Background: The homeostasis of metal ions, such as iron, copper, zinc and calcium, in the brain is crucial for maintaining normal physiological functions. Studies have shown that imbalance of these metal ions in the brain is closely related to the onset and progression of Alzheimer's disease (AD), the most common neurodegenerative disorder in the elderly. Main body: Erroneous deposition/distribution of the metal ions in different brain regions induces oxidative stress. The metal ions imbalance and oxidative stress together or independently promote amyloid-β (Aβ) overproduction by activating βor γ-secretases and inhibiting α-secretase, it also causes tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3β (GSK-3β), cyclin-dependent protein kinase-5 (CDK5), mitogenactivated protein kinases (MAPKs), etc., and inhibiting protein phosphatase 2A (PP2A). The metal ions imbalances can also directly or indirectly disrupt organelles, causing endoplasmic reticulum (ER) stress; mitochondrial and autophagic dysfunctions, which can cause or aggravate Aβ and tau aggregation/accumulation, and impair synaptic functions. Even worse, the metal ions imbalance-induced alterations can reversely exacerbate metal ions misdistribution and deposition. The vicious cycles between metal ions imbalances and Aβ/tau abnormalities will eventually lead to a chronic neurodegeneration and cognitive deficits, such as seen in AD patients. Conclusion: The metal ions imbalance induces Aβ and tau pathologies by directly or indirectly affecting multiple cellular/ subcellular pathways, and the disrupted homeostasis can reversely aggravate the abnormalities of metal ions transportation/ deposition. Therefore, adjusting metal balance by supplementing or chelating the metal ions may be potential in ameliorating AD pathologies, which provides new research directions for AD treatment.

S U M M A R Y3-D V P and V S models for the crust and upper mantle beneath the Taiwan area have been determined using selected high-resolution earthquake data from an island-wide seismic network and two local seismic arrays. Lateral structural variations in the upper crust, as also evident from surface geology, are responsible for the observed large traveltime residuals or station corrections. Prior shallow velocity information inferred from traveltime residuals and joint hypocentral determination (JHD) station corrections for the uppermost crust is essential to facilitate a reliable tomographic inversion. A finite-difference method, that is efficient and accurate for a highly heterogeneous velocity structure, is applied to calculate P-and S-wave traveltimes from the source to receiving stations. All earthquakes in the Taiwan Central Weather Bureau's catalogue are then relocated using the resultant 3-D V P and V S models. The depth of the Moho varies significantly, especially along the east-west direction. In the western Coastal Plain and Western Foothills the depth of the Moho is around 35 km, which deepens gradually eastward, reaches a maximum depth of ∼55 km beneath the eastern Central Mountain Range, shallows up rapidly beneath the Longitudinal Valley and Coastal Range, and merges with the thin Philippine Sea Plate offshore of eastern Taiwan. In central Taiwan, the Central Mountain Range is bounded to the east and west by two steeply westward dipping active faults from the upper crust to a depth of about 30 km. Therefore, the uplifted and thickened Central Mountain Range serves as a backstop for the converging Eurasian and Philippine Sea plates. The crust beneath the Central Mountain Range is characterized by a brittle, high-velocity and seismically active upper crust (<15 km) and a ductile, low-velocity and aseismic mid-to-lower crust (below 15 km), most probably due to the high geothermal activity from the excess heat supplied from the hot upper mantle beneath the thin oceanic crust to the east, from the surrounding hotter upper mantle beneath the thickened continental crust, and from shear heating during active collision. The collision zone in eastern Taiwan is characterized by an active and steeply eastward dipping seismic zone along a region of low V P and high V P /V S ratio near the Taitung region in southeastern Taiwan. It transforms into an active westward steeply dipping seismic zone along a transition zone between the high V P and V S oceanic crust and the low V P and V S continental crust near Hualien region in central eastern Taiwan. There is no apparent seismicity within many sedimentary basins imaged from the tomographic inversion. However, a few basins are either bounded on one side by an active fault or are characterized by blind faults beneath. The geometry of the subduction zone in northeastern Taiwan can be clearly imaged from the relocated earthquake locations. Behind the subduction, a region of low V P and high V P /V S ratio at depths of 5 to 10 km can be identified beneath the Tatun-Ch...

Peroxisome proliferator-activated receptor γ (PPARγ) is an important member of the nuclear receptor superfamily. Previous studies have shown the satisfactory anti-inflammatory role of PPARγ in experimental colitis models, mainly through negatively regulating several transcription factors such as nuclear factor-κB (NF-κB). Therefore, regulating PPARγ and PPARγ-related pathways has great promise for treating ulcerative colitis (UC). In the present study, our objective was to explore the potential effect of naringin on dextran sulfate sodium (DSS) induced UC in mice and its involved potential mechanism. We found that naringin significantly relieved DSS-induced disease activities index (DAI), colon length shortening, and colonic pathological damage. Exploration of the potential mechanisms demonstrated that naringin significantly activated DSS-induced PPARγ and subsequently suppressed NF-κB activation. PPARγ inhibitor GW9662 largely abrogated the roles of naringin in vitro. Moreover, DSS induced the activation of mitogen-activated protein kinase (MAPK) and (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome was inhibited by naringin. Tight junction (TJ) architecture in naringin groups was also maintained by regulating zonula occludens-1 (ZO-1) expression. These results suggested that naringin may be a potential natural agent for protecting mice from DSS-induced UC.

Oral administration of phloretin, mainly found in apples and strawberries, ameliorates ulcerative colitis in mice.

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