Total Syntheses and In Vivo Quantitation of Novel Neurofuran and Dihomo‐isofuran Derived from Docosahexaenoic Acid and Adrenic Acid

Neurofurans (NeuroFs) and dihomo‐isofurans (dihomo‐IsoFs) are produced in vivo by non‐enzymatic free‐radical pathways from docosahexaenoic and adrenic acids, respectively. As these metabolites are produced in minute amounts, their analyses in biological samples remain challenging. Syntheses of neurofuran and dihomo‐isofurans described are based on a pivotal strategy, thanks to an enantiomerically enriched intermediate, which allowed, for the first time, access to both families: the alkenyl and enediol. Owing to this formation, quantitation of specific NeuroF and dihomo‐IsoFs in biological samples was attainable.     

In vivo longitudinal Myelin Water Imaging in rat spinal cord following dorsal column transection injury

Longitudinal Myelin Water Imaging was carried out in vivo to characterize white matter damage following dorsal column transection (DC Tx) injury at the lumbar level L1 of rat spinal cords. A transmit–receive implantable coil system was used to acquire multiple spin-echo (MSE) quantitative T2 data from the lumbar spinal cords of 16 rats at one week pre-injury as well as 3 and 8 weeks post-injury (117 microns in-plane resolution and 1.5 mm slice thickness). In addition, ex vivo MSE and DTI data were acquired from cords fixed and excised at 3 or 8 weeks post injury using a solenoid coil. The MSE data were used to generate Myelin Water Fractions (MWFs) as a surrogate measure of myelin content, while DTI data were acquired to study damage to the axons. Myelin damage was assessed histologically with Eriochrome cyanine (EC) and Myelin Basic Protein in degenerated myelin (dgen-MBP) staining, and axonal damage was assessed by neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining. These MRI and histological measures of injury were studied in the dorsal column at 5 mm cranial and 5 mm caudal to injury epicenter. MWF increased significantly at 3 weeks post-injury at both the cranial and caudal sites, relative to baseline. The values on the cranial side of injury returned to baseline at 8 weeks post-injury but remained elevated on the caudal side. This trend was found in both in vivo and ex vivo data. This MWF increase was likely due to the presence of myelin debris, which were cleared by 8 weeks on the cranial, but not the caudal, side. Both EC and dgen-MBP stains displayed similar trends. MWF showed significant correlation with EC staining (R = 0.63, p = 0.005 in vivo and R = 0.74, p = 0.0001 ex vivo). MWF also correlated strongly with the dgen-MBP stain, but only on the cranial side (R = 0.64, p = 0.05 in vivo; R = 0.63, p = 0.038 ex vivo). This study demonstrates that longitudinal MWI in vivo can accurately characterize white matter damage in DC Tx model of injury in the rat spinal cord.     

A Convenient Method for the Synthesis of Alkenes from Vic-diols via Cyclic Sulfates with Magnesium Iodide

Reaction of cyclic sulfates of vic-diols with magnesium iodide in acetonitrile produced the corresponding olefins in excellent isolated yields at room temperature. Cyclic sulfates of trans-diols gave trans-alkenes exclusively. Cyclic sulfates of cis-diols gave a mixture of cis- and trans- alkenes. However, the cyclic sulfate of cyclic cis-diol afforded the corresponding cis-alkene only.     

Microfluidic synthesis of tail‐shaped alginate microparticles using slow sedimentation

This study reports the synthesis of tail‐shaped alginate particles using a microfluidic platform combined with a sedimentation strategy. By utilizing microfluidic emulsification in the cross‐junction channel, the formation of regular droplets was achieved. Following a facile and convenient sedimentation process and an ionic crosslinking process, sodium‐alginate droplets became tail‐shaped and then gradually developed into calcium‐alginate microparticles. The effects of the concentration of the CaCl₂ crosslinker and the viscosity of the alginate solution on the shape and/or size of the particles were further investigated. The proposed synthesis methodology has the advantages of actively controlling the tail‐shape formation, having a narrow size distribution, as well as being a facile and convenient process with a high throughput. This approach can be applied to many applications in the pharmaceutical and biomedical arena.     

The Chaperone‐like Activity and Structure of Mutant H119G of Rat Lens αB‐crystallin: A Study of Divalent Metal Ion Binding Site

