Efficacy and Mechanism of Qianshan Huoxue Gao in Acute Coronary Syndrome via Regulation of Intestinal Flora and Metabolites.

Purpose: To study the efficacy of Qianshan Huoxue Gao (QS) in treating acute coronary syndrome (ACS) and to explore the mechanism of action from the perspective of intestinal flora regulation. Methods: Male Sprague-Dawley rats were divided into control, model, QS, and atorvastatin groups; except for the control group, rats underwent ligation of the left anterior descending branch of the coronary artery. Following treatment for 28 days, cardiac function was evaluated using an echocardiographic assay; ELISAs for serum creatine kinase isoenzyme (CK-MB), cardiac troponin I (cTnI), high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α); assessment of cardiac enzymes and inflammatory response; hematoxylin and eosin (HE) staining for histopathological changes in the heart, skin, and viscera; 16S rRNA gene sequencing for intestinal flora diversity and structural differences analysis; and we further investigated intestinal contents using metabolomics. Results: Compared with controls, CK-MB and cTnI were increased (P<0.01); ejection factor and fractional shortening were decreased (P<0.01); left ventricular internal end-diastolic dimension and left ventricular internal end-systolic dimension were increased (P<0.01); and IL-2, IL-6, TNF-α, and hs-CRP were increased in the model group. Myocardial damage and inflammation were also observed by HE staining. QS improved these indexes, similar to the atorvastatin group; therefore, QS could effectively treat ACS. QS modulates the structure and abundance of the intestinal flora in ACS model rats, among which Bacteroides, Lactobacillus, and Rikenellaceae_RC9_gut_group are associated with cardiovascular disease. Metabolomics revealed that the intestinal metabolite content changed in ACS, with ethanolamine (EA) being the most relevant metabolite for ACS treatment by QS. EA was significantly positively correlated with Eubacterium xylanophilum group, Ruminococcus, unclassified f__Oscillospiraceae, Intestinimonas, Eubacterium siraeum group, Lachnospiraceae NK4A136 group, and norank f__Desulfovibrionaceae. Conclusion: QS can effectively treat ACS and can restore regulation of the intestinal flora. EA may be the primary metabolite of QS, exerting a therapeutic effect in ACS.

Mesoporous MgO enriched in Lewis base sites as effective catalysts for efficient CO2 capture.

Capturing CO2 has become increasingly important. However, wide industrial applications of conventional CO2 capture technologies are limited by their slow CO2 sorption and desorption kinetics. Accordingly, this research is designed to overcome the challenge by synthesizing mesoporous MgO nanoparticles (MgO-NPs) with a new method that uses PEG 1500 as a soft template. MgO surface structure is nonstoichiometric due to its distinctive shape; the abundant Lewis base sites provided by oxygen vacancies promote CO2 capture. Adding 2 wt % MgO-NPs to 20 wt % monoethanolamine (MEA) can increase the breakthrough time (the time with 90% CO2 capturing efficiency) by ∼3000% and can increase the CO2 absorption capacity within the breakthrough time by ∼3660%. The data suggest that MgO-NPs can accelerate the rate and increase CO2 desorption capacity by up to ∼8740% and ∼2290% at 90 °C, respectively. Also, the excellent stability of the system within 50 cycles is verified. These findings demonstrate a new strategy to innovate MEA absorbents currently widely used in commercial post-combustion CO2 capture plants.

Neuroblastoma Differentiation: The Untapped Potential of Mitochondrial Uncouplers.

