[Rectacted] miR­106b­5p promotes cell cycle progression of malignant melanoma by targeting PTEN.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the colony formation data shown in Fig. 2C on p. 333 had already appeared in previously published articles written by different authors at different research institutes. Owing to the fact that the contentious data in the above article had already been published prior to its submission to Oncology Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 39: 331­337, 2018; DOI: 10.3892/or.2017.6099].

Inhibiting KLRB1 expression is associated with impairing cancer immunity and leading to cancer progression and poor prognosis in breast invasive carcinoma patients.

BACKGROUND: The association between Killer cell lectin like receptor B1 (KLRB1) and cancer has been reported, but the roles of KLRB1 in breast invasive carcinoma (BRCA) has not been fully revealed. METHODS: Our study utilized the Cancer Genome Atlas (TCGA), Kaplan-Meier (K-M) Plotter, and TIMER databases to investigate the expression and clinical relevance of KLRB1 in BRCA and to explore its roles and mechanism in BRCA progression using gene set enrichment analysis, CCK-8, migration, apoptosis, and western blotting. We examined the relationship between KLRB1 expression and the BRCA immune microenvironment, using data from TCGA, and Gene Expression Profiling Interactive Analysis (GEPIA) databases and validated these findings in K-M Plotter databases. RESULTS: A significant decrease of KLRB1 expression was observed in BRCA patients. BRCA patients with low KLRB1 levels were associated with older age, advanced disease stage, HER2-positivity, poor prognosis, and a decreased survival probability compared to the high-expression group. Increased KLRB1 expression levels were correlated with inhibition of breast cancer cell proliferation, migration, and invasion, as well as promotion of cell apoptosis, possible through regulation of the NF-κB, PI3K/AKT, and TNF signaling pathways. Moreover, the study also indicated that decreased KLRB1 expression correlated with tumor purity, immune score, and immune cell infiltration (B cells, CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells, among others), cell markers, and immunotherapy. CONCLUSION: Decreased KLRB1 expression in BRCA is associated with poor prognosis and immune microenvironment. This study also highlights KLRB1 as a potential molecular marker for poor prognosis in BRCA patients, and therefore, it may provide clinical implications for the management of patients with BRCA.

Advanced QuEChERS Method Using Core-Shell Magnetic Molecularly Imprinted Polymers (Fe3O4@MIP) for the Determination of Pesticides in Chlorophyll-Rich Samples.

Graphitized carbon black (GCB) in the traditional QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was used to remove the interfering substance chlorophyll in vegetable and fruit samples for pesticide residues determination. However, it not only adsorbs pigments, but also adsorbs some planar and aromatic pesticides. In order to solve the shortcoming, a core-shell magnetic molecularly imprinted polymer (Fe3O4@MIP) that can specifically recognize and adsorb chlorophyll was synthesized, and an advanced QuEChERS method with the Fe3O4@MIP as a purification material was developed. This advanced method presents detection that is highly sensitive, specific, and reproducible for planar and aromatic pesticides. The limits of detection (LOD) ranged from 0.001-0.002 mg kg-1, and the limit of quantification (LOQ) was 0.005 mg kg-1. The recovery for the planar and aromatic pesticides was within 70-110% with the associated relative standard deviations < 15% in leek samples by the advanced QuEChERS method. However, in the traditional QuEChERS method with GCB, the recovery of most planar and aromatic pesticides was <60%. It may also be useful for the determination of other pesticides in vegetable samples with quick and easy sample purification.

Mechanism and evolutionary analysis of Yarrowia lipolytica CA20 capable of producing erythritol with a high yield based on comparative genomics.

