Relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage: a prospective observational study.

BACKGROUND: It is found that there are great differences in the efficacy of quetiapine at the same dose in many patients with bipolar disorders. Therefore, therapeutic drug monitoring (TDM) is a valuable tool for guiding treatment with quetiapine. The aims of this study were to assess the relationship between serum concentration and clinical response of quetiapine in adolescents and adults with bipolar disorders in acute stage. METHODS: The study design was prospective and observational. Within the naturalistic setting of a routine TDM service at the First Affiliated Hospital, Zhejiang University School of Medicine. Psychiatric symptoms were assessed using the HAMD (Hamilton Depression Scale), YRMS (Young manic rating scale) and CUDOS-M (Clinically Useful Depression Outcome Scale-Mixed Subscale). The decline of HAMD and YMRS scores was were used to assess clinical outcome of bipolar disorders respectively. RESULTS: 169 inpatients (23.7 % male, 76.3 % female) were enrolled in the study. We found that there was a strong correlation between quetiapine serum concentrations and clinical outcomes (rs = 0.702, p < 0.001). While, quetiapine daily dose was not correlated with clinical outcome. We found that when the quetiapine serum level is >146.85 ng/ml in depression episodes patients could obtain a satisfactory treatment effect after 2 weeks of hospitalization. CONCLUSIONS: We found a significant positive relationship between serum concentration and clinical outcome, and also determined the serum concentration of quetiapine for the treatment of bipolar depression.

[Urbanization and ecological effect in mid-southern Liaoning urban agglomeration, China]. / 辽中南城市群城市化及生态效应.

China has entered the stage of rapid urbanization since the 1990s, resulting in a series of environmental problems. Based on the nighttime light remote sensing data and land use data from 1995 to 2020, we extracted the compound night light index (CNLI) to measure the urbanization level of mid-southern Liaoning urban agglomeration, evaluated habitat quality by InVEST model. We examined the relationship between urbanization level and habitat quality in mid-southern Liaoning urban agglomeration by using the correlation analysis method and the geographic weighted regression model. The results showed that CNLI increased by 0.14 from 1995 to 2020. The urbanization level increased continuously, with a pattern of "low in the east and high in the west". The habitat quality decreased by 0.005, showing a pattern of "high in the east and low in the west". The ecological environment became worse. There was a significant negative spatial correlation between urbanization level and habitat quality in mid-southern Liaoning urban agglomeration. The negative impact of urbanization level on habitat quality gradually decreased. In order to alleviate habitat degradation caused by urbanization and realize the coordinated and sustainable development of regional social economy, it was urgent to take a series of measures, such as delimiting the ecological protection red line, improving the intensive use of land, delimiting the urban boundary, promoting the coordinated development of regional integration.

[Cloning of transcription factor PcFBA-1 in Pogostemon cabin and its interaction with FPPS promoter].

Farnesyl diphosphate synthase(FPPS) is a key enzyme at the branch point of the sesquiterpene biosynthetic pathway, but there are no reports on the transcriptional regulation of FPPS promoter in Pogostemon cabin. In the early stage of this study, we obtained the binding protein PcFBA-1 of FPPS gene promoter in P. cabin. In order to explore the possible mechanism of PcFBA-1 involved in the regulation of patchouli alcohol biosynthesis, this study performed PCR-based cloning and sequencing analysis of PcFBA-1, analyzed the expression patterns of PcFBA-1 in different tissues by fluorescence quantitative PCR and its subcellular localization using the protoplast transformation system, detected the binding of PcFBA-1 protein to the FPPS promoter in vitro with the yeast one-hybrid system, and verified its transcriptional regulatory function by dual-luciferase reporter gene assay. The findings demonstrated that the cloned PcFBA-1 had an open reading frame(ORF) of 1 131 bp, encoding a protein of 376 amino acids, containing two conserved domains named F-box-like superfamily and FBA-1 superfamily, and belonging to the F-box family. Moreover, neither signal peptide nor transmembrane domain was contained, implying that it was an unstable hydrophilic protein. In addition, as revealed by fluorescence quantitative PCR results, PcFBA-1 had the highest expression in leaves, and there was no significant difference in expression in roots or stems. PcFBA-1 protein was proved mainly located in the cytoplasm. Furthermore, yeast one-hybrid screening and dual-luciferase reporter gene assay showed that PcFBA-1 was able to bind to FPPS promoter both in vitro and in vivo to enhance the activity of FPPS promoter. In summary, this study identifies a new transcription factor PcFBA-1 in P. cabin, which directly binds to the FPPS gene promoter to enhance the promoter activity. This had laid a foundation for the biosynthesis of patchouli alcohol and other active ingre-dients and provided a basis for metabolic engineering and genetic improvement of P. cabin.

