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The expending of elderly population worldwide has resulted in a dramatic rise in the incidence of chronic diseases such as Alzheimer's disease (AD). Inadequate understanding of the mechanisms underlying AD has hampered the development of efficient tools for definitive diagnosis and curative interventions. Previous studies have attempted to discover reliable biomarkers of AD, but these biomarkers can only be measured through invasive (neuropathological markers in cerebrospinal fluid) or expensive (positron emission tomography scanning or magnetic resonance imaging) techniques. Metabolomics is a high-throughput technology that can detect and catalog large numbers of small metabolites and may be a useful tool for characterization of AD and identification of biomarkers. In this study, we used ultra-performance liquid chromatography-mass spectrometry based untargeted metabolomics to measure the concentrations of plasma metabolites in a cohort of subjects with AD (n=44) and cognitively normal controls (Ctrl, n=94). The AD group showed marked reductions in levels of polyunsaturated fatty acids, acyl-carnitines, degradation products of tryptophan, and elevated levels of bile acids compared to the Ctrl group. We then validated the results using an independent cohort that included subjects with AD (n=30), mild cognitive impairment (MCI, n=13), healthy controls (n=43), and non-AD neurological disease controls (NDC, n=31). We identified five metabolites comprising cholic acid, chenodeoxycholic acid, allocholic acid, indolelactic acid, and tryptophan that were able to distinguish patients with AD from both Ctrl and NDC with satisfactory sensitivity and specificity. The concentrations of these metabolites were significantly correlated with disease severity. Our results also suggested that altered bile acid profiles in AD and MCI might indicate early risk for the development of AD. These findings may allow for development of new approaches for diagnosis of AD and may provide novel insights into AD pathogenesis.

Chalcones (1,3-diaryl-2-propen-1-ones) are precursors for flavonoids and isoflavonoids, which are common simple chemical scaffolds found in many naturally occurring compounds. Many chalcone derivatives were also prepared due to their convenient synthesis. Chalcones as weandhetic analogues have attracted much interest due to their broad biological activities with clinical potentials against various diseases, particularly for antitumor activity. The chalcone family has demonstrated potential in vitro and in vivo activity against cancers via multiple mechanisms, including cell cycle disruption, autophagy regulation, apoptosis induction, and immunomodulatory and inflammatory mediators. It represents a promising strategy to develop chalcones as novel anticancer agents. In addition, the combination of chalcones and other therapies is expected to be an effective way to improve anticancer therapeutic efficacy. However, despite the encouraging results for their response to cancers observed in clinical studies, a full description of toxicity is required for their clinical use as safe drugs for the treatment of cancer. In this review, we will summarize the recent advances of the chalcone family as potential anticancer agents and the mechanisms of action. Besides, future applications and scope of the chalcone family toward the treatment and prevention of cancer are brought out.

To address the clinical need for readily available small diameter vascular grafts, biomimetic tubular scaffolds were developed for rapid in situ blood vessel regeneration. The tubular scaffolds were designed to have an inner layer that is porous, interconnected, and with a nanofibrous architecture, which provided an excellent microenvironment for host cell invasion and proliferation. Through the synthesis of poly(spirolactic-co-lactic acid) (PSLA), a highly functional polymer with a norbornene substituting a methyl group in poly(l-lactic acid) (PLLA), we were able to covalently attach biomolecules onto the polymer backbone via thiol-ene click chemistry to impart desirable functionalities to the tubular scaffolds. Specifically, heparin was conjugated on the scaffolds in order to prevent thrombosis when implanted in situ. By controlling the amount of covalently attached heparin we were able to modulate the physical properties of the tubular scaffold, resulting in tunable wettability and degradation rate while retaining the porous and nanofibrous morphology. The scaffolds were successfully tested as rat abdominal aortic replacements. Patency and viability were confirmed through dynamic ultrasound and histological analysis of the regenerated tissue. The harvested tissue showed excellent vascular cellular infiltration, proliferation, and migration with laminar cellular arrangement. Furthermore, we achieved both complete reendothelialization of the vessel lumen and native-like media extracellular matrix. No signs of aneurysm or hyperplasia were observed after 3 months of vessel replacement. Taken together, we have developed an effective vascular graft able to generate small diameter blood vessels that can function in a rat model.