Combined mutagenesis is widely applied for the breeding of robust Yarrowia lipolytica used in the production of erythritol. However, the changes of genome after mutagenesis remains unclear. This study aimed to unravel the mechanism involved in the improved erythritol synthesis of CA20 and the evolutionary relationship between different Y. lipolytica by comparative genomics analysis. The results showed that the genome size of Y. lipolytica CA20 was 20,420,510 bp, with a GC content of 48.97%. There were 6330 CDS and 649 ncRNA (non-coding RNA) in CA20 genome. Average nucleotide identity (ANI) analysis showed that CA20 genome possessed high similarity (ANI > 99.50%) with other Y. lipolytica strains, while phylogenetic analysis displayed that CA20 was classified together with Y. lipolytica IBT 446 and Y. lipolytica H222. CA20 shared 5342 core orthologous genes with the 8 strains while harbored 65 specific genes that mainly participated in the substrate and protein transport processes. CA20 contained 166 genes coding for carbohydrate-active enzymes (CAZymes), which was more than that found in other strains (108－137). Notably, 4, 2, and 13 different enzymes belonging to glycoside hydrolases (GHs), glycosyltransferases (GTs), and carbohydrate esterases (CEs), respectively, were only found in CA20. The enzymes involved in the metabolic pathway of erythritol were highly conserved in Y. lipolytica, except for transaldolase (TAL1). In addition, the titer and productivity of erythritol by CA20 were 190.97 g/L and 1.33 g/L/h, respectively, which were significantly higher than that of WT5 wherein 128.61 g/L and 0.92 g/L/h were obtained (P< 0.001). Five frameshift mutation genes and 15 genes harboring nonsynonymous mutation were found in CA20 compared with that of WT5. Most of these genes were involved in the cell division, cell wall synthesis, protein synthesis, and protein homeostasis maintenance. These findings suggested that the genome of Y. lipolytica is conserved during evolution, and the variance of living environment is one important factor leading to genome divergence. The varied number of CAZymes existed in Y. lipolytica is one factor that contributes to the performance difference. The increased synthesis of erythritol by Y. lipolytica CA20 is correlated with the improvement of the stability of cell structure and internal environment. The results of this study provide a basis for the directional breeding of robust strains used in erythritol production.

Dual roles of the Arabidopsis PEAT complex in histone H2A deubiquitination and H4K5 acetylation.

Histone H2A monoubiquitination is associated with transcriptional repression and needs to be removed by deubiquitinases to facilitate gene transcription in eukaryotes. However, the deubiquitinase responsible for genome-wide H2A deubiquitination in plants has yet to be identified. In this study, we found that the previously identified PWWP-EPCR-ARID-TRB (PEAT) complex components interact with both the ubiquitin-specific protease UBP5 and the redundant histone acetyltransferases HAM1 and HAM2 (HAM1/2) to form a larger version of PEAT complex in Arabidopsis thaliana. UBP5 functions as an H2A deubiquitinase in a nucleosome substrate-dependent manner in vitro and mediates H2A deubiquitination at the whole-genome level in vivo. HAM1/2 are shared subunits of the PEAT complex and the conserved NuA4 histone acetyltransferase complex, and are responsible for histone H4K5 acetylation. Within the PEAT complex, the PWWP components (PWWP1, PWWP2, and PWWP3) directly interact with UBP5 and are necessary for UBP5-mediated H2A deubiquitination, while the EPCR components (EPCR1 and EPCR2) directly interact with HAM1/2 and are required for HAM1/2-mediated H4K5 acetylation. Collectively, our study not only identifies dual roles of the PEAT complex in H2A deubiquitination and H4K5 acetylation but also illustrates how these processes collaborate at the whole-genome level to regulate the transcription and development in plants.

Dynamic human exposure to airborne bacteria-associated antibiotic resistomes revealed by longitudinal personal monitoring data.

Airborne antibiotic-resistant bacteria (ARB) can critically impact human health. We performed resistome profiling of 283 personal airborne exposure samples from 15 participants spanning 890 days and 66 locations. We found a greater diversity and abundance of airborne bacteria community and antibiotic resistomes in spring than in winter, and temperature contributed largely to the difference. A total of 1123 bacterial genera were detected, with 16 genera dominating. Of which, 7/16 were annotated as major antibiotic resistance gene (ARG) hosts. The participants were exposed to a highly dynamic collection of ARGs, including 322 subtypes conferring resistance to 18 antibiotic classes dominated by multidrug, macrolide-lincosamide-streptogramin, ß-lactam, and fosfomycin. Unlike the overall community-level bacteria exposure, an extremely high abundance of specific ARG subtypes, including lunA and qacG, were found in some samples. Staphylococcus was the predominant genus in the bacterial community, serving as a primary bacterial host for the ARGs. The annotation of ARG-carrying contigs indicated that humans and companion animals were major reservoirs for ARG-carrying Staphylococcus. This study contextualized airborne antibiotic resistomes in the precision medicine framework through longitudinal personal monitoring, which can have broad implications for human health.

