Revealing the effect of conductive carbon materials on the sodium storage performance of sodium iron sulfate.

Na2Fe2(SO4)3 (NFS), as a promising cathode for sodium-ion batteries, is still plagued by its poor intrinsic conductivity. In general, hybridization with carbon materials is an effective strategy to improve the sodium storage performance of NFS. However, the role of carbon materials in the electrochemical performance of NFS cathode materials has not been thoroughly investigated. Herein, the effect of carbon materials was revealed by employing various conductive carbon materials as carbon sources. Among these, the NFS coated with Ketjen Black (NFS@KB) shows the largest specific surface area, which is beneficial for electrolyte penetration and rapid ionic/electronic migration, leading to improved electrochemical performance. Therefore, NFS@KB shows a long cycle life (74.6 mA h g-1 after 1000 cycles), superior rate performance (61.5 mA h g-1 at a 5.0 A g-1), and good temperature tolerance (-10 °C to 60 °C). Besides, the practicality of the NFS@KB cathode was further demonstrated by assembling a NFS@KB//hard carbon full cell. Therefore, this research indicates that a suitable carbon material for the NFS cathode can greatly activate the sodium storage performance.

Investigation of the Catalytic Mechanism of a Soluble N-glycosyltransferase Allows Synthesis of N-glycans at Noncanonical Sequons.

The soluble N-glycosyltransferase from Actinobacillus pleuropneumoniae (ApNGT) can establish an N-glycosidic bond at the asparagine residue in the Asn-Xaa-Ser/Thr consensus sequon and is one of the most promising tools for N-glycoprotein production. Here, by integrating computational and experimental strategies, we revealed the molecular mechanism of the substrate recognition and following catalysis of ApNGT. These findings allowed us to pinpoint a key structural motif (215DVYM218) in ApNGT responsible for the peptide substrate recognition. Moreover, Y222 and H371 of ApNGT were found to participate in activating the acceptor Asn. The constructed models were supported by further crystallographic studies and the functional roles of the identified residues were validated by measuring the glycosylation activity of various mutants against a library of synthetic peptides. Intriguingly, with particular mutants, site-selective N-glycosylation of canonical or noncanonical sequons within natural polypeptides from the SARS-CoV-2 spike protein could be achieved, which were used to investigate the biological roles of the N-glycosylation in membrane fusion during virus entry. Our study thus provides in-depth molecular mechanisms underlying the substrate recognition and catalysis for ApNGT, leading to the synthesis of previously unknown chemically defined N-glycoproteins for exploring the biological importance of the N-glycosylation at a specific site.

Petite Integration Factor 1 knockdown enhances gemcitabine sensitivity in pancreatic cancer cells via increasing DNA damage.

Chemoresistance is still a vital obstacle in various tumors chemotherapy. This study aimed to explore the role of Petite Integration Factor 1 (PIF1) in the sensitivity of gemcitabine response to pancreatic cancer cells. Gene Expression Profiling Interactive Analysis (GEPIA) database was employed for evaluating the level of PIF1 in pancreatic cancer tissues and normal tissues. The mRNA level of PIF1 was detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. The relative protein expression of PIF1, cleaved caspase-3, and phosphorylated histone H2Ax (γH2Ax) was assessed through western blot. Cell viability and apoptosis were assessed via Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. Moreover, lactate dehydrogenase (LDH) release and caspase-3 activity were determined via the corresponding LDH Cytotoxicity Assay Kit and caspase-3 colorimetric assay kit. PIF1 expression was upregulated in pancreatic cancer tissues and cells. Knockdown of PIF1 exhibited the repressive impact on the viability of AsPC-1 and PANC-1 cells. PIF1 knockdown enhanced LDH release and apoptosis in both AsPC-1 and PANC-1 cells. PIF1 downregulation could augment the sensitivity of gemcitabine in pancreatic cancer cells, as evidenced by lower cell viability and higher LDH release and apoptosis rate after knocking down PIF1 in gemcitabine-treated pancreatic cancer cells relative to pancreatic cancer cells treated with gemcitabine alone. Moreover, PIF1 knockdown increased γH2Ax protein expression and DNA damage, and gemcitabine treatment-induced DNA damage in AsPC-1 and PANC-1 cells was exacerbated by PIF1 silencing. Furthermore, gemcitabine treatment-caused increase of DNA damage was alleviated by PIF1 overexpression; whereas, this effect of PIF1 upregulation was reversed by thymidine, a DNA synthesis inhibitor. In addition, the decreased gemcitabine sensitivity response to pancreatic cancer cells caused by PIF1 upregulation was also hindered by thymidine treatment. In conclusion, PIF1 silencing enhanced gemcitabine sensitivity response to pancreatic cancer cells through aggrandizing DNA damage.

