Search Results (1,072)

Acellular bone matrix, with its natural extracellular matrix components, has been considered a potential alternative platform for bone grafting. Our study focused on fabricating acellular bovine bone matrix (ABBM) and evaluating its in vitro characteristics and in vivo effect on bone repair. The bovine cancellous bone was subjected to ABBM preparation, which included partial demineralization and decellularization processing. The effects of the ABBM on human bone marrow-derived stem cells (hBMSCs) were evaluated, including viability, migration, attachment, and proliferation. A rabbit bone defect model was implanted with ABBM and histologically assessed for bone healing. The acellular properties were determined by the absence of nuclear material and the accepted minimum residual DNA content. An in vitro study indicated the ABBM’s positive effect on the migration of hBMSCs. ABBM was also demonstrated to support hBMSC attachment and proliferation. In vivo testing was performed in rabbits with a cranial bone defect, which showed complete bone healing after 8 weeks of grafting with ABBM. Overall, the fabricated ABBM demonstrated in vitro and in vivo biocompatibility and effective support for bone healing in vivo, and therefore represents a potential xenogeneic biomaterial for bone tissue repair. Full article

This study investigates the influence of cold-working deformation on the electromotive force (EMF) calibration characteristics, hysteresis behavior, and long-term stability of the Type-K mineral-insulated metal-sheathed (MIMS) thermocouples used in Combination Fixed In-Core Detector Assemblies for pressurized water reactor nuclear power plants. Reduction ratios of 12%, 28%, and 38% were investigated, and samples were subjected to heating–cooling calibration and in situ aging tests. The results show that increased cold-working deformation leads to greater negative EMF deviation and larger heating–cooling hysteresis, mainly affected by the degradation of the positive KP thermoelement. Cold-working lowers the atomic diffusion activation energy and accelerates element migration, resulting in pronounced EMF drift during isothermal aging at 350 °C for 720 h. After aging below the order–disorder transition temperature, stable ordered structures form in the thermoelement alloys and hysteresis is significantly reduced. However, within the range investigated in this study, deformation above 28% imparts irreversible effects. The EMFs of 28% and 38% deformed samples remained lower than that of the undeformed state even after isothermal aging at 700 °C for 500 h. These findings reveal that excessive cold-working deformation severely impairs the measurement accuracy and long-term stability of the thermocouples, highlighting the necessity of the strict control of drawing deformation to ensure the reliability of nuclear-grade thermocouples under both normal and abnormal reactor operating conditions. Full article

Background: Routine use of the chorioallantoic membrane (CAM) tumor model in nuclear imaging studies is hampered by small tumors, embryonic movements and laborious volume-restricted intravenous tracer/drug administration. We sought a workaround by using fast-growing tumors, high-resolution autoradiography and non-intravenous tracer administration. Methods: Dekalb White chicken eggs were grafted with C3H mammary carcinoma fragments or MOC2 oral squamous cell carcinoma fragments from donor mice. The tumor uptake of ¹⁸F-fluorodeoxyglucose (FDG) following in-yolk-sac injection, dripping after CAM scoring or allantoic cavity injection was evaluated using positron emission tomography (PET) and autoradiography. Using in-yolk-sac injection, eggs were administered different tracer mixtures, namely (1) pimonidazole (hypoxia-marker), FDG and ¹⁴C-2-deoxyglucose (¹⁴C-2DG), (2) pimonidazole, FDG and ¹⁴C-acetate or (3) pimonidazole, the hypoxia-selective tracer ¹⁸F-fluoroazomycin-arabinoside (FAZA) and ¹⁴C-2DG. For comparison, tumor-bearing mice were administered FDG/¹⁴C-acetate/pimonidazole. Gross tumor uptake was evaluated using PET. Tumor cryosections were analyzed using dual-tracer autoradiography. Complementary autoradiograms were co-registered, covered by a square grid (0.5 × 0.5 mm). Pearson correlation coefficients (PCC) were calculated from scatterplots. Results: C3H tumors reached a mean weight (with 95% confidence interval) of 0.32 g (0.28–0.37 g), while for MOC2, it was 0.19 g (0.09–0.29 g). In-yolk-sac tracer injection was simple and effective, producing high tracer uptake and contrast 3 h post-administration. Spatial tracer overlap (PCC) was: FDG vs. ¹⁴C-2DG, 0.95–0.97; FAZA vs. ¹⁴C-2DG, 0.71–0.79 and FDG vs. ¹⁴C-acetate, 0.26–0.84 (0.15–0.76 in mice). Pimonidazole revealed tumor hypoxia. Conclusions: Direct-grafting from donor mice generated larger tumors than previously reported. In-yolk-sac tracer administration was practical and allowed larger injected volumes. Autoradiography revealed that: (1) FDG and ¹⁴C-2DG can be used interchangeably, (2) ¹⁴C-2DG was elevated in FAZA-positive areas, suggesting that in some tumors FDG-PET may provide information on the intratumoral distribution of hypoxic areas, and (3) FDG and ¹⁴C-acetate showed variable overlap. We conclude that in-yolk-sac tracer injection and autoradiography simplify and optimize CAM-based nuclear imaging research. Full article

