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A new method to quantify the mycotoxin ochratoxin A (OTA) in coffee and tea samples is proposed based on second-order multivariate calibration and excitation-emission fluorescence matrix (EEFM) data. Experimental conditions were optimized by studying the effect of pH and various organized media on the fluorescence signal of OTA. For each analysed matrix (coffee grains and tea leaves), several sample pretreatments and calibration methods (external or standard addition) and data processing by chemometric models (e.g., parallel factor analysis/PARAFAC and multivariate curve resolution-alternating least squares/MCR-ALS) were evaluated and discussed. The MCR-ALS algorithm provided an adequate fit to the data for both samples, while PARAFAC was satisfactory only for the tea samples. Regarding the figures of merit, the limits of detection were in the range of 0.2-0.3 ng mL-1; furthermore, low relative prediction errors, between 2% and 4%, were achieved in both the fortified and real samples. Accordingly, the proposed methodology was applied to analyse fortified roasted and green coffee and real tea leaf samples. Satisfactory recoveries were achieved (ranging from 92 to 110%), and the obtained concentrations were in agreement with the values obtained by the reference method (based on high-performance liquid chromatography with fluorescence detection/HPLC-FLD). In addition, all samples contained OTA levels lower than the maximum permissible levels. Finally, the proposed strategy allows the use of green analytical chemistry principles; for instance, the use of organic solvents and the generation of waste products were significantly lower than for similar analytical methods reported in the literature.Selenocysteine (Sec, pKa 5.8) is genetically encoded 21st amino acid into the active site of selenoproteins, which have broad functions relevant to various diseases, tissues or organs and subcellular organelles. However, many selenoproteins involved cellular functions still remains unclear. In addition, since biothiols such as glutathione (GSH, pKa 8.3), possessing similar chemical properties with Sec, commonly exist in living systems at high levels. Thus, it is of great importance and high challenge to identify novel probes for selectively monitoring Sec over biothiols. In this paper, we proposed a smart strategy which allowed us to develop a lysosome targetable probe for specifically sensing Sec. By restricting weak acidic microenvironment, the probe shows a specific detection for Sec with 85-fold fluorescence enhancement owing to the remaining high activity of Sec at pH 5.0. Moreover, being low cytotoxicity to the cells verified by MTS assay, the probe was then successfully applied for imaging exogenous and endogenous Sec in lysosomes, indicating its potential for the biological investigation of Sec in subcellular organelles.Currently, only a small subset of cancer patients can benefit from anti-PD-1/PD-L1 monotherapy, indicating that further predictive biomarkers are needed. In the retrospective study, plasma samples were collected before anti-PD-L1/PD-L1 treatment in two subsets of patients. A total of 59 immunological factors, including cytokines, chemokines, and soluble immune checkpoints, were measured by using a multiplex immunoassay kit. Moreover, multiplex immunohistochemistry (mIHC) was performed in a subgroup of patients. In the discovery cohort, multiplex immunoassay profiling data revealed that both soluble PD-L1 and C-C motif chemokine 5 (CCL5/RANTES) showed rising trends across the three subgroups PD, SD and CR/PR. Further investigation demonstrated the predictive and prognostic value of the pre-treatment levels of PD-L1, CCL5/RANTES, and their combinatorial signature the "2-cytokine signature". As expected, the signature-high patients displayed a remarkably increased disease control rate (DCR) and prolonged survival versus that of the lower subgroup. More importantly, the relevance between the three signatures and the efficiency of immunotherapy was confirmed in the pan-cancer validation cohort. Notably, the significant association between the "2-cytokine signature" and longer survival was validated. Further quantitative analyses of the tumor microenvironment composition suggested a link between the "2-cytokine signature" and NK cell infiltration. In conclusion, a combined peripheral signature comprising CCL5/RANTES and soluble PD-L1 appears to be an effective biomarker to predict benefit from anti-PD-1/PD-L1 monotherapy. Our study underscores that peripheral immunological features may play an essential role in guiding patient selection and are worthy of future prospective investigations.Chronic pain is a common symptom of most clinical diseases, which seriously affects the psychosomatic health of patients and brings some pain to patients. Due to its pathological mechanism is very complicated and the treatment of chronic pain has always been a difficult problem in clinical. Normally, drugs are usually used to relieve pain, but the analgesic effect is not good, especially for cancer pain patients, the analgesic effect is poor. Therefore, exploring the pathogenesis and treatment of chronic pain has aroused the interest of many researchers. A large number of studies have shown that the role of ATP and P2X4 receptor (P2X4R) play an important role in the pathogenesis of chronic pain. P2X4R is dependent on ATP ligand-gated ion channel receptor, which can be activated by ATP and plays an important role in the information transmission of nerve system and the formation of pain. Therefore, in this paper, we comprehensively described the structure and biological functions of P2X4R, and outlined behavioral evaluation methods of chronic pain models. GS-0976 Moreover, we also explored the inherent relationship between P2X4R and chronic pain, and described the therapeutic effect of P2X4R antagonist on chronic pain, and provided some valuable help for the treatment of chronic pain.Glioma is the deadliest disease in human central nerve system. Abnormal expression of long noncoding RNA (lncRNA) expression has been demontrated to be implicated in various cancers. The oncogenic role of lncRNA NCK1-AS1 has been validated in cervical cancer, wheras its role in glioma remians obscure. Our research findings suggested that NCK1-AS1 was upregulated in glioma tissues and cells. NCK1-AS1 deficiency hindered cell proliferation and enhanced cell apoptosis. Additionally, the chemoresistance and radioresistance of glioma cells were impaired by NCK1-AS1 depletion. Moreover, miR-22-3p, a downstream gene of NCK1-AS1, could weaken glioma cell chemoresistance and radioresistance. Similarly, IGF1R was the downstream target gene of miR-22-3p. Further mechanism and function assays demonstrated that NCK1-AS1 promoted glioma cell growth, chemoresistance and radioresistance via sponging miR-22-3p to upregulate IGF1R. Finally, the tumor facilitator function of NCK1-AS1 was also verified by in vivo experiments. Taken together, NCK1-AS1 contributes to glioma cell proliferation, radioresistance and chemoresistance via miR-22-3p/IGF1R ceRNA pathway, which might provide a new insight for improving the radiotherapy and chemotherapy treatments of glioma.
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