Sulfonium Cation in the Service of π-Acid Catalysis.

While still rare, cationic ligands offer much promise as tunable electron-withdrawing ligands for π-acid catalysis. Recently, we introduced pincer-type sulfonium cations into the list of available strongly π-acidic ancillary ligands. However, the M-S bond in sulfonium complexes of these ligands was found highly labile, precluding their catalytic applications. Herein we demonstrate that this obstacle can be overcome by increasing the rigidity of the sulfonium pincer scaffold. X-ray analyses confirm that despite bearing a formal positive charge, the sulfur atom of this newly designed sulfonium ligand maintains its coordination to the Pt(II)-center, while DFT calculations indicate that by doing so it strongly enhances the electrophilic character of the metal. Kinetic studies carried out on three model cycloisomerization reactions prove that such a tris-cationic sulfonium-Pt(II) complex is highly reactive, compared to its thioether-based analogue. This proof-of-concept study presents the first example of employing sulfonium-based ligands in homogeneous catalysis.

Type†I Photoinitiator Based on Sustainable Carbon Dots.

Sustainable carbon dots comprising surficial oxime ester groups following homolytic bond cleavage exhibit potential as photoinitiators for traditional free radical photopolymerization. Carbon dots were made following a solvothermal procedure from sustainable furfural available from lignocellulose. Surficial aldehyde moieties reacted with hydroxylamine to the respective oxime while reaction with benzoyl chloride resulted in a biobased Type I photoinitiator comprising sustainable carbon dot (CD-PI). Photoinitiating ability was compared with the traditional photoinitiator (PI) ethyl (2,4,6-trimethyl benzoyl) phenyl phosphinate (TPO-L) by real-time FTIR with UV exposure at 365 nm. Photopolymer composition based on a mixture of urethane dimethacrylate (UDMA) and tripropylene glycol diacrylate (TPGDA) resulted in a similar final conversion of about 70 % using either CD-PI or TPO-L. Nevertheless, it appeared homogeneous in the case of compositions processed with CD-PI, while those made with TPO-L were heterogeneous as shown by two glass transition temperatures. Moreover, the migration rate of CD-PI in the cured samples was lower in comparison with those samples using TPO-L as PI.

The female germ unit is essential for pollen tube funicular guidance in Arabidopsis thaliana.

In angiosperm, two immotile sperm cells are delivered to the female gametes for fertilization by a pollen tube, which perceives guidance cues from ovules at least at two critical sites, micropyle for short-distance guidance and funiculus for comparably longer distance guidance. Compared with the great progress in understanding pollen tube micropylar guidance, little is known about the signaling for funicular guidance. Here, we show that funiculus plays an important role in pollen tube guidance and report that female gametophyte (FG) plays a critical role in funicular guidance by analysis of a 3-dehydroquinate synthase (DHQS) mutant. Loss function of DHQS in FG interrupts pollen tube funicular guidance, suggesting that the guiding signal is generated from FG. We show the evidence that the capacity of funicular guidance is established during FG functional specification after the establishment of cell identity. Specific expression of DHQS in the synergid cells, central cells, or egg cells can rescue funicular guidance defect in dhqs/+, indicating all the female germ unit cells are involved in the funicular guidance. The finding reveals that the attracting signal of pollen tube funicular guidance was generated at a site and stage manner and provides novel clue to locate and search for the signal.

Development and validation of a nomogram for predicting overall survival in patients with early-onset endometrial cancer.

