Untargeted LC-MS metabolomics reveals the metabolic responses in olive flounder subjected to hirame rhabdovirus infection.

Hirame novirhabdovirus (HIRRV), which mainly infects the olive flounder (Paralichthys olivaceus), is considered to be one of the most serious viral pathogens threatening the global fish culture industry. However, little is known about the mechanism of host-pathogen interactions at the metabolomic level. In this study, in order to explore the metabolic response of olive flounder to HIRRV infection, liquid chromatography mass spectrometry (LC-MS) was used to detect the changes of endogenous compounds of the olive flounder after HIRRV infection. A total of 954 unique masses were obtained, including 495 metabolites and 459 lipids. Among them, 7 and 173 qualified differential metabolites were identified at 2 days and 7 days post-infection, respectively. Distinct metabolic profiles were observed along with viral infection. At the early stage of infection, only a few metabolites were perturbed. Among them, the level of inosine and carnosine were increased and the potential antiviral ability of these two metabolites was further confirmed by exogenous addition experiment. At the late stage of HIRRV infection, the metabolic profiles changed remarkably. The changes in amino acids and nucleotides especially the 7-methylguanine also accelerated the amplification of viral particles. And the down-regulation of glutathione (GSH) implied an elevated level of ROS (reactive oxygen species) that attenuated the immune system of flounders. HIRRV also induced the accumulation of purine and reduction of pyrimidine, and elevated LPC and LPE levels. The unbalanced purine/pyrimidine and altered lipid profile may be beneficial for the replication and infection of HIRRV at the late stage of infection. These findings provide new insights into the pathogenic mechanism of HIRRV infection in olive flounder.

A smartphone-assisted paper-based ratio fluorescent probe for the rapid and on-site detection of tetracycline in food samples.

Rapid, sensitive and portable analytical methods for on-site detection of tetracycline (TC) in food samples is of critical importance for food safety and public health. In this study, a dual-emission ratio fluorescent probe (Gd0.9@Eu0.1) was prepared and utilized for the detection of tetracycline (TC) by observing the fluorescence color change from blue to red. The detection process exhibits a wide linear range (0-52.0 µM), good selectivity and low detection limit (14 nM). A paper-based probe and a colorimetric card was constructed for the visual detection of TC. Furthermore, a novel and portable detection platform combining smartphone and test strip was exploited for the quantitative and on-site detection of TC in real pork sample. The developed method was validated through intra- (n = 5) and inter-day (n = 2) measurements, as well as comparison with a traditional HPLC method. These statistical result validate the reliability and accuracy of the developed method. This intelligent detection platform represents a promising approach for the rapid, sensitive and visual detection of TC in food samples.

A highly selective and sensitive europium-organic framework sensor for the fluorescence detection of fipronil in tea.

A europium-based metal organic framework (Eu-TFPA-MOF) was used for the fluorescence detection of fipronil in green tea and oolong tea for the first time. The red fluorescence of Eu-TFPA-MOF could be quenched significantly by low concentration (0.24 mM) of fipronil, and the "turn off" process exhibited quick response time (2 min), high sensitivity and selectivity, low detection limits (4.4 nM) and wide linear range (0-0.15 mM). The mechanism of fluorescence quenching was mainly attributed to static quenching process and the competitive absorption of excitation energy. Besides, the spiked and recovery test indicated that Eu-TFPA-MOF could be used in the fluorescence detection of fipronil in real green tea and oolong tea sample and the process had the advantages of simple pretreatment and satisfactory recoveries (98.33-106.17 %). More importantly, a simple, portable and low-cost smartphone-assisted test strip were designed for the visual detection of fipronil in real tea samples. The detection platform will be beneficial for tea quality safety and human heath, and is expected to be applied in other agricultural product safety field.

A phase II study of antiangiogenic therapy (Apatinib) plus chemotherapy as second-line treatment in advanced small cell lung cancer.

INTRODUCTION: Currently, only a few options are available for the treatment of patients with small-cell lung cancer (SCLC) after the failure of first-line platinum-based chemotherapy. The present study aimed to evaluate the efficacy and safety of apatinib plus chemotherapy for second-line treatment of advanced SCLC. PATIENTS AND METHODS: This prospective clinical trial recruited patients treated with apatinib plus second-line chemotherapy until disease progression or intolerable toxicity. Logrank test power analysis was used for calculating samples. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. RESULTS: A total of 29/31 enrolled patients were available for response evaluation until October 2019. The ORR and DCR were 27.59% (8/29) and 96.55% (28/29), respectively. The median PFS and OS were 7.36 months and 14.16 months, respectively, indicating better efficacy compared with the standard second-line chemotherapies. The most common adverse events (AEs) were neutropenia (41.94%, 13/31), followed by leucopenia (35.48%, 11/31) and thrombocytopenia (25.81%, 8/31). The grade 3-4 AEs occurred in 12 (38.71%) patients, of which neutropenia (19.35%, 6/31), leucopenia (9.68%, 3/31), and proteinuria (6.45%, 2/31) were most common. Patients receiving an initial dose of apatinib 250 mg had a better tolerance. CONCLUSION: Antiangiogenic therapy plus chemotherapy had encouraging efficacy in advanced SCLC patients, which provides an insight into the current status of second-line therapy in SCLC.

Coexistence of atypical adenomatous hyperplasia, minimally invasive adenocarcinoma and invasive adenocarcinoma: Gene mutation analysis.

Multiple primary lung cancer (MPLC) refers to the simultaneous occurrence of two or more lung primary malignant tumors in one individual. The detection rate of MPLC has increased significantly in recent years, and the distinction between MPLC and lung metastasis has strong clinical significance. Whole exome sequencing (WES) can clearly identify the heterogeneity between MPLC nodules. Here, we report a case of a 50-year-old Asian female without a history of smoking. She underwent a lung computed tomography (CT) scan and three ground-glass nodules (GGNs) were found which were pathologically confirmed as atypical adenomatous hyperplasia (AAH), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IA), respectively. We performed WES on the three pulmonary nodules and analyzed the sequencing results. We believe that this is the first published report of a case of "three phases" of lung adenocarcinoma analyzed by WES. Under the same genetic background and internal environment, these three nodules showed significant genetic differences and developed into "three phases" of lung adenocarcinoma. Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: We used WES to analyze the gene mutation status of three tumors in one individual. We found that even if under the same genetic background, AAH, MIA and IA showed significant genetic differences and developed into "three phases" of lung adenocarcinoma. WHAT THIS STUDY ADDS: Analysis of the WES results supported the lung adenocarcinoma model from AAH to MIA and IA, and explored possible potential driver genes and therapeutic targets.