Identification of the ageing-related prognostic gene signature, and the associated regulation axis in skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) has substantial malignancy and a poor prognosis. The function of ageing-related genes (ARGs) in SKCM is unknown. In this study, a prognostic risk-scoring model for ARG was constructed based on SKCM RNA-seq, mutation, and clinical data in The Cancer Genome Atlas. Our novel prognostic model, which included four ARGs (IRS2, PDGFRA, TFAP2A, and SOD2), could distinguish between low-risk and high-risk groups. Low-risk patients benefited more from immunotherapy and commonly used targeted and chemotherapy drugs than high-risk patients. There were also considerable differences in immunocyte infiltration and tumour microenvironment between the two groups. Furthermore, multivariate Cox regression analysis revealed that age, pT_stage, pM_stage, body mass index, tumour mutation burden, and risk score were independent factors influencing the prognosis of patients with SKCM; therefore, we devised a prognosis nomogram. Last, a long non-coding (lncRNA) NEAT1/miR-33a-5p/IRS2 regulatory axis of the competing endogenous RNA network was built to investigate the mechanisms of SKCM metastasis progression. Grouping based on the scoring system could predict the prognosis of SKCM and predict the sensitivity of patients to immunotherapy, targeted therapy, and chemotherapy. This could facilitate the formulation of individualised treatment strategies and help drug research and development. These findings highlight the regulatory axis of the lncRNA NEAT1/miR-33a-5p/IRS2, which may play a role in SKCM metastasis.

Combination of Soxhlet extraction and catalytic hydrodebromination for remediation of tetrabromobisphenol A contaminated soil.

As a widely used brominated flame retardants (BFRs), tetrabromobisphenol A (TBBPA) has been detected in various environmental matrices and is known to cause negative effects on both the environment and human health. In this study, a combined method was developed for the abatement of TBBPA contaminated soil based on successive steps of solvent extraction (SE) and catalytic hydrodebromination (HDB) over Pd/C. The results showed that TBBPA could be efficiently extracted from the TBBPA contaminated soil with polar solvents. Subsequently, TBBPA could be completely hydrodebrominated over Pd/C in ethanol, via multistep ultimately yielding bisphenol A. Moreover, NaOH, NH3H2O, and Et3N were more favorable to promote the HDB of 4-TBBPA over Pd/C, and 100% bromide atom removal ratio of TBBPA was achieved within 40 min when [NaOH]0/[organic-Br]0 was more than 1.10 in ethanol. However, the catalytic activity of Pd/C decreased with the repeated use in ethanol. To study the mechanism for this phenomenon, fresh and used catalysts were analyzed by characterization techniques including scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and energy dispersive X-ray spectrometer (EDS). It was found that the deactivation of Pd/C catalyst caused by the gradual accumulation of NaBr could be recovered by washing with water. On the basis of these studies, an effective and practical system for the combined method of SE and catalytic HDB over Pd/C was developed to dispose BFRs contaminated soils.

Prognosis and Genomic Landscape of Liver Metastasis in Patients With Breast Cancer.