Russian state-sponsored disinformation has been described in policy and the operational literature, but it is less often formalized in game-theoretic terms. Here, a two-layered formal model is developed showing how adversarial perturbation of a communication channel can collapse cross-group felt understanding—the third-order intentional state/belief structure, established empirically by Livingstone, in which one group believes its perspectives are recognized and accepted as valid by another. The Analytical Model is a static Bayesian signaling game with binary types and a noisy channel parameterized by perturbation rate π. The Analytical Model shows that when recognition benefits exceed signaling costs, there exists a perturbation threshold π* = 1 − c_R/(u_R · p) above which mutual misrecognition becomes the unique Perfect Bayesian Equilibrium outcome. The Computational Model embeds this logic in an agent-based simulation on a homophilic stochastic block model and scale-free networks with continuous recognition capacity. Four substantive findings emerge: the closed-form analytical threshold from the Analytical Model predicts the boundary of collapse in the dynamic networked simulation; high network homophily protects cooperative behavior below π* but provides no rescue above it; bridge seeding—the placement of recognition-capable agents at structurally central cross-group positions—is the most effective of three policy interventions tested, rescuing cooperation even above π*; and uniform adversarial volume is approximately as damaging as strategically targeted adversarial precision across both small dense and large scale-free topologies, qualifying the operational claim that targeted disinformation should strictly outperform volume-based approaches. The model is illustrated with the German Atomausstieg (nuclear phase-out) case, and implications for clinical psychology, public policy, and intergroup recognition under psychological warfare are discussed. Full article

Oxidative stress and inflammation are central environmental contributors to skin aging, accelerating extracellular matrix (ECM) breakdown and loss of dermal structure. Although Nypa fruticans is recognized for its antioxidant properties, the constituents responsible for these effects remain undefined. To address this, we screened five major polyphenols—protocatechuic acid (PA), hydroxybenzoic acid (HA), procyanidin B1 (PB), catechin (CA), and epicatechin (EC)—for protective activity in two inflammatory skin cell models: human dermal fibroblasts (HDFs) stimulated with tumor necrosis factor-α (TNF-α), and human epidermal keratinocytes (HEKs) co-stimulated with TNF-α and interferon-γ (IFN-γ). PB emerged as the most consistently active compound. In fibroblasts, it suppressed intracellular reactive oxygen species, limited matrix metalloproteinase-1 (MMP-1) release, and restored pro-collagen I α1 output. In keratinocytes, it reduced both pro-inflammatory cytokines—interleukin (IL)-6, IL-8, and IL-1β and inflammatory mediators, including prostaglandin E₂ (PGE₂), cyclooxygenase-2 (COX-2), and nitric oxide (NO). At the transcriptional level, PB shifted the ECM balance by lowering MMP expression while elevating collagen- and hyaluronan-associated genes. Collectively, these results position PB as a principal driver of the protective activity of Nypa fruticans (N. fruticans) leaves under inflammatory conditions. Mechanistically, PB suppressed nuclear factor kappa B (NF-κB) activation and promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation in keratinocytes, supporting its dual anti-inflammatory and antioxidant activities. Full article

