Spatial variations of fungal community assembly and soil enzyme activity in rhizosphere of zonal Stipa species in inner Mongolia grassland.

Rhizosphere soil fungal and enzyme activities affect the nutrient cycling of terrestrial ecosystems, and rhizosphere fungi are also important participants in the ecological process of vegetation succession, responding to changes in plant communities. Stipa is an excellent forage grass with important ecological and economic value, and has the spatial distribution pattern of floristic geographical substitution. In order to systematically investigate the synergistic response strategies of fungal communities and enzyme activities in the rhizosphere under the vegetation succession. Here we explored the turnover and assembly mechanisms of Stipa rhizosphere fungal communities and the spatial variation of metabolic activity under the succession of seven Stipa communities in northern China grassland under large scale gradients. The results indicated that the composition, abundance and diversity of fungal communities and microbial enzyme activities in rhizosphere soil differed among different Stipa species and were strikingly varied along the Stipa community changes over the geographic gradient. As the geographical distribution of Stipa community changed from east to west in grassland transect, Mortierellomycetes tended to be gradually replaced by Dothideomycetes. The null models showed that the rhizosphere fungal communities were governed primarily by the dispersal limitation of stochastic assembly processes, which showed decreased relative importance from S. grandis to S. gobica. Moreover, the MAT and MAP were the most important factors influencing the changes in the fungal community (richness, ß-diversity and composition) and fungal community assembly, while SC and NP also mediated fungal community assembly processes. These findings deepen our understanding of the responses of the microbial functions and fungal community assembly processes in the rhizosphere to vegetation succession.

Metabolomics analysis of Ligustri Lucidi Fructus at different harvest times during the whole growing period based on ultra-high-performance liquid chromatography with mass spectrometry.

After medicinal market research, it was found that the harvest time of Ligustri Lucidi Fructus (LLF) was chaotic in practice. In order to determine the optimal harvest period of LLF to ensure its pharmacological activity, metabolomics analysis of LLF at different harvest times based on ultra-high-performance liquid chromatography-triple quadrupole-(linear ion trap)-tandem mass spectrometry was established. In this study, 166 differential metabolites (DMs) in 448 metabolites at different harvest times were screened out based on variable importance in projection value, and among them, 94 DMs with regular trends of change in relative content (59 increased and 35 decreased with the growth period) were chosen to further research. The result of the multivariate statistical analysis showed that November was the optimal harvest period of LLF. Additionally, 10-hydroxyligustroside, oleoside 11-methyl ester, and salidroside were screened out to be used as the evaluation indicators of immature LLF, while specnuezhenide, nuezhenoside G13, and neonuezhenide were the evaluation indicators of mature LLF. This study provides fundamental insight for metabolite identification and proposes the best harvest period of LLF to avoid confusion in the medicinal market.

Simultaneous determination and quality evaluation of 16 compounds in Ligustri Lucidi Fructus covering different regions and processed products using ultra-high-performance liquid chromatography-mass spectrometry.

A quantitative analysis method and a chemical pattern recognition method were developed to evaluate raw Ligustri Lucidi Fructus (LLF) from different regions and different processed products. In this study, a comprehensive strategy using ultra-high-performance liquid chromatography-mass spectrometry quantitative analysis method was established for the simultaneous determination of 16 components in 47 batches of LLF covering 19 regions belonging to 8 provinces and 24 batches of different processed products (steamed LLF without auxiliary material, wine-steamed LLF, salt-steamed LLF, and vinegar-steamed LLF). The results of this study indicated that the proposed method was reliable and accurate for the rapid analysis proved by detection limit, quantification limit, precision, and accuracy. Furthermore, principal component analysis and hierarchical cluster analysis were employed to analyze the experimental data, showing that the best-quality samples of 47 batches of raw LLF were S47 (Lantian, Shaanxi), S39 (Pingyang-2, Shandong), S38 (Pingyang-1, Shandong), and S45 (Lingbao, Henan), whereas the worst-quality samples were S7-S16 (Huzhou, Zhejiang). In 24 batches of processed products, the best-quality samples were S48 (salt steamed 2 h), S60 (wine steamed 2 h), and S61 (wine steamed 4 h). Meanwhile, the heat map showed that the contents of triterpenoid saponins, including C16 (ursolic acid), C15 (oleanic acid), and C14 (maslinic acid), were higher than those of other compounds in 71 batches of samples. These results suggested that the quality of raw LLF in the central and northern regions was better than that in the southern regions, and regarding the processed products, different auxiliary materials had little effect on the quality of LLF, but steaming time of 2 h was appropriate. Briefly, this study proposed a multiparameter quantitative analysis method for the overall quality control of raw LLF samples covering different regions in China and different processed LLF.

