Epidemiological and preclinical studies indicate that polyphenol intake from moderate consumption of red wines may lower the relative risk for developing Alzheimer's disease (AD) dementia. There is limited information regarding the specific biological activities and cellular and molecular mechanisms by which wine polyphenolic components might modulate AD. We assessed accumulations of polyphenols in the rat brain following oral dosage with a Cabernet Sauvignon red wine and tested brain-targeted polyphenols for potential beneficial AD disease-modifying activities. We identified accumulations of select polyphenolic metabolites in the brain. We demonstrated that, in comparison to vehicle-control treatment, one of the brain-targeted polyphenol metabolites, quercetin-3-O-glucuronide, significantly reduced the generation of β-amyloid (Aβ) peptides by primary neuron cultures generated from the Tg2576 AD mouse model. Another brain-targeted metabolite, malvidin-3-O-glucoside, had no detectable effect on Aβ generation. Moreover, in an in vitro analysis using the photo-induced cross-linking of unmodified proteins (PICUP) technique, we found that quercetin-3-O-glucuronide is also capable of interfering with the initial protein-protein interaction of Aβ(1-40) and Aβ(1-42) that is necessary for the formation of neurotoxic oligomeric Aβ species. Lastly, we found that quercetin-3-O-glucuronide treatment, compared to vehicle-control treatment, significantly improved AD-type deficits in hippocampal formation basal synaptic transmission and long-term potentiation, possibly through mechanisms involving the activation of the c-Jun N-terminal kinases and the mitogen-activated protein kinase signaling pathways. Brain-targeted quercetin-3-O-glucuronide may simultaneously modulate multiple independent AD disease-modifying mechanisms and, as such, may contribute to the benefits of dietary supplementation with red wines as an effective intervention for AD.

Here we introduce a new synthetic approach to grow mesoporous silica thin films with vertical mesochannels on centimeter-sized substrates via an oil-induced co-assembly process. Adding an oil, i.e., decane, into a CTAB-EtOH-TEOS ammonia solution leads to thin-film formation of mesoporous silica of controlled thickness between 20 and 100 nm with vertical mesochannels on various surfaces. The vertical mesoporous channels were evidenced by grazing incidence small-angle X-ray scattering (GISAXS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) characterizations. Decane played two roles: (a) as a pore expansion agent (up to 5.7 ± 0.5 nm) and (b) inducing vertically oriented hexagonal mesophases of micelle-silica composite. The production of periodic and vertical nanochannels is very robust, over many different substrate surfaces (from silicon to polystyrene), various silica precursors (TEOS, fumed silica, or zeolite seed), and many oils (decane, petroleum ether, or ethyl acetate). This wide robustness in the formation of vertical nanophases is attributed to a unique mechanism of confined synthesis of surfactant-silicate between two identical thin layers of oils on a substrate.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol, and Concord grape juice extract), with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ) mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ)-induced long term potentiation (LTP) deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

Organic nonvolatile transistor memory devices of the n-type semiconductor N,N'-bis(2-phenylethyl)-perylene-3,4:9,10-tetracarboxylic diimide (BPE-PTCDI) were prepared using various electrets (i.e., three-armed star-shaped poly[4-(diphenylamino)benzyl methacrylate] (N(PTPMA)3) and its blends with 6,6-phenyl-C61-butyric acid methyl ester (PCBM), 6,13-bis(triisopropylsilylethynyl)pentacene (TIPS-pen) or ferrocene). In the device using the PCBM:N(PTPMA)3 blend electret, it changed its memory feature from a write-once-read-many (WORM) type to a flash type as the PCBM content increased and could be operated repeatedly based on a tunneling process. The large shifts on the reversible transfer curves and the hysteresis after implementing a gate bias indicated the considerable charge storage in the electret layer. On the other hand, the memory characteristics showed a flash type and a WORM characteristic, respectively, using the donor/donor electrets TIPS-pen:N(PTPMA)3 and ferrocene:N(PTPMA)3. The variation on the memory characteristics was attributed to the difference of energy barrier at the interface when different types of electret materials were employed. All the studied memory devices exhibited a long retention over 10(4) s with a highly stable read-out current. In addition, the afore-discussed memory devices by inserting another electret layer of poly(methacrylic acid) (PMAA) between the BPE-PTCDI layer and the semiconducting blend layer enhanced the write-read-erase-read (WRER) operation cycle as high as 200 times. This study suggested that the energy level and charge transfer in the blend electret had a significant effect on tuning the characteristics of nonvolatile transistor memory devices.

We present an antibody-free approach for the high-purity and high-throughput dielectrophoretic (DEP) isolation of circulating tumour cells (CTCs) from blood in a microfluidic chip. A hydrodynamic sheath flow is designed upstream in the chip to direct the suspension samples to the channel side walls, thus providing a queue to allow DEP-induced lateral displacements. High-throughput continuous cancer cell sorting (maximum flow rate: ~2.4 mL h(-1), linear velocity: ~4 mm s(-1)) is achieved with a sustained 3D lateral DEP (LDEP) particle force normal to the continuous through-flow. This design allows the continuous fractionation of micro/nanosized particles into different downstream subchannels based on the differences in their different critical negative DEP strengths/mobilities. The main advantage of this separation strategy is that increasing the channel length can effectively increase the throughput proportionally. The effective separation of rare cancer cells (<0.001%) from diluted human blood in a handheld chip is demonstrated. An enrichment factor of 10(5) and a recovery rate of ~85% from a 0.001% cancer cell sample are achieved at an optimal flow rate of 20 μL min(-1) passing through a 6 cm long LDEP channel with an appropriate voltage at a frequency of 10 kHz. A higher throughput of 2.4 mL h(-1) is also achieved with a 13 cm long metal-based microchannel.