While the goal of most anticancer treatments is to kill cancer cells, some therapies halt cancer progression by inducing cancer cell differentiation. For example, retinoic acid induces neuroblastoma cell differentiation in vitro and is used as maintenance therapy for children with high-risk neuroblastoma. A new study by Jiang and colleagues has revealed the mitochondrial uncoupler niclosamide ethanolamine (NEN) induces neuroblastoma cell differentiation in vitro and slows neuroblastoma tumor growth in vivo. Mitochondrial uncoupler molecules alter cell metabolism by forcing cells to "burn" more nutrients, resulting in a switch from anabolic to catabolic metabolism. NEN-induced neuroblastoma cell differentiation was associated with disruption of Warburg metabolism, epigenetic remodeling, and downregulation of key oncogenic drivers of neuroblastoma development, including MYCN. NEN is currently used as an antiparasitic worm treatment and is safe to use in children but has poor pharmacokinetic properties. However, derivatives of NEN and structurally distinct uncouplers that have improved pharmacokinetic properties are in development. Results of this study ignite the idea that mitochondrial uncouplers could be used as differentiating agents and expand the pharmacotherapy toolkit to treat cancer, including neuroblastoma. See related article by Jiang et al., p. 181.

The Effect of Oleoylethanolamide (OEA) Add-On Treatment on Inflammatory, Oxidative Stress, Lipid, and Biochemical Parameters in the Acute Ischemic Stroke Patients: Randomized Double-Blind Placebo-Controlled Study.

Methods: Sixty patients with a mean age of 68.60 ± 2.10 comprising 29 females (48.33%), who were admitted to an academic tertiary care facility within the first 12 hours poststroke symptoms onset or last known well (LKW), in case symptom onset time is not clear, were included in this study. AIS was confirmed based on a noncontrast head CT scan and also neurological symptoms. Patients were randomly and blindly assigned to OEA of 300 mg/day (n = 20) or 600 mg/day (n = 20) or placebo (n = 20) in addition to the standard AIS treatment for three days. A blood sample was drawn at 12 hours from symptoms onset or LKW as the baseline followed by the second blood sample at 72 hours post symptoms onset or LKW. Blood samples were assessed for inflammatory and biochemical parameters, oxidative stress (OS) biomarkers, and lipid profile. Results: Compared to the baseline, there is a significant reduction in the urea, creatinine, triglyceride, high-density lipoprotein, cholesterol, alanine transaminase, total antioxidant capacity, malondialdehyde (MDA), total thiol groups (TTG), interleukin-6 (IL-6), and C-reactive protein levels on the follow-up blood testing in the OEA (300 mg/day) group. In patients receiving OEA (600 mg/day) treatment, there was only a significant reduction in the MDA level comparing baseline with follow-up blood testing. Also, the between-group analysis revealed a statistically significant difference between patients receiving OEA (300 mg/day) and placebo in terms of IL-6 and TTG level reduction when comparing them between baseline and follow-up blood testing. Conclusion: OEA in moderate dosage, 300 mg/day, add-on to the standard stroke treatment improves short-term inflammatory, OS, lipid, and biochemical parameters in patients with AIS. This effect might lead to a better long-term neurological prognosis.

[Molluscicidal effect of 25% wettable powder of pyriclobenzuron sulphate in hilly schistosomiasis-endemic regions].

OBJECTIVE: To evaluate the molluscicidal effect of 25% wettable powder of pyriclobenzuron sulphate (WPPS) against Oncomelania snails in hilly schistosomiasis-endemic regions and test its toxicity to fish. METHODS: In October 2020, a snail-infested setting which had been cleared was selected in Nanjian County, Yunnan Province and divided into several blocks, and the natural snail mortality was estimated. 25% WPPS was prepared into solutions at concentrations of 1 and 2 g/L, and 25% wettable powder of niclosamide ethanolamine salt (WPNES) was prepared into solutions at a concentration of 2 g/L. The different concentrations of drugs were sprayed evenly, and the same amount of water was used as blank control. Snails were surveyed using the systematic sampling method 1, 3 and 7 days post-treatment, and snail survival was observed. A fish pond was selected in Nanjian County, and 2 kg 25% WPPS was evenly sprayed on the water surface to allow the effective concentration of 20 g/L. Fish mortality was estimated 8, 24, 48 and 72 h post-treatment. RESULTS: One-day treatment with 1 and 2 g/L WPPS and 2 g/L WPNES resulted in 97.99%, 97.99% and 94.11% adjusted snail mortality rates (χ2 = 3.509 and 3.509, both P values > 0.05), and the adjusted snail mortality was all 100% 3 d post-treatment with 1 and 2 g/L WPPS and 2 g/L WPNES, while 7-day treatment with 1 and 2 g/L WPPS and 2 g/L WPNES resulted in 91.75%, 86.57% and 57.76% adjusted snail mortality rates (χ2 = 14.893 and 42.284, both P values < 0.05). Treatment with 2 g/L WPPS for 72 h resulted in a 0.67% cumulative mortality rate of fish. CONCLUSIONS: 25% WPPS is effective for snail control and highly safe for fish, which is feasible for use in hilly schistosomiasis-endemic regions.

