Insoluble-Phytate Improves Plant Growth and Arsenic Accumulation in As-Hyperaccumulator Pteris vittata: Phytase Activity, Nutrient Uptake, and As-Metabolism.

Phytate, the principal P storage in plant seeds, is also an important organic P in soils, but it is unavailable for plant uptake. However, the As-hyperaccumulator Pteris vittata can effectively utilize soluble Na-phytate, while its ability to utilize insoluble Ca/Fe-phytate is unclear. Here, we investigated phytate uptake and the underlying mechanisms based on the phytase activity, nutrient uptake, and expression of genes involved in As metabolisms. P. vittata plants were cultivated hydroponically in 0.2-strength Hoagland nutrient solution containing 50 µM As and 0.2 mM Na/Ca/Fe-phytate, with 0.2 mM soluble-P as the control. As the sole P source, all three phytates supported P. vittata growth, with its biomass being 3.2-4.1 g plant-1 and Ca/Fe-phytate being 19-29% more effective than Na-phytate. Phytate supplied soluble P to P. vittata probably via phytase hydrolysis, which was supported by 0.4-0.7 nmol P min-1 g-1 root fresh weight day-1 phytase activity in its root exudates, with 29-545 µM phytate-P being released into the growth media. Besides, compared to Na-phytate, Ca/Fe-phytate enhanced the As contents by 102-140% to 657-781 mg kg-1 in P. vittata roots and by 43-86% to 1109-1447 mg kg-1 in the fronds, which was accompanied by 21-108% increase in Ca and Fe uptake. The increased plant As is probably attributed to 1.3-2.6 fold upregulation of P transporters PvPht1;3/4 for root As uptake, and 1.8-4.3 fold upregulation of arsenite antiporters PvACR3/3;1/3;3 for As translocation to and As sequestration into the fronds. This is the first report to show that, besides soluble Na-phytate, P. vittata can also effectively utilize insoluble Ca/Fe-phytate as the sole P source, which sheds light onto improving its application in phytoremediation of As-contaminated sites.

Selenium Increased Arsenic Accumulation by Upregulating the Expression of Genes Responsible for Arsenic Reduction, Translocation, and Sequestration in Arsenic Hyperaccumulator Pteris vittata.

Selenate enhances arsenic (As) accumulation in As-hyperaccumulator Pteris vittata, but the associated molecular mechanisms are unclear. Here, we investigated the mechanisms of selenate-induced arsenic accumulation by exposing P. vittata to 50 µM arsenate (AsV50) and 1.25 (Se1.25) or 5 µM (Se5) selenate in hydroponics. After 2 weeks, plant biomass, plant As and Se contents, As speciation in plant and growth media, and important genes related to As detoxification in P. vittata were determined. These genes included P transporters PvPht1;3 and PvPht1;4 (AsV uptake), arsenate reductases PvHAC1 and PvHAC2 (AsV reduction), and arsenite (AsIII) antiporters PvACR3 and PvACR3;2 (AsIII translocation) in the roots, and AsIII antiporters PvACR3;1 and PvACR3;3 (AsIII sequestration) in the fronds. The results show that Se1.25 was more effective than Se5 in increasing As accumulation in both P. vittata roots and fronds, which increased by 27 and 153% to 353 and 506 mg kg-1. The As speciation analyses show that selenate increased the AsIII levels in P. vittata, with 124-282% more AsIII being translocated into the fronds. The qPCR analyses indicate that Se1.25 upregulated the gene expression of PvHAC1 by 1.2-fold, and PvACR3 and PvACR3;2 by 1.0- to 2.5-fold in the roots, and PvACR3;1 and PvACR3;3 by 0.6- to 1.1-fold in the fronds under AsV50 treatment. Though arsenate enhanced gene expression of P transporters PvPht1;3 and PvPht1;4, selenate had little effect. Our results indicate that selenate effectively increased As accumulation in P. vittata, mostly by increasing reduction of AsV to AsIII in the roots, AsIII translocation from the roots to fronds, and AsIII sequestration into the vacuoles in the fronds. The results suggest that selenate may be used to enhance phytoremediation of As-contaminated soils using P. vittata.