Surface Defect Segmentation Algorithm of Steel Plate Based on Geometric Median Filter Pruning.

Problems such as redundancy of detection model parameters make it difficult to apply to factory embedded device applications. This paper focuses on the analysis of different existing deep learning model compression algorithms and proposes a model pruning algorithm based on geometric median filtering for structured pruning and compression of defect segmentation detection networks on the basis of structured pruning. Through experimental comparisons and optimizations, the proposed optimization algorithm can greatly reduce the network parameters and computational effort to achieve effective pruning of the defect detection algorithm for steel plate surfaces.

Involvement of elevated ASF1B in the poor prognosis and tumorigenesis in pancreatic cancer.

Anti-silencing function 1B (ASF1B) has been reported to be associated with the occurrence of many kinds of tumors. However, the biological effect and action mechanism of ASF1B in pancreatic cancer (PC) tumorigenesis remain unclear. The expression and prognosis value of ASF1B in PC were analyzed using GEPIA, GEO, and Kaplan-Meier plotter databases. The diagnostic value of ASF1B in PC was determined by receiver operating characteristic curve. The relationship between ASF1B expression and the clinical feathers in PC was investigated based on TCGA. qRT-PCR and western blot analyses were used to measure ASF1B expression in PC cells. Cell proliferation was evaluated by MTT and EdU assays, and apoptosis was examined by TUNEL and caspase-3 activity assays. Western blot analysis was utilized to detect the expression of proliferating cell nuclear antigen (PCNA), cyclin D1, Bax, Bcl-2, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling proteins. ASF1B was overexpressed in several digestive cancers, including PC. Upregulated ASF1B was correlated with the poor prognosis and clinical features in PC patients. The area under the curve (AUC) value of ASF1B was 0.990. ASF1B was also overexpressed in PC cells. ASF1B silencing inhibited PC cell proliferation, promoted apoptosis, and increased caspase-3 activity, which were accompanied by the reduction of PCNA and cyclin D1 expression and increase of the ratio of Bax/Bcl-2 expression. Additionally, ASF1B silencing suppressed the PI3K/Akt pathway and 740Y-P treatment partially abolished the effects of ASF1B knockdown on PC cells. In conclusion, ASF1B silencing retarded proliferation and promoted apoptosis in PC cells by inactivation of the PI3K/Akt pathway.

Inhibition of gap junction communication between cells can induce apoptosis of corpus cavernosum smooth muscle in guinea pigs.

In this study, we aimed to investigate the effect of gap junction (GJ) on apoptosis of smooth muscle. Forty adult male guinea pigs were randomly divided into four groups with 10 guinea pigs in each group. Adeno-associated virus (AAV) and Gap27 were injected at the root of the corpus cavernosum. Two weeks later, the corpus cavernosum tissue was taken to be tested. The expression of Cx43 and α-SMC protein was detected by immunofluorescence and Western blotting. The content of corpus cavernosum smooth muscle was detected by Masson trichrome staining. Apoptosis was detected by TUNEL staining and Western blotting. The results showed that Gap27 did not affect Cx43 but decreased the expression of smooth muscle. The results of TUNEL staining and detection of apoptosis-related proteins showed that apoptosis was induced by Gap27. In addition, we found that corpus cavernosum injection of AAV could induce obvious apoptosis. In this study, we examined the effect of inhibition of gap junction on smooth muscle, and suggested that the decrease of gap junction function may be a potential mechanism of smooth muscle apoptosis.