Isofenphos-methyl (IFP), a highly toxic and persistent organophosphate pesticide (OP), is widely used for soil pest control in crops but poses severe risks to ecological safety and human health because of its environmental accumulation and bioaccumulation. Herein, a sensitive and specific indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) was developed for rapid IFP detection in vegetables. A novel IFP hapten was rationally designed and synthesized via computer-aided molecular simulation, and its structure was validated by liquid chromatography–tandem mass spectrometry (LC–MS/MS) and nuclear magnetic resonance (NMR). High-specificity anti-IFP monoclonal antibodies (mAbs) with strong anti-matrix interference were prepared for the first time using a matrix effect-enhanced screening strategy. The optimized ic-ELISA showed high sensitivity, with an IC₅₀ of 6.087 ng/mL and a detection range of 1.165–30.490 ng/mL, and no cross-reactivity with other common OPs. Spiked recovery experiments in celery and chili pepper matrices yielded recoveries of 81.87–97.95% (RSD < 5.44%), with highly consistent LC–MS/MS results. The method exhibited a weak positive matrix effect in vegetable matrices, eliminating complex pretreatment and enabling rapid onsite detection. Full article

Large-scale asymmetric doubly curved thick shells made of high-strength steel are key components in deep-sea and nuclear pressure vessels. Integral pressing is an important manufacturing method for such components, but it still faces two major challenges: excessive clamping force and poor springback predictability. To address these issues, this study conducts a combined experimental and numerical investigation on a 16 mm thick Q890 high-strength steel plate. First, the through-thickness plastic gradient and cyclic stress–strain response of the material were characterized, and a mixed hardening model incorporating through-thickness gradient plasticity was established. To suppress the lateral force induced by the asymmetric geometry, a blank positioning strategy was proposed, reducing the lateral force to below 2 t (Reduced by 65%). More critically, a striking phenomenon is revealed: during the final 1 mm of the clamping stroke, the forming force surges abruptly from approximately 680 t to 5090 t. Detailed analysis identifies the root cause as the synergistic effects of a sharp increase in contact area, a drastic rise in frictional resistance, and the onset of localized upsetting in regions already in contact with the die. To suppress the load surge while maintaining forming accuracy, a normal-direction over-compensation strategy was proposed. By deliberately increasing the normal compensation, the blank retains a bending-dominant deformation mode at the target clamping position, thereby avoiding the critical contact expansion, frictional buildup, and localized upsetting that trigger the force surge. Through iterative simulations, the optimal die surface is determined, achieving a forming force below 1000 t with a simulated shape deviation within 0.96 mm. Experimental validation using a purpose-built die on a 1000 t press successfully produces the shell with a maximum profile deviation of 1.67 mm, meeting high-accuracy requirements. This work establishes a new paradigm for low-load, high-accuracy forming of thick high-strength steel shells by actively managing contact evolution and deformation mode via normal-direction over-compensation, offering a practical pathway to one-shot tryout success for critical pressure hulls. Full article

Background/Objectives: DNA-targeting small molecules that induce replication stress represent a promising strategy in anticancer drug development. 1,8-Naphthalimide (NI) derivatives are well-established DNA-intercalating agents, and heterocyclic annulation offers a rational approach to enhancing their potency and tumor selectivity. Here, we report the synthesis and biological evaluation of a novel series of benzofuran-containing naphthalimide derivatives, with particular focus on the lead dinitro-substituted compound 5d. Methods: Cytotoxic activity was assessed using the MTT assay in A549 (p53 wild-type), H1299 (p53-null), and MRC-5 cells. Long-term antiproliferative effects were evaluated by clonogenic survival assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Replication stress and DNA damage were quantified by EdU incorporation and γH2AX immunofluorescence, respectively. Apoptosis was assessed by Annexin V/PI staining and caspase-3/7 activation assay. p53 nuclear accumulation and autophagy induction were evaluated by immunofluorescence and Western blot, using LC3 as an autophagic marker. Results: All compounds exhibited cytotoxic activity in the nanomolar range, with 5d emerging as the most potent and selective. Clonogenic survival was significantly reduced, indicating durable suppression of proliferative capacity. Treatment with 5d induced G₁ arrest in A549 cells and the accumulation of H1299 cells in G₂/M, consistent with p53-dependent and p53-independent checkpoint activation, respectively. EdU incorporation was markedly reduced, while γH2AX intensity increased, collectively supporting a replication stress-driven mechanism of DNA damage. Apoptosis was confirmed by increased Annexin V-positive populations and caspase-3/7 activation. LC3 puncta formation and LC3-I/LC3-II conversion were increased, indicating LC3 processing and autophagosome accumulation consistent with the activation of autophagy-related processes. Conclusions: 5d induces a cellular phenotype consistent with replication stress, including reduced EdU incorporation, γH2AX accumulation, cell cycle arrest, and apoptotic cell death in a p53 status-dependent manner. These findings establish benzofuran-annulated naphthalimides as a promising scaffold for the development of anticancer agents that exploit replication stress vulnerabilities in tumor cells. Full article

