-
Journal of Anxiety Disorders Jun 2024Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure... (Meta-Analysis)
Meta-Analysis
Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.
Topics: Propranolol; Animals; Fear; Extinction, Psychological; Rats; Humans; Adrenergic beta-Antagonists; Male; Memory; Midazolam; Adult; Bayes Theorem; Female; Conditioning, Classical; Young Adult
PubMed: 38733644
DOI: 10.1016/j.janxdis.2024.102870 -
Biotechnology Letters Aug 2024Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using...
Chiral epichlorohydrin (ECH) is an attractive intermediate for chiral pharmaceuticals and chemicals preparation. The asymmetric synthesis of chiral ECH using 1,3-dicholoro-2-propanol (1,3-DCP) catalyzed by a haloalcohol dehalogenase (HHDH) was considered as a feasible approach. However, the reverse ring opening reaction caused low optical purity of chiral ECH, thus severely restricts the industrial application of HHDHs. In the present study, a novel selective conformation adjustment strategy was developed with an engineered HheC to regulate the kinetic parameters of the forward and reverse reactions, based on site saturation mutation and molecular simulation analysis. The HheC mutant E85P was constructed with a markable change in the conformation of (S)-ECH in the substrate pocket and a slight impact on the interaction between 1,3-DCP and the enzyme, which resulted in the kinetic deceleration of the reverse reactions. Compared with HheC, the catalytic efficiency (k/K) of the reversed reaction dropped to 0.23-fold (from 0.13 to 0.03 mM s), while the catalytic efficiency (k/K) of the forward reaction only reduced from 0.83 to 0.71 mM s. With 40 mM 1,3-DCP as substrate, HheC E85P catalyzed the synthesis of (S)-ECH with the yield up to 55.35% and the e.e. increased from 92.54 to >99%. Our work provided an effective approach for understanding the stereoselective catalytic mechanism as well as the green manufacturing of chiral epoxides.
Topics: Epichlorohydrin; Hydrolases; Kinetics; Stereoisomerism; Escherichia coli; Protein Engineering; alpha-Chlorohydrin
PubMed: 38733437
DOI: 10.1007/s10529-024-03479-y -
International Journal of Molecular... May 2024Biodegradable (BP) poly(D,L-lactic acid) (PDLLA) membranes are widely used in tissue engineering. Here, we investigate the effects of varying concentrations of...
Biodegradable (BP) poly(D,L-lactic acid) (PDLLA) membranes are widely used in tissue engineering. Here, we investigate the effects of varying concentrations of PDLLA/gelatin membranes electrospun in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP; CHFO) solvent on their mechanical and physical properties as well as their biocompatibility. Regardless of the environmental conditions, increasing the gelatin content resulted in elevated stress and reduced strain at membrane failure. There was a remarkable difference in strain-to-failure between dry and wet PDLLA/gelatin membranes, with wet strains consistently higher than those of the dry membranes because of the hydrophilic nature of gelatin. A similar wet strain (ε = 2.7-3.0) was observed in PDLLA/gelatin membranes with a gelatin content between 10 and 40%. Both dry and wet stresses increased with increasing gelatin content. The dry stress on PDLLA/gelatin membranes (σ = 6.7-9.7 MPa) consistently exceeded the wet stress (σ = 4.5-8.6 MPa). The water uptake capacity (WUC) improved, increasing from 57% to 624% with the addition of 40% gelatin to PDLLA. PDLLA/gelatin hybrid membranes containing 10 to 20 wt% gelatin exhibited favorable wet mechanical properties (σ = 5.4-6.3 MPa; ε = 2.9-3.0); WUC (337-571%), degradability (11.4-20.2%), and excellent biocompatibility.
Topics: Biocompatible Materials; Gelatin; Materials Testing; Membranes, Artificial; Polyesters; Stress, Mechanical; Tissue Engineering; Water
PubMed: 38732241
DOI: 10.3390/ijms25095022 -
Foods (Basel, Switzerland) Apr 2024The objective of this study was to develop a simultaneous analytical method for the determination of lignans, tocols, phytosterols, and squalene using high-performance...
The objective of this study was to develop a simultaneous analytical method for the determination of lignans, tocols, phytosterols, and squalene using high-performance liquid chromatography coupled with a diode array and fluorescence detector (HPLC-DAD-FLD). The method employed a Vertisep UPS silica HPLC column (4.6 × 250 mm, 5 µm) with a mobile phase mixture of n-hexane/tetrahydrofuran/2-propanol. This approach enabled the simultaneous analysis of ten compounds within 22 min. The linear correlation (R) exceeded 0.9901. The limit of detection (LOD) and limit of quantitation (LOQ) were up to 0.43 µg mL for lignans and tocopherols and up to 326.23 µg mL for phytosterol and squalene. The precision and accuracy of the intra-day and inter-day variation were less than 1.09 and 3.32% relative standard deviations (RSDs). Furthermore, the developed method was applied for the analysis of targeted compounds in twenty-eight sesame oil samples (1775-8965 µg g total lignans, 29.7-687.9 µg g total tocopherols, 2640-9500 µg g phytosterol, and 245-4030 µg g squalene). The HPLC method that has been developed was proven to be a reliable and effective tool for the determination of those functional compounds among sesame oil samples.
