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Objective: To investigate the role of N-glycosylation modification of proteins in adipocyte differentiation during the adipogenic process., Methods: SVF cells and adipocytes were analyzed for proteomics and intact N-glycopeptide modificationomics.Differential expression of proteins, glycoforms, and sites between the two groups was screened and subjected to Gene Ontology (GO) functional enrichment analysis, KEGG pathway enrichment analysis, and protein-protein interaction (PPI) network analysis. The top 20 most significantly differentially expressed adipogenic differentiation-related proteins were identified, and the most pronouncedly altered proteins were analyzed for glycoforms, glycan chains, and sites., Results: Proteomics analysis identified 39,392 peptides and 5208 proteins, while intact N-glycopeptide modification profiling identified 3293 intact glycopeptides, 426 proteins, and 161 glycan chains. Proteomics identified 2510 differentially expressed proteins, with CD36 (Cluster of Differentiation 36, CD36) significantly upregulated. In adipocytes, CD36 had 4 N-glycosylation sites: N79, N220, N320, N417, with N320 being a newly identified site. GO enrichment results indicated that CD36 is associated with fatty acid oxidation, lipid oxidation, and fatty acid uptake into cells., Conclusion: Multiple proteins undergo N-glycosylation modification during adipocyte differentiation, with CD36, a fatty acid translocase, being significantly expressed in adipocytes. This suggests that N-glycosylation modification of CD36 may play a crucial role in adipocyte differentiation, providing a foundation for further investigation into the function of CD36 N-glycosylation in adipocyte differentiation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon‑carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid β (Aβ)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aβ-induced neuronal damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The precise determination of polypeptide antibiotics (PPTs) in foods has been always challenging because of the interference of various endogenous peptides in complex matrix. Herin, a novel large-pore covalent organic framework (TABPT-SPDA-COF) with accessible pore size of 7.9 nm was synthesized as a solid phase extraction (SPE) absorbent for efficiently enriching four PPTs existed in foods originating from animals. The parameters of SPE process were systematically optimized. Subsequently, four PPTs were determined by UHPLC-MS/MS. Under the optimal conditions, TABPT-SPDA-COF shows outstanding enrichment capacity for PPTs in contrast to commercial absorbents ascribed to size selectivity and multiple interaction effects. The method exhibits excellent linear range (0.005-100 ng mL -1 ), satisfactory limits of detection (0.1 pg mL -1 ) as well as relative recoveries (86.2-116 %). This work offers a practicable platform to monitor trace PPTs from complex animal-derived foodstuffs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Red tides occur every year in the Qinhuangdao sea area of China, including a variety of toxic algae and non-toxic algae. Toxic red tide algae have caused great damage to the marine aquaculture industry in China and seriously endangered human health, but most of non-toxic algae are important bait for marine plankton. Therefore, it is very important to identify the type of mixed red tide algae in Qinhuangdao sea area. In this paper, three-dimensional fluorescence spectroscopy and chemometrics were applied to the identification of typical toxic mixed red tide algae in Qinhuangdao. Firstly, the three-dimensional fluorescence spectrum data of typical mixed red tide algae in Qinhuangdao sea area were measured by f-7000 fluorescence spectrometer, and the contour map of algae samples was obtained. Secondly, the contour spectrum analysis is carried out to find the excitation wavelength of the peak position of the three-dimensional fluorescence spectrum and form the new three-dimensional fluorescence spectrum data selected by the feature interval. Then, the new three-dimensional fluorescence spectrum data are extracted by principal component analysis (PCA). Finally, the feature extraction data and the data without feature extraction are used as the input of the genetic optimization support vector machine (GA-SVM) and particle swarm optimization support vector machine (PSO-SVM) classification models, respectively, to obtain the classification model of mixed red tide algae, and the two feature extraction analysis methods and two classification algorithms are compared. The results show that the classification accuracy of the test set using the principal component feature extraction and GA-SVM classification method is 92.97 %, when the excitation wavelengths are 420 nm, 440 nm, 480 nm, 500 nm and 580 nm, and the emission wavelengths are 650-750 nm. Therefore, it is feasible and effective to apply the three-dimensional fluorescence spectrum characteristics and genetic optimization support vector machine classification method to the identification of toxic mixed red tide algae in Qinhuangdao sea area., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Large amounts of microplastics (MPs) enter the soil along with the amendment of sludge to soil. However, it is still unclear about the response of MPs occurrence and the adsorption behaviors of cadmium (Cd)on MPs to typical agricultural environmental scenarios. In present work, three kinds of MPs (polyethylene, polypropylene, and polystyrene) were chosen to investigate that response in three agricultural environmental scenarios with sludge-amended soil, including dry-wet alteration (7 d, five cycles), microbial addition (Bacillus subtilis, 0.05 g/g soil), and Ultraviolet (UV) irradiation (340 nm, 4 × 15 W, 4 d). The results showed that there was the highest adsorption capacity of Cd on MPs (36.21, 45.15, 12.43 μg/g for PE, PP, PS, respectively) after UV irradiation exceeding those from MPs triggered by other two scenarios). UV irradiation caused an increase in the abundance of Streptomyces, an expansion in specific surface area, a significant change in surface morphologies, an improvement in crystallinity or the formation of new crystals, and an enhancement in C-O and CO content, and then resulted in the incremental adsorption capacity of Cd on MPs. The findings are important of significance for controlling the environmental risks from sludge MPs via carrying heavy metals in the soil-plant systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: Glycyrrhizic acid is a natural anti-non-alcoholic fatty liver disease (NAFLD) compound isolated from licorice, while its action mechanism deserves to be fully elucidated., Materials and Methods: Enlightened by the widely discovered associations between the NAFLD and gut microbiota, this study aimed to explore whether glycyrrhizic acid, licorice flavonoids, and licorice extract can regulate the gut microbiota of rats fed a high-fat diet., Key Findings: It was found that glycyrrhizic acid, licorice flavonoids, and licorice extract could significantly reduce the level of triglycerides in the liver of NAFLD model rats, and the effect of glycyrrhizic acid was stronger than licorice flavonoids and licorice extract. Moreover, they caused significant changes in the structural composition of the gut microbiota. Correlation analysis showed that the regulation of hepatic total cholesterol and triglyceride levels by glycyrrhizic acid treatment was closely related to the decrease of the relative abundances of Lachnospiraceae, Coriobacteriaceae, Blautia, and Collinsella and the increase of the relative abundances of Romboutsia and Turicibacter on the gut microbiota. Meanwhile, the functional predictive analysis of the gut microbiota indicated that the function of carbohydrate transport and metabolism was significantly decreased by drugs treatment, which might contribute to the decrease of fat accumulation in the liver of rats., Significance: In conclusion, this study revealed the ameliorating effects of glycyrrhizic acid, licorice flavonoids, and licorice extract on NAFLD, and suggested that the effect of glycyrrhizic acid on NAFLD may be related to the improvement of the dysbiosis of gut microbiota., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Background & Aims: Numerous studies have evaluated the effects of dietary protein on specific health outcomes. The aim of our umbrella review was to summarize the existing evidence between the intake of dietary proteins and multiple health outcomes, and assess their strength and validity., Methods: Our study was registered at PROSPERO (No. CRD42021255938). We systematically searched PubMed, Embase, and Web of Science databases from inception to May 18, 2021, to identify relevant systematic reviews and meta-analyses of observational studies. The validated "A Measurement Tool to Assess Systematic Reviews" for assessing the methodological quality of included systematic reviews was utilized. For each association, we estimated the summary effect size using fixed and random effects methods, and the 95% confidence and prediction intervals. We also evaluated heterogeneity, evidence of small-study effects, and excess significance bias., Results: Overall, 16 articles with 58 meta-analyses were included. All studies were categorized as over moderate quality. On employing the random-effects model, fourteen (24.1%) meta-analyses were found to be significant at P < 0.05, whereas only one (1.7%) remained significant at P < 10 -6 . Twenty-two (37.9%) meta-analyses had large or very large heterogeneity. Evidence of small-study effects and excess significance bias was found for three (5.2%) meta-analyses, respectively. One meta-analysis was supported by highly suggestive evidence, indicating that a 5% increase in energy intake from animal protein was associated with 12% higher risk of type 2 diabetes (95% confidence interval [CI]: 1.08-1.17). Of note, the intake of animal and plant proteins had different health effects on type 2 diabetes, all-cause mortality, and risk of cardiovascular disease mortality., Conclusions: Although the intake of dietary protein was associated with certain health outcomes, the strength of evidence was limited for most outcomes. Moreover, the source of dietary protein is an important factor that requires better consideration in future studies., Competing Interests: Conflicts of Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Microplastics (MPs) are emerging pollutants that are enriched in sludge. They enter soil through sludge soil amendment, landfill, and discard, which will cause inescapable environmental pollution risks. Sludge treatment technology commonly used in China include anaerobic digestion (AD), thermal drying (TD), thermal hydrolysis (TH) and aerobic composting (AC). In this study, characteristics of MPs in sewage sludge from four representative large cities in China (Zhengzhou, Chongqing, Guangzhou, and Guilin) were analyzed. Effects of four representative sludge treatment technology on sludge MPs were also studied. In addition, the amount of MPs input to soil from sludge in China was estimated. The abundance range of sludge MPs of representative cities in China was 1448-11,125 n∙kg -1 DW. Previous studies indicate that this abundance range is low among other domestic cities and is close to that of European countries. MPs were predominantly fiber-shaped, accounting for 46.66%; 56.5% MPs were white and transparent, and 62.5% were polypropylene and polyethylene. The abundance of MPs in the sludge increased after TH, indicating that MPs broke into smaller particles. However, the other three treatment methods had no significant influence on the abundance of MPs. Scanning electron microscopy analysis showed that the micro-morphology of sludge MPs surface were rougher after AD, and MPs cracked following TD and TH. Furthermore, broken edges were more blurred after TH, and surfaces of MPs were damaged and eroded after AC. The input quantities of MPs in sludge to soil was deduced to be 10 13 particles per year. These results are important for controlling the potential risk of sludge MPs in China., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Adverse effects from exposure to particulate matter <2.5 μm in diameter (PM 2.5 ) on health-related outcomes have been found in a range of experimental and epidemiological studies. This study aimed to assess the significance, validity, and reliability of the relationship between long-term PM 2.5 exposure and various health outcomes. The Embase, PubMed, Web of Science, CNKI, WANFANG, VIP, and SinoMed databases and reference lists of the retrieved review articles were searched to obtain meta-analysis and systematic reviews focusing on PM 2.5 -related outcomes as of August 31, 2021. Random-/fixed-effects models were applied to estimate summary effect size and 95% confidence intervals (CIs). The quality of included meta-analyses was evaluated based on the AMSTAR 2 tool. Small-study effect and excess significance bias studies were conducted to further assess the associations. Registered PROSPERO number: CRD42020200606. This included 24 articles involving 71 associations between PM 2.5 exposure and the health outcomes. The evidence for the positive association of 10 μg/m 3 increments of long-term exposure to PM 2.5 and stroke incidence in Europe was convincing (effect size = 1.07, 95% CI: 1.05-1.10). There was evidence that was highly suggestive of a positive association between 10 μg/m 3 increments of long-term exposure to PM 2.5 and the following health-related outcomes: mortality of lung cancer (effect size = 1.11, 95% CI: 1.08-1.13) and Alzheimer's disease (effect size = 4.79, 95% CI: 2.79-8.21). There was highly suggestive evidence that chronic obstructive pulmonary disease risk is positively associated with higher long-term PM 2.5 exposure versus lower long-term PM 2.5 exposure (effect size = 2.32, 95% CI: 1.88-2.86). In conclusion, the positive association of long-term exposure to PM 2.5 and stroke incidence in Europe was convincing. Given the validity of numerous associations of long-term exposure to PM 2.5 and health-related outcomes is subject to biases, more robust evidence is urgently needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier B.V.)

