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Aging is a primary risk factor for neurodegenerative diseases, such as Alzheimer's disease (AD). SIRT2, an NAD+(nicotinamide adenine dinucleotide)-dependent deacetylase, accumulates in the aging brain. Here, we report that, in the amyloid precursor protein (APP)/PS1 transgenic mouse model of AD, genetic deletion of SIRT2 or pharmacological inhibition of SIRT2 ameliorates cognitive impairment. We find that suppression of SIRT2 enhances acetylation of APP, which promotes non-amyloidogenic processing of APP at the cell surface, leading to increased soluble APP-α (sAPPα). We discover that lysines 132 and 134 of the major pathogenic protein β-amyloid (Aβ) precursor are acetylated and that these residues are deacetylated by SIRT2. Strikingly, exogenous expression of wild-type or an acetylation-mimic APP mutant protects cultured primary neurons from Aβ42 challenge. Our study identifies SIRT2-mediated deacetylation of APP on K132 and K134 as a regulated post-translational modification (PTM) and suggests inhibition of SIRT2 as a potential therapeutic strategy for AD. [Display omitted] • SIRT2 interacts with and deacetylates the highly conserved N terminus of APP • SIRT2 inhibition promotes APP non-amyloidogenic processing at the cell surface • Acetylation of APP-K132/134 is neuroprotective in cultured hippocampal neurons • SIRT2 inhibition improves cognitive deficiency in Alzheimer's disease mouse model Bai et al. show that SIRT2, a sirtuin deacetylase, interacts with the high-affinity ligand E1 domain of APP. Inhibition of SIRT2 has beneficial effects in APP/PS1 mice by maintaining acetylation of APP on the K132 and K134 residues, promoting production of neuroprotective sAPPα. [ABSTRACT FROM AUTHOR]

Organic anodes for K-storage have attracted much attention because of high theoretical capacity, low cost and extensive natural resource although facing serious dissolving issues with conventional electrolytes and persistent capacity decay. Therefore, 2-methylimidazole (mIm), an imidazolium-based small molecule restricted with high electronic conductivity carbon nanotubes (mIm/CNTs) is applied for potassium-ion batteries (PIBs). Furthermore, this as-prepared anode is accompanied to the potassium bis(fluorosulfonyl)imide (KFSI)-ethylene carbonate (EC) and diethyl carbonate (DEC) electrolytes (KFSI/EC + DEC) with modifiable solvation structures. At current density of 50 mA g−1, the mIm/CNTs composite coupled with the optimized 3 mol L−1 KFSI/EC + DEC electrolyte provides an average reversible capacity of 240 mAh g−1 (composites) with coulombic efficiency (CE) of 99.5 %. After 500 cycles, a high sustained capacity of 200 mAh g−1 (composites) is attained at 200 mA g−1. This enhanced K-storage performance of mIm/CNTs in 3 mol L−1 KFSI/EC + DEC electrolyte can be attributed to distinctive solvation structure, which is dominated by contact ion pairs (CIPs) and aggregates (AGGs). This structure intensively mitigates dissolution issues and greatly promotes K+ reaction kinetics. This work emphasizes the significance of electrolyte regulation for organic anodes and will supply a comprehensive appreciating of electrochemistry performance for advanced energy storage systems. A novel mIm/CNTs anode, fabricated via restricting mIm with high electronic conductivity carbon nanotubes (CNTs), exhibited a high average reversible capacity of 240 mAh g−1 (composites) at 50 mA g−1 with a high coulombic efficiency (CE) up to 99.5 %, and maintained 200 mAh g−1 (composites) after 500 cycles at 200 mA g−1 (99.3 % of CE) in 3 M KFSI/EC + DEC electrolyte, demonstrating the superior electrochemical performance with enhanced capacity and cycle life when compared with previous organic anode potassium-ion batteries. [Display omitted] • A novel imidazolium-based molecule is proposed as K-storage anode. • An optimized ester-based electrolyte is matched with the organic anode. • Superior capacity of 240 mAh g−1 after 200 cycles at 50 mA g−1 is achieved. • Enhanced properties are attributed to electrolyte regulation. [ABSTRACT FROM AUTHOR]

