Ni-catalyzed arylation of alkynes with organoboronic acids and aldehydes to access stereodefined allylic alcohols.

A new, efficient and practical method for the three-component arylative coupling of aldehydes, alkynes and arylboronic acids has been developed through nickel catalysis. This transformation provides diverse Z-selective tetrasubstituted allylic alcohols without the use of any aggressive oragnometallic nucleophiles or reductants. Moreover, benzylalcohols are viable coupling partners via oxidation state manipulation and arylative coupling in one single catalytic cycle. This reaction features a direct and flexible approach for the preparation of stereodefined arylated allylic alcohols with broad substrate scope under mild conditions. The utility of this protocol is demonstrated through the synthesis of diverse biologically active molecular derivatives.

miR-24 protects against ischemia-induced brain damage in rats via regulating microglia polarization by targeting Clcn3.

Microglia and macrophages play important roles in ischemic brain injury. Changes in their M1/M2 polarization phenotypes significantly impact disease progression. The M2 microglia/macrophages are anti-inflammatory and have a protective effect against ischemic injury. The microRNA 24 (miR-24) promotes M2 macrophage polarization and suppresses inflammation. We tested the hypothesis that miR-24 is protective in ischemic brain injury by regulating microglia polarization. We treated rats with miR-24 inhibitor or mimic and subsequently subjected the rats to middle cerebral artery occlusion (MCAO) to induce ischemic brain injury. Neurological deficit and infarct volume were analyzed. Microglia and macrophages were assessed by fluorescence-activated cell sorting. Microglia polarization was determined by genes specific for M1 and M2 both in vivo and in BV-2 cells. The effect of miR-24 target Clcn3 on microglia polarization was examined. We found that miR-24 inhibition aggravated MCAO induced damage, while miR-24 overexpression alleviated brain injury by suppressing microglia/macrophage infiltration. miR-24 suppressed M1 and promoted M2 microglia polarization both in vivo and in vitro. Finally, we showed that miR-24 targeted Clcn3 to regulate microglia polarization. Our study indicates that miR-24 plays a neuroprotective role by promoting anti-proinflammatory microglia polarization during ischemic brain injury.

The Accumulated Response of Deciduous Liquidambar formosana Hance and Evergreen Cyclobalanopsis glauca Thunb. Seedlings to Simulated Nitrogen Additions.

Nitrogen depositions in the Yangtze River Delta have is thought to shift the coexistence of mixed evergreen and deciduous species. In this study, the seedlings of the dominant evergreen species Cyclobalanopsis glauca Thunb. and the deciduous species Liquidambar formosana Hance from the Yangtze River Delta were chosen to test their responses to simulated N additions using an ecophysiological approach. N was added to the tree canopy at rates of 0 (CK), 25 kg N ha-1 year-1 (N25), and 50 kg N ha-1 year-1 (N50). The leaf N content per mass (N m, by 44.03 and 49.46%) and total leaf chlorophyll content (Chl, by 72.15 and 63.63%) were enhanced for both species, and C. glauca but not L. formosana tended to allocate more N to Chl per leaf area (with a higher slope). The enhanced N availability and Chl promoted the apparent quantum yield (AQY) significantly by 15.38 and 43.90% for L. formosana and C. glauca, respectively. Hydraulically, the increase in sapwood density (ρ) for L. formosana was almost double that of C. glauca. Synchronous improved sapwood specific hydraulic conductivity (K S, by 37.5%) for C. glauca induced a significant reduction in stomatal conductance (g s) (p < 0.05) in the N50 treatments, which is in contrast to the weak varied g s accompanied by a 59.49% increase in K S for L. formosana. As a result, the elevated maximum photosynthesis (A max) of 12.19% for L. formosana in combination with the increase in the total leaf area (indicated by a 37.82% increase in the leaf area ratio-leaf area divided by total aboveground biomass) ultimately yielded a 34.34% enhancement of total biomass. In contrast, the A max and total biomass were weakly promoted for C. glauca. The reason for these distinct responses may be attributed to the lower water potential at 50% of conductivity lost (P 50) for C. glauca, which enables higher hydraulic safety at the cost of a weak increase in Amax due to the stomatal limitation in response to elevated N availability. Altogether, our results indicate that the deciduous L. formosana would be more susceptible to elevated N availability even if both species received similar N allocation.

TGF-ß/Smads Signaling Affects Radiation Response and Prolongs Survival by Regulating DNA Repair Genes in Malignant Glioma.

To understand the molecular mechanism underlying the causal relationship between aberrant upregulation of transforming growth factor beta (TGF-ß) and radio-resistance in glioma. The mouse glioma cell GL261 was irradiated, and relative expression of TGF-ß/Smad signaling genes was determined by real-time PCR and western blotting. The DNA repair response on exogenous TGF-ß or LY2109761 was evaluated by quantification of diverse genes by real-time PCR and western blotting. Xenograft mice were employed for in vivo investigation to assess the response to irradiation and LY2109761 either alone or in combination. The expression of DNA repair genes was further determined in the xenograft tumor. The TGF-ß/Smad signaling pathway was activated by radiation in the GL261 cell line. The exogenous complement of TGF-ß significantly stimulated DNA repair response. Administration of LY2109761 suppressed DNA repair genes. Simultaneous treatment with LY2109761 abrogated the upregulation of DNA repair genes in GL261. In the xenograft tumor model, LY2109761 synergistically improved the therapeutic effect of radiation via improvement of sensitivity. Our data suggested that LY2109761 treatment re-sensitized glioma to radiation via antagonizing TGF-ß/Smad-induced DNA repair.