Neuroprotection of N-benzyl Eicosapentaenamide in Neonatal Mice Following Hypoxic–Ischemic Brain Injury

Maca (Lepidium meyenii) has emerged as a popular functional plant food because of its medicinal properties and nutritional value. Macamides, as the exclusively active ingredients found in maca, are a unique series of non-polar, long-chain fatty acid N-benzylamides with multiple bioactivities such as antifatigue characteristics and improving reproductive health. In this study, a new kind of macamide, N-benzyl eicosapentaenamide (NB-EPA), was identified from maca. We further explore its potential neuroprotective role in hypoxic–ischemic brain injury. Our findings indicated that treatment with biosynthesized NB-EPA significantly alleviates the size of cerebral infarction and improves neurobehavioral disorders after hypoxic–ischemic brain damage in neonatal mice. NB-EPA inhibited the apoptosis of neuronal cells after ischemic challenge. NB-EPA improved neuronal cell survival and proliferation through the activation of phosphorylated AKT signaling. Of note, the protective property of NB-EPA against ischemic neuronal damage was dependent on suppression of the p53–PUMA pathway. Taken together, these findings suggest that NB-EPA may represent a new neuroprotectant for newborns with hypoxic–ischemic encephalopathy.     

Design,Synthesis, and Evaluation of Dihydropyranopyrazole Derivatives as Novel PDE2 Inhibitors for the Treatment of Alzheimer’s Disease

Phosphodiesterase 2 (PDE2) has been regarded as a novel target for the treatment of Alzheimer’s disease (AD). In this study, we obtained (R)-LZ77 as a hit compound with moderate PDE2 inhibitory activity (IC₅₀ = 261.3 nM) using a high-throughput virtual screening method based on molecular dynamics. Then, we designed and synthesized 28 dihydropyranopyrazole derivatives as PDE2 inhibitors. Among them, compound (+)-11h was the most potent PDE2 inhibitor, with an IC₅₀ value of 41.5 nM. The molecular docking of PDE2-(+)-11h reveals that the 4-(trifluoromethyl)benzyl)oxyl side chain of the compound enters the H-pocket and forms strong hydrophobic interactions with L770/L809/F862, which improves inhibitory activity. The above results may provide insight for further structural optimization of highly potent PDE2 inhibitors and may lay the foundation for their use in the treatment of AD.     

Copper Nanoparticles In鄄Situ Anchored on Nitrogen鄄Doped Carbon for High鄄Efficiency Oxygen Reduction Reaction Electrocatalyst北大核心CSCD

Compared with noble metal platinum (Pt)-based catalysts, inexpensive non-noble metal electrocatalysts have attracted extensive attention for oxygen reduction reaction (ORR). Herein, chitosan as a kind of biomass resource rich in nitrogen and carbon was used to prepare nitrogen-doped carbon (N-C) and N-C in-situ anchored by copper nanoparticles (Cu/N-C). The as-obtained N-C and Cu/N-C nanoparticles were successfully used as non-noble eletrocatalysts tested for ORR. Compared with the N-C, the Cu/N-C showed the high surface area of 607.3 m2窑g-1 with the mean pore size of 2.5 nm and the pore volume of 0.40 cm3窑g-1. The most positive Gibbs free energy change was the rate determining step for ORR process with the 4e mechanism, where the value of the Cu (111)/N-C(-0.39 eV) was lower than that of the N-C(-0.26 eV). The Cu/N-C exhibited superior onset and half-wave potentials (0.96 V and 0.84 V, respectively) in alkaline media (0.1 mol窑L-1 KOH), all of which are much better than those measured for N-C and commercial Pt/C. Furthermore, the Cu/N-C showed superior methanol crossover avoidance and oxygen reduction stability. © 2021 Authors. All rights reserved.     

Amorphous Carbon Film with Self-modified Carbon Nanoparticles Synthesized by Low Temperature Carbonization of Phenolic Resin for Simultaneous Sensing of Dopamine and Uric Acid

A self-modified film electrode consisting of homogeneous snowflake-shaped nanoparticles on the amorphous carbon substrate (HNAC) was prepared by low temperature carbonization of phenolic resin. Such a unique structure was beneficial to enhance the electroanalysis signal responds. Simultaneous detection of DA and UA was performed on the HNAC using differential pulse voltammetry (DPV) at pH 8 phosphate buffer. The well-defined oxidation peak potential separation reached 260 mV between DA and UA. Meanwhile, the detection limit of HNAC were 0.401 μM (DA) and 2.800 μM (UA).     

