Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Association of atopic dermatitis and headache disorder: a systematic review and meta-analyses.

Background: Growing evidence suggests that headache disorders and atopic dermatitis share similar pathological mechanisms and risk factors. The aim of this study was to assess the risk for headache disorders in patients with atopic dermatitis. Methods: We systematically searched the PubMed and Embase databases from inception to December 1, 2023, for observational studies that examined risk of migraine in subjects with atopic dermatitis. Risk estimates from individual studies were pooled using random-effects models. Results: Ten studies with 12,717,747 subjects were included in the meta-analysis. Our results showed that patients with atopic dermatitis were associated with a higher risk of headache disorder (OR, 1.46, 95% CI = 1.36-1.56; P < 0.001; I2 = 98%) or migraine (OR, 1.32, 95% CI = 1.18-1.47; P < 0.001; I2 = 98.9%). Most of the results of the subgroup analyses were consistent with the overall results. Conclusion: The findings of this meta-analysis suggest that atopic dermatitis is a potential risk indicator for headache disorder or migraine. Further studies are still needed to verify our findings due to the substantial heterogeneity in our analyses.

MEAs-Filter: a novel filter framework utilizing evolutionary algorithms for cardiovascular diseases diagnosis.

Cardiovascular disease management often involves adjusting medication dosage based on changes in electrocardiogram (ECG) signals' waveform and rhythm. However, the diagnostic utility of ECG signals is often hindered by various types of noise interference. In this work, we propose a novel filter based on a multi-engine evolution framework named MEAs-Filter to address this issue. Our approach eliminates the need for predefined dimensions and allows adaptation to diverse ECG morphologies. By leveraging state-of-the-art optimization algorithms as evolution engine and incorporating prior information inputs from classical filters, MEAs-Filter achieves superior performance while minimizing order. We evaluate the effectiveness of MEAs-Filter on a real ECG database and compare it against commonly used filters such as the Butterworth, Chebyshev filters, and evolution algorithm-based (EA-based) filters. The experimental results indicate that MEAs-Filter outperforms other filters by achieving a reduction of approximately 30% to 60% in terms of the loss function compared to the other algorithms. In denoising experiments conducted on ECG waveforms across various scenarios, MEAs-Filter demonstrates an improvement of approximately 20% in signal-to-noise (SNR) ratio and a 9% improvement in correlation. Moreover, it does not exhibit higher losses of the R-wave compared to other filters. These findings highlight the potential of MEAs-Filter as a valuable tool for high-fidelity extraction of ECG signals, enabling accurate diagnosis in the field of cardiovascular diseases.

Microstructure and Mechanical Properties of AlTiVCuN Coatings Prepared by Ion Source-Assisted Magnetron Sputtering.

The AlTiVCuN coatings were deposited by magnetron sputtering with anode layer ion source (ALIS) assistance, and the microstructure and mechanical properties were significantly affected by the ion source power. With increasing the ion source power from 0 to 1.0 kW, the deposition rate decreased from 2.6 to 2.1 nm/min, and then gradually increased to 4.0 nm/min at 3.0 kW, and the surface roughness gradually decreased from 28.7 nm at 0 kW to 9.0 nm at 3.0 kW. Due to the enhanced ion bombardment effect, the microstructure of the coatings changed from a coarse into a dense columnar structure at 1.0 kW, and the grain size increased at higher ion source powers. All the coatings exhibited c-TiAlVN phase, and the preferred orientation changed from the (220) to the (111) plane at 3.0 kW. Due to the low Cu contents (1.0~3.1 at.%), the Cu atoms existed as an amorphous phase in the coatings. Due to the microstructure densification and high residual stress, the highest hardness of 32.4 GPa was achieved for the coating deposited at 1.0 kW.

Comprehensive genomic analysis of puerarin in inhibiting bladder urothelial carcinoma cell proliferation and migration.