Impact of a Telephone Intervention on Bowel Preparation Quality for Colonoscopy in the Elderly.

Bowel preparation is the basis of colonoscopy, and adequate bowel preparation is essential to the success of colonoscopy. Studies have been reported that telephone intervention can improve the quality of bowel preparation, while it remains unclear regarding effectiveness with the elderly. The purpose of this study was to evaluate the effect of telephone intervention on the quality of bowel preparation for colonoscopy in elderly outpatients. In total, 162 outpatients older than 65 years were enrolled and randomly divided into a control group and a study group. Patients in the study group were re-educated through telephone by a specific nurse 2 days before colonoscopy, whereas participants in the control group received education only on the day of appointment. The Ottawa score was used to evaluate the quality of bowel preparation between the two groups. In this study, no significant differences were observed in age, gender, body mass index, educational level, smoking and/or alcohol drinking, waiting time to colonoscopy, reasons for colonoscopy, and colonoscopic findings between the control group and the study group. Participants in the study group had higher adequate bowel preparation and compliance than the control group (83.1% vs. 59.5%, p = .03; 96.4% vs. 74.7%, p < .001). Univariate analysis showed that only noncompliance with start time was significantly associated with satisfactory bowel preparation in elderly patients. In conclusion, telephone intervention 2 days before colonoscopy can improve the quality of bowel preparation in the elderly.

[Mechanism of paeonol combined with paeoniflorin against myocardial ischemia injury:based on proteomics].

The study aims to investigate the effect of the compatibility of paeonol and paeoniflorin(hereinafter referred to as the compatibility) on the expression of myocardial proteins in rats with myocardial ischemia injury and explore the underlying mechanism of the compatibility against myocardial ischemia injury. First, the acute myocardial infarction rat model was established by ligation of the anterior descending branch of the left coronary artery. The model rats were given(ig) paeonol and paeoniflorin. Then protein samples were collected from rat cardiac tissue and quantified by tandem mass tags(TMT) to explore the differential proteins after drug intervention. The experimental results showed that differential proteins mainly involved phagocytosis engulfment, extracellular space, and antigen binding, as well as Kyoto encyclopedia of genes and genomes(KEGG) pathways of complement and coagulation cascades, syste-mic lupus erythematosus, and ribosome. In this study, the target proteins and related signaling pathways identified by differential proteomics may be the biological basis of the compatibility against myocardial ischemia injury in rats.

Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Geniposide protects against ox-LDL-induced foam cell formation through inhibition of MAPKs and NF-kB signaling pathways.

Atherosclerosis (AS) is characterized by the significant accumulation of low-density lipoprotein (LDL)-cholesterol in macrophages that reside in the vessel wall and the resultant inflammatory response. Therefore, inhibition of LDL-induced inflammation is a promising interference for AS. Many traditional Chinese medicine prescriptions have been developed for AS treatment. Geniposide (GEN) is an iridoid glycoside mainly found in Gardenia jasminoides fruit. Although GEN has previously been shown to possess anti-atherosclerotic activities, its effects on the formation of macrophage-derived foam cells remain poorly characterized. In our current study, we demonstrated that GEN could significantly inhibit oxidized light-density lipoprotein (ox-LDL) induced macrophage foam cell formation and the expression of pro-inflammatory cytokines in a dose-dependent manner. In addition, treatment of GEN in bone-marrow derived macrophages repressed iNOS expression and NO expression. GEN could also alleviate ox-LDL-dependent up-regulation of CD36 expression by blocking the phosphorylation of p38 MAPK, ERK, JNK and NF-kB p65. The results of our current study demonstrate that GEN exhibits significant therapeutic effects against ox-LDA-induced foam cell formation and inflammation. Therefore, GEN is promising agent for treating AS.

microRNA-219-5p inhibits epithelial-mesenchymal transition and metastasis of colorectal cancer by targeting lymphoid enhancer-binding factor 1.