The NaI(TI) detector is highly favored in gamma radiation detection and widely applied in fields such as environmental radiation monitoring, nuclear medicine, and laboratory gamma-ray spectroscopy. Its detection performance determines the results of quantitative gamma-ray detection, making it a crucial indicator in detector design and development. This study employs the Monte Carlo method and utilizes TopMC 1.0 software to establish a NaI(TI) detector model. First, the effects of crystal size, ray energy, cladding thickness, and distance on the detector’s detection efficiency were investigated. Subsequently, the energy resolution and peak-to-total ratio of the detector were simulated and calculated, with comparisons made to experimental values. The results indicate that all three detection efficiencies of the NaI(TI) detector are positively correlated with crystal size and exhibit an initial increase followed by a decrease with rising gamma-ray energy. Both the absolute detection efficiency and full-energy peak detection efficiency first increase and then decrease with increasing cladding thickness, while showing a negative correlation with detection distance. The intrinsic detection efficiency is almost unaffected by cladding thickness and initially rises before declining with increasing detection distance. The simulated values of energy resolution closely match experimental values, improving with higher gamma-ray energy. The deviation between simulated and experimental values for different source peak-to-total ratios remains within 6.25%, verifying the model’s reliability and the accuracy of simulation data. These findings provide valuable references and guidance for optimizing detection performance, conducting source-free efficiency calibration, and structural design of NaI(TI) detectors. Full article

Background: Nuclear medicine healthcare professionals (NMHP) sustain chronic occupational exposure to iodine-131 (I-131), conferring an elevated risk of radiation-induced solid thyroid cancer. Established radiobiological prediction tools derive risk coefficients from atomic bomb survivor data but are not configured for rapid individualized risk assessment in occupational exposure settings. This study examined whether machine learning algorithms can serve as high-precision computational surrogates for excess relative risk estimation in NMHP. Aim: The study aimed to (i) develop and validate three machine learning algorithms for predicting the excess relative risk per unit absorbed dose for radiation-induced solid thyroid cancer (ERR/Gy.RST), (ii) characterize relationships between dosimetric and demographic features and predicted risk, and (iii) identify the optimal algorithm for deployment in occupational health surveillance. Methods: A dataset of 4657 observations was constructed from Life Span Study-derived ERR/Gy parameters, adapted to occupational low-dose conditions, using a dose-and-dose-rate effectiveness factor of 2.0, per ICRP Publication 103. Five features (gender, age at exposure, current age, distance from the I-131 source, and cumulative absorbed dose in the thyroid) were used to train a decision tree regressor (dtcr), a random forest regressor (rfr), and a multilayer perceptron (MLP) neural network algorithm. Results: Cumulative absorbed dose in the thyroid correlated positively with ERR/Gy.RST (r = 0.63, p < 0.01), while radiation source distance demonstrated a strong inverse association (r = −0.38, p < 0.01). The MLP algorithm achieved R² score = 0.999, MSE = 0.002, and MAE = 0.010, substantially outperforming the rfr (R² score = 0.700, MSE = 0.410, MAE = 0.295) and the dtcr (R² score = 0.510, MSE = 0.654, MAE = 0.289). Conclusions: The MLP algorithm provides a high-fidelity surrogate for established ERR/Gy.RST projection tools in the NMHP context, enabling computationally efficient, feature-integrated occupational radiation-induced thyroid cancer risk quantification. These findings suggest that machine learning-based surrogate modeling is a practical, scalable complement for occupational health practitioners and radiation protection officers to support individualized surveillance of radiation-induced thyroid cancer risk in nuclear medicine departments. Full article