BACKGROUND: Bladder urothelial carcinoma (BUC) ranks second in the incidence of urogenital system tumors, and the treatment of BUC needs to be improved. Puerarin, a traditional Chinese medicine (TCM), has been shown to have various effects such as anti-cancer effects, the promotion of angiogenesis, and anti-inflammation. This study investigates the effects of puerarin on BUC and its molecular mechanisms. METHODS: Through GeneChip experiments, we obtained differentially expressed genes (DEGs) and analyzed these DEGs using the Ingenuity® Pathway Analysis (IPA®), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) pathway enrichment analyses. The Cell Counting Kit 8 (CCK8) assay was used to verify the inhibitory effect of puerarin on the proliferation of BUC T24 cells. String combined with Cytoscape® was used to create the Protein-Protein Interaction (PPI) network, and the MCC algorithm in cytoHubba plugin was used to screen key genes. Gene Set Enrichment Analysis (GSEA®) was used to verify the correlation between key genes and cell proliferation. RESULTS: A total of 1617 DEGs were obtained by GeneChip. Based on the DEGs, the IPA® and pathway enrichment analysis showed they were mainly enriched in cancer cell proliferation and migration. CCK8 experiments proved that puerarin inhibited the proliferation of BUC T24 cells, and its IC50 at 48 hours was 218µmol/L. Through PPI and related algorithms, 7 key genes were obtained: ITGA1, LAMA3, LAMB3, LAMA4, PAK2, DMD, and UTRN. GSEA showed that these key genes were highly correlated with BUC cell proliferation. Survival curves showed that ITGA1 upregulation was associated with poor prognosis of BUC patients. CONCLUSION: Our findings support the potential antitumor activity of puerarin in BUC. To the best of our knowledge, bioinformatics investigation suggests that puerarin demonstrates anticancer mechanisms via the upregulation of ITGA1, LAMA3 and 4, LAMB3, PAK2, DMD, and UTRN, all of which are involved in the proliferation and migration of bladder urothelial cancer cells.

METTL3 boosts mitochondrial fission and induces cardiac fibrosis by enhancing LncRNA GAS5 methylation.

Dysregulated mitochondrial metabolism occurs in several pathological processes characterized by cell proliferation and migration. Nonetheless, the role of mitochondrial fission is not well appreciated in cardiac fibrosis, which is accompanied by enhanced fibroblast proliferation and migration. We investigated the causes and consequences of mitochondrial fission in cardiac fibrosis using cultured cells, animal models, and clinical samples. Increased METTL3 expression caused excessive mitochondrial fission, resulting in the proliferation and migration of cardiac fibroblasts that lead to cardiac fibrosis. Knockdown of METTL3 suppressed mitochondrial fission, inhibiting fibroblast proliferation and migration for ameliorating cardiac fibrosis. Elevated METTL3 and N6-methyladenosine (m6A) levels were associated with low expression of long non-coding RNA GAS5. Mechanistically, METTL3-mediated m6A methylation of GAS5 induced its degradation, dependent of YTHDF2. GAS5 could interact with mitochondrial fission marker Drp1 directly; overexpression of GAS5 suppressed Drp1-mediated mitochondrial fission, inhibiting cardiac fibroblast proliferation and migration. Knockdown of GAS5 produced the opposite effect. Clinically, increased METTL3 and YTHDF2 levels corresponded with decreased GAS5 expression, increased m6A mRNA content and mitochondrial fission, and increased cardiac fibrosis in human heart tissue with atrial fibrillation. We describe a novel mechanism wherein METTL3 boosts mitochondrial fission, cardiac fibroblast proliferation, and fibroblast migration: METTL3 catalyzes m6A methylation of GAS5 methylation in a YTHDF2-dependent manner. Our findings provide insight into the development of preventative measures for cardiac fibrosis.

Vina-GPU 2.0: Further Accelerating AutoDock Vina and Its Derivatives with Graphics Processing Units.