Aberrant expression of microRNAs (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. microRNA-219-5p (miR-219-5p) has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR-219-5p and colorectal cancer (CRC) metastasis remains unclear. In the present study, miR-219-5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer-binding factor 1 (LEF1) as a direct target of miR-219-5p. Overexpression of miR-219-5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial-mesenchymal transition (EMT). Furthermore, silencing LEF1 phenocopied this metastasis-suppressive function. The recovery experiment showed that re-expression of LEF1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR-219-5p. Additionally, we demonstrated that miR-219-5p exerted this tumor-suppressive function by blocking activation of the AKT and ERK pathways. Finally, a nude mice experiment showed that miR-219-5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR-219-5p inhibits metastasis and EMT of CRC by targeting LEF1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis.

Low expression of long non-coding RNA GAS5 is associated with poor prognosis of patients with thyroid cancer.

The study aims to investigate the role of long non-coding RNA (lncRNA) GAS5 in the diagnosis and prognosis of patients suffering from thyroid cancer (TC). A total of 212 patients with TC and 61 patients with benign thyroid tumor were enrolled in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the lncRNA GAS5 expression in TC and benign tumor tissues. All TC patients were categorized into high-risk and low-risk groups according to the MACIS, AGES and AMES prognostic scoring system. A 5-year follow-up was conducted in order to determine the disease free survival (DFS) rates and overall survival (OS) rates. The associations between lncRNA GAS5 expression and prognosis of TC patients were analyzed by The Kaplan-Meier survival curves and the Cox regression models. There was a decrease in the lncRNA GAS5 expression in TC tissues in comparison to benign tumor tissues. Expression of lncRNA GAS5 showed significant association with tumor node metastasis (TNM) staging, lymph node metastasis and the multiple cancer foci of TC. AMES high-risk patients showed a decreased expression of lncRNA GAS5 expression than the AMES low-risk patients. The AGES and MACIS high-risk patients showed lower lncRNA GAS5 expression than low-risk patients. The survival rate of TC patients with high lncRNA GAS5 expression was higher than that of TC patients with low lncRNA GAS5 expression during the DFS and OS periods. Cox regression analysis indicated that lncRNA GAS5 expression, TNM staging, lymph node metastasis and multiple cancer foci were independent risk factors for poor prognosis in TC patients. LncRNA GAS5 may be closely related to the diagnosis and prognosis of TC.

Design, synthesis and anticancer activity of novel hybrid compounds between benzofuran and N-aryl piperazine.

A series of novel hybrid compounds between benzofuran and N-aryl piperazine have been designed and prepared. These derivatives were evaluated for their in vitro anti-tumor activity against a panel of human tumor cell lines by MTT assay. The results demonstrated that amide derivatives were more bioactive than sulfonamide compounds in general, and that chloro or trifluoromethyl substituent was vital for modulating cytotoxic activity. In particular, compound 13 was found to be the most potent compound against 4 strains human tumor cell lines, and exhibited cytotoxic activity selectively against Hela (0.03µM).

Case-fatality ratio and effectiveness of ribavirin therapy among hospitalized patients in china who had severe fever with thrombocytopenia syndrome.

BACKGROUND: The wide distribution and high case-fatality ratio of severe fever with thrombocytopenia syndrome (SFTS) have made it a significant public health problem. This study was designed to identify the predictors of fatal outcomes and to evaluate the effectiveness of antiviral therapy in treating SFTS virus (SFTSV)-infected patients. METHODS: A cross-sectional study was performed in a general hospital located in Xinyang city, whereas the largest number of patients with SFTS in China were treated during 2011-2012. The primary outcome for the treatment effect analysis was death. Other outcomes included sequential platelet levels and viral loads observed throughout the hospitalization and the interval between the initiation of ribavirin therapy and the return of the platelet count to a normal level. RESULTS: A total of 311 SFTSV-infected patients were included in the study. The most frequent clinical presentations were fever, weakness, myalgia, and gastrointestinal symptoms. Each patient had thrombocytopenia, leukopenia, or both. The case-fatality ratio (CFR) was 17.4% (95% confidence interval [CI], 13.1%-21.6%). Older age (odds ratio [OR], 1.061; 95% CI, 1.023-1.099; P = .001), decreased level of consciousness (OR, 5.397; 95% CI, 2.660-10.948; P < .001), and elevated levels of lactate dehydrogenase (>1200 U/L; OR, 2.620; 95% CI, 1.073-6.399; P = .035) and creatine kinase (>800 U/L; OR, 2.328; 95% CI, 1.129-4.800; P = .022) were significantly associated with fatal outcome. The CFRs were similar between patients who received ribavirin and those who did not. Ribavirin treatment showed no significant effect on either platelet counts or viral loads during hospitalization of patients with fatal or nonfatal cases. CONCLUSIONS: These findings can improve knowledge about the characteristics of patients with fatal outcomes and the use of antiviral drug for SFTS.

