Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a wait-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.

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A high-throughput screening assay on a microfluidic chip was developed for the determination of charge variants of monocolonal antibodies (mAbs) in pI range of 7-10. This method utilizes microchip zone electrophoresis for rapid separation (<90 s) of mAb charge variants that are labeled fluorescently without altering the overall charge. The microfluidic assay achieves between 8- and 90-fold times faster separation time over conventional methods while maintaining comparable resolution and profiles of charge variant distributions. We further characterized the assay with respect to (i) the effect of pH on resolution, (ii) the effect of excipients and buffering agents, (iii) the performance of the assay compared to conventional methods, and (vi) the reproducibility of charge variant profiles. Finally, we explored the utility of the assay with four case studies: (i) monitoring C-terminal lysine modification of a mAb, (ii) quantifying the extent of deamidation of a mAb, (iii) providing charge variant information on which to base clone selection, and (iv) making process parameter-related decisions from a "design of experiment" (DoE) study. The results of these case studies demonstrate the applicability of the microfluidic assay for high-throughput monitoring of mAb quality in process development of biopharmaceuticals.

WWOX acts as a tumor suppressor in human NSCLC models in a short-chain dehydrogenase/reductase domain-dependent manner. This activity is independent of sensitization to apoptotic cell death. WWOX expression as detected by immunohistochemistry may be a prognostic biomarker in surgically resected, early-stage NSCLC.