Modern drug discovery typically faces large virtual screens from huge compound databases where multiple docking tools are involved for meeting various real scenes or improving the precision of virtual screens. Among these tools, AutoDock Vina and its numerous derivatives are the most popular and have become the standard pipeline for molecular docking in modern drug discovery. Our recent Vina-GPU method realized 14-fold acceleration against AutoDock Vina on a piece of NVIDIA RTX 3090 GPU in one virtual screening case. Further speedup of AutoDock Vina and its derivatives with graphics processing units (GPUs) is beneficial to systematically push their popularization in large-scale virtual screens due to their high benefit-cost ratio and easy operation for users. Thus, we proposed the Vina-GPU 2.0 method to further accelerate AutoDock Vina and the most common derivatives with new docking algorithms (QuickVina 2 and QuickVina-W) with GPUs. Caused by the discrepancy in their docking algorithms, our Vina-GPU 2.0 adopts different GPU acceleration strategies. In virtual screening for two hot protein kinase targets, RIPK1 and RIPK3, from the DrugBank database, our Vina-GPU 2.0 reaches an average of 65.6-fold, 1.4-fold, and 3.6-fold docking acceleration against the original AutoDock Vina, QuickVina 2, and QuickVina-W while ensuring their comparable docking accuracy. In addition, we develop a friendly and installation-free graphical user interface tool for their convenient usage. The codes and tools of Vina-GPU 2.0 are freely available at https://github.com/DeltaGroupNJUPT/Vina-GPU-2.0, coupled with explicit instructions and examples.

IGFBP3 epigenetic promotion induced by METTL3 boosts cardiac fibroblast activation and fibrosis.

Cardiac fibrosis remains an unresolved problem in heart disease. Its etiology is directly caused by the activation and proliferation of cardiac fibroblasts (CFs). However, there is limited information regarding the biological role of cardiac fibroblasts in cardiac fibrosis. Herein, we screened out a gene, IGFBP3, whose expression significantly increased in TGF-ß1-stimulated human primary CFs by mining RNA-Seq data for differential and WGCNA. We verified the IGFBP3's expression in transverse aortic constriction (TAC) surgery, isoproterenol (ISO)-induced cardiac fibrosis models, and TGFß1-stimulated mouse primary CFs. We also found that the knockdown of IGFBP3 could inhibit the migration and proliferation ability of CFs. Furthermore, we found that aberrant N6-methyladenosine(m6A) mRNA modifications in the animal model and activated CFs may regulate the expression of IGFBP3 in developing cardiac fibrosis. Silencing METTL3 could downregulate the expression of IGFBP3 and inhibit the activation of CFs and the degree of cardiac fibrosis both in vitro and in vivo. Indeed, we also verified the expression of METTL3 and IGFBP3 in the atrial tissues of patients with atrial fibrillation (AF). Thus, METTL3 may regulate IGFBP3's expression and CFs activation via RNA epigenetic modifications, laying the foundation for a specific and novel therapeutic target in cardiac fibrosis.

Epigenetic control of LncRNA NEAT1 enables cardiac fibroblast pyroptosis and cardiac fibrosis.

Cardiac fibroblasts (CFs) drive extracellular matrix remodeling after inflammatory injury, leading to cardiac fibrosis and diastolic dysfunction. Recent studies described the role of epigenetics in cardiac fibrosis. Nevertheless, detailed reports on epigenetics regulating CFs pyroptosis and describing their implication in cardiac fibrosis are still unclear. Here, we found that DNMT3A reduces the expression of lncRNA Neat1 and promotes the NLRP3 axis leading to CFs pyroptosis, using cultured cells, animal models, and clinical samples to shed light on the underlying mechanism. We report that pyroptosis-related genes are increased explicitly in cardiac fibrosis tissue and LPS-treated CFs, while lncRNA Neat1 decreased. Mechanistically, we show that loss of DNMT3A or overexpression of lncRNA Neat1 in CFs after LPS treatment significantly enhances CFs pyroptosis and the production of pyroptosis-related markers in vitro. It has been demonstrated that DNMT3A can decrease lncRNA Neat1, promoting NLRP3 axis activation in CFs treated with LPS. In sum, this study is the first to identify that DNMT3A methylation decreases the expression of lncRNA Neat1 and promotes CFs pyroptosis and cardiac fibrosis, suggesting that DNMT3A and NEAT1 may function as an anti-fibrotic therapy target in cardiac fibrosis.

