Harmine Ameliorates Cognitive Impairment by Inhibiting NLRP3 Inflammasome Activation and Enhancing the BDNF/TrkB Signaling Pathway in STZ-Induced Diabetic Rats

Diabetes mellitus (DM) is considered a risk factor for cognitive dysfunction. Harmine not only effectively improves the symptoms of DM but also provides neuroprotective effects in central nervous system diseases. However, whether harmine has an effect on diabetes-induced cognitive dysfunction and the underlying mechanisms remain unknown. In this study, the learning and memory abilities of rats were evaluated by the Morris water maze test. Changes in the nucleotide-binding oligomerization domain-containing protein (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and brain-derived neurotrophic factor (BDNF)/TrkB signaling pathway were determined in both streptozotocin (STZ)-induced diabetic rats and high glucose (HG)-treated SH-SY5Y cells by western blotting and histochemistry. Herein, we found that harmine administration significantly ameliorated learning and memory impairment in diabetic rats. Further study showed that harmine inhibited NLRP3 inflammasome activation, as demonstrated by reduced NLRP3, ASC, cleaved caspase-1, IL-1β, and IL-18 levels, in the cortex of harmine-treated rats with DM. Harmine was observed to have similar beneficial effects in HG-treated neuronal cells. Moreover, we found that harmine treatment enhanced BDNF and phosphorylated TrkB levels in both the cortex of STZ-induced diabetic rats and HG-treated cells. These data indicate that harmine mitigates cognitive impairment by inhibiting NLRP3 inflammasome activation and enhancing the BDNF/TrkB signaling pathway. Thus, our findings suggest that harmine is a potential therapeutic drug for diabetes-induced cognitive dysfunction

Activating TiO₂ through the Phase Transition-Mediated Hydrogen Spillover to Outperform Pt for Electrocatalytic pH-Universal Hydrogen Evolution.

Endowing conventional materials with specific functions that are hardly available is invariably of significant importance but greatly challenging. TiO2 is proven to be highly active for the photocatalytic hydrogen evolution while intrinsically inert for electrocatalytic hydrogen evolution reaction (HER) due to its poor electrical conductivity and unfavorable hydrogen adsorption/desorption behavior. Herein, the first activation of inert TiO2 for electrocatalytic HER is demonstrated by synergistically modulating the positions of d-band center and triggering hydrogen spillover through the dual doping-induced partial phase transition. The N, F co-doping-induced partial phase transition from anatase to rutile phase in TiO2 (AR-TiO2|(N,F)) exhibits extraordinary HER performance with overpotentials of 74, 80, and 142 mV at a current density of 10 mA cm-2 in 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline electrolytes, respectively, which are substantially better than pure TiO2, and even superior to the benchmark Pt/C catalysts. These findings may open a new avenue for the development of low-cost alternative to noble metal catalysts for electrocatalytic hydrogen production

Markedly Different Decomposition Temperature and Products of Biomass Pyrolysis at Low Temperature—Differentiation of Acids in Their Effects on Pretreatment

Pine as a softwood and poplar as a hardwood pretreated with hydrochloric acid (HCl), phosphoric acid (H3PO4), and hypophosphorous acid (H3PO2) are studied for the pyrolytic properties and products in thermogravimetry (TG) and fixed bed reactor. The pyrolysis performances are pronouncedly distinguished due to the compositional and structural changes induced by the acid pretreatments. Reduction in the mineral content in the biomass feedstocks by pretreatment with the acids results in significant changes in the pyrolytic products. The residual P in the H3PO2-pretreated biomass apparently catalyzed the biomass deeper dehydration in pyrolysis compared to the other two mineral acids. TG analysis shows a shift of the temperature of maximum mass loss (Tmax) by more than 40 °C to lower temperature in the decomposition of the H3PO2-pretreated biomass from that of the untreated and the HCl- and H3PO4-pretreated biomass. Inspired by the striking differences in TG profiles of biomass pretreated by the three acids, thermal pyrolysis of pretreated biomass was carried out in a fixed bed reactor aimed at producing biochemicals at low temperatures (330 °C and 400 °C). The liquid products obtained from the fixed bed reactor show remarkably different major anhydrosugars as a result of pretreatment by the three acids. While phenolics dominate in the collected pyrolysis liquid from untreated biomass samples, biomass pretreated with all three acids results in substantially reduced phenolics in the bio-oils. The reduction in phenolic compounds in the bio-oil may be attributed to the reduction in mineral content in the feedstock. Consequently, the yields of anhydrosugars, mainly levoglucosan (LG) and levoglucosenone (LGO) are increased. LG yields of 20.9–28.5% from the cellulose content are obtained from HCl- and H3PO4-pretreated pine/poplar, with very low LGO yield (less than 1.7%). However, H3PO2-pretreated biomass is selective to produce LGO, especially at 330 °C. LGO yields of 7.4% and 6.7% are obtained from H3PO2-pretreated pine and poplar, respectively