Acccurate identification whether red tide has ithyotoxicity is very significant for microalgae monitoring. In order to realize the rapid and non-destructive detection of ichthyotoxic red tide algae, a detection method combining three-dimensional (3D) fluorescence spectrum and particle swarm optimization support vector machine (PSO-SVM) was developed to monitor the ichthyotoxic red tide algae with cell concentrations from 10 4 cells/mL to 10 6 cells/mL. The contour maps contracted form three-dimensional fluorescence spectra of six common species of ichthyotoxic algae and eight common species of non-ichthyotoxic algae,which are analyzed to select the optimal emission and excitation wavelength span. The new feature data are acquired by using the emission spectrum data at 480 nm and 510 nm excitation wavelengths. The new feature data are used as the input of particle swarm optimization support vector machine to establish the optimal classification model of ichthyotoxic algae, which achieves an classification accuracy of 100% for the test set. The optimal classification model is successfully applied to identify the ichthyotoxicity of different algae including Heterosigma akashiwo, Chattonella marina, Phaeocystis globosa, Prorocentrum donghaiense, Karenia dunnii, Isoscelina galbana, Isosceles globosa and Skeletonema costatum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Evidence for a role of single nutrition or foods on ovarian cancer (OC) survival has been limited and inconclusive. Due to the potentially complex interactions in dietary, we applied dietary patterns to this study to firstly explore the relationship between the pre-diagnosis overall diet and OC survival., Methods: The prospective cohort study was conducted among 853 OC patients aged 18-79 years during 2015-2020. Dietary intake was collected using a validated 111-item food frequency questionnaire. Deaths were obtained by medical records and cancer registry up to March 31, 2021. Cox proportional hazards regression models was used to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of pre-diagnosis dietary patterns with overall survival (OS)., Results: Overall, during the follow-up period (median: 37.57 months, interquartile: 25.00-50.17 months), 130 (18.49%) OC patients died. Four dietary patterns were identified: healthy pattern, ethnic pattern, animal foods pattern, and sweet pattern. The highest tertile of the healthy pattern scores was related to better OS compared with the lowest tertile scores (HR = 0.54, 95% CI = 0.30-0.98, p trend <0.05), whereas OC patients with highest adherence to the animal foods pattern was associated with worse OS than those with the lowest adherence (HR = 1.90, 95% CI = 1.14-3.17, p trend <0.05). We found no significant associations between adherence to ethnic pattern and sweet pattern and OS of OC patients., Conclusion: Pre-diagnosis healthy patterns was associated with better OC survival, whereas animal pattern was associated with worse survival among OC survivals., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In view of the problem of the paralytic shellfish poison producing algae on-line measurement and identification, a new feature extraction method of paralytic shellfish poison producing algae measurement and identification based on quaternion principal component analysis (QPCA) is investigated. The three-dimensional (3D) fluorescence spectra of three common species of paralytic shellfish poison producing algae and eight species common of non paralytic shellfish poison producing algae are analyzed. The quaternion parallel representation model of algae three-dimensional fluorescence spectrum data is established, then the features of quaternion principal component is extracted to use as the input of k-nearest neighbor (KNN) classifier, and the identification of paralytic shellfish poison producing algae is realized by the three-dimensional fluorescence spectra coupled with quaternion principal component analysis. The results show that under the quaternion parallel representation model, the recognition accuracy rate of multiplication feature, modulus feature and summation feature is 90%, 95% and 100% respectively. Compared with that of the principal component analysis feature extraction method, the recognition accuracy rate in pure samples by summation feature of quaternion principal component is improved by 10%. This study provides an experimental basis for the accurate monitoring technology of three-dimensional fluorescence spectrum of paralytic shellfish poison producing algae., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Increasing intestinal barrier function is one of the basic methods to suppress inflammation in the progression from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). Luteolin exists widely in vegetables, fruits and natural herbs and has various biological activities, including benefits on nonalcoholic fatty liver disease (NAFLD). However, its regulatory effects on the gut microbiota and involvement in its biological activities remain to be investigated. We fed rats a high-fat diet containing 0.5% luteolin for 12 weeks and determined the effects of luteolin on lipid