Correlation between family environment and depressive symptoms among adolescents / 中国学校卫生

Objective@#To understand the relationship between family environment and depressive symptoms among adolescent, and to provide a reference for adolescent mental health promotion and intervention.@*Methods@#From September to December in 2021, a questionnaire survey on family environment and depressive symptoms was conducted among 8 102 middle school students by random cluster sampling method in Shanghai, Urumqi, Changsha and Kunming. The Chi square test was used to compare the depression status of students in different family environments. Multivariate Logistic regression analysis was used to explore the relationship between family environment and depressive symptoms.@*Results@#The detection rates of possible depression, likely depression and severe depression in adolescents were 11.2%, 5.9% and 8.4%, respectively. There were significant differences in the detection rate of depression by gender, academic period, urban and rural areas, family forms and only child statu( χ 2=87.60, 27.19, 6.65, 45.59, 4.78, P <0.05). Logistic regression analysis showed that adolescents in single parent families ( OR =1.45) and reorganized families( OR =1.69) were positively correlated with the occurrence of depressive symptoms compared with those in nuclear families( P <0.01).@*Conclusion@#Compared with nuclear families, the risks of adolescent depressive symptoms in single parent families and reorganized families are higher. Attention should be paid to the mental health education of teenagers from single parents and reorganized families to ensure the development of their physical and mental health.

Shift the focus to earlier prevention and control of adolescent depression / 中国学校卫生

Abstract@#Depression severely affects the healthy development of adolescents and has become a major public health challenge in China. The outbreak and normalization of COVID-19 have posed a serious challenge to the prevention and treatment of depression in adolescents. Given the characteristics of adolescent physical and mental development and depression pathology, the prevention and control of depression in adolescents should be shifted to an earlier stage. "Screening and dynamic monitoring" should be an important way to shift the focus of prevention and control of depression in adolescents. "Population based prevention" should be an important guarantee for achieving the shift toward early prevention and control of depression in adolescents, which builds a solid barrier for the mental health protection and promotion among Chinese adolescents.

METTL3 boosts glycolysis and cardiac fibroblast proliferation by increasing AR methylation.

Dysregulated glycolysis has been noted in several pathological processes characterized by supporting cell proliferation. Nonetheless, the role of glycolysis reprogramming is not well appreciated in cardiac fibrosis which is accompanied by increased fibroblasts proliferation. In this study, we investigated the cause and consequence of glycolysis reprogramming in cardiac fibrosis, using clinical samples, animal models, and cultured cells. Herein, we report that methyltransferase-like 3 (METTL3) facilitates glycolysis and cardiac fibroblasts proliferation, leading to cardiac fibrosis. The augmentation of glycolysis, an essential event during cardiac fibroblasts proliferation, is dependent on an increased expression of METTL3. A knockdown of METTL3 suppressed glycolysis, and inhibited cardiac fibroblast proliferation and cardiac fibrosis. Mechanistically, METTL3 epigenetically repressed androgen receptor (AR) expression in an m6A-YTHDF2- dependent manner, by targeting the specific AR m6A site. AR could interact with the glycolysis marker HIF-1α, and down-regulation of AR activates HIF-1α signaling, resulting in enhanced glycolysis and cardiac fibroblast proliferation. In contrast, the overexpression of AR significantly reduced the HIF-1α axis, decreased expression of glycolytic enzymes HK3, inhibited glycolysis, and repressed cardiac fibroblasts proliferation. Notably, increased METTL3 and YTHDF2 levels, decreased AR expression, increased HIF-1α and Postn expression and augmented glycolysis, and increased cardiac fibrosis were detected in human atrial fibrillation heart tissues. Our results found a novel mechanism by which METTL3-catalyzed m6A modification in cardiac fibrosis, wherein it facilitated glycolysis and cardiac fibroblasts proliferation by increasing AR methylation in an m6A-YTHDF2- dependent manner and provided new insights strategies to intervene cardiac fibrosis.

