Baicalin Blocks Colon Cancer Cell Cycle and Inhibits Cell Proliferation through miR-139-3p Upregulation by Targeting CDK16.

Baicalin was reported to facilitate the apoptosis of colon cells and inhibit tumor growth in vivo. This study aimed to explore the specific mechanism and function of baicalin on colon cells. Relative mRNA levels were tested via qPCR. Cell proliferation, viability, and cell cycle phases were evaluated using MTT, colony formation, and flow cytometry assays, respectively. The interaction between miR-139-3p and cyclin-dependent kinase 16 (CDK16) was measured via a dual-luciferase reporter assay. Immunohistochemistry was used to count the positivity cells in tumor tissues collected from treated xenografted tumor mice. The results showed that baicalin increased miR-139-3p expression while also decreasing CDK16 levels, blocking the cell cycle, and inhibiting cell proliferation in colon cancer cells. miR-139-3p silencing or CDK16 overexpression abolished the inhibitory effects of baicalin on colon cancer proliferation. miR-139-3p directly targeted and interacted with CDK16 at the cellular level. The protective functions of miR-139-3p knockdown on tumor cells were abrogated by silencing CDK16. The combination of baicalin treatment and CDK16 knockdown further inhibited tumor growth of xenografted tumor mice compared with the groups injected with only sh-CDK16 or baicalin in vivo. In conclusion, baicalin inhibited colon cancer growth by modulating the miR-139-3p/CDK16 axis.

Palitantin derivatives from the Antarctic fungus Geomyces sp. 3-1.

Two new polyketides, palitantins B and C (1 and 2), along with one known related compound (+)-palitantin (3) were obtained from the culture of the Antarctic fungus Geomyces sp. 3-1. The structures of the new compounds were elucidated by detailed analysis of HRESIMS, NMR, CD, and ECD data. Compound 3 showed potent PTP1B inhibitory activity with an IC50 value of 7.9 µM (ursolic acid as positive control, IC50 = 8.3 µM).

A phase II trial of concurrent chemoradiotherapy with weekly paclitaxel and carboplatin in advanced oesophageal carcinoma.

BACKGROUND: This study was performed to assess the efficacy and feasibility of definitive chemoradiotherapy consisting of weekly doses of combined paclitaxel and carboplatin concurrent with radiation therapy, followed by 2 cycles of consolidation chemotherapy for advanced esophageal carcinoma. METHODS: Eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; Eastern Cooperative Oncology Group (ECOG) score ≤ 2; and adequate organ function. Patients received concurrent chemoradiation therapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and carboplatin (area under the curve, AUC = 2) on days 1, 8, 15, 22 and 29. The two-cycle consolidation chemotherapy protocol was paclitaxel (175 mg/m2) plus carboplatin (AUC = 5) administered on days 57 and 85, after concurrent chemoradiotherapy. RESULTS: Between August 2013 and February 2015, 65 patients with oesophageal carcinoma were enrolled in the study; 34 (52.3%) were newly diagnosed and 31 (47.6%) had postoperative local regional lymph node metastasis. The median overall survival time was 21.7 months (95% confidence interval [CI] 16.7-26.6), and the median progression-free survival time was 12.1 months (95% CI 9.0-15.3). A total of 96.9% (63/65) and 67.6% (44/65) patients completed ≥5 cycles and all 7 cycles of chemotherapy, respectively. A total of 93.8% (61/65) patients completed radiation therapy. The 1- and 2-year overall survival rates were 73.7 and 42.0%, respectively. The 1- and 2-year progression-free survival rates were 50.6 and 31.1%, respectively. Grade 3-4 toxicity during chemoradiotherapy included neutropenia (24.5%), thrombocytopenia (4.6%), fatigue (1.5%), anaemia (1.5%), radiation dermatitis (1.5%), pneumonitis (1.5%), oesophagitis (4.6%) and vomiting (1.5%). CONCLUSIONS: In patients with locally advanced oesophageal cancer, the combination of weekly doses of paclitaxel and carboplatin was well tolerated and produced comparable results. A three-arm randomised phase III trial (NCT02459457) comparing paclitaxel in combination with cisplatin, carboplatin or 5-fluorouracil with concurrent radiotherapy is on-going at our hospital.