Soil nitrification, mediated mainly by ammonia oxidizing archaea (AOA) and bacteria (AOB), converts ammonium (NH4 +) to nitrite (NO2 -) and thence nitrate (NO3 -). To better understand ecological differences between AOA and AOB, we investigated the nitrification kinetics of AOA and AOB under eight replicated cropped and unmanaged ecosystems (including two fertilized natural systems) along a long-term management intensity gradient in the upper U.S. Midwest. For five of eight ecosystems, AOB but not AOA exhibited Haldane kinetics (inhibited by high NH4 + additions), especially in perennial and successional systems. In contrast, AOA predominantly exhibited Michaelis-Menten kinetics, suggesting greater resistance to high nitrogen inputs than AOB. These responses suggest the potential for NH4 +-induced niche differentiation between AOA and AOB. Additionally, long-term fertilization significantly enhanced maximum nitrification rates (Vmax ) in the early successional systems for both AOA and AOB, but not in the deciduous forest systems. This was likely due to pH suppression of nitrification in the acidic forest soils, corroborated by a positive correlation of Vmax with soil pH but not with amoA gene abundance. Results also demonstrated that soil nitrification potentials were relatively stable, as there were no seasonal differences. Overall, results suggest that (1) NH4 + inhibition of AOB but not AOA could be another factor contributing to niche differentiation between AOA and AOB in soil, and (2) nitrification by both AOA and AOB can be significantly promoted by long-term nitrogen inputs.

Background Bacterial predation is an important selective force in microbial community structure and dynamics. However, only a limited number of predatory bacteria have been reported, and their predatory strategies and evolutionary adaptations remain elusive. We recently isolated a novel group of bacterial predators, Bradymonabacteria, representative of the novel order Bradymonadales in δ-Proteobacteria. Compared with those of other bacterial predators (e.g., Myxococcales and Bdellovibrionales), the predatory and living strategies of Bradymonadales are still largely unknown. Results Based on individual coculture of Bradymonabacteria with 281 prey bacteria, Bradymonabacteria preyed on diverse bacteria but had a high preference for Bacteroidetes. Genomic analysis of 13 recently sequenced Bradymonabacteria indicated that these bacteria had conspicuous metabolic deficiencies, but they could synthesize many polymers, such as polyphosphate and polyhydroxyalkanoates. Dual transcriptome analysis of cocultures of Bradymonabacteria and prey suggested a potential contact-dependent predation mechanism. Comparative genomic analysis with 24 other bacterial predators indicated that Bradymonabacteria had different predatory and living strategies. Furthermore, we identified Bradymonadales from 1552 publicly available 16S rRNA amplicon sequencing samples, indicating that Bradymonadales was widely distributed and highly abundant in saline environments. Phylogenetic analysis showed that there may be six subgroups in this order; each subgroup occupied a different habitat. Conclusions Bradymonabacteria have unique living strategies that are transitional between the “obligate” and the so-called facultative predators. Thus, we propose a framework to categorize the current bacterial predators into 3 groups: (i) obligate predators (completely prey-dependent), (ii) facultative predators (facultatively prey-dependent), and (iii) opportunistic predators (prey-independent). Our findings provide an ecological and evolutionary framework for Bradymonadales and highlight their potential ecological roles in saline environments.

