The synthesis and dialkyl abstraction chemistry as well as the unusual cocatalytic characteristics in metallocene-mediated polymerization of two distinctive borane and aluminate cocatalysts tris(2,2‘,2‘‘-nonafluorobiphenyl)borane (PBB) and triphenyl carbenium tris(2,2‘,2‘‘-nonafluorobiphenyl)fluoroaluminate, (Ph3C+PBA-) are reported. Reaction of PBB with Cp‘2ThMe2 (Cp‘ = η5-C5Me5), CGCZrMe2 (CGC = Me2Si(η5-Me4C5)( t BuN)), and Cp‘MMe3 (M = Zr, Hf) cleanly affords base-free cationic complexes Cp‘2ThMe+MePBB- (1), CGCZrMe+MePBB- (5), and Cp‘MMe2 +MePBB- (M = Zr, 7; Hf, 8). In case of CGCTiMe2 and dimethyl zirconocenes, μ-methyl dinuclear cationic complexes [(CGCTiMe)2(μ-Me)]+MePBB- (6) and [(L2ZrMe)2(μ-Me)]+MePBB- (L = η5-C5H5 (Cp), 2; η5-1,2-Me2C5H3 (Cp‘‘), 3; Cp‘, 4; L2 = Me2Si(Ind)2, Ind = η5-C9H6, 9; L2 = Me2C(Flu)(Cp), Flu = η5-C13H8, 10) are formed. A similar reaction with Ph3C+PBA- results in the corresponding complexes CGCZrCH3 +PBA- (M = Zr, 19; Ti, 20) and L2ZrCH3 +PBA- (L = Cp, 15b; Cp‘‘, 16; η5-1,3-(SiMe2)2C5H3, 17; Cp‘, 18; L2 = Me2Si(Ind)2, 21; L2 = Me2C(Flu)(Cp), 22). Two dinuclear complexes 3 and 13 ([Me2C(Flu)(Cp)Zr(C6F5)]2(μ-F)+MeB(C6F5)3 -) derived from borane PBB and B(C6F5)3, respectively, and three other PBA--based monomeric complexes 14 (Ph3C+PBA-), 19, and 21 have been characterized by X-ray diffraction, and these determinations allow detailed analysis of the ion pairing in the solid state. In combination with solution dynamic NMR, all data indicate MePBB-−cation interactions to be considerably weaker than those involving MeB(C6F5)3 -, while the strongly ion-paired chiral PBA- converts previously enantiomeric cations into pairs of diastereomers. As revealed by dynamic 1H NMR studies, ion pair reorganization/symmetrization in 5 is significantly more rapid than in the MeB(C6F5)3 - analogue, suggesting much looser ion pairing in 5. On the other hand, PBA- racemization is a rapid process (e.g., ΔG ‡(58 °C) = 16.9(2) kcal/mol for 16), while cation−PBA- ion pairs have higher barriers for ion pair symmetrization than in analogous fluoroaryl borates. Dinuclear complexes 2 and 3 initiate efficient polymerization of methyl methacrylate (MMA) to produce syndiotactic poly(methyl methacrylate) (PMMA), while 9 produces highly isotactic PMMA, and sterically more accessible complexes 6 and 10 exhibit no activity. For olefin polymerization and copolymerization, PBB-derived cationic complexes, both monomeric and dinuclear, generally exhibit higher catalytic activity and comonomer incorporation levels than the MeB(C6F5)3 - analogues, with CGC catalysts exhibiting the greatest activity contrasts. On the other hand, PBA--derived complexes exhibit a remarkable sensitivity of olefin polymerization characteristics and ion pairing to ancillary ligand bulk, with activity differences of up to 106-fold observed. In regard to stereospecific polymerization, PBA--derived chiral complex 21 produces highly isotactic polypropylene while B(C6F5)4 --derived analogue produces isotactic polypropylene with lower i...

