Novel genome-wide DNA methylation profiling reveals distinct epigenetic landscape, prognostic model and cellular composition of early-stage lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) has been a leading cause of cancer-related mortality worldwide. Early intervention can significantly improve prognosis. DNA methylation could occur in the early stage of tumor. Comprehensive understanding the epigenetic landscape of early-stage LUAD is crucial in understanding tumorigenesis. METHODS: Enzymatic methyl sequencing (EM-seq) was performed on 23 tumors and paired normal tissue to reveal distinct epigenetic landscape, for compared with The Cancer Genome Atlas (TCGA) 450K methylation microarray data. Then, an integrative analysis was performed combined with TCGA LUAD RNA-seq data to identify significant differential methylated and expressed genes. Subsequently, the prognostic risk model was constructed and cellular composition was analyzed. RESULTS: Methylome analysis of EM-seq comparing tumor and normal tissues identified 25 million cytosine-phosphate-guanine (CpG) sites and 30,187 differentially methylated regions (DMR) with a greater number of untraditional types. EM-seq identified a significantly higher number of CpG sites and DMRs compared to the 450K microarray. By integrating the differentially methylated genes (DMGs) with LUAD-related differentially expressed genes (DEGs) from the TCGA database, we constructed prognostic model based on six differentially methylated-expressed genes (MEGs) and verified our prognostic model in GSE13213 and GSE42127 dataset. Finally, cell deconvolution based on the in-house EM-seq methylation profile was used to estimate cellular composition of early-stage LUAD. CONCLUSIONS: This study firstly delves into novel pattern of epigenomic DNA methylation and provides a multidimensional analysis of the role of DNA methylation revealed by EM-seq in early-stage LUAD, providing distinctive insights into its potential epigenetic mechanisms.

Preparation of (S)-epichlorohydrin using a novel halohydrin dehalogenase by selective conformation adjustment.

Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheCPS to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheCPS mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheCPS, the catalytic efficiency (kcat(S)-ECH/Km(S)-ECH) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM-1 s-1), while the catalytic efficiency (kcat(1,3-DCP)/Km(1,3-DCP)) of the forward reaction only reduced from 0.83 to 0.71 mM-1 s-1. With 40 mM 1,3-DCP as substrate, HheCPS E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.

LncRNA 4930581F22Rik promotes myogenic differentiation by regulating the ERK/MAPK signaling pathway.

The skeletal muscle is the largest organ in mammals and is the primary motor function organ of the body. Our previous research has shown that long non-coding RNAs (lncRNAs) are significant in the epigenetic control of skeletal muscle development. Here, we observed progressive upregulation of lncRNA 4930581F22Rik expression during skeletal muscle differentiation. Knockdown of lncRNA 4930581F22Rik hindered skeletal muscle differentiation and resulted in the inhibition of the myogenic markers MyHC and MEF2C. Furthermore, we found that lncRNA 4930581F22Rik regulates myogenesis via the ERK/MAPK signaling pathway, and this effect could be attenuated by the ERK-specific inhibitor PD0325901. Additionally, in vivo mice injury model results revealed that lncRNA 4930581F22Rik is involved in skeletal muscle regeneration. These results establish a theoretical basis for understanding the contribution of lncRNAs in skeletal muscle development and regeneration.

Photo-Healable Fabrics: Achieving Structural Control via Photochemical Solid-Liquid Transitions of Polystyrene/Azobenzene-Containing Polymer Blends.

While polymer fabrics are integral to a wide range of applications, their vulnerability to mechanical damage limits their sustainability and practicality. Addressing this challenge, our study introduces a versatile strategy to develop photohealable fabrics, utilizing a composite of polystyrene (PS) and an azobenzene-containing polymer (PAzo). This combination leverages the structural stability of PS to compensate for the mechanical weaknesses of PAzo, forming the fiber structures. Key to our approach is the reversible trans-cis photoisomerization of azobenzene groups within the PAzo under UV light exposure, enabling controlled morphological alterations in the PS/PAzo blend fibers. The transition of PAzo sections from a solid to a liquid state at a low glass transition temperature (Tg ∼ 13.7 °C) is followed by solidification under visible light, thus stabilizing the altered fiber structures. In this study, we explore various PS/PAzo blend ratios to optimize surface roughness and mechanical properties. Additionally, we demonstrate the capability of these fibers for photoinduced self-healing. When damaged fabrics are clamped and subjected to UV irradiation for 20 min and pressed for 24 h, the mobility of the cis-form PAzo sections facilitates healing while retaining the overall fabric structure. This innovative approach not only addresses the critical issue of durability in polymer fabrics but also offers a sustainable and practical solution, paving the way for its application in smart clothing and advanced fabric-based materials.