metabolism, inflammation, and the gut microbiota. Supplementation with luteolin for 12 weeks significantly reduced blood lipids and hepatic lipid levels and improved liver fat accumulation and inflammation. Moreover, supplementation with luteolin led to the significant enrichment of more than 10% of gut bacterial species, which contributed to increase the abundance of ZO-1, reduce intestinal permeability, reduce plasma lipopolysaccharide, and inhibit the TLR4/NF-κB pathway. In summary, the anti-inflammatory effect of luteolin might be related to changes in the gut microbiota and contribute to preventing the progression from SS to NASH. Our research provides new insights into the anti-inflammatory mechanism of luteolin and supports its use as a dietary supplement for NAFLD patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Microplastics (MPs) are an emerging global pollutant. MPs research is mainly concentrated on water, with limited research on MPs in sewage sludge. MPs from various sources are collected into sewage and most of the MPs are trapped in the sludge during the sewage treatment process. Sludge is not only a sink of MPs, but also a source. Soil amendment with sludge provides nutrients into the soil, but it can also import substantial MPs into the soil, which has certain environmental risks. Therefore, we focused on the MPs in sludge and sludge-amended soil and conducted a literature review to summarize the sources, physical properties and fate of the MPs in sludge, as well as their separation, identification and statistical methods. MPs can accumulate in the soil, influence the properties of the soil, and also migrate, which might result in the pollution of deep soils and groundwater. In addition, the adsorption by MPs of heavy metals, organic pollutants, antibiotics and antibiotic resistance genes cannot be ignored as sewage sludge generally contains substantial concentrations of these pollutants. They can be adsorbed by the MPs and transferred into the soil with sludge amendment of soil. The combination and interaction of MPs with its adsorbed pollutants might increase environmental risk, further leading to possibility of them being uptaken by plants. The specific long-term risks to the environment caused by MPs in soil with sludge amendment require further exploration and investigation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Large-scale production of an antibacterial hydrogel is of critical importance for its practical application in biomedical field. In this regard, herein we report on the construction of a double-syringe injection device by using all the commercial parts and its use for continuous production of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel fiber. The resultant CMCh-Zn hydrogel fibers exhibit good stretchability and knittability. The Zn loading into the hydrogel fibers can be easily controlled by adjusting the concentration of Zn 2+ solution. Scanning electron microscope measurements indicate that the CMCh-Zn hydrogel fibers have a relatively smooth and thin skin layer, as well as, a 3-dimensional interconnected microporous interior architecture. Antibacterial activities of the CMCh-Zn hydrogel fibers against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli are also investigated. The results show that the intrinsic blue fluorescence of the as-prepared CMCh-Zn hydrogel fibers can be employed as optical indicator of their antibacterial effectiveness., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Bot flies (Oestridae) are obligate endoparasites of mammals, and their extraordinary diversification is of great importance in understanding the evolution of parasitism. However, evolutionary analysis of Oestridae has long been impeded by lack of information. Here, the first three mitochondrial genomes of nasal bot flies (Cephalopina titillator, Cephenemyia trompe and Rhinoestrus usbekistanicus) and a comparative mitochondrial genomic analysis between subfamilies of Oestridae are presented. Contrasting to many other parasites, mitochondrial genomes of oestrids are conserved in structure, and genes have retained the same order and direction as the ancestral insect mitochondrial genome. Nucleotide composition is highly heterogenous, with Gasterophilinae possessing highest GC content and smallest genomic size. Mitochondrial evolutionary rates vary considerably, with Hypodermatinae and Oestrinae exhibiting a faster average rate than Cuterebrinae and Gasterophilinae. In addition, the first phylogenomic analysis covering all four bot fly subfamilies was conducted, supporting monophyly of Oestridae and a sister-group relationship of Hypodermatinae and Oestrinae. The only topological ambiguity is Cuterebrinae being a sister-group of either (Hypodermatinae + Oestridae) or Gasterophilinae. Thus, we suggest that mitochondrial genomes carry a great potential for phylogenetic analysis of Oestridae, and more information of Cuterebrinae is needed to illuminate the early evolutionary radiation and parasite-host coevolution of bot flies., Competing Interests: Declaration of competing interest The authors have no conflicts of interests to declare., (Copyright © 2020. Published by Elsevier B.V.)

