to dihydroxyeicosatrienoic acids. EETs are formed from arachidonic acid during myocardial ischemia and play a protective role against ischemic cell death. Deletion of sEH has been shown to be protective against myocardial ischemia in the isolated heart preparation. We tested the hypothesis that sEH inactivation by targeted gene deletion or pharmacological inhibition reduces infarct size (I) after regional myocardial ischemia-reperfusion injury in vivo. Male C57BL‫6گ‬J wildtype or sEH knockout mice were subjected to 40 min of left coronary artery (LCA) occlusion and 2 h of reperfusion. Wild-type mice were injected intraperitoneally with 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester (AUDA-BE), a sEH inhibitor, 30 min before LCA occlusion or during ischemia 10 min before reperfusion. 14,15-EET, the main substrate for sEH, was administered intravenously 15 min before LCA occlusion or during ischemia 5 min before reperfusion. The EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (EEZE) was given intravenously 15 min before reperfusion. Area at risk (AAR) and I were assessed using fluorescent microspheres and triphenyltetrazolium chloride, and I was expressed as I/AAR. I was significantly reduced in animals treated with AUDA-BE or 14,15-EET, independent of the time of administration. The cardioprotective effect of AUDA-BE was abolished by the EET antagonist 14,15-EEZE. Immunohistochemistry revealed abundant sEH protein expression in left ventricular tissue. Strategies to increase 14,15-EET, including sEH inactivation, may represent a novel therapeutic approach for cardioprotection against myocardial ischemia-reperfusion injury.14,15-epoxyeicosatrienoic acids; 12-(3-adamantan-1-yl-ureido)-dodecanoic acid butyl ester THE P-450 EPOXYGENASE PATHWAY metabolizes arachidonic acid into four biologically active eicosanoids, referred to as epoxyeicosatrienoic acids (5,6-, 8,9-, 11,12-, and 14,15-EET) (10). EETs play an important role in regulating tissue perfusion in both cardiac and extracardiac organs. The actions of EETs are terminated by conversion to dihydroxyeicosatrienoic acids (DHETs) by epoxide hydrolases (11). Two major epoxide hydrolases are found in mammalian tissues, the microsomal (mEH) and soluble epoxide hydrolases (sEH) (2). However, sEH is the primary enzyme involved in the in vivo metabolism of EETs (19). In addition to their vascular effects, EETs exhibit a cardioprotective effect, which has been linked to activation of the reperfusion injury salvage kinase pathway (18) and mediated in part through activation of the phosphatidylinositol 3-kinase/Akt pathway and the mitochondrial ATP-sensitive K ϩ channels (5, 15). Augmenting endogenously released EETs by inhibiting the converting enzyme sEH represents an attractive strategy to increase ischemic tolerance. Our laboratory has recently used this strategy to show that pharmacological inhibition (20) and gene deletion (21) are protective against experimental stroke in vivo. Similarly, using the isolated heart preparation, Seubert et al. (16) demonstrat...

The vertical composition distribution and crystallinity of photoactive layers are considered to have critical roles in photovoltaic performance. In this concise contribution, the layer-by-layer (LBL) solution process is used to fabricate efficient polymer solar cells. The results show that the vertical composition distribution can be finely regulated via employing solvent additive 1,8-diiodooctane (DIO). The favorable vertical component distribution in tandem with improved crystallinity induced by DIO contributes to the efficient exciton dissociation, charge transportation and extraction, and limited charge recombination loss. Therefore, the optimized LBL devices yield an efficiency of 16.5%, which is higher than that of the control bulk heterojunction solar cells with an efficiency of 15.8%. Importantly, the ternary solar cells based on PM6/ Y6:PC 71 BM LBL active layers demonstrate a promising efficiency of >17%, which is the record efficiency for LBL solar devices reported to date. These findings make clear that the solvent additive-assisted LBL solution process has broader implications for the further optimization of solar cells.

