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Lytic induction therapy was devised to selectively combat malignancies associated with Epstein–Barr virus (EBV) by triggering viral reactivation from latency. At present, the major challenges of lytic induction therapy are to maximize reactivating efficiencies and meanwhile minimize infectious virion production. C210, a novel curcumin derivative with potent Hsp90 inhibitory activity, was explored for EBV-reactivating and virion-producing effects in EBV-positive nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC) cell lines. And the molecular mechanisms underlying these effects were determined. Follow C210 treatment, EBV lytic RNAs and proteins were upregulated, but infectious virions were not produced. Knockdown of heat shock protein 90 (Hsp90) induced expression of lytic RNAs and proteins, and diminished C210-driven EBV lytic induction. Pretreatment with an X box binding protein 1 (XBP1) inhibitor reduced C210-induced EBV lytic RNA. Furthermore, we demonstrated that C210 inhibited the binding of Hsp90 with its clients, signal transducer and activator of transcription 3 (STAT3) and xeroderma pigmentosum group B-complementing protein (XPB), which subsequently promoted their proteasomal degradation. Degradation of STAT3 by C210 enhanced the EBV-reactivating and anticancer capacity of suberoylanilide hydroxamic acid (SAHA). Depletion of XPB blocked SAHA-induced expression of late viral genes and production of infectious virions. These results elucidate a novel Hsp90 inhibitor targeting EBV lytic phase and extend the research on lytic induction strategy, which may offer reference value in the treatment of EBV-positive malignancies. [ABSTRACT FROM AUTHOR]

This research investigated spatial inequalities in transportation accessibility to social infrastructures (SIs) in South Korea, using a multi-dimensional methodological approach, including descriptive/bivariate analysis, explanatory factor analysis (EFA), K-Mean cluster analysis, and multinomial logit model (MNL). Our study confirmed pronounced spatial disparities in transportation accessibility to SIs, highlighting significantly lower access in rural and remote regions compared to urban centers and densely populated areas, consistent with existing literature. Building on prior findings, several additional findings were identified. First, we uncovered significant positive correlations among accessibility to different types of SIs in four critical categories: green and recreation spaces, health and aged care facilities, educational institutions, and justice and emergency services, revealing prevalent spatial inequality patterns. Second, we identified three distinct accessibility clusters (High, Middle, and Low) across the critical SI categories. Specifically, residents within the High cluster benefited from the closest average network distances to all SIs, while those in the Low cluster faced significant accessibility burdens (e.g., 22.9 km for welfare facilities, 20.1 km for hospitals, and 19.2 km for elderly care facilities). Third, MNL identified factors such as population density and housing prices as pivotal in spatial stratification of accessibility. Specifically, areas with lower SI accessibility tended to have a higher proportion of elderly residents. Also, decreased accessibility correlated with diminished traffic volumes across all transportation modes, particularly public transportation. This research contributes to enhancing our understanding of spatial inequalities in transportation accessibility to SIs and offers insights crucial for transportation and urban planning. [ABSTRACT FROM AUTHOR]

The present study investigates the effect of an oxidized nanocrystalline diamond (O-NCD) coating functionalized with bone morphogenetic protein 7 (BMP-7) on human osteoblast maturation and extracellular matrix mineralization in vitro and on new bone formation in vivo. The chemical structure and the morphology of the NCD coating and the adhesion, thickness and morphology of the superimposed BMP-7 layer have also been assessed. The material analysis proved synthesis of a conformal diamond coating with a fine nanostructured morphology on the Ti6Al4V samples. The homogeneous nanostructured layer of BMP-7 on the NCD coating created by a physisorption method was confirmed by AFM. The osteogenic maturation of hFOB 1.19 cells in vitro was only slightly enhanced by the O-NCD coating alone without any increase in the mineralization of the matrix. Functionalization of the coating with BMP-7 resulted in more pronounced cell osteogenic maturation and increased extracellular matrix mineralization. Similar results were obtained in vivo from micro-CT and histological analyses of rabbit distal femurs with screws implanted for 4 or 12 weeks. While the O-NCD-coated implants alone promoted greater thickness of newly-formed bone in direct contact with the implant surface than the bare material, a further increase was induced by BMP-7. It can be therefore concluded that O-NCD coating functionalized with BMP-7 is a promising surface modification of metallic bone implants in order to improve their osseointegration. [ABSTRACT FROM AUTHOR]