Iron-sulfur protein odyssey: exploring their cluster functional versatility and challenging identification.

Iron-sulfur (Fe-S) clusters are an essential and ubiquitous class of protein-bound prosthetic centers that are involved in a broad range of biological processes (e.g. respiration, photosynthesis, DNA replication and repair and gene regulation) performing a wide range of functions including electron transfer, enzyme catalysis, and sensing. In a general manner, Fe-S clusters can gain or lose electrons through redox reactions, and are highly sensitive to oxidation, notably by small molecules such as oxygen and nitric oxide. The [2Fe-2S] and [4Fe-4S] clusters, the most common Fe-S cofactors, are typically coordinated by four amino acid side chains from the protein, usually cysteine thiolates, but other residues (e.g. histidine, aspartic acid) can also be found. While diversity in cluster coordination ensures the functional variety of the Fe-S clusters, the lack of conserved motifs makes new Fe-S protein identification challenging especially when the Fe-S cluster is also shared between two proteins as observed in several dimeric transcriptional regulators and in the mitoribosome. Thanks to the recent development of in cellulo, in vitro, and in silico approaches, new Fe-S proteins are still regularly identified, highlighting the functional diversity of this class of proteins. In this review, we will present three main functions of the Fe-S clusters and explain the difficulties encountered to identify Fe-S proteins and methods that have been employed to overcome these issues.

Chirality-Driven Orbital Angular Momentum and Circular Dichroism in CoSi.

Chiral crystals and molecules were recently predicted to form an intriguing platform for unconventional orbital physics. Here, we report the observation of chirality-driven orbital textures in the bulk electronic structure of CoSi, a prototype member of the cubic B20 family of chiral crystals. Using circular dichroism in soft x-ray angle-resolved photoemission, we demonstrate the formation of a bulk orbital-angular-momentum texture and monopolelike orbital-momentum locking that depends on crystal handedness. We introduce the intrinsic chiral circular dichroism, icCD, as a differential photoemission observable and a natural probe of chiral electron states. Our findings render chiral crystals promising for spin-orbitronics applications.

Long noncoding RNA small nucleolar RNA host genes as prognostic molecular biomarkers in hepatocellular carcinoma: A meta-analysis.

BACKGROUND: Recently, increasing data have suggested that the lncRNA small nucleolar RNA host genes (SNHGs) were aberrantly expressed in hepatocellular carcinoma (HCC), but the association between the prognosis of HCC and their expression remained unclear. The purpose of this meta-analysis was to determine the prognostic significance of lncRNA SNHGs in HCC. METHODS: We systematically searched Embase, Web of Science, PubMed, and Cochrane Library for eligible articles published up to February 2024. The prognostic significance of SNHGs in HCC was evaluated by hazard ratios (HRs) and 95% confidence intervals (CIs). Odds ratios (ORs) were used to assess the clinicopathological features of SNHGs. RESULTS: This analysis comprised a total of 25 studies covering 2314 patients with HCC. The findings demonstrated that over-expressed SNHGs were associated with larger tumor size, multiple tumor numbers, poor histologic grade, earlier lymphatic metastasis, vein invasion, advanced tumor stage, portal vein tumor thrombosis (PVTT), and higher alpha-fetoprotein (AFP) level, but not with hepatitis B virus (HBV) infection, and cirrhosis. In terms of prognosis, patients with higher SNHG expression were more likely to have shorter overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). CONCLUSIONS: In conclusion, upregulation of SNHGs expression correlates with shorter OS, RFS, DFS, tumor size and numbers, histologic grade, lymphatic metastasis, vein invasion, tumor stage, PVTT, and AFP level, suggesting that SNHGs may serve as prognostic biomarkers in HCC.

