5 ng/mL. The accuracy of all analytes for intra- and inter-day ranged from -4.3% to 14.6%, while precision were ≤9.0%. The recovery of each substance was > 81.0%, and no significant matrix effects were observed. The stabilities of all analytes under different conditions met all requirements for the quantitation in plasma samples. In addition, our developed UPLC-MS/MS method could also be employed to measure the pharmacokinetic profiles of acalabrutinib, ACP-5862, ibrutinib, and PCI-45227 in beagle dog plasma.Sigma-1 receptors are found throughout the nervous system and play a role in regulating nociception. They are highly expressed in nerve injury, making them a potential target for the treatment of neuropathic pain. Although sigma-1 receptor antagonists have been shown to have anti-nociceptive and anti-allodynic effects, improved selectivity of these ligands is needed to further investigate their potential to treat neuropathic pain. MCI-92 is a novel, selective sigma-1 receptor ligand developed to address this need.  https://www.selleckchem.com/products/frax597.html  A sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of MCI-92 in mouse plasma and brain homogenate. A structural analog of the analyte, MCI-147, was used as the internal standard (IS). The chromatographic separation was achieved on an Acquity UPLC BEH C18 column using a mobile phase consisting of water acidified with 0.1 % v/v formic acid and acetonitrile with gradient elution over 3.2 min. The method was linear over a concentration range of 1-200 ng/mL. Multiple reaction monitoring in the positive ionization mode was used for the mass spectrometric quantitation using m/z transitions 369.2 > 126.0 for MCI-92 and 448.9 > 350.1 for the IS. The method was successfully applied to the analysis of plasma and brain samples obtained in the course of oral and intravenous pharmacokinetic studies in CD-1 mice. MCI-92 showed a high volume of distribution (11.3 ± 0.6 L/kg) and rapid clearance (6.1 ± 0.8 L/h/kg) from systemic circulation. The concentration of the MCI-92 was higher in the brain than in plasma throughout all terminal time points, indicating high blood-to-brain partitioning and slow brain clearance.The picoplankton is an important component of aquatic food webs and plays a significant biogeochemical and ecological role in the environment. Little is known about this fraction of the plankton in temperate estuaries and especially in South America. In this article, we study the absolute and relative importance of the picoplankton along an annual cycle, and their relationship with physical and chemical variables in the Río de la Plata estuary. We also review the existing research in estuaries around the world concerning this community and present our results in a global context. The seasonal variation in the abundance of the different groups analyzed was very noticeable. Phycocyanin-rich picocyanobacteria (Pcy) were the main component (in abundance and in biovolume) of the picophytoplankton (PPP) almost during the whole year, with a maximum abundance of 7.3 × 105 cell mL-1 in summer, three orders of magnitude higher compared to autumn-winter. Picoeukaryotes, larger phytoplankton and heterotrophic bacteria showed the same seasonal trend, although with a lower range of variation than that of the Pcy. Considering all the phototrophic planktonic fractions, in terms of biomass, the PPP reached a maximum of 43% of the total biomass in spring. The dynamics of PPP found in this area are consistent with the observed in other temperate estuaries, where temperature is the main variable that influences its development, and with a high seasonal variation. Additionally, the absolute and relative importance of Pcy showed a consistently increasing trend towards lower latitude estuaries. The review also showed us that there is scarce information related to the picoplankton fraction in the Southern Hemisphere, its sanitary implications due to their potential of toxicity or their ecological role in coastal zones. The results presented here show the importance of this fraction, not only in Río de la Plata, but in many estuaries of the world, with a clear increase of relative abundance as we approach the equator.We previously reported that active muscle stiffness could be evaluated in vivo. However, we were not able to investigate active muscle stiffness as more than 250 deg·s-1 due to the limitation of the torque motor of dynamometer. The aim of the present study was to investigate the effect of angular velocities (including higher angular velocities of more than 250 deg·s-1) on active muscle stiffness. Eighteen males volunteered for this study. Active muscle stiffness of the medial gastrocnemius muscle was calculated according to changes in the estimated muscle force and fascicle length during fast lengthening at five different angular velocities (100, 200, 300, 500, and 600 deg·s-1). Electromyographic activities of the lateral gastrocnemius muscle (LG) and soleus muscle (SOL) were evaluated over two different phases before the stretch (mEMGa) and after the stretch (mMEGb). Active muscle stiffness was higher at 300 than at 100 deg·s-1, but decreased as the angular velocity increased from 300 to 600 deg·s-1. There were no differences in mEMGa and mEMGb values among the five angular velocities, whereas mEMGb values were higher than mEMGa for all angular velocities. In conclusion, active muscle stiffness was highest at 300 deg·s-1 and decreased at both slower and faster angular velocities.In the current study, we investigated the effect of lengthening velocity during eccentric exercise on the modulation of the physiological cross-sectional area (PCSA) and fascicle length of the vastus lateralis (VL) muscle. We hypothesized a greater increase in muscle PCSA after training with lower lengthening velocities and a greater increase in fascicle length after higher lengthening velocities. Forty-seven young men were randomly assigned to either a control (n = 14) or an intervention group (n = 33). The participants of the intervention group were randomly allocated to one of four isokinetic eccentric training protocols of the knee extensors, with four different knee angular velocities (45°/s, 120°/s, 210°/s and 300°/s), yet similar range of motion (25-100° knee joint angle), load magnitude (100% of isometric maximum) and load volume (i.e. similar time under tension for one training set). Before and after an 11-week training period with 3 times per week exercise, muscle volume, pennation angle, fascicle length and PCSA of the VL muscle were measured using magnetic resonance imaging and ultrasonography.