The molecular chaperone αB‐crystallin, the major player in maintaining the transparency of the eye lens, preventing the aggregation of stress‐damaged and aging lens proteins from aggregation. In nonlenticular cells, it is involved in various neurological diseases, diabetes, and cancer. The role of some metal ions in the αB‐crystallin biology has been reported. Theoretical calculations have proposed that the coordination sites involving His101, His119, Lys121, His18 and Glu99 of human αB‐crystallin were the binding sites for divalent metal ions. Our previous mutagenesis study suggested that His18 rat lens αB‐crystallin is a crucial binding site for Cu(II) and Zn(II) in terms of chaperone‐like activity and structure. In this study mutant H119G of rat lens αB‐crystalin was cloned and expressed to investigate whether His119 is the coordination binding site. Copper and zinc at 1 mM concentration significantly increase the chaperone‐like activity in wild type αB‐crystalin, whereas zinc, copper and magnesium at 1 mM reduced the activity of H119G significantly. The results from chaperone‐like activity, ANS fluorescence measurement and Far‐and Near‐UV CD studies suggest that the replacement of His119 with Glycine resulted in a conformational and minor environmental changes that decrease chaperone‐like activity in the presence of divalent ions suggested that His119 was a crucial binding site for Cu(II) and Zn(II), which was similar to our previous study results of His18. Both results together suggest that His18 and His119 coordinates each other for the binding site of Cu(II) and Zn(II) in terms of improving the chaperone‐like activity and stability of crystallin/metal ion complex.     

Effective synthesis of cyclic peptide yunnanin C and analogues via Ser/Thr ligation (STL)-mediated peptide cyclization

Cyclic peptide yunnanin C isolated from the root of Stellaria yunnanensis was efficiently synthesized in which the linear peptide was prepared by Boc-SPPS and the cyclization was realized by serine/threonine ligation (STL)-mediated cyclization. In addition, nine yunnanin C analogues, including mutations of Tyr7Gly, Tyr7Val, Tyr7Pro, Tyr7Phe, Ser1Thr, Pro2Val, Gly5Pro, Phe6Ala and Ile4Ala, were prepared in the same fashion. Here, we demonstrated that STL-mediated peptide cyclization could be an effective approach to construct cyclic peptides. Except that proline at the C-terminus could retard the cyclization process, cyclization of yunnanin C analogues with various C-terminal amino acids proceeded with fast cyclization rate (<4 h) and only trace amount of dimers (<5%) at a working concentration of 5 mM.     

Synthesis,Discovery, and Quantitation of Dihomo‐Isofurans: Biomarkers for In Vivo Adrenic Acid Peroxidation

The growing importance of lipidomics, and the interest of non‐enzymatic metabolites of polyunsaturated fatty acids (PUFAs) prompted us to initiate the synthesis of novel dihomo‐IsoF compounds. Such metabolites of adrenic acid, the main PUFA in white matter, were synthesized using a divergent approach based on an orthoester cyclization. LC‐MS/MS investigation on pig brains showed the potential of this novel biomarker for the first time, as a powerful new tool for brain lipid peroxidation assessment.     

New D‐A‐A’‐Configured Small Molecule Donors Employing Conjugation to Red‐shift the Absorption for Photovoltaics

Four new donor‐acceptor‐acceptor’ (D‐A‐A’)‐configured donors, CPNT , DCPNT , CPNBT , and DCPNBT equipped with naphtho[1,2‐c:5,6‐c′]bis([1,2,5]‐thiadiazole) (NT) or naphtho[2,3‐c][1,2,5]thiadiazole (NBT) as the central acceptor (A) unit bridging triarylamine donor (D) and cyano or dicyanovinylene acceptor (A’), were synthesized and characterized. All molecules exhibit bathochromic absorption shifts as compared to those of the benzothiadiazole (BT)‐based analogues owing to improved electron‐withdrawing and quinoidal character of NT and NBT cores that lead to stronger intramolecular charge transfer. Favorable energy level alignments with C₇₀, together with the good thermal stability and the antiparallel dimeric packing render CPNT and DCPNT suitable donors for vacuum‐processed organic photovoltaics (OPV)s. OPVs based on DCPNT : C₇₀ active layers displayed the best power conversion efficiency (PCE)=8.3%, along with an open circuit voltage of 0.92 V, a short circuit current of 14.5 mA cm^?2 and a fill factor of 62% under 1 sun intensity, simulated AM1.5G illumination. Importantly, continuous light‐soaking with AM 1.5G illumination has verified the durability of the devices based on CPNT :C₇₀ and DCPNT : C₇₀ as the active blends. The devices were examined for their feasibility of indoor light harvesting under 500 lux illumination by a TLD‐840 fluorescent lamp, giving PCE=12.8% and 12.6%, respectively. These results indicate that the NT‐based D‐A‐A’‐type donors CPNT and DCPNT are potential candidates for high‐stability vacuum‐processed OPVs suitable for indoor energy harvesting.     

Extending the intensity model with joint defaults to incorporate the lasting effects from common credit events

This paper studies how the lasting effects of common credit events influence default probability distribution and the prices of multiname credit derivatives. Based on a joint defaults model where common credit events are used to generate simultaneous defaults, we extend the model to allow for their impacts to last for a longer while. The default intensity of each entity is heightened significantly while the impact still has an influence, until some time later when this effect fades away. Incorporating these lasting effects helps to generate higher default correlation, which is more consistent with today's highly correlated financial markets. The proposed model can be either formulated as a Markov chain or implemented by Monte Carlo simulation in order to calculate the default probability distributions and multiname derivatives prices. Our numerical results demonstrate the strong influences from the lasting effects and provide a justification of their incorporation.