Quetiapine Significantly Improves the Effectiveness of Radiotherapy in Combating Hepatocellular Carcinoma Progression in a Hep3B Xenograft Mouse Model.

BACKGROUND/AIM: In hepatocellular carcinoma (HCC) treatment, radiotherapy (RT) stands as a pivotal approach, yet the emergence of radioresistance poses a formidable challenge. This study aimed to explore the potential synergy between quetiapine and RT for HCC treatment. MATERIALS AND METHODS: A Hep3B xenograft mouse model was used, the investigation tracked tumor progression, safety parameters, and molecular mechanisms. RESULTS: The findings revealed a synergistic anti-HCC effect when quetiapine was coupled with RT that prolonged tumor growth time and a significantly higher growth inhibition rate compared to the control group. Safety assessments indicated minimal pathological changes, suggesting potential of quetiapine in mitigating RT-induced alterations in liver and kidney functions. Mechanistically, the combination suppressed metastasis and angiogenesis-related proteins, while triggering the activation of apoptosis-related proteins via targeting Epidermal growth factor receptor (EGFR)-mediated signaling. CONCLUSION: The potential of the quetiapine and RT combination is emphasized, offering enhanced anti-HCC efficacy, a safety profile, and positioning quetiapine as a radiosensitizer for HCC treatment.

Transabdominal motor evoked potential neuromonitoring of lumbosacral spine surgery.

BACKGROUND CONTEXT: Transcranial Motor Evoked Potentials (TcMEPs) can improve intraoperative detection of femoral plexus and nerve root injury during lumbosacral spine surgery. However, even under ideal conditions, TcMEPs are not completely free of false-positive alerts due to the immobilizing effect of general anesthetics, especially in the proximal musculature. The application of transcutaneous stimulation to activate ventral nerve roots directly at the level of the conus medularis (bypassing the brain and spinal cord) has emerged as a method to potentially monitor the motor component of the femoral plexus and lumbosacral nerves free from the blunting effects of general anesthesia. PURPOSE: To evaluate the reliability and efficacy of transabdominal motor evoked potentials (TaMEPs) compared to TcMEPs during lumbosacral spine procedures. DESIGN: We present the findings of a single-center 12-month retrospective experience of all lumbosacral spine surgeries utilizing multimodality intraoperative neuromonitoring (IONM) consisting of TcMEPs, TaMEPs, somatosensory evoked potentials (SSEPs), electromyography (EMG), and electroencephalography. PATIENT SAMPLE: Two hundred and twenty patients having one, or a combination of lumbosacral spine procedures, including anterior lumbar interbody fusion (ALIF), lateral lumbar interbody fusion (LLIF), posterior spinal fusion (PSF), and/or transforaminal lumbar interbody fusion (TLIF). OUTCOME MEASURES: Intraoperative neuromonitoring data was correlated to immediate post-operative neurologic examinations and chart review. METHODS: Baseline reliability, false positive rate, true positive rate, false negative rate, area under the curve at baseline and at alerts, and detection of pre-operative deficits of TcMEPs and TaMEPs were compared and analyzed for statistical significance. The relationship between transcutaneous stimulation voltage level and patient BMI was also examined. RESULTS: TaMEPs were significantly more reliable than TcMEPs in all muscles except abductor hallucis. Of the 27 false positive alerts, 24 were TcMEPs alone, and 3 were TaMEPs alone. Of the 19 true positives, none were detected by TcMEPs alone, 3 were detected by TaMEPs alone (TcMEPs were not present), and the remaining 16 true positives involved TaMEPs and TcMEPs. TaMEPs had a significantly larger area under the curve (AUC) at baseline than TcMEPs in all muscles except abductor hallucis. The percent decrease in TcMEP and TaMEP AUC during LLIF alerts was not significantly different. Both TcMEPs and TaMEPs reflected three pre-existing motor deficits. Patient BMI and TaMEP stimulation intensity were found to be moderately positively correlated. CONCLUSIONS: These findings demonstrate the high reliability and predictability of TaMEPs and the potential added value when TaMEPs are incorporated into multimodality IONM during lumbosacral spine surgery.