BAG3 is a member of the cochaperone BAG family and often highly expressed in various cancers. Recently, evidences show that BAG3 promotes stemness of human cancer cells. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule, which is covalently conjugated with substrates to form ISGylated proteins. Global screening BAG3 interacting partners demonstrated that ISG15 might be a potential binding partner. The current study revealed that BAG3 did not interact with ISG15, but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer (PDAC). It was further found that BAG3 deletion stabilized ISG15 mRNAs, while suppressed its translation via increasing Serine phosphorylation of Ago2 at position 387 (S387). Both BAG3 deletion and ISG15 knockdown suppressed stem cell-like phenotypes of PDAC cells, including clonogenicity, invasiveness and spheroid formation. In addition, ectopic ISG15 expression rescued the suppressive role of BAG3 deletion in cancer stem cell (CSC)-like phenotypes of PDAC cells, and this effect of ISG15 was independent of its ISGylation function. The current study implies that BAG3 and ISG15 may provide a therapeutic advantage for PDAC., (Copyright © 2019. Published by Elsevier B.V.)

Species of Gasterophilus are obligate parasites of equids and may induce severe, even lethal myiasis. However, identification of the third instar Gasterophilus larva at the species level is still problematic predominantly due to a shortage of diagnostic morphological features and incomplete molecular libraries. Testing the suitability of three different molecular markers showed that the traditional 650 bp barcode region near the 5' terminus of the cytochrome c oxidase subunit I (COI) served as a better tool for species-level identification than a 663 bp region near the 3' terminus of COI and a 554 bp region near the 5' terminus of the large subunit ribosomal RNA. We found that barcoding discriminates G. intestinalis, G. nasalis, G. nigricornis and G. pecorum but not G. haemorrhoidalis and G. inermis. A comparative morphological study using scanning electron microscopy was conducted to promote the identification of the third instar larvae. Photographs of fresh mature third instar larvae are provided for all species, and the remarkable green body colour of third instar G. nigricornis is fully documented for the first time. Two morphological keys are provided, one is suitable for quick identification, and the other based on ultrastructural details is provided for further comparative morphological investigation. A new term 'oral plate' instead of 'mandible' was proposed for a pair of sclerites of uncertain homology emerging from the secondary mouth opening. Our data shows that DNA barcodes cannot replace morphology for identification of third instars of Gasterophilus species, and a scaffold is provided for an integrated taxonomic reference system, which will contribute to monitoring gasterophilosis for equid welfare and protection, and also facilitate further studies in functional anatomy, phylogenetic analyses and host-parasite co-evolutionary investigations of Gasterophilus., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Bioassay-guided fractionation of the dichloromethane-soluble portion of the stems of Garcinia paucinervis led to the isolation of eight new xanthones, including three pairs of enantiomers, (+) and (-) paucinervins L-N (1a-3a, and 1b-3b), one optically pure compound, (-) paucinervin O (4), and one new analogue, paucinervin P (5), as well as thirteen known xanthones (6-18). Their structures were established by detailed analysis of extensive spectroscopic data. The absolute configurations of 1-4 were confirmed by ECD calculations. All the isolates 1-18 displayed antiproliferative effect against HL-60 with IC 50 values ranging from 0.87 to 29.14 μM, of which compound 5 was the most active. Compounds 6, and 14 exhibited potential inhibitory activity against PC-3 cells, while compounds 5-7, 14, and 16-17 displayed cytotoxic potency against Caco-2 cells. A preliminary structure-activity relationship was also discussed., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Five pairs of new 2-oxoindole alkaloids, (±)-peganumalines A-E (1-5), and a new indole alkaloid, peganumaline F (6), along with two known analogues, were isolated from the seeds of Peganum harmala. Their structures and absolute configurations were elucidated through spectroscopic analyses and quantum chemistry calculations. Notably, (±)-peganumalines A (1) represent a pair of rare 2-oxoindole dimeric alkaloid enantiomer with the hitherto unknown carbon skeleton. All isolates were tested for antiproliferative and antibacterial