The complete chloroplast genome of Acanthopanax brachypus (Araliaceae), a famous medicinal plant in China.

Acanthopanax brachypus (Araliaceae) is an important medicinal plant originated from China. Here, we reported the first chloroplast genome sequence of A. brachypus. The plastome of A. brachypu is 156,802 bp in length, including a large single-copy (LSC) of 86,742 bp, a small single-copy (SSC) of 18,184 bp, and a pair of inverted repeat regions (IRa and IRb) of 25,938 bp. It contains 113 unique genes consisting of 80 protein-coding genes, 29 tRNA genes, and 4 rRNA genes.

[Extraction of land-cover and wetland area in Bohai Rim region based on Google Earth Engine.] / 基于Google Earth Engine的环渤海地区土地覆盖分类.

The land cover of Bohai Rim region has changed greatly due to urbanization and economic development. Monitoring the land cover with high accuracy and real time is the most important basis for relevant researches. Traditional single-machine processing mode is difficult to realize rapid monitoring for large-scale and long-time series. The emergence of remote sensing big data makes it possible to combine computing platform and massive data. The land cover maps of study area were interpreted based on Google Earth Engine (GEE) platform with decision tree (CART) method from 2000 to 2019. The land cover change was analyzed, and the interpretation results using different data sources were compared. The results showed that the GEE platform could realize the rapid land cover interpretation in a large area, which interpreted coastal wetlands and other cover types with high accuracy over 80% comparing the surveyed points. Compared with Landsat images, the Sentinel-2A images interpretation results had a great improvement in accuracy, which increased from 85% to 95%, and thus more detailed surface information could be reflected. In 2000, the area of wetland, build-up area, farmland, forest, and water in the study area were 1612.5, 5734.9, 32074.8, 11853 and 3504.3 km2, accounting for 2.9%, 10.5%, 58.6%, 21.6% and 6.4% respectively. By 2019, wetlands had been reduced by 775.1 km2, with a decline of 40.1%; built-up area increased by 5310.5 km2 with an increasing rate of 92.6%. The area of farmland, forestland and water area decreased 1841.6, 1823.5 and 870.3 km2, with a decreasing rate of 5.7%, 24.8% and 48.1%, respectively. The coastal urbanization process caused the occupation of built-up area to other land use types, which was the main driving force of land cover change in the study area.

[Potential distribution of Spartinal alterniflora in China coastal areas based on Maxent niche model]. / 基于Maxent生态位模型的互花米草在我国沿海的潜在分布.

Maxent niche model was used to project the potential distribution of alien plant species Spartina alterniflora in China, with 96 S. alterniflora records and marine and climatic data along China coastal area. The results showed that suitable area for the distribution of S. alterniflora occupied 85% of coastal areas, with the highly suitable area, the medium, and low suitable area accounting for 18%, 34% and 33%, respectively. Only 15% of the coastal areas were regions with distribution possibility of less than 5%. Its distribution suitability was mainly related to annual lowest seawater temperature, annual mean seawater temperature, annual mean air temperature, and annual lowest temperature in January. However, the importance of annual mean precipitation, annual mean daily diurnal range, seawater salinity, annual highest seawater temperature, annual highest tempe-rature in June and current velocity was relatively small. At the highly suitable areas for S. alterni-flora, the annual lowest seawater temperature ranged from 0.62 to 24.81 ℃, the annual mean seawater temperature ranged from 10.46 to 27.29 ℃, the annual mean air temperature was between 9 to 25 ℃, and the annual lowest temperature in January was between -13.5 and 16.7 ℃. The distribution possibility of S. alterniflora in the northern coastal area was over 20%, indicating it has a great potential to invade further north in China, especially in Bohai Bay areas. According to the current distribution records and climatic data in China, the invasion risk of S. alterniflora in central and southern coasts of Hainan and most regions of Taiwan Province was low, but the possibility of future invasion can not be excluded.