Identification and Functional Analysis of lncRNAs Responsive to Hypoxia in Eospalax fontanierii.

Subterranean rodents could maintain their normal activities in hypoxic environments underground. Eospalax fontanierii, as one kind of subterranean rodent found in China can survive very low oxygen concentration in labs. It has been demonstrated that long non-coding RNAs (lncRNAs) have important roles in gene expression regulations at different levels and some lncRNAs were found as hypoxia-regulated lncRNAs in cancers. We predicted thousands of lncRNAs in the liver and heart tissues by analyzing RNA-Seq data in Eospalax fontanierii. Those lncRNAs often have shorter lengths, lower expression levels, and lower GC contents than mRNAs. Majors of lncRNAs have expression peaks in hypoxia conditions. We found 1128 DE-lncRNAs (differential expressed lncRNAs) responding to hypoxia. To search the miRNA regulation network for lncRNAs, we predicted 471 and 92 DE-lncRNAs acting as potential miRNA target and target mimics, respectively. We also predicted the functions of DE-lncRNAs based on the co-expression networks of lncRNA-mRNA. The DE-lncRNAs participated in the functions of biological regulation, signaling, development, oxoacid metabolic process, lipid metabolic/biosynthetic process, and catalytic activity. As the first study of lncRNAs in Eospalax fontanierii, our results show that lncRNAs are popular in transcriptome widely and can participate in multiple biological processes in hypoxia responses.

Olaparib effectively treats local recurrence of extrahepatic cholangiocarcinoma in a patient harboring a BRCA2-inactivating mutation: a case report.

Cholangiocarcinoma (CCA) is a malignant tumor with poor prognosis and high recurrence rate. There is no standard treatment for advanced CCA beyond first-line chemotherapy, which provides only limited benefits. In this study, we report a case of a postoperative recurrence ECC patient harboring a breast cancer 2 (BRCA2)-inactivating rearrangement mutation that had an obvious reaction to olaparib therapy. The patient was a 68-year-old man with postoperative recurrence of extrahepatic CCA (ECC) who declined systemic chemotherapy. In August 2015, abdominal computed tomography (CT) of the patient revealed intrahepatic bile duct dilatation, obstruction at the hepatic hilar region proximal to the common hepatic duct, and splenomegaly, and radical surgical resection was performed. Postoperative histopathology diagnosis was ECC without metastases. In February 2017, abdominal CT revealed local recurrence, and the patient refused chemotherapy. BRCA2 rearrangement were detected by next-generation sequencing. Oral administration of olaparib was initiated. The patient achieved stable disease 1 month later, progression-free survival for >10 months without any significant adverse reactions, and an overall survival (OS) of 27 months. This is the first report demonstrating the clinical benefits of olaparib in a BRCA2 rearrangement-harboring patient with ECC. This observation would help determine the best treatment option for advanced ECC patients.

Design, synthesis and antitumor activities of thiazole-containing mitochondrial targeting agents.

In this study, a novel batch of thiazole-containing mitochondrial targeting agents were designed and synthesized. Four kinds of mitochondrial targeting moieties and six kinds of linkers were designed. Their structures were confirmed by NMR and HR-MS. The screening of antiproliferative activity revealed that most compounds displayed cytotoxicity on HeLa cancer cell. In particular, D1 has an IC50 value of 35.32 µmol·L-1 against HeLa cell. In addition, cellular respiratory activities were also tested on HeLa cancer cells. D1 had a basal oxygen consumption rate of 8.84 pmol·s-1·mL-1. Also, D1 inhibited the mitochondrial respiration of HeLa cell significantly at 5 µmol·L-1, as well as a complete inhibitory of oxygen consumption for cellular ATP coupling. Furthermore, the pKa, logP, and logD under different pH conditions of all the compounds were calculated by the ACD/Percepta-PhysChem Suite, and the results manifested the correlation between physicochemical properties and chemical activity of compounds. The results identify D1 as a promising mitochondria inhibitor and anticancer agent with appropriate physicochemical properties.