Background: Synaptic plasticity in neurodegenerative disorders (NDs), cognitive impairment, and mental health conditions is regulated by brain-derived neurotrophic factor (BDNF). Even healthy individuals have different levels, which are affected by complex epigenetic, inflammatory, and metabolic regulation. BDNF expression changes are associated with both typical and abnormal aging, as well as mental health conditions. These changes affect brain areas that are crucial for memory, such as the hippocampus and the parahippocampal cortex. Neurotrophins (NTs), including nerve growth factor (NGF) and BDNF, are essential for neuronal differentiation via tropomyosin receptor kinase B (TrkB) and the p75 neurotrophin receptor (p75NTR). Dysregulated NTs signaling contributes to synaptic dysfunction and neuroinflammation. Objective: This systematic review synthesizes preclinical evidence of the potential of naturally derived compounds to modulate NTs for neuroprotection and their incorporation into novel foods. Methodology: A review of major databases found studies that examined the impact of dietary polyphenols and other bioactive substances on NT signaling oxidative stress, inflammation, and neuronal plasticity. Results: Compounds such as epigallocatechin gallate, resveratrol, curcumin, quercetin, and flavanols, can positively impact NTs, reducing reactive oxygen species/reactive nitrogen species, enhancing cell survival, and increasing the expression of trophic factors such as nuclear factor erythroid 2-related factor 2 (Nrf2), NGF, and vascular endothelial growth factor in neural stem cells. However, their bioavailability, optimal dosage, and dietary interactions require further research. Conclusions: The consumption of BDNF-promoting foods can potentially stimulate BDNF synthesis, support optimal neurotransmission, and fortify neural plasticity. Evidence supports a polyphenol-rich diet for preventing NDs and promoting brain health. Observational studies consistently support the protective effects of polyphenols on brain health through their impact on the gut–brain axis. Full article

Although calcium overload dysregulation has been implicated in cellular senescence, its role in ionizing radiation (IR)-induced osteocyte senescence, a key pathogenic mechanism underlying radiotherapy-associated bone injury, remains poorly explored. This study investigated whether IR-induced osteocyte senescence is mediated through the Ca²⁺-NFATc1-ATF3 pathway. Exposure to 2 Gy X-rays impaired osteocyte homeostasis, manifesting as reduced viability and proliferation, G2/M phase arrest, and dendritic retraction. IR also induced persistent DNA damage response and senescence-associated phenotypes, including increased γ-H2AX foci, SA-β-gal activity, condensed punctate DAPI-dense nuclear foci, p16/p21 expression, and pro-inflammatory SASP profile. Intracellular Ca²⁺ levels surged within 6 h post-irradiation and remained elevated for at least 72 h in a dose-dependent manner. Pharmacological Ca²⁺ modulation with BAPTA-AM or verapamil attenuated IR-induced intracellular Ca²⁺ accumulation, G2/M arrest, SA-β-gal positivity, p21/p53 upregulation, and SASP secretion. Conditioned medium from irradiated osteocytes inhibited BMSC-mediated osteogenesis and enhanced BMM-driven osteoclastogenesis, whereas Ca²⁺ modulation partially mitigated these paracrine effects. Mechanistically, IR promoted NFATc1 nuclear translocation and ATF3 upregulation. Collectively, these findings support an important role for pathological intracellular Ca²⁺ elevation in IR-induced osteocyte senescence and suggest that the Ca²⁺-NFATc1-ATF3 axis may represent a potential therapeutic target for mitigating radiation-associated disruption of bone homeostasis. Full article

