Scientific Reports最新文献

Bullous pemphigoid (BP) is a chronic autoimmune condition characterized by painful blistering wounds. While effective, conventional treatments often have significant side effects. This study evaluates the therapeutic efficacy of Ozone Liquid Dressing (OLD), an innovative adjunct treatment, in enhancing wound healing, reducing infection rates, and alleviating pain associated with BP. A total of 120 BP patients were assigned to either an observation group (standard care + OLD) or a control group (standard care alone). The dressing was applied daily until wound healing, or the two-week observation period concluded. Efficacy was measured by healing rates, infection reduction (assessed by positive bacterial cultures in wound exudates), and pain levels (assessed by the Numeric Rating Scale, NRS). Statistical analyses were performed using SPSS software, employing t-tests and Chi-square tests as appropriate. The observation group showed significantly higher complete healing rates (61.70% vs. 38.33%, p < 0.05) compared to the control group. In terms of overall efficacy, the observation group achieved 91.70%, compared to the control group's 80.00% (p = 0.116). A marked reduction in positive bacterial cultures was observed in the observation group, beginning on day 3 (p < 0.01), and pain scores decreased significantly by day 10 (p < 0.001). OLD significantly enhances wound healing and reduces pain in BP patients, demonstrating clinical potential. Further studies are necessary to confirm the long-term benefits and clinical applicability of OLD in managing BP wounds.

Based on single-stranded DNA library method, we established an efficient workflow to parallelly construct targeted genomic and epigenomic sequencing libraries from a small amount of DNA. We applied the protocol to nine pediatric brain cancer DNA samples containing various extents of damage from formalin fixation and/or DNA oxidation. Compared to our previous study, the new exome protocol showed superior uniformity of coverage. Many artifactual mutation calls introduced by DNA damages were eliminated by bioinformatics filtering tools. After filtration, 89.4-97.0% of somatic single nucleotide variant (SNV) calls generated by double-stranded DNA library were reproduced in formalin-fixed paraffin-embedded (FFPE) samples, which was achieved with substantially reduced DNA input amounts (26.7-50ng). In methylome analysis, we obtained methylation calls for 78-92% of target CpGs with at least 10x coverage when using 100ng of FFPE DNA, which is comparable to those obtained from fresh frozen samples. We also obtained SNV calls from methylome data, recovering 39-76% of filtered SNVs from exome data in nine brain cancer samples. In conclusion, we present a simple protocol for parallel construction of targeted exome and methylome sequencing libraries, which was successfully applied to damaged brain cancer DNA samples from FFPE tissues stored for prolonged periods.

The DfrA1 protein provides trimethoprim resistance in bacteria, especially Klebsiella pneumoniae and Escherichia coli, by modifying dihydrofolate reductase, which reduces the binding efficacy of the antibiotic. This study identified inhibitors of the trimethoprim-resistant DfrA1 protein through high-throughput computational screening and optimization of 3,601 newly synthesized chemical compounds from the ChemDiv database, aiming to discover potential drug candidates targeting DfrA1 in K. pneumoniae and E. coli. Through this approach, we identified six promising DCs, labeled DC1 to DC6, as potential inhibitors of DfrA1. Each DC showed a strong ability to bind effectively to the DfrA1 protein and formed favorable chemical interactions at the binding sites. These interactions were comparable to those of Iclaprim, a well-known antibiotic effective against DfrA1. To confirm our findings, we explored how the promising DCs work at the molecular level, focusing on their thermodynamic properties. Additionally, molecular dynamics simulations confirmed the ability of these six DCs to effectively inhibit the DfrA1 protein. Our results showed that DC4 (an organofluorinated compound) and DC6 (a benzimidazole compound) exhibited potential efficacy against the DfrA1 protein than the control drug, particularly regarding stability, solvent-accessible surface area, solvent exposure, polarity, and binding site interactions, which influence their residence time and efficacy. Overall, findings of this study suggest that DC4 and DC6 have the potential to act as inhibitors against the DfrA1, offering promising prospects for the treatment and management of infections caused by trimethoprim-resistant K. pneumoniae and E. coli in both humans and animals. However, further in vitro validations are necessary.