Transcriptome analysis of the liver of Eospalax fontanierii under hypoxia.

Hypoxia can induce cell damage, inflammation, carcinogenesis, and inhibit liver regeneration in non-adapted species. Because of their excellent hypoxia adaptation features, subterranean rodents have been widely studied to clarify the mechanism of hypoxia adaptation. Eospalax fontanierii, which is a subterranean rodent found in China, can survive for more than 10 h under 4% O2 without observable injury, while Sprague-Dawley rats can survive for less than 6 h under the same conditions. To explore the potential mechanism of hypoxia responses in E. fontanierii, we performed RNA-seq analysis of the liver in E. fontanierii exposed to different oxygen levels (6.5% 6h, 10.5% 44h, and 21%). Based on the bioinformatics analysis, 39,439 unigenes were assembled, and 56.78% unigenes were annotated using public databases (Nr, GO, Swiss-Prot, KEGG, and Pfam). In total, 725 differentially expressed genes (DEGs) were identified in the response to hypoxia; six with important functions were validated by qPCR. Those DEGs were mainly involved in processes related to lipid metabolism, steroid catabolism, glycolysis/gluconeogenesis, and the AMPK and PPAR signaling pathway. By analyzing the expression patterns of important genes related to energy associated metabolism under hypoxia, we found that fatty acid oxidation and gluconeogenesis were increased, while protein synthesis and fatty acid synthesis were decreased. Furthermore, the upregulated expression of specific genes with anti-apoptosis or anti-oxidation functions under hypoxia may contribute to the mechanism by which E. fontanierii tolerates hypoxia. Our results provide an understanding of the response to hypoxia in E. fontanierii, and have potential value for biomedical studies.

Intelligent Detection of Steel Defects Based on Improved Split Attention Networks.

The intelligent monitoring and diagnosis of steel defects plays an important role in improving steel quality, production efficiency, and associated smart manufacturing. The application of the bio-inspired algorithms to mechanical engineering problems is of great significance. The split attention network is an improvement of the residual network, and it is an improvement of the visual attention mechanism in the bionic algorithm. In this paper, based on the feature pyramid network and split attention network, the network is improved and optimised in terms of data enhancement, multi-scale feature fusion and network structure optimisation. The DF-ResNeSt50 network model is proposed, which introduces a simple modularized split attention block, which can improve the attention mechanism of cross-feature graph groups. Finally, experimental validation proves that the proposed network model has good performance and application prospects in the intelligent detection of steel defects.

Astaxanthin improves serum cytokine expression and semen quality of diabetes mellitus KKAy mice.

The present study aims to explore the effects of astaxanthin on the semen quality of diabetes mellitus (DM) KKAy mice. A total of 60 DM KKAy mice with similar body weights and initial blood glucose and serum lipid levels were assigned to four groups, namely, one control and three astaxanthin treatments (10, 50, or 100 mg/kg astaxanthin). Results show that oral astaxanthin administration reduced fasting blood glucose and serum total cholesterol, low-density lipoprotein cholesterol, insulin and nitrate oxide levels in the testis of DM KKAy mice. Astaxanthin also improved the high-density lipoprotein cholesterol, protein and superoxide dismutase levels in the testis; serum interleukin-11, tumour necrosis factor-α and interferon-γ levels; and sperm density, sperm movement and normal morphology rate of DM KKAy mice. Based on the results, astaxanthin can effectively affect serum cytokines and ameliorate semen quality of DM KKAy mice; thus, it may be developed as an adjuvant drug to treat diabetes mellitus-induced infertility.

Interwoven Molecular Chains Obtained by Ionic Self-Assembly of Two Iron(III) Porphyrins with Opposite and Mismatched Charges.