Furanone derivative and sesquiterpene from Antarctic marine-derived fungus Penicillium sp. S-1-18.

A new furanone derivative, butanolide A (1), and a new sesquiterpene, guignarderemophilane F (2), together with six known compounds, were isolated from the fungus Penicillium sp. S-1-18 derived from Antarctic marine. The new structures were determined by spectroscopic studies such as 1D- and 2D-NMR and MS analyses. The absolute configuration of 1 was determined by the modified Mosher's method, while the absolute configuration of 2 was determined by calculated ECD spectroscopy. The isolated secondary metabolites were evaluated for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Compound 1 showed moderate inhibitory activity against PTP1B with IC50 value of 27.4 µM.

Assessment of heavy metal pollution in surficial sediments from a tropical river-estuary-shelf system: A case study of Kelantan River, Malaysia.

To understand the source-to-sink of pollutants in the Kelantan River estuary and the adjacent shelf area in Malaysia, a total of 42 surface sediment samples were collected in the Kelantan River-estuary-shelf system to analyze for grain size, total organic carbon (TOC) content, Al and heavy metals (Cr, Ni, Cu, Zn, Cd and Pb). The surficial sediments were mainly composed of clayey silt and the TOC content in sediments decreased from the river to the shelf. The surficial sediments experienced Pb pollution; Cr only showed a certain level of pollution in the coastal area of the estuary but not in other areas, and Ni, Cu, Zn, and Cd showed no pollution. The heavy metals mainly originated from natural weathering and erosion of rocks and soils in the catchment and enriched near the river mouth. Total organic carbon can promote the enrichment of heavy metals in sediments.

Genetic analysis and identification of candidate genes for two spotted-leaf mutants (spl101 and spl102) in rice.

Spotted-leaf mutants form spots in leaves or leaf sheaths under normal condition. The spotted-leaf phenotypes are similar to hypersensitive reaction of plants attacked by pathogen. Identification and characterization of the spotted-leaf mutants are helpful for understanding the mechanisms of resistance to plant diseases. Here, we identify two spotted-leaf mutants spl101 and spl102 from an EMS-treated elite japonica cultivar KYJ (Kuanyejing). spl101 and spl102 form serious spots at the late heading stage. Genetic analyses show that the spotted-leaf phenotypes of both spl101 and spl102 are caused by a single recessive mutation, respectively. By employing the Mutmap method, we reveal that both spl101 and spl102 contain mutations in the OsEDR1 gene. The spl101 mutation occurs in the 5°-splicing site of the 6th intron of OsEDR1, which causes abnormal recognition of the 6th intron and leads to the frameshift mutation. The spl102 mutant contains a mutation in the tenth exon of OsEDR1, resulting in an amino acid change from the phenylalanine (F) to the cysteine (C). OsEDR1 has been reported to regulate pathogen-resistant reaction, and loss of OsEDR1 function produces similar phenotypes to those of spl101 and spl102. Here, two newly identified alleles of OsEDR1 will be benefit for further understanding the molecular mechanisms of the OsEDR1 gene in disease resistance, and will be helpful for enriching the rice germplasm resources. In addition, our results also validate the effectiveness of the Mutmap method in cloning the candidate mutations.

A phase II study of concurrent chemoradiotherapy combined with a weekly paclitaxel and 5-fluorouracil regimen to treat patients with advanced oesophageal carcinoma.

