O-GlcNAc has crosstalk with ADP-ribosylation via PARG.

O-linked N-acetylglucosamine (O-GlcNAc) glycosylation, a prevalent protein post-translational modification (PTM) that occurs intracellularly, has been shown to crosstalk with phosphorylation and ubiquitination. However, it is unclear whether it interplays with other PTMs. Here we studied its relationship with ADP-ribosylation, which involves decorating target proteins with the ADP-ribose moiety. We discovered that the poly(ADP-ribosyl)ation "eraser", ADP-ribose glycohydrolase (PARG), is O-GlcNAcylated at Ser26, which is in close proximity to its nuclear localization signal. O-GlcNAcylation of PARG promotes nuclear localization and chromatin association. Upon DNA damage, O-GlcNAcylation augments the recruitment of PARG to DNA damage sites and interacting with proliferating cell nuclear antigen (PCNA). In hepatocellular carcinoma (HCC) cells, PARG O-GlcNAcylation enhances the poly(ADP-ribosyl)ation of DNA damage-binding protein 1 (DDB1) and attenuates its auto-ubiquitination, thereby stabilizing DDB1 and allowing it to degrade its downstream targets, such as c-Myc. We further demonstrated that PARG-S26A, the O-GlcNAc-deficient mutant, promoted HCC in mouse xenograft models. Our findings thus reveal that PARG O-GlcNAcylation inhibits HCC, and we propose that O-GlcNAc glycosylation may crosstalk with many other PTMs.

[Effect of Fuzheng Huayu capsule on serum metabolomics in rats with liver fibrosis induced by dimethylnitrosamine].

To investigate the effect of Fuzheng Huayu capsule(FHC) on serum metabolomics in rats with liver fibrosis induced by dimethylnitrosamine(DMN). The metabolic profiles of rat serum of normal group, model group, and FHC group were established by liquid chromatography-mass spectrometry technology. Furthermore, the levels of endogenous metabolites such as amino acids and bile acids were measured in each group. The results showed that there were significant differences in the serum metabolic fingerprints between the FHC group and the model group. Moreover, 5 potential lysophosphatidylcholines biomarkers were identified by using principal component analysis(PCA) and partial least squares discriminant analysis (PLS-DA). Quantitative analysis of amino acids and bile acids in serum of rats showed that 14 kinds of amino acids and 5 kinds of bile acids returned to normal levels after four weeks of FHC treatment. In conclusion, the anti-hepatic fibrosis mechanisms of FHC may be related to the metabolic process of lysophosphatidylcholines, amino acids and bile acids.

Semantic embedding based online cross-modal hashing method.

Hashing has been extensively utilized in cross-modal retrieval due to its high efficiency in handling large-scale, high-dimensional data. However, most existing cross-modal hashing methods operate as offline learning models, which learn hash codes in a batch-based manner and prove to be inefficient for streaming data. Recently, several online cross-modal hashing methods have been proposed to address the streaming data scenario. Nevertheless, these methods fail to fully leverage the semantic information and accurately optimize hashing in a discrete fashion. As a result, both the accuracy and efficiency of online cross-modal hashing methods are not ideal. To address these issues, this paper introduces the Semantic Embedding-based Online Cross-modal Hashing (SEOCH) method, which integrates semantic information exploitation and online learning into a unified framework. To exploit the semantic information, we map the semantic labels to a latent semantic space and construct a semantic similarity matrix to preserve the similarity between new data and existing data in the Hamming space. Moreover, we employ a discrete optimization strategy to enhance the efficiency of cross-modal retrieval for online hashing. Through extensive experiments on two publicly available multi-label datasets, we demonstrate the superiority of the SEOCH method.

ULK1-dependent phosphorylation of PKM2 antagonizes O-GlcNAcylation and regulates the Warburg effect in breast cancer.

Pyruvate kinase M2 (PKM2) is a central metabolic enzyme driving the Warburg effect in tumor growth. Previous investigations have demonstrated that PKM2 is subject to O-linked ß-N-acetylglucosamine (O-GlcNAc) modification, which is a nutrient-sensitive post-translational modification. Here we found that unc-51 like autophagy activating kinase 1 (ULK1), a glucose-sensitive kinase, interacts with PKM2 and phosphorylates PKM2 at Ser333. Ser333 phosphorylation antagonizes PKM2 O-GlcNAcylation, promotes its tetramer formation and enzymatic activity, and decreases its nuclear localization. As PKM2 is known to have a nuclear role in regulating c-Myc, we also show that PKM2-S333 phosphorylation inhibits c-Myc expression. By downregulating glucose consumption and lactate production, PKM2 pS333 attenuates the Warburg effect. Through mouse xenograft assays, we demonstrate that the phospho-deficient PKM2-S333A mutant promotes tumor growth in vivo. In conclusion, we identified a ULK1-PKM2-c-Myc axis in inhibiting breast cancer, and a glucose-sensitive phosphorylation of PKM2 in modulating the Warburg effect.