Reconstruction mechanism and strategy of global maritime green supply chain against the backdrop of nuclear pollution.

Owing to the nuclear accident at Fukushima, everyone involved in the supply chain began to reflect on the ongoing efforts to minimize the environmental impact. Being part of the green supply chain, it is important for maritime companies to restructure their mechanism and strategy for the future. This study analyzes the framework of the reconstruction mechanism and strategy of the global maritime green supply chain against the backdrop of nuclear pollution in four dimensions, namely, ecology, management, economy, and society. On the basis of these four dimensions, 20 suitable evaluation indicators are constructed to develop an expert questionnaire. These indicators are used to identify the importance of the maritime green supply chain through the fuzzy analytic hierarchy process so that decision makers can discover the intrinsic key competencies. According to the results of the study, the indicators of critical success factors (CSFs) are as follows: 1. "Reduction of waste discharge and pollution treatment"; 2. "Construction of environmentally friendly fleets, desulfurization retrofit, and fleet replacement to comply with the International Maritime Organization's regulations and improve energy efficiency"; 3. " Regular audit, assessment, and review of compliance with environmental laws and regulations"; 4. "Priority access to ports and increased profitability by participating in the Green Ship Incentive Program"; and 5. " Dedicated management units and departments responsible for policies related to green capabilities." The results provide a reference for the decision making of maritime companies to identify the key reconstruction mechanism and CSFs in the maritime green supply chain and explore future service models as a way to build competitive advantage and ensure sustainable operations. This study integrates the ecological theory and concept of the green supply chain management. Furthermore, the results of this study provide policy implications for stakeholders, such as maritime companies and governments, in implementing and promoting green supply chain practices.

MTHFR epigenetic derepression protects against diabetes cardiac fibrosis.

BACKGROUND: Diabetes cardiac fibrosis is associated with altered DNA methylation of fibrogenic genes; however, the underlying mechanisms remain unclear. OBJECTIVES: In this study, we investigate the critical role of DNA methylation aberration-associated suppression of MTHFR in diabetes cardiac fibrosis, and the protective effects of folate on diabetes cardiac fibrosis, using cultured cells, animal models, and clinical samples. METHODS AND RESULTS: Herein, we report that DNA methylation repression of MTHFR, critically involved in diabetes cardiac fibrosis, mediates the significant protective effects of folate in a mouse model of diabetes cardiac fibrosis induced by STZ. Heart MTHFR expression was markedly suppressed in diabetes cardiac fibrosis patients and mice, accompanied by increased DNMT3A and MTHFR promoter methylation. Knockdown of DNMT3A demethylated MTHFR promoter, recovered the MTHFR loss, and alleviated the diabetes cardiac fibrosis pathology and cardiac fibroblasts pyroptosis. Mechanistically, DNMT3A epigenetically repressed MTHFR expression via methylation of the promoter. Interestingly, folate supplementation can rescue the effect of MTHFR loss in diabetes cardiac fibrosis, suggesting that inactivation of MTHFR through epigenetics is a critical mediator of diabetes cardiac fibrosis. CONCLUSIONS: The current study identifies that MTHFR repression due to aberrant DNMT3A elevation and subsequent MTHFR promoter hypermethylation is likely an important epigenetic feature of diabetes cardiac fibrosis, and folate supplementation protects against diabetes cardiac fibrosis.

