Mechanical analysis of the femoral head is mostly conducted through finite element analysis (FEA), the operation of which is relatively complex. In this study, the correlation between computed tomography (CT) quantitative analysis and FEA in the diagnosis of osteonecrosis of the femoral head (ONFH) was analyzed. This retrospective study involved 30 hips from patients with Steinberg stage II ONFH who had not received treatment. The average CT density was measured, and an FEA model was constructed on the basis of the CT images of each case. The correlation between the average CT density and the FEA measurements was analyzed. The average CT density of the coronal midline plane was 370.47 ± 16.85 HU, and that of the maximum necrotic layer was 420.73 ± 22.24 HU. According to the FEA results, the maximum total displacement was 0.42 ± 0.04 mm, the maximum displacement in the Z direction was 0.25 ± 0.02 mm, the maximum equivalent stress in the stress concentration zone of the head was 1.81 ± 0.02 MPa, and the failure coefficient was 0.34 ± 0.02. The average CT density of the maximum necrotic layer was not correlated with the maximum total displacement or maximum displacement in the Z direction but was correlated with the maximum equivalent stress (r = 0.65; P < 0.1001) and failure coefficient (r=-0.58; P < 0.001). The average CT intensity of the maximum slice (P = 0.004) and the average failure coefficient (P = 0.020) significantly differed between the collapse and noncollapse groups. CT quantification can reflect the load distribution and bearing capacity of ONFH to some extent. The higher the average CT density of the maximum slice, the lower are the average failure coefficient of the femoral head and the clinical risk of collapse.
Primary mediastinal liposarcomas are exceedingly rare mesenchymal tumors that can grow to a massive size before becoming symptomatic, often leading to diagnostic and therapeutic challenges. We present the case of a 45-year-old male with a giant, well-differentiated liposarcoma occupying the entire left hemithorax, anterior mediastinum and extending into the contralateral hemithorax, causing complete collapse of the left lung. The patient underwent a successful complete surgical resection via a single posterolateral thoracotomy, leading to an excellent postoperative outcome. This case highlights the importance of considering this rare entity in the differential diagnosis of large thoracic masses and underscores the feasibility and efficacy of complete surgical excision even for tumors of exceptional size.
We study the threshold of gravitational collapse in spherically symmetric spacetimes governed by the Einstein-Maxwell-Vlasov equations. We numerically construct solutions describing a collapsing distribution of charged matter that either forms a charged black hole or eventually disperses. We first consider a region of parameter space where the solutions at the threshold of black hole formation are stationary, horizonless shells. These solutions terminate at a critical point, with their charge-to-mass ratio approaching unity from below, and the instability timescale diverging. Beyond the critical point, we find a new region of parameter space where the threshold solution is an extremal black hole. We measure the scaling of the dynamical time period of the near threshold solutions and discuss how they are connected in the two regimes. If a similar picture to the one found here holds for known families of stationary solutions of rotating matter that approach the exterior of an extremal Kerr spacetime, they could provide a route to forming an extremal spinning black hole.
Intradiscal platelet-rich plasma (PRP) has emerging evidence for the treatment of discogenic low back pain. However, procedural access becomes technically challenging at the L5-S1 level in the presence of severe disc collapse, steep lumbosacral lordosis, or high iliac crest morphology, which may preclude standard posterolateral or transforaminal trajectories. A 42-year-old man with chronic discogenic low back pain demonstrated severe L5-S1 degeneration (modified Pfirrmann grade 6) with approximately 3-mm residual disc height, rendering conventional intradiscal access unsafe or impossible. A modified computed tomography-guided interlaminar trajectory passing briefly through the thecal sac was used to achieve intradiscal access. Two milliliters of ultra-high cell-count PRP was injected into the disc nucleus. During controlled needle withdrawal, small aliquots of PRP were deposited at the dural puncture sites to biologically reinforce the needle tract. Our case describes a technically feasible intradiscal PRP delivery route for end-stage L5-S1 disc collapse when all conventional access methods are obstructed. No postprocedure cerebrospinal fluid leak symptoms or neurological complications occurred, and early symptomatic improvement was reported. Further investigation is warranted to evaluate safety, reproducibility, and broader clinical applicability.