OBJECTIVE: The prognosis of breast cancer liver metastasis (BCLM) is poor, and its molecular mechanism is unclear. We aimed to determine the factors that affect the prognosis of patients with BCLM and investigate the genomic landscape of liver metastasis (LM). METHODS: We described the prognosis of patients with BCLM and focused on prognosis prediction for these patients based on clinicopathological factors. Nomogram models were constructed for progression-free survival (PFS) and overall survival (OS) by using a cohort of 231 patients with BCLM who underwent treatment at Shandong Cancer Hospital and Institute (SCHI). We explored the molecular mechanism of LM and constructed driver genes, mutation signatures by using a targeted sequencing dataset of 217 samples of LM and 479 unpaired samples of primary breast cancer (pBC) from Memorial Sloan Kettering Cancer Center (MSKCC). RESULTS: The median follow-up time for 231 patients with BCLM in the SCHI cohort was 46 months. The cumulative incidence of LM at 1, 2, and 5 years was 17.5%, 45.0%, and 86.8%, respectively. The median PFS and OS were 7 months (95% CI, 6-8) and 22 months (95% CI, 19-25), respectively. The independent factors that increased the progression risk of patients with LM were Karnofsky performance status (KPS) ≤ 80, TNBC subtype, grade III, increasing trend of CA153, and disease-free interval (DFS) ≤ 1 year. Simultaneously, the independent factors that increased the mortality risk of patients with LM were Ki-67 ≥ 30%, grade III, increasing trend of CA153, pain with initial LM, diabetes, and DFI ≤ 1 year. In the MSKCC dataset, the LM driver genes were ESR1, AKT1, ERBB2, and FGFR4, and LM matched three prominent mutation signatures: APOBEC cytidine deaminase, ultraviolet exposure, and defective DNA mismatch repair. CONCLUSION: This study systematically describes the survival prognosis and characteristics of LM from the clinicopathological factors to the genetic level. These results not only enable clinicians to assess the risk of disease progression in patients with BCLM to optimize treatment options, but also help us better understand the underlying mechanisms of tumor metastasis and evolution and provide new therapeutic targets with potential benefits for drug-resistant patients.

Promoted liquid-phase hydrodechlorination of chlorophenol over Raney Ni via controlling base: Performance, mechanism, and application.

The potential effect of base on Raney Ni-catalyzed hydrodechlorination (HDC) of chlorophenol was studied. Compared to weak inorganic bases, strong inorganic bases (NaOH and KOH) and triethylamine (Et3N) were more favorable to promote Raney Ni-catalyzed HDC reaction. Moreover, a stoichiometric amount of NaOH/Et3N was found to be optimal for the HDC reaction, and up to 100% conversion of 4-chlorophenol was achieved within 30 min. Catalyst characterization (SEM, EDXS, and XRD) combined with ICP-OES analysis were introduced to better understand the mechanism for the promoted effect of base on the HDC reaction. The results showed that the optimal amount of strong inorganic bases and Et3N efficiently eliminated HCl corrosion to Raney Ni, greatly reduced the active phase Ni and Al leaching, and avoided collapse of the catalyst framework. Based on the mechanism, the best bases and their optimal amount were developed for further disposal of polychlorinated phenols, and excellently stepwise HDC of polychlorinated phenols was achieved. Recycling tests showed that Raney Ni could be reused at least 5 times for the HDC reaction with the stoichiometric amount of NaOH, which was a promising option for the HDC of wastewater containing chlorophenols over Raney Ni.

Effect of the supports on catalytic activity of Pd catalysts for liquid-phase hydrodechlorination/hydrogenation reaction.

Carbon nanotubes (CNTs), activated carbon (AC), graphene, and aluminum oxide (Al2O3) supported 5% Pd catalysts were prepared by the conventional impregnation method, and catalytic activity was tested in the hydrogenation of 4-chlorophenol (4-CP) and nitrobenzene (NB) under ambient conditions (313 K and atmospheric pressure). It was found that catalytic activity was greatly affected by the supports. Moreover, Pd/CNTs catalyst exhibited much higher catalytic activity than the other three supported Pd catalysts. The mechanism of this phenomenon was studied through catalyst characterization (ICP-MS, Brunauer-Emmett-Teller [BET], TEM, and SEM). It was found that the mean particle size of Pd nanoparticles for Pd/CNTs (4.3 nm) was smaller than that for Pd/AC (6.9 nm), Pd/Al2O3 (5.0 nm), and Pd/graphene (5.2 nm). Moreover, the actual loading amounts of Pd and BET surface areas were not the main reasons for the different catalytic activity of the four supported Pd catalysts. Above all, the smaller Pd particles of Pd/CNTs enabled the Pd/CNTs catalyst to exhibit much higher catalytic activity for the hydrogenation reactions.

Involved-field irradiation for elderly bladder cancer patients.