Effects of sulfate concentration on anaerobic treatment of wastewater containing monoethanolamine using an up-flow anaerobic sludge blanket reactor.

Monoethanolamine (MEA), a toxic organic chemical, is widely used in industries and is found in their wastewater. Anaerobic MEA degradation is an appropriate strategy to reduce energy and cost for treatment. Industry wastewaters also contain sulfate, but information on the effects of sulfate on MEA degradation is limited. Here, an up-flow anaerobic sludge blanket (UASB) for MEA-containing wastewater treatment was operated under psychrophilic conditions (18-20 ºC) to investigate the effects of sulfate on the microbial characteristics of the retained sludge. To acclimatize the sludge, the proportion of MEA in the influent (containing sucrose, acetate, and propionate) was increased from 15% to 100% of total COD (1500 mg L-1); sulfate was then added to the influent. The COD removal efficiency remained above 95% despite the increase in MEA and sulfate. However, granular sludge disintegration was observed when sulfate was increased from 20 to 330 mg L-1. Batch tests revealed that propionate and acetate were produced as the metabolites of MEA degradation. In response to sulfate acclimation, methane-producing activities for propionate and hydrogen declined, while sulfate-reducing activities for MEA, propionate, and hydrogen increased. Accordingly, acclimation and changes in dominant microbial groups promoted the acetogenic reaction of propionate by sulfate reduction.

Exergy, advance exergy, and exergo-environmental based assessment of alkanol amine- and piperazine-based solvents for natural gas purification.

Purification of Natural gas is vital for utilizing it as a source of energy harvesting for the world. Amine-based chemical absorption technique is the most utilized in the gas field for the purification of gas that ensures the purity of the sweet gas stream with the elimination of carbon dioxide. However, it is considered an energy-intensive process to deal with considerable energy loss and environmental damage to the ecosystem. Five cases have been developed in this study based on various blends comprising mono and tertiary amines in combination with piperazine with a focus on the use of Aqueous Monodiethanolamine (Aq. MDEA), Aqueous Monoethanolamine (Aq. MEA) and piperazine (Pz) for the CO2 sequestration from the sour natural gas extracted from the remote location located in the province of Baluchistan in Pakistan. The use of exergy, advanced exergy, and exergo environment for optimizing and selecting a suitable solvent combination that may result in an effective separation process has been proposed. Five cases have been developed based on various blends such as mono and tertiary amines combined with piperazine. From the results of all the studied scenarios, Case IV, based on the combination of Aqueous monoethanolamine and piperazine, provides reduced exergy destruction of 2551.7 KW. It was observed that the maximum removal of CO2 around 99.87 wt% is achieved in case IV. In addition, advance exergy analysis also highlights that case-IV has a venue of 25% exergy destruction avoidable, which would further enhance its performance. Nevertheless, still, case-IV has 75% exergy destruction unavoidable. The environmental factors show that Case-IV has a reduced exergy destruction factor of 0.96, a highly environmentally benign choice as a solvent with a high value of 1.03, and case-IV has the higher operational stability and higher exergy efficiency with an exergy stability value of 0.40. Therefore, monoethanolamine combined with piperazine to be an effective and efficient solvent blend that could be an energy-effective approach for sweetening the natural gas.

Mechanism-Based Design of the First GlnA4-Specific Inhibitors.