ScRNA-seq reveals novel immune-suppressive T cells and investigates CMV-TCR-T cells cytotoxicity against GBM.

BACKGROUND: Glioblastoma (GBM) is a fatal primary brain malignancy in adults. Previous studies have shown that cytomegalovirus (CMV) is a risk factor for tumorigenesis and aggressiveness for glioblastoma. However, little is known about how CMV infection affects immune cells in the tumor microenvironment of GBM. Furthermore, there has been almost no engineered T-cell receptor (TCR)-T targeting CMV for GBM research to date. METHODS: We evaluated the CMV infection status of patients with GBM's tumor tissue by immune electron microscopy, immunofluorescence, and droplet digital PCR. We performed single-cell RNA sequencing for CMV-infected GBM to investigate the effects of CMV on the GBM immune microenvironment. CellChat was applied to analyze the interaction between cells in the GBM tumor microenvironment. Additionally, we conducted single-cell TCR/B cell receptor (BCR) sequencing and Grouping of Lymphocyte Interactions with Paratope Hotspots 2 algorithms to acquire specific CMV-TCR sequences. Genetic engineering was used to introduce CMV-TCR into primary T cells derived from patients with CMV-infected GBM. Flow cytometry was used to measure the proportion and cytotoxicity status of T cells in vitro. RESULTS: We identified two novel immune cell subpopulations in CMV-infected GBM, which were bipositive CD68+SOX2+ tumor-associated macrophages and FXYD6+ T cells. We highlighted that the interaction between bipositive TAMs or cancer cells and T cells was predominantly focused on FXYD6+ T cells rather than regulatory T cells (Tregs), whereas, FXYD6+ T cells were further identified as a group of novel immunosuppressive T cells. CMV-TCR-T cells showed significant therapeutic effects on the human-derived orthotopic GBM mice model. CONCLUSIONS: These findings provided an insight into the underlying mechanism of CMV infection promoting the GBM immunosuppression, and provided a novel potential immunotherapy strategy for patients with GBM.

Design, Synthesis, and Evaluation of Dihydropyrimidine Derivatives as Selective PDE1 Inhibitors for the Treatment of Liver Fibrosis.

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives. Lead 13h exhibited the IC50 of 10 nM against PDE1, high selectivity over other PDEs, as well as good safety properties. Administration of 13h exerted significant anti-liver fibrotic effects in bile duct ligation-induced fibrosis rats, which also prevented TGF-ß-induced myofibroblast differentiation in vitro, confirming that PDE1 could work as a potential target for liver fibrosis.

Detection of early pulmonary emphysema by multi-contrast x-ray Talbot-Lau interferometer.

BACKGROUND: Pulmonary emphysema is a part of chronic obstructive pulmonary disease, which is an irreversible chronic respiratory disease. In order to avoid further damage to lung tissue, early diagnosis and treatment of pulmonary emphysema is essential. PURPOSE: Early pulmonary emphysema diagnosis is difficult with conventional radiographic imaging. Recently, x-ray phase contrast imaging has proved to be an effective and promising imaging strategy for soft tissue, due to its high sensitivity and multi-contrast. The aim of this study is to diagnose pulmonary emphysema early utilizing an x-ray Talbot-Lau interferometer (TLI). METHODS: We successfully established the mouse model of emphysema by porcine pancreatic elastase treatment, and then used the established x-ray TLI to perform imaging experiments on the mice with different treatment time. The traditional absorption CT and phase contrast CT were obtained simultaneously through TLI. The CT results and histopathology of mice lung in different treatment time were quantitatively analyzed. RESULTS: By imaging mice lungs, it can be found that phase contrast has higher sensitivity than absorption contrast in early pulmonary emphysema. The results show that the phase contrast signal could distinguish the pulmonary emphysema earlier than the conventional attenuation signal, which can be consistent with histological images. Through the quantitative analysis of pathological section and phase contrast CT, it can be found that there is a strong linear correlation. CONCLUSIONS: In this study, we quantitatively analyze mean linear intercept of histological sections and CT values of mice. The results show that the phase contrast signal has higher imaging sensitivity than the attenuation signal. X-ray TLI multi-contrast imaging is proved as a potential diagnostic method for early pulmonary emphysema in mice.