Autotrophic nitrification is mediated by ammonia oxidizing bacteria (AOB) or ammonia oxidizing archaea (AOA) and nitrite oxidizing bacteria (NOB). Mounting studies have examined the impact of nitrogen (N) fertilization on the dynamic and diversity of AOA and AOB, while we have limited information on the response of the activity, abundance, and diversity of NOB to N fertilization. We investigated the influence of organic and inorganic N fertilizers on soil NOB in silage corn field plots that received contrasting nitrogen (N) treatments: control (no additional N), ammonium sulfate (AS 100 and 200 kg N ha−1), and compost (200 kg N ha−1). Nitrifying community was examined using a universal marker (16S rRNA gene), functional gene markers (AOB amoA and Nitrospira nxrB), and metagenomics. The overall nitrifying community was not altered after the first fertilization but was significantly shifted by 4-year repeated application of ammonium fertilizers. Nitrospira were the dominant NOB (>99.7%) in our agricultural soil. Both community compositions of AOB and Nitrospira were significantly changed by ammonium fertilizers but not by compost after 4 years of repeated applications. All nitrifiers, including comammox, were recovered in soil metagenomes based on a gene-targeted assembly, but their sequence counts were very low. Although N treatment did not affect the abundance of Nitrospira nxrB determined by real-time quantitative PCR, ammonium fertilizers significantly promoted rates of potential nitrite oxidation determined at 0.15 mM nitrite in soil slurries. Understanding the response of both ammonia oxidizers and nitrite oxidizers to N fertilization may initiate or improve strategies for mitigating potential environmental impacts of nitrate production in agricultural ecosystems.

Unclarified molecular mechanism and lack of practical diagnosis biomarkers hinder the effective treatment of non-small-cell lung cancer. Herein, we performed liquid chromatography-mass spectrometry-based nontargeted metabolomics analysis in 131 patients with their lung tissue pairs to study the metabolic characteristics and disordered metabolic pathways in lung tumor. A total of 339 metabolites were identified in metabolic profiling. Also, 241 differential metabolites were found between lung carcinoma tissues (LCTs) and paired distal noncancerous tissues; amino acids, purine metabolites, fatty acids, phospholipids, and most of lysophospholipids significantly increased in LCTs, while 3-phosphoglyceric acid, phosphoenolpyruvate, 6-phosphogluconate, and citrate decreased. Additionally, pathway enrichment analysis revealed that energy, purine, amino acid, lipid, and glutathione metabolism are markedly disturbed in lung cancer (LCa). Using binary logistic regression, we further defined candidate biomarkers for different subtypes of lung tumor. Xanthine and PC 35:2 were selected as combinational biomarkers for distinguishing benign from malignant lung tumors with a 0.886 area under curve (AUC) value, and creatine, myoinositol and LPE 16:0 were defined as combinational biomarkers for discriminating adenocarcinoma from squamous cell lung carcinoma with a 0.934 AUC value. Overall, metabolic characterization and pathway disturbance demonstrated apparent metabolic reprogramming in LCa. The defined candidate metabolite marker panels are useful for subtyping of lung tumors to assist clinical diagnosis.

BackgroundA simulation and model (SM) teaching aid using 3D printing was developed to improve a training course for total hip arthroplasty of adult developmental dysplasia of the hip (adult DDH-THA). We named this new method Surgery Simulation Teaching based on a Real Reconstruction Aid (RRA-SST). A prospective randomized comparison was performed with the traditional surgical live teaching method to evaluate the training effectiveness of RRA-SST for adult DDH-THA.MethodsTwenty-six trainees, who were already practicing but were not experienced, participated in the study. We randomly divided the trainees into two groups: Group A (n = 13) received RRA-SST and group B (n = 13) received traditional surgical live teaching. A surgery simulation test and a questionnaire were used for evaluation. Next, each group received training with the other teaching method, and then the test and questionnaire were used again for evaluation.ResultsAfter the first test, the RRA-SST method was shown to produce better results than the traditional surgical live teaching method. After the second test, the results showed the training effect in both groups reached the same level, which was level as Group A RRA-SST results. Analysis of the questionnaire results showed that the training effect of RRA-SST was higher than that of traditional surgical live teaching, from multiple perspectives.ConclusionsThe use of RRA-SST improved participant performance according to simulation assessment. RRA-SST can be helpful for trainees who are already practicing but not experienced when developing proficiency in adult DDH-THA surgical techniques.