γ-Glutamylamine synthetases are an important class of enzymes that play a key role in glutamate-based metabolism. Methionine sulfoximine (MSO) is a well-established inhibitor for the archetypal glutamine synthetase (GS) but inhibitors for most GS-like enzymes are unknown. Assuming a conserved catalytic mechanism for GS and GS-like enzymes, we explored if subtype-selective inhibitors can be obtained by merging MSO with the cognate substrates of the respective GS-like enzymes. Using GlnA4Sc from Streptomyces coelicolor, an enzyme recently shown to produce γ-glutamylethanolamine, we demonstrate that MSO can be reengineered in a straightforward fashion into potent and selective GlnA4Sc inhibitors. Linkage chemistry as well as linker length between the MSO moiety and the terminal hydroxyl group derived from ethanolamine were in agreement with the postulated phosphorylated catalytic intermediate. The best GlnA4 inhibitor 7 b potently blocked S. coelicolor growth in the presence of ethanolamine as the sole nitrogen source. Our results provide the first GlnA4Sc -specific inhibitors and suggest a general strategy to develop mechanism-based inhibitors for GS-like enzymes.

Localization and interaction studies of the Salmonella enterica ethanolamine ammonia-lyase (EutBC), its reactivase (EutA), and the EutT corrinoid adenosyltransferase.

Some prokaryotes compartmentalize select metabolic capabilities. Salmonella enterica subspecies enterica serovar Typhimurium LT2 (hereafter S. Typhimurium) catabolizes ethanolamine (EA) within a proteinaceous compartment that we refer to as the ethanolamine utilization (Eut) metabolosome. EA catabolism is initiated by the adenosylcobalamin (AdoCbl)-dependent ethanolamine ammonia-lyase (EAL), which deaminates EA via an adenosyl radical mechanism to yield acetaldehyde plus ammonia. This adenosyl radical can be quenched, requiring the replacement of AdoCbl by the ATP-dependent EutA reactivase. During growth on ethanolamine, S. Typhimurium synthesizes AdoCbl from cobalamin (Cbl) using the ATP:Co(I)rrinoid adenosyltransferase (ACAT) EutT. It is known that EAL localizes to the metabolosome, however, prior to this work, it was unclear where EutA and EutT localized, and whether they interacted with EAL. Here, we provide evidence that EAL, EutA, and EutT localize to the Eut metabolosome, and that EutA interacts directly with EAL. We did not observe interactions between EutT and EAL nor between EutT and the EutA/EAL complex. However, growth phenotypes of a ΔeutT mutant strain show that EutT is critical for efficient ethanolamine catabolism. This work provides a preliminary understanding of the dynamics of AdoCbl synthesis and its uses within the Eut metabolosome.

Acinetobacter baumannii Catabolizes Ethanolamine in the Absence of a Metabolosome and Converts Cobinamide into Adenosylated Cobamides.

Acinetobacter baumannii is an opportunistic pathogen typically associated with hospital-acquired infections. Our understanding of the metabolism and physiology of A. baumannii is limited. Here, we report that A. baumannii uses ethanolamine (EA) as the sole source of nitrogen and can use this aminoalcohol as a source of carbon and energy if the expression of the eutBC genes encoding ethanolamine ammonia-lyase (EAL) is increased. A strain with an ISAba1 element upstream of the eutBC genes efficiently used EA as a carbon and energy source. The A. baumannii EAL (AbEAL) enzyme supported the growth of a strain of Salmonella lacking the entire eut operon. Remarkably, the growth of the above-mentioned Salmonella strain did not require the metabolosome, the reactivase EutA enzyme, the EutE acetaldehyde dehydrogenase, or the addition of glutathione to the medium. Transmission electron micrographs showed that when Acinetobacter baumannii or Salmonella enterica subsp. enterica serovar Typhimurium strain LT2 synthesized AbEAL, the protein localized to the cell membrane. We also report that the A. baumannii genome encodes all of the enzymes needed for the assembly of the nucleotide loop of cobamides and that it uses these enzymes to synthesize different cobamides from the precursor cobinamide and several nucleobases. In the absence of exogenous nucleobases, the most abundant cobamide produced by A. baumannii was cobalamin. IMPORTANCE Acinetobacter baumannii is a Gram-negative bacterium commonly found in soil and water. A. baumannii is an opportunistic human pathogen, considered by the CDC to be a serious threat to human health due to the multidrug resistance commonly associated with this bacterium. Knowledge of the metabolic capabilities of A. baumannii is limited. The importance of the work reported here lies in the identification of ethanolamine catabolism occurring in the absence of a metabolosome structure. In other bacteria, this structure protects the cell against damage by acetaldehyde generated by the deamination of ethanolamine. In addition, the ethanolamine ammonia-lyase (EAL) enzyme of this bacterium is unique in that it does not require a reactivase enzyme to remain active. Importantly, we also demonstrate that the A. baumannii genome encodes the functions needed to assemble adenosylcobamide, the coenzyme of EAL, from the precursor cobinamide.

