Browse Articles

Carcinogenic and non-carcinogenic risk assessment of elemental impurities and bioactive compounds in six wild mushrooms using Monte Carlo simulation

Abstract Mushrooms, which can bioaccumulate environmental risk elements, have historically been considered a valuable and beneficial food source because of their nutritional and medicinal properties. In this context, the present study aimed to evaluate the natural bioactive potential of mushrooms and the levels of toxic elements. In this study, six edible mushroom species, Infundibulicybe geotropa , Tricholoma populinum , Tricholoma scalpturatum , Morchella importuna , Laccaria laccata , and Pholiota carbonaria , collected from their natural habitats in Bingöl and Van provinces of Türkiye, were investigated. Mushroom samples were collected from 2018 to 2020. The phenolic content and bioactivity of ethanol-extracted mushrooms were analyzed to determine their antioxidant bioactivity profiles. Simultaneously, inductively coupled plasma-mass spectrometry (ICP-MS) was used to evaluate the amounts of cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg) in the mushroom samples. The accuracy of the ICP–MS measurements was assessed using certified reference materials (CRMs), and recoveries were calculated as the ratio between measured and accredited values, ranging from 87.0% to 92.1%. The results were used to calculate the total carcinogenic risk (TCR), target hazard coefficient (THQ), hazard index (HI), and estimated daily intake (EDI) for adults and children. Monte Carlo simulation was also used to perform a probabilistic risk assessment, taking into account uncertainty in the exposure parameters. Antioxidant activity has been observed in mushroom species. Among mushrooms with antioxidant capacity, T. scalpturatum did not appear to pose a non-carcinogenic risk in adults due to elemental impurities (HI < 1); however, this risk increases in children and may pose a health risk (HI > 1). All mushrooms were found to pose a potential carcinogenic health concern (TCR ≥ 1 × 10 − 4 ) to adults and children, and their consumption may pose a potential health risk. L. laccata , in particular, stands out as the riskiest species for public health, with both low antioxidant activity and high elemental contamination.

D-amino acid aminotransferase1 regulates grain chalkiness in rice by modulating endoplasmic reticulum stress response

D-amino acids are key components of the bacterial cell wall and play important roles in neural communication and inflammatory responses in animals. However, knowledge about D-amino acid metabolism and physiological functions in plants is limited. Here, we isolated and characterized a rice D-amino acid aminotransferase1 , OsDAAT1 , which maternally regulates rice grain chalkiness through map-based cloning and a subsequent complementation test. We found that OsDAAT1 is highly expressed in the vascular tissue of rice nodes and is capable of interconverting different D-amino acids in vitro. Mutation of OsDAAT1 results in elevated D-alanine levels in stems, nodes, and developing grains. The disruption of D-amino acid metabolism subsequently leads to significantly altered peptide/protein isomerization, including some key enzymes involved in starch and protein biosynthesis. These changes trigger severe endoplasmic reticulum stress and ultimately leads to chalky grains. Furthermore, we identified OsDAAT1 Hap1 as a low-chalkiness haplotype, and historical frequency analysis suggests that OsDAAT1 may have undergone selection during rice domestication. Overall, our findings uncover a previously unrecognized role in D-amino acid metabolism in plants and facilitate the practical use of OsDAAT1 in grain appearance quality improvement in rice.

Longitudinal changes in cardiorespiratory fitness and risk of depressive and anxiety disorders in a nationwide cohort of 7 million participants

Water quality index and human health risk analysis in urban drinking water sources

