Background:The nature of endoplasmic reticulum (ER) stress in chronic pancreatitis (CP) is not known. Results: ER stress is activated early, independently of trypsinogen activation, and remains sustained in CP. Conclusion: Pathologic ER stress activation may be a novel pathogenic mechanism of CP. Significance: ER stress is a key event independent of the traditional central event of pancreatitis-trypsinogen activation.

BACKGROUND & AIMS Experimental studies in acute pancreatitis (AP) suggest strong association of acinar cell injury with cathepsin-B dependent intracellular activation of trypsin. However, the molecular events subsequent to trypsin activation and their role, if any, in cell death have not been studied. In this study, we have explored, for the first time, intra-acinar events downstream of trypsin activation which lead to acinar cell death. METHODS Acinar cells prepared from the pancreas of rats or mice (wild-type, trypsinogen-7 or cathepsin-B deleted) were stimulated with supramaximal caerulein and cytosolic activity of cathepsin-B and trypsin was evaluated. Permeabilzed acini were used to understand the differential role of cytosolic trypsin vs cytosolic cathepsin-B in activation of apoptosis. Cell death was evaluated by measuring specific markers for apoptosis and necrosis. RESULTS Both in vitro and in vivo studies suggest that during AP cathepsin-B leaks into the cytosol from co-localized organelles, through a mechanism dependent on active trypsin. Cytosolic cathepsin-B but not trypsin activates the intrinsic pathway of apoptosis through cleavage of bid and activation of bax. Finally, excessive release of cathepsin-B into the cytosol can lead to cell death through necrosis. CONCLUSIONS This is the first report which defines the role of trypsin in AP and demonstrates that cytosolic cathepsin-B but not trypsin activates cell death pathways. This is also the first report to suggest that trypsin is requisite for AP only because it causes release of cathepsin-B into the cytosol.

Morphine treatment worsens the severity of acute pancreatitis and delays resolution and regeneration. Considering our results, the safety of morphine for analgesia during acute pancreatitis should be re-evaluated in future human studies.

An efficient orange‐light‐emitting polymer (PFTO‐BSeD5) has been developed through the incorporation of low‐bandgap benzoselenadiazole (BSeD) moieties into the backbone of a blue‐light‐emitting polyfluorene copolymer (PFTO poly{[9,9‐bis(4‐(5‐(4‐tert‐butylphenyl)‐[1,3,4]‐oxadiazol‐2‐yl)phenyl)‐9′,9′‐di‐n‐octyl‐[2,2′]‐bifluoren‐7,7′‐diyl]‐stat‐[9,9‐bis(4‐(N,N‐di(4‐n‐butylphenyl)amino)phenyl)‐9′,9′‐di‐n‐octyl‐[2,2′]‐bifluoren‐7,7′‐diyl]}) that contains hole‐transporting triphenylamine and electron‐transporting oxadiazole pendent groups. A polymer light‐emitting device based on this copolymer exhibits a strong, bright‐orange emission with Commission Internationale de L'Eclairage (CIE) color coordinates (0.45,0.52). The maximum brightness is 13 716 cd m–2 and the maximum luminance efficiency is 5.53 cd A–1. The use of blends of PFTO‐BSeD5 in PFTO leads to efficient and stable white‐light‐emitting diodes—at a doping concentration of 9 wt %, the device reaches its maximum external quantum efficiency of 1.64 % (4.08 cd A–1). The emission color remains almost unchanged under different bias conditions: the CIE coordinates are (0.32,0.33) at 11.0 V (2.54 mA cm–2, 102 cd m–2) and (0.31,0.33) at 21.0 V (281 mA cm–2, 7328 cd m–2). These values are very close to the ideal CIE chromaticity coordinates for a pure white color (0.33,0.33).

[reaction: see text] A series of carbazole/fluorene (CBZm-Fn) hybrids were effectively synthesized through Friedel-Crafts-type substitution of the carbazole rings. These compounds were thermally and morphologically stable host materials for OLED applications. Efficient blue phosphorescent OLEDs were obtained when employing CBZ1-F2 as the host and FIrpic as the guest.

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Aurora kinases have emerged as attractive targets for the design of anticancer drugs. Through structure-based virtual screening, novel pyrazole hit 8a was identified as Aurora kinase A inhibitor (IC(50) = 15.1 microM). X-ray cocrystal structure of 8a in complex with Aurora A protein revealed the C-4 position ethyl carboxylate side chain as a possible modification site for improving the potency. On the basis of this insight, bioisosteric replacement of the ester with amide linkage and changing the ethyl substituent to hydrophobic 3-acetamidophenyl ring led to the identification of 12w with a approximately 450-fold improved Aurora kinase A inhibition potency (IC(50) = 33 nM), compared to 8a. Compound 12w showed selective inhibition of Aurora A kinase over Aurora B/C, which might be due to the presence of a unique H-bond interaction between the 3-acetamido group and the Aurora A nonconserved Thr217 residue, which in Aurora B/C is Glu and found to sterically clash with the 3-acetamido group in modeling studies.

We have synthesized three novel distyrylcarbazole derivatives for use as simultaneously hole-transporting and light-emitting layers in blue light-emitting diodes. Each compound, which contains a rigid carbazole core and two 2,2-diphenylvinyl end groups substituted through either the 3,6-or the 2,7-position, forms films satisfactorily and exhibits a blue emission with its PL maximum in the range 459-470 nm. Photophysical measurements indicate that twisting of the adjacent C-C bonds in the 3,6-position of the carbazole core in dilute solutions causes an efficient nonradiative relaxation to occur, yielding a much smaller quantum yield for fluorescence in 3,6-linked carbazoles. As intense emissions of 2,7-linked carbazoles are observed, such deactivation from an excited-state is inefficient therein. Electrochemical studies revealed that incorporation of the carbazole core increased the HOMO energy effectively; this feature facilitates hole injection. These distyrylcarbazole derivatives are promising bifunctional, blue-emitting, holetransporting molecules for use in simple double-layer devices of a general structure ITO/emitting layer/TPBI/Mg : Ag, in which TPBI-1,3,5-tris(N-phenylbenzimidazol-2-yl)benzene-serves as a hole-blocking and electron-transporting material. The devices prepared using 2,7distyrylcarbazole as the emitter produced bright blue emissions having activating voltages below 3.0 V. A DPVTCz-based device attained a luminance efficiency of 3.11 cd A 21 at 5 V, a brightness of 3062 cd m 22 , and CIE color coordinates of (0.14, 0.22).