BACKGROUND: This study aimed to investigate the differences in the clinicopathological characteristics of younger and older patients with endometrial cancer (EC) and develop a nomogram to assess the prognosis of early onset EC in terms of overall survival. METHODS: Patients diagnosed with EC from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015 were selected. Clinicopathological characteristics were compared between younger and older patients, and survival analysis was performed for both groups. Prognostic factors affecting overall survival in young patients with EC were identified using Cox regression. A nomogram was created and internal validation was performed using the consistency index, decision curve analysis, receiver operating characteristic curves, and calibration curves. External validation used data from 70 patients with early onset EC. Finally, Kaplan-Meier curves were plotted to compare survival outcomes across the risk subgroups. RESULTS: A total of 1042 young patients and 12,991 older patients were included in this study. Younger patients were divided into training (732) and validation (310) cohorts in a 7:3 ratio. Cox regression analysis identified age, tumorsize, grade, FIGO stage(International Federation of Gynecology and Obstetrics) and surgery as independent risk factors for overall survival, and a nomogram was constructed based on these factors. Internal and external validations demonstrated the good predictive power of the nomogram. In particular, the C-index for the overall survival nomogram was 0.832 [95% confidence interval (0.797-0.844)] in the training cohort and 0.839 (0.810-0.868) in the internal validation cohort. The differences in the Kaplan-Meier curves between the different risk subgroups were statistically significant. CONCLUSIONS: In this study, a nomogram for predicting overall survival of patients with early onset endometrial cancer based on the SEER database was developed to help assess the prognosis of patients and guide clinical treatment.

A prognostic risk model for ovarian cancer based on gene expression profiles from gene expression omnibus database.

This study explored prognostic genes of ovarian cancer and built a prognostic model based on these genes to predict patient's survival, which is of great significance for improving treatment of ovarian cancer. GSE26712 dataset was downloaded from Gene Expression Omnibus database as training set, while OV-AU dataset was downloaded from ICGC website as validation set. All genes in GSE26712 were analyzed by univariate Cox regression, Lasso regression, and multivariate Cox regression analyses. Then prognosis-related feature genes were screened to construct a multivariate risk model. Meanwhile, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed on samples in the high/low-risk groups using Gene Set Enrichment Analysis (GSEA) software. Finally, survival curve and receiver operating characteristic curve were drawn to verify the validity of the model. Ten feature genes related to prognosis of ovarian cancer were obtained: CMTM6, COLGALT1, F2R, GPR39, IGFBP3, RNF121, MTMR9, ORAI2, SNAI2, ZBTB16. GSEA enrichment analysis showed that there were notable differences in biological pathways such as gap junctions and homologous recombination between the high/low-risk groups. Through further verification of training set and validation set, the 10-gene prognostic model was found to be effective for the prognosis of ovarian cancer patients. In this study, we constructed a 10-gene prognostic model which predicted the prognosis of ovarian cancer patients well by integrating clinical prognostic parameters. It may have certain reference value for subsequent clinical treatment research of ovarian cancer patients and help in clinical treatment decision-making.

Fluorine-doped BiVO4 photocatalyst: Preferential cleavage of C-N bond for green degradation of glyphosate.

With increasing concerns on the environment and human health, the degradation of glyphosate through the formation of less toxic intermediates is of great importance. Among the developed methods for the degradation of glyphosate, photodegradation is a clean and efficient strategy. In this work, we report a new photocatalyst by doping F ion on BiVO4 that can efficiently degrade glyphosate and reduce the toxic emissions of aminomethylphosphonic acid (AMPA) through the selective (P)-C-N cleavage in comparison of BiVO4 catalyst. The results demonstrate that the best suppression of AMPA formation was achieved by the catalyst of 0.3F@BiVO4 at pH = 9 (AMPA formation below 10%). In situ attenuated total reflectance Fourier transforms infrared (ATR-FTIR) spectroscopy indicates that the adsorption sites of glyphosate on BiVO4 and 0.3F@BiVO4 are altered due to the difference in electrostatic interactions. Such an absorption alteration leads to the preferential cleavage of the C-N bond on the N-C-P skeleton, thereby inhibiting the formation of toxic AMPA. These results improve our understanding of the photodegradation process of glyphosate catalyzed by BiVO4-based catalysts and pave a safe way for abiotic degradation of glyphosate.

Periodontitis and Number of Teeth in the Risk of Coronary Heart Disease: An Updated Meta-Analysis.