WRKY transcription factors and OBERON histone-binding proteins form complexes to balance plant growth and stress tolerance.

WRKY transcription factors in plants are known to be able to mediate either transcriptional activation or repression, but the mechanism regulating their transcriptional activity is largely unclear. We found that group IId WRKY transcription factors interact with OBERON (OBE) proteins, forming redundant WRKY-OBE complexes in Arabidopsis thaliana. The coiled-coil domain of WRKY transcription factors binds to OBE proteins and is responsible for target gene selection and transcriptional repression. The PHD finger of OBE proteins binds to both histones and WRKY transcription factors. WRKY-OBE complexes repress the transcription of numerous stress-responsive genes and are required for maintaining normal plant growth. Several WRKY and OBE mutants show reduced plant size and increased drought tolerance, accompanied by increased expression of stress-responsive genes. Moreover, expression levels of most of these WRKY and OBE genes are reduced in response to drought stress, revealing a previously uncharacterized regulatory mechanism of the drought stress response. These results suggest that WRKY-OBE complexes repress transcription of stress-responsive genes, and thereby balance plant growth and stress tolerance.

5'tiRNA-Pro-TGG, a novel tRNA halve, promotes oncogenesis in sessile serrated lesions and serrated pathway of colorectal cancer.

BACKGROUND: Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are small fragments that form when tRNAs severe. tRNA halves (tiRNAs), a subcategory of tsRNA, are involved in the oncogenic processes of many tumors. However, their specific role in sessile serrated lesions (SSLs), a precancerous lesion often observed in the colon, has not yet been elucidated. AIM: To identify SSL-related tiRNAs and their potential role in the development of SSLs and serrated pathway of colorectal cancer (CRC). METHODS: Small-RNA sequencing was conducted in paired SSLs and their adjacent normal control (NC) tissues. The expression levels of five SSL-related tiRNAs were validated by q-polymerase chain reaction. Cell counting kit-8 and wound healing assays were performed to detect cell proliferation and migration. The target genes and sites of tiRNA-1:33-Pro-TGG-1 (5'tiRNA-Pro-TGG) were predicted by TargetScan and miRanda algorithms. Metabolism-associated and immune-related pathways were analyzed by single-sample gene set enrichment analysis. Functional analyses were performed to establish the roles of 5'tiRNA-Pro-TGG based on the target genes. RESULTS: In total, we found 52 upregulated tsRNAs and 28 downregulated tsRNAs in SSLs compared to NC. The expression levels of tiRNA-1:33-Gly-CCC-2, tiRNA-1:33-Pro-TGG-1, and tiRNA-1:34-Thr-TGT-4-M2 5'tiRNAs were higher in SSLs than those in NC, while that of 5'tiRNA-Pro-TGG was associated with the size of SSLs. It was demonstrated that 5'tiRNA-Pro-TGG promoted cell proliferation and migration of RKO cell in vitro. Then, heparanase 2 (HPSE2) was identified as a potential target gene of 5'tiRNA-Pro-TGG. Its lower expression was associated with a worse prognosis in CRC. Further, lower expression of HPSE2 was observed in SSLs compared to normal controls or conventional adenomas and in BRAF-mutant CRC compared to BRAF-wild CRC. Bioinformatics analyses revealed that its low expression was associated with a low interferon γ response and also with many metabolic pathways such as riboflavin, retinol, and cytochrome p450 drug metabolism pathways. CONCLUSION: tiRNAs may profoundly impact the development of SSLs. 5'tiRNA-Pro-TGG potentially promotes the progression of serrated pathway CRC through metabolic and immune pathways by interacting with HPSE2 and regulating its expression in SSLs and BRAF-mutant CRC. In the future, it may be possible to use tiRNAs as novel biomarkers for early diagnosis of SSLs and as potential therapeutic targets in serrated pathway of CRC.

Natural Coumarin Isomers with Dramatically Different AIE Properties: Mechanism and Application.