A Human Brain Model Mimicking Umbilical Cord Mesenchymal Stem Cells for the Treatment of Hypoxic-Ischemic Brain Injury.

We used an in vitro model of the human brain immune microenvironment to simulate hypoxic-ischemic brain injury (HIBI) and treatment with human umbilical cord mesenchymal stem cells (hUMSCs) to address the transformation barriers of gene differences between animals and humans in preclinical research. A co-culture system, termed hNAME, consisted of human hippocampal neurons (N), astrocytes (A), microglia (M), and brain microvascular endothelial cells (E). Flow cytometry measured the apoptosis rates of neurons and endothelial cells. hNAME-neurons and endothelial cells experienced more severe damage than monolayer cells, particularly after 48 h and 24 h of reoxygenation (OGD48/R24). Western blotting identified neuroinflammatory response markers, including HIF-1α, C1q, C3, TNF-α, and iNOS. Inflammatory factors originated from the glial chamber rather than the neurons and vascular endothelial chambers. A gradual increase in the release of inflammatory factors was observed as the OGD and reoxygenation times increased, peaking at OGD48/R24. The hNAME value was confirmed in human umbilical cord mesenchymal stem cells (hUMSCs). Treatment with hUMSCs resulted in a notable decrease in the severity of neuronal and endothelial cell damage in hNAME. The hNAME is an ideal in vitro model for simulating the immune microenvironment of the human brain because of the interactions between neurons, vessels, astrocytes, and microglia.

Discovery and therapeutic implications of bioactive dihydroxylated phenolic acids in patients with severe heart disease and conditions associated with inflammation and hypoxia.

Our initial studies detected elevated levels of 3,4-dihydroxyphenyllactic acid (DHPLA) in urine samples of patients with severe heart disease when compared with healthy subjects. Given the reported anti-inflammatory properties of DHPLA and related dihydroxylated phenolic acids (DPAs), we embarked on an exploratory multi-centre investigation in patients with no urinary tract infections to establish the possible pathophysiological significance and therapeutic implications of these findings. Chinese and Caucasian patients being treated for severe heart disease or those conditions associated with inflammation (WBC ≥ 10 ×109/L or hsCRP ≥ 3.0 mg/L) and/or hypoxia (PaO2 ≤ 75 mmHg) were enrolled; their urine samples were analyzed by HPLC, HPLC-MS, GC-MS and biotransformation assays. DHPLA was detected in urine samples of patients, but undetectable in healthy volunteers. Dynamic monitoring of inpatients undergoing treatment showed their DHPLA levels declined in proportion to their clinical improvement. In DHPLA-positive patients' fecal samples, Proteus vulgaris and P. mirabilis were more abundant than healthy volunteers. In culture, these gut bacteria were capable of reversible interconversion between DOPA and DHPLA. Furthermore, porcine and rodent organs were able to metabolize DOPA to DHPLA and related phenolic acids. The elevated levels of DHPLA in these patients suggest bioactive DPAs are generated de novo as part of a human's defense mechanism against disease. Because DHPLA isolated from Radix Salvia miltiorrhizae has a multitude of pharmacological activities, these data underpin the scientific basis of this medicinal plant's ethnopharmacological applications as well as highlighting the therapeutic potential of endogenous, natural or synthetic DPAs and their derivatives in humans.