Revealing the hidden carbon flows in global industrial Sectors-Based on the perspective of linkage network structure.

This paper interprets the implicit carbon flows in global industrial sectors from a network perspective. Using the SNA-IO integrated model, along with cross-border input-output data from Eora26 (2000-2020) and global energy balance data, the implicit carbon emissions of global industrial sectors and their evolution are analyzed. A carbon emission network structure from an industrial chain perspective is proposed. The results indicate that the carbon emissions responsibility of an industry is not only associated with its own energy consumption. It also involves the carbon emissions transfer resulting from the exchange of products and services between upstream and downstream industries. Block model analysis reveals the carbon emission transfer relationships and their interconnections among global industrial sectors, tending towards an industry clustering pattern where "production side" converges with "demand side" coexisting in supply and demand. There are noticeable inequalities in wealth gains and environmental burdens between these blocks. This paper can provide targeted carbon reduction policy recommendations for various industrial sectors to participate in global responsibility allocation and promote the formation of a low-carbon global industrial sector network.

Anomalous Detachment Behavior and Directional Reconstruction Regulation of Leaching-Type Precatalysts for Industrial Water Electrolyzers.

Current reconstruction chemistry studies are mainly operated at the laboratory scale, where the operating parameters are different from those used in industrial water electrolyzers. This gap leads to unclear reconstruction behaviors under industrial conditions and constrains the application of catalysts. Here, this work presents a new reconstruction mechanism and anomalous detachment phenomena observed in leaching-type oxygen-evolving precatalysts under industrial conditions, different from the reported results obtained under laboratory conditions. The identified detachment issues are closely linked to the production of a potassium salt separate phase, which proves sensitive to the local environment, and its instability easily leads to catalyst stripping from the substrate. By establishing detachment critical point and operating parameter-detachment correlation, a targeted reconstruction strategy is proposed to achieve smooth ligand leaching and effectively solve the detachment issue. Theoretical analyses validate the dual-site regulation in directionally reconstructed catalysts with optimized intermediate adsorption. Under industrial conditions, the coupled electrolyzer delivers an industrial-level current density at low cell voltage with prolonged durability, 1 A cm-2 at 2 V for over 340 h. This work bridges the gap of leaching-type precatalysts between laboratory test conditions and industrial operating conditions.

Gene variants and clinical characteristics of children with sitosterolemia.

OBJECTIVE: To enhance the detection, management and monitoring of Chinese children afflicted with sitosterolemia by examining the physical characteristics and genetic makeup of pediatric patients. METHODS: In this group, 26 children were diagnosed with sitosterolemia, 24 of whom underwent genetic analysis. Patient family medical history, physical symptoms, tests for liver function, lipid levels, standard blood tests, phytosterol levels, cardiac/carotid artery ultrasounds, fundus examinations, and treatment were collected. RESULTS: The majority (19, 73.1%) of the 26 patients exhibited xanthomas as the most prevalent manifestation. The second most common symptoms were joint pain (7, 26.9%) and stunted growth (4, 15.4%). Among the 24 (92.3%) patients whose genetics were analyzed, 16 (66.7%) harbored ABCG5 variants (type 2 sitosterolemia), and nearly one-third (8, 33.3%) harbored ABCG8 variants (type 1 sitosterolemia). Additionally, the most common pathogenic ABCG5 variant was c.1166G > A (p.Arg389His), which was found in 10 patients (66.7%). Further analysis did not indicate any significant differences in pathological traits among those carrying ABCG5 and ABCG8 variations (P > 0.05). Interestingly, there was a greater abundance of nonsense variations in ABCG5 than in ABCG8 (P = 0.09), and a greater frequency of splicing variations in ABCG8 than ABCG5 (P = 0.01). Following a change in diet or a combination of ezetimibe, the levels of cholesterol and low-density lipoprotein were markedly decreased compared to the levels reported before treatment. CONCLUSION: Sitosterolemia should be considered for individuals presenting with xanthomas and increased cholesterol levels. Phytosterol testing and genetic analysis are important for early detection. Managing one's diet and taking ezetimibe can well control blood lipids.

