes and other novel Pol III transcribed RNAs, thus expanding the known Pol III transcriptome. Critically, DRAP3R also enables discrimination between co- and post-transcriptional RNA modifications such as pseudouridine (Ψ) and N 6 -methyladenosine (m 6 A) at single-nucleotide resolution across all examined transcript types and reveals differential Ψ installation patterns across tRNA isodecoders and other ncRNAs. Finally, applying DRAP3R to epithelial cells infected with Herpes Simplex Virus Type 1 reveals an extensive remodelling of both the Pol III transcriptome and epitranscriptome. Our findings thus establish DRAP3R as a powerful tool for systematically studying Pol III transcribed RNAs and their modifications in diverse cellular contexts.

Slot fidelity and ligation-dependent tribology in personalized brackets made by casting versus selective laser melting: an in vitro study

Abstract Reliable chairside adoption of digital orthodontics depends on micrometre-scale slot fidelity and stable bracket–wire tribology. A single computer-aided design for a personalized second-premolar bracket was manufactured by lost-wax casting and by selective laser melting (SLM) (n = 36 per method). Slot height and inter-wall angle were measured on both the support-facing and non-support surfaces. Static and dynamic friction were evaluated using stainless-steel rectangular wires ligated either with tightly twisted stainless-steel ties or with elastomeric modules. Mean slot height was 480.88 ± 73.90 µm for casting and 421.47 ± 32.03 µm for SLM, against a nominal 480 µm. Overall height error did not differ between methods ( P  = 0.673), whereas angle er-ror was greater for SLM (17.76 ± 11.29°) than for casting (9.56 ± 8.88°, P  < 0.001). The support-facing wall consistently showed reduced accuracy: in casting, height error in-creased on the support side ( P  = 0.001); in SLM, both height and angle errors increased on the support side (both P  < 0.001). Across conditions, static friction exceeded dynamic friction (all P  < 0.001). With steel ligation, friction was higher for casting than SLM (median static 6.00 N vs 4.35 N, P  = 0.007; median dynamic 5.03 N vs 3.83 N, P  = 0.011). With elastomeric ligation, the ranking reversed, with higher friction for SLM (median static 2.95 N vs 2.05 N, P  < 0.001; median dynamic 2.54 N vs 2.03 N, P  = 0.003). In this standardized local in vitro model, findings suggest a surface-dependent reduction in accuracy at the support-facing wall and a fabrication-by-ligation interaction that may alter the frictional ranking between steel and elastomeric ligations. Cast brackets showed more consistent full-wire seating, whereas SLM brackets may benefit from calibrated design offsets and targeted finishing to limit undersized or tapered slots; validation beyond this setup is needed.

Data-driven superresolution imaging in disordered media

We propose a methodology that exploits large and diverse datasets to accurately estimate the ambient medium’s Green’s functions in strongly scattering media. Given these estimates, excellent imaging results are achieved, with a resolution that is better than that of a homogeneous medium. This phenomenon, known as superresolution, arises because the ambient scattering medium effectively enlarges the physical imaging aperture. While superresolution has been demonstrated and analyzed extensively in the context of physical time reversal, time reversal itself is not imaging. Our proposed methodology, based on either conventional optimization methods or neural networks, makes it possible to achieve superresolution imaging in complex media.

Reconfigurable all-solid-state topological lasing at arbitrary sites

Developmental trajectories of head and eye cue integration in gaze perception

Abstract Gaze perception is a foundational social skill. Here, we investigated how head and eye cue integration in gaze perception changes across development. Across five experiments involving 195 Japanese children (ages 4–16) and 126 adults (ages 18–58), we tested eye gaze perception using both Wollaston illusion images, where eye regions remain identical across head orientations, and Normal images with naturally varying eye regions. We found that the attractive influence of head orientation, whereby perceived gaze is biased toward the head direction, decreased from early childhood to adolescence. Notably, children aged 10–16 years did not show the attractive effect of head orientation characteristic of the Wollaston illusion. Adults consistently showed the illusion as expected. These findings highlight adolescence as a critical transitional period. A follow-up experiment with 7–9-year-old children showed that perceived gaze direction was more strongly biased toward head orientation in smaller images where iris and pupil positional details are less clearly visible, suggesting that the influence of head orientation is flexibly modulated by the clarity of eye region as well as age. The findings provide new insights into the dynamic development of social cue integration and perceptual decision-making across childhood, adolescence, and adulthood.