Overexpression of miR-125b, a novel regulator of innate immunity, in eosinophilic chronic rhinosinusitis with nasal polyps.

RATIONALE: Eosinophilic chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) represents a hard-to-treat subtype of CRS. OBJECTIVES: To determine the pattern of expression and biologic role of microRNAs (miRNAs) in CRS, particularly in eosinophilic CRSwNP. METHODS: Global miRNA expression in sinonasal mucosa from controls, CRS without nasal polyps (CRSsNP), and patients with eosinophilic CRSwNP was compared using miRNA microarrays. MiR-125b expression was detected by means of quantitative reverse-transcriptase polymerase chain reaction. The cellular localization of miR-125b was determined by in situ hybridization. MiR-125b functional assays were performed on airway epithelial cells and mice. MiR-125b expression regulation was studied by tissue and cell culture. MEASUREMENTS AND MAIN RESULTS: CRSsNP and eosinophilic CRSwNP exhibited distinct miRNA expression profiles. MiR-125b was specifically up-regulated in eosinophilic CRSwNP. MiR-125b was mainly expressed by sinonasal and bronchial epithelial cells. EIF4E-binding protein 1 (4E-BP1) was identified as a direct target of miR-125b. MiR-125b mimic or inhibitor enhanced or decreased IFN-α/ß production elicited by dsRNA in vitro or in vivo, respectively. 4E-BP1 expression was decreased, whereas IFN regulatory factor-7 and IFN-ß expression was increased, in eosinophilic CRSwNP. IFN-ß mRNA levels positively correlated with IL-5 mRNA levels and eosinophil infiltration in sinonasal mucosa. IFN-ß stimulated B cell-activating factor of the tumor necrosis factor family production in airway epithelial cells. miR-125b could be induced by lipopolysaccharide, dsRNA, and IL-10. CONCLUSIONS: The up-regulated expression of miR-125b may enhance type I IFN expression through suppressing 4E-BP1 protein expression in airway epithelial cells, which potentially contributes to mucosal eosinophilia in eosinophilic CRSwNP.

Arsenic induced plant growth by increasing its nutrient uptake in As-hyperaccumulator Pteris vittata: Comparison of arsenate and arsenite.

Arsenic-hyperaccumulator Pteris vittata is efficient in taking up arsenate (AsV) and arsenite (AsIII), however, their impacts on P. vittata growth and nutrient uptake remain unclear. The uptake of AsV and AsIII, their influences on nutrient uptake and plant biomass, and As speciation were investigated in P. vittata after exposing to 5 or 50 µM AsV or AsIII for 12 d under hydroponics. The results show that AsV uptake in P. vittata was 1.2 times more efficient than AsIII, corresponding to 1.7-2.1 fold greater biomass than the control at 50 µM As. While AsV was dominant in the roots at ∼60%, AsIII was more dominant in the fronds at ∼70% in all treatments. Macronutrients P, K, Ca, and S were increased by 118-185% at 50 µM As, with greater uptake of micronutrients Fe, Mn, Cu, and Zn at 5 µM As. Further, positive correlations between P. vittata biomass and its As contents (r = 0.97), and P. vittata biomass and its S, Mg, P, or Ca contents (r = 0.70-0.98) were observed. Our results suggest that its increased nutrient uptake probably enhanced P. vittata growth under As exposure.

Tetraspanin CD63 reduces the progression and metastasis of head and neck squamous cell carcinoma via KRT1-mediated cell cycle arrest.