BACKGROUND A positive link between periodontitis and chronic systemic disease has been indicated. However, few studies focused on the loss of teeth. Our analysis aims to analyze the relationship of periodontitis and number of teeth with the risk of coronary heart disease (CHD). MATERIAL AND METHODS A meta-analysis was conducted on qualified data extracted from the PubMed, Embase, and Cochrane Library databases. Only cohort studies were included in this study. We screened articles that assessed the periodontal condition and teeth number as well as the incidence or mortality of CHD. Hazard ratio (HR) and relative risk (RR) were calculated by Stata SE software. RESULTS A total of 11 prospective studies with over 200 000 total participants were analyzed. Ten studies reported on periodontitis and CHD, and 4 studies included data on number of teeth. After adjusting for multivariate factors, there was a significant association between periodontitis and the risk of CHD (RR, 1.18; 95% confidence interval [CI], 1.10-1.26); the RR of CHD in the edentulous population was 1.20 (95% CI, 1.08-1.34). Moreover, results on the RR values for number of teeth were as follows: 24-17 teeth (RR, 1.12; 95% CI, 1.05-1.19); 16-11 (RR, 1.28; 95% CI, 1.15-1.42); and £10 (RR, 1.55; 95% CI, 1.43-1.69). CONCLUSIONS Our study showed that periodontitis is a risk factor for CHD and that the number of removed teeth is positively correlated with the risk of CHD. During clinical assessment, both factors need to be considered as factors associated with cardiovascular risks.

Spatial distribution, risk assessment, and source identification of heavy metals in water from the Xiangxi River, Three Gorges Reservoir Region, China.

Heavy metals (HMs) contamination in rivers has attracted wide concern due to its persistence and potential risks to the natural environment and human health. In this study, eight HMs (As, Hg, Cu, Pb, Ca, Zn, Mn, and Ni) were measured by inductively coupled plasma mass spectrometry in 24 water samples to investigate HMs contamination levels in the Xiangxi River of the Yangtze River basin. A geographic information systems kriging interpolation method was used to reveal the spatial distribution of HMs contamination. The results indicate that most HMs occurred at acceptable levels below the Surface Water Quality Standard (GB 3838-2002), with the highest concentration (23.23 mg kg-1) of Mn being observed at sampling site X20. The values of the potential ecological risk index (RI) suggest that high potential ecological risks were present at sampling sites X1, X3, X4, X14, X16, X17, and X24, which reached moderate risk level. The highest value of RI (279.56) was observed at site X17. HM spatial distributions show that upstream pollution is more severe than downstream. The hazard index was below 1 for all HMs except for Mn, indicating that HMs in Xiangxi River pose a low risk to human health. HM source identification was accomplished using principal component analysis and Pearson's correlation. Cu, Cd, Ni, and Hg originate primarily from agriculture, while Pb, Zn, and As originate primarily from transportation and mining. This research provides a reference on the risks posed by HMs in Xiangxi River and will support efforts to protect and improve water quality in Xiangxi River.

Green and efficient degradation of cefoperazone sodium by Bi4O5Br2 leading to the production of non-toxic products: Performance and degradation pathway.

Photocatalytic process represents a promising approach to overcome the pollution challenge associated with the antibiotics-containing wastewater. This study provides a green, efficient and novel approach to remove cephalosporins, particularly cefoperazone sodium (CFP). Bi4O5Br2 was chosen for the first time to systematically study its degradation for CFP, including the analysis of material structure, degradation performance, the structure and toxicity of the transformation products, etc. The degradation rate results indicated that Bi4O5Br2 had an excellent catalytic activity leading to 78% CFP removal compared with the pure BiOBr (38%) within 120 min of visible light irradiation. In addition, the Bi4O5Br2 presents high stability and good organic carbon removal efficiency. The effects of the solution pH (3.12 - 8.75) on catalytic activity revealed that CFP was mainly photocatalyzed under acidic conditions and hydrolyzed under alkaline conditions. Combined with active species and degradation product identification, the photocatalytic degradation pathways of CFP by Bi4O5Br2 was proposed, including hydrolysis, oxidation, reduction and decarboxylation. Most importantly, the identified products were all hydrolysis rather than oxidation byproducts transformed from the intermediate of ß-lactam bond cleavage in CFP molecule, quite different from the mostly previous studies. Furthermore, the final products were demonstrated to be less toxic through the toxicity analysis. Overall, this study illustrates the detailed mechanism of CFP degradation by Bi4O5Br2 and confirms Bi4O5Br2 to be a promising material for the photodegradation of CFP.

Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation.

BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) is overexpressed in many squamous cell carcinomas and promotes tumor development and invasion. The association between TROP2 expression and occurrence and development of oral squamous cell carcinoma (OSCC) remains to be understood. METHODS: We investigated the role of TROP2 in OSCC patients using a combination of biophysical approaches. A total of 108 OSCC patient specimens with varying degrees of differentiation were subjected to hematoxylin and eosin staining, immunohistochemistry, Kaplan-Meier survival curve analysis, and atomic force microscopy to analyze TROP2 expression, morphology, and mechanical properties of OSCC tissues. RESULTS: TROP2 was overexpressed in 34% of poorly differentiated OSCC samples. High levels of TROP2 were associated with 10.2% survival rate lower than 45.4% and patient age (odds ratio [OR] = 0.437, P = 0.039, 95% confidence interval [CI, 0.198-0.966]), tumor size (OR = 13.148, P = 0.000, 95% CI [5.060-34.168]), and TNM stage (OR = 0.141, P = 0.000, 95% CI [0.082-0.244]). Average surface roughness of low, medium, and highly differentiated OSCC tissues were 448.9 ± 54.8, 792.7 ± 83.6, and 993.0 ± 104.3 nm, respectively. The Pearson coefficient revealed a negative association between tumor stiffness and TROP2 expression (r = - 0.84, P < 0.01). CONCLUSION: Overexpression of TROP2 negatively associated with patient survival, degree of tumor differentiation, and tissue mechanics. Taken together, our findings demonstrated that TROP2 may be an indicator of OSCC differentiation leading to the altered mechanical properties of OSCC tissues.

RETRACTED: Knockdown of long non-coding RNA CCAT1 suppresses proliferation and EMT of human cervical cancer cell lines by down-regulating Runx2.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Following the concerns raised about the background pattern of the Western Blots from Figures 3A and 3C, the corresponding author has contacted the journal to request the retraction of the article. Given the comments of Dr Elisabeth Bik regarding this article "This paper belongs to a set of over 400 papers (as per February 2020) that share very similar Western blots with tadpole-like shaped bands, the same background pattern, and striking similarities in title structures, paper layout, bar graph design, and - in a subset - flow cytometry panels", the journal requested the authors to provide the raw data. However, the authors were not able to fulfil this request and therefore the Editor-in-Chief decided to retract the article.

Virtual versus jaw simulation in Oral implant education: a randomized controlled trial.

BACKGROUND: This research aims to investigate the evaluation methods of teaching oral implant clinical courses and estimate the effectiveness of a virtual simulation platform. METHODS: Eighty second- and third-year undergraduates in Lanzhou University were recruited and randomized to either three experimental groups or one control group. The subjects undertook theoretical examinations to test their basic level of knowledge after training in similarly unified knowledge courses. Each student group then participated in an eight-hour operating training session. An operation test on pig mandible was conducted, followed by a second theoretical examination. The assessment consists of three distinct parts: a subjective operating score by a clinical senior teacher, an implant accuracy analysis in cone-beam computed tomography (angular, apical, and entrance deviation), and comparison of the two theoretical examinations. Finally, students completed a questionnaire gauging their understanding of the virtual simulation. RESULTS: There was no significant difference between the four groups in first theoretical examination (P > 0.05); the second theoretical scores of the V-J and J-V group (62.90 ± 3.70, 60.05 ± 2.73) were significantly higher than the first time (57.05 ± 3.92, P < 0.05), while no difference between the V (57.10 ± 3.66) and J (56.89 ± 2.67) groups was found. Thus, the combination of V-J was effective in improving students' theoretical scores. The V-J and J-V groups had higher scores on operation (73.98 ± 4.58, 71.85 ± 4.67) and showed better implant precision. CONCLUSION: Virtual simulation education, especially with a jaw simulation model, could improve students' implantology achievements and training. Currently study found that the V-J group may performed better than the J-V group in oral implant teaching.