Role of contrast-enhanced ultrasonography in MR-guided focused ultrasound ablation on uterus fibroids: lesion selection and assessment of ablative effects.

OBJECTIVES: To determine whether contrast-enhanced ultrasonography (CEUS) can be used for selecting lesions and assessing the ablative effects of MRgFUS ablation on uterus fibroids, compared with MR imaging. METHODS: This retrospective study was approved by the institutional review board of our hospital. From April 2018 to November 2019, a total of 44 symptomatic fibroids in 38 patients who underwent MRgFUS ablation were included. The association between pre-ablation characteristics on CEUS/MR imaging and the non-perfusion volume (NPV) after ablation was analyzed using multivariable linear regression analysis. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve values was compared between the CEUS and MR imaging regression models. NPV after ablation was compared between CEUS and enhanced MR imaging. RESULTS: On CEUS, entangled branch vessels, fast-in, and fast-out patterns were significantly associated with NPV, with an AUC of 0.95 (95% CI; 0.88, 1.00). On MR imaging, hyper-intensity on T2-weighted images (T2WI), hyper-intense ring-like signal on T2WI images, and hyper-enhancement on contrast-enhanced T1WI images were correlated with NPV, with an AUC of 0.86 (95% CI; 0.70, 1.00). After ablation, no differences in NPV were noted between contrast-enhanced T1WI (84.13 ± 75.42 cm3) and CEUS (80.22 ± 76.49 cm3). CONCLUSIONS: Some pre-ablation characteristics of uterine fibroids on CEUS were associated with NPV after MRgFUS. CEUS may contribute to the evaluation of ablative outcomes and patient selection, similar to MR imaging. KEY POINTS: • Contrast-enhanced ultrasonography (CEUS) is effective for selecting the appropriate uterine fibroids before MR-guided focused ultrasound (MRgFUS) ablation and evaluating non-perfusion volumes (NPV) after ablation, as a potential alternative to MR imaging. • Before ablation, entangled branch vessels, fast-in, and fast-out patterns on CEUS were significantly associated with NPV after MRgFUS. • No significant differences in NPV were detected between contrast-enhanced T1WI and CEUS after ablation.

Inhibition of N-Acetyltransferase 10 Suppresses the Progression of Prostate Cancer through Regulation of DNA Replication.

Cancer suppression through the inhibition of N-acetyltransferase 10 (NAT10) by its specific inhibitor Remodelin has been demonstrated in a variety of human cancers. Here, we report the inhibitory effects of Remodelin on prostate cancer (PCa) cells and the possible associated mechanisms. The prostate cancer cell lines VCaP, LNCaP, PC3, and DU145 were used. The in vitro proliferation, migration, and invasion of cells were measured by a cell proliferation assay, colony formation, wound healing, and Transwell assays, respectively. In vivo tumor growth was analyzed by transplantation into nude mice. The inhibition of NAT10 by Remodelin not only suppressed growth, migration, and invasion in vitro, but also the in vivo cancer growth of prostate cancer cells. The involvement of NAT10 in DNA replication was assessed by EdU labeling, DNA spreading, iPOND, and ChIP-PCR assays. The inhibition of NAT10 by Remodelin slowed DNA replication. NAT10 was detected in the prereplication complex, and it could also bind to DNA replication origins. Furthermore, the interaction between NAT10 and CDC6 was analyzed by Co-IP. The altered expression of NAT10 was measured by immunofluorescence staining and Western blotting. Remodelin markedly reduced the levels of CDC6 and AR. The expression of NAT10 could be altered under either castration or noncastration conditions, and Remodelin still suppressed the growth of in vitro-induced castration-resistant prostate cancers. The analysis of a TCGA database revealed that the overexpression of NAT10, CDC6, and MCM7 in prostate cancers were correlated with the Gleason score and node metastasis. Our data demonstrated that Remodelin, an inhibitor of NAT10, effectively inhibits the growth of prostate cancer cells under either no castration or castration conditions, likely by impairing DNA replication.