Despite the fact that metastasis is the leading cause of death in patients with head and neck squamous cell carcinoma, fundamental questions about the mechanisms that enable or inhibit metastasis remain unanswered. Tetraspanin CD63 has been linked to tumor progression and metastasis. However, few studies have examined the role of CD63 in HNSCC. In this study, we discovered that CD63 levels were abnormally altered in HNSCC tissue compared to adjacent tissue (n = 69 pairs), and that this was linked to prognosis. Through functional in vitro and in vivo experiments, the roles of CD63 in HNSCC were confirmed. Overexpression of CD63 inhibited the progression and metastasis of HNSCC cells. Using mass spectrometry and co-immunoprecipitation assays, we discovered that KRT1 could be a direct interacting partner of CD63. Furthermore, both CD63 and KRT1 expression was significantly decreased in metastatic tissue compared with primary tumor tissue (n = 13 pairs), suggesting that CD63 and KRT1 play a role in reducing the metastasis of HNSCC. In summary, we reveal a previously unrecognized role of CD63 in regulating KRT1-mediated cell cycle arrest in HNSCC cells, and our findings contribute to defining an important mechanism of HNSCC progression and metastasis.

Flavonoids from Scutellaria amoena C. H. Wright alleviate mitochondrial dysfunction and regulate oxidative stress via Keap1/Nrf2/HO-1 axis in rats with high-fat diet-induced nonalcoholic steatohepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is among the most common liver diseases in the world. Flavonoids from Scutellaria amoena (SAF) are used in the treatment of hepatopathy in China. However, the effect and mechanism against NASH remain unclear. We investigated the alleviating effect of SAF on NASH via regulating mitochondrial dysfunction and oxidative stress. METHODS: The effects of SAF on NASH were evaluated using in vitro and in vivo methods. L02 cells were induced by fat emulsion to establish an adipocytes model, followed by treatment with SAF for 24 h. NASH rat models were established by the administration of a high-fat diet for 12 weeks and were administered SAF for six weeks. Changes in body weight, organ indexes, lipid levels, inflammatory cytokines, mitochondrial indicators, and fatty acid metabolism were investigated. RESULTS: SAF significantly improved body weight, organ indexes, lipid levels, liver injury, and inflammatory infiltration in NASH rats. SAF notably regulated interleukin-6, tumor necrotic factor-alpha, superoxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA), kelch-like ECH-associated protein 1 (Keap1), nuclear factor-erythroid factor 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). Additionally, SAF improved mitochondrial dysfunction, increased the levels of GSH, SOD, ATP synthase, complex I and II, and decreased the level of MDA in liver mitochondria. SAF regulated the expression of ß-oxidation genes, including peroxisome proliferator-activated receptor -gamma coactivator-1alpha (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) A, CPT1B, medium-chain acyl-CoA dehydrogenase, long-chain acyl-CoA dehydrogenase, very long-chain acyl-CoA dehydrogenase, and PPARα. CONCLUSION: SAF can alleviate NASH by regulating mitochondrial function and oxidative stress via the Keap1/Nrf2/HO-1 axis.

Copper enhanced arsenic-accumulation in As-hyperaccumulator Pteris vittata by upregulating its gene expression for As uptake, translocation, and sequestration.

In contaminated soils, arsenic (As) often co-exists with copper (Cu). However, its effects on As accumulation and the related mechanisms in As-hyperaccumulator Pteris vittata remain unclear. In this study, P. vittata plants were exposed to 50 µM As and/or 50 µM Cu under hydroponics to investigate the effects of Cu on plant growth and As accumulation, as well as gene expression related to arsenic uptake (P transporters), reduction (arsenate reductases), and translocation and sequestration (arsenite antiporters). After 14 d of growth and compared to the As treatment, the As concentration in P. vittata fronds increased by 1.4-times from 793 to 1131 mg·kg-1 and its biomass increased by 1.2-fold from 18.0 to 21.1 g·plant-1 in the As+Cu treatment. Copper-enhanced As accumulation was probably due to upregulated gene expressions related to As-metabolisms including As uptake (1.9-fold in P transporter PvPht1;3), translocation (2.1-2.4 fold in arsenite antiporters PvACR3/3;2) and sequestration (1.5-2.0 fold in arsenite antiporters PvACR3;1/3;3). Our results suggest that moderate amount of Cu can help to increase the As accumulation efficiency in P. vittata, which has implication in its application in phytoremedation in As and Cu co-contaminated soils.