Molecular Dynamic Insights into the Distinct Solvation Structures of Aromatic and Aliphatic Compounds in Monoethanolamine-Based Deep Eutectic Solvents.

Deep eutectic solvents (DESs) are developing as an alternate medium for aromatic extraction, especially benzene and thiophene from aliphatic hydrocarbon mixtures. In this work, molecular dynamics (MD) simulations were first used to investigate the solvation structure of benzene, thiophene, and n-hexane in monoethanolamine-based DESs. It reveals the liquid structures in the adjacent neighbor shells, which is a function of electron-withdrawing sulfur attached to thiophene and the π-electron cloud of benzene. The intermolecular forces between aromatic, aliphatic, and DES components are analyzed in van der Waals and hydrogen bond interactions. The chloride ions serve as a charge carrier bridge between choline and monoethanolamine precursors. The solvation of benzene, thiophene, and n-hexane in the DESs depends on volume expansion and minor solvent structural changes. Density functional theory results provided information on the mechanism of short-range interactions between organic solutes and studied DES. It aids in understanding the structural orientations of a DES with the addition of solutes, essential to the formation of DES. The solvation shell structure and characteristics were investigated in tandem with the possibility of benzene and thiophene clustering. The 1H NMR and 2D 1H-1H-NOESY were used to investigate the intermolecular interactions between benzene, thiophene, and n-hexane with monoethanolamine-based solvents. It concludes that high-ordered DES1 is more inclined to higher solubility than lower-ordered ones with a higher molar ratio of monoethanolamine. The solvation was reduced because the entropy gain was not maximized in the lower ordered DESs.

Experimental and Theoretical Study on the Enhancement of Alkanolamines on Sulfuric Acid Nucleation.

Alkanolamines such as monoethanolamine (MEA), diethanolamine (DEA), and triethanolamine (TEA) are extensively used for CO2 capture and consumer products. Despite their prevalence in industrial applications, the fate of alkanolamines in the atmosphere remains relatively unknown. One likely reaction pathway for these chemicals in the atmosphere is new particle formation with sulfuric acid. Here, we present the first experimental results showing the formation of sulfuric acid dimers enhanced by MEA, DEA, and TEA from the measurement of molecular clusters. This study examines the nucleation reactions of MEA, DEA, and TEA with sulfuric acid in a clean, laminar flow reactor. The chemical compositions and concentrations of the freshly nucleated clusters were analyzed using a custom-built atmospheric pressure chemical ionization long time-of-flight mass spectrometer known as the Pittsburgh Cluster CIMS. Quantum chemical calculations and kinetic modeling of sulfuric acid-MEA/DEA/TEA clusters were also performed to determine relative cluster stabilities between these sulfuric acid-base systems. Experimental results indicate that MEA, DEA, and TEA at the part per trillion by volume (pptv) concentrations can enhance sulfuric acid dimer formation rates but to a lesser extent than dimethylamine (DMA). Thus, MEA, DEA, and TEA will potentially play an important role in new particle formation in industrial cities where these alkanolamines are emitted.