Endocrine therapy is an effective and common treatment strategy for estrogen receptor (ER)-positive breast cancers. However, the development of endocrine resistance, through genetic mutations and epigenetic alterations, in about 40% of treated patients remains a significant therapeutic challenge. Liver X receptors (LXRs) are nuclear receptors that regulate lipid metabolism and cholesterol homeostasis and have been implicated in metabolic reprogramming in breast cancers and other malignancies. We previously identified a novel LXR ligand GAC0001E5 (1E5), with potent antiproliferative activity across breast cancer subtypes. Here, we investigate its mechanisms of action in responsive (MCF-7) and endocrine-resistant (MCF-7-TamR) ER-positive breast cancer cells. Treatment with 1E5 resulted in the downregulation of LXR and its target genes, and significantly reduced ERα expression and the expression of ER-responsive genes. Aberrant expression of androgen receptor (AR) and human epidermal growth factor receptor 2 (HER2), both implicated in endocrine resistance, were downregulated following 1E5 treatment. siRNA-mediated knockdown of LXR expression only partially recapitulated the actions of 1E5, suggesting the involvement of LXR-dependent and independent mechanisms. Collectively, these findings reveal potential crosstalk between LXR and the genetic and epigenetic regulation of pathways involved in endocrine response and alternative signaling mechanisms, highlighting potential targets in endocrine-resistant breast cancer. Full article

Deep tight sandstone reservoirs are characterized by strong microscopic pore structure heterogeneity and commonly exhibit a high-porosity, low-permeability profile, posing significant challenges for effective reservoir evaluation and “sweet spot” prediction. The microscopic pore structure of 209 tight sandstone samples from the deeply buried Huagang Formation in the Xihu Depression, East China Sea Basin, was systematically characterized by integrating multiple analytical techniques, including casting thin sections, scanning electron microscopy (SEM), X-ray diffraction (XRD), nuclear magnetic resonance (NMR), and high-pressure mercury injection (HPMI). The results indicate that the reservoir space is dominated by mesopores (55.48%) and transition pores (32.39%), with macropores (2.09%) and micropores (10.04%) being relatively underdeveloped. A significant vertical heterogeneity in reservoir quality is observed. The H4 member exhibits superior properties, characterized by a higher average movable fluid saturation (averaging 46%) and better pore connectivity. In contrast, the H5 member is more compact, with a notably higher proportion of bound fluid (averaging 47%). The differences in reservoir quality are controlled by a sedimentary–diagenetic coupling mechanism. High-energy, coarse-grained facies underwent a constructive pathway involving chlorite coating protection and dissolution enhancement, forming high-quality pore networks. In contrast, low-energy, fine-grained facies experienced a destructive pathway dominated by intense compaction and cementation, leading to the deterioration of pore structure. The petrophysical properties of the deep reservoirs are primarily governed by the three-dimensional connectivity and spatial distribution of effective “pore-throat assemblages” composed of dominant throats. Accordingly, a “binary” pore structure development pattern is established for the deep tight sandstone reservoirs in the study area. This pattern posits that the reservoir space is heterogeneously composed of a minority of connected “effective percolation assemblages” and a majority of isolated “ineffective assemblages”. Full article

The transition of thermal power systems toward lower-carbon electricity raises a critical strategic question: whether to rely on cross-border electricity imports or reactivate domestic nuclear capacity under supply constraints. This study examines the trade-offs between these alternatives within a sustainable finance framework. A contingent-claim model is developed in which a life insurer provides long-term financing to a biomass-energy supplier, a thermal power plant, and a nuclear power plant operating under carbon-pricing regulation. The framework links electricity-market decisions with financial risk valuation, allowing the joint effects of biomass utilization, carbon regulation, electricity imports, and nuclear-security risks to be evaluated. The results show that biomass integration and tighter carbon regulation reduce short-term profitability in thermal generation but support long-run decarbonization. Cross-border electricity imports improve system flexibility and reduce operational volatility, strengthening the financial position of thermal producers. In contrast, nuclear-security disruptions significantly increase default risk for nuclear assets, reflecting their exposure to operational and regulatory uncertainty. By integrating energy-transition strategies with contingent-claim valuation, the analysis highlights the role of financial intermediation in shaping investment incentives and risk allocation in the electricity sector. The findings suggest that coordinated policies combining market integration, low-carbon transition strategies, and stable financing mechanisms can enhance system resilience. Full article