Gas exchange and chlorophyll fluorescence responses of Camellia sinensis grown under various cultivations in different seasons.

Sod culture (SC) and conventional agriculture (CA) represent two distinct field management approaches utilized in the cultivation of tea plants in Taiwan. In this study, we employed gas exchange and chlorophyll fluorescence techniques to assess the impact of SC and CA methods on the photosynthetic machinery of Camellia sinensis cv. TTES No.12 (Jhinhsuan) in response to variable light intensities across different seasons. In spring, at photosynthetic photon flux densities (PPFD) ranging from 800 to 2,000 µmol photon m-2 s-1, the net photosynthesis rate (Pn, 10.43 µmol CO2 m-2 s-1), stomatal conductance (Gs, 126.11 mmol H2O m-2 s-1), electron transport rate (ETR, 137.94), and ΔF/Fm' and Fv/Fm (50.37) values for plants grown using SC were comparatively higher than those cultivated under CA. Conversely, the non-photochemical quenching (NPQ) values for SC-grown plants were relatively lower (3.11) compared to those grown under CA at 800 to 2,000 PPFD in spring. Additionally, when tea plants were exposed to PPFD levels below 1,500 µmol photon m- 2 s- 1, there was a concurrent increase in Pn, Gs, ETR, and NPQ. These photosynthetic parameters are crucial for devising models that optimize cultivation practices across varying seasons and specific tillage requirements, and for predicting photosynthetic and respiratory responses of tea plants to seasonally or artificially altered light irradiances. The observed positive impacts of SC on maximum photosynthetic rate (Amax), Fv/Fm, Gs, water-use efficiency (WUE), and ETR suggest that SC is advantageous for enhancing the productivity of tea plants, thereby offering a more adaptable management model for tea gardens.

Regulations of mitoNEET by the key redox homeostasis molecule glutathione.

Human mitoNEET (mNT) and CISD2 are two NEET proteins characterized by an atypical [2Fe-2S] cluster coordination involving three cysteines and one histidine. They act as redox switches with an active state linked to the oxidation of their cluster. In the present study, we show that reduced glutathione but also free thiol-containing molecules such as ß-mercaptoethanol can induce a loss of the mNT cluster under aerobic conditions, while CISD2 cluster appears more resistant. This disassembly occurs through a radical-based mechanism as previously observed with the bacterial SoxR. Interestingly, adding cysteine prevents glutathione-induced cluster loss. At low pH, glutathione can bind mNT in the vicinity of the cluster. These results suggest a potential new regulation mechanism of mNT activity by glutathione, an essential actor of the intracellular redox state.

The influence of Mg/Al molar ratio on the performance of CuMgAl-x catalysts for CO2 hydrogenation to methanol.

The CuMgAl-x catalysts derived from hydrotalcite precursors with different Mg/Al molar ratios were synthesized and applied to CO2 hydrogenation to methanol reaction. In this study, the effects of Mg/Al molar ratio on the structure and surface properties of CuMgAl-x catalysts were investigated by XRD, N2 adsorption-desorption, SEM, TEM, H2-TPR, CO2-TPD, XPS, and in situ DRIFTS characterization methods. The results showed that an appropriate Mg/Al molar ratio can enhance the Cu-MgO interaction, increasing the basic sites and obtaining suitable acid sites. The dispersion of active Cu on the CuMgAl-x catalysts can be improved by strong Cu-MgO interaction, which enhances the adsorption capacity of CO2 and makes H2 activation easier, accelerates the conversion of intermediate species CO3 * and HCO3 *to HCOO*, and facilitates further conversion to CH3O* and CH3OH. The strong interaction between Cu and MgO was conducive to the formation of Cu+, which can inhibit the desorption of CO in the reverse water gas shift reaction. The CuMgAl-3 catalyst showed the highest CO2 Conversion rate (14.3%), methanol selectivity (94.5%), and STY of methanol (419.3 g⋅kgcat. -1⋅h-1) at 240°C and 2.5 MPa. The results obtained in this paper can provide a new idea for the design of high-performance catalysts for CO2 hydrogenation to methanol.