• Species-specific second-order rate constants between IMD and PMS/PDS were determined. • Over 100 transformation products of IMD in the degradation by PMS/PDS were identified. • Five dominant reaction pathways for the degradation of IMD by PMS/PDS were proposed. • Transformation products of IMD with PMS/PDS showed lower bioconcentration factors. • The removal performance of six neonicotinoid insecticides by PMS/PDS was compared. Neonicotinoid insecticides (NNIs), which have been detected across diverse aquatic environments, have sparked substantial concerns regarding their potential adverse ecological and health risks. In this study, the removal of NNIs by unactivated peroxymonosulfate (PMS) and peroxydisulfate (PDS) was systematically investigated. Results showed that PMS/PDS direct oxidation is mainly responsible for the degradation of imidacloprid (IMD), and the degradation kinetics can be well described by a second-order kinetics model, first-order in both IMD and PMS/PDS concentration. The species-specific reaction rate constants of HSO 5 − and SO 5 2− with IMD were calculated to be 429.36 ± 15.41 M−1h−1 and 9.72 ± 35.48 M−1h−1, while the corresponding rate constant between S 2 O 8 2- and IMD is 25.04 ± 3.04 M−1h−1. Over 100 transformation products in the degradation of IMD by PMS/PDS were identified by HPLC/Q-Orbitrap HRMS, and five major reaction pathways were proposed thereafter: hydroxylation on imidazolidine ring, olefin reaction on imidazolidine ring, desnitro reaction on nitroguanidine moiety, and two chain-breaking reactions between imidazolidine ring and chloro-pyridyl moiety. Toxicity evaluation on the transformation products found that their ecotoxicity is various at a wide range with an overall indeterminacy, while their bioconcentration factors show a definite decrease. The reactivity of six NNIs with PMS/PDS was found varied by structures but generally low, indicating that in-situ oxidation with unactivated PMS/PDS is safe but inefficiency for the mitigation of NNIs. It is thus suggested that further investigations into activated PMS/PDS systems involving radicals promise enhanced remediation of NNIs, and fundamental data in this study has laid the groundwork. [Display omitted] [ABSTRACT FROM AUTHOR]

Five bioactive dehydroabietylamine Schiff-base derivatives ( L 1 -L 5 ) had been synthesized from Dehydroabietylamine ( L 0 ), and the complex Cu(L 1 ) 2 had been obtained from the compound L 1 and copper(II) acetate. Their activities against Hela (cervix), MCF-7 (breast), A549 (lung), HepG2 (liver) and HUVEC (umbilical vein, normal cell) in vitro were investigated. The toxicity of L 1 -L 5 and Cu(L 1 ) 2 was all lower than L 0 . For MCF-7 cell, L 1 , L 3 , L 4 , L 5 and Cu(L 1 ) 2 had higher antitumor activity than L 0 . The smallest IC 50 value was 2.58  μ M of L 5 . For A549 cell, the IC 50 value of the compound L 4 was smaller than L 0 , which indicated that the compound L 4 had higher anti-A549 activity than L 0 . For HepG2 cell, the IC 50 value of L 4 ( 0.24  μ M) and L 5 (0.14  μ M) were much smaller than L 0 , which suggested L 4 and L 5 had higher anti-HepG2 activity. L 5 was 180 times more effective at inhibiting cultured HepG2 cells survival than normal cells, with average IC 50 values of 0.14 and 25.56  μ M. Furthermore, L 0 , L 4 and L 5 contrasting with Doxorubicin had been measured with the ability to induce apoptosis. It turned out that L 4 and L 5 could induce more HepG2 cells apoptosis, which suggested they may be potential antitumor drugs. [ABSTRACT FROM AUTHOR]

Modified graphite (MG) with rough edges and reduced crystal particles is developed via ball-milling treatment for commercializable K-storage anode. Importantly, rational electrolyte regulation significantly improves the reaction dynamics as well as reversibility of potassiation/depotassiation behaviors, resulting into a high and stable reversible capacity of 277 mA h g−1 at 200 mA g−1 after 250 cycles in the optimized 3 M KFSI/EC + DEC electrolyte. The enhanced K+-solvents interaction with aggregates (AGGs)-rich solvated structures is revealed to be responsible for the excellent K-storage performance. Furthermore, electrolyte flammability evaluation confirms the remarkably suppressed flammability of the optimized 3 M KFSI/EC + DEC, providing enough security for practical applications of PIBs. [Display omitted] • A commercial-based modified graphite has been simply developed. • A reversible capacity of 300 mAh g−1 with 0.017% per cycle decline is achieved. • Improved reaction kinetics by electrolyte regulation was responsible for K-storage. • The non-inflammability of the optimized electrolyte was enhanced. [ABSTRACT FROM AUTHOR]