OBJECTIVES: Considering that adjuvant radiation therapy is one of the most common treatment methods and the influence of the clinical target volume to treatment-related toxicity, this study aimed to observe the differences in treatment failures about involved-field irradiation (IFI) without lymph node areas versus elective nodal irradiation (ENI) with lymph node areas in elderly patients with bladder cancer. MATERIAL AND METHODS: Ninety-two elderly bladder cancer patients were analyzed from January 2010 to December 2014 in one institution. The primary inclusion criteria were previous after transurethral resection of bladder tumor or partial cystectomy with adjuvant radiotherapy, and the radiation techniques included IFI or ENI. The study required that elderly patients did not received radiotherapy before treatment. We observed treatment-related toxicity and tumor failures, evaluated local progression-free survival, estimated the 3-year overall survival, and analyzed prognostic factors, after IFI and ENI in elderly bladder cancer patients. The outcomes were determined by chi square tests, Kaplan-Meier method and Cox multiple factors analysis. RESULTS: In the experimental group, 42 patients (45.65%) received IFI, and a matched group of 50 patients (54.35%) received ENI. With a median follow-up of 31.47 months (range 4.00-86.00 months), the Kaplan-Meier analysis with a log-rank test demonstrated a statistical difference between the IFI group and the ENI group in acute toxicity (45.23% vs 72.00%, P = 0.008). However, there were no statistical differences in the 3-year overall survival rate (45.20% vs 48.00%, P = 0.860) or the duration of local progression-free survival (24.98 vs 34.30, P =0.729). CONCLUSIONS: IFI is feasible in elderly bladder cancer patients, as shown by a decrease in acute toxicity and no increase in local failure. We need a large number of clinical trials and data to further confirm these results.

Thoracic radiation therapy could give survival benefit to elderly patients with extensive-stage small-cell lung cancer.

AIM: To evaluate the effect of thoracic radiation therapy (TRT) in elderly patients (aged ≥65 years) with extensive-stage small-cell lung cancer (ES-SCLC). PATIENTS & METHODS: This study reviewed the records of 118 elderly patients with ES-SCLC (all with distant metastasis) through January 2006-December 2013. The patients were divided into either a chemotherapy (ChT)/TRT-combination group or a ChT-alone group. RESULTS: The median survival time and 3-year overall survival rates in the ChT/TRT group were significantly higher than those in the ChT-alone group (17.0 vs 11.7 months; 18.1 vs 14.9%; p = 0.014). The 3-year overall survival rates in patients who received prophylactic cranial irradiation were also higher than the rates in patients who did not receive prophylactic cranial irradiation (18.1 vs 5.1%; p = 0.708). CONCLUSION: TRT combined with ChT could provide a survival benefit to elderly patients with ES-SCLC.

Purification of quercetin-3-O-sophoroside and isoquercitrin from Poacynum hendersonii leaves using macroporous resins followed by Sephadex LH-20 column chromatography.

In China, Poacynum hendersonii is frequently used as a substitute for Apoacynum venetum L (Luobuma), which is a famous traditional Chinese medicine. Quercetin-3-O-sophoroside and isoquercitrin are two major flavonoids in Poacynum hendersonii leaves. In this work, a suitable method was established for the large-scale preparation of quercetin-3-O-sophoroside (QOS) and isoquercitrin (ISO) from Poacynum hendersonii leaves using macroporous resin combined with Sephadex LH-20 column chromatography. The adsorption/desorption capacities and desorption ratios of six macroporous resins were evaluated using static experiments. The HPD-300 resin had the best adsorption performance because it had the largest surface area, and was selected for further study. Compared with pseudo-first-order and intraparticle diffusion kinetics models, the pseudo-second-order model could better fit the adsorption kinetics of both QOS and ISO on the HPD-300 resin. In addition, the adsorption isotherms of the two compounds on the HPD-300 resin were fitted well to the Langmuir model. Under optimal conditions, the purities of QOS and ISO in the product were increased from 2.16% and 1.26% to 21.34% and 10.70% with recovery yields of 82.1% and 77.3%, respectively. Subsequently, Sephadex LH-20 column chromatography was employed for improving the purities of the two compounds. After separation by Sephadex LH-20 column chromatography, the purities of QOS and ISO achieved 93.5% and 95.6%, respectively.