MnO2-based capacitive system enhances ozone inactivation of bacteria by disrupting cell membrane.

The application of ozone (O3) disinfection has been hindered by its low solubility in water and the formation of disinfection by-products (DBPs). In this study, capacitive disinfection is applied as a pre-treatment for O3 oxidation, in which manganese dioxide with a rambutan-like hollow spherical structure is used as the electrode to increase the charge density on the electrode surface. When a voltage is applied, the negative-charged microbes are attracted to the electrodes and killed by electrical interactions. The contact between microbes and capacitive electrodes leads to changes in cell permeability and burst of reactive oxygen species, thereby promoting the diffusion of O3 into the cells. After O3 penetrates the cell membrane, it can directly attack the cytoplasmic constituents, accelerating fatal and irreversible damage to pathogens. As a result, the performance of the capacitance-O3 process is proved better than the direct sum of the two individual process efficiencies. The design of capacitance-O3 system is beneficial to reduce the ozone dosage and DBPs with a broader inactivation spectrum, which is conducive to the application of ozone in primary water disinfection.

An internet traffic classification method based on echo state network and improved salp swarm algorithm.

Internet traffic classification is fundamental to network monitoring, service quality and security. In this paper, we propose an internet traffic classification method based on the Echo State Network (ESN). To enhance the identification performance, we improve the Salp Swarm Algorithm (SSA) to optimize the ESN. At first, Tent mapping with reversal learning, polynomial operator and dynamic mutation strategy are introduced to improve the SSA, which enhances its optimization performance. Then, the advanced SSA are utilized to optimize the hyperparameters of the ESN, including the size of the reservoir, sparse degree, spectral radius and input scale. Finally, the optimized ESN is adopted to classify Internet traffic. The simulation results show that the proposed ESN-based method performs much better than other traditional machine learning algorithms in terms of per-class metrics and overall accuracy.

Acetylcholinesterase inhibitive activity-guided isolation of two new alkaloids from seeds of Peganum nigellastrum Bunge by an in vitro TLC- bioautographic assay.

Acetylcholinesterase inhibitors (AChEIs) currently form the basis of the newest drugs available for the treatment of Alzheimer's disease. For the aim of screening effective AChEIs, the methanol extracts of the seeds of genus Peganum were found to show significant inhibitory activity of acetylcholinesterase enzyme (AChE) using an in vitro TLC-bioautographic assay. In further studies to seed of P. nigellastrum Bunge, activity-guided fractionation led to the isolation of two new alkaloids nigellastrine I (9) and nigellastrine II (10), and along with eight known alkaloids, vasicinone (1), vasicine (2), harmine (3), deoxyvasicinone (4), deoxyvasicine (5), harmaline (6), harmol (7), harman (8), in which harmol and harman were first isolated from species P. nigellastrum Bunge. As active constituents, all compounds showed good inhibitory activities against AChE. The results of in vitro semi-quality TLC-bioautographic assay showed that harmine, harmaline and harmol displayed a similar AChE inhibitive activities comparing to galanthamine. These results indicated that these alkaloids in P. nigellastrum Bunge could be a potent class of AChEIs.

Development of microbial community within the cathodic biofilm of single-chamber air-cathode microbial fuel cell.

The aim of this study was to investigate the development of microbial community within the cathodic biofilm of single-chamber air-cathode microbial fuel cell (MFC). To analyze microbial community structures within cathodic biofilm, cathodic biofilm samples were stratified into three layers, i.e., the cathode-side layer (0-40 µm), the middle layer (40-80 µm), and the anolyte-side layer (80-120 µm). After four starting cycles (0-188 h), the maximum power densities of the MFC fed with 1 g/L acetate decreased from 1056 ±â€¯110 to 410 ±â€¯50 mW/m2 within 15 cycles (~30 d) of operation. The relative abundance of Pseudomonas gradually increased from 18.9% in the 1st cycle to 50.2% in the 4th cycle. After 15 cycles, the relative abundance of Pseudomonas became 53.8%, 16.4%, and 8.90% in the middle, anolyte-side, and cathode-side layers, respectively. The aerobic bacteria within the cathodic biofilm increased from 24% in the anodyte-side layer to 43% in the cathode-side layer. The relative abundance of Methanobrevibacter was 42.1% and 37.2% after 3 and 15 cycles, respectively. The bacterial community structures were similar among cycles 2, 3, and 4, but significantly different in the 15th cycle. The results from this study should be useful to understand the mechanism of the cathodic biofilm formation and to develop strategies to enhance performance of the MFC.