Reverse engineering what makes a symbol memorable

Symbols may represent the first form of human visual communication, yet little is known about the cognitive and neural mechanisms supporting memory for these pervasive graphics. By investigating memory for everyday symbols, we can understand how abstract concepts are concretized with simple referents and later processed in visual memory systems. Recently, symbols have been found to be highly memorable, especially relative to words, but it remains unclear what drives their heightened memorability. We identified the key visual and conceptual attributes driving high memorability for symbols. Participants were tested on their memory for conventional symbols (e.g., !@#$%) before sorting them based on visual or conceptual features. Principal component analyses performed on the sorting data revealed which of these features predict memory for symbols. Generative AI was then used to accentuate or downplay these predictive features to create a set of memorable and forgettable novel symbols. A memory test revealed that symbols designed to be memorable were not only better recognized than those designed to be forgettable, but they also afforded superior recall of associated abstract words. This work demonstrates that certain stimulus features drive memory for images beyond distinctiveness or context and offers clear evidence that memory can be intentionally engineered.

Proteomic analysis of tissue-derived extracellular vesicles shows region-specific molecular changes in a rat model of takotsubo syndrome

Abstract Takotsubo syndrome (TS) is characterized by transient regional wall motion abnormalities (RWMA) of the heart following stress. Extracellular vesicles (EVs) play a significant role in cellular communication and disease pathophysiology, but remain unexplored in TS. Using a high-fidelity rat model of TS induced by isoprenaline infusion (n = 16), we isolated EVs from the tissue of affected apical and unaffected basal segments of the left ventricle at 24 h post-induction. The TS phenotype and cardiac function were assessed using high-resolution echocardiography. EVs were characterized by electron microscopy, western blot, and nanoparticle tracking analysis (NTA). Moreover, EV protein analysis was performed using tandem mass tag (TMT) proteomics. Pure, cup-shaped vesicles ranging from 50 to 500 nm were successfully isolated. NTA revealed lower particle concentrations in EVs isolated from the apex of TS24h hearts compared to their corresponding basal segments. Western blot experiments confirmed the presence of typical EV markers, including Flotillin 1, TSG101, and CD63. We identified 2093 proteins, with 238 differentially expressed (|FC| > 0.58, adj. P  < 0.05) proteins between TS-apex and control-apex, and 562 between TS-apex and TS-base, indicating a unique molecular adaptation in the affected apex. Functional enrichment analysis showed increased abundance of proteins associated with immune response, tissue repair, and survival signalling pathways. Proteins related to mitochondrial function showed decreased abundance. Network analysis revealed an association between proteins involved in lipid processes and inflammation. Overall, this study presents the first proteomic characterization of EVs in TS hearts. Our results demonstrate a distinct EV protein abundance profile in the affected apical segments of TS hearts, with marked changes in proteins related to inflammatory responses, tissue repair mechanisms, energy metabolism, and cell survival pathways. This comprehensive proteomic profile of EVs in TS hearts provides potential candidates for therapeutic targets and diagnostic biomarkers, warranting further mechanistic and clinical validation studies.

The geometry of Nature’s stingers is universal due to stochastic mechanical wear

Despite their ubiquity in Nature, spikes or stingers rarely exhibit sharp tips. Instead, a closer inspection of their roughly conical tips reveals a striking similarity in their profiles: They adhere to a power-law, z ∼ r n , where n ≈ 2 . This conformity persists across diverse spatial scales and materials. The mechanistic basis for this universality was recently attributed to evolutionary selection for ease of piercing [H. Quan et al ., Proc. Natl. Acad. Sci. U.S.A. 121 , e2316320121 (2024)]. However, the transient nature of their morphology, progressively modified by repeated use and inevitable wear, has received little scrutiny. In this work, we combine tabletop experiments with continuum analysis to demonstrate that the universal tip morphology can result from stochastic weathering processes. This finding is particularly significant in light of recent observations of the same tip geometry on dissolving or melting solids and geomorphic structures in addition to biological stingers. Our results suggest that the prevalence of this power-law profile may not be the result of evolutionary selection, but rather an inevitable consequence of exposure to random erosive processes.