Poria cocos polysaccharides reduces high-fat diet-induced arteriosclerosis in ApoE-/- mice by inhibiting inflammation.

Atherosclerosis (AS) is a common chronic inflammatory disease of the arteries, which is closely related to dyslipidemia, inflammatory factors, and oxidative stress. Poria cocos polysaccharides (PCP) are one of the main active ingredients of Poria, which has significant pharmacological effects. In this study, the potential protective mechanism of PCP on AS was discussed in the ApoE-/- mice model induced by high-fat diet. These pathological changes were evaluated by H&E and oil red O staining. The levels of pro-inflammatory cytokines in aortic tissue were measured by enzyme-linked immunosorbent assay kit. These protein expressions were detected by Western blot and immunohistochemistry. The results showed that PCP inhibited the serum inflammatory mediators (tumor necrosis factor-α, interleukin-6, and nitric oxide) and lipids (low-density lipoprotein-cholesterol, triglyceride, and total cholesterol) increase. Moreover, PCP also reduced the concentration of malondialdehyde, increased the activity of superoxide dismutase, and improved the pathological changes of the aorta. Finally, PCP inhibited the activation of the TLR4/NF-κB pathway in the aorta and blocked the expression of matrix metalloproteinase 2 and intercellular adhesion molecule 1 proteins. In short, PCP intervenes in AS by reducing inflammatory factors and blood lipid levels.

Genomic and transcriptomic profiling of carcinogenesis in patients with familial adenomatous polyposis.

OBJECTIVE: Familial adenomatous polyposis (FAP) is characterised by the development of hundreds to thousands of adenomas at different evolutionary stages in the colon and rectum that will inevitably progress to adenocarcinomas if left untreated. Here, we investigated the genetic alterations and transcriptomic transitions from precancerous adenoma to carcinoma. DESIGN: Whole-exome sequencing, whole-genome sequencing and single-cell RNA sequencing were performed on matched adjacent normal tissues, multiregionally sampled adenomas at different stages and carcinomas from six patients with FAP and one patient with MUTYH-associated polyposis (n=56 exomes, n=56 genomes and n=8,757 single cells). Genomic alterations (including copy number alterations and somatic mutations), clonal architectures and transcriptome dynamics during adenocarcinoma carcinogenesis were comprehensively investigated. RESULTS: Genomic evolutionary analysis showed that adjacent lesions from the same patient with FAP can originate from the same cancer-primed cell. In addition, the tricarboxylic acid cycle pathway was strongly repressed in adenomas and was then slightly alleviated in carcinomas. Cells from the 'normal' colon epithelium of patients with FAP already showed metabolic reprogramming compared with cells from the normal colon epithelium of patients with sporadic colorectal cancer. CONCLUSIONS: The process described in the previously reported field cancerisation model also occurs in patients with FAP and can contribute to the formation of adjacent lesions in patients with FAP. Reprogramming of carbohydrate metabolism has already occurred at the precancerous adenoma stage. Our study provides an accurate picture of the genomic and transcriptomic landscapes during the initiation and progression of carcinogenesis, especially during the transition from adenoma to carcinoma.

Metabolomics in renal cell carcinoma: From biomarker identification to pathomechanism insights.

Renal cell carcinoma (RCC) is a frequently diagnosed cancer with high prevalence, which is inversely associated with survival benefit. Although myriad studies have shed light on disease causality, unfortunately, thus far, RCC diagnosis is faced with numerous obstacles partly due to the insufficient knowledge of effective biomarkers, hinting deeper mechanistic understanding are urgently needed. Metabolites are recognized as final proxies for gene-environment interactions and physiological homeostasis as they reflect dynamic processes that are ongoing or have been taken place, and metabolomics may therefore offer a far more productive and cost-effective route to disease discovery, particularly within the arena for new biomarker identification. In this review, we primarily expatiate recent advances in metabolomics that may be amenable to novel biomarkers or therapeutic targets for RCC, which may expand our armaments to win more bettles against RCC.