BACKGROUND: A phase II study was performed to investigate the safety and efficacy of weekly doses of combined paclitaxel and 5-fluorouracil (5-FU) with concurrent radiation therapy, followed by 2 cycles of consolidation chemotherapy to treat patients with advanced oesophageal carcinoma. METHODS: The eligibility criteria included local, advanced, newly diagnosed and postoperative local regional lymph node metastasis; an Eastern Cooperative Oncology Group (ECOG) score of ≤ 2; and adequate organ function. Patients received chemoradiotherapy consisting of radiotherapy (50.4 Gy/28 Fx or 61.2 Gy/34 Fx) and concurrent paclitaxel (50 mg/m2) and 5-FU (300 mg/m2) for 96 h on days 1, 8, 15, 22, and 29. The two-cycle consolidation chemotherapy protocol included paclitaxel (175 mg/m2) plus continuously infused 5-FU (1800 mg/m2) for 72 h administered on days 57 and 85, after concurrent chemoradiotherapy. RESULTS: Between February 2012 and August 2013, 53 patients with oesophageal carcinoma were enrolled in the study. Among these patients, 33 (62.2%) were newly diagnosed and 20 (37.7%) had postoperative local regional lymph node metastasis. The median overall survival (OS) time was 17.9 months (95% CIs = 11.9-23.9), and the median progression-free survival (PFS) time was 12.4 months (95% CIs = 8.6-16.1). Approximately 84.9% (45/53) and 50.9% (27/53) of the patients completed ≥ 5 cycles and all 7 cycles of chemotherapy, respectively. Approximately 86.7% (46/53) of patients completed radiation therapy. The 1-, 2-, and 3-year OS rates were 66.0%, 37.7%, and 35.8%, respectively. The 1-, 2-, and 3-year local control rates were 76.9%, 66.4%, and 66.4%, respectively. Seventeen patients (32%) experienced grade 3 or higher toxicity. Grade 3 to 5 toxicity during chemoradiotherapy included neutropaenia (7.5%), thrombocytopaenia (1.8%), fatigue (7.5%), anaemia (1.8%), dermatitis radiation (1.8%), pneumonitis (5.6%), oesophagitis (9.4%) and vomiting (3.7%). CONCLUSIONS: The combination of weekly doses of paclitaxel and 5-FU was well tolerated and produced comparable results among patients with locally advanced oesophageal cancer. A randomised phase III trial (NCT01591135) comparing paclitaxel plus 5-FU with cisplatin plus 5-FU is on-going at our hospital.

Down-regulation of BnDA1, whose gene locus is associated with the seeds weight, improves the seeds weight and organ size in Brassica napus.

Brassica napus L. is an important oil crop worldwide and is the main raw material for biofuel. Seed weight and seed size are the main contributors to seed yield. DA1 (DA means big in Chinese) is an ubiquitin receptor and negatively regulates seed size. Down-regulation of AtDA1 in Arabidopsis leads to larger seeds and organs by increasing cell proliferation in integuments. In this study, BnDA1 was down-regulated in B. napus by over expressed of AtDA1R358K , which is a functional deficiency of DA1 with an arginine-to-lysine mutation at the 358th amino acid. The results showed that the biomass and size of the seeds, cotyledons, leaves, flowers and siliques of transgenic plants all increased significantly. In particular, the 1000 seed weight increased 21.23% and the seed yield per plant increased 13.22% in field condition. The transgenic plants had no negative traits related to yield. The candidate gene association analysis demonstrated that the BnDA1 locus was contributed to the seeds weight. Therefore, our study showed that regulation of DA1 in B. napus can increase the seed yield and biomass, and DA1 is a promising target for crop improvement.

[Genetic analysis and identification of candidate genes for a narrow leaf mutant (zy17) in rice].

Control of organ size by cell proliferation and cell expansion is a fundamental process in plant development, but little is known about the genetic and molecular mechanisms that determine organ size in plants. To understand the genetic and molecular mechanisms of organ growth control, we isolate a set of mutants with altered leaf size and identify the narrow leaf mutant, zhaiye 17 (zy17) (zhaiye means narrow leaf in Chinese). zy17 exhibits narrow leaves, slightly short plants, small panicles, reduced panicle branches and decreased grain numbers per panicle compared with the wild type. Our cytological analyses show that the narrow leaf phenotype of zy17 is caused by the reduced number of cells, indicating that ZY17 regulates cell proliferation. Genetic analyses show that the zy17 mutant phenotypes are controlled by a single gene. Using the whole genome resequencing approach and linkage analysis, we identify Os02g22390, Os02g28280 and Os02g29530 as candidate genes. Os02g22390 encodes a retrotransposon protein with the mutation occurring in the intronic region; Os02g28280 encodes a protein with unknown function with a base substitution resulting in non-synonymous mutation; Os02g29530 encodes a protein containing the PFAM domain related to glycosyltransferase, with a 2 bp deletion mutation causing a premature termination. Further studies on these three candidate genes will be helpful for understanding the molecular mechanism of organ size control in rice.

