Macrophage polarization plays essential and diverse roles in most diseases, such as atherosclerosis, adipose tissue inflammation, and insulin resistance. Homeostasis dysfunction in M1/M2 macrophage polarization causes pathological conditions and inflammation. Neuroinflammation is characterized by microglial activation and the concomitant production of pro-inflammatory cytokines, leading to numerous neurodegenerative diseases and psychiatric disorders. Decreased neuroinflammation can be obtained by using natural compounds, including flavonoids, which are known to ameliorate inflammatory responses. Among flavonoids, quercetin possesses multiple pharmacological applications and regulates several biological activities. In the present study, we found that quercetin effectively inhibited the expression of lipocalin-2 in both macrophages and microglial cells stimulated by lipopolysaccharides (LPS). The production of nitric oxide (NO) and expression levels of the pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2, were also attenuated by quercetin treatment. Our results also showed that quercetin significantly reduced the expression levels of the M1 markers, such as interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β, in the macrophages and microglia. The M1 polarization-associated chemokines, C–C motif chemokine ligand (CCL)-2 and C-X-C motif chemokine ligand (CXCL)-10, were also effectively reduced by the quercetin treatment. In addition, quercetin markedly reduced the production of various reactive oxygen species (ROS) in the microglia. The microglial phagocytic ability induced by the LPS was also effectively reduced by the quercetin treatment. Importantly, the quercetin increased the expression levels of the M2 marker, IL-10, and the endogenous antioxidants, heme oxygenase (HO)-1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), and NAD(P)H quinone oxidoreductase-1 (NQO1). The enhancement of the M2 markers and endogenous antioxidants by quercetin was activated by the AMP-activated protein kinase (AMPK) and Akt signaling pathways. Together, our study reported that the quercetin inhibited the effects of M1 polarization, including neuroinflammatory responses, ROS production, and phagocytosis. Moreover, the quercetin enhanced the M2 macrophage polarization and endogenous antioxidant expression in both macrophages and microglia. Our findings provide valuable information that quercetin may act as a potential drug for the treatment of diseases related to inflammatory disorders in the central nervous system.

Antrodia camphorata (A. camphorata) is well known in Taiwan as a traditional Chinese medicine, and it has been shown to exhibit antioxidant effects. In this study, the ability of A. camphorata to induce apoptosis was studied in cultured human premyelocytic leukemia HL-60 cells. Treatment of the HL-60 cells with a variety of concentrations of the fermented culture broth of A. camphorata (25-150 microg/ml) resulted in dose- and time-dependent sequences of events marked by apoptosis, as shown by loss of cell viability, chromatin condensation, and internucleosomal DNA fragmentation. Furthermore, apoptosis in the HL-60 cells was accompanied by the release of cytochrome c, activation of caspase-3, and specific proteolytic cleavage of poly (ADP-ribose) polymerase (PARP). This increase in A. camphorata-induced apoptosis was also associated with a reduction in the levels of Bcl-2, a potent cell-death inhibitor, and an increase in those of the Bax protein, which heterodimerizes with and thereby inhibits Bcl-2. The data suggest that A. camphorata exerts antiproliferative action and growth inhibition on HL-60 cells through apoptosis induction and that it may have anticancer properties valuable for application in drug products.

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Since DeepMind’s AlphaZero, Zero learning quickly became the state-of-the-art method for many board games. It can be improved using a fully convolutional structure (no fully connected layer). Using such an architecture plus global pooling, we can create bots independent of the board size. The training can be made more robust by keeping track of the best checkpoints during the training and by training against them. Using these features, we release Polygames, our framework for Zero learning, with its library of games and its checkpoints. We won against strong humans at the game of Hex in 19 × 19, including the human player with the best ELO rank on LittleGolem; we incidentally also won against another Zero implementation, which was weaker than humans: in a discussion on LittleGolem, Hex19 was said to be intractable for zero learning. We also won in Havannah with size 8: win against the strongest player, namely Eobllor, with excellent opening moves. We also won several first places at the TAAI 2019 competitions and had positive results against strong bots in various games.

The aim of this study was to evaluate peripheral nerve regeneration across a 15-mm gap in the sciatic nerve of the rat, using a silicone rubber nerve guide filled with different concentrations of astragaloside (0, 50, 100, and 200 microM). Collagen was also filled in the chambers to prevent the astragaloside from leakage. At the end of 8 weeks, animals from the group treated with astragaloside, especially at the concentration of 50 microM, had a higher rate of successful regeneration across the wide gap, a significantly larger number of myelinated axons, and a greater evoked action potential than the control group. However, the high-dose astragaloside (200 microM) completely reversed this positive effect of growth-promoting capability and inhibited nerve regeneration. Thus, astragaloside plays a dual role in anastomosis, being salutary in aiding the growth of axons in peripheral nerve but also detrimental, terminating the nerve regenerative processes if improperly applied.