Electrophilic C(sp2)-H Cyanation with Inorganic Cyanate (OCN-) by PIII/PV=O-Catalyzed Phase Transfer Activation.

An organophosphorus redox-catalyzed method for the direct electrophilic cyanation of C(sp2)-H nucleophiles with sodium cyanate (NaOCN) is reported. The catalytic deoxyfunctionalization of the OCN- anion is enabled by the use of a small-ring phosphacyclic (phosphetane) catalyst in combination with a terminal hydrosilane O-atom acceptor and a malonate-derived bromenium donor. In situ spectroscopy under single-turnover conditions demonstrate that insoluble inorganic cyanate anion is activated by bromide displacement on a bromophosphonium catalytic intermediate to give a reactive N-bound isocyanatophosphonium ion, which delivers electrophilic "CN+" equivalents to nucleophilic (hetero)arenes and alkenes with loss of a phosphine oxide. These results demonstrate the feasibility of deoxyfunctionalization of insoluble inorganic salts by PIII/PV=O catalyzed phase transfer activation.

Glycolysis characteristics of intracellular polysaccharides from Agaricus bitorquis (Quél.) sacc. Chaidam and its effects on intestinal flora from different altitudes of mice in vitro fermentation.

The glycolysis characteristics and effects on intestinal flora of polysaccharides from Agaricus bitorquis (Quél.) Sacc. Chaidam (ABIPs) in vitro fermentation by different altitudes of mice feces was examined, including low, medium, and high altitudes groups (LG, MG, and HG). In vitro, fermentation of ABIPs forty-eight hours resulted in a remarkable decrease in total sugar content and improvement of short-chain fatty acids (SCFAs) (mainly acetate, propionate, and butyrate), which simultaneously induced the composition of monose and uronic acids and SCFAs continuously change. Besides, ABIPs influenced the abundance and composition of the intestinal flora, generally increasing the abundance of probiotic bacteria (such as Bifidobacterium and Faecalibacterium) and decreasing the abundance of harmful bacteria (such as Phenylobacterium and Streptococcus) in all groups, with the highland biology core genus Blautia significantly enriched in LG and MG groups. It was also found that ABIPs enhanced pathways associated with biosynthesis and metabolism. In addition, correlation analysis speculated that the metabolism of SCFAs by ABIPs may be associated with genera such as Anaerostipes, Roseburia, and Weissella. ABIPs may protect organismal health by regulating hypoxic intestinal flora composition and metabolic function, and more superior fermentation performance was observed in MG compared to other groups.

Mechanism of Enhanced Triplet-Triplet Upconversion in Organic Molecules.

We use time-dependent density functional theory (TDDFT) to investigate the mechanism of efficient triplet-triplet upconversion (TTU) in certain organic materials. In particular, we focus on materials where some singlets are generated in a two-step spin-nonconserving process (T1 + T1 → T2 → S1). For this mechanism to contribute significantly, the intersystem crossing (ISC) from the high-lying triplet to the singlet (T2 → S1) must outcompete the internal conversion (IC) to the low-lying triplet (T2 → T1). By considering multiple families of materials, we show that the T2 → S1 ISC can be enhanced in a number of ways: the substitution of electron-donating (ED) and electron-withdrawing (EW) groups at appropriate positions; the substitution of bulky groups that distort the molecular geometry; and the substitution of heavy atoms that enhance the spin-orbit coupling (SOC). In the first two cases, the enhancements are consistent with El-Sayed's rule in that rapid T2 → S1 ISC requires significant differences in the characters of the S1 and the T2 wavefunctions. Together, these effects enable a wide tunability of T2 → S1 ISC rates over at least 5 orders of magnitude. Meanwhile, the T2 → T1 IC is inhibited in these systems due to the large T2 - T1 energy gap >0.5 eV, which entails a high energy barrier to the T2 → T1 IC and the prediction of a slow rate regardless of the substituents or the presence of heavy atoms. In this way, tuning the T2 → S1 ISC appears to provide an effective strategy to achieve systematic improvement of TTU materials.

Tandem C/N-Difunctionalization of Nitroarenes: Reductive Amination and Annulation by a Ring Expansion/Contraction Sequence.