[Streptozotocin induction of type 2 diabetes in tree shrew].

The aim of this study was to induce type 2 diabetes in tree shrew (Tupaia belangeri chinensis). Streptozotocin (STZ), a glucosamine derivative of nitrosourea and preferentially toxic to pancreatic beta cells, has been commonly used to induce type 1 and 2 diabetes in experimental animals. Tree shrews were treated with different low doses of STZ (60, 70, and 80 mg/kg), with six control tree shrews receiving citrate buffer. After STZ injection, tree shrews displayed increased fasting blood and urine glucose, impaired oral glucose tolerance test, and disturbed lipids metabolism and renal function. However, STZ induced tree shrews showed no diabetic complications such as diabetic lactic acidosis and hyperglycemic hyperosmolar. Animals with the above type 2 diabetic-like symptoms were variable across the three groups from 66.7% to 100%, and mortality ranged from 16.7% to 33.3%. Thus, two 80 mg/kg STZ dose injections were appeared more appropriate than other doses to induce tree shrew model of type 2 diabetes. Our results demonstrated that type 2 diabetes could be induced with favorable STZ application in tree shrew.

[Control of organ shape and size by YUAN1 in Arabidopsis thaliana].

Control of organ shape and size by cell proliferationandcell expansion is a fundamental process in plant development. However, little is known about the molecular mechanisms that set the shape and size of determinate organs in plants. We have previously demonstrated that the Arabidopsis gene DA1 controls the final size of organs by restricting cell proliferation. Through an activation tagging screen for modifiers of da1-1, we have identified a semi-dominant mutant (yuan1-1D) with altered leaf shape and size. The yuan1-1D mutation results in reduced plant height, short and round leaves and short petioles due to defects in cell elongation. YUAN1 encodes a PHD zinc finger domain-containing protein. The GFP-YUAN1 fusion protein is localized to the nucleus. Overexpression of YUAN1 leads to round leaves and short petioles. Genetic analyses show that YUAN1 acts independently of DA1, ROTUNDIFOLIA 3 (ROT3) and ROTUNDIFOLIA4 (ROT4) to influence leaf shape and size. Collectively, our findings show that Arabidopsis YUAN1, a PHD zinc finger domain-containing protein, controls organ shape and size by restricting cell elongation, and give insight into how plants control their organ shape and size.

[Impact of typhoon "Fung-wong" on the distribution patterns of heavy metals in the Quanzhou Bay].

Based on the inductively coupled plasma mass spectroscopy (ICP-MS) data of concentrations of 7 heavy metals (including Cr, Ni, Cu, Zn, Cd, Pb and As) in suspended particles and surface sediments samples collected at 6 and 1 13-hours-mooring stations, respectively, in Quanzhou Bay 4 days after the landing of typhoon "Fung-wong". The average contents of Cr, Ni, Cu, Zn, As, and Cd are 60.4, 50.3, 26.5, 101.7, 3.36, 40.0 and 0.180 microg/g, respectively, in the surface sediments, and are 1.108-7.408, 0.476-3. 394, 0.809-5.046, 3.190-19.337, 0.087-0.595, 2.621-10.073 microg/L and 4.160-50.828 ng/L, respectively, in different stations in the suspended particles. The contents and distribution patterns of 7 heavy metals during a tidal cycle were significantly changed after typhoon "Fung-wong" by contrasting with that in same stations and tidal time at an ordinary situation. The contents of heavy metals, besides Ni, evidently decreased but the distribution patterns were similar with that in an ordinary condition with relatively large grads after typhoon "Fung-wong" in the surface sediments at station Q4. While in the suspended particles, the contents of heavy metals were evidently increased with the distribution patterns varied obviously and differently due to their geographical position after typhoon "Fung-wong". These impacts of typhoon "Fung-wong" to the contents and distribution patterns of heavy metals could be attribute to the "second contamination" and the increased supply of particles materials from continent during the typhoon process. The results of this study provide a reference to accurate assessing and scientific governing the heavy metals' contamination, and provide a directly support to evaluating the integrated impacts of typhoon process on the contamination of heavy metals in the Quanzhou Bay.

