Browse Articles

Divergent philosophical commitments in neuroscience: Evidence from a global survey

The mind–brain relationship is a foundational yet underexplored dimension of contemporary neuroscience, shaping research framing, data interpretation, and public communication. We conducted a large-scale international survey of 2,657 neuroscientists to assess their views on the mind–brain problem, free will, and the future of the discipline. Our results reveal a complex and sometimes paradoxical worldview. While 64% of participants endorse reductive physicalism—the view that mental activity is fully reducible to brain function—only 17.5% reject free will. Despite estimating that current knowledge covers only a limited portion of brain structure and function (30%), respondents express marked optimism about the future of neuroscience, including the prospect of fully understanding the human being and mental disorders through neuroscience, and even achieving mind reading and mental uploading. A principal component analysis identified five latent dimensions, some of which vary systematically across sociodemographic and disciplinary factors. These findings indicate that neuroscientists hold diverse philosophical commitments that diverge from common narratives of hard determinism. The prevalence of neuroessentialist views further highlights the need for sustained interdisciplinary dialogue to address the conceptual, ethical, and societal implications of neuroscientific progress.

Physicochemical analysis and comparative toxicity of Juniperus phoenicea L. essential oil against Planococcus citri and Planococcus ficus

Endosomal TPC1–mediated Ca ²⁺ nanodomains regulate transferrin receptor trafficking and iron homeostasis

Two-pore channel 1 (TPC1) is an endosomal Na + /Ca 2+ -selective channel implicated in membrane trafficking, endosome tubulation, and excitability, but how TPC1 regulates membrane trafficking is unknown. Using TPC1-null human cells, we demonstrate that TPC1 drives transferrin receptor (TfR) trafficking and recycling via Ca 2+ , and not Na + fluxes or endosomal pH changes, since channel-targeted Ca 2+ -buffers inhibited trafficking, whereas a Na + -deficient Ca 2+ -permeable TPC1 mutant fully supported trafficking. TPC1 was unique since other Ca 2+ sources did not support TfR trafficking. TPC1 activity depended on the lipid PI(3,5)P 2 , since trafficking was impaired by a lipid-insensitive TPC1 or inhibitors of lipid synthesis. Finally, a corollary of this reduced TfR trafficking is an iron-deficiency and storage phenotype in TPC1-deficient HeLa cells and mice. Our findings highlight endosomes as unique Ca 2+ stores mobilized by a phosphoinositide-induced TPC1 channel that generates local Ca 2+ nanodomains crucial for maintaining TfR trafficking and consequent iron homeostasis.

Deterioration behavior and model of alkali-activated fly ash-slag concrete under freeze–thaw cycles

Abstract Concrete components in highways and bridges are susceptible to freeze–thaw deterioration in cold regions, compromising their service safety. Alkali-activated fly ash-slag concrete (AAFSC), which fully replaces Portland cement with industrial by-products, offers promising environmental and application benefits. However, research on its freeze–thaw damage remains limited, hindering its use in cold-region infrastructure. This study presents a systematic experimental and theoretical investigation into the freeze–thaw deterioration of AAFSC. For the first time, the damage process is described within the Kachanov–Rabotnov evolution framework, establishing an exponential damage model with well-defined physical boundary conditions—extending continuum damage mechanics to freeze–thaw action in concrete. The model quantitatively captures damage progression in AAFSC and demonstrates broad applicability across various concrete types reported in the literature. This work provides important guidance for predicting the freeze–thaw durability of AAFSC-based transportation infrastructure components in cold regions.

Artistic visions shape and respond to Mars missions

COVLIAS 3.5: integration of attention-based segmentation technique with fuzzy dilated convolutional neural networks for improved classification of chest X-ray scans for multiclass pneumonia diagnosis