Effect of salt stress on the photosynthetic characteristics and endogenous hormones, and: A comprehensive evaluation of salt tolerance in Reaumuria soongorica seedlings

Salinity is a major limiting factor in desert ecosystems, where Reaumuria soongarica is a dominant species. It is crucial to study the growth and physiological response mechanisms of R. soongorica under salt stress for the protection and restoration of the desert ecosystems. However, the effects of salt concentration and stress duration on endogenous hormonal content and photosynthetic efficiency and salt injury index of R. soongorica leaves have not been reported. Currently, there is no systematic evaluation system to determine physiological adaptation strategies of R. soongorica seedlings in response to salt stress. In this study, simulation experiments were performed with NaCl solution mixed with soil. Enzyme-linked immunosorbent assay and LI-6800 portable photosynthesis analyzer were used to measure indole acetic acid (IAA), corn nucleoside hormone (ZR), abscisic acid (ABA), and photosynthesis-related parameters in leaves of R. soongorica seedlings at 0 (24–48 h after salt treatment), 3, 6, and 9 days. At the same time, growth indicators (salt injury index, root-to-shoot ratio), reactive oxygen species content, superoxide dismutase enzyme (SOD) activity, osmolyte content, membrane peroxidation, and leaf pigment content were measured at different salt concentrations and treatment times. Finally, principal component analysis and membership function method were used to comprehensively evaluate the salt tolerance of seedlings. The results showed that treatment with 200 mM NaCl for 3 days significantly increased SOD activity, the content of osmotic adjustment substances (proline, soluble protein), endogenous hormone content (ABA, ZR), root-to-shoot ratio, and Chla/Chlb values but decreased malondialdehyde content (MDA) in the leaves of R. soongorica seedlings. Leaf water content (LRWC), net photosynthetic rate (Pn), transpiration rate (Tr), water use efficiency (WUE), and IAA content in R. soongorica seedlings were lower than those in the control, when exposed to 400 and 500 mM NaCl solutions. Finally, the principal component analysis revealed endogenous hormone content and antioxidant enzyme activity to be useful for the comprehensive evaluation of salt tolerance in R. soongorica seedlings. The R. soongorica seedlings showed the strongest salt tolerance when exposed to 200 mM NaCl for 3 days. This study provides a theoretical foundation for gene mining and breeding of salt-tolerant species in the future

Advance in the Hydrogenation of 5-Hydroxymethylfurfural to Produce 1-Hydroxyhexane-2,5-dione

Recently, catalytic transformation of biobased 5-hydroxymethylfurfural (5-HMF) has been paid much more attentions. 1-Hydroxyhexane-2,5-dione (HHD) is a potential feedstock to synthesize valuable chemicals. The recent remarkable progress of HHD preparation, which utilized 5-HMF as a starting material, is a green and atom economic method. In this review, the approaches of HHD preparation from 5-HMF are summarized based on the homogeneous and heterogeneous catalysis

Immune checkpoint inhibitors for the treatment of non-small cell lung cancer brain metastases