Forward and reverse mutations in stages of cancer development.

BACKGROUND: Massive occurrences of interstitial loss of heterozygosity (LOH) likely resulting from gene conversions were found by us in different cancers as a type of single-nucleotide variations (SNVs), comparable in abundance to the commonly investigated gain of heterozygosity (GOH) type of SNVs, raising the question of the relationships between these two opposing types of cancer mutations. METHODS: In the present study, SNVs in 12 tetra sample and 17 trio sample sets from four cancer types along with copy number variations (CNVs) were analyzed by AluScan sequencing, comparing tumor with white blood cells as well as tissues vicinal to the tumor. Four published "nontumor"-tumor metastasis trios and 246 pan-cancer pairs analyzed by whole-genome sequencing (WGS) and 67 trios by whole-exome sequencing (WES) were also examined. RESULTS: Widespread GOHs enriched with CG-to-TG changes and associated with nearby CNVs and LOHs enriched with TG-to-CG changes were observed. Occurrences of GOH were 1.9-fold higher than LOH in "nontumor" tissues more than 2 cm away from the tumors, and a majority of these GOHs and LOHs were reversed in "paratumor" tissues within 2 cm of the tumors, forming forward-reverse mutation cycles where the revertant LOHs displayed strong lineage effects that pointed to a sequential instead of parallel development from "nontumor" to "paratumor" and onto tumor cells, which was also supported by the relative frequencies of 26 distinct classes of CNVs between these three types of cell populations. CONCLUSIONS: These findings suggest that developing cancer cells undergo sequential changes that enable the "nontumor" cells to acquire a wide range of forward mutations including ones that are essential for oncogenicity, followed by revertant mutations in the "paratumor" cells to avoid growth retardation by excessive mutation load. Such utilization of forward-reverse mutation cycles as an adaptive mechanism was also observed in cultured HeLa cells upon successive replatings. An understanding of forward-reverse mutation cycles in cancer development could provide a genomic basis for improved early diagnosis, staging, and treatment of cancers.

Waterborne exposure to BPS causes thyroid endocrine disruption in zebrafish larvae.

Bisphenol S (BPS) is widely used as a raw material in industry, resulting in its ubiquitous distribution in natural environment, including the aqueous environment. However, the effect of BPS on the thyroid endocrine system is largely unknown. In this study, zebrafish (Danio rerio) embryos were exposed to BPS at 1, 3, 10, and 30 µg/L, from 2 h post-fertilization (hpf) to 168hpf. Bioconcentration of BPS and whole-body thyroid hormones (THs), thyroid-stimulating hormone (TSH) concentrations as well as transcriptional profiling of key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were examined. Chemical analysis indicated that BPS was accumulated in zebrafish larvae. Thyroxine (T4) and triiodothyronine (T3) levels were significantly decreased at ≥ 10 and 30 µg/L of BPS, respectively. However, TSH concentration was significantly induced in the 10 and 30 µg/L BPS-treated groups. After exposure to BPS, the mRNA expression of corticotrophin releasing hormone (crh) and thyroglobulin (tg) genes were up-regulated at ≥10 µg/L of BPS, in a dose-response manner. The transcription of genes involved in thyroid development (pax8) and synthesis (sodium/iodide symporter, slc5a5) were also significantly increased in the 30 µg/L of BPS treatment group. Moreover, exposure to 10 µg/L or higher concentration of BPS significantly up-regulated genes related to thyroid hormone metabolism (deiodinases, dio1, dio2 and uridinediphosphate glucoronosyltransferases, ugt1ab), which might be responsible for the altered THs levels. However, the transcript of transthyretin (ttr) was significantly down-regulated at ≥ 3 µg/L of BPS, while the mRNA levels of thyroid hormone receptors (trα and trß) and dio3 remained unchanged. All the results indicated that exposure to BPS altered the whole-body THs and TSH concentrations and changed the expression profiling of key genes related to HPT axis, thus triggering thyroid endocrine disruption.