Abstract This study aims to improve pneumonia diagnosis by integrating attention-based U-Net models for lung segmentation with fuzzy logic-enhanced CNNs for classification. This approach addresses the limitations of inadequate modelling of complex spatial relationships in medical images. The underutilization of fuzzy logic with dilated convolutions has restricted the extraction of multiscale features. We utilized 18,608 chest X-ray (CXR) images. Subsequently, these images were segmented using four models namely: U-Net, Attention U-Net, Pruned U-Net and U-Net++. Fuzzy logic system was used to process the segmented data. Additionally, we show that the dilated CNN architecture for improved classification performance. In lung segmentation, our experimental results indicate that Attention U-Net (AU) achieved  1% better mean accuracy,  2% better mean Jaccard and Dice than U-Net, pruned U-Net and U-Net++. In the classification, the model has demonstrated 10% better mean accuracy over augmented U-Net and Attention U-Net based segmented data. ROCs have shown that augmented effect has  15% better AUC in bacterial pneumonia class. Additionally, we saw a 4% improvement with fuzzy logic. The integration of fuzzy dilated CNN with Attention U-Net segmentation presents a 1% better accuracy compared to U-Net. Best AUC achieved was 0.98 in bacterial pneumonia. Our findings underscore the critical role of attention mechanisms and augmentation in enhancing medical image analysis. The integration of Attention U-Net for segmentation and fuzzy dilated CNN for multi-class classification significantly improves diagnostic accuracy and reliability. This approach has the potential to revolutionize pneumonia diagnosis, leading to better patient outcomes and more efficient healthcare delivery.

Hydration and hydrolysis define antibiotic resistance conferred by macrolide esterases

Macrolides are an antibiotic class widely used in both human and veterinary medicine, and function by interfering with protein synthesis. Regrettably, numerous strategies for evading the antibiotic properties of macrolides have been found in bacteria, including enzyme-mediated inactivation. These mechanisms are now widely disseminated among pathogenic, animal-associated, and environmental bacteria making them a One Health issue. Macrolide esterases, which hydrolyze the macrolactone’s ester bond, confer one such resistance mechanism. Two types of macrolide esterases have thus far been identified, the well-studied erythromycin esterases and the recently discovered Est-type enzymes that belong to the α/β-hydrolase superfamily. We present detailed structure–function studies for four diverse Est type esterases: which only share 44 to 66% sequence identity (EstT Sf , EstT St , EstT Bc , and EstX Ec ). In addition to resistance profiling and substrate specificity studies, we present structures for all four enzymes, including structures for EstT Bc and EstX Ec in complex with tylosin and tylvalosin macrolides, posthydrolysis. Complementing the data with mutational and kinetic studies allowed for a detailed analysis of the structural basis for macrolide–enzyme interactions. Combined, the data suggest that promiscuous binding and imprecise positioning, mediated by a water-cage, dictate substrate specificity for Est-type macrolide resistance enzymes. These insights may prove beneficial for next-generation antibiotic development.

Genomic surveillance of multidrug-resistant Enterobacterales in a long-term care facility in Northern Italy based on a point prevalence screening

Homer condensates orchestrate YAP–Wnt signaling crosstalk downstream of the Crumbs polarity complex

The Hippo pathway governs cell growth, proliferation, and differentiation and is frequently deregulated in cancer. Yes-associated protein (YAP) is the central transcriptional coactivator of the Hippo pathway and interacts with β-catenin to coordinate YAP–Wnt signaling crosstalk. Both pathways are modulated by diverse upstream signals including mechanical cues, cell density, and cell polarity, yet how such signals are integrated remains poorly understood. Here, we demonstrate that Homer scaffolding proteins coordinate YAP and Wnt signaling downstream of the Crumbs polarity complex. Homers interact directly via their EVH1 domains with the Crumbs component PATJ and the NDR kinase scaffold Furry-like (FRYL). Homers antagonize FRYL to promote YAP activation while cooperating with FRYL to enhance Wnt/β-catenin signaling, revealing pathway-selective regulation. PATJ, in contrast, recruits Homers to the cortex and restrains YAP activity. We further show that Homers form biomolecular condensates in nonpolarized epithelial and colorectal cancer cells, whose assembly and signaling properties are differentially modulated by PATJ and FRYL. Whereas FRYL promotes the formation of cytoplasmic droplets, PATJ drives the assembly of phase-separated compartments at or near the plasma membrane. Collectively, our findings establish Homer-driven phase separation as a tunable signaling mechanism to translate polarity cues into transcriptional output.