An increasing number of research have suggested that ferroptosis plays an important role in endometriosis (EMS). This study was to identify a ferroptosis-related diagnosis gene in EMS by using bioinformatics. R Bioconductor package limma was used to analyzed the differentially expressed genes (DEGs) between the EMS groups and control groups. CIBERSORT was used to analyze the differences between the EMS group and control group of 22 immune cells. Quantitative real-time PCR (RT-qPCR) and Western blot (WB) were used to validate the expression level of FZD7 in tissue samples. The study found that FZD7 was upregulated and showed good diagnostic value in five EMS transcriptome databases. RT-qPCR and WB experiments also verified that FZD7 was upregulated in EMS. Moreover, we found that macrophages, especially M2 macrophages, were significantly infiltrated in EMS. FZD7 was positively correlated with M2 macrophage infiltration, and was up-regulated in the endometrial stromal cells co-cultured with macrophages. The study identified an ferroptosis repressor gene, FZD7, validated in five EMS transcriptome datasets, which is significantly up-regulated in ectopic lesions of EMS and is a potential target for the treatment of EMS.

The dynamic remodeling of the nascent vascular network into a mature hierarchy is essential for embryo survival. Cell behaviors and signaling mechanisms are often investigated with animal models and perfused microchannels, giving insights into this process. To support these studies and enrich our understanding, we demonstrate a complementary approach using vascular organoids. Organoids initially form a primitive endothelial plexus lined with NG2⁺/PDGFRβ⁺ mural cell progenitors containing immature pericytes, but there is no formation of large-diameter vessels covered with αSMA⁺ cells containing immature vascular smooth muscle cells (vSMCs). After transplantation to the chick chorioallantoic membrane, the network reorganizes into a branched architecture with large-diameter vessels covered by αSMA⁺ cells. We additionally show that blood flow from the host circulation perfuses the organoid. Compared with the developing skin vasculature in mouse embryos, organoids successfully recapitulate vascular morphogenesis, both in vitro and after transplantation. The model described here presents a further approach to enhance the study of vascular remodeling.

The objective was to pinpoint specific circulating angiogenic and inflammatory markers of refractory and active RA. We used Luminex technology to measure the concentrations of 17 RA-representative serum angiogenic and inflammatory markers in 211 RA patients categorized into three groups: refractory (failure of 2 or more targeted therapies) active (persistence of objective signs of disease activity) RA, non-refractory (failure of ≥ 1 csDMARDs or a first line of targeted therapy) active RA and non-active RA (DAS28 ≤ 3.2). Refractory and non-refractory active RA patients differed in disease duration, structural damage and the utilization of biologic therapy. The concentrations of the 17 markers failed to distinguish refractory from non-refractory RA patients. The comparison of active and non-active RA only revealed a strong increase of IL-6 concentration in active RA. Refractory active RA exhibited a limited correlation profile showing only three correlations with markers of disease activity, not significantly different from whose of non-active RA. By contrast, in non-refractory active RA patients, correlograms revealed an extensive proinflammatory and proangiogenic correlation profile with 12 markers correlating with inflammation markers or disease activity. In conclusion, no classical marker of RA emerged as specific for refractory disease in this study. Moreover, refractory and active RA patients exhibited only few correlations with disease activity markers, despite the persistence of clinical and biological signs of disease activity. This may suggest that additional molecules may be implicated in refractory disease outside those herein selected. These findings also highlight the potential limitations of serum analysis in refractory active RA.

Accurate molecular property prediction is crucial for drug discovery and computational chemistry, facilitating the identification of promising compounds and accelerating therapeutic development. Traditional machine learning falters with high-dimensional data and manual feature engineering, while existing deep learning approaches may not capture complex molecular structures, leaving a research gap. We introduce Deep-CBN, a novel framework designed to enhance molecular property prediction by capturing intricate molecular representations directly from raw data, thus improving accuracy and efficiency. Our methodology combines convolutional neural networks (CNNs) with a BiFormer attention mechanism, employing both the forward-forward algorithm and backpropagation. The model operates in three stages: (1) feature learning, extracting local features from SMILES strings using CNNs; (2) attention refinement, capturing global context with a BiFormer module enhanced by the forward-forward algorithm; and (3) prediction subnetwork tuning, fine-tuning via backpropagation. Evaluations on benchmark datasets-including Tox21, BBBP, SIDER, ClinTox, BACE, HIV, and MUV-show that Deep-CBN achieves near-perfect ROC-AUC scores, significantly outperforming state-of-the-art methods. These findings demonstrate its effectiveness in capturing complex molecular patterns, offering a robust tool to accelerate drug discovery processes.