Expressions of CD8+TILs, PD-L1 and Foxp3+TILs in stage I NSCLC guiding adjuvant chemotherapy decisions.

PURPOSE: Currently, adjuvant chemotherapy is recommended for patients with high risk stage I non-small cell lung cancer (NSCLC). However, identifying high risk patients remains a challenge. This study aims to identify the patient cohorts more likely to benefit from adjuvant chemotherapy based on the tumor micro-immune environment. RESULTS: CD8+TILs significantly associated with disease-free survival (DFS) and overall survial (OS) (p=0.002; 0.040). Patients with high risk factors may also predict shorter DFS (P=0.056). When compared together, patients with high-CD8+TILs showed better DFS than patients with low-CD8+TILs, no matter their risk factors status. There's no correlation between PD-L1 expressions and survival. PD-L1 was highly expressed in men, squamous and well differentiated carcinoma. In addition, Foxp3+TILs alone didn't show any prognostic effects, but low-Foxp3/high-CD8+TILs were associated with prolonged DFS (p=0.031). METHODS: A total of 126 patients with surgically resected stage I NSCLC were included to perform immunohistochemistry of CD8+ tumor infiltrating lymphocytes (TILs), programmed death ligand-1(PD-L1) and forkhead box P3 (Foxp3)+TILs. CONCLUSION: CD8+TILs are effective prognostic predictors. Patients with surgically resected stage I NSCLC showing low CD8+TILs could be considered for adjuvant chemotherapy, even if they have no high risk features.

Comparative study on catalytic hydrodehalogenation of halogenated aromatic compounds over Pd/C and Raney Ni catalysts.

Catalytic hydrodehalogenation (HDH) has proved to be an efficient approach to dispose halogenated aromatic compounds (HACs). Liquid-phase HDH of single and mixed halobenzenes/4-halophenols with H2 over 5% Pd/C and Raney Ni catalyst are investigated and compared. For liquid-phase HDH of single HACs, hydrogenolytic scission reactivity of C-X bonds decreases in order of C-Br > C-Cl > C-I > C-F over Pd/C catalyst, and in order of C-I > C-Br > C-Cl > C-F over Raney Ni catalyst. To clarify the reason why hydrogenolytic scission reactivity of C-X bonds over Pd/C and Raney Ni catalysts exhibits different trends, liquid-phase HDH of mixed HACs over Pd/C and Raney Ni catalysts were studied, and catalysts are characterized by SEM, EDX, and XRD techniques. It was found that the high adsorption of iodoarenes on Pd/C catalyst caused the HDH reactivity of iodoarenes to be lower than that of chloroarenes and bromoarenes in the HDH of single HACs. Moreover, the adsorption of in situ produced iodine ion (I(-)) to catalyst surface would result in the decline of catalytic activity, which might be the main reason why the HDH reactivity of HACs in the presence of NaI is rather low.

Chemical constituents and their bioactivities from the fruits of Vitex negundo var. cannabifolia.

Phytochemical investigation of the fruits of Vitex negundo var. cannabifolia led to the isolation of 22 compounds (1-22). Their structures were elucidated mainly by spectroscopic analysis and comparison with the literature data. Among them, compounds 1 and 2 were two new artificial lignans. Primary bioassay showed that the polymethoxyflavones 9-12 displayed moderate-to-weak cytotoxicity against human HepG2 and rat C6 cell lines, while the triterpenoids 13-17 exhibited significant brine shrimp lethality with LC50values of 7.5-29.4 µM.

Potential impact of (18)FDG-PET/CT on surgical approach for operable squamous cell cancer of middle-to-lower esophagus.