Retraction Note: Hydrogen-induced microstructural evolution in a nickel-based alloy under high-temperature and high-pressure conditions

Dosage compensation and meiotic sex chromosome inactivation are maintained under relaxed selection

Dosage compensation and meiotic sex chromosome inactivation (MSCI) are key mechanisms regulating gene expression from the X chromosome in male-heterogametic species. While the convergent evolution of these mechanisms is well documented, their evolutionary fate under relaxed selection remains poorly understood. Here, we test whether dosage compensation and MSCI persist following three independent transitions to parthenogenesis in stick insects, where selection on male phenotypes is relaxed. Using rare males occasionally produced by parthenogenetic females, chromosome-level genome assemblies, RNA-seq from multiple tissues, and immunocytochemistry, we find that dosage compensation is fully conserved across all seven studied somatic tissues. This is even the case in the oldest, approximately 1.5 My old all-female lineage and for tissue-specific genes for which dosage variation is not expected to be very deleterious. Meiotic X inactivation in the germline is also conserved. Surprisingly, however, expression data and cytological markers indicate that MSCI signatures are even stronger in parthenogenetic males, a pattern likely driven by prolonged autosomal transcription during meiosis. These results indicate that X-targeting dosage compensation and MSCI are highly stable over evolutionary time and may be maintained in all-female lineages by a combination of evolutionary constraint, pleiotropy, or very weak selection, whereas autosomal expression during meiosis shifts rapidly under relaxed selection.

Effects of a “Food Is Medicine” Intervention on Glucose Control Among Medicaid-Insured Patients With Type 2 Diabetes: A Randomized Controlled Trial

BACKGROUND: Although medically tailored groceries (MTG) hold promise to improve food and nutrition security and health among patients with diet-related illnesses and social needs, few randomized trials have been performed. METHODS: We enrolled 460 Medicaid-insured adults with type 2 diabetes and elevated hemoglobin A1c (HbA1c) between November 2021 and July 2022 in a randomized controlled trial of MTG in southern California. Eligibility was based on at least 2 HbA1c measurements ≥7.5% in the past year. Participants were randomized 1:1:1 to usual-care (N=153), lower-dose MTG (N=153), or higher-dose MTG (N=154) for 6 months, with the prespecified primary assessment comparing the combined MTG groups with control. MTG was provided as weekly home deliveries of healthy produce, scaled to household size ($100 to $170 per month for the lower dose and $135 to $210 per month for the higher dose), along with matched recipes and telenutrition counseling. The primary outcome was a change in HbA1c at 6 months. Secondary outcomes included changes in food security and nutrition security, measured by surveys, and hypertension and body mass index, measured during clinical care encounters; evaluation of dose-response comparing the lower-dose and higher-dose arms; and effects in key population subgroups. RESULTS: At baseline, mean (SD) age was 59.2 (13.2) years, 284 (64.8%) were women, 373 (85.2%) reported Hispanic ethnicity, 254 (58%) reported food insecurity, and mean (SD) HbA1c was 9.40 (1.53). Among intervention participants, 244 (83.3%) reported eating most or all food provided, and 63 (21.5%) engaged in telenutrition counseling. Compared with baseline, HbA1c declined by 0.66 points in the intervention and 0.25 points in the control group, a treatment difference of –0.40 points (95% CI, –0.73, –0.08; P =0.016). Higher-dose and lower-dose MTG produced similar reductions. Odds of food security and nutrition security increased by 2.12 (95% CI, 1.13, 3.99; P =0.020) and 3.65 (95% CI, 1.84, 7.25; P <0.001), respectively. Hypertension and body mass index did not significantly change. Results were consistent in prespecified subgroup analyses by sex, education, baseline food security, baseline nutrition security, and baseline HbA1c level. Findings were similar in analyses adjusting for baseline demographics, food insecurity, nutrition insecurity, self-reported health, comorbidities, and medication changes. CONCLUSIONS: In this randomized trial among Medicaid-insured, racially/ethnically diverse patients with type 2 diabetes, MTG lowered HbA1c and improved food and nutrition security. REGISTRATION: URL: https://clinicaltrials.gov ; Unique identifier: NCT05407376.

Personalized content generation in family education based on deep learning

Tumor-derived cytokine enhances bitter sensing through remote control of bitter taste neurons via the Upd3/Spz5/Toll-6 axis in <i>Drosophila</i>

The sense of taste is essential as it governs appetite and the feeding process. However, it is largely unknown whether and how tumors in a host communicate with peripheral taste sensing. Using the well-established yki S168A tumor models in Drosophila melanogaster , we found that flies carrying brain or gut tumors exhibit enhanced avoidance of bitter compounds such as caffeine but showed no avoidance of sucrose, and the degree of the avoidance was correlated with severity of the tumor phenotype. Through RNAi screening of upregulated cytokines secreted by malignant tumors, we identified Upd3 as a key factor in this process. Tumor-derived Upd3 promotes systematic increase of Spz5 expression, a fly neurotrophin, which in turn activates the Toll-6 receptor in peripheral bitter sensing neurons, leading to upregulation of the bitter-sensing receptor Gr66a. In vivo Ca 2+ imaging demonstrated heightened responses to caffeine by Gr66a + neurons in tumor-bearing flies. Interestingly, a similar phenomenon was observed in murine tumor models, where tumors also caused behavioral hypersensitivity to bitter tastants. Our findings reveal how tumors affect animals’ feeding behavior as well as the underlying mechanism. Our findings also suggest that such tumor-induced behavioral alterations are likely conserved across species.