Downregulation of miR-222-3p Reverses Doxorubicin-Resistance in LoVo Cells Through Upregulating Forkhead Box Protein P2 (FOXP2) Protein.

BACKGROUND Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat colon cancer. Despite impressive initial clinical responses, drug resistance has dramatically compromised the effectiveness of DOX. However, the underlying mechanisms of chemotherapeutic resistance in colon cancer remain poorly understood. MATERIAL AND METHODS In this study, we compared the expression of miR-222-3p in DOX-resistant colon cancer cells (LoVo/ADR) with the corresponding DOX-sensitive parental cells (LoVo/S) using quantitative real-time PCR. In addition, miR-222-3p inhibitors were infected into LoVo/ADR cell lines and the effects of this treatment were assessed. The Cell Counting Kit 8 assay was employed to verify the sensitivity of colon cancer cell lines to DOX. EdU (5-ethynyl-2'-deoxyuridine) assay, flow cytometry, and in vivo subcutaneous tumorigenesis were used to assess cell proliferation and apoptosis. Transwell and wound healing assays were used to investigate cell migration after adding DOX. Additionally, the expression of forkhead box protein P2 (FOXP2), P-glycoprotein (P-gp) and caspase pathway-associated markers was assessed by western blotting. RESULTS Our results showed that miR-222-3p was upregulated in LoVo/ADR compared with the expression in LoVo/S cells. Additionally, downregulation of miR-222-3p in LoVo/ADR cells increased their sensitivity to DOX, reduced P-gp expression, and activated the caspase pathway. However, the downregulation of FOXP2 could efficiently reverse the effect of miR-222-3p inhibitors on LoVo/ADR cells. CONCLUSIONS Taken together, our results showed that miR-222-3p induced DOX resistance via suppressing FOXP2, upregulating P-gp, and inhibiting the caspase pathway.

Next-Generation Sequencing Analysis of mRNA Profile in Cisplatin-Resistant Gastric Cancer Cell Line SGC7901.

BACKGROUND Cisplatin-resistant gastric cancer (GC) occurs in patients with GC treated with cisplatin-based chemotherapy, which results in disease progression and early recurrence during the treatment. MATERIAL AND METHODS To understand the initiation and developmental mechanism underlying cisplatin-resistant GC, we developed cisplatin-resistant SGC7901 cells (SGC7901/DDP) from the parental cells (SGC7901/S) by continuous exposure to increasing concentrations of cisplatin and subjected these 2 cell lines to RNA sequencing analysis. The data were verified by quantitative polymerase chain reaction and their functional role was evaluated by cell counting kit 8 assay and cell apoptosis and cell cycle flow cytometric analysis. Bioinformatics analysis was performed to classify the differentially-expressed genes (DEGs) involved in the development of cisplatin resistance. RESULTS In comparison with SGC7901/S cells, SGC7901/DDP cells showed a total of 3165 DEGs (2014 upregulated and 1151 downregulated, fold change ≥2, and adjusted P value <0.001). qRT-PCR confirmed the reliability of the RNA sequencing results. Depletion of the top 5 upregulated mRNAs reversed the resistant index, increased apoptotic SGC7901/DDP cells, and arrested the cells at G2/M phase. Gene ontology analysis revealed that the DEGs mainly regulate metabolic process, immune system, locomotion, cell adhesion, cell growth, cell death, cytoskeleton organization, cell binding, signal transducing activity, and antioxidant activity. Kyoto Encyclopedia of Genes and Genomes analysis showed that the DEGs were mainly involved in the PI3K-Akt signaling pathway, Rap1 signaling pathway, proteoglycans in cancer, regulation of actin cytoskeleton, and pathways in cancer. CONCLUSIONS The present study is the first to interrogate mRNAs profiles in human GC cells with cisplatin resistance using RNA sequencing, which may assist in discovering potential therapeutic targets for cisplatin-resistant GC patients.

Recent Progress of Janus 2D Transition Metal Chalcogenides: From Theory to Experiments.