BACKGROUND: Fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) is reported to have a significant advantage over CT for staging esophageal cancer (EC). However, whether PET/CT may play a useful role in guiding surgical approach remains undetermined. METHODS: Patients with potentially resectable squamous cell EC were randomized into either PET/CT group or CT group. The surgical data and survival outcomes were compared. RESULTS: Compared to the CT group, the right-sided approach was more frequently used (42.6% versus 25.5%, P=0.065) in the PET/CT group in order to allow surgical access to radiographically suspicious lymph nodes inaccessible from the left, thus enabling the removal of more involved lymph nodes (2.83 versus 1.76; P=0.039) as well as their stations (1.65 versus 1.08; P=0.042). Although the overall survival between the two groups was similar, the PET/CT group had a longer disease-free survival (DFS) than the CT group (27.1 months versus 18.9 months; P=0.019), especially in the subgroup of node-positive patients (22.5 months versus 13.5 months; P=0.02). Preoperative imaging arm was the only prognostic factor found to independently influence DFS. CONCLUSION: For patients with middle-to-lower EC, surgical approaches directed by PET/CT may increase the likelihood of complete resection and affect DFS.

Rapid on-site evaluation during endobronchial ultrasound-guided transbronchial needle aspiration for the diagnosis of hilar and mediastinal lymphadenopathy in patients with lung cancer.

The purpose of this study was to assess the usefulness of rapid on-site evaluation (ROSE) during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and the interpretation of its results. Based on the criterion of using ROSE or not, 236 patients with known or suspected lung cancer undergoing EBUS-TBNA were allocated into the ROSE group (122 patients with 252 lymph nodes) and non-ROSE group (114 patients with 260 lymph nodes). In the ROSE group, the percentages of the suspicious specimens on cytology and non-diagnostic specimens on pathology were both significantly lower than that in the non-ROSE group (8.7% vs. 14.6%, p = 0.038; and 0.9% vs. 4.4%, p = 0.018, respectively), and 13 out of 22 suspicious lesions on ROSE were confirmed with definite diagnoses on TBNA pathology. The diagnostic yield stratified by pathology was significantly higher in the ROSE group than that in the non-ROSE group (90.5% vs. 81.2%, p = 0.003). These results suggest that ROSE during EBUS-TBNA allows for a low rate of suspicious results and therefore improves the diagnostic yield stratified by pathology when sampling hilar or mediastinal lymphadenopathy in patients with lung cancer.

The prognostic factors in the elderly patients with small cell lung cancer: a retrospective analysis from a single cancer institute.

OBJECTIVES: We conducted a retrospective study to evaluate the prognostic factors of elderly patients with small cell lung cancer (SCLC). PATIENTS AND METHODS: The records of elderly patients (≥ 65 years) with histologically-proven SCLC were reviewed. The patients' information including demographic, clinical and laboratory parameters, staging status on the Veterans Administration Lung Study Group staging system, and treatment modalities were registered. Univariate and multivariate survival analysis was performed by the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS: Between January 2004 and December 2012, 247 elderly patients with SCLC were analyzed, 129 patients initially presented with limited stage (LS) and 118 with extensive disease (ES). The median age of the patients was 70.7 years (range, 65-83 years). The median follow-up period for all patients was 22.0 months (range, 1.0-84.0 months) and 39.9 months for the surviving patients (range, 4.7-84.0 months). The median survival time (MST) was 17.3 months, and the 2-year and 3-year OS rates were 36.3% and 22.7%, respectively. The MST, 2-year and 3-year OS rates were 22 months, 45.0% and 30.5% in patients with limited stage, versus 13.4 months, 26.5% and 13.7% in patients having extensive diseases, respectively. Multivariate analysis revealed that disease extent (HR = 3.034; P < 0.001) and the number of chemotherapy cycles (HR = 0.486; P = 0.003) were independent prognostic factors for the OS. Additionally, a normal serum NSE level (HR = 0.447, P = 0.017) at the time of diagnosis was independent positive prognostic factors for patients with LS-SCLC, but not for ES-SCLC. CONCLUSION: Disease extent and the number of chemotherapy cycles were independent prognostic factors of elderly patients with SCLC. The fit cohort might benefit from positive treatment.