Sirolimus-Eluting Balloon With Provisional Stenting Versus Systematic Drug-Eluting Stent Implantation to Treat De Novo Coronary Lesions: A Randomized, Open-Label, Noninferiority Trial

BACKGROUND: Implantation of drug eluting stents (DESs) is currently the default approach for percutaneous coronary interventions, but long-term adverse events still exist. An approach with minimal stenting deserves to be assessed in a randomized trial. We studied a novel sirolimus-eluting balloon (SEB) that elutes sirolimus over a 90-day period using a biodegradable polymer microreservoir technology. METHODS: In a multicenter, open-label, randomized trial, we compared an SEB-based strategy with provisional DES with one of systematic DES for de novo lesions in coronary arteries between 2 and 5 mm in diameter. Subjects were randomized 1:1 before percutaneous coronary intervention. The primary end point was target vessel failure, a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization. It was tested for noninferiority at 1 year with the use of an absolute margin equal to 50% of the combined event rate at a significance level of 0.025. The primary analysis population included all randomized subjects with completed or attempted percutaneous revascularization, analyzed according to the intention-to-treat principle. A sensitivity analysis was performed on the per-protocol population. RESULTS: Between August 27, 2021, and July 29, 2024, 3323 participants were randomized and treated in 62 sites. Among 1661 participants in the SEB strategy group, bailout stenting was performed in 343 (20.7%). Target vessel failure occurred over 365 days in 88 (5.3%) and 73 (4.4%) participants in the SEB and the systematic DES strategy groups, respectively (risk difference, 0.91% [95% CI –0.55% to 2.38%]; 1-sided P =0.02 for noninferiority with a 2.44% noninferiority margin). Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group (3.3% versus 2.1%; risk difference, 1.22% [95% CI, 0.11%–2.33%). Safety events, including lesion thrombosis, were low and similar in both groups. Although the results of the per-protocol population (3194 participants, 96%) did not confirm noninferiority (upper boundary of the 95% CI, 2.63; P =0.04), they were similar to the intention-to-treat results in both magnitude and direction. CONCLUSIONS: At 1 year, in the primary intention-to-treat analysis population, a strategy of percutaneous coronary intervention with SEB and provisional DES was noninferior to the systematic use of DES for the primary end point of target vessel failure. The per-protocol population sensitivity analysis did not confirm noninferiority. Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group. At 5 years, target vessel failure will be tested again for noninferiority and for superiority if noninferiority is achieved. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04859985.

Spatial inequalities in out-of-hospital cardiac arrest in Lombardy, Italy are associated with ageing, population density and low income

Bursa of Fabricius–independent B cells establish an IgA-mediated intestinal barrier that safeguards gut–liver homeostasis

The bursa of Fabricius (BF), a specialized lymphoid structure in birds, regulates avian B-cell development. However, the BF starts to regress posthatching, suggesting that as-yet-unidentified structures assume this function during maturation. This study reveals that BF-independent B-cell genesis involving the gut cecal tonsils (CTs) predominates over the BF-dependent pathway posthatching. Although B-cell progenitors originating from the bone marrow (BM) typically migrate to the BF, we identified a population that instead migrates to the CTs through CXCL12/CXCR4-mediated chemotaxis. These BF-independent CXCR4 + pre-B cells acquired surface IgM expression within the CT follicular region (FR) and differentiated into immunoglobulin A (IgA)-producing plasma cells. Inhibition of CXCR4 + cell influx from the BM impaired formation of the FR, altered the responsiveness of intestinal IgA to commensal bacteria, promoted gut dysbiosis, allowed translocation of pathogenic bacteria (e.g., Streptococcus alactolyticus ) to the liver, and ultimately caused hepatic inflammation and metabolic dysfunction. These abnormalities were reversed by administering an IgA-enriched fecal preparation derived from healthy chickens. Collectively, these results reveal the existence of a population of BF-independent B cells that function in CTs. These cells represent a promising target for maintaining and improving the immunological and microbiological environment of the avian intestinal tract, which is closely linked to hepatic homeostasis.