A synthetic method for the reductive transformation of nitroarenes into ortho-aminated and -annulated products is reported. The method operates via the exhaustive deoxygenation of nitroarenes by an organophosphorus catalyst and a mild terminal reductant to access aryl nitrenes, which after ring expansion, are trapped by amine nucleophiles to give dearomatized 2-amino-3H-azepines. Treatment of these ring-expanded intermediates with acyl electrophiles triggers 6π electrocyclization to extrude the nitrogen atom and restore aromaticity of the phenyl ring, which delivers via C-H functionalization 2-aminoanilide and benzimidazole products.

Inhibition of Ubiquitin-Specific Protease-13 Improves Behavioral Performance in Alpha-Synuclein Expressing Mice.

Ubiquitin-Specific Protease-13 (USP13) promotes protein de-ubiquitination. USP13 levels are upregulated in post-mortem Parkinson's disease, whereas USP13 knockdown via shRNA reduces alpha-synuclein levels in animal models. We studied the role of USP13 in knockout mice expressing lentiviral human alpha-synuclein and investigated the impact of a small molecule inhibitor of USP13, BK50118-C, on alpha-synuclein pathology and animal behavior. Alpha-synuclein was expressed unilaterally in substantia nigra (SN) of USP13 deficient mice that were treated with a daily intraperitoneal injection of 100 mg/kg BK50118-C or DMSO for four consecutive weeks, and behavioral and functional assays were performed. Wild-type USP13+/+ mice expressing lentiviral human alpha-synuclein showed motor and behavioral defects that were not seen in partially (USP13+/-) or completely (USP13-/-) deficient USP13 mice. BK50118-C displayed a wide and favorable therapeutic dose range in vivo. Treatment with BK50118-C significantly reduced ubiquitinated alpha-synuclein, increased dopamine levels, and improved motor and behavioral symptoms in wild-type (USP13+/+), but not USP13 deficient, mice. These data suggest that USP13 is critical to the neuropathology of alpha-synuclein, whereas a novel small molecule inhibitor of USP13 is a potential therapeutic agent of alpha-synucleinopathies.

Combination of Phase Matching and Phase-Reversal Approaches for Thermal Damage Assessment by Second Harmonic Lamb Waves.

It is known that measurement and extraction of the tiny amplitude of second harmonic Lamb waves are the main difficulties for practical applications of the nonlinear Lamb wave technique. In this study, phase-reversal approaches and phase matching technique are combined to build up the second-harmonic generation (SHG) of Lamb waves. A specific Lamb wave mode pair, which satisfied phase matching conditions, is selected to ensure the generation of cumulative second harmonic waves. Lamb wave signals with the same frequency but in reverse phase, propagating in the given specimen, are added together to counteract the fundamental waves, and simultaneously to enhance the signals of the second harmonic generated. The obtained results show that the phase-reversal approach can enhance the signals of second harmonic Lamb waves, and effectively counteract that of the fundamental waves. The approach is applied to assess the thermal-induced material degradation in the stainless steel plates. Distinctions of the acoustic nonlinearity parameters under different degraded levels are clearly shown in an improved repeatable and reliable manner, while those of linear wave velocity in the specimens are neglectable. The experimental investigations performed indicate that the proposed approach can be taken as a promising alternative for assessment of material degradation in its early stages.

Inhibition of prostate cancer cell growth in vivo with short hairpin RNA targeting SATB1.

Despite previous advances, the treatment options for prostate cancer remain limited. For the purposes of gene knockdown, the utility of RNA interference has been demonstrated and is considered to have therapeutic potential. In the present study, a short hairpin RNA (shRNA) was used to assess the effect of special AT-rich sequence binding protein (SATB1) downregulation on the growth and metastatic potential of prostate cancer in xenograft nude mice. A plasmid carrying shRNA targeting SATB1, pSilencer-SATB1-shRNA, was successfully engineered. Using this plasmid, significant downregulation of SATB1 mRNA and protein expression in the DU145 prostate cancer cells was observed. pSilencer-SATB1-shRNA was demonstrated to be markedly efficacious against prostate cancer xenografts in nude mice. These results may lead to a novel method of improving gene therapy efficacy against prostate cancer via regulating the function of SATB1.