Effects of Tylophora yunnanensis Schltr on regulating the gut microbiota and its metabolites in non-alcoholic steatohepatitis rats by inhibiting the activation of NOD-like receptor protein 3.

ETHNOPHARMACOLOGICAL RELEVANCE: Tylophora yunnanensis Schltr (TYS) is widely distributed in Yunnan, Guizhou, and other places in China. It is commonly used by folks to treat hepatitis and other liver-related diseases; however, its mechanism of action is still unclear. AIM OF THE STUDY: This study aimed to determine the effects of TYS on regulating gut microbiota and its metabolites in non-alcoholic steatohepatitis (NASH) rats by inhibiting the activation of NOD-like receptor protein3 (NLRP3). MATERIAL AND METHODS: An HFD-induced rat model was established to investigate if the intragastric administration of TYS could mediate gut microbiota and their metabolites to ultimately improve the symptoms of NASH. The improving effects of TYS on NASH rats were assessed by measuring their body weight, lipid levels, histopathology, and inflammatory factor levels in the rat models. The regulatory effects of TYS on NLRP3 in the NASH rats were analyzed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), which determined the levels of NLRP3-related factors. The changes in the composition of the gut microbiota of NASH rats were analyzed using 16S rRNA gene sequencing technology. Meanwhile, the Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for the non-targeted analysis of metabolites in the cecum contents. RESULTS: The results showed that TYS could improve NASH by decreasing the body weight and levels of lipid, AST, ALT, LPS, FFA, VLDL, IL-1ß, IL-6, TNF-α, TGF-ß, NLRP3, ASC, and Caspase-1 in the NASH rats. The analysis of gut microbiota showed that TYS could improve the diversity and abundance of gut microbiota and alter their composition by decreasing the Firmicutes/Bacteroidetes (F/B) ratio and relative abundances of Lachnospiraceae, Christensenellaceae, Blautia, etc. while increasing those of Muribaculaceae, Rumiaococcus, Ruminococcaceae, etc. The analysis of metabolites in the cecum contents suggested that the arachidonic acid metabolism, bile secretion, serotonergic synapse, Fc epsilon RI signaling pathway, etc. were regulated by TYS. The metabolites enriched in these pathways mainly included chenodeoxycholic acid, prostaglandin D2, TXB2, 9-OxoODE, and 13(S)-HOTrE. CONCLUSIONS: These findings suggested that TYS could alleviate the NASH symptoms by decreasing the body weight, regulating the lipid levels, reducing the inflammatory response, and inhibiting the expression levels of NLRP3, ASC, and Caspase-1 in the NASH rats. The changes in the composition of gut microbiota and their metabolic disorder were closely related to the activation of NLRP3. TYS could significantly inhibit the activation of NLRP3 and regulate the composition of gut microbiota and the disorder of metabolites during NASH modeling.

Improved mammalian family phylogeny using gap-rare multiple sequence alignment: A timetree of extant placentals and marsupials.

The timing of mammalian diversification in relation to the Cretaceous-Paleogene (KPg) mass extinction continues to be a subject of substantial debate. Previous studies have either focused on limited taxonomic samples with available whole-genome data or relied on short sequence alignments coupled with extensive species samples. In the present study, we improved an existing dataset from the landmark study of Meredith et al. (2011) by filling in missing fragments and further generated another dataset containing 120 taxa and 98 exonic markers. Using these two datasets, we then constructed phylogenies for extant mammalian families, providing improved resolution of many conflicting relationships. Moreover, the timetrees generated, which were calibrated using appropriate molecular clock models and multiple fossil records, indicated that the interordinal diversification of placental mammals initiated before the Late Cretaceous period. Additionally, intraordinal diversification of both extant placental and marsupial lineages accelerated after the KPg boundary, supporting the hypothesis that the availability of numerous vacant ecological niches subsequent to the mass extinction event facilitated rapid diversification. Thus, our results support a scenario of placental radiation characterized by both basal cladogenesis and active interordinal divergences spanning from the Late Cretaceous into the Paleogene.

[Analysis of a 452C/T single nucleotide polymorphism in γ-glutamyl hydrolase gene in children with acute leukemia].