Aggregation-induced emission luminogens (AIEgens) are of great importance in optoelectronics and biomedical fields. However, the popular design philosophy by combining rotors with traditional fluorophores limits the imagination and structural diversity of AIEgens. Inspired by the fluorescent roots of the medicinal plant Toddalia asiatica, we discovered two unconventional rotor-free AIEgens, 5-methoxyseselin (5-MOS) and 6-methoxyseselin (6-MOS). Interestingly, a slight structural difference of the coumarin isomers leads to completely contrary fluorescent properties upon aggregation in aqueous media. Further mechanism investigation indicates that 5-MOS forms different extents of aggregates with the assistance of protonic solvents, leading to electron/energy transfer, which is responsible for its unique AIE feature, i.e., reduced emission in aqueous media but enhanced emission in crystal. Meanwhile, for 6-MOS, the conventional restriction of the intramolecular motion (RIM) mechanism is responsible for its AIE feature. More interestingly, the unique water-sensitive fluorescence property of 5-MOS enables its successful application for wash-free mitochondria imaging. This work not only demonstrates an ingenious tactic to seek new AIEgens from natural fluorescent species but also benefits the structure design and application exploration of next-generation AIEgens.

Expert Consensus on the Diagnosis and Treatment of Anticancer Drug-Induced Interstitial Lung Disease.

Drug-induced interstitial lung disease (DILD) is the most common pulmonary adverse event of anticancer drugs. In recent years, the incidence of anticancer DILD has gradually increased with the rapid development of novel anticancer agents. Due to the diverse clinical manifestations and the lack of specific diagnostic criteria, DILD is difficult to diagnose and may even become fatal if not treated properly. Herein, a multidisciplinary group of experts from oncology, respiratory, imaging, pharmacology, pathology, and radiology departments in China has reached the "expert consensus on the diagnosis and treatment of anticancer DILD" after several rounds of a comprehensive investigation. This consensus aims to improve the awareness of clinicians and provide recommendations for the early screening, diagnosis, and treatment of anticancer DILD. This consensus also emphasizes the importance of multidisciplinary collaboration while managing DILD.

Dimeric benzylisoquinoline alkaloids from Thalictrum delavayi and their biological activities.

A phytochemical investigation of the whole plants of T. delavayi led to the isolation of five new dimeric benzylisoquinoline alkaloids, thalidelavines A-E (1-5), together with six known congeners (6-11). The structures and absolute configurations of new compounds were established based on analyses of spectroscopic data, ECD calculations, and single crystal X-ray crystallography. Thalidelavines A-E (1-5) were structurally complex bisbenzylisoquinoline alkaloids with various configurations. These isolated alkaloids were evaluated for their cytotoxic and immunosuppressive effects. Among them, both 9 and 10 displayed significant cytotoxicities against T98G cell lines with an IC50 value of 2.1 µM, compared with the positive CPT-11 (IC50 = 3.0 µM). In addition, 5-7 showed remarkable immunosuppressive effects. These findings not only enrich the structural diversity of bisbenzylisoquinoline alkaloids, but also provide potential candidates for the further development of the antitumor and immunosuppressive agents.

A new risk model for CSTA, FAM83A, and MYCT1 predicts poor prognosis and is related to immune infiltration in lung squamous cell carcinoma.

OBJECTIVES: To create a prognostic model based on differentially expressed genes (DEGs) in early lung squamous cell carcinoma (LUSC) and characterize the relationship between risk scores and tumor immune infiltration. METHODS: We identified DEGs in normal and tumor tissues that overlapped between LUSC-related data sets from the Gene Expression Omnibus and the Cancer Genome Atlas and evaluated their roles in the diagnosis and prognosis of LUSC by Kaplan-Meier survival analysis, receiver operating characteristic (ROC) analysis, meta-analysis and nomogram analysis. We then constructed a risk model based on Cox regression analysis and the Akaike information criterion and identified the relationship between LUSC risk scores and immune infiltration. RESULTS: Sixty-two overlapping DEGs were involved with keratinocyte differentiation, epidermal cell differentiation, neutrophil migration, granulocyte chemotaxis, granulocyte migration, leukocyte aggregation, and positive regulation of nuclear factor-κB (NF-κB) activity. Overexpression of family with sequence similarity 83 member A (FAM83A) and MYC target 1 (MYCT1), kallikrein related peptidase 8 (KLK8), and downregulation of ADP ribosylation factor like GTPase 14 (ARL14), caspase recruitment domain family member 14 (CARD14), cystatin A (CSTA), dickkopf WNT signaling pathway inhibitor 4 (DKK4), desmoglein 3 (DSG3), and keratin 6B (KRT6B) were associated with a poor prognosis in LUSC and had significant value for LUSC diagnosis. The expression of CSTA, FAM83A, and MYCT1 and high-risk scores were independent risk factors for a poor prognosis in LUSC. A risk nomogram revealed that risk scores could predict the prognosis of LUSC. The risk score was associated with neutrophils, naive B cells, helper follicular T cells, and activated dendritic cells. CONCLUSIONS: The expression levels of CSTA, FAM83A, and MYCT1 are related to the diagnosis and prognosis of LUSC and may have potential as therapeutic targets in LUSC. A risk model and nomogram based on CSTA, FAM83A, and MYCT1 can predict the prognosis of LUSC.