Enhanced sampling methods enable the mechanistic study of complex biophysical processes at atomistic resolution, addressing the key timescale limitations of brute-force molecular dynamics (MD) simulation. However, selecting appropriate collective variables (CVs) for enhanced sampling simulation to explore the relevant phase space of the system is challenging. In recent years machine learning (ML) algorithms have shown promise in the design of efficient CVs for enhanced sampling and improvements over traditional intuitive order parameters (OPs) in free energy surface (FES) exploration. However, the lack of interpretability and high cost of evaluation make it difficult to apply these ML-based CVs across diverse systems. Moreover, transferability of ML-guided CVs is a critical issue and can't be directly applied in different systems with similar mechanistic details without retraining. In this study, we introduce a surrogate model assisted enhanced sampling method using an elastic net (EN) regression model which expresses the relevance of different OPs as a linear combination locally at the transition state (TS) region. We demonstrate the successful applications of surrogate model-based TS-derived CV in exploring the landscapes of polymer collapse transition with varying lengths. This method shows improvements in achieving a faster free energy convergence within very short simulation time over other OPs tested in this study. Moreover, we demonstrate that this approach is transferable across different lengths of polymer systems without the requirement of large training data for each system. Overall, this study provides a general and interpretable approach to run enhanced sampling simulations with surrogate model-assisted TS-derived CV which can be extrapolated beyond their training system.
Mantle plumes are a fundamental component of the Earth's convective regime, but their long-term behaviour remains poorly understood. The Iceland plume, which is bisected by the Mid-Atlantic Ridge, presents an opportunity to constrain plume evolution. Here, we reconstruct its influence upon seafloor spreading by exploiting the geochemistry of basalts drilled south of Iceland during International Ocean Discovery Program (IODP) Expedition 395. Trace element and isotopic measurements, combined with contextual geophysical observations, demonstrate that plume influence waned after continental break-up at  ~ 55 Ma, collapsed rapidly at  ~ 38 Ma, and then was progressively re-established to the present day. Recovered  ~ 32 Ma basalt samples have rare earth element compositions equivalent to mid-Atlantic Ridge dredge samples located south of the present-day plume influence. These compositions can be modelled by passive upwelling and melting of depleted MORB mantle with a potential temperature of  ~ 1300 ∘C. In contrast, basalts recovered from younger (i.e. 0-14 Ma) sites show unequivocal evidence for plume influence. Together, these results imply dramatic changes in the extent of plume-ridge interaction across the North Atlantic region, providing key chemical constraints for geodynamic models of plume evolution and its imprint upon the geological record.
The lifetime of the J^{π}=2^{+} state in the self-conjugate ^{88}Ru nucleus has been determined in an experiment performed using rare-isotope beams provided by the new Facility for Rare Isotope Beams. This is the heaviest N=Z nucleus for which such a measurement has been achieved. ^{88}Ru was populated by both one-neutron knockout and charge-exchange reactions, and the lifetime of 14.3_{-3.4}^{+2.5}  ps was determined using the triple-foil plunger technique. The extracted electromagnetic transition strength shows that the quadrupole collectivity has dropped significantly compared with the highly deformed N=Z region around A∼80. These results are compared with state-of-the-art large-scale shell-model and discrete nonorthogonal shell-model calculations. The theoretical calculations indicate a moderate triaxial deformation and suggest that low-lying states in this nucleus are no longer dominated by strong many-particle many-hole excitations, unlike the lighter, highly deformed N=Z nuclei nearby.
