Steroid-associated hip joint collapse in bipedal emus

In this study we established a bipedal animal model of steroid-associated hip joint collapse in emus for testing potential treatment protocols to be developed for prevention of steroid-associated joint collapse in preclinical settings. Five adult male emus were treated with a steroid-associated osteonecrosis (SAON) induction protocol using combination of pulsed lipopolysaccharide (LPS) and methylprednisolone (MPS). Additional three emus were used as normal control. Post-induction, emu gait was observed, magnetic resonance imaging (MRI) was performed, and blood was collected for routine examination, including testing blood coagulation and lipid metabolism. Emus were sacrificed at week 24 post-induction, bilateral femora were collected for micro-computed tomography (micro-CT) and histological analysis. Asymmetric limping gait and abnormal MRI signals were found in steroid-treated emus. SAON was found in all emus with a joint collapse incidence of 70%. The percentage of neutrophils (Neut %) and parameters on lipid metabolism significantly increased after induction. Micro-CT revealed structure deterioration of subchondral trabecular bone. Histomorphometry showed larger fat cell fraction and size, thinning of subchondral plate and cartilage layer, smaller osteoblast perimeter percentage and less blood vessels distributed at collapsed region in SAON group as compared with the normal controls. Scanning electron microscope (SEM) showed poor mineral matrix and more osteo-lacunae outline in the collapsed region in SAON group. The combination of pulsed LPS and MPS developed in the current study was safe and effective to induce SAON and deterioration of subchondral bone in bipedal emus with subsequent femoral head collapse, a typical clinical feature observed in patients under pulsed steroid treatment. In conclusion, bipedal emus could be used as an effective preclinical experimental model to evaluate potential treatment protocols to be developed for prevention of ON-induced hip joint collapse in patients

Visualization 1.mp4

particle dynamics of 1 micron beads in the uncorrected and corrected vortice

Stiched Raw Images 1

27 serial 2D coronal section images stitched from raw microscopic images with strong negative staining background covering Pnmt-Cre/ChR2 mouse heart

Processed Images

The stitched raw images were analysed and rigidly registered. The pixels in the images were classified as positive/negative staining based on intensity. Down-sampling was applied multiple times to reduce the size of the images

Stitched Raw Images 2

21 serial 2D coronal section images stitched from raw microscopic images with weak negative staining background covering Pnmt-Cre/ChR2 mouse heart

Mechanistic Insights into the Directed Hydrogenation of Hydroxylated Alkene Catalyzed by Bis(phosphine)cobalt Dialkyl Complexes

The mechanism of directed hydrogenation of hydroxylated alkene catalyzed by bis­(phosphine)cobalt dialkyl complexes has been studied by DFT calculations. The possible reaction channels of alkene hydrogenation catalyzed by catalytic species (<b>0</b>_<b>T</b>, <b>0</b>_<b>P</b>, and <b>0</b>) were investigated. The calculated results indicate that the preferred catalytic activation processes undergo a 1,2 alkene insertion. <b>0</b>_<b>P</b> and <b>0</b> prefer the β hydrogen elimination mechanism with an energy barrier of 9.5 kcal/mol, and <b>0</b>_<b>T</b> prefers the reductive elimination mechanism with an energy barrier of 11.0 kcal/mol. The second H₂ coordination in the σ bond metathesis mechanism needs to break the agostic H²–βC bond of metal–alkyl intermediates (<b>2</b>_<b>1P</b> and <b>2</b>_<b>1T</b>), which owns the larger energetic span compared to the reductive elimination. This theoretical study shows that the most favorable reaction pathway of alkene hydrogenation is the β hydrogen elimination pathway catalyzed by the planar (dppe)­CoH₂. The hydrogenation activity of Co­(II) compounds with redox-innocent phosphine donors involves the Co(0)–Co­(II) catalytic mechanism

DFT Mechanistic Study on Alkene Hydrogenation Catalysis of Iron Metallaboratrane: Characteristic Features of Iron Species