Association between the dietary literacy of children's daily diet providers and school-age children's nutritional status and eating behaviours: a cross-sectional study.

BACKGROUND: Overweight and obesity rates have increased rapidly in Chinese school-age children, and previous studies have indicated that poor dietary literacy can lead to unhealthy eating behaviours. However, few studies have investigated the association between the dietary literacy of daily diet providers and the eating behaviours and nutritional status of school-age children raised by the providers. Thus, we aimed to explore this association. METHODS: We collected data on the eating behaviours and nutritional status of children in two primary schools in Anhui Province, as well as the dietary literacy of their daily diet providers. T-tests, one-way ANOVA, chi-square tests, and multiple linear regression were used to analyse the association. RESULTS: We found significant differences in the scores on the Questionnaire of Children's Daily Diet Providers' Dietary Literacy (QCDDPDL) by region, relationship with the child, age, and educational level of the daily diet provider (all p < .05). Moreover, the children in the low QCDDPDL score group were inclined to engage in unhealthy eating behaviours such as emotional undereating and overeating (p < .05). In addition, the incidence of overweight and obesity was higher in the low QCDDPDL attitude score group than in the high score group (p = .006). CONCLUSIONS: Our study showed that the dietary literacy of diet providers may influence children's health and eating behaviours. Improving the dietary literacy of diet providers may promote the health status and eating behaviours of school-age children.

Aminopolyol-Dependent Assembly of Heterometallic Lanthanide-Iron-Oxo Clusters.

Lanthanide-iron clusters usually display interesting structures and outstanding magnetic properties. However, due to the high reactivity (acidity) of the Fe3+-H2O bond and the inability to form a terminal oxo ligand, the preparation of high-nuclearity Ln-Fe clusters is a great challenge. Herein, a series of lanthanide-iron-oxo clusters with the formulas [Y6Fe(HL)10(NO3)2(EG)2(µ3-OH)8(H2O)4]·ClO4·N-H2BDEA·2H2O (Y6Fe, 1, H2L = 3-hydroxypivalic acid, EG = ethylene glycol, N-H2BDEA = 2,2'-(butylimino)diethanol), [Ln8Fe3(H2TEOA)2(HTEOA)2(HL)10(µ3-OH)9(µ2-OH)(µ4-O)2(H2O)4]·(NO3)3·xH2O (Ln = Y, x = 13 for 2, Y8Fe3; Ln = Dy, x = 10 for 3, Dy8Fe3; H3TEOA = triethanolamine), and [Ln12Fe14(HL)16(µ3-OH)20(µ2-OH)12(µ4-O)12(H2O)12]·(NO3)6·xH2O (Ln = Y, x = 40 for 4, Y12Fe14; Ln = Dy, x = 30 for 5, Dy12Fe14) were obtained by adjusting the pH with different aminopolyols as organic alkalis. Structural analysis showed that a cubane-like unit was the main structural unit in compounds 1-5. Compound 1 was formed by two {Y3Fe(µ3-OH)4} units with the common vertices, and compounds 2 and 3 were formed by two {Y3Fe(µ3-OH)3(µ4-O)} units with the common vertices bridging a quadrilateral unit {Ln2Fe2(µ3-OH)3(µ2-OH)}. The basic structural units of cubane-like {Ln2Fe2(µ3-OH)(µ4-O)3}, triangular {LnFe2(µ3-OH)2(µ4-O)}, and neutral iron-hydroxyl {Fe(µ3-OH)(µ2-OH)2} were found in compounds 4 and 5. The universality of building blocks for the assembly has been demonstrated in high-nuclearity lanthanide-iron-oxo clusters. Meanwhile, the structural regulation of the lanthanide-iron-oxo clusters 1-5 was realized by adjusting the pH with different organic alkalis, which provided the reference for the effective synthesis of high-nuclearity lanthanide-iron-oxo clusters. Magnetic studies showed that 3 and 5 displayed a slow magnetic relaxation behavior.