To identify risk factors and develop a simple model to predict early prognosis of acute paraquat (PQ) poisoning patients, we performed a retrospective cohort study of acute PQ poisoning patients (n = 1199). Patients (n = 913) with PQ poisoning from 2011 to 2018 were randomly divided into training (n = 609) and test (n = 304) samples. Another two independent cohorts were used as validation samples for a different time (n = 207) and site (n = 79). Risk factors were identified using a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated using a latent class analysis. The prediction score was developed based on the training sample and was evaluated using the testing and validation samples. Eight factors, including age, ingestion volume, creatine kinase-MB [CK-MB], platelet [PLT], white blood cell [WBC], neutrophil counts [N], gamma-glutamyl transferase [GGT], and serum creatinine [Cr] were identified as independent risk indicators of in-hospital death events. The risk model had C statistics of 0.895 (95% CI 0.855–0.928), 0.891 (95% CI 0.848–0.932), and 0.829 (95% CI 0.455–1.000), and predictive ranges of 4.6–98.2%, 2.3–94.9%, and 0–12.5% for the test, validation_time, and validation_site samples, respectively. In the training sample, the risk model classified 18.4%, 59.9%, and 21.7% of patients into the high-, average-, and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. We developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This risk scoring system could be helpful for identifying high-risk patients and reducing mortality due to PQ poisoning. [ABSTRACT FROM AUTHOR]

The purpose of the present work was to study how chemical reactions and the electronic structure of atoms are affected by confinement at the sub-nanometer scale. To reach this goal, we studied the H atom in talc, a layered clay mineral. Talc is a highly 2D-confining material with the width of its interlayer space close to angstrom. We investigated talc with a particle accelerator-based spectroscopic method that uses elementary particles. This technique generates an exotic atom, muonium (Mu), which can be considered as an isotope of the H atom. Moreover, the technique allows us to probe a single atom (H atom) at any time and explore the effects of the layered clay on a single ion (proton) or atom. The cation/electron recombination happens in two time windows: one faster than a nanosecond and the other one at longer than microseconds. This result suggests that two types of electron transfer processes take place in these clay minerals. Calculations demonstrated that the interlayer space acts as a catalytic surface and is the primary location of cation/electron recombination in talc. Moreover, the studies of the temperature dependence of Mu decay rates, due to the formation of the surrogate of H2, is suggestive of an "H2" formation reaction that is thermally activated above 25 K, but governed by quantum diffusion below 25 K. The experimental and computational studies of the hyperfine coupling constant of Mu suggest that it is formed in the interlayer space of talc and that its electronic structure is extremely changed due to confinement. All these results imply that the chemistry could be strongly affected by confinement in the interlayer space of clays. [ABSTRACT FROM AUTHOR]

Several prediction models for progression of age-related macular degeneration (AMD) have been developed, but the added value of using genetic information in those models in addition to clinical characteristics is ambiguous. In this prospective cohort study, we explored the added value of genetics using a genetic risk score (GRS) based on 52 AMD-associated variants, in addition to the clinical severity grading at baseline as quantified by validated drusen detection software, to predict disease progression in 177 AMD patients after 6.5 years follow-up. The GRS was strongly associated with the drusen coverage at baseline (P < 0.001) and both the GRS and drusen coverage were associated with disease progression. When the GRS was added as predictor in addition to the drusen coverage, R2 increased from 0.46 to 0.56. This improvement by the GRS was predominantly seen in patients with a drusen coverage <15%. In patients with a larger drusen coverage, the GRS had less added value to predict progression. Thus, genetic information has added value over clinical characteristics in predicting disease progression in AMD, but only in patients with a less severe disease stage. Patients with a high GRS should be made aware of their risk and could be selected for clinical trials for arresting progression. [ABSTRACT FROM AUTHOR]