Experimental investigations and the modeling approach for CO2 solubility in aqueous blended amine systems of monoethanolamine, 2-amino-2-methyl-1-propanol, and 2-(butylamino)ethanol.

In this work, new CO2 solubility data on three types of aqueous amine blends were reported to complement existing databases. The experiments were conducted at temperatures of 313 K (absorption condition) and 363 K (desorption condition). The effect of the MEA concentration on the CO2 solubility in several amine blends at low CO2 partial pressure (8 to 50.65 kPa) were studied in this work, including 0.1, 0.3, 0.5 mol/L MEA + 2 mol/L AMP; 0.1, 0.3, 0.5 mol/L MEA + 2 mol/L BEA; and 0.1, 0.3, 0.5 mol/L MEA + 1, 2 mol/L AMP + 1, 2 mol/L BEA. Besides, an additional group of equilibrium CO2 solubility data were conducted at 298 K in order to estimate the heat of CO2 absorption of the blended solvents at a temperature range from 298 to 313 K. A new simplified Kent-Eisenberg model was developed for the predictions of blended solvents, and a multilayer neural network model with Levenberg-Marquardt backpropagation algorithm was developed upon five hundred reliable published experimental data. The predictions from two methods are both in good agreement with the experimental CO2 solubility data.

Experimental and Mathematical Modelling of Factors Influencing Carbon Dioxide Absorption into the Aqueous Solution of Monoethanolamine and 1-Butyl-3-methylimidazolium Dibutylphosphate Using Response Surface Methodology (RSM).

This paper investigated the solubility of carbon dioxide (CO2) in an aqueous solution of monoethanolamine (MEA) and 1-butyl-3-methylimidazolium dibutylphosphate ((BMIM)(DBP)) ionic liquid (IL) hybrid solvents. Aqueous solutions of MEA-(BMIM)(DBP) hybrid solvents containing different concentrations of (BMIM)(DBP) were prepared to exploit the amine's reactive nature, combined with the IL's non-volatile nature for CO2 absorption. Response surface methodology (RSM) based on central composite design (CCD) was used to design the CO2 solubility experiments and to investigate the effects of three independent factors on the solubility of CO2 in the aqueous MEA-(BMIM)(DBP) hybrid solvent. The three independent factors were the concentration of (BMIM)(DBP) (0-20 wt.%), temperature (30 °C-60 °C) and pressure of CO2 (2-30 bar). The experimental data were fitted to a quadratic model with a coefficient of determination (R2) value of 0.9791. The accuracy of the developed model was confirmed through additional experiments where the experimental values were found to be within the 95% confidence interval. From the RSM-generated model, the optimum conditions for CO2 absorption in aqueous 30 wt% MEA-(BMIM)(DBP) were 20 wt% of (BMIM)(DBP), a temperature of 41.1 °C and a pressure of 30 bar.

Homogeneous assays for aptamer-based ethanolamine sensing: no indication of target binding.

Ethanolamine is an important analyte for environmental chemistry and biological sciences. A few DNA aptamers were previously reported for binding ethanolamine with a dissociation constant (Kd) as low as 9.6 nM. However, most of the previous binding assays and sensing work used either immobilized ethanolamine or immobilized aptamers. In this work, we studied three previously reported DNA sequences, two of which were supposed to bind ethanolamine while the other could not bind. Isothermal titration calorimetry revealed no binding for any of these sequences. In addition, due to their guanine-rich sequences, thioflavin T was used as a probe. Little fluorescence change was observed with up to 1 µM ethanolamine. Responses within the millimolar range of ethanolamine were attributed to the general fluorescence quenching effect of ethanolamine instead of aptamer binding. Finally, after studying the adsorption of ethanolamine to gold nanoparticles (AuNPs), we confirmed the feasibility of using AuNPs as a probe when the concentration of ethanolamine was below 0.1 mM. However, no indication of specific aptamer binding was observed by comparing the three DNA sequences for their color changing trends. This work articulates the importance of careful homogeneous binding assays using free target molecules.