Herein, we report a practical and efficient fluorosulfonylation of the various alkenes with sulfonyl radical sources (RSO 2 NHNH 2) and Et 3 N·3HF as cost-effective fluorination reagents under mild conditions. Remarkably, this protocol features very green and sustainable conditions obviating the need of chemical oxidants and transition metal catalyst. A variety of substituents on both sulfonyl hydrazides and alkenes are tolerated to give vicinal fluorinated sulfones in moderate to excellent yields. Also, the synthetic utility of this transformation is further demonstrated by a gram-scale reaction and the late-stage functionalization of complex molecules. [Display omitted] [ABSTRACT FROM AUTHOR]

• μ selective analogs displayed superior analgesic efficacy and potency to the parent peptide. • Analog 2 and 3 stimulate the κ opioid receptor activity through a μ opioid receptor regulatory pathway. • Analog 2 and 3 stimulate the release of endogenous opioid peptides. • Acute tolerance was not observed after i.t. administration for analogs 2 and 3. • Analogs display different pharmacological profiles as compared with parent peptide. Endomorphin analogs containing unnatural amino acids have demonstrated potent analgesic effects in our previous studies. In the present study, the differences in antinociception and the mechanisms thereof for analogs 1-3 administered intracerebroventricularly and intrathecally were explored. All analogs at different routes of administration produced potent analgesia compared to the parent peptide endomorphin-1. Multiple antagonists and antibodies were used to explore the mechanisms of action of these analogs, and it was inferred that analogs 1-3 stimulated the μ opioid receptor to induce antinociception. Moreover, the antibody data suggested that analog 2 may induce the release of immunoreactive [Leu5-enkephaline and [Met5-enkephaline to produce a secondary component of antinociception at the spinal level and analog 3 may stimulate the the release of immunoreactive [Met5-enkephaline at the spinal level. Finally, analogs 2 and 3 produced no acute tolerance in the spinal cord. We hypothesize that the unique characteristics of the endomorphin analogs result from their capacities to stimulate the release of endogenous antinociceptive substances. [ABSTRACT FROM AUTHOR]

Endomorphin (EM)-1 and EM-2 are the most effective endogenous analgesics with efficient separation of analgesia from the risk of adverse effects. Poor metabolic stability and ineffective analgesia after peripheral administration were detrimental for the use of EMs as novel clinical analgesics. Therefore, here, we aimed to establish new EM analogs via introducing different bifunctional d -amino acids at position 2 of [(2-furyl)Map4]EMs. The combination of [(2-furyl)Map4]EMs with D-Arg2 or D-Cit2 yielded analogs with enhanced binding affinity to the μ -opioid receptor (MOR) and increased stability against enzymatic degradation (t 1/2 > 300 min). However, the agonistic activities of these analogs toward MOR were slightly reduced. Similar to morphine, peripheral administration of the analog [D-Cit2, (2-furyl)Map4]EM-1 (10) significantly inhibited the pain behavior of mice in multiple pain models. In addition, this EM-1 analog was associated with reduced tolerance, less effect on gastrointestinal mobility, and no significant motor impairment. Compared to natural EMs, the EM analogs synthesized herein had enhanced metabolic stability, bioavailability, and analgesic properties. [ABSTRACT FROM AUTHOR]

Simple, commercially available Grignard reagents have been used as highly efficient precatalysts for the hydroboration of a wide range of aldehydes and ketones. The reaction employs very low catalyst loadings (aldehydes: 0.05 mol%, ketones: 0.5 mol%), and proceeds rapidly (aldehydes: 10 min, ketones: 20 min) under neat condition at room temperature. The Grignard reagent catalyst demonstrated good substrate scope, functional group tolerance, and high chemoselectivity in the carbonyl hydroboration. DFT calculations were performed to investigate the possible reaction mechanism. In contrast to the traditional stoichiometric use of Grignard reagents, this newly developed protocol provides a catalytic application of these reagents for molecular transformations. Image 1 • Grignard reagents have been employed as efficient precatalysts for various carbonyl hydroboration. • The Grignard reagent catalyst shows a high functional group tolerance and high chemoselectivity. • In contrast to the traditional stoichiometric use of Grignard reagents, this protocol provides a catalytic application. [ABSTRACT FROM AUTHOR]