Susceptible host dynamics explain pathogen resilience to perturbations

Interventions to slow the spread of SARS-CoV-2 significantly disrupted the transmission of other pathogens. As interventions lifted, whether and when human pathogens would eventually return to their prepandemic dynamics remains to be answered. Here, we present a framework for estimating pathogen resilience based on how fast epidemic patterns return to their prepandemic dynamics. By analyzing time series data from Hong Kong, Canada, Korea, and the United States, we quantify the resilience of common respiratory pathogens and further predict when each pathogen will eventually return to its prepandemic dynamics. Our predictions are able to distinguish which pathogens should have returned already, and deviations from these predictions reveal long-term impacts of pandemic perturbations. We find a faster rate of susceptible replenishment underlies pathogen resilience and sensitivity to both large and small perturbations. Overall, our analysis highlights the persistent nature of common respiratory pathogens compared to vaccine-preventable infections, such as measles.

Behavioral uncertainty in EV charging drives heterogeneous grid load variability under climate goals

Retraction Note: The effect of Ganoderma lucidum polysaccharide extract on sensitizing prostate cancer cells to flutamide and docetaxel: an in vitro study

Striatal cholinergic interneurons exhibit compartment-specific anatomical and functional organization in the mouse

Striatal output is dynamically modulated by cholinergic interneurons (CINs), the primary source of acetylcholine in the striatum. CINs have been classically viewed as a random and homogeneous population, but recent evidence suggests heterogeneity in their anatomical and functional organization. Here, using systematic mapping and quantitative spatial analyses, we found that—contrary to current dogma—CINs exhibited striking enrichment and nonrandom clustering in the striosome compartment, particularly in the lateral striatum. Similar analyses carried out for parvalbumin- and somatostatin-expressing interneurons revealed that compartmental organization is interneuron specific. The strong “striosome preference” exhibited by CINs was confined within striosome borders, not extending to the surrounding matrix. We further found that striosome and matrix CINs differed in their expression levels of phospho-S6 ribosomal protein-Ser240/244 and choline acetyltransferase, suggesting functional differences, and clustered CINs differed from unclustered CINs in their intrinsic membrane properties. Finally, CINs expressing Lhx6, which defines a distinct γ-aminobutyric acid (GABA) coreleasing population, were notably absent from regions where highly clustered striosomal CINs appeared. Collectively, our findings uncover important dimensions of CIN organization, suggesting that modulation of regional and compartmental striatal output may depend upon the spatial–functional heterogeneity of CINs.

Unconventional polaronic ground state in superconducting LiTi2O4

Advancing censored geochemical Au prediction through Bayesian spatial models and Random Forest with fractal-based background separation

Abstract Censored geochemical data, particularly below detection limits, challenge mineral exploration by biasing anomaly delineation and spatial patterns. This study presents a multi-stage framework combining Bayesian Gaussian Random Field (BGRF) modeling with Random Forest (RF) learning, enhanced by fractal-based background separation, to accurately predict censored Au concentrations. 14 samples with gold concentrations below 5 ppb were hypothesized as censored data to enable a more accurate evaluation of the model’s performance based on their real Au concentrations. Unlike constant substitution methods, the framework preserves censored information and reconstructs spatial variability through probabilistic inference and nonlinear learning. The BGRF model incorporates spatial coordinates and Cu as the principal covariate to capture spatial autocorrelation and inter-element associations, producing probabilistic estimates for hypothesized censored data (HCD) that are then used to train the RF under a 5-fold out-of-fold scheme. The HCD estimated by spatial BGRF covariate model were performed as inputs for RF prediction model. A targeted calibration and scaling procedure reduces detection-limit bias and improves low-range predictions. Comparative analyses show that the calibrated and scaled RF–BGRF model substantially enhances accuracy and preserves realistic geochemical structures, outperforming half the detection limit (LD-half) or the detection limit divided by the square root of two (LD-rad2) approaches. This framework offers a promising tool for refining left-censored geochemical data in complex geological environments.