Less-Energy Consumed Hydrogen Evolution Coupled with Electrocatalytic Removal of Ethanolamine Pollutant in Saline Water over Ni@Ni3 S2 /CNT Nano-Heterostructured Electrocatalysts.

Energy crises, environmental pollution, and freshwater deficiency are critical issues on the planet. Electrolytic hydrogen generation from saline water, particularly from salt-contained hazardous wastewater, is significant to both environment and energy concerns but still challenging due to the high energy cost, severe corrosion, and the absence of competent electrocatalysts. Herein, a novel strategy is proposed for energy-efficient hydrogen production coupled with electro-oxidation removal of ethanolamine pollutant in saline water. To achieve this, an active and durable heterostructured electrocatalyst is developed by in situ growing Ni@Ni3 S2 core@shell nanoparticles in cross-linked 3D carbon nanotubes' (CNTs) network, achieving high dispersibility and metallic property, low packing density, and enriched exposed active sites to facilitate fast electron/mass diffusion. The unique Ni@Ni3 S2 /CNTs nano-heterostructures are competent for long-term stably electro-oxidizing environmental-unfriendly ethanolamine at a high current density of 100 mA cm-2 in saline water, which not only suppresses oxygen and chloride evolution reactions but also decreases the energy consumption to boost hydrogen production. Associated with experimental results, density functional theory studies indicate that the collaborative adsorption of electrolyte ions and ethanolamine molecules can synergistically modulate the adsorption/desorption properties of catalytic active centers on Ni@Ni3 S2 /CNTs surface, leading to long-term stabilized electrocatalysis for efficient ethanolamine oxidation removal and less-energy hydrogen simultaneous production in saline water.

Niclosamide Ethanolamine Salt Alleviates Idiopathic Pulmonary Fibrosis by Modulating the PI3K-mTORC1 Pathway.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pneumonia characterized by chronic progressive fibrosis, ultimately leading to respiratory failure and early mortality. Although not fully explored, the major causative factors in IPF pathogenesis are dysregulated fibroblast proliferation and excessive accumulation of extracellular matrix (ECM) deposited by myofibroblasts differentiated from pulmonary fibroblasts. More signalling pathways, including the PI3K-Akt-mTOR and autophagy pathways, are involved in IPF pathogenesis. Niclosamide ethanolamine salt (NEN) is a highly effective multitarget small-molecule inhibitor reported in antitumor studies. Here, we reported that in an IPF animal model treated with NEN for 14 days, attractive relief of pulmonary function and hydroxyproline content were observed. To further explore, the therapeutic effect of NEN in IPF and pathological changes in bleomycin-challenged mouse lung sections were assessed. Additionally, the effects of NEN on abnormal proliferation and ECM production in IPF cell models established with TGF-ß1-stimulated A549 cells or DHLF-IPF cells were studied. In nonclinical studies, NEN ameliorated lung function and histopathological changes in bleomycin-challenged mice, and the lung hydroxyproline content was significantly diminished with NEN treatment. In vitro, NEN inhibited PI3K-mTORC1 signalling and arrested the cell cycle to prevent uncontrolled fibroblast proliferation. Additionally, NEN inhibited TGF-ß1-induced epithelial-mesenchymal transition (EMT) and ECM accumulation via the mTORC1-4EBP1 axis. Furthermore, NEN-activated noncanonical autophagy resensitized fibroblasts to apoptosis. The above findings demonstrated the potential antifibrotic effect of NEN mediated via modulation of the PI3K-mTORC1 and autophagy pathways. These data provide strong evidence for a therapeutic role for NEN in IPF.

Specificity of Loxosceles α clade phospholipase D enzymes for choline-containing lipids: Role of a conserved aromatic cage.