Since the discovery of graphene, 2D materials with various properties have gained increasing attention in fields such as novel electronic, optic, spintronic, and valleytronic devices. As an important derivative of 2D materials, Janus 2D materials, such as Janus transition metal chalcogenides (TMDs), have become a research hot spot in recent years. Janus 2D materials with mirror asymmetry display novel properties, such as the Rashba effect and normal piezoelectric polarization, providing great promise for their application in sensors, actuators, and other electromechanical devices. Here, the current theoretical and experimental progresses made in the development of Janus 2D TMDs, including their structure and stability, electronic properties, fabrication, and the results of their characterization are reported. Finally, the future prospects for the further development of Janus 2D materials are considered.

In Vitro and In Vivo Antioxidant Activities of the Flowers and Leaves from Paeonia rockii and Identification of Their Antioxidant Constituents by UHPLC-ESI-HRMSn via Pre-Column DPPH Reaction.

The genus Paeonia, also known as the "King of Flowers" in China, is an important source of traditional Chinese medicine (TCM). Plants of this genus have been used to treat a range of cardiovascular and gynecological diseases. However, the potential pharmacological activity of one particular species, Paeonia rockii, has not been fully investigated. In the first part of the present study, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), reducing power assays, and metal ion chelating assays were used to investigate the in vitro antioxidant activities of Paeonia rockii. In the second portion of the study, a mouse model of d-galactose-induced aging was used to validate the antioxidant effects of the flowers from Paeonia rockii in vivo. Lastly, potential antioxidant constituents were screened and identified by ultra-high pressure liquid chromatography and electrospray ionization coupled with high-resolution mass spectrometry (UHPLC-ESI-HRMSn) combined with the DPPH assay. Results indicated that the flowers and leaves exhibited stronger antioxidant activity than ascorbic acid in vitro. The therapeutic effect of Paeoniarockii was determined in relation to the levels of biochemical indicators, such as 8-iso-prostaglandin F2α (8-iso PGF2α) in the serum, superoxide dismutase (SOD), protein carbonyl, malondialdehyde (MDA), and glutathione (GSH) in the liver and brain, after daily intra-gastric administration of different concentrations of extracts (100, 200 and 400 mg/kg) for three weeks. The levels of 8-iso PGF2α (p < 0.01) and protein carbonyl groups (p < 0.01) were significantly reduced, whereas those of SOD (p < 0.05) had significantly increased, indicating that components of the flowers of Paeonia rockii had favorable antioxidant activities in vivo. Furthermore, UHPLC-ESI-HRMSn, combined with pre-column DPPH reaction, detected 25 potential antioxidant compounds. Of these, 18 compounds were tentatively identified, including 11 flavonoids, four phenolic acids, two tannins, and one monoterpene glycoside. This study concluded that the leaves and flowers from Paeonia rockii possess excellent antioxidant properties, highlighting their candidacy as "new" antioxidants, which can be utilized therapeutically to protect the body from diseases caused by oxidative stress.

Purified Phlorizin from DocynIa Indica (Wall.) Decne by HSCCC, Compared with Whole Extract, Phlorizin and Non-Phlorizin Fragment Ameliorate Obesity, Insulin Resistance, and Improves Intestinal Barrier Function in High-Fat-Diet-Fed Mice.

Natural products generally contain complex and multiple bioactive compounds that are responsible for the effects on health through complicated synergistic and/or suppressive actions. As an important raw material of local ethnic minority tea, ethnomedicines and food supplements in southwestern areas of China, Docynia indica (Wall.) Decne (DID) mainly consists of phlorizin (PHZ), which is the main active component. In this study, the holistic activities and the interactions of components of PHZ, non-phlorizin (NP) in the DID extract (DIDE) were evaluated. A rapid and effective high-speed counter-current chromatography (HSCCC) was performed to knock out PHZ from DIDE and the purity of PHZ was 96.01% determined by HPLC, with a recovery rate of 96.76%. After 13 weeks of treatment course in a high-fat diet (HFD)-induced obese mice model, the results revealed that the DIDE and PHZ significantly decreased weight gain, blood lipid levels, hyperplasia of adipocytes and alleviated inflammation (p < 0.05). Both DIDE and PHZ improves insulin resistance (p < 0.001). Meanwhile, the intestinal barrier function was improved compared to HFD group, through the determination of serum lipopolysaccharides (LPS), glucagon-likepeptide-2 (GLP-2) and hematoxylin-eosin staining of jejunum. Interestingly, after NP treatment, the metabolic syndrome of the HFD-induced obesity appeared to have a similar improvement. All the experiments showed that there is a synergistic weakening phenomenon when PHZ and NP interact with each other in the mixed state. In conclusion, for the PHZ and NP showing a good effect on anti-obesity, anti-inflammation, and intestinal barrier function, DIDE could be a good source of functional food to prevent obesity.