Aconitine (AC) ranks among the leading causes of fatal herbal poisoning globally due to its narrow therapeutic window. Although its cardiovascular toxicity has been extensively studied, the precise molecular mechanisms underlying AC-induced central nervous system damage remain unclear. This study aimed to investigate the role of glycerol-3-phosphate dehydrogenase 1 (GPD1) in AC-induced neurotoxicity and to elucidate the underlying metabolic and molecular mechanisms. In a rat model of acute AC poisoning, significant neurological impairments, anxiety-like behaviors, and neuron-specific cell death were observed. Transcriptomic analyses revealed marked metabolic reprogramming following AC exposure, characterized by upregulation of GPD1 and suppression of the peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway. Mechanistically, AC disrupted GPD1/PPARγ signaling homeostasis, leading to pathological lipid droplet accumulation and mitochondrial dysfunction, as evidenced by loss of membrane potential and ATP depletion, ultimately resulting in neuronal apoptosis. Notably, targeted knockdown of Gpd1 using shRNA alleviated lipid accumulation, restored mitochondrial function, and significantly improved survival rates and neurological outcomes in poisoned rats. These findings identify the aconitine-GPD1-lipid/mitochondrial axis as a key mechanism underlying AC-induced neurotoxicity and suggest GPD1 as a potential therapeutic target.
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This study presents a detailed seismic fragility and collapse performance assessment of geometrically irregular continuous reinforced concrete rigid-frame (CRCR) bridges based on a representative bridge in Iran. A regular configuration was first established as the reference, after which a systematic set of bridge models was generated by varying the span-length ratio, pier-height ratio, and pier skew angle to investigate their individual and combined effects on seismic response. Detailed three-dimensional nonlinear finite element models were developed in OpenSees and analyzed under a comprehensive set of far-field and near-field earthquake ground motions. Seismic fragility curves were constructed based on pier drift demand corresponding to four damage states ranging from minor damage to collapse, defined by the attainment of the complete damage state. The results indicate that geometric irregularities significantly amplify seismic vulnerability, particularly at higher damage states. Across a range of span-length ratios, bridges with pronounced pier-height irregularity exhibit up to 50-60% higher probabilities of exceeding severe damage at the same intensity level compared to the regular configuration, while the median seismic intensity associated with collapse is reduced by approximately 55% in highly irregular cases. Among the investigated parameters, pier-height irregularity was identified as the most influential factor governing fragility and collapse behavior, followed by pier skewness, whereas span-length irregularity showed a comparatively smaller effect. The resulting fragility functions and collapse metrics provide quantitative insight into the seismic performance of CRCR bridges and support fragility-based assessment and performance-based seismic design in earthquake-prone regions.
With the rising incidence of psychological crisis among university students, the research focus has gradually shifted from a symptom-based to a protective-factor perspective, in which school connectedness is considered a potential protective factor. This study aimed to examine the network structure linking school connectedness and psychological crisis among university students, thereby providing empirical evidence for understanding the associations between these constructs. A total of 3,580 undergraduates from five universities in Henan Province, China, were surveyed using the School Connectedness Questionnaire and the Psychological Crisis Questionnaire. Network analysis was employed to reveal the associative patterns between the two constructs. (i) The network structure of school connectedness and psychological crisis was stable, with relatively strong internal connections within each cluster. In the cross-cluster network, a covariation was observed between "I can rely on my classmates when facing difficulties" (PS1) and "People around me hold prejudices against me" (CD4). (ii) Centrality analysis revealed that "Feeling lonely and helpless, as if on the verge of emotional collapse" (EBD8) and "Feeling incapable of doing anything well" (CD7) exhibited the highest expected influence. (iii) Bridge centrality results showed that "I can rely on my classmates when facing difficulties" (PS1) and "My classmates share happiness and sorrow with me" (PS3) had the strongest connections to the psychological crisis network, whereas "Feeling lonely and helpless, as if on the verge of emotional collapse" (EBD8) and "Having pessimistic or suicidal thoughts" (CD1) had the strongest connections to the school connectedness network. (iv) The global connectivity strength invariance test indicated that the global strength of the female network was significantly higher than that of the male network. This study employed psychological network analysis to systematically construct a school connectedness-psychological crisis network model among Chinese university students, revealing the complex associative structure between protective factors and crisis symptoms. Alleviating loneliness, correcting negative self-perceptions, and strengthening peer support may serve as three core targets for the prevention and intervention of psychological crisis among university students, potentially contributing to improved mental health and school adaptation.