Spider venom GDPD-like phospholipases D (SicTox) have been identified to be one of the major toxins in recluse spider venom. They are divided into two major clades: the α clade and the ß clade. Most α clade toxins present high activity against lipids with choline head groups such as sphingomyelin, while activities in ß clade toxins vary and include preference for substrates containing ethanolamine headgroups (Sicarius terrosus, St_ßIB1). A structural comparison of available structures of phospholipases D (PLDs) reveals a conserved aromatic cage in the α clade. To test the potential influence of the aromatic cage on membrane-lipid specificity we performed molecular dynamics (MD) simulations of the binding of several PLDs onto lipid bilayers containing choline headgroups; two SicTox from the α clade, Loxosceles intermedia αIA1 (Li_αIA) and Loxosceles laeta αIII1 (Ll_αIII1), and one from the ß clade, St_ßIB1. The simulation results reveal that the aromatic cage captures a choline-headgroup and suggest that the cage plays a major role in lipid specificity. We also simulated an engineered St_ßIB1, where we introduced the aromatic cage, and this led to binding with choline-containing lipids. Moreover, a multiple sequence alignment revealed the conservation of the aromatic cage among the α clade PLDs. Here, we confirmed that the i-face of α and ß clade PLDs is involved in their binding to choline and ethanolamine-containing bilayers, respectively. Furthermore, our results suggest a major role in choline lipid recognition of the aromatic cage of the α clade PLDs. The MD simulation results are supported by in vitro liposome binding assay experiments.

CO2 Absorption Mechanism by the Deep Eutectic Solvents Formed by Monoethanolamine-Based Protic Ionic Liquid and Ethylene Glycol.

Deep eutectic solvents (DESs) have been widely used to capture CO2 in recent years. Understanding CO2 mechanisms by DESs is crucial to the design of efficient DESs for carbon capture. In this work, we studied the CO2 absorption mechanism by DESs based on ethylene glycol (EG) and protic ionic liquid ([MEAH][Im]), formed by monoethanolamine (MEA) with imidazole (Im). The interactions between CO2 and DESs [MEAH][Im]-EG (1:3) are investigated thoroughly by applying 1H and 13 C nuclear magnetic resonance (NMR), 2-D NMR, and Fourier-transform infrared (FTIR) techniques. Surprisingly, the results indicate that CO2 not only binds to the amine group of MEA but also reacts with the deprotonated EG, yielding carbamate and carbonate species, respectively. The reaction mechanism between CO2 and DESs is proposed, which includes two pathways. One pathway is the deprotonation of the [MEAH]+ cation by the [Im]- anion, resulting in the formation of neutral molecule MEA, which then reacts with CO2 to form a carbamate species. In the other pathway, EG is deprotonated by the [Im]-, and then the deprotonated EG, HO-CH2-CH2-O-, binds with CO2 to form a carbonate species. The absorption mechanism found by this work is different from those of other DESs formed by protic ionic liquids and EG, and we believe the new insights into the interactions between CO2 and DESs will be beneficial to the design and applications of DESs for carbon capture in the future.

Liquid chromatography enantiomeric separation of chiral ethanolamine substituted compounds.

Eleven racemic ethanolamine derivatives were prepared, and their enantiomers were separated using liquid chromatography with various chiral columns. These derivatives included chiral vicinal amino alcohols, ß-hydroxy ureas, ß-hydroxy thioureas, and ß-hydroxy guanidines, all of which are present in many active pharmaceutical ingredients. The screening study was performed with six chiral stationary phase containing columns, including four recently introduced superficially porous particles bonded with two macrocyclic glycopeptides, a cyclodextrin derivative and a cyclofructan derivative. The two remaining columns contained chiral stationary phases, based on either a cellulose derivative or derivatized amylose, both bonded to fully porous particles. The cyclodextrin and cellulose-based chiral stationary phases proved to be the most broadly effective selectors and were able to separate 8 and 7 of the 11 tested compounds, respectively. With respect to analyte structural features, marked differences in enantiorecognition were observed between compounds containing phenyl and cyclohexyl groups adjacent to the stereogenic center. Additionally, replacing a small electronegative oxygen atom by a larger and less electronegative sulfur atom induced a significant difference in chiral recognition by the cellulose derivative as well as by the vancomycin-based chiral selectors.