Psychological Resilience Mediates the Association Between Childhood Maltreatment and Self-Harm Phenotype in Chinese Early Adolescents.

Self-harm (SH) increases significantly in early adolescence with great variability, and childhood maltreatment (CM) contributes to this increase. Understanding the developmental pathway from CM to SH could provide clues for SH prevention. This study used latent class analysis (LCA) to detect the phenotype of SH and explored the role of psychological resilience in the pathway from the CM to SH phenotype among 5724 early adolescents (52.5% male). Three interpretable phenotypes of SH were identified: low SH (57.8%), medium SH (29.0%), and high SH (13.2%). Furthermore, CM was positively associated with the SH phenotype, psychological resilience mediated the association between CM and the SH phenotype (all ps < 0.001), and a larger mediating effect was observed in the medium SH (22.41%). Our findings offer new perspectives that improving psychological resilience can be used as an efficient intervention to reduce the risk of SH among early adolescents who have experienced CM.

TRAT1 overexpression delays cancer progression and is associated with immune infiltration in lung adenocarcinoma.

The roles and mechanisms of T-cell receptor (TCR)-associated transmembrane adaptor 1 (TRAT1) in lung adenocarcinoma (LAC) have not yet been reported in the relevant literature. Therefore, this study aimed to understand the roles and mechanisms of TRAT1 in LAC using bioinformatics and in vitro experiments. TRAT1 expression levels in LAC samples were analysed using various databases. TRAT1 co-expressed genes were acquired by the correlation analysis of LAC tissues. The functional mechanisms and protein network of TRAT1 co-expressed genes were analysed using bioinformatics analysis. The expression of TRAT1 was activated in LAC cells, and the roles of TRAT1 overexpression in the growth and migration of cancer cells was investigated using flow cytometry, Cell Counting Kit-8 (CCK-8), and migration and invasion assays. The relationship between TRAT1 overexpression, the immune microenvironment, and RNA modification was evaluated using correlation analysis. TRAT1 expression levels were significantly abnormal at multiple mutation sites and were related to the prognosis of LAC. TRAT1 co-expressed genes were involved in cell proliferation, adhesion, and differentiation, and TRAT1 overexpression significantly inhibited cell viability, migration, and invasion and promoted apoptosis of A549 and H1299 cells, which might be related to the TCR, B cell receptor (BCR), MAPK, and other pathways. TRAT1 expression levels were significantly correlated with the ESTIMATE, immune, and stromal scores in the LAC microenvironment. Additionally, TRAT1 expression levels were significantly correlated with the populations of B cells, CD8 T cells, cytotoxic cells, and other immune cells. TRAT1 overexpression was significantly correlated with the expression of immune cell markers (such as PDCD1, CD2, CD3E) and genes involved in RNA modification (such as ALKBH1, ALKBH3, ALKBH5). In conclusions, TRAT1 overexpression inhibited the growth and migration of LAC cells, thereby delaying cancer progression, and was correlated with the LAC microenvironment and RNA modifications.

Toxic effects and transcriptional responses in zebrafish liver cells following perfluorooctanoic acid exposure.