Loss of ATP-Dependent Citrate Lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling

BACKGROUND: Metabolic adaptation and maladaptation are hallmarks of the failing heart and may be a target for therapeutic interventions. For example, sustained glucose oxidation during cardiac stress is associated with increased activity and abundance of ACL (ATP-dependent citrate lyase, Acly ), which produces acetyl–coenzyme A (CoA) from citrate and CoA and supports de novo lipid synthesis. However, our understanding of how ACL supports cardiac metabolic adaptation and its potential to modulate disease pathophysiology has not yet been investigated. METHODS: We used human heart tissue samples from healthy donors and patients with nonischemic cardiomyopathy. Next, we used CRISPR (clustered, regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated 9) gene editing to inactivate Acly in cardiomyocytes of Myh6-Cas9 mice. In vivo positron emission tomography and ex vivo stable isotope tracer labeling were used to quantify metabolic flux changes in response to Acly knockdown. We conducted a multi-omics analysis using RNA sequencing and mass spectrometry–based metabolomics and proteomics. Experimental data were integrated into computational modeling using the metabolic network CardioNet to identify significantly dysregulated metabolic processes at a systems level. RESULTS: We observed reduced ACL abundance and activity in human heart tissue samples from patients with nonischemic cardiomyopathy, which correlated with decreased abundance of Krebs cycle intermediates. Using CRISPR/Cas9 gene editing, we found that cardiac-specific loss of ACL reduces acetyl-CoA synthesis, leading to altered cardiac metabolism characterized by increased glucose uptake and oxidation, impaired energy flux, and elevated AMP to ATP ratios, which collectively promote left ventricular dysfunction. Transcriptomic and mass spectrometry–based metabolomics, as well as proteomic data, reveal compensatory cardiac lipid remodeling and reduced histone 3 acetylation. This metabolic stress promotes activation of AMPK (AMP kinase) and PKA (protein kinase A), which in turn mediates YAP (Yes-associated protein) inhibition through phosphorylation. Stable isotope tracer studies combined with CardioNet simulations demonstrated that increased IDH1 (isocitrate dehydrogenase 1) activity prevents allosteric inhibition of glycolysis from cytosolic citrate accumulation. AAV9-mediated cardiac Idh1 deletion improved cardiac function and energy provision, reducing YAP phosphorylation and restoring downstream YAP signaling. CONCLUSIONS: Our findings suggest that ACL plays a pivotal role in cardiac metabolism through regulating lipid synthesis and cardiac function. Exploiting compensatory pathways of citrate metabolism may improve cardiac function during heart failure.

Impaired left ventricular transmural strain gradient linked to septal flash in complete left bundle branch block

Targeted α-synuclein mRNA degradation by PMO-based RNA-degrading chimeras

α-Synucleinopathies are devastating neurodegenerative diseases characterized by pathological accumulation of a neuronal protein, α-synuclein (αSyn). Lowering soluble αSyn levels is a promising therapeutic strategy to limit aggregation and neurotoxicity, but directly targeting this protein is hindered by its intrinsically disordered structure and other factors, such as its conformational heterogeneity and intracellular drug delivery barriers. Consequently, increasing attention has been directed toward targeting the SNCA transcript, which encodes αSyn. Here, we developed phosphorodiamidate morpholino oligonucleotide (PMO)-based RNA-degrading chimeras (RDCs) that selectively bind the 5′ untranslated region of SNCA messenger RNA (mRNA) and recruit RNase L for targeted RNA degradation. Through the systematic evaluation of nine RDCs, we identified and optimized 4-D1, which effectively reduced SNCA mRNA and αSyn protein expression in HEK293T cells in an RNase L-dependent manner. 4-D1 lowered SNCA transcript and αSyn protein levels in both primary cortical neurons from humanized SNCA mice and in human induced pluripotent stem cell–derived cortical neurons. This reduction prevented prion-like seeding induced by patient-derived αSyn fibrils and protected neurons from fibril-induced cytotoxicity. Finally, in vivo studies confirmed the efficacy of 4-D1 in reducing αSyn mRNA expression in humanized SNCA mice. These findings indicate that PMO-based RDCs may represent a promising therapeutic modality for α-synucleinopathies.