Abstract. Lung cancer has the highest risk of brain metastasis (BM) among all solid carcinomas. The emergence of BM has a significant impact on the selection of oncologic treatment for patients. Immune checkpoint inhibitors (ICIs) are the most promising treatment option for patients without druggable mutations and have been shown to improve survival in patients with non-small cell lung cancer (NSCLC) BM in clinical trials with good safety. Moreover, ICI has shown certain effects in NSCLC BM, and the overall intracranial efficacy is comparable to extracranial efficacy. However, a proportion of patients showed discordant responses in primary and metastatic lesions, suggesting that multiple mechanisms may exist underlying ICI activity in BM. According to studies pertaining to tumor immune microenvironments, ICIs may be capable of provoking immunity in situ. Meanwhile, systematic immune cells activated by ICIs can migrate into the central nervous system and exert antitumor effects. This review summarizes the present evidence for ICI treatment efficacy in NSCLC BM and proposes the possible mechanisms of ICI treatment for NSCLC BMs based on existing evidence

Structure dependent toxicity of lignin phenolics and PEG detoxification in VHG ethanol fermentation

The inhibition of lignin phenolics on fermenting microbes has become one of the major barriers in developing an economically viable process for cellulosic ethanol production. In this study, the toxicity to yeast cells and the inhibition to the very high gravity (VHG) fermentation of the phenolic compounds were investigated in the absence or presence of polyethylene glycol (PEG). It was found that the inhibitory effects of phenolic compounds on VHG ethanol fermentation depend on the activity of their hydroxyl (-OH) hydrogen. 250 g L-1 PEG-1000 detoxified 2.0 g LL-1 guaiacol in the fermentation broth, and boosted the ethanol concentration from 131 g LL-1 to 173 g LL-1. The inhibitory effect of 5.0 g LL-1 guaiacol on ethanol fermentation was also alleviated, and the ethanol concentration was increased from 51 g LL-1 to 151 g LL-1 after detoxification with 250 g LL-1 PEG-1000. The H-1-NMR of hydroxyl group (-OH) of phenolic compounds in PEG revealed the role of hydrogen bonding formation on the in situ detoxification mechanism of PEG, and the order in the strength of the intermolecular hydrogen bond between phenolic compounds and PEG. Furthermore, the kinetics of VHG ethanol fermentation in the presence of phenolic compounds were determined. The obtained kinetic model (phenolic compounds inhibitory effect) fits well the kinetics of ethanol production from lignocellulosic hydrolyzates using batch VHG ethanol fermentation technology

A catalytic aldol condensation system enables one pot conversion of biomass saccharides to biofuel intermediates

Producing bio-intermediates from lignocellulosic biomass with minimal process steps has a far-reaching impact on the biofuel industry. We studied the metal chloride catalyzed aldol condensation of furfural with acetone under conditions compatible with the upstream polysaccharide conversions to furfurals. In situ far infrared spectroscopy (FIR) was applied to guide the screening of aldol condensation catalysts based on the distinguishing characteristics of metal chlorides in their coordination chemistries with carbonyl-containing compounds. NiCl2, CoCl2, CrCl3, VCl3, FeCl3, and CuCl2 were selected as the potential catalysts in this study. The FIR results further helped to rationalize the excellent catalytic performance of VCl3 in furfural condensation with acetone, with 94.7% yield of biofuel intermediates (C8, C13) in 1-butyl-3-methylimidazolium chloride ([BMIM] Cl) solvent. Remarkably, addition of ethanol facilitated the acetal pathway of the condensation reaction, which dramatically increased the desired product selectivity over the furfural pathway. Most significantly, we demonstrate for the first time that VCl3 catalyzed aldol condensation in acidic medium is fully compatible with upstream polysaccharide hydrolysis to monosaccharide and the subsequent monosaccharide isomerization and dehydration to furfurals. Our preliminary results showed that a 44% yield of biofuel intermediates (C8, C13) can be obtained in one-pot conversion of xylose catalyzed by paired metal chlorides, CrCl2 and VCl3. A number of prior works have shown that the biofuel intermediates derived from the one-pot reaction of this work can be readily hydrogenated to biofuels