Antioxidant, antiapoptotic and amino acid balance regulating activities of 1,7-dihydroxy-3,4,8-trimethoxyxanthone against dimethylnitrosamine-induced liver fibrosis.

Liver fibrosis represents the consequences of a sustained wound healing response to chronic liver injury which could be caused by viral, autoimmune, drugs, and so on. Unfortunately, there was no effective therapy available for liver fibrosis in clinic. In this study, we identified the anti-fibrotic effects of 1,7-dihydroxy-3,4,8-trimethoxyxanthone (ZYC-1) on the dimethylnitrosamine (DMN)-induced rat model. ZYC-1 was isolated from Swertia punicea Hemsl and was administrated to DMN-induced rat model. ZYC decreased the hyaluronic acid (HA), type IV collagen (CIV) and hydroxyproline (Hyp) levels and inhibited the expression of α smooth muscle actin (α-SMA) and transforming growth factor beta 1 (TGF-1ß). The anti-fibrotic effect of ZYC-1 was also confirmed by Sirius Red staining. Finally, we identified 42 differentially expressed proteins by using proteomics analysis after ZYC-1 treatment, of which 17 were up-regulated and 25 were down-regulated. These Most of the 42 proteins are involved in the oxidative stress pathway, the mitochondrial-mediated apoptotic pathway and the amino acid metabolism pathway. Our study presented the first elucidated mechanisms of xanthone on liver fibrosis in vivo. This study pointed out that ZYC-1 may be used as a lead compound for hepatofibrosis treatment.

Neuropsychological profile in Chinese patients with Parkinson's disease and normal global cognition according to Mini-Mental State Examination Score.

OBJECT: Cognitive impairments have been reported to be more common in non-demented patients with Parkinson's disease (PD) and education levels play an important role in intelligence. The studies on cognitive impairments in Chinese PD patients with higher education levels and normal global cognition according to Mini-Mental State Examination Score (MMSE) have not been reported. METHODS: We enrolled 69 consecutive PD patients with over 6 years education levels and a MMSE score above 24 (of 30) and performed a battery of neuropsychological scales. RESULTS: There are extensive cognitive domain impairments in PD patients with "normal" global cognitive according to MMSE. Montreal Cognitive Assessment (MoCA) is a highly sensitive scale to screen cognitive impairments in PD. CONCLUSION: The cutoff score of 28 on the MMSE screening for cognitive impairment in Chinese PD patients with high education levels may be more appropriate.

Two xanthones from Swertia punicea with hepatoprotective activities in vitro and in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia punicea Hemsl. (Gentianaceae) is more commonly known as "Ganyan-cao" and used mainly as a traditional Chinese folk medicine for the treatment of acute bilious hepatitis, cholecystitis, fever, intoxification and jaundice. MATERIALS AND METHODS: The active hepatoprotective constituents of Swertia punicea were purified using various column chromatography techniques. The structures of two isolated compounds were determined on the basis of spectroscopic data interpretation such as NMR analysis. The hepatoprotective activities of isolated compounds were evaluated by using hepatotoxicity in vitro and dimethylnitrosamine-induced rat hepatic fibrosis in vivo, respectively. RESULTS: Two xanthones, 1, 7-dihydroxy-3, 4, 8-trimethoxyxanthone (1) and bellidifolin (2) were isolated from the stems of Swertia punicea. The compounds 1 and 2 exhibited notable hepatoprotective activities against carbon tetrachloride (CCl4) -induced HepG2 cell damage, and effectively alleviated the levels of aspartate transaminase (AST), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malonic dialdehyde (MDA) induced by CCl4 in a concentration-dependent manner. Co-treatment with compound 2 significantly increased the cell viability compared with N-acetyl-p-aminophenol (APAP) treatment. Compound 2 also alleviated APAP-induced hepatotoxicity by increasing glutathione (GSH) content and decreasing hydroxyl free radical (·OH) levels and reactive oxygen specises (ROS) production. In addition, the protective effect of compound 1 significantly alleviated DMN-induced liver inflammation and fibrosis. Oral administration of compound 1 recovered the reduction of albumin (ALB) and reversed the elevation of serum alanine transaminase (ALT), AST and total bilirubin (TBIL) in dimethylnitrosamine (DMN)-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by a 1.5-fold elevation in MDA and a fall in the SOD activity, and treatment with compound 1 protected against these adverse effects. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by compound 1 is also confirmed by H&E and Masson stained histopathological evaluation of liver tissue. CONCLUSION: Two xanthones from Swertia punicea exhibited hepatoprotective activities in vitro (compounds 1 and 2) and in vivo (compound 1), respectively.