Growth and optical properties of Pr<Superscript>3+</Superscript>:KLu(WO<Subscript>4</Subscript>)<Subscript>2</Subscript> laser crystal: a candidate for red emission laser

A Pr³⁺:KLu(WO₄)₂ crystal with dimension of 30 × 30 × 15 mm³ was grown in the K₂W₂O₇ flux. A slice was cut from the crystal, and the polarized absorption and fluorescence spectra were measured at room temperature. Based on the J-O theory, the oscillator intensity parameters Ω _t (t = 2, 4, 6), spontaneous emission probabilities and branch ratios were estimated and good results had been obtained. Furthermore, the crystal has a relatively large emission cross-section in the region of 615–630 nm with the highest value of 14.5 × 10^?20 cm², which indicates that the crystal is good for the application in red emission laser. The emission decay time for ¹D₂ and ³P₀ multiplets was discussed. By adapting the I-H model to fit the emission decay curves, the lifetime for ¹D₂ at 607 nm and ³P₀ at 615 nm are 19.72 μs and 8.95 μs, respectively. Then the corresponding fluorescence quantum efficiencies of the two multiplets reach 83.7 % and 87.9 %, respectively. All the studies illustrate that this crystal is potential in red emission laser application.     

High-throughput screening against $$\sim $$6.1 million structurally diverse,lead-like compounds to discover novel ROCK inhibitors for cerebral injury recovery

Rho-associated protein kinase (ROCK) has been recognized as an attractive therapeutic target to promote neurogenesis, neuroregeneration, and neurorecovery after cerebral injury. Here, a high-throughput screening protocol was described to discover novel ROCK inhibitors from a large chemical library containing \(\sim \)6.1 million structurally diverse, lead-like compounds. The protocol employed empirical rules such as ADMET evaluation and chemical similarity analysis to exclude those of drug-unlike candidates, and then molecular docking and binding affinity predictions were performed to suggest few promising candidates with high scores. Consequently, five compounds were successfully identified to have satisfactory activity profile with \(\hbox {IC}_{50}\) values at nanomolar level. In order to elucidate the molecular mechanism of inhibitor binding to target, the complex structures of ROCK kinase domain with the five identified compounds were modeled and examined in detail. A number of polar chemical forces such as hydrogen bonds and cation-\(\pi \) interactions as well as nonpolar contacts such as \(\pi \)–\(\pi \) stacking and hydrophobic forces were revealed at the complex interface, conferring high affinity and strong specificity to inhibitor binding. In addition, several key residues around the kinase active site, including Val90, Lys105, Asn203, and Phe368, were found to play an important role in binding.     

Observation of two resonant structures in e+ e- -->pi+ pi- psi(2S) via initial-state radiation at Belle

The cross section for e+ e- --> pi+ pi- psi(2S) between threshold and sqrt[s]=5.5 GeV is measured using 673 fb(-1) of data on and off the Upsilon(4S) resonance collected with the Belle detector at KEKB. Two resonant structures are observed in the pi+ pi- psi(2S) invariant-mass distribution, one at 4361 +/- 9 +/- 9 MeV/c2 with a width of 74 +/- 15 +/- 10 MeV/c2, and another at 4664 +/- 11 +/- 5 MeV/c2 with a width of 48 +/- 15 +/- 3 MeV/c2, if the mass spectrum is parametrized with the coherent sum of two Breit-Wigner functions. These values do not match those of any of the known charmonium states.     

Metallic state in cubic FeGe beyond its quantum phase transition

We report on results of electrical resistivity and structural investigations on the cubic modification of FeGe under high pressure. The long-wavelength helical order (T(C) = 280 K) is suppressed at a critical pressure p(c) approximately 19 GPa. An anomaly at T(X)(p) and strong deviations from a Fermi-liquid behavior in a wide pressure range above p(c) suggest that the suppression of T(C) disagrees with the standard notion of a quantum critical phase transition. The metallic ground state persisting at high pressure can be described by band-structure calculations if zero-point motion is included. The shortest FeGe interatomic distance display discontinuous changes in the pressure dependence close to the T(C)(p) phase line.