Nowadays, the climate change crisis is an urgent matter in which carbon dioxide (CO₂) is a major greenhouse gas contributing to global warming. Amine solvents are commonly used for CO₂ capture with high efficiency and absorption rates. However, solvent regeneration consumes an extensive amount of energy. One of alternative approaches is amine regeneration through microalgae. Recently, living biocomposites, intensifying traditional suspended cultivation, have been developed. With this technology, immobilizing microalgae on biocompatible materials with binder outperformed the suspended system in terms of CO₂ capture rates. In this study, living microalgae-loofah biocomposites with immobilized Scenedesmus acuminatus TISTR 8457 using 5%v/v acrylic medium were tested to remove CO₂ from CO₂-rich triethanolamine (TEA) solutions. The test using 1 M TEA at various CO₂ loading ratios (0.2, 0.4, 0.6, and 0.8 mol CO₂/mol TEA) demonstrated that the biocomposites achieved CO₂ removal rates 3 to 5 times higher than the suspended cell system over 28 days, with the highest removal observed at the 1 M with 0.4 mol CO₂/mol TEA (4.34 ± 0.20 g_CO2/g_biomass). This study triggers a new exploration of integration between biological and chemical processes that could elevate the traditional amine-based CO₂ capture capabilities. Nevertheless, pilot-scale investigations are necessary to confirm the biocomposites's efficiency.

Prestressed bolts have been increasingly used in underground engineering as a practical solution to control the instability of surrounding rock masses. However, blindly increasing the density of prestressed bolt has limited influence on the performance improvement of tunnel surrounding rock mass. Therefore, the accurate design of the parameters of the prestressed bolt in the support system is a significant method to improve the bearing capacity of the tunnel surrounding rock. To solve this problem, we carried out large-scale physical model tests of anchored rock block with nonpersistent joints. An innovative method for prestressed bolt simulation is proposed by using the code independently developed in PFC^3D, and then a series of numerical model compression tests of anchored rock block with different prestressed bolt densities are extended based on physical model tests. The results indicate that the original failure mode of the rock block is not changed by adding bolt. And an increase in the density of the prestressed bolt leads to a change in the anchoring mechanism of the rock block. When the density of prestressed bolt is low, the upper load is mainly borne by rock block, and the increase of the density of bolt will mobilize more intact rock to participate in the load. When the density of prestressed bolt increases to a certain extent, the upper load is mainly borne by the prestressed bolt. And the performance improvement of prestressed bolt to rock block is limited. When the prestress and density of bolt reach a certain degree, the strength of rock mass is only increased by 10% when the prestress and density of bolt are doubled. The increase of the density of prestressed bolt makes the deformation of rock block more stable, and the ɛ₃/ɛ₁ ratio of the anchored rock block is always less than 1.0. The research results have important guiding significance for tunnel surrounding rock masses support design.

In this study, a commercial epoxy resin (KER 828) was employed as the organic component of the organic inorganic hybrid coating to enhance corrosion resistance while reducing production costs via the sol-gel method. Hybrid coatings were formulated with varying weight percentages and subsequently applied to 304 stainless steel substrates to assess their effectiveness against corrosion. The Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), scanning electron microscopy (SEM), pull off test and water contact angle (WCA) techniques were employed to characterize the obtained coatings. The corrosion behavior of both the uncoated stainless steel and the coated samples was evaluated through Potentiodynamic Polarization test. Additionally, the electrochemical impedance spectroscopy (EIS) analysis was employed over time intervals of 1 h, 1 day, 1 week and 1 month exposure to 3.5 wt% NaCl solution. The results demonstrated that coatings with equal weight percentages of the organic and inorganic phases (1:1:1) exhibited the highest corrosion resistance, which can be attributed to the enhanced Si-O-Si network formation. Then SiO₂ nanoparticles were incorporated into the optimal coating formulation to examine the barrier effect and the impact of nanoparticles presence on the hybrid coating performance (1:1:1:0.01). The results acquired from Potentiodynamic polarization (E_corr of - 0.327 V and i_corr of 9.83 × 10^-11 A.cm^-2), EIS (R_ct of 158320 Ω.cm² after 1 month of immersion) and WCA (81.67°) analysis indicated that coating containing SiO₂ nanoparticles (1:1:1:0.01) provided superior surface protection compared to all other synthesized hybrid coatings.