The variable coordination geometries, multiple spin states, and high density of states of first row transition metals offer a new frontier in the catalytic chemistry. A DFT study has been performed in order to unveil these characteristic features of iron metallaboratrane complex in alkene hydrogenation. A detailed spin-state analysis reveals there exist two minimum energy crossing points in the formation of (TPB)­(μ-H)­Fe­(H) <b>3</b>^{<b>triplet</b>} from (TPB)­Fe­(N₂) <b>1</b>^{<b>triplet</b>}. In the catalytic cycle, <b>3</b>^{<b>triplet</b>} at triplet state plays a role of active species, and the hydrogenation at triplet state is more favorable than that at singlet state. The dissociation of phosphine arm of TPB ligand from Fe center occurs easily in the triplet state, because the antibonding dσ is singly occupied in <b>3</b>^{<b>triplet</b>}. However, a nondissociative pathway without any phosphine ligand dissociation is not likely to occur. The product is formed via the σ-bond metathesis between a dihydrogen molecule and a Fe-styryl moiety. The usual direct reductive elimination involving bridging hydride (μ-H) is very difficult because the μ-H is strongly bonded with Fe and B atoms

Mechanistic Studies on the Carboxylation of Hafnocene and <i>ansa</i>-Zirconocene Dinitrogen Complexes with CO₂

A DFT study on the carboxylation of hafnocene and <i>ansa</i>-zirconocene dinitrogen complexes with CO₂ indicates that the most favorable initial CO₂ insertion into M–N (M = Hf, Zr) proceeds by a stepwise path rather than a concerted [2 + 2] path. The calculated results explain the regioselectivity of the N–C formation in experiments. In addition, a comparative analysis of ring tension and charge distribution unveils the different activities of N–N bond cleavage in the CO and CO₂ direct N–C bond formation reactions

Unique catalytic activities and scaffolding of p21 activated kinase-1 in cardiovascular signaling

P21 activated kinase-1 (Pak1) has diverse functions in mammalian cells. Although a large number of phosphoproteins have been designated as Pak1 substrates from in vitro studies, emerging evidence has indicated that Pak1 may function as a signaling molecule through a unique molecular mechanism - scaffolding. By scaffolding, Pak1 delivers signals through an auto-phosphorylation-induced conformational change without transfer of a phosphate group to its immediate downstream effector(s). Here we review evidence for this regulatory mechanism based on structural and functional studies of Pak1 in different cell types and research models as well as in vitro biochemical assays. We also discuss the implications of Pak1 scaffolding in disease-related signaling processes and the potential in cardiovascular drug development

Homolytic or Heterolytic Dihydrogen Splitting with Ditantalum/Dizirconium Dinitrogen Complexes? A Computational Study

Transition metal complexes play a key role in creating efficient molecular catalysis processes leading to the ammonia production from earth-abundant dinitrogen. It is indispensable to examine the mechanism and influence of transition metal complexes on dinitrogen hydrogenation. In this paper, the mechanism of the dinitrogen hydrogenation triggered by bimetallic complexes [L₂M]₂(μ-η²:η²-N₂) (M = Ta and Zr, L = Sita-type or Chirik-type ligand) is investigated by density functional theory calculation. Our results show that the side-on ditantalum dinitrogen complex with Sita-type ligands favors the pathway of homolytic dihydrogen splitting when hydrogenation products are generated. However, the dihydrogen splitting switches to the heterolytic pathway as the dominant mechanism when Zr is the metal center. The ditantalum dinitrogen complex undergoes hydrogenation much easier from the side-on coordination mode than the side-on-end-on mode with Sita-type or Chirik-type ligands. With these findings from the computational study, this work identifies that different metal centers and coligands (Sita-type or Chirik-type) in different binding modes (side-on-end-on or side-on bridged) dictate the pathway of dihydrogen cleavage triggered by the bimetallic complexes. This work should provide insights on factors impacting the dinitrogen hydrogenation process and shed light on designing new transition metals and ligands for dinitrogen hydrogenation catalysts in the future