Aspergillus niger (A. niger) is a pathogenic fungus responsible for severe and potentially fatal invasive pulmonary aspergillosis. For the first time, this study elucidates the antifungal mechanism of fishery-waste-derived chitosan (CTS) against A. niger using synchrotron-based X-ray microscopy integrated with conventional assays, enabling 3D visualization of the inactivation process. CTS (2.0 g L-1) exhibited potent efficacy, achieving a 6.05-log reduction within 6 h. Crucially, transmission X-ray microscopy revealed a transition from spherical spores to centrally collapsed structures, while cryo-soft X-ray microscopy showed pronounced organelle shrinkage and plasma-membrane detachment within 2 h, followed by severe structural rupture at 6 h, with cell volume decreasing from 34.9 to 6.5 μm3. Atomic force microscopy further demonstrated reduced cell height (4.55 to 1.90 nm) and increased surface adhesion (0.72 to 2.21 nN) and roughness (3.51 to 13.03 nm). Fluorescence imaging and potassium-leakage assays confirmed significant ion efflux that disrupted osmotic balance and cellular homeostasis. Collectively, the results indicate that CTS compromises cell integrity through electrostatic interactions between protonated amino groups and the fungal surface, leading to cytoplasmic leakage and irreversible intracellular collapse. This work identifies CTS as an effective carbohydrate-based antifungal agent and highlights the power of synchrotron imaging for resolving subcellular antimicrobial mechanisms under near-native conditions.
Kinetics of microbially induced carbonate precipitation (MICP) in hypersaline matrices are difficult to resolve because bulk assays collapse nucleation and growth into endpoint metrics, thereby masking interfacial heterogeneity. Here, we use an in situ microfluidic platform with time-lapse imaging and automated crystal tracking to probe how ionic strength reshapes bacteria-mineral biointerface interactions and thereby regulates CaCO3 precipitation by Staphylococcus succinus J3 across 0-100 g L-1 NaCl. Microfluidic observations reveal an ionic-strength-dependent nucleation-growth switch: low salinity is associated with the rapid appearance of abundant microcrystals and early growth saturation, whereas high salinity yields fewer observable nuclei but sustained post-nucleation growth, producing sparse yet much larger, calcite-dominated crystals. These trends were interpreted qualitatively using literature-based concepts from classical nucleation theory and double-layer interactions, suggesting that low ionic strength favors nucleation, whereas high ionic strength suppresses nucleation but promotes growth on existing surfaces. To test this mechanism, we introduced low salinity biogenic nuclei into hypersaline produced water, thereby increasing hardness removal from 91.32% to 98.67% and generating larger particles with improved separability. Overall, this work provides a biointerface-based mechanistic rationale for tuning MICP under high ionic strength and highlights microfluidics as a practical tool for resolving biomineralization kinetics in complex fluids.
Intervertebral disc degeneration (IDD), a leading cause of low back pain, involves progressive dysfunction of nucleus pulposus (NP) cells and extracellular matrix degradation. The pathological mechanisms underlying IDD remain complex and lack comprehensive elucidation. This study identifies the RNA-binding protein TDP43 as a central driver of IDD pathogenesis through analysis of human clinical specimens and rodent models. We demonstrate that TDP43 expression escalates proportionally with disc degeneration severity and aberrantly accumulates in the mitochondria of degenerative NP cells. This mitochondrial mislocalization triggers nuclear pore complex impairment, mitochondrial membrane potential collapse, and irreversible cellular senescence. Critically, TDP43 is secreted within mitochondrial-derived vesicles, which function as intercellular mediators that propagate pro-inflammatory cytokines and senescence phenotypes to neighboring NP cells. Both genetic and pharmacological inhibition of vesicular TDP43 effectively attenuated mitochondrial dysfunction and reduced cellular senescence and ultimately decelerated IDD progression in vivo and in vitro. Our findings establish TDP43-loaded mitochondrial-derived vesicles as novel mediators of intercellular pathology and nominate TDP43 as a therapeutic target for IDD intervention.