Correction to: Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells.

The article "Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells", written by "Yaqian Wu, Yanan Cao, Haijing Liu, Mengfei Yao, Ningning Ma and Bo Zhang", was originally published electronically on the publisher's internet portal https://link.springer.com/article/10.1007/s11010-020-03776-w on 11 June 2020 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 6 July 2020 to © Springer Science+Business Media, LLC, part of Springer Nature 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.

Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells.

Hypoxia-inducible factors (HIFs) are key mediators expressed under hypoxic condition and involved in many kinds of disease such as cancer and abnormal angiogenesis. Thus, development of their inhibitor has been extensively explored. Here, we describe a finding that Remodelin, a specific inhibitor of NAT10, could also inhibit the expression of HIFs. The presence of Remodelin could suppress the elevated level of HIF-1α protein and its nuclear translocation induced by either treatment of cobalt chloride (CoCl2) or hypoxia in dose or time-dependent way. More importantly, Remodelin could also inhibit the constitutional expression of HIF-1α and HIF-2α in VHL mutant 786-0 cells. With using of cells with depletion of NAT10 by shRNA or Crispr-Cas9 edited, we further demonstrated that inhibition of HIFs by Remodelin should need NAT10 activity. In biological analysis, the treatment of cultured HUVECs with Remodelin could inhibit in vitro cell migration and invasion and tube-formation. Our investigation implied that Remodelin could be a new potential inhibitor of HIFs for using in angiogenesis targeting therapy in either cancers or inflammatory diseases.

The nuclear GSK-3ß regulated post-transcriptional processing of mRNA through phosphorylation of SC35.

Glycogen synthase kinase-3ß (GSK-3ß) is a multifunctional serine/threonine kinase and regulates a variety of biological processes. Recent studies show GSK-3ß can regulate pre-mRNA processing and transcription through phosphorylation of multiple splicing factors, but the detailed mechanism is still undetermined. In this study, we further proved that GSK-3ß could specifically co-localize with SC35 in nuclear speckles depending on its kinase activity. Immunofluorescence and FISH studies showed the activity of nuclear GSK-3ß regulated the assembly of nuclear speckles and consequently modulated the post-transcriptional processing of mRNA. In addition, GSK-3ß phosphorylated SC35 and promoted its hyperphosphorylation, in which the unique C-terminal sequences were particularly important to efficiently sequential multiple phosphorylation of SC35. Hyperphosphorylated SC35 converged into cluster and lost its ability to perform splicing in nuclear speckles. More importantly, the nuclear GSK-3ß activity could be a part of Wnt/ß-catenin signaling activation by TCF4 and might take part in embryonic or tumorigenesis of cells.

Ultrasound-Guided Intratumoral Radiofrequency Ablation Coagulation to Facilitate Meningioma Resection: Preliminary Experience.

OBJECTIVES: This study aimed to explore the feasibility and safety of intratumoral radiofrequency ablation (RFA) in meningioma resection. METHODS: This study was approved by the Xijing Ethics Committee, and informed consent was obtained from all of the patients. Thirteen patients with meningiomas were recruited in the Neurosurgery Department of Xijing Hospital. These patients were treated with intratumoral RFA and surgery. We also chose 13 patients with meningiomas treated with traditional surgery as the control group. Two-dimensional ultrasound, color Doppler flow imaging, contrast-enhanced ultrasound, and magnetic resonance imaging were used to identify the location, border, and blood supply of the meningiomas preoperatively and to assess the therapeutic effect intraoperatively. Finally, the meningiomas were dissected and removed by surgery. RESULTS: All procedures were technically successful without serious complications. Intraoperative ultrasound was able to provide a clear display of the location, shape, size, and boundary of the tumor and its relationship with other tissues and reveal the vascular distribution in and around the tumors. With intratumoral RFA, coagulative necrosis was induced, and the meningiomas became hard in texture with a decreased blood supply. Blood loss was significantly lower in the RFA group versus control group (320.0 ± 24.8 versus 390.4 ± 36.8 mL; P < .001). The RFA group spent fewer days in the hospital (6.0 ± 0.9 versus 7.0 ± 1.2 days; P = .022). However, the surgical time of the RFA group was relatively longer (3.5 ± 0.5 versus 3.0 ± 0.3 hours, P = .007). CONCLUSIONS: The application of intratumoral RFA in meningioma resection is effective and safe. It may be a useful adjunct for meningioma treatment.