We report ionic self-assembly of positively charged FeIII meso-tetra(N-methyl-4-pyridyl) porphyrin (FeIIINMePyP) with negatively charged FeIII meso-tetra(4-sulfonatophenyl) porphyrin (FeIIITPPS4), leading to the formation of flower-like nanostructures composed of unprecedented three-dimensional (3D) entangled chains of porphyrin dimers. Molecular dynamics (MD) simulations show that the 3D entanglement of porphyrin chains closely correlates to mismatched charges present in porphyrin dimers like [FeIII(H2O)2NMePyP]5+/[FeIII(H2O)2TPPS4]3- that requires extra interactions or entanglement with neighboring ones to achieve electric neutrality. Interestingly, the interwoven chains bring in excellent thermal stability as evidenced by well maintenance of the flower-like morphology after pyrolysis at 775 °C in argon, which is in good agreement of high-temperature MD simulations. Meanwhile, heat treatment of the flower-like porphyrin nanostructure leads to the formation of a non-noble metal electrocatalyst (NNME) with largely inherited morphology. This exemplifies a new approach by combining ionic self-assembly with subsequent pyrolysis for the synthesis of NNMEs with desired control over the morphology of template-free NNMEs that has rarely been achieved prior to this study. Furthermore, our electrocatalyst exhibits excellent activity and durability toward oxygen reduction reaction as well as much better methanol tolerance compared with commercial Pt/C in alkaline solutions.

DNA hypermethylation of aurora kinase A in hepatitis C virus­positive hepatocellular carcinoma.

Changes in the methylation levels of tumor suppressor genes or proto­oncogenes are involved in the pathogenesis of hepatitis C virus (HCV) infection­induced hepatocellular carcinoma (HCC). The aim of the present study was to identify novel aberrantly methylated differentially expressed genes by integrating mRNA expression profile (GSE19665 and GSE62232) and methylation profile (GSE60753) microarrays downloaded from the Gene Expression Omnibus database. Functional enrichment analysis of screened genes was performed using the DAVID software and BinGO database. Protein­protein interaction (PPI) networks were constructed using the STRING database, followed by module analysis with MCODE software. The transcriptional and translational expression levels of crucial genes were confirmed using The Cancer Genome Atlas (TCGA) datasets and Human Protein Atlas database (HPA). A total of 122 downregulated/hypermethylated genes and 63 upregulated/hypomethylated genes were identified. These genes were enriched in the Gene Ontology biological processes terms of 'inflammatory response' [Fos proto­oncogene, AP­1 transcription factor subunit (FOS)] and 'cell cycle process' [aurora kinase A (AURKA), cyclin dependent kinase inhibitor 3 (CDKN3) and ubiquitin conjugating enzyme E2 C (UBE2C)]. PPI network and module analysis indicated that human oncogenes FOS, AURKA, CDKN3 and UBE2C may be hub genes. mRNA, protein expression and methylation levels of AURKA and FOS were validated by TCGA and HPA data. In conclusion, aberrantly methylated AURKA and FOS may be potential therapeutic targets for HCV­positive HCC.

Synthesis and structural characterization of iron complexes bearing N-aryl-phenanthren-o-iminoquinone ligands.

Treatments of N-aryl-phenanthren-o-iminoquinone (aryl = 2,6-Me2C6H3 (MeL); 2,6-iPr2C6H3 (iPrL)) with iron powder in THF at 75 °C generate complexes [η2L]2Fe[η1LH] (1a, L = MeL; 1b, L = iPrL) in moderate yields. The X-ray crystallography analysis reveals that the molecule of 1b consists of a Fe(iii) center coordinated by three phenanthren-o-iminosemiquinone ligands, two of which are in an η2 fashion while the remaining one is in an η1 fashion. The analysis of the bond parameters of ligands indicates that the η2-fashioned ligands are radical anions and the η1-fashioned one is in an aminephenolato form. Reactions of MeL and iPrL with FeCl2 in THF produce Fe(iii) complexes [L]2FeCl (2a, L = MeL; 2b, L = iPrL) with the two ligands in the radical anionic form. However, similar reactions of PIQ ligands with FeCl2 in CH2Cl2 yield ion-pair complexes {[L]2FeCl}+[FeCl4]- (3a, L = MeL; 3b, L = iPrL), in which the iron center chelated by two neutral ligands can be formulated as Fe(ii). Reduction of 2b with sodium provides a salt-type complex [iPrL2-]2Fe(ii)Na2 (4), in which a high spin Fe(ii) atom is ligated by two amidophenolate ligands, and the sodium atoms attached to the oxygen atoms of ligands are η3-coordinated by the aryl ring in amido moieties.