14,15-EET Suppresses Neuronal Apoptosis in Ischemia-Reperfusion Through the Mitochondrial Pathway.

Neuronal apoptosis mediated by the mitochondrial apoptosis pathway is an important pathological process in cerebral ischemia-reperfusion injury. 14,15-EET, an intermediate metabolite of arachidonic acid, can promote cell survival during ischemia/reperfusion. However, whether the mitochondrial apoptotic pathway is involved this survival mechanism is not fully understood. In this study, we observed that infarct size in ischemia-reperfusion injury was reduced in sEH gene knockout mice. In addition, Caspase 3 activation, cytochrome C release and AIF nuclear translocation were also inhibited. In this study, 14,15-EET pretreatment reduced neuronal apoptosis in the oxygen-glucose deprivation and re-oxygenation group in vitro. The mitochondrial apoptosis pathway was also inhibited, as evidenced by AIF translocation from the mitochondria to nucleus and the reduction in the expressions of cleaved-caspase 3 and cytochrome C in the cytoplasm. 14,15-EET could reduce neuronal apoptosis through upregulation of the ratio of Bcl-2 (anti-apoptotic protein) to Bax (apoptosis protein) and inhibition of Bax aggregation onto mitochondria. PI3K/AKT pathway is also probably involved in the reduction of neuronal apoptosis by EET. Our study suggests that 14,15-EET could suppress neuronal apoptosis and reduce infarct volume through the mitochondrial apoptotic pathway. Furthermore, the PI3K/AKT pathway also appears to be involved in the neuroprotection against ischemia-reperfusion by 14,15-EET.

DNA methylation and histone deacetylation regulating insulin sensitivity due to chronic cold exposure.

In this study, we investigated the causal relationship between chronic cold exposure and insulin resistance and the mechanisms of how DNA methylation and histone deacetylation regulate cold-reduced insulin resistance. 46 adult male mice from postnatal day 90-180 were randomly assigned to control group and cold-exposure group. Mice in cold-exposure group were placed at temperature from -1 to 4 °C for 30 days to mimic chronic cold environment. Then, fasting blood glucose, blood insulin level and insulin resistance index were measured with enzymatic methods. Immunofluorescent labeling was carried out to visualize the insulin receptor substrate 2 (IRS2), Obese receptor (Ob-R, a leptin receptor), voltage-dependent anion channel protein 1 (VDAC1), cytochrome C (cytC), 5-methylcytosine (5-mC) positive cells in hippocampal CA1 area. Furthermore, the expressions of some proteins mentioned above were detected with Western blot. The results showed: ① Chronic cold exposure could reduce the insulin resistance index (P < 0.01) and increase the number of IRS2 positive cells and Ob-R positive cells in hippocampus (P < 0.01). ② The expressions of mitochondrial energy-relative proteins, VDAC1 and cytC, were higher in cold-exposure group than in control group with both immunohistochemical staining and Western blot (P < 0.01). ③ Chronic cold exposure increased DNA methylation and histone deacetylation in the pyramidal cells of CA1 area and led to an increase in the expression of histone deacetylase 1 (HDAC1) and DNA methylation relative enzymes (P < 0.01). In conclusion, chronic cold exposure can improve insulin sensitivity, with the involvement of DNA methylation, histone deacetylation and the regulation of mitochondrial energy metabolism. These epigenetic modifications probably form the basic mechanism of cold-reduced insulin resistance.