Evaluation of menopausal status among breast cancer patients with chemotherapy-induced amenorrhea.

OBJECTIVE: In patients with chemotherapy-induced amenorrhea (CIA), the menopausal status is ambiguous and difficult to evaluate. This study aimed to establish a discriminative model to predict and classify the menopausal status of breast cancer patients with CIA. METHODS: This is a single center hospital-based study from 2013 to 2016. The menopausal age distribution and accumulated incidence rate of CIA are described. Multivariate models were adjusted for established and potential confounding factors including age, serum concentration of estradiol (E2) and follicle-stimulating hormone (FSH), feeding, pregnancy, parity, abortions, and body mass index (BMI). The odds ratio (OR) and 95% confidence interval (95% CI) of different risk factors were estimated. RESULTS: A total of 1,796 breast cancer patients were included in this study, among whom, 1,175 (65.42%) were premenopausal patients and 621 (34.58%) were post-menopause patients. Five hundred and fifty patients were included in CIA analysis, and a cumulative CIA rate of 81.64% was found in them. Age (OR: 1.856, 95% CI: 1.732-1.990), serum concentration of E2 (OR: 0.976, 95% CI: 0.972-0.980) and FSH (OR: 1.060, 95% CI: 1.053-1.066), and menarche age (OR: 1.074, 95% CI: 1.009-1.144) were found to be associated with the patients' menopausal status. According to multivariate analysis, the discriminative model to predict the menopausal status is Logit (P)=-28.396+0.536Age-0.014E2+0.031FSH. The sensitivities for this model were higher than 85%, and its specificities were higher than 89%. CONCLUSIONS: The discriminative model obtained from this study for predicting menstrual state is important for premenopausal patients with CIA. This model has high specificity and sensitivity and should be prudently used.

Subcellular Relocalization and Positive Selection Play Key Roles in the Retention of Duplicate Genes of Populus Class III Peroxidase Family.

Gene duplication is the primary source of new genes and novel functions. Over the course of evolution, many duplicate genes lose their function and are eventually removed by deletion. However, some duplicates have persisted and evolved diverse functions. A particular challenge is to understand how this diversity arises and whether positive selection plays a role. In this study, we reconstructed the evolutionary history of the class III peroxidase (PRX) genes from the Populus trichocarpa genome. PRXs are plant-specific enzymes that play important roles in cell wall metabolism and in response to biotic and abiotic stresses. We found that two large tandem-arrayed clusters of PRXs evolved from an ancestral cell wall type PRX to vacuole type, followed by tandem duplications and subsequent functional specification. Substitution models identified seven positively selected sites in the vacuole PRXs. These positively selected sites showed significant effects on the biochemical functions of the enzymes. We also found that positive selection acts more frequently on residues adjacent to, rather than directly at, a critical active site of the enzyme, and on flexible regions rather than on rigid structural elements of the protein. Our study provides new insights into the adaptive molecular evolution of plant enzyme families.

Divergence in Enzymatic Activities in the Soybean GST Supergene Family Provides New Insight into the Evolutionary Dynamics of Whole-Genome Duplicates.