Soil aggregates, with complex spatial and nutritional heterogeneity, are clearly important for regulating microbial community ecology and biogeochemistry in soils. However, how the taxonomic composition and functional attributes of N-cycling-microbes within different soil particle-size fractions under a long-term fertilization treatment remains largely unknown. Here, we examined the composition and metabolic potential for urease activity, nitrification, N2 O production and reduction of the microbial communities attached to different sized soil particles (2000-250, 250-53 and

Autophagy is a mechanism that enables cells to maintain cellular homeostasis by removing damaged materials and mobilizing energy reserves in conditions of starvation. Although nutrient availability strongly impacts the process of autophagy, the specific metabolites that regulate autophagic responses have not yet been determined. Recent results indicate that S‐adenosylmethionine (SAM) represents a critical inhibitor of methionine starvation–induced autophagy. SAM is primarily involved in four key metabolic pathways: transmethylation, transsulphuration, polyamine synthesis and 5′‐deoxyadenosyl 5′‐radical–mediated biochemical transformations. SAM is the sole methyl group donor involved in the methylation of DNA, RNA and histones, modulating the autophagic process by mediating epigenetic effects. Moreover, the metabolites of SAM, such as homocysteine, glutathione, decarboxylated SAM and spermidine, also exert important influences on the regulation of autophagy. From our perspective, nuclear‐cytosolic SAM is a conserved metabolic inhibitor that connects cellular metabolic status and the regulation of autophagy. In the future, SAM might be a new target of autophagy regulators and be widely used in the treatment of various diseases., Working model for SAM‐mediated modulation of autophagy. SAM is an essential metabolite that acts as a high‐energy methyl donor for most methylation modifications of non‐histone, histone, DNA and RNA, which epigenetically affect autophagic flux. Moreover, SAM is the biosynthetic precursor for HCY and cysteine and other sulphur‐containing metabolites such as GSH. All of these roles significantly contribute to the modulation of autophagy. In addition, the SAM metabolite SPD has also been shown to be a physiological inducer of autophagy. Collectively, the metabolites of SAM and the key enzymes in SAM biosynthesis and metabolism influence the core autophagy machinery. S‐adenosylmethionine: SAM, homocysteine: HCY, glutathione: GSH, spermidine: SPD, AMP‐dependent protein kinase: AMPK, mechanistic target of rapamycin: mTOR, migration inhibitory factor: MIF, cystic fibrosis transmembrane conductance regulator: CFTR, mTOR complex 1: mTORC1, protein phosphatase 2A: PP2A, nitrogen permease regulating protein: NPR2P, ten‐eleven translocation methylcytosine dioxygenases: TET, N6‐methyladenosine RNA methylation, m6A RNA methylation

Stroke is a cerebrovascular disease that results in decreased blood flow. Although Panax notoginseng (PN), a Chinese herbal medicine, has been proven to promote stroke recovery, its molecular mechanism remains unclear. In this study, middle cerebral artery occlusion (MCAO) was induced in rats with thrombi generated by thread and subsequently treated with PN. After that, staining with 2,3,5-triphenyltetrazolium chloride was employed to evaluate the infarcted area, and electron microscopy was used to assess ultrastructural changes of the neurovascular unit. RNA-Seq was performed to determine the differential expressed genes (DEGs) which were then verified by qPCR. In total, 817 DEGs were identified to be related to the therapeutic effect of PN on stroke recovery. Further analysis by Gene Oncology analysis and Kyoto Encyclopedia of Genes and Genomes revealed that most of these genes were involved in the biological function of nerves and blood vessels through the regulation of neuroactive live receptor interactions of PI3K-Akt, Rap1, cAMP, and cGMP-PKG signaling, which included in the 18 pathways identified in our research, of which, 9 were reported firstly that related to PN’s neuroprotective effect. This research sheds light on the potential molecular mechanisms underlying the effects of PN on stroke recovery.