[Response Characteristics of Soil Microbial Community Under Long-term Film Mulching].

Film mulching is an important practice to increase the yield and income in agricultural production. Soil samples were collected from four farmland sites with different mulching years to reveal the effect of long-term plastic mulching on characteristics of soil microbial community structure. In order to explore the long-term effect of soil microbial community change and its effect on the microbial ecological environment, high-throughput sequencing technology was used to analyze the changes in soil bacterial and fungal community structure. The results showed that long-term film mulching had no significant effect on soil bacterial diversity but decreased fungal diversity. Long-term film mulching decreased the abundance of Acidobacteriota and Mortierellomycetes and increased the abundance of Actinobacteriota. Long-term film mulching enriched the beneficial microbial communities such as Bacillus, Nocardioidaceae, Aspergillus, and Hypocreales in soil. However, long-term film mulching indued a simple and fragile soil fungal co-occurrence network pattern. The unidentified Sordariales under Ascomycota was the only key species in the fungal co-occurrence network, which resulted in potential risks to the ecological environment of the farmland soil. This study provided a theoretical basis for further understanding the effects of long-term film mulching on the ecological and environmental effects of microorganisms in farmland.

Proteomic Analysis Reveals the Vital Role of Synaptic Plasticity in the Pathogenesis of Temporal Lobe Epilepsy.

Temporal lobe epilepsy (TLE) is a chronic neurological disorder that is often resistant to antiepileptic drugs. The pathogenesis of TLE is extremely complicated and remains elusive. Understanding the molecular mechanisms underlying TLE is crucial for its diagnosis and treatment. In the present study, a lithium-pilocarpine-induced TLE model was employed to reveal the pathological changes of hippocampus in rats. Hippocampal samples were taken for proteomic analysis at 2 weeks after the onset of spontaneous seizure (a chronic stage of epileptogenesis). Isobaric tag for relative and absolute quantization (iTRAQ) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was applied for proteomic analysis of hippocampus. A total of 4173 proteins were identified from the hippocampi of epileptic rats and its control, of which 27 differentially expressed proteins (DEPs) were obtained with a fold change > 1.5 and P < 0.05. Bioinformatics analysis indicated 27 DEPs were mainly enriched in "regulation of synaptic plasticity and structure" and "calmodulin-dependent protein kinase activity," which implicate synaptic remodeling may play a vital role in the pathogenesis of TLE. Consequently, the synaptic plasticity-related proteins and synaptic structure were investigated to verify it. It has been demonstrated that CaMKII-α, CaMKII-ß, and GFAP were significant upregulated coincidently with proteomic analysis in the hippocampus of TLE rats. Moreover, the increased dendritic spines and hippocampal sclerosis further proved that synaptic plasticity involves in the development of TLE. The present study may help to understand the molecular mechanisms underlying epileptogenesis and provide a basis for further studies on synaptic plasticity in TLE.

Accelerating AutoDock Vina with GPUs.

AutoDock Vina is one of the most popular molecular docking tools. In the latest benchmark CASF-2016 for comparative assessment of scoring functions, AutoDock Vina won the best docking power among all the docking tools. Modern drug discovery is facing a common scenario of large virtual screening of drug hits from huge compound databases. Due to the seriality characteristic of the AutoDock Vina algorithm, there is no successful report on its parallel acceleration with GPUs. Current acceleration of AutoDock Vina typically relies on the stack of computing power as well as the allocation of resource and tasks, such as the VirtualFlow platform. The vast resource expenditure and the high access threshold of users will greatly limit the popularity of AutoDock Vina and the flexibility of its usage in modern drug discovery. In this work, we proposed a new method, Vina-GPU, for accelerating AutoDock Vina with GPUs, which is greatly needed for reducing the investment for large virtual screens and also for wider application in large-scale virtual screening on personal computers, station servers or cloud computing, etc. Our proposed method is based on a modified Monte Carlo using simulating annealing AI algorithm. It greatly raises the number of initial random conformations and reduces the search depth of each thread. Moreover, a classic optimizer named BFGS is adopted to optimize the ligand conformations during the docking progress, before a heterogeneous OpenCL implementation was developed to realize its parallel acceleration leveraging thousands of GPU cores. Large benchmark tests show that Vina-GPU reaches an average of 21-fold and a maximum of 50-fold docking acceleration against the original AutoDock Vina while ensuring their comparable docking accuracy, indicating its potential for pushing the popularization of AutoDock Vina in large virtual screens.