Long non-coding RNA NEAT1 promotes malignant progression of thyroid carcinoma by regulating miRNA-214.

The long non­coding RNA nuclear enrich abundant transcript 1 (NEAT1) has been identified to be carcinogenic in various cancers and elevated NEAT1 expression was tightly linked to tumorigenesis and progression. However, the mechanism has not been revealed in progression of thyroid cancer. Tumor xenograft mouse model was established and tumor size was evaluated. Arg­1, NEAT1 and miR­214 expression in CBMs, TAMs, BMDMs and RAW 264.7 cell lines were detected. TPC­1 cells were subjected to si­NEAT1 transfection in vitro for cell viability study. A direct target of miRNA­214 (ß­catenin) was assessed, cell survival and invasion in TAMs were investigated. NEAT1, Arg­1 was highly expressed and miRNA­214 had lower expression in patients with thyroid cancer. NEAT1 knockout inhibited thyroid cancer cell survival, migration and invasion, along with reduced ß­catenin (a direct target of miRNA­214) protein expression. Furthermore, NEAT1 significantly accelerated thyroid cancer cell growth and metastasis in vitro and increased tumor size in vivo. Upregulation of NEAT1 decreased the expression of miRNA­214, presenting a reciprocal repression correlation. In conclusion, these results suggest that high expression of NEAT1 promoted the onset of thyroid carcinoma. In addition, NEAT1 promoted the malignant progression of thyroid cancer through regulating miRNA­214 expression, which adds to our understanding of the molecular mechanisms in thyroid carcinoma.

Overexpression of Thy1 and ITGA6 is associated with invasion, metastasis and poor prognosis in human gallbladder carcinoma.

Gallbladder cancer (GBC) is a rare but highly aggressive cancer for which no well-accepted prognostic biomarkers have been identified. Thymus cell antigen 1 (Thy1), also known as cluster of differentiation (CD)90, and integrin α6 (ITGA6), also known as CD49f, are important molecules in cancer and putative markers of various stem cell types. However, their role in GBC remains to be elucidated. In the present study, Thy1 and ITGA6 expression status in clinical GBC samples, which comprised squamous cell/adenosquamous carcinoma (SC/ASC) and adenocarcinoma (AC) subtypes, was investigated. The associations between Thy1 and ITGA6 expression and clinical parameters and survival rate were analyzed separately. The THY1 and ITGA6 messenger RNA levels were significantly higher in both SC/ASC and AC tissues than in adjacent non-tumor tissues (all P<0.001). These results were subsequently confirmed by immunohistochemical analyses. Overexpression of Thy1 and ITGA6 was correlated with poor differentiation, large tumor size, lymph node metastasis and great invasiveness in SC/ASC (Thy1, P=0.045, P=0.005, P=0.003 and P=0.009, respectively, and ITGA6, P=0.029, P=0.011, P=0.009 and P=0.004, respectively) and AC (Thy1, P=0.027, P<0.001, P=0.003 and P 0.004, respectively, and ITGA6, P=0.002, P=0.003, P=0.006 and P=0.006, respectively). Both Thy1 and ITGA6 were expressed at higher levels in AC with advanced tumor-node-metastasis stage (TNM) than in AC with low TNM stage (P=0.001 and P=0.018, respectively). In addition, patients with elevated Thy1 or ITGA6 expression had shorter overall survival than those with negative Thy1 or ITGA6 expression. Multivariate Cox regression analysis demonstrated that Thy1 (SC/ASC, P=0.001 and AC, P=0.005) and ITGA6 (both P=0.003) were independent predictors of poor prognosis in both SC/ASC and AC patients. In conclusion, Thy1 and ITGA6 could be clinical prognostic markers for GBC.