Noradrenergic activity as a key target in modulating consciousness

Abstract How the brain generates conscious experiences remains profoundly mysterious. Pharmacological interventions that alter the state of consciousness have been proposed as a tool to investigate the neural mechanisms of consciousness. However, we have recently demonstrated that the sedative Propofol influences both conscious and unconscious neural processing. Altered arousal, and other pharmacological effects, therefore cannot be assumed a priori to provide information specifically on conscious neural processes. Instead, effects on both conscious and unconscious processes need to be considered. Here we investigated the role of noradrenergic activity in conscious and unconscious visuospatial processing. In Study 1 we used Dexmedetomidine, a sedative that specifically targets α2A noradrenergic receptors. In Study 2, we used sleep deprivation as a natural state of altered arousal, which exerts partially overlapping effects on noradrenaline levels. Unlike Propofol, both Dexmedetomidine and sleep deprivation selectively altered brain activity (fMRI BOLD signal change) during conscious processing. However, the two methods produced distinct effects on visuospatial bias during low arousal: while Dexmedetomidine reduced leftward bias, sleep deprivation increased leftward bias. These differential effects on spatial bias were explained by an unexpected increase in sympathetic drive, as indexed by increased activity in the central autonomic network and in heart rate, from sleep deprivation, that indicate increased rather than decreased noradrenaline levels during task performance. Together, these findings emphasize noradrenergic activity as a target for pharmacological manipulations of consciousness, which could open a window to its neurophysiological underpinnings.

TigCLaF: a cross-lingual large language model framework for sentiment-aware text classification in low-resource tigrigna

Counterproductive: coinfection of a water flea by a fungus and a microsporidium reduces the reproductive outputs of all parties

Exploring mechanisms governing cartilage interstitial fluid load support in lubrication through experimental and computational analysis

Abstract Articular cartilage enables nearly frictionless joint motion by regulating how interstitial fluid pressurizes and supports mechanical loads. Loss of this function is a key contributor to osteoarthritis, yet the mechanisms linking tissue composition, fluid pressurization, and lubrication remain poorly understood. Here we combine tribological testing of healthy and enzymatically degraded bovine cartilage with sample-specific finite element (FE) modeling to investigate how interstitial fluid load support (IFLS) governs the coefficient of friction (COF). While direct measurement of IFLS is technically demanding, our FE-based approach enables empirical estimation of IFLS. Cartilage plugs were articulated against each other under creep loading and lubricated with either synovial fluid or saline. The finite element model enabled empirical quantification of IFLS during testing, which we validated against previously reported experimental data. We observed that once interstitial fluid load support declined to low levels, lubrication became increasingly dependent on the external medium. While the strain–IFLS relationship remained linear across all conditions, degeneration disrupted the otherwise consistent IFLS–COF relationship. These findings help clarify how fluid pressurization and tissue integrity jointly regulate cartilage lubrication, providing a functional framework for evaluating cartilage repair strategies and extending to other biphasic materials such as hydrogels and engineered tissues.

Punicalagin with anti-inflammatory activities affects Brd-4 mediated chromatin remodeling for attenuating inflammatory osteolysis

Abstract Inflammatory osteolysis is primarily characterized by an extensive macrophage-mediated inflammatory response coupled with osteoclast (OC) formation, triggered by bacterial byproducts and/or environmental stressors. And Osteoarthritis (OA) is one of the most common degenerative diseases in clinical medicine. Currently, anti-inflammatory drugs and intra-articular drug injection are mainly used, but the treatments only relieve symptoms. Punicalagin (PUN), a hydrolyzable tannin derived from pomegranate extract, the suppression of pro-inflammatory cytokine production in macrophages. The therapeutic potential of PUN in alleviating inflammatory osteolysis remains inadequately elucidated. PUN demonstrated favourable biocompatibility and therapeutic potential in vitro, including potent anti-osteoclastic activity, ROS scavenging capacity, and epigenetic regulatory functions. PUN was found to inhibit bromodomain-containing protein 4 (Brd4)-mediated chromatin space remodeling, consequently upregulating the production of endogenous anti-inflammatory factors and antioxidant factors. This study reveals a new therapeutic mechanism that PUN exerts anti-inflammatory effects and regulates epigenetic regulation by influencing Brd4-mediated chromatin remodeling. These findings showed the therapeutic potential of PUN for inflammatory diseases, especially inflammatory osteolysis. Notably, our work identifies a new strategy that synergistically combines osteoclast inhibition with epigenetic regulation, providing a promising direction for the therapies for bone-related inflammatory diseases.