A Novel Strategy for Large-Scale Metabolomics Study by Calibrating Gross and Systematic Errors in Gas Chromatography-Mass Spectrometry.

Metabolomics is increasingly applied to discover and validate metabolite biomarkers and illuminate biological variations. Combination of multiple analytical batches in large-scale and long-term metabolomics is commonly utilized to generate robust metabolomics data, but gross and systematic errors are often observed. The appropriate calibration methods are required before statistical analyses. Here, we develop a novel correction strategy for large-scale and long-term metabolomics study, which could integrate metabolomics data from multiple batches and different instruments by calibrating gross and systematic errors. The gross error calibration method applied various statistical and fitting models of the feature ratios between two adjacent quality control (QC) samples to screen and calibrate outlier variables. Virtual QC of each sample was produced by a linear fitting model of the feature intensities between two neighboring QCs to obtain a correction factor and remove the systematic bias. The suggested method was applied to handle metabolic profiling data of 1197 plant samples in nine batches analyzed by two gas chromatography-mass spectrometry instruments. The method was evaluated by the relative standard deviations of all the detected peaks, the average Pearson correlation coefficients, and Euclidean distance of QCs and non-QC replicates. The results showed the established approach outperforms the commonly used internal standard correction and total intensity signal correction methods, it could be used to integrate the metabolomics data from multiple analytical batches and instruments, and it allows the frequency of QC to one injection of every 20 real samples. The suggested method makes a large amount of metabolomics analysis practicable.

The ligand redox behavior and role in 1,2-bis[(2,6-diisopropylphenyl)imino]-acenaphthene nickel-TMA(MAO) systems for ethylene polymerization.

The BIAN ligands in Brookhart catalysts were proved to be redox-active during the catalyst activation with alkylaluminum or MAO, and the neutral catalytically active species with a radical anionic BIAN rather than the cationic ones with a neutral BIAN ligand were confirmed to be formed in the catalytic system.

[Computed tomographic diagnosis of intrahepatic cholangiocarcinoma].

OBJECTIVE: To explore the computed tomographic (CT) manifestations and their values in the diagnosis of intrahepatic cholangiocarcinoma (IHC) and improve the understanding of IHC. METHODS: A total of 58 IHC patients confirmed pathologically from January 2006 to December 2012 were reviewed. RESULTS: On plain CT scans, all lesions were of low density with lower density region (n = 37), retraction of liver capsule (n = 11), dilation of intrahepatic biliary duct (n = 22), bile duct calculus (n = 13) and atrophy of liver lobe (n = 14).On enhanced scans, most tumor showed obvious circular enhancement on arterial phase, stripe and network enhancement of internal region on portal phase and obvious enhancement on delayed phase. CONCLUSION: CT manifestations of intrahepatic cholangiocarcinoma are specific for its diagnosis.

[Diagnosis and treatment of focal nodular hyperplasia of liver].

OBJECTIVE: To explore the diagnosis and treatment of focal nodular hyperplasia (FNH) of liver. METHODS: The clinical data were retrospectively analyzed for 26 cases with confirmed FNH of liver from January 2006 to July 2011. Enhanced computed tomography and magnetic resonance imaging were performed. RESULTS: Among them, 22 cases underwent surgical resection, including left hemihepatectomy (n = 4), left lateral lobe hepatectomy (n = 5) and partial hepatectomy (n = 13). The pathological diagnosis was FNH. Most tumors were of soft texture. The gross surface was brown or yellow-brown in color. Central scar and radiating fibrous septas were spotted in some cases. There was no recurrence during a follow-up period of 4 months to 5 years. Serial observations were conducted for 4 cases with a follow-up period of 2 - 4 years. No growth was observed. CONCLUSIONS: Enhanced CT and MRI are important diagnostic tools. The confirmed cases may be followed up. Surgical resection is effective with an excellent prognosis.