Seismic risk assessment is a probabilistic approach that evaluates the likelihood of earthquake occurrence, structural response, expected damage levels, economic losses, and potential casualties by incorporating the inherent uncertainties associated with seismic hazards and urban building characteristics. The primary objective of this study is to quantify and spatially characterize the distribution of damage states at the urban scale. Buildings were classified according to their structural system, age, and number of stories. The structures were initially modeled, analyzed, and designed in ETABS, and the beam and column section properties were extracted for each structural type. Finite element models were subsequently developed in OpenSees, and Incremental Dynamic Analysis, IDA, was performed to evaluate the seismic performance of building groups and large-scale seismic risk. The application of this approach to urban-scale seismic risk evaluation distinguishes this research from similar previous investigations. Given the considerable number of models, the extensive dataset, and the necessity for updating results under varying input conditions, a Bayesian Probabilistic Network was employed. In addition, GIS-based mapping was used to present the findings, including the exceedance probabilities of different damage states and the spatial distribution of collapse probability. The outcomes of this study identify areas that may exhibit relatively higher seismic vulnerability, emphasizing the potential need for targeted retrofitting strategies or, enhanced preparedness for post-earthquake emergency response and rescue operations.
We study the behavior of an institution that broadcasts reputational signals to facilitate trust in a population. Using an online marketplace as a motivating example, we develop a theoretical model in which buyers and sellers are matched on a platform to engage in transactions involving moral hazard: After receiving payment, sellers may either faithfully deliver goods or renege. Although buyers do not observe a seller's true strategy-good-faith or bad-faith-the platform broadcasts binary reputation signals about sellers. Buyers condition their purchase decisions on these signals, sellers adapt their strategies over time, and the resulting market composition determines the platform's commission revenue and players' welfare. Our analysis reveals a second layer of moral hazard at the institutional level. Because revenue depends on transaction volume, the platform has an incentive to inflate ratings, making good-faith and bad-faith sellers more difficult to distinguish. This distortion is self-limiting, however: Excessive inaccuracy erodes buyer trust and collapses trade. When signal accuracy is costless, the platform maximizes profit by perfectly identifying good sellers while tolerating some false positives. When accuracy is costly, the platform has an incentive to actively erode signal quality, even at a cost. If the platform can also set commission fees, higher fees are accompanied by stronger incentives to maintain accuracy. These results clarify when institutional incentives align with, or diverge from, the welfare of buyers and good-faith sellers who rely on reputational information.
eIF4G2 (DAP5/NAT1) is a non-canonical translation initiation factor, but its role in homeostasis is unclear. Using inducible Eif4g2 knockout mice and intestinal organoids, we show that eIF4G2 loss collapses Lgr5+ intestinal stem cell (ISC) and secretory maturation programs while preserving villus architecture. Transcriptomic and single-nucleus multiome analyses reveal a durable fetal-like/regenerative state with YAP-TEAD activation and regenerative absorptive cells. Ribosome profiling identifies selective translation-efficiency loss among chromatin regulators, especially the KAT3 coactivators CREBBP and EP300, resulting in reduced KAT3 abundance and global histone acetylation; chemical KAT3 inhibition phenocopies this state. CUT&Tag and assay for transposase-accessible chromatin sequencing (ATAC-seq) demonstrate that reduced eIF4G2-KAT3 output drives locus-selective enhancer remodeling, with loss of adult ISC/Wnt-Notch elements and activation of TEAD-enriched fetal loci, without inflammatory or integrated stress response programs driving the transition. Fetal intestinal spheroids remain viable despite similar biochemical defects, highlighting a stage-specific requirement for translational buffering in maintaining adult identity.
