Ischemic stroke is a debilitating clinical disorder that affects millions of people, yet lacks effective neuroprotective treatments. Fish oil is known to exert beneficial effects against cerebral ischemia. However, the underlying protective mechanisms are not fully understood. The present study tests the hypothesis that omega-3 polyunsaturated fatty acids (n-3 PUFAs) attenuate ischemic neuronal injury by activating nuclear factor E2-related factor 2 (Nrf2) and upregulating heme oxygenase-1 (HO-1) in both in vitro and in vivo models. We observed that pretreatment of rat primary neurons with docosahexaenoic acid (DHA) significantly reduced neuronal death following oxygen-glucose deprivation. This protection was associated with increased Nrf2 activation and HO-1 upregulation. Inhibition of HO-1 activity with tin protoporphyrin IX attenuated the protective effects of DHA. Further studies showed that 4-hydroxy-2E-hexenal (4-HHE), an end-product of peroxidation of n-3 PUFAs, was a more potent Nrf2 inducer than 4-hydroxy-2E-nonenal derived from n-6 PUFAs. In an in vivo setting, transgenic mice overexpressing fatty acid metabolism-1, an enzyme that converts n-6 PUFAs to n-3 PUFAs, were remarkably resistant to focal cerebral ischemia compared with their wild-type littermates. Regular mice fed with a fish oil-enhanced diet also demonstrated significant resistance to ischemia compared with mice fed with a regular diet. As expected, the protection was associated with HO-1 upregulation, Nrf2 activation, and 4-HHE generation. Together, our data demonstrate that n-3 PUFAs are highly effective in protecting the brain, and that the protective mechanisms involve Nrf2 activation and HO-1 upregulation by 4-HHE. Further investigation of n-3 PUFA neuroprotective mechanisms may accelerate the development of stroke therapies.

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An electrochemical sensor was developed for attomolar Hg 2+ detection. Three single-stranded DNA probes were rationally designed for selective and sensitive detection of the target, which combined T-Hg 2+ -T coordination chemistry and the characteristic of convenient modification of electrochemical signal indicator. Graphene and nanoAu were successively electrodeposited on a glass carbon electrode surface to improve the electrode conductivity and functionalize with the 10-mer thymine-rich DNA probe (P1). NanoAu carriers functionalised with 29-mer guanine-rich DNA probe (P3) labeled methyl blue (MB-nanoAu-P3s) were used to further strengthen signal response. In the presence of Hg 2+ , a T-T mismatched dsDNA would occur between P1 and a 22-mer thymine-rich DNA probe (P2) on the electrode surface due to T-Hg 2+ -T coordination chemistry. Followed by adding the MB-nanoAu-P3s for hybridization with P2, square wave voltammetry was executed. Under optimal conditions, Hg 2+ could be detected in the range from 1.0 aM to 100 nM with a detection limit of 0.001 aM. Selectivity measurements reveal that the sensor is specific for Hg 2+ even with interference by high concentrations of other metal ions. Three different environmental samples were analyzed by the sensor and the results were compared with that from an atomic fluorescence spectrometry.The developed sensor was demonstrated to achieve excellent detectability. It may be applied to development of ultrasensitive detection strategies.Mercury is a heavy metal known for its severe effects on human health and the environment owning to its neurotoxicity and physiological toxicity. 1,2 The annual total global mercury emission from nature and human activities is approximately 7500 tons per year. 3Increasing efforts are being made to understand mercury distribution and pollution to address mercury exposure and improve public health. 4,5 Thus, many methods have been developed for mercury detection, including inductively coupled plasma mass spectrometry, 6 atomic absorption/emission spectroscop, 7 cold vapor atomic fluorescence spectrometry, 8 high-performance liquid chromatography, 9 ion chromatography, 10 and sensing strategy. [11][12][13][14][15][16][17][18][19][20][21] Although no one method has proven to be superior, sensing strategy is often reported due to its tremendous versatility. It negates the use of sophisticated instrumentation and complicated sample preparation process. In the last decade, mercury-sensing strategies based on thymine-Hg 2+ -thymine (T-Hg 2+ -T) coordination chemistry and the resulting Hg 2+ -stabilized hybridization of oligonucleotides with T-T mismatches have been developed rapidly. Indeed, since the specific recognition ability of Hg 2+ using T-T base pairs in DNA duplexes was observed, 11 several strategies for the detection of Hg 2+ , based upon electrochemistry, 12,13 fluorescence, 14,15 colorimetry, 16,17 photoelectrochemistry, 18,19 surface plasmon resonance, 20 and surface resonance Raman scattering 21 have been developed. The application of ...

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