OBJECTIVE: To investigate the distribution of γ-glutamyl hydrolase gene (GGH) 452C/T genotype and allele frequency in children with acute leukemia (AL) and healthy children. METHODS: Bone marrow samples from 92 children with AL and peripheral blood samples from 124 healthy children were obtained to prepare complementary DNAs (cDNAs). The cDNAs were analyzed for a GGH 452C/T polymorphism by reverse transcriptase-polymerase chain reaction-denaturing gradient gel electrophoresis (RT-PCR-DGGE) and direct sequencing. RESULTS: The frequencies of the AL patients with TT, CT and CC genotypes were 2.2%, 13.0% and 84.8%, and the frequencies of the control children were 1.6%, 16.9% and 81.5%, respectively. There was no significant difference in GGH genotype or T allele frequency between the two groups (P> 0.05). However, the T allele frequency in Han Chinese children was significantly different from those reported in Japanese, Mexican and African-American populations. CONCLUSION: The frequency of 452C/T polymorphism of GGH gene in Han Chinese children has been determined. The results suggested that an ethnic difference may exist.

[Solid variant of mammary adenoid cystic carcinoma with basaloid features: a clinicopathologic and immunohistochemical study].

OBJECTIVE: To investigate the clinicopathologic and immunohistochemical features as well as the differential diagnoses of the solid variant of mammary adenoid cystic carcinoma with basaloid features. METHODS: Clinical and pathological data were collected in four cases of the solid variant of mammary adenoid cystic carcinoma with basaloid features, and microscopic pathological examination and immunohistochemistry EnVision method were performed. The relevant literature was also reviewed. RESULTS: The four patients were female, with age ranged from 46 - 65 years old (average 56 years) and the maximum tumor diameter ranged from 1.5 to 2.5 cm. Microscopically, the tumors exhibited a predominantly solid architecture with a myxoid or hyalinized stroma. The tumor cells showed moderate to marked nuclear atypia, and a basaloid appearance with scanty cytoplasm and inconspicuous nucleoli, and ≥ 5 mitotic figures per 10 high power fields. Glandular space embedded within tumor islands could be noticed. These spaces were genuine glandular structures and the cells lining these true glandular lumens had more abundant and eosinophilic cytoplasm. Pseudoglandular spaces of cribriform pattern or variable shape were also occasionally seen, and these cysts contained homogenous eosinophilic material. Focal necrosis was found. All cases were negative for ER, PR and HER2. Immunohistochemical staining for CK5/6, CK7 and CK14 was positive in the genuine glandular structures. All cases were positive for CD10, but also positive with varying intensity from weak to strong for vimentin and CD117. Staining for Ki-67 in three patients showed 10% - 50% positive. CONCLUSIONS: The solid variant of mammary adenoid cystic carcinoma with basaloid features is a histologically distinctive and also a rare subset of the mammary adenoid cystic carcinoma. Awareness of its pathological features can help with the diagnosis as well as differential diagnosis. More cases are still needed for accurately assessing the prognosis of this particular tumor.

[A novel missense mutation of folypolyglutamate synthetase gene].

OBJECTIVE: To examine allelic frequencies of coding single nucleotide polymorphisms (cSNPs) of folypolyglutamate synthetase (FPGS) gene in Chinese Han children with acute leukemia (AL), in order to provide a basis for detecting the relationship between FPGS genetic polymorphisms and tumor individualized chemotherapy. METHODS: cSNPs of exon 5 were detected with polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) in 91 children with AL and 124 children with upper respiratory infection as controls. Genotypes and allelic frequencies were examined. RESULTS: A novel missense mutation, 502/490 T>C (L151/101P), was found in exon 5 of FPGS from control children. The novel mutation was found in mitochondrial variants in two cases and cytosolic variants in three cases. The cytosolic and mitochondrial variants displayed allelic frequencies of 0.70 % and 0.47 % respectively. The novel mutation was not associated with susceptibility to AL. CONCLUSIONS: A novel missense mutation 502/490 T>C (L151/101P) in exon 5 of FPGS gene is firstly found in Chinese Han children, and the cytosolic and mitochondrial variants display allelic frequencies of 0.70 % and 0.47 % respectively.