activities., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Three new diterpenoids, ebractenoids O~Q (1-3), and a new phenolic glucoside, γ-pyrone-3-O-β-d-(6-galloyl)-glucopyranoside (4), together with 6 known compounds, were isolated from the 95% ethanol extract of the roots of Euphorbia ebracteolata, and their structures were elucidated on the basis of spectroscopic data. The absolute configurations of 1-3 were determined by electronic circular dichroism (ECD) calculations. The inhibitory effects of all the isolates with exception of compounds 8 and 10 on the NO production in lipopolysaccharide (LPS)-induced macrophages were evaluated. All of them exhibited significant inhibitory activity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Posttranscriptional regulation process plays important roles in renal disease pathogenesis. AU-rich element RNA-binding protein (AUF1) interacts with and destabilizes mRNAs containing AU-rich elements (AREs) in their 3'UTR. The current study demonstrated that AUF1 was increased in unilateral ureteral obstruction (UUO) animal models. While proliferation and migration of HK2 cells was unaltered by AUF1 downregulation under normal condition, proliferative inhibition and migratory promotion mediated by TGF-β was significantly compromised. Mechanically, AUF1 downregulation decreased phosphorylated Smad2/3 via increasing their E3 ligase Nedd4L at the posttranscriptional level. In addition, the current study identified Nedd4L as a previously unreported target of AUF1. AUF1 regulates Nedd4L expression at the posttranscriptional level by interaction with AREs in the 3'UTR of the Nedd4L mRNA. Collectively, the current study indicates that AUF1 might be a potential player in renal tubulointerstitial fibrosis through modulation of TGF-β signal transduction via posttranscriptional regulation of Nedd4L., (Copyright © 2017. Published by Elsevier B.V.)

Bcl-2 associated athanogene 3 (BAG3) contains a modular structure, through which BAG3 interacts with a wide range of proteins, thereby affording its capacity to regulate multifaceted biological processes. BAG3 is often highly expressed and functions as a pro-survival factor in many cancers. However, the oncogenic potential of BAG3 remains not fully understood. The cell cycle regulator, S-phase kinase associated protein 2 (Skp2) is increased in various cancers and plays an important role in tumorigenesis. The current study demonstrated that BAG3 promoted proliferation of ovarian cancer cells via upregulation of Skp2. BAG3 stabilized Skp2 mRNA via its 3'-untranslated region (UTR). The current study demonstrated that BAG3 interacted with Skp2 mRNA. In addition, miR-21-5p suppressed Skp2 expression, which was compromised by forced BAG3 expression. These results indicated that at least some oncogenic functions of BAG3 were mediated through posttranscriptional regulation of Skp2 via antagonizing suppressive action of miR-21-5p in ovarian cancer cells., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) characterized by the translocation t (11; 14) (q13; q32). Drug resistance remains a formidable obstacle to treatment and the median survival for MCL patients is between 3 and 5 years. Thus, there is an urgent need to discover novel approaches to MCL therapy. The signal transducer and activation of transcription 3 (STAT3) has been found to be constitutively activated in several subtypes of MCL cell lines and MCL tumors. WP1066, a small-molecule inhibitor of STAT3, exerted antitumor activity in hematological and solid malignancies by inhibiting key survival and growth signaling pathways. In the present study, we evaluated the antiproliferative and proapoptotic activity of WP1066 combined with pan-histone deacetylase (HDAC) inhibitor vorinostat (SAHA) in a panel of MCL cell lines. In addition, potential mechanisms involved were also explored. The outcome showed that combination of WP1066 with SAHA resulted in synergistic growth inhibition and apoptosis induction in MCL cell lines in vitro. Furthermore, combination of WP1066 with SAHA inhibited the constitutive STAT3 activation and modulated mRNA expressions of anti- and pro-apoptotic genes. Our findings suggest that agents targeting the STAT3 pathway such as WP1066 may be useful therapeutic drugs for MCL when combined with SAHA., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We have previously reported that the PI3K/Akt signaling pathway is involved in hepatocyte growth factor (HGF)-induced differentiation of adult rat pancreatic ductal epithelial cells (PDECs) into islet β-cells in vitro. The transcription factor CREB is one of the downstream key effectors of the PI3K/Akt