Soil extracellular enzymes play a significant role in the N mineralization process. However, few studies have documented the linkage between enzyme activity and the microbial community that performs the function. This study examined the effects of inorganic and organic N fertilization on soil microbial communities and their N mineralization functions over 4 years. Soils were collected from silage corn field plots with four contrasting N treatments: control (no additional N), ammonium sulfate (AS; 100 and 200 kg of N ha−1), and compost (200 kg of N ha−1). Illumina amplicon sequencing was used to comprehensively assess the overall bacterial community (16S rRNA genes), bacterial ureolytic community (ureC), and bacterial chitinolytic community (chiA). Selected genes involved in N mineralization were also examined using quantitative real-time PCR and metagenomics. Enzymes (and marker genes) included protease (npr and sub), chitinase (chiA), urease (ureC), and arginase (rocF). Compost significantly increased diversity of overall bacterial communities even after one application, while ammonium fertilizers had no influence on the overall bacterial communities over four seasons. Bacterial ureolytic and chitinolytic communities were significantly changed by N fertilization. Compost treatment strongly elevated soil enzyme activities after 4 years of repeated application. Functional gene abundances were not significantly affected by N treatments, and they were not correlated with corresponding enzyme activities. N mineralization genes were recovered from soil metagenomes based on a gene-targeted assembly. Understanding how the structure and function of soil microbial communities involved with N mineralization change in response to fertilization practices may indicate suitable agricultural management practices that improve ecosystem services while reducing negative environmental consequences. IMPORTANCE Agricultural N management practices influence the enzymatic activities involved in N mineralization. However, specific enzyme activities do not identify the microbial species directly involved in the measured process, leaving the link between the composition of the microbial community and the production of key enzymes poorly understood. In this study, the application of high-throughput sequencing, real-time PCR, and metagenomics shed light on how the abundance and diversity of microorganisms involved in N mineralization respond to N management. We suggest that N fertilization has significantly changed bacterial ureolytic and chitinolytic communities.

Soil ammonia-oxidizing bacteria and archaea (AOB and AOA) convert ammonium/ammonia to nitrite in the process of nitrification. However, the potentially differential responses of these AO to substrate and temperature and the effects of conventional and organic nitrogen management on these responses remains poorly understood. We determined the response of nitrification to ammonium substrate concentration and temperature using an AOB specific inhibitor to distinguish the contribution of AOB and AOA to nitrification. Soils were sampled from cornfield plots that had been treated for four years with contrasting nitrogen sources: control (no additional N), ammonium sulfate at two rates and compost. Nitrification potential and net rates were stimulated for one month after fertilization with ammonium sulfate compared to relatively lower and stable rates in control and compost treated soils. For soils that had been fertilized with ammonium sulfate, the proportion of nitrification mediated by AOB in slurry assays was over 90% at 1.0 mM but less than 50% at 0.01 mM. Kinetic analysis showed maximum nitrification activity (Vmax) for AOB ranged from 0.32 to 4.8 mmol N kg−1d−1 with a half saturation constant (Km) of 14–160 μM ammonium; parameters were higher for soils from ammonium sulfate treated plots. Vmax and Km for AOA averaged 0.24 mmol N kg−1d−1 and 4.28 μM ammonium with no effect of field treatment. The proportion of nitrification due to AOA was lowest at 5 °C, increased with temperature, and was near to 100% at 50 °C; optimum temperature was 41 °C for AOA versus 31 °C for AOB. Understanding the kinetic and temperature response of microbes responsible for nitrification may allow ecosystem models to include these populations as dynamic components driving nitrogen flux.