Whole-genome duplication (WGD), or polyploidy, is a major force in plant genome evolution. A duplicate of all genes is present in the genome immediately following a WGD event. However, the evolutionary mechanisms responsible for the loss of, or retention and subsequent functional divergence of polyploidy-derived duplicates remain largely unknown. In this study we reconstructed the evolutionary history of the glutathione S-transferase (GST) gene family from the soybean genome, and identified 72 GST duplicated gene pairs formed by a recent Glycine-specific WGD event occurring approximately 13 Ma. We found that 72% of duplicated GST gene pairs experienced gene losses or pseudogenization, whereas 28% of GST gene pairs have been retained in the soybean genome. The GST pseudogenes were under relaxed selective constraints, whereas functional GSTs were subject to strong purifying selection. Plant GST genes play important roles in stress tolerance and detoxification metabolism. By examining the gene expression responses to abiotic stresses and enzymatic properties of the ancestral and current proteins, we found that polyploidy-derived GST duplicates show the divergence in enzymatic activities. Through site-directed mutagenesis of ancestral proteins, this study revealed that nonsynonymous substitutions of key amino acid sites play an important role in the divergence of enzymatic functions of polyploidy-derived GST duplicates. These findings provide new insights into the evolutionary and functional dynamics of polyploidy-derived duplicate genes.

A Facile Route to Bimetal and Nitrogen-Codoped 3D Porous Graphitic Carbon Networks for Efficient Oxygen Reduction.

Bimetal nitrogen-doped carbon with both Fe and Co, derived from the pyrolysis carbon of iron and cobalt phthalocyanine-based conjugated polymer networks, possesses a few-layer graphene-like texture with hierarchical porosity in meso/micro multimodal pore size distribution. The novel electrocatalyst exhibits Pt-like catalytic activity and much higher catalytic durability for oxygen reduction.

Pyrolysis of Animal Bones with Vitamin B12: A Facile Route to Efficient Transition Metal-Nitrogen-Carbon (TM-N-C) Electrocatalysts for Oxygen Reduction.

By pyrolyzing cattle bones, hierarchical porous carbon (HPC) networks with a high surface area (2520 m(2) g(-1) ) and connected pores were prepared at a low cost and large scale. Subsequent co-pyrolysis of HPC with vitamin B12 resulted in the formation of three-dimensional (3D) hierarchically structured porous cobalt-nitrogen-carbon (Co-N-HPC) electrocatalysts with a surface area as high as 859 m(2) g(-1) as well as a higher oxygen reduction reaction (ORR) electrocatalytic activity, better operation stability, and higher tolerance to methanol than the commercial Pt/C catalyst in alkaline electrolyte.

TEIF associated centrosome activity is regulated by EGF/PI3K/Akt signaling.

Centrosome amplification, which is a characteristic of cancer cells, has been understood as a driving force of genetic instability in the development of cancer. In previous work, we demonstrated that TEIF (transcriptional element-interacting factor) distributes in the centrosomes and regulates centrosome status under both physiologic and pathologic conditions. Here we identify TEIF as a downstream effector in EGF/PI3K/Akt signaling. The addition of EGF or transfection of active Akt stimulates centrosome TEIF distribution, resulting in an increase of centrosome splitting and amplification, while inhibitors of either PI3K or Akt attenuate these changes in TEIF and the associated centrosome status. A consensus motif for Akt phosphorylation (RHRVLT) proved to be involved in centrosomal TEIF localization, and the 469-threonine of this motif may be phosphorylated by Akt both in vitro and in vivo. Elimination of this phosphorylated site on TEIF caused reduced centrosome distribution and centrosome splitting or amplification. Moreover, TEIF closely co-localized with C-NAP1 at the proximal ends of centrioles, and centriolar loading of TEIF stimulated by EGF/Akt could displace C-NAP1, resulting in centrosome splitting. These findings reveal linkage of the EGF/PI3K/Akt signaling pathway to regulation of centrosome status which may act as an oncogenic pathway and induce genetic instability in carcinogenesis.