Polyimide (PI) aerogels represent a class of organic aerogels endowed with exceptional integrated mechanical and thermal properties. Despite their substantial promise as structural components for mechanical-thermal-coupled protective applications, PI aerogels suffer from a stiffness mismatch with other rigid skins when integrated into structural assemblies. This study fabricates density-graded PI aerogels with positive gradient (PG) and negative gradient (NG) configurations. The mechanical and thermal properties of the aerogels under quasi-static compression (0.001-1 s-1) and low-velocity impact (100 s-1) were investigated. Results demonstrate that gradient PI aerogels exhibit strain-rate insensitivity, which is in sharp contrast to the pronounced strain-rate dependence of homogeneous PI aerogels. PG configurations achieve a superior energy absorption performance over NG counterparts via ordered layer-by-layer collapse with the volumetric energy absorption up to 3.46 MJ·m-3 and gravimetric energy absorption up to 19.80 J·g-1. In addition, the high-density regions of gradient PI aerogels retain excellent thermal insulation performance after impact. This study elucidates the critical role of density gradient direction and layer configuration in regulating the mechanical and thermal performances of PI aerogels. The findings provide mechanistic insights for the rational design of gradient PI aerogel-based protective structures requiring balanced lightweight, energy absorption, and thermal insulation under static and dynamic loading conditions.
Anaerobic digestion (AD) often suffers operation failure from ammonia inhibition and volatile fatty acids (VFAs) accumulation under high organic loading rates (OLRs). To overcome these limitations, this study employed granular activated carbon coupled with riboflavin (RFGAC) by stimulating direct interspecies electron transfer (DIET). A semi-continuous AD experiment was conducted for 145 days with OLRs ranging from 2.25 to 11.25 kg COD/(m3·d). The results showed that the RFGAC group achieved the highest methane content of 78%, and maintained a COD removal rate above 95%, outperforming the GAC group and the control. At an OLR of 6.75 kg COD/(m3·d), the control collapsed due to severe acidification when the pH dropped lower than 6.5, while the RFGAC group stably operated with effluent COD of 2200-5300 mg/L and seldom VFAs accumulation. Microbial community analysis revealed that RFGAC selectively shifted microbial community composition especially at high OLR, promoting Methanosarcina to form a synergistic consortium. The Pearson correlation analysis of digestion performance and metagenome revealed that Methanosarcina had a stronger correlation with methanogenesis than Methanothrix, which was enriched in the presence of GAC alone. Metabolic pathway analysis confirmed key DIET-related functional genes, hdrA2 and methyl transfer-associated mtrH, were respectively upregulated by 7-fold and 5-fold. This study offers a viable strategy to improve chicken manure AD, and provides deep mechanistic insights on RFGAC modulation of microbial community succession and functional gene expression.
Pleurotus florida (P. florida) mushrooms are widely valued for their nutritional, medicinal and bioactive properties. Selenium (Se) biofortification of edible mushrooms offers a sustainable strategy to mitigate global micronutrient deficiencies, however the narrow margin between the nutritional benefits and toxicity of Se necessitates precise physiological optimization. This study presents a comprehensive in vitro evaluation of Se-induced growth modulation, oxidative stress, ultrastructural responses and uptake dynamics in P. florida cultivated under sodium selenite concentrations. Mycelial growth on PDA exhibited a highly reproducible biphasic response across three independent experiments. Low Se concentrations (10-15 mg L⁻¹) significantly enhanced radial growth and biomass accumulation. Elevated concentrations (≥40 mg L⁻¹) caused sharp declines in growth and biomass, accompanied by abnormal colony morphology and reduced mycelial density. Lipid peroxidation analysis revealed a strong dose-dependent increase in oxidative membrane damage, with Se concentration explaining nearly 90% of the observed variation, indicating a shift from antioxidant support at low doses to pro-oxidant toxicity at higher levels. Scanning electron microscopy (SEM) confirmed enhanced hyphal branching and structural organization at optimal Se concentrations, while severe ultrastructural damage including hyphal collapse and filament breakage was evident under high Se stress. Scanning Electron Microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDS) analysis showed Se-induced alterations in mycelial surface composition and inductively coupled plasma mass spectrometry (ICP-MS) based mass-balance analysis demonstrated high Se removal efficiency (>80%), with excessive biomass-normalized accumulation at high concentrations reflecting stress rather than efficient biofortification. Collectively, this study defines a narrow Se tolerance window in P. florida and identifies 15 mg L⁻¹ as the optimal concentration for safe and effective Se biofortification.