Multi-cause-induced interstitial lung disease, particularly pulmonary fibrosis, is a serious clinical concern. Fibroblasts have been suggested to have a major role, with it recently being revealed that some of these fibroblasts are derived from alveolar epithelial cells through epithelial-mesenchymal transition (EMT). Eukaryotic translation initiation factor 3 subunit A (EIF3A) is a protein that in humans is encoded by the EIF3A gene, and has been suggested to play roles in regulating translation of a subset of mRNAs and in regulating cell cycle progression and cell proliferation. In the present study, we chose a well-known TGFβ1-induced EMT model in alveolar epithelial cells to investigate the functional role of EIF3A. TGFβ1-induced EIF3A expression and EMT process in alveolar epithelial cells, after EIF3A knockdown, the EMT process could be partially reversed. Online tools and luciferase assays showed that miR-497 could inhibit EIF3A expression by directly binding to the 3'UTR of EIF3A. Ectopic miR-497 expression partially reversed TGFβ1-induced EMT in alveolar epithelial cells. In addition, miR-497 could suppress TGFβ1-induced pulmonary fibroblast proliferation and EIF3A, Collagen I and α-SMA protein levels. Taken together, EIF3A could promote TGFβ1-induced EMT in alveolar epithelial cells; miR-497 suppressed TGFβ1-induced EMT in alveolar epithelial cells TGFβ1-induced excessive proliferation and ECM in pulmonary fibroblast through inhibiting EIF3A by targeting. MiR-497/EIF3A axis shows the potential to be effective in the treatment of pulmonary fibrosis. J. Cell. Biochem. 118: 3401-3408, 2017. © 2017 Wiley Periodicals, Inc.

Resistant starch (RS) has been reported to reduce body fat in obese mice. However, this effect has not been demonstrated in humans. In this study, we tested the effects of RS in 19 volunteers with normal body weights. A randomized, double-blinded and crossover design clinical trial was conducted. The study subjects were given either 40 g high amylose RS2 or energy-matched control starch with three identical diets per day throughout the study. The effect of RS was evaluated by monitoring body fat, glucose metabolism, gut hormones, gut microbiota, short-chain fatty acids (SCFAs) and metabolites. The visceral and subcutaneous fat areas were significantly reduced following RS intake. Acetate and early-phase insulin, C-peptide and glucagon-like peptide-1 (GLP-1) secretion were increased, and the low-density lipoprotein cholesterol (LDL-C) and blood urea nitrogen (BUN) levels were decreased after the RS intervention. Based on 16S rRNA sequencing, certain gut microbes were significantly decreased after RS supplementation, whereas the genus Ruminococcaceae_UCG-005 showed an increase in abundance. Other potential signatures of the RS intervention included Akkermansia, Ruminococcus_2, Victivallis, and Comamonas. Moreover, the baseline abundance of the genera Streptococcus, Ruminococcus_torques_group, Eubacterium_hallii_group, and Eubacterium_eligens_group was significantly associated with the hormonal and metabolic effects of RS. These observations suggest that a daily intake of 40 g of RS is effective in modulating body fat, SCFAs, early-phase insulin and GLP-1 secretion and the gut microbiota in normal-weight subjects.

Agriculture is responsible for over half of the input of reactive nitrogen (N) to terrestrial systems; however improving N availability remains the primary management technique to increase crop yields in most regions. In the majority of agricultural soils, ammonium is rapidly converted to nitrate by nitrification, which increases the mobility of N through the soil matrix, strongly influencing N retention in the system. Decreasing nitrification through management is desirable to decrease N losses and increase N fertilizer use efficiency. We review the controlling factors on the rate and extent of nitrification in agricultural soils from temperate regions including substrate supply, environmental conditions, abundance and diversity of nitrifiers and plant and microbial interactions with nitrifiers. Approaches to the management of nitrification include those that control ammonium substrate availability and those that inhibit nitrifiers directly. Strategies for controlling ammonium substrate availability include timing of fertilization to coincide with rapid plant update, formulation of fertilizers for slow release or with inhibitors, keeping plant growing continuously to assimilate N, and increasing microbial N assimilation (immobilization). Another effective strategy is to inhibit nitrifiers directly with either synthetic or biological nitrification inhibitors. Commercial nitrification inhibitors are effective but their use is complicated by a changing climate and by organic management requirements. The interactions of the nitrifying organisms with plants or microbes producing biological nitrification inhibitors is a promising approach but just beginning to be critically examined. Climate smart agriculture will need to carefully consider optimized seasonal timing for these strategies to remain effective management tools.

