Isolation and characterization of elicitors from the oral secretion of lepidoptera larvae

Insect herbivory on plants is a complex interaction between several organisms, various chem-ical factors and fine tuned plant signaling cascades. The oral secretion (OS) from insect lar-vae contains a “pool” of chemicals which could trigger diverse plant defense reactions. Espe-cially, the oral secretion from lepidopteran larvae showed channel-forming activity in the black lipid membrane (BLM) assay, which was common for several lepidopteran species. Therefore this PhD work mainly concentrated on the discovery of new elicitor(s) which have the channel-forming activity, and further investigate the corresponding functions in plant de-fense. Here, a porin like protein (PLP) has been partially purified through diverse column chromatography and identified as a channel-forming compound present in the OS of S. littoralis larvae. Following the BLM-guided fractionation of 10 mL OS (collected from 500 larvae in the 4th instar stage) and proteomic analysis of several BLM active fractions, the identified peptides (ATIAGTYAFGPAK and TDAYFNLAYAK) were matched to the porin type protein derived from Gram-negative Ralstonia pickettii 12J by stringent database search-ing of MS/MS spectra (MASCOT) and homology-based approach (de novo MS BLAST). Due to the limited amount of OS, it was impossible to get the pure PLP from the final active fraction. Fortunately, the commercially available porin α-hemolysin (α-HL, 41) showed comparable BLM activity compare to the crude oral secretion and active fractions. This fur-ther confirmed the interpretation of proteomic data and indicated that the porin-like protein (PLP) from OS is one of the factors responsible for the channel-forming activity

Melatonin enhances the anti-tumor effect of fisetin by inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways.

Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy

The experience of long-stay patients in a forensic psychiatric hospital in China: a qualitative study

open access articleBackground Long stay in forensic psychiatric hospitals is common in patients who are defined as “not criminally responsible on account of mental disorder”. However, little is known about how these patients experience and perceive the long stay within these settings. The aim of this study is to explore the perception and needs of long-stay patients in forensic psychiatric hospitals in China. Methods In-depth semi-structured interviews were conducted with 21 participants who had lived in the forensic psychiatry hospital for more than 8 years. We used thematic analysis strategies to analyse the qualitative data. Results Participants’ perceptions clustered seven themes: hopelessness, loneliness, worthlessness, low mood, sleep disturbances, lack of freedom, and lack of mental health intervention. Conclusions The views and opinions expressed by long-stay patients showed that psychological distress is prevailing in forensic psychiatric hospitals. Adequate and effective care and mental health interventions are recommended to be tailored for their special needs

Nivolumab Versus Sorafenib as First-Line Therapy for Advanced Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Objective: Nivolumab improves overall survival (OS) and is associated with fewer adverse events than sorafenib for the treatment of advanced hepatocellular carcinoma (aHCC). However, the cost-effectiveness of nivolumab compared with sorafenib treatment for aHCC remains unclear. This study evaluated the cost-effectiveness of nivolumab and sorafenib in the treatment of aHCC.Materials and methods: A partitioned survival model that included three mutually exclusive health states was used to evaluate the cost-effectiveness of nivolumab and sorafenib for treating aHCC. The clinical characteristics and outcomes of the patients in the model were obtained from the CheckMate 459. We performed deterministic one-way sensitivity and probabilistic sensitivity analyses to evaluate the robustness of the model. Subgroup analyses were also performed. Costs, life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were measured.Results: The base case analysis showed that compared with sorafenib, treatment with nivolumab was associated with an increment of 0.50 (2.45 vs. 1.95) life-years and an increment of 0.32 (1.59 vs. 1.27) QALYs, as well as a $69,762 increase in cost per patient. The ICER was$220,864/QALY. The INHB and INMB were −0.15 QALYs and −$22,362 at a willingness-to-pay (WTP) threshold of$150,000/QALY, respectively. The probabilistic sensitivity analysis demonstrated that the probability of nivolumab being cost-effective was only 10.38% at a WTP threshold of $150,000/QALY. The model was most sensitive to the costs of sorafenib and nivolumab according to the one-way sensitivity analysis. When the price of sorafenib exceeded$0.93/mg or nivolumab was less than 24.23/mg, nivolumab was more cost-effective. The subgroup analysis illustrated that the probability of cost-effectiveness was >50% in the Barcelona Clinic Liver Cancer Stage B subgroups for nivolumab at a WTP threshold of 150,000/QALY. This study also showed that the probability of cost-effectiveness was <50% in most subgroups.Conclusion: Nivolumab was not cost-effective, although it was associated with better clinical benefit and a favorable safety profile for the treatment of aHCC compared with sorafenib from the third-party payer perspective in the United States. If the price of nivolumab is substantially reduced, favorable cost-effectiveness can be achieved among patients with aHCC

Preparation of Pb-doped tailings-based nano-TiO2 and study on photocatalytic degradation of PAM wastewater