As a typical type of persistent organic pollutant, perfluorooctanoic acid (PFOA) is pervasive in the environment. Multiple studies have found that PFOA has hepatotoxicity, but the mechanism remains poorly understood. In this study, the toxic effects of different concentrations of PFOA on zebrafish liver cells were systematically assessed by recording cell survival, ultrastructural observations, and transcriptome analyses. The results showed that the inhibition of cell viability and the massive accumulation of autophagic vacuoles were observed at 400 µM PFOA, while transcriptomic changes occurred with treatments of 1 and 400 µM PFOA. The transcription levels of 1055 (977 up- and 78 down-regulated genes) and 520 (446 up- and 74 down-regulated genes) genes were significantly changed after treatment with 1 and 400 µM PFOA, respectively. Based on Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, significant expression changes were observed in autophagy, tight junction, signal transduction, immune system, endocrine system, and metabolism-related pathways, indicating that such processes were greatly affected by PFOA exposure. The findings of this study will provide a scientific basis for the toxic effects and potential toxic mechanisms of PFOA on zebrafish, and provide information for ecological risk assessments.

[Pharmacokinetic interaction of Jiaotai Pills and Fluoxetine in rats with CUMS-induced depression].

A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.

Characterization of an autonomous pathway complex that promotes flowering in Arabidopsis.

Although previous studies have identified several autonomous pathway components that are required for the promotion of flowering, little is known about how these components cooperate. Here, we identified an autonomous pathway complex (AuPC) containing both known components (FLD, LD and SDG26) and previously unknown components (EFL2, EFL4 and APRF1). Loss-of-function mutations of all of these components result in increased FLC expression and delayed flowering. The delayed-flowering phenotype is independent of photoperiod and can be overcome by vernalization, confirming that the complex specifically functions in the autonomous pathway. Chromatin immunoprecipitation combined with sequencing indicated that, in the AuPC mutants, the histone modifications (H3Ac, H3K4me3 and H3K36me3) associated with transcriptional activation are increased, and the histone modification (H3K27me3) associated with transcriptional repression is reduced, suggesting that the AuPC suppresses FLC expression at least partially by regulating these histone modifications. Moreover, we found that the AuPC component SDG26 associates with FLC chromatin via a previously uncharacterized DNA-binding domain and regulates FLC expression and flowering time independently of its histone methyltransferase activity. Together, these results provide a framework for understanding the molecular mechanism by which the autonomous pathway regulates flowering time.

[Effect of miltirone on proliferation and apoptosis of leukemia THP-1 cells].

To investigate the toxicity and related mechanism of miltirone to human acute myeloid leukemia THP-1 cells. To be specific, the active components and targets of miltirone were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the target proteins were converted into standard gene names with UniProt. Acute leukemia-rela-ted target genes were screened from GeneCards and DisGeNET. Venn diagram was constructed with Venny 2.1 to yield the common targets of the disease and the drug. The protein-protein interaction(PPI) network was constructed by STRING and Cytoscape 3.8.2. THP-1 cells in the logarithmic growth phase were treated with dimethyl sulfoxide(DMSO), and 2.5, 5, 10, 15, and 20 µmol·L~(-1) miltirone for 24 h, respectively. The proliferation rate of cells was analyzed by carboxyfluorescein diacetate succinimidyl ester(CFSE), apoptosis rate by flow cytometry with Annexin V-PE/7 AAD staining, and cell morphology by acridine orange staining. Real-time quantitative PCR(qPCR) was employed to detect the mRNA levels of nuclear receptor coactivator 2(NCOA2), poly(ADP-ribose) polymerase-1(PARP1), B-cell lymphoma-2(Bcl-2)-associated X protein(Bax), Bcl-2, and cysteine aspartyl protease-3(caspase-3). The effect of miltirone on apoptosis was detected in presence of caspase inhibitor Z-VAD-FMK. A total of 26 targets of miltirone, 1 046 genes related to acute leukemia, and 6 common targets of the two were screened out. Flow cytometry result showed miltirone at 10 µmol·L~(-1) can inhibit proliferation and promote apoptosis of THP-1 cells. The typical manifestations of apoptosis, such as cell shrinkage, nuclear rupture, and chromatin agglomerate were displayed by acridine orange staining. The decreased mRNA levels of NCOA2 and PARP1 and increased Bax/Bcl-2 ratio and the activity of pro-apoptotic protein caspase-3 were observed. Z-VAD-FMK can attenuate the apoptosis-inducing effect of miltirone. This study indicates that miltirone can inhibit the proliferation and promote the apoptosis of THP-1 cells, by down-regulating NCOA2 and PARP1, raising Bax/Bcl-2 ratio, and activating caspase-3.