All-polymer solar cells (all-PSCs) are proven to possess outstanding thermal and mechanical stabilities. However, concurrently achieving appropriate phase-separated pattern, efficient charge transportation, and adequate charge transfer between donor and acceptor components is still a challenge, and thus, only a few polymer−polymer bulk heterojunction (BHJ) blends have yielded BHJ device power conversion efficiency (PCE) values of >8%. Generally, polymer backbone substitutions may have a direct influence on the device performance. Thus, this report examines a set of wide bandgap polymer donor analogues composed of thienothiophene (TT) or thiazolothiazole (TTz) motif, and their all-PSC device performance with N2200. Results show that all-PSCs based on the imine-substituted derivative PBDT-TTz exhibit PCE values as high as 8.4%, which largely outperform the analogue PBDT-TT-based ones with PCEs of only 0.7%. This work reveals that the imine substitution in polymer backbones of PBDT-TTz not only increases the ionization potential (IP) and electron affinity (EA), narrows the optical gap (E opt ), but also has significantly impacts on the BHJ film morphologies. PBDT-TTz:N2200 BHJ blends present better miscibility, suppressed phase separation, much stronger crystallinity, and face-on ordering, which contribute to efficient exciton dissociation, charge transportation, and therefore, high-efficiency in all-PSCs. This study demonstrates that the iminesubstituted polymers composed of TTz motif, which can be easily synthesized through a facile two-step procedure, are a promising class of wide-bandgap polymer donors for efficient all-PSCs.

The vertical composition distribution of a bulk heterojunction (BHJ) photoactive layer is known to have dramatic effects on photovoltaic performance in polymer solar cells. However, the vertical composition distribution evolution rules of BHJ films are still elusive. In this contribution, three BHJ film systems, composed of polymer donor PBDB-T, and three different classes of acceptor (fullerene acceptor PCBM, small-molecule acceptor ITIC, and polymer acceptor N2200) are systematically investigated using neutron reflectometry to examine how donor–acceptor interaction and solvent additive impact the vertical composition distribution. Our results show that those three BHJ films possess homogeneous vertical composition distributions across the bulk of the film, while very different composition accumulations near the top and bottom surface were observed, which could be attributed to different repulsion, miscibility, and phase separation between the donor and acceptor components as approved by the measurement of the donor–acceptor Flory–Huggins interaction parameter χ. Moreover, the solvent additive 1,8-diiodooctane (DIO) can induce more distinct vertical composition distribution especially in nonfullerene acceptor-based BHJ films. Thus, higher power conversion efficiencies were achieved in inverted solar cells because of facilitated charge transport in the active layer, improved carrier collection at electrodes, and suppressed charge recombination in BHJ solar cells.

In the present study, we investigated the role of tyrosine kinase, MAPK, and phosphatidylinositol 3-kinase (PI3K) signaling in ME-induced protection. Ca 2ϩ -tolerant, adult rabbit cardiomyocytes were isolated by collagenase digestion and subjected to simulated ischemia for 180 min. ME was administered 15 min before the 180 min of simulated ischemia; blockers were administered 15 min before ME. Cell death was assessed by trypan blue as a function of time. The epidermal growth factor receptor (EGFR) kinase inhibitor AG-1478 (250 nM) blocked ME-induced protection, but the inactive analog AG-9 (100 M) did not. Treatment with herbimycin (1 M) completely eliminated ME-induced protection. To verify that ME activates EGFR and to determine the involvement of Src, Western blotting of EGFR was performed after ME administration with and without herbimycin A. ME resulted in herbimycin-sensitive robust phosphorylation of EGFR at Tyr 992 and Tyr 1068 . Administration of the selective MAPK inhibitor PD-98059 (10 nM) and the specific MEK1/2 inhibitor U-0126 (10 M) also inhibited ME-induced cardioprotection. ME-induced ERK1/2 phosphorylation was significantly reduced by PD-98059, the EGFR kinase inhibitor PD-153035 (10 M), and chelerythrine (2 M). The PI3K inhibitor LY-294002 (20 M) abrogated ME-induced protection, and ME-induced Akt phosphorylation at Ser 473 was suppressed by LY-294002, PD-153035, and chelerythrine. We conclude that ME-induced cardioprotection is mediated via Src-dependent EGFR transactivation and activation of the PI3K and MAPK pathways.