Differentiation of confluent hepatic fibrosis and infiltrative hepatocellular carcinoma on MR imaging.

BACKGROUND: To identify reliable magnetic resonance imaging (MRI) features that can differentiate confluent fibrosis (CF) from infiltrative hepatocellular carcinoma (HCC). METHODS: A retrospective analysis was conducted on Twenty CF patients and 28 infiltrative HCC patients who underwent upper abdomen MRI scans. The imaging features of lesions were analyzed, and the apparent diffusion coefficient (ADC) of lesions were measured. Accuracy, sensitivity and specificity for the diagnosis of CF were calculated for each category individually and combined. RESULTS: Compared to infiltrative HCC, hepatic capsular retraction at the site of lesion, hepatic volume loss at the site of lesion and "nodular surround sign" were more common in patients with CF (all P < 0.001). Hepatic volume loss at the site of lesion, no or mild enhancement in arterial phase, and hyper-enhancing in delayed phase to the background parenchyma showed superior diagnostic accuracy (83.3%, 85.4%, 97.9%, respectively). When the lesion exhibited hepatic volume loss at the site of lesion or no or mild enhancement in arterial phase or hyper-enhancing in delayed phase, a sensitivity of 100.0% for the diagnosis of CF was achieved. When the lesion was positive for any two of three categories, or positive for all three categories, a specificity of 100.0% was achieved. The ADC values of CF were higher than those of infiltrative HCC (P < 0.001). CONCLUSION: The combination of the hepatic volume loss at the site of lesion, no or mild enhancement in arterial phase, and hyper-enhancing in delayed phase to the background parenchyma can be considered reliable MR features for the diagnosis of CF, as they allow differentiation from infiltrative HCC.

Identification of Hedyotis diffusa Willd-specific mRNA-miRNA-lncRNA network in rheumatoid arthritis based on network pharmacology, bioinformatics analysis, and experimental verification.

Hedyotis diffusa Willd (HDW) possesses heat-clearing, detoxification, anti-cancer, and anti-inflammatory properties. However, its effects on rheumatoid arthritis (RA) remain under-researched. In this study, we identified potential targets of HDW and collected differentially expressed genes of RA from the GEO dataset GSE77298, leading to the construction of a drug-component-target-disease regulatory network. The intersecting genes underwent GO and KEGG analysis. A PPI protein interaction network was established in the STRING database. Through LASSO, RF, and SVM-RFE algorithms, we identified the core gene MMP9. Subsequent analyses, including ROC, GSEA enrichment, and immune cell infiltration, correlated core genes with RA. mRNA-miRNA-lncRNA regulatory networks were predicted using databases like TargetScan, miRTarBase, miRWalk, starBase, lncBase, and the GEO dataset GSE122616. Experimental verification in RA-FLS cells confirmed HDW's regulatory impact on core genes and their ceRNA expression. We obtained 11 main active ingredients of HDW and 180 corresponding targets, 2150 RA-related genes, and 36 drug-disease intersection targets. The PPI network diagram and three machine learning methods screened to obtain MMP9, and further analysis showed that MMP9 had high diagnostic significance and was significantly correlated with the main infiltrated immune cells, and the molecular docking verification also showed that MMP9 and the main active components of HDW were well combined. Next, we predicted 6 miRNAs and 314 lncRNAs acting on MMP9, and two ceRNA regulatory axes were obtained according to the screening. Cellular assays indicated HDW inhibits RA-FLS cell proliferation and MMP9 protein expression dose-dependently, suggesting HDW might influence RA's progression by regulating the MMP9/miR-204-5p/MIAT axis. This innovative analytical thinking provides guidance and reference for the future research on the ceRNA mechanism of traditional Chinese medicine in the treatment of RA.