Phytotoxic Azaphilones From the Mangrove-Derived Fungus Penicillium sclerotiorum HY5.

Mangrove is a unique marine ecosystem growing in the intertidal zone of tropical and subtropical coast, with the characteristics of hypoxia tolerance, high salinity, and high humidity. In order to discover novel leading compounds with potent phytotoxicity, seven pairs of azaphilones E/Z isomers, isochromophilone H (1a/1b), sclerotiorins A and B (2a/2b and 3a/3b), ochlephilone (4a/4b), isochromophilone IV (5a/5b), isochromophilone J (6a/6b), and isochromophilone I (7a/7b), were isolated from the culture broth of the mangrove-derived fungus, the Penicillium sclerotiorum HY5, by various chromatographic methods. Among them, 1a, 1b, 2a, 3a, 4a, 5a, 6a, and 6b were new compounds. Their chemical structures and absolute configurations were elucidated based on high resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D nuclear magnetic resonance (NMR) spectroscopic analysis, and comparisons of electronic circular dichroism (ECD) data. Compounds 3, 4, and 7 exhibited potent phytotoxicity against the growth of radicle and plumule on Amaranthus retroflexus L., with EC50 values ranging from 234.87 to 320.84 µM, compared to the positive control glufosinate-ammonium, with EC50 values of 555.11 µM for radicle, and 656.04 µM for plumule. Compounds 4 and 7 also showed inhibitory effects on the growth of velvetleaf (Abutilon theophrasti Medikus), with EC50 values ranging from 768.97 to 1,201.52 µM. This study provides new leading compounds for the research and development of marine-derived bioherbicides.

Potential Blood DNA Methylation Biomarker Genes for Diagnosis of Liver Fibrosis in Patients With Biopsy-Proven Non-alcoholic Fatty Liver Disease.

Background and objective: This pilot study aimed to identify potential blood DNA methylation (BDM) biomarker genes for the diagnosis of liver fibrosis in non-alcoholic fatty liver disease (NAFLD). Methods: We included a total of 16 NAFLD patients with significant (SLF, liver fibrosis stage ≥ 2) and 16 patients with non-significant liver fibrosis (NSLF, fibrosis stages 0-1). The association between BDM and liver fibrosis was analyzed. Genes were selected based on a stepwise-filtering with CpG islands containing significant differentially methylated probes. Results: The two groups of patients were distinguishable through both t-distributed stochastic neighbor embedding (t-SNE) analysis and unsupervised hierarchical clustering analysis based on their BDM status. BDM levels were significantly higher in the NSLF group than in the SLF group. The methylation levels in the island and shelf regions were also significantly higher in the NSLF group, as well as the methylation levels in the first exon, 3'-untranslated region, body, ExonBnd, non-intergenic region, transcription start site (TSS)1500, and TSS200 regions (all p < 0.05). BDM status was associated with greater histological liver fibrosis, but not with age, sex, or other histological features of NAFLD (p < 0.05). The methylation levels of the hypomethylated CpG island region of CISTR, IFT140, and RGS14 genes were increased in the NSLF group compared to the SLF group (all p < 0.05). Conclusion: BDM may stratify NAFLD patients with significant and non-significant liver fibrosis. The CISTR, IFT140, and RGS14 genes are potential novel candidate BDM biomarkers for liver fibrosis and these pilot data suggest further work on BDM biomarkers is warranted.