Direct Addition of Amides to Glycals Enabled by Solvation-Insusceptible 2-Haloazolium Salt Catalysis

The direct 2‐deoxyglycosylation of nucleophiles with glycals leads to biologically and pharmacologically important 2‐deoxysugar compounds. Although the direct addition of hydroxyl and sulfonamide groups have been well developed, the direct 2‐deoxyglycosylation of amide groups has not been reported to date. Herein, we show the first direct 2‐deoxyglycosylation of amide groups using a newly designed Brønsted acid catalyst under mild conditions. Through mechanistic investigations, we discovered that the amide group can inhibit acid catalysts, and the inhibition has made the 2‐deoxyglycosylation reaction difficult. Diffusion‐ordered two‐dimensional NMR spectroscopy analysis implied that the 2‐chloroazolium salt catalyst was less likely to form aggregates with amides in comparison to other acid catalysts. The chlorine atom and the extended π‐scaffold of the catalyst played a crucial role for this phenomenon. This relative insusceptibility to inhibition by amides is more responsible for the catalytic activity than the strength of the acidity

Time-Dependent Springback of Various Sheet Metals: An Experimental Study

In the present study, draw-bending tests were conducted to investigate the effects of holding time at the bottom dead center (holding-time dependency) and elapsed time after releasing from dies (elapsed-time dependency) on springback in steel, Al alloy, Mg alloy, and CP-Ti sheets experimentally. The amount of springback decreased with increasing the holding time, irrespective of the material. The decreasing amounts from the holding time of 5 min to 600 min were 29%, 11%, 8.1%, and 5.7% respectively for the Mg alloy, CP-Ti, Al alloy, and steel sheets. On the contrary to previous studies, it was presumed from simple analyses that the holding-time dependency would presumably be explained in terms of not only stress relaxation but also unloading behavior following stress relaxation. The amount of springback gradually increased with the elapsed time regardless of the material. The amounts of increase from just after releasing from dies were approximately 5.9% for one month in the CP-Ti sheet, 4.1% for 1.5 months in the Al alloy sheet, 1.6% for 1.5 months in the Mg alloy sheet, and 1.1% for 1.5 months in the steel sheet. This magnitude relationship was different from that of creep strains, indicating that the mechanism of the elapsed-time dependency could not be explained only from the creep behavior and there would be other factors that affect the elapsed-time dependency

Direct N-Glycofunctionalization of Amides with Glycosyl Trichloroacetimidate by Thiourea/Halogen Bond Donor Co-Catalysis

This article also appears in: European Symposium on Organic Chemistry 2019Using a halogen bond (XB) donor and Schreiner's thiourea as cooperative catalysts, various amides, including the asparagine residues of several peptides, were directly coupled with glycosyl trichloroacetimidates to give unique N‐acylorthoamides in good yields. Synthetic applications of N‐acylorthoamides, including rearrangement to the corresponding β‐N‐glycoside, were also demonstrated

Effect of Functional Electrical Stimulation of the Gluteus Medius during Gait in Patients following a Stroke

Many stroke patients rely on cane or ankle-foot orthosis during gait rehabilitation. The purpose of this study was to investigate the immediate effect of functional electrical stimulation (FES) to the gluteus medius (GMed) and tibialis anterior (TA) on gait performance in stroke patients, including those who needed assistive devices. Fourteen stroke patients were enrolled in this study (mean poststroke duration: 194.9±189.6 d; mean age: 72.8±10.7 y). Participants walked 14 m at a comfortable velocity with and without FES to the GMed and TA. After an adaptation period, lower-limb motion was measured using magnetic inertial measurement units attached to the pelvis and the lower limb of the affected side. Motion range of angle of the affected thigh and shank segments in the sagittal plane, motion range of the affected hip and knee extension-flexion angle, step time, and stride time were calculated from inertial measurement units during the middle ten walking strides. Gait velocity, cadence, and stride length were also calculated. These gait indicators, both with and without FES, were compared. Gait velocity was significantly faster with FES (p=0.035). Similarly, stride length and motion range of the shank of the affected side were significantly greater with FES (stride length: p=0.018; motion range of the shank: p=0.026). Meanwhile, cadence showed no significant difference (p=0.238) in gait with or without FES. Similarly, range of motion of the affected hip joint, knee joint, and thigh did not differ significantly depending on FES condition (p=0.115‐0.529). FES to the GMed and TA during gait produced an improvement in gait velocity, stride length, and motion range of the shank. Our results will allow therapists to use FES on stroke patients with varying conditions

Pharmacological Inhibition of miR-130 Family Suppresses Bladder Tumor Growth by Targeting Various Oncogenic Pathways via PTPN1

Previously, we have revealed that the miR-130 family (miR-130b, miR-301a, and miR-301b) functions as an oncomiR in bladder cancer. The pharmacological inhibition of the miR-130 family molecules by the seed-targeting strategy with an 8-mer tiny locked nucleic acid (LNA) inhibits the growth, migration, and invasion of bladder cancer cells by repressing stress fiber formation. Here, we searched for a functionally advanced target sequence with LNA for the miR-130 family with low cytotoxicity and found LNA #9 (A(L)^i^i^A(L)^T(L)^T(L)^G(L)^5(L)^A(L)^5(L)^T(L)^G) as a candidate LNA. LNA #9 inhibited cell growth in vitro and in an in vivo orthotopic bladder cancer model. Proteome-wide tyrosine phosphorylation analysis suggested that the miR-130 family upregulates a wide range of receptor tyrosine kinases (RTKs) signaling via the expression of phosphorylated Src (pSrcTyr416). SILAC-based proteome analysis and a luciferase assay identified protein tyrosine phosphatase non-receptor type 1 (PTPN1), which is implicated as a negative regulator of multiple signaling pathways downstream of RTKs as a target gene of the miR-130 family. The miR-130-targeted LNA increased and decreased PTPN1 and pSrcTyr416 expressions, respectively. PTPN1 knockdown led to increased tumor properties (cell growth, invasion, and migration) and increased pSrcTyr416 expression in bladder cancer cells, suggesting that the miR-130 family upregulates multiple RTK signaling by targeting PTPN1 and subsequent Src activation in bladder cancer. Thus, our newly designed miR-130 family targeting LNA could be a promising nucleic acid therapeutic agent for bladder cancer