Separation of vitexin-4″-O-glucoside and vitexin-2″-O-rhamnoside from hawthorn leaves extracts using macroporous resins.

Vitexin-4″-O-glucoside and vitexin-2″-O-rhamnoside are the major flavonoids of hawthorn leaves. In this work, the adsorption and desorption characteristics of vitexin-4″-O-glucoside and vitexin-2″-O-rhamnoside on seven macroporous resins were evaluated. Among the tested resins, the HPD-400 resin showed the best adsorption and desorption capacities. Adsorption isotherms were constructed for the HPD-400 resin and well fitted to Langmuir and Freundlich models. Dynamic adsorption and desorption tests were performed on column packed with the HPD-400 resin to optimize the chromatographic parameters. After one run treatment with the HPD-400 resin, the contents of vitexin-4″-O-glucoside and vitexin-2″-O-rhamnoside in the product were increased 8.44-fold and 8.43-fold from 0.720% and 2.63% to 6.08% and 22.2% with recovery yields of 79.1% and 81.2%, respectively. These results show that the developed method is a promising basis for the large-scale purification of vitexin-4″-O-glucoside and vitexin-2″-O-rhamnoside from hawthorn leaves and other plant materials.

Tumor infiltrating lymphocytes (TILs) before and after neoadjuvant chemoradiotherapy and its clinical utility for rectal cancer.

BACKGROUNDS: Radiotherapy (RT) and chemotherapy (CT) can potentiate systemic antitumor immune effect. However, immunomodulation during RT or CT and their clinical implications in rectal cancer have not been thoroughly investigated. METHODS: We investigated alterations in the densities of tumor infiltrating lymphocytes (TILs) during chemoradiation and their clinical utilities in patients with rectal cancer. We analyzed 136 rectal cancer patients who underwent neoadjuvant RT, CT or chemoradiotherapy (CRT), followed by radical resection retrospectively. Pretreatment biopsy specimens and posttreatment resected specimens of all patients were immunostained for CD3 and CD8. The predictive value of TILs to neoadjuvant treatment and prognosis were examined. RESULTS: Densities of CD3+ and CD8+TILs in posttreatment specimens after RT, CT or CRT were all significantly higher than those in pretreatment specimens. There were no significant differences between each two of these three groups. High pretreatment CD3+ and CD8+TILs were associated with good response (TRG ≥ 3) after neoadjuvant treatments (P = 0.033 and 0.021). High CD3+TILs and CD8+TILs in pretreatment biopsy specimens were significantly associated with favorable disease free survival (DFS) (P = 0.010 and P = 0.022) and overall survival (OS) (P = 0.019 and P = 0.003). CONCLUSIONS: We may, thus, conclude that chemoradiation can enhance local immune response by increased TILs. High TILs densities before treatment are associated with good response to neoadjuvant chemoradiotherapy and a favorable prognosis.

Tumor-infiltrating lymphocytes, forkhead box P3, programmed death ligand-1, and cytotoxic T lymphocyte-associated antigen-4 expressions before and after neoadjuvant chemoradiation in rectal cancer.