GalNAc-T13 maintains neurite architecture and memory retention via O-GalNAc glycosylation of seizure protein 6

Glycosylation, a key and prevalent modification in brain proteins and lipids, is essential for brain development and function. O-GalNAc glycosylation, initiated by the family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts, GALNT s), is the most abundant type of O-glycosylation in the brain. Despite growing evidence linking GALNT variations to neuropsychiatric disorders, the molecular roles and underlying mechanisms by which O-GalNAc glycosylation contributes to brain functions remain poorly characterized. Here, we focus on GalNAc-T13, a member of the GalNAc-T family that is highly expressed in the brain. We established a brain-specific Galnt13 conditional knockout mouse model and found that these mice exhibited reduced neurite length, simplified dendritic branching, and decreased dendritic spine density in the cerebral cortex across embryonic and adult stages. Behavioral analyses further revealed impaired spatial memory consolidation following Galnt13 knockout. Mechanistically, we identified seizure protein 6 (SEZ6), a neurodevelopment-related protein, as a key substrate of GalNAc-T13 using a lectin-based mass spectrometry glycoproteomic approach. Our results demonstrated that GalNAc-T13 regulates the O-GalNAc glycosylation levels of SEZ6 with high catalytic efficiency in vitro and in vivo, improving protein stability and its interaction with PRSS12 at the cell surface to promote neurite outgrowth. Collectively, these findings suggest a critical role for GalNAc-T13 in maintaining cortical neurite architecture and memory retention, providing a mechanistic example for understanding the function of O-GalNAc glycosylation in the brain.

Repellent activity against Aedes aegypti and metabolomic profiling of Myrica gale L. essential oils from Irish boglands

Agile legged locomotion in reconfigurable modular robots

Legged machines are becoming increasingly agile and adaptive, but they have so far lacked the morphological diversity of legged animals, which have been rearranged and reshaped to fill millions of niches. Unlike their biological counterparts, legged machines have largely converged over the past decade to canonical quadrupedal and bipedal architectures that cannot be easily reconfigured to meet new tasks or recover from injury. Here, we introduce autonomous modular legs: agile yet minimal, single-degree-of-freedom jointed links that can learn complex dynamic behaviors and may be freely attached to form multilegged machines at the meter scale. This enables rapid repair, redesign, and recombination of highly dynamic modular agents that move quickly and acrobatically (nonquasistatically) through unstructured environments. Because each module is itself a complete agent, the bodies that contain them can sustain deep structural damage that would completely disable other legged robots. We also show how to encode the vast space of possible body configurations into a compact latent design space that can be efficiently explored, revealing a wide diversity of novel legged forms.

Dynamic fog node placement optimization using adaptive dynamic pufferfish optimization for real-time IoT networks

Unveiling hidden intermediate states in protein folding with AI-based conditional transition clustering

Revealing the complex mechanisms of protein folding, including the transient intermediate states that govern the process, is a fundamental goal in computational biophysics. While molecular dynamics (MD) simulations generate vast amounts of data to this end, extracting a clear kinetic model from these complex, high-dimensional trajectories remains a significant challenge. We present AI-Based conditional transition clustering (CTC), a framework for analyzing MD trajectories that directly addresses the limitations of state-centric methods. Conventional approaches, such as Markov state models, rely on predefined geometric clustering or assume fixed linear dynamics, which can bias the discovery of protein conformational states. CTC operates on a “dynamics-centric” principle, defining a conformational state as a kinetically trapped region identified after analyzing the system dynamics, not before. By leveraging AI-based normalizing flows to estimate conditional transition probabilities from the MD data, CTC identifies states as “kinetic islands” with low escape probabilities. Applying CTC to protein-folding simulations successfully identifies critical intermediate and transition states, revealing folding pathways without prior assumptions about the number of states or their kinetic properties. This approach provides a more objective and physically grounded method for uncovering the complex mechanisms of biomolecular systems.