Hereditary cholestasis in childhood and infancy with normal serum gamma‐glutamyltransferase (GGT) activity is linked to several genes. Many patients, however, remain genetically undiagnosed. Defects in myosin VB (MYO5B; encoded by MYO5B) cause microvillus inclusion disease (MVID; MIM251850) with recurrent watery diarrhea. Cholestasis, reported as an atypical presentation in MVID, has been considered a side effect of parenteral alimentation. Here, however, we report on 10 patients who experienced cholestasis associated with biallelic, or suspected biallelic, mutations in MYO5B and who had neither recurrent diarrhea nor received parenteral alimentation. Seven of them are from two study cohorts, together comprising 31 undiagnosed low‐GGT cholestasis patients; 3 are sporadic. Cholestasis in 2 patients was progressive, in 3 recurrent, in 2 transient, and in 3 uncategorized because of insufficient follow‐up. Liver biopsy specimens revealed giant‐cell change of hepatocytes and intralobular cholestasis with abnormal distribution of bile salt export pump (BSEP) at canaliculi, as well as coarse granular dislocation of MYO5B. Mass spectrometry of plasma demonstrated increased total bile acids, primary bile acids, and conjugated bile acids, with decreased free bile acids, similar to changes in BSEP‐deficient patients. Literature review revealed that patients with biallelic mutations predicted to eliminate MYO5B expression were more frequent in typical MVID than in isolated‐cholestasis patients (11 of 38 vs. 0 of 13). Conclusion: MYO5B deficiency may underlie 20% of previously undiagnosed low‐GGT cholestasis. MYO5B deficiency appears to impair targeting of BSEP to the canalicular membrane with hampered bile acid excretion, resulting in a spectrum of cholestasis without diarrhea. (Hepatology 2017;65:1655‐1669).

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy. Long non‐coding RNAs (lncRNAs) are important regulators in pathological processes, yet their potential roles in PDAC are poorly understood. Here, we identify a fundamental role for a novel lincRNA, linc00511, in the progression of PDAC. Linc00511 levels in PDAC tissue specimens and cell lines were examined by quantitative real‐time PCR. Corresponding adjacent non‐neoplastic tissues were used as controls. The function of linc00511 in PDAC cell lines was determined by RNA interference approach in vitro and in vivo. Fluorescence in situ hybridization (FISH) was used to characterize linc00511 expression in PDAC cells. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were obtained from bioinformatic analysis, luciferase assays and RIP assays. The association between the linc00511/hsa‐miR29b‐3p axis and VEGFA was verified by Western blotting assay. Immunohistochemistry was performed to evaluate the expression of VEGFA in PDAC samples. The aberrant up‐regulation of linc00511 was detected in PDAC cell lines and patient specimens compared with controls. An increase in linc00511 expression indicates the adverse clinical pathological characteristics and poor prognosis. Functionally, linc00511 depletion in PDAC cells decreased proliferation, migration, invasion and endothelial tube formation. Mechanistically, linc00511 could up‐regulate VEGFA via its competing endogenous RNA (ceRNA) activity on hsa‐miR‐29b‐3p. In summary, our results define an important axis controlling proliferation, invasion and tumour angiogenesis in PDAC. Linc00511 is a novel lncRNA that plays a significant regulatory role in the pathogenesis and progression of PDAC. Thus, Linc00511 represents a new prognostic biomarker to predict clinical outcome of PDAC patients after surgery and may serve as a potential therapeutic target for PDAC treatment.

The binuclear "constrained geometry catalyst" (CGC) (mu-CH2CH2-3,3'){(eta5-indenyl )[1-Me2Si(tBuN)](ZrMe2)}2 [EBICGC(ZrMe2)2; Zr2] and the trityl bisborate dianion (Ph3C+)2[1,4-(C6F5)3BC6F4B(C6F5)3]2- (B2) have been synthesized to serve as new types of multicenter homogeneous olefin polymerization catalysts and cocatalysts, respectively. Additionally, the complex [1-Me2Si(3-ethylindenyl)(tBuN)]ZrMe2 (Zr1) was synthesized as a mononuclear control. For the bimetallic catalyst or bisborate cocatalyst, high effective local active site concentrations and catalyst center-catalyst center cooperative effects are evidenced by bringing the catalytic centers together via either covalent or electrostatic bonding. For ethylene homopolymerization at constant conversion, the branch content of the polyolefin products (primarily ethyl branches) is dramatically increased as catalyst or cocatalyst nuclearity is increased. Moreover, catalyst and cocatalyst nuclearity effects are approximately additive. Compared to the catalyst derived from monometallic Zr1 and monofunctional Ph3C+B(C6F5)4- (B1), the active catalyst derived from bimetallic Zr2 and bifunctional B2 produces approximately 11 times more ethyl branches in ethylene homopolymerization via a process which is predominantly intradimer in character. Moreover, approximately 3 times more 1-hexene incorporation in ethylene + 1-hexene copolymerization and approximately 4 times more 1-pentene incorporation in ethylene + 1-pentene copolymerization are observed for Zr2 + B2 versus Zr1 + B1.