Preclinical studies have suggested that cytotoxic agents and radiation may partly deliver their antitumor activities by activating antitumor immune response. However, the alterations of tumor immune microenvironment including immunosuppressive molecules during chemoradiotherapy and their associations with clinical features and prognosis in rectal cancer have not been thoroughly investigated. Therefore, we investigate the densities of cluster of differentiation 8 (CD8) positive tumor-infiltrating lymphocytes (TILs), CD4+TILs, natural killer cell (NK)-TILs, myeloid-derived suppressor cells (MDSCs), transcription factor forkhead box P3 (FOXP3)+TILs, programmed death ligand-1 (PD-L1), and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) before and after neoadjuvant chemoradiotherapy (nCRT) in rectal cancer patients to determine their predictive and prognostic effects. We screen 62 rectal cancer patients who underwent nCRT followed by radical surgery. Pretreatment biopsy specimens and posttreatment surgically resected specimens of all patients are retrieved to perform the immunohistochemistry of CD8, CD4, CD56, FOXP3, CD33, CD11b, PD-L1, and CTLA-4. The CD8+TILs and CD4+TILs in post-nCRT resected specimens are significantly higher than that in pre-nCRT biopsy specimens (P = 0.004 and 0.005, respectively). Expressions of MDSC, FOXP3+TILs, and CTLA-4 are relative stable after nCRT. Tumors with high density of CD8+TILs, CD4+TILs, and low MDSC-TILs are more sensitive to nCRT (P = 0.022, 0.022 and 0.005, respectively). High pretreatment CD8+TILs are associated with better disease-free survival and overall survival (P = 0.016 and 0.022, respectively). NK-TILs are detected only in 6 of 62 rectal cancer specimens evaluated. Cell surface PD-L1 positive by tumor cells (1 of 62) and stroma cells (3 of 62) are very low. We may conclude that tumor immunity is activated after nCRT by increased infiltrating CD8+ and CD4+ T cells and relative stable numbers MDSC-TILs, FOXP3+TILs, and coinhibitory molecules. Pre-nCRT CD8+TILs, CD4+TILs, and MDSC-TILs are sensitive predictive marker for response to CRT, and high CD8+TILs are associated with better prognosis.

A new minor diketopiperazine from the sponge-derived fungus Simplicillium sp. YZ-11.

Chemical investigation of the cultures of a sponge-derived fungus Simplicillium sp. YZ-11 led to the isolation of a new minor diketopiperazine alkaloid cyclo-(2-hydroxy-Pro-Gly) (1) and a natural lactone (S)-dihydro-5-[(S)- hydroxyphenylmethyl]-2(3H)-furanone (2), together with five known ergostane-type sterols (3-7). Their structures were established based on extensive spectroscopic methods ((1)H and (13)C NMR, (1)H-(1)H COSY, HSQC and HMBC) and optical rotation analysis.

Two new withanolides from the halophyte Datura stramonium L.

Eight steroids, including five withanolides (1-5) and three other ergostane-type steroids (6-8), were isolated from the aerial parts of the halophyte Datura stramonium L., which were collected from the Yellow River Delta in China. Their structures were elucidated on the basis of extensive spectroscopic methods, especially 1D and 2D NMR techniques. Compounds 1 and 2 were new compounds and characterised as (22R)-27-hydroxy-7α-methoxy-1-oxowitha-3,5,24-trienolide and its 27-O-ß-d-glucopyranoside. Compound 3 was a new natural product and identified as (22R)-27-hydroxy-1-oxowitha-2,5,24-trienolide and isolated from nature for the first time.

Toxic effects of environment-friendly antifoulant nonivamide on Phaeodactylum tricornutum.

Nonivamide, a synthetic derivate of natural capsaicin, has an effective antifouling activity. However, the poor understanding of the toxicity mechanism limits the application of nonivamide in antifouling paints. The present study investigated the inhibitory effects and toxicity mechanism of nonivamide on Phaeodactylum tricornutum. Under a 1.5 × 10(5) cells/ml of initial algal density (IAD), the effective concentration causing 50% inhibition at 4- d (4 d-EC50) value of nonivamide was 5.1 mg/L. Reactive oxygen species (ROS) level was significantly increased in nonivamide-treated algae. Algal antioxidants, including catalases (CAT), peroxidases (POD), superoxide dismutases (SOD), and glutathione (GSH), were all stimulated by the ROS burst. The excessive ROS substances led to the loss of algal photosynthetic pigments and also damage to the integrity of the lipid membrane. Furthermore, ROS-related genes, including psbA, psbD, psaB, rbcL, nad1, and cob, were found to be suppressed in the chloroplasts and mitochondria of nonivamide-treated algae, and the concentration of cytoplasmic Ca(2+) , an important regulator of chloroplast and mitochondrion, was elevated. The present study demonstrates that nonivamide could cause peroxidative damages to P. tricornutum by inducing ROS overproduction, which may be initiated by the suppression of ROS-related genes in algal chloroplasts and mitochondria.