Background: Streptococcus agalactiae is a serious zoonotic pathogen that causes disease in humans and other animals worldwide. Objectives: Due to the increasing prevalence of S. agalactiae, as well as the transmission risk of S. agalactiae from animals to human, it was important to identify the serotype diversity and molecular typing population structure of S. agalactiae isolated from human, bovine, rabbit, and fish. Methods: Capsular polysaccharide serotypes (CPS), multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE) technologies were used to compare the genetic diversity of 56 S. agalactiae isolates from human, rabbit, bovine, and fish sources in China. Results: We found that two serotypes (Ia, III) existed, with serotype Ia being the most common (85.7%). The 56 isolates were assigned to nine sequence types (STs) and seven clonal complexes (CCs) using MLST. Themost common ST was ST891 (35.7%). The ST19 and ST103 were found in two different isolates, while the remaining STs were found in one isolate. A total of 18 PFGE clusters were identified, however, only cluster P was found in both human and bovine isolates. Conclusions: Our findings suggest that serotypes, STs and PFGE, had no obvious correlation with particular host species. However, the similarity of genotypes of S. agalactiae isolated from different host species, speculating cross-infection possibility between them at genetic level.

Hemangioma (HA) can be exposed to bisphenol A (BPA) through direct skin absorption. Although numerous studies indicated that BPA can trigger the progression of cancers, there is no study concerning the effects of BPA on development of HA. Our present study revealed that nanomolar BPA can significantly increase the in vitro migration and invasion of HA cells via induction of epithelial-mesenchymal transition (EMT), which was evidenced by the upregulation of vimentin and downregulation of E-cadherin. The BPA treatment also significantly increased the expression and nuclear localization of Snail and the key transcription factor of EMT, while it had no effect on the expression of other transcription factors such as Slug, Twist, or ZEB1. Silencing of Snail by small interfering RNAs attenuated BPA-induced downregulation of cadherin and upregulation of vimentin, suggesting that Snail is essential for BPA-induced EMT. Both estrogen receptor α (ERα) and G protein-coupled estrogen receptor (GPER) were expressed in HA cells; furthermore, BPA treatment can increase the expression of both ERα and GPER. However, only the inhibitor of ERα (ICI 182, 780), and not GPER (G15), can abolish BPA-induced upregulation of Snail. It suggested that ERα is involved in BPA-induced EMT of HA cells. Collectively, our data suggested that BPA can trigger the EMT of HA cells via ERα/Snail signals. It indicated that more attention should be paid to the skin exposure to BPA for HA patients.

In the majority of agricultural soils, ammonium (NH4+) is rapidly converted to nitrate (NO3−) in the biological ammonia and nitrite oxidation processes known as nitrification. The often rate-limiting step of ammonia oxidation to nitrite is mediated by ammonia oxidizing bacteria (AOB) and ammonia oxidizing archaea (AOA). The response of AOA and AOB communities to organic and conventional nitrogen (N) fertilizers, and their relative contributions to the nitrification process were examined for an agricultural silage corn system using a randomized block design with 4 N treatments: control (no additional N), ammonium sulfate (AS) fertilizer at 100 and 200 kg N ha−1, and steer-waste compost (200 kg total N ha−1) over four seasons. DNA was extracted from the soil, and real-time PCR and 454-pyrosequencing were used to evaluate the quantity and diversity of the amoA gene which encodes subunit A of ammonia monooxygenase. Soil pH, nitrate pools, and nitrification potentials were influenced by ammonium and organic fertilizers after the first fertilization, while changes in AOB abundance and community structure were not apparent until after the second fertilization or later. The abundance of AOA was always greater than AOB but was unaffected by N treatments. In contrast, AOB abundance and community structure were changed significantly by ammonium fertilizers. Specific inhibitors of nitrification were used to evaluate the relative contribution of AOA and AOB to nitrification. We found that AOB dominantly contributed to potential nitrification activity determined at 1 mM ammonium in soil slurries and nitrification potential activity was higher in soils treated with ammonium fertilizers relative to control soils. However, AOA dominated gross nitrification activity in moist soils. Our result suggests that AOB activity and community are more responsive to ammonium fertilizers than AOA, but that in situ nitrification rate is controlled by ammonium availability in this agricultural soil. Understanding this response of AOA and AOB to N fertilizers may contribute to improving strategies for the management of nitrate production in agricultural soils.