signaling pathway. Recent studies showing that CREB is required for the survival of certain cell types prompted us to examine whether CREB is a nuclear target for activation via the HGF-dependent Ser/Thr kinase Akt/PKB in the differentiation of pancreatic duct cell into islet β-cells. In this study, we first attempted to examine whether HGF modulates the Akt-dependent activation of target gene CREB and then investigated whether CREB activity affects the differentiation of HGF-induced PDECs. Finally, we studied the role of CREB in modulating the expression of transcription factors in PDECs during the differentiation of HGF-induced PDECs. Our results demonstrated that CREB is a regulatory target for the protein kinase Akt/PKB in the differentiation of pancreatic ductal cells into islet β-cells mediated by HGF., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Pancreatic ductal epithelial cells (PDECs) were induced to differentiate into insulin-producing cells by hepatocyte growth factor (HGF) in our previous study, but the mechanism through which this induction occurs is still unknown. HGF is a ligand that activates a tyrosine kinase encoded by the c-Met proto-oncogene. This activation is followed by indirect activation of multiple downstream signal transduction pathways (including MAPKs and the PI3K/AKT signaling pathways) that initiate various biological effects. Therefore, we speculated that the differentiation of PDECs is through either the MAPK signaling pathway or the PI3K/AKT signaling pathway. To test this hypothesis, isolated PDECs from adult rats were stimulated by adding HGF to their medium for 28days. Then, the expression levels of several protein kinases, including MAPKs (ERK1/2, p38, and JNK) and AKT, were determined by Western blotting to determine if specific protein kinases are activated in these pathways. Subsequently, re-isolated from adult rats and cultured PDECs were pre-treated with specific inhibitors of proteins shown to be activated in these signaling pathways; these cells were then induced to differentiate by the addition of HGF. The expression levels of protein kinases were determined by Western blotting, and the differentiation rate of insulin-positive cells was determined by flow cytometry. The change of PDEC differentiation rates were compared between the groups in which cells with or without inhibitors pretreatment to determine the specific signaling pathway(s) that may be involved in HGF-induced differentiation of PDECs. After isolating PDECs and stimulating them with HGF for 28days, the expression levels of phosphorylated ERK1/2 as well as total and phosphorylated AKT of cultured cells were significantly increased compared to the normal control group (p<0.05), suggesting that the signaling pathways involving ERK1/2 and Akt (MEK-ERK and PI3K-AKT) are activated during HGF-induced PDEC differentiation. MEK1/2 or PI3K inhibitors were separately added to the culture medium of PDECs pre-treated with HGF. These results show that compared to the HGF-treated group, the differentiation rate of insulin-positive cells was significantly decreased in the HGF/LY294002 (PI3K inhibitor) group (13.47+/-1.57% vs. 33.47+/-1.34%, p<0.05); however, the differentiation rate of insulin-positive cells was not significantly different in the HGF/PD98059 (MEK1/2 inhibitor) group. These data suggest that HGF induces PDECs to differentiate into insulin-producing cells through the PI3K/AKT signaling pathway., (Copyright 2010 Elsevier Inc. All rights reserved.)

The present study was conducted to identify effective factors that could induce differentiation of pancreatic ductal epithelial cells (PDECs) into insulin-producing cells. We examined the effect of hepatocyte growth factor (HGF) and betacellulin-delta4 (BTC-delta4) on PDECs. We isolated PDECs from adult rats and stimulated them with HGF and BTC-delta4 for 28days. We observed several characteristics of PDECs after induction, including functional changes in PDECs, differentiation rate, and expression levels of critical transcription factors. We observed that insulin content and glucose-induced insulin secretion were significantly higher in induced PDECs compared to control PDECs. The expression of markers specific to mature beta-cells, i.e., insulin and glucose transporter-2 (GLUT2) was also observed. An analysis of the expression of different transcription factors (PDX-1, Ngn3, NeuroD, and Pax4) revealed that cell-specific gene expression patterns varied from 7 to 28days after treatment. Hence, we conclude that treatment with a combination of HGF and BTC-delta4 is effective in inducing the differentiation of PDECs into insulin-secreting cells.