As an efficient flocculant, polyacrylamide (PAM) is widely used in water treatment process. The acrylamide monomer (AM) produced by depolymerization of residual PAM has been listed as a class IIA carcinogen, and its treatment is imminent. Flotation tailing (TC) was used as raw material to prepare a modified tailing matrix by alkali excitation. Nano-TiO2 was loaded onto the modified tailing matrix by hydrothermal method to prepare tailing-based nano-TiO2 composite (TiO2/TC) and Pb-doped tailing-based nano-TiO2 composite (Pb-TiO2/TC). The photocatalytic degradation properties of TC, modified coal matrix, TiO2/TC and Pb-TiO2/TC were analyzed with PAM as the target pollutant. The samples were characterized by XRD, SEM, UV-vis and BET, and the degradation products were analyzed and studied by high performance liquid chromatography-mass spectrometry. The degradation mechanism of PAM was explored. The results show that TC is irregular and the surface is rough; the surface of TiO2/TC is loose, the pore structure is obvious, and the fine tubular TiO2 is uniformly coated on the surface of modified tailings. The structure of Pb-TiO2/TC is more fluffy, and the modified coal matrix is loaded with more tubular TiO2. The band gap of TiO2/TC was 3.16 eV, and Pb2+ doping reduced the band gap of Pb-TiO2/TC to 3.08 eV. The specific surface area of TiO2 is 286.66 m2/g, the specific surface area of TiO2/TC and Pb-TiO2/TC are 360.33 m2/g and 358.54 m2/g. The higher specific surface area provides more active sites for the reaction, and the adsorption-catalytic synergistic effect significantly improves the photocatalytic efficiency. The degradation rates of PAM by TC and modified tailing matrix were 3.39% and 4.68%. The degradation rates of polyacrylamide by TiO2/TC and Pb-TiO2/TC loaded with TiO2 increased to 38.92% and 63.87%. After five cycles, the photocatalytic properties of TiO2/TC and Pb-TiO2/TC remained basically unchanged. In the degradation process of PAM, the macromolecular PAM breaks into small molecular weight PAM molecules, and further decomposes into NO3−, acrylic acid, acetamide and acetic acid

Comparison of Nasopharyngeal MR, 18 F-FDG PET/CT, and 18 F-FDG PET/MR for Local Detection of Natural Killer/T-Cell Lymphoma, Nasal Type.

Objectives The present study aims to compare the diagnostic efficacy of MR, 18F-FDG PET/CT, and 18F-FDG PET/MR for the local detection of early-stage extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). Patients and Methods Thirty-six patients with histologically proven early-stage ENKTL were enrolled from a phase 2 study (Cohort A). Eight nasopharyngeal anatomical regions from each patient were imaged using 18F-FDG PET/CT and MR. A further nine patients were prospectively enrolled from a multicenter, phase 3 study; these patients underwent 18F-FDG PET/CT and PET/MR after a single 18F-FDG injection (Cohort B). Region-based sensitivity and specificity were calculated. The standardized uptake values (SUV) obtained from PET/CT and PET/MR were compared, and the relationship between the SUV and apparent diffusion coefficients (ADC) of PET/MR were analyzed. Results In Cohort A, of the 288 anatomic regions, 86 demonstrated lymphoma involvement. All lesions were detected by 18F-FDG PET/CT, while only 70 were detected by MR. 18F-FDG PET/CT exhibited a higher sensitivity than MR (100% vs. 81.4%, χ2 = 17.641, P < 0.001) for local detection of malignancies. The specificity of 18F-FDG PET/CT and MR were 98.5 and 97.5%, respectively (χ2 = 0.510, P = 0.475). The accuracy of 18F-FDG PET/CT was 99.0% and the accuracy of MR was 92.7% (χ2 = 14.087, P < 0.001). In Cohort B, 72 anatomical regions were analyzed. PET/CT and PET/MR have a sensitivity of 100% and a specificity of 92.5%. The two methods were consistent (κ = 0.833, P < 0.001). There was a significant correlation between PET/MR SUVmax and PET/CT SUVmax (r = 0.711, P < 0.001), and SUVmean (r = 0.685, P < 0.001). No correlation was observed between the SUV and the ADC. Conclusion In early-stage ENKTL, nasopharyngeal MR showed a lower sensitivity and a similar specificity when compared with 18F-FDG PET/CT. PET/MR showed similar performance compared with PET/CT

Targeted discovery of tetrapeptides and cyclic polyketide-peptide hybrids from a fungal antagonist of farming termites

Herein, we report the targeted isolation and characterization of four linear nonribosomally synthesized tetrapeptides (pseudoxylaramide A–D) and two cyclic nonribosomal peptide synthetase- polyketide synthase-derived natural products (xylacremolide A and B) from the termite-associated stowaway fungus Pseudoxylaria sp. X187. The fungal strain was prioritized for further metabolic analysis based on its taxonomical position and morphological and bioassay data. Metabolic data were dereplicated based on high-resolution tandem mass spectrometry data and global molecular networking analysis. The structure of all six new natural products was elucidated based on a combination of 1D and 2D NMR analysis, Marfey’s analysis and X-ray crystallography.The Deutsche Forschungsgemeinschaft (DFG)https://chemistry-europe.onlinelibrary.wiley.com/journal/14397633am2020BiochemistryGeneticsMicrobiology and Plant Patholog