As the most common form of aortic aneurysm, abdominal aortic aneurysm (AAA) is associated with the proliferation and apoptosis of vascular smooth muscle cells (VSMCs). Our present study found that during H2O2 or NaAsO2 induced injury of VSMC, the expression of miR-155-5p significantly increased. While silencing of miR-155-5p can attenuate H2O2 or NaAsO2 suppressed viability and induced apoptosis of VSMCs. In silico analysis and western blot analysis suggested that miR-155-5p can suppress the expression of FOS and ZIC3 in VSMCs by targeting their 3'UTR. Over expression of FOS or ZIC3 can abolish H2O2 treatment and miR-155-5p induced suppression of VSMC viability. The inhibitor of NF-κB (p65), while not STAT3, can abolish H2O2 induced expression of miR-155-5p and cell apoptosis. In addition, H2O2 treatment can increase the phosphorylation and nuclear translocation of p65 in VSMCs. The expression of miR-155-5p in cells isolated from participants diagnosed with AAA were significantly greater than that in the normal group. Further, miR-155-5p was negative correlated with the expression of FOS and ZIC3 in cells from AAA patients. Collectively, miR-155-5p can regulate the viability and apoptosis of VSMCs to trigger the progression of AAA. It might be an effective therapeutic target for the treatment of AAA in clinical practice.

Periodical changes of steroid hormones have a great impact on the homeostasis of the female. However, there are few studies concerning the metabolome changes during the cycle. To study the periodic metabolic changes, a female cohort was enrolled with time-series serum samples collected during a menstrual cycle. To meet the requirement of the large-scale sample analysis, a high throughput metabolomics method was established by using an efficient sample preparation on a 96 well filter plate and a rapid LC condition in 12 min, which reduces about 70% of the samples preprocessing time and 60% analysis time. Evaluation of metabolite coverage and separation performances reflected that the method was robust for the large-scale metabolomics study. Using this method, we found that 12.6% of total detected ions including lipids, amino acids, citric acid, and so on were significantly changed during a menstrual cycle. Some metabolites were found periodically changed, which is similar to hormones (estrone and progesterone) during the cycle. These results show the novel high throughput method can be applied in large-scale metabolomics studies.

The present study aimed to investigate the effect of picfeltarraenin IA (IA) on respiratory inflammation by analyzing its effect on interleukin (IL)-8 and prostaglandin E2 (PGE2) production. The expression of cyclooxygenase 2 (COX2) in human pulmonary adenocarcinoma epithelial A549 cells in culture was also examined. Human pulmonary epithelial A549 cells and the human monocytic leukemia THP-1 cell line were used in the current study. Cell viability was measured using a methylthiazol tetrazolium assay. The production of IL-8 and PGE2 was investigated using an enzyme-linked immunosorbent assay. The expression of COX2 and nuclear factor-κB (NF-κB)-p65 was examined using western blot analysis. Treatment with lipopolysaccharide (LPS; 10 µg/ml) resulted in the increased production of IL-8 and PGE2, and the increased expression of COX2 in the A549 cells. Furthermore, IA (0.1-10 µmol/l) significantly inhibited PGE2 production and COX2 expression in cells with LPS-induced IL-8, in a concentration-dependent manner. The results suggested that IA downregulates LPS-induced COX2 expression, and inhibits IL-8 and PGE2 production in pulmonary epithelial cells. Additionally, IA was observed to suppress the expression of COX2 in THP-1 cells, and also to regulate the expression of COX2 via the NF-κB pathway in the A549 cells, but not in the THP-1 cells. These results indicate that IA regulates LPS-induced cytokine release in A549 cells via the NF-κB pathway.