LSD1 promotes prostate cancer cell proliferation by upregulating PRAC1 expression

Abstract PRAC1 , which is specifically expressed in prostate, rectal, and distal colon tissues, plays a critical role in the maintenance and self-renewal of prostate epithelial stem cells. However, the role of PRAC1 in prostate cancer is unclear. In this study, we found that PRAC1 expression is upregulated in prostate cancer cells and that PRAC1 knockdown represses the proliferation of prostate cancer cells. Moreover, lysine-specific demethylase 1 (LSD1) promoted prostate cancer cell proliferation by upregulating PRAC1 expression. TAK-418, an LSD1 inhibitor, suppressed prostate cancer cell proliferation by downregulating PRAC1 expression. Our results highlight PRAC1 or LSD1 inhibition as promising avenues for prostate cancer treatment.

Mechanical performance of hybrid polymer–lipid vesicles with leaflet asymmetry engineered using microfluidics

Lipid vesicles consist of aqueous cores surrounded by a bilayer of phospholipids. Hybrid polymer–lipid vesicles incorporate both polymers and lipids, offering promising properties for developing pharmaceuticals, biosensors, and artificial cells. The hybrid vesicles can be symmetric, with two leaflets of identical compositions, or asymmetric, in with leaflets of dissimilar compositions, which can lead to dramatically altered properties. However, existing methods for producing symmetric and asymmetric hybrid vesicles often result in heterogenous compositions and sizes, making it challenging to quantify the effect of asymmetry and limiting applications. Here, we use a microfluidic approach to produce hybrid vesicles with either symmetric or asymmetric leaflets and precisely engineered compositions. We find that the vesicles with asymmetric leaflets are significantly stiffer and tougher than those with symmetric leaflets; moreover, the lateral diffusivity of lipids is greatly decreased. The structure for improved toughness consists of a stretchable lipid inner leaflet and a fully continuous polymer outer leaflet. This approach to precisely engineer asymmetric structures can be applied to hybrid vesicles composed of block copolymers and phospholipids soluble in chloroform and hexane, further expanding their applications.

Trust in medical art is the most effective coping mechanism for predicting treatment satisfaction in elective neurosurgery

Abstract Patient expectations and satisfaction are critical outcomes in cranial and spinal neurosurgery, yet discrepancies between anticipated and actual results can hinder postoperative adjustment. This prospective longitudinal study investigated how coping strategies and preoperative patient education influence satisfaction with surgical outcomes. Two self-developed questionnaires assessed expectations, perceived illness burden, patient education quality, hospital experience, postoperative recovery, and overall satisfaction after surgery. Coping strategies were evaluated using the validated Essen Coping Questionnaire . Data from 277 patients were analyzed, stratified by surgical complexity. No significant difference in patient education quality was found between complexity groups (mean difference 0.62, 95% CI [–1.65, 0.41];  t (221) = –1.19,  p  = .237). Patients undergoing less complex procedures reported higher preoperative burden (mean difference 1.72, 95% CI [–3.33, –0.10];  t (231) = –2.09,  p  = .038). Linear regression revealed that the quality of preoperative education, postoperative burden, and coping strategies  trust in medical art  and  willingness to accept help significantly predicted satisfaction ( F (10,79) = 3.41,  p  < .001). These findings highlight the importance of patient-doctor communication, tailored education, and psychological preparedness in shaping patient-reported outcomes. Enhancing preoperative support and fostering adaptive coping may improve satisfaction and postoperative adjustment, advocating for a more personalized approach to neurosurgical care.