A neutralizing APOA5 monoclonal antibody reduces amounts of lipoprotein lipase in capillaries and triggers hypertriglyceridemia

Apolipoprotein AV (APOA5) regulates intravascular triglyceride metabolism by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its ability to unfold the native conformation of lipoprotein lipase (LPL). LPL unfolding results in loss of catalytic activity and the detachment of LPL from the surface of cells. An APOA5 truncation mutation (identified in two patients with hypertriglyceridemia) had suggested that the last 35 amino acids of APOA5 are important for its function. We reasoned that a monoclonal antibody (mAb) against carboxyl-terminal sequences in APOA5 could clarify functionally important amino acid residues in APOA5 and assist in elucidating the mechanism by which APOA5 regulates plasma triglyceride metabolism. Because carboxyl-terminal APOA5 sequences are evolutionarily conserved, we began by screening a human Fab bacteriophage library for binders of carboxyl-terminal APOA5 sequences. We identified one such binder and used phage DNA sequences to build a chimeric IgG 1 mAb (IBA707) against APOA5. The binding of IBA707 to APOA5 was abolished by nonconservative amino acid substitutions in conserved sequences (residues L337–I348) within a C-terminal α-helix in APOA5. The same substitutions disrupted APOA5’s ability to bind and inhibit ANGPTL3/8 activity. IBA707-mediated blockade of APOA5 function reduced intracapillary LPL levels and triggered elevated plasma levels of triglycerides and ANGPTL3/8 in both fasted and refed mice. IBA707 was cleared rapidly from the plasma in Apoa5 +/+ mice but slowly in Apoa5 –/– mice. Our studies identified functionally important amino acids in APOA5 and revealed that APOA5 controls plasma triglyceride metabolism in part by modulating plasma levels of ANGPTL3/8.

NTAC: Neuronal type assignment from connectivity

Robust federated learning for cloud environments using evolutionary optimization and blockchain

ZENN: A thermodynamics-inspired computational framework for heterogeneous data–driven modeling

Traditional entropy-based methods—such as cross-entropy loss in classification problems—have long been essential tools for representing the information uncertainty and physical disorder in data and for developing artificial intelligence algorithms. However, the rapid growth of data across various domains has introduced new challenges, particularly the integration of heterogeneous datasets with intrinsic disparities. To address this, we introduce a zentropy-enhanced neural network (ZENN), extending zentropy theory into the data science domain via intrinsic entropy, enabling more effective learning from heterogeneous data sources. ZENN simultaneously learns both energy and intrinsic entropy components, capturing the underlying structure of multisource data. To support this, we redesign the neural network architecture to better reflect the intrinsic properties and variability inherent in diverse datasets. We demonstrate the effectiveness of ZENN on classification tasks and energy landscape reconstructions, showing its superior generalization capabilities and robustness-particularly in predicting high-order derivatives. In image and text classification tasks, ZENN demonstrates superior generalization by introducing a learnable temperature variable that models latent multisource heterogeneity, allowing it to surpass state-of-the-art models on CIFAR-10/100, BBC News, and AG News. As a practical application in materials science, we employ ZENN to reconstruct the Helmholtz energy landscape of Fe 3 Pt using data generated from density functional theory and capture key material behaviors, including negative thermal expansion and the critical point in the temperature–pressure space. Overall, this work presents a zentropy-grounded framework for data-driven machine learning, positioning ZENN as a versatile and robust approach for scientific problems involving complex, heterogeneous datasets.

Sirt6 deficiency in mast cells promotes adipose fibroinflammation in obesity through galectin-3 signaling

The association between cultural engagement and mental health in Chinese higher vocational students: a cross-sectional study

Vapor-mediated wetting and imbibition control on micropatterned surfaces

Wetting of micropatterned surfaces is ubiquitous in nature and key to many technological applications like spray cooling, inkjet printing, and semiconductor processing. Overcoming the intrinsic, chemistry- and topography-governed wetting behaviors often requires specific materials which limits applicability. Here, we demonstrate that droplet spreading and wicking on hydrophilic patterns can be controlled by the vapor of a lower-surface-tension liquid. Condensation of the vapor induces Marangoni forces that delay capillary wicking and contract liquid into a droplet on top of the imbibed film. Thereby, macroscopic droplets can be maintained in an apparent partial wetting state, effectively cloaking the pattern. We quantify how pattern characteristics and vapor condensation compete, balancing in different wetting states from pinning to complete imbibition. Since this balance is the result of nonequilibrium processes rather than static wetting phenomena, it can be reversibly tuned by modifying the vapor concentration. This way, we guide droplets across patterns and even extract previously imbibed liquids, devising strategies for coating, cleaning, and drying functional surfaces.