[Distribution patterns of heavy metals in suspended particles of the Quanzhou Bay and their influence factors].

Based on the inductively coupled plasma mass spectroscopy (ICP-MS) data of concentrations of 7 heavy metals (including Cr, Ni, Cu, Zn, Cd, Pb and As) in suspended particles and surface sediments samples collected at 6 and 2 13-hours-mooring stations, respectively, in Quanzhou Bay. The average contents of Cr, Ni, Cu, Zn, As, Pb, and Cd are 1.610-0.359, 0.730-0.150, 2.249-0.319, 6.421-1.266, 0.131-0.027, 4.176-1.101 microg/L and 17.526-2.260 ng/L, respectively, in different stations in the suspended particles and are 65.3-82.6, 37.8-39.8, 37.4-51.4, 121.0-172.8, 3.3-3.4, 42.2-76.9 and 0.217-0.493 microg/g, respectively, in the surface sediments of two stations. The concentrations of heavy metals in suspended particles varied significantly and the distribution patterns corresponded to the tidal and estuarine processes at the estuary area in a tidal cycle. While at the outer area, the varieties of concentrations were relatively unobvious and the re-suspension from surface sediments might play a significant role on distribution patterns of heavy metals in suspended particles. In a tidal cycle, the varieties of heavy metals concentrations in surface sediments were corresponding to that in suspended particles', which indicated that exchanges of heavy metals existed between surface sediments and suspended particles. These study results provide a reference to comprehensive understanding on distribution, migration and exchange of heavy metals in the Quanzhou Bay.

[Distribution patterns of heavy metals in surface sediments of the Quanzhou Bay and environmental quality assessment].

The concentrations of 7 heavy metals were determined in 48 surface sediments in the Quanzhou Bay by an inductively coupled plasma mass spectroscopy (ICP-MS). The average contents of Cr, Ni, Cu, Zn, As, Cd and Pb are 47.66, 52.2, 30.86, 111.6, 5.29, 0.399 and 50.3 microg x g(-1), respectively. The Cd, Pb, Zn and As were mainly discharged into the Quanzhou Bay by Jinjiang River, while the materials near the Bay might supply a considerable amount of Cr, Ni and Cu. The result of the multi-analysis ecological risk index analyses revealed that Cr, Ni, Cu, Zn, Pb and As were moderately contaminated and presented low potential ecological risk, while Cd was heavily contaminated and raised high potential ecological risk. In general, moderately contaminated and potential ecological risk were occurred in whole Quanzhou Bay with the dominated polluted metals were Ni and Cd. The heavily contaminated area was corresponded to the high potential ecological risk area, which located at the confluent area of Jinjiang River and Luoyangjiang River. From the results of this study, we conclude that the Quanzhou Bay has been heavily polluted by heavy metals, therefore much environmental control should be continued and strengthen to Quanzhou Bay and its adjacent areas.

Mapping and quantitative trait loci analysis of verticillium wilt resistance genes in cotton.

Verticillium wilt is one of the most serious constraints to cotton production in almost all of the cotton-growing countries. In this study, "XinLuZao1" (XLZ1), a susceptible cultivar Gossypium hirsutum L. and "Hai7124" (H7124), a resistant line G. barbadense, and their F(2:3) families were used to map and study the disease index induced by verticillium wilt. A total of 430 SSR loci were mapped into 41 linkage groups; the map spanned 3,745.9 cM and the average distance between adjacent loci was 8.71 cM. Four and five quantitative trait loci (QTLs) were detected based on the disease index investigated on July 22 and August 24 in 2004, respectively. These nine QTLs explained 10.63-28.83% of the phenotypic variance, six of them were located on the D sub-genome. Two QTLs located in the same marker intervals may partly explain the significant correlation of the two traits. QTLs explaining large phenotypic variation were identified in this study, which may be quite useful in cotton anti-disease breeding.