Tobiasenedmondson2770

Pursuing scalable production of porous carbon with facile and environmentally friendly synthesis methodology is a global goal. Herein, a unique hierarchical porous graphitic carbon (HPGC) with outstanding textural characteristics is achieved by a special synergistic activation mechanism, in which the low-temperature molten state of polymorphisms can induce a high-rate liquid phase porous activation. HPGC with high specific surface area (SSA, ∼2571 m2 g-1) and large pore volume (PV, ∼2.21 cm3 g-1) can be achieved, which also possesses the capability to tune textural characteristics (i.e., SSA, PV, pore size distribution, etc.) within a wide range. Furthermore, the pilot-scale production of HPGC is accomplished, which shows similar textural characteristics to the lab-scale HPGC. Due to the unique structure of HPGC and the capability of the textural control, it can be applicable in a variety of energy storage, energy conversion, and catalysis applications. The applications of pilot-scale HPGC products in supercapacitors and lithium sulfur batteries are highlighted in this work. Furthermore, the synergistic activation strategy can be promoted to other alkali-based carbon activation routes, which can open up new possibilities for the activated carbon production and lead to more widespread industrialized applications of HPGC.Methamphetamine (METH) is a widely abused and highly addictive psychoactive stimulant that can induce neuronal apoptosis. Lipocalin-2 (LCN2) is a member of the lipocalin family, and its upregulation is involved in cell death in the adult brain. However, the role of LCN2 in METH-induced neurotoxicity has not been reported. In this study, we found that LCN2 was predominantly expressed in hippocampal astrocytes after METH exposure and that recombinant LCN2 (Re LCN2) can induce neuronal apoptosis in vitro and in vivo. The inhibition of LCN2 and LCN2R, a cell surface receptor for LCN2, reduced METH- and Re LCN2-induced mitochondrion-related neuronal apoptosis in cultures of primary rat neurons and animal models. Our study supports the role of reactive oxygen species (ROS) generation and the PRKR-like ER kinase (PERK)-mediated signaling pathway in the upregulation of astrocyte-derived LCN2 after METH exposure. Additionally, the serum and cerebrospinal fluid (CSF) levels of LCN2 were significantly upregulated after METH exposure. These results indicate that upregulation of astrocyte-derived LCN2 binding to LCN2R is involved in METH-induced mitochondrion-related neuronal apoptosis.Rich chemistry and surface functionalization provide MXenes enhanced electrochemical activity yet severely exacerbate their self-discharge behavior in supercapacitors. However, this self-discharge behavior and its related mechanism are still remaining issues. Herein, we propose a chemically interface-tailored regulation strategy to successfully unravel and efficiently alleviate the self-discharge behavior of Ti3C2Tx MXene-based supercapacitors. As a result, Ti3C2Tx MXenes with fewer F elements (∼0.65 atom %) show a positive self-discharge rate decline of ∼20% in comparison with MXenes with higher F elements (∼8.09 atom %). Such decline of the F elements can highly increase tight-bonding ions corresponding to an individual self-discharge process, naturally resulting in a dramatic 50% increase of the transition potential (VT). Therefore, the mixed self-discharge rate from both tight-bonding (contain fewer F elements) and loose-bonding ions (contain more F elements) is accordingly lowered. Through chemically interface-tailored engineering, the significantly changed average oxidation state and local coordination information on MXene affected the interaction of ion counterparts, which was evidently revealed by X-ray absorption fine structures. Theoretically, this greatly improved self-discharge performance was proven to be from higher adsorption energy between the interface of the electrode and the electrolyte by density functional theory. Therefore, this chemically interface-tailored regulation strategy can guide the design of high-performance MXene-based supercapacitors with low self-discharge behavior and will promote its wider commercial applications.RNA repeat expansions cause more than 30 neurological and neuromuscular diseases with no known cures. Since repeat expansions operate via diverse pathomechanisms, one potential therapeutic strategy is to rid them from disease-affected cells, using bifunctional small molecules that cleave the aberrant RNA. Such an approach has been previously implemented for the RNA repeat that causes myotonic dystrophy type 1 [DM1, r(CUG)exp] with Cugamycin, which is a small molecule that selectively binds r(CUG)exp conjugated to a bleomycin A5 cleaving module. Herein, we demonstrate that, by replacing bleomycin A5 with deglycobleomycin, an analogue in which the carbohydrate domain of bleomycin A5 is removed, the selectivity of the resulting small-molecule conjugate (DeglycoCugamycin) was enhanced, while maintaining potent and allele-selective cleavage of r(CUG)exp and rescue of DM1-associated defects. In particular, DeglycoCugamycin did not induce the DNA damage that is observed with high concentrations (25 μM) of Cugamycin, while selectively cleaving the disease-causing allele and improving DM1 defects at 1 μM.(+)-(2S,6S,11S)- and (-)-(2R,6R,11R)-Benzomorphan derivatives have a different binding affinity for sigma-1 (σ1R) and opioid receptors, respectively. Metformin ic50 In this study, we describe the synthesis of the (+)-enantiomer [(+)-LP1] of the benzomorphan MOR agonist/DOR antagonist LP1 [(-)-LP1]. The binding affinity of both (+)-LP1 and (-)-LP1 for σ1R and sigma-2 receptor (σ2R) was tested. Moreover, (+)-LP1 opioid receptor binding affinity was also investigated. Finally, (+)-LP1 was tested in a mouse model of inflammatory pain. Our results showed a nanomolar σ1R and binding affinity for (+)-LP1. Both (+)-LP1 and (-)-LP1 elicited a significant analgesic effect in a formalin test. Differently from (-)-LP1, the analgesic effect of (+)-LP1 was not reversed by naloxone, suggesting a σ1R antagonist profile. Furthermore, σ1R agonist PRE-084 was able to unmask the σ1R antagonistic component of the benzomorphan compound. (+)-LP1 could constitute an useful lead compound to develop new analgesics based on mechanisms of action alternative to opioid receptor activation.