PubMed: 38731739
DOI: 10.3390/foods13091368 -
Foods (Basel, Switzerland) Apr 20243-Methylthio-1-propanol (3-Met) is an important flavor compound in various alcoholic beverages such as and . To maintain the content of 3-Met in these alcoholic...
3-Methylthio-1-propanol (3-Met) is an important flavor compound in various alcoholic beverages such as and . To maintain the content of 3-Met in these alcoholic beverages, it is necessary to screen a micro-organism with high yield of 3-Met from the brewing environment. In this study, the ability of yeast strains from the brewing to produce 3-Met was analyzed, aiming to obtain yeast with high-yield 3-Met, and its fermentation conditions were optimized. Firstly, 39 yeast strains were screened using 3-Met conversion medium. The results showed that the majority of the strains from brewing sources could produce 3-Met, and nearly half of the strains produced more than 0.5 g/L of 3-Met. Among these, yeast F10404, Y03401, and Y8#01, produced more than 1.0 g/L of 3-Met, with yeast Y03401 producing the highest amount at 1.30 g/L. Through morphological observation, physiological and biochemical analysis, and molecular biological identification, it was confirmed that yeast Y03401 was a . Subsequently, the optimal fermentation conditions for 3-Met production by this yeast were obtained through single-factor designs, Plackett-Burman test, steepest ascent path design and response surface methodology. When the glucose concentration was 60 g/L, yeast extract concentration was 0.8 g/L, L-methionine concentration was 3.8 g/L, initial pH was 4, incubation time was 63 h, inoculum size was 1.6%, shaking speed was 150 rpm, loading volume was 50 mL/250 mL, and temperature was 26 °C, the content of 3-Met produced by Y03401 reached a high level of 3.66 g/L. It was also noteworthy that, in contrast to other study findings, this yeast was able to create substantial amounts of 3-Met even in the absence of L-methionine precursor. Based on the clear genome of and its characteristics in 3-Met production, Y03401 had broad prospects for application in alcoholic beverages such as .
PubMed: 38731667
DOI: 10.3390/foods13091296 -
Molecules (Basel, Switzerland) May 2024The cyclometalated terpyridine complexes [Ru(η-OAc)(NC-tpy)(PP)] (PP = dppb , (,)-Skewphos , (,)-Skewphos ) are easily obtained from the acetate derivatives...
The cyclometalated terpyridine complexes [Ru(η-OAc)(NC-tpy)(PP)] (PP = dppb , (,)-Skewphos , (,)-Skewphos ) are easily obtained from the acetate derivatives [Ru(η-OAc)(PP)] (PP = dppb, (,)-Skewphos , (,)-Skewphos ) and tpy in methanol by elimination of AcOH. The precursors , are prepared from [Ru(η-OAc)(PPh)] and Skewphos in cyclohexane. Conversely, the NNN complexes [Ru(η-OAc)(NNN-tpy)(PP)]OAc (PP = (,)-Skewphos , (,)-Skewphos ) are synthesized in a one pot reaction from [Ru(η-OAc)(PPh)], PP and tpy in methanol. The neutral NC-tpy , , and cationic NNN-tpy , complexes catalyze the transfer hydrogenation of acetophenone (S/C = 1000) in 2-propanol with NaOPr under light irradiation at 30 °C. Formation of ()-1-phenylethanol has been observed with , in a MeOH/PrOH mixture, whereas the -enantiomer is obtained with , (50-52% ). The tpy complexes show cytotoxic activity against the anaplastic thyroid cancer 8505C and SW1736 cell lines (ED = 0.31-8.53 M), with the cationic displaying an ED of 0.31 M, four times lower compared to the enantiomer .
Topics: Humans; Catalysis; Ruthenium; Cell Line, Tumor; Pyridines; Antineoplastic Agents; Coordination Complexes; Molecular Structure; Photochemical Processes
PubMed: 38731639
DOI: 10.3390/molecules29092146 -
Acta Crystallographica Section B,... Jun 2024The molecule of anti-epileptic drug lamotrigine [LAM; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is capable of the formation of multicomponent solids. Such an...
The molecule of anti-epileptic drug lamotrigine [LAM; 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine] is capable of the formation of multicomponent solids. Such an enhanced tendency is related to the diverse functionalities of the LAM chemical groups able to form hydrogen bonds. Two robust synthons are recognized in the supramolecular structure of LAM itself formed via N-H...N hydrogen bond: homosynthon, so-called aminopyridine dimer or synthon 1 [R(8)] and larger homosynthon 2 [R(8)]. The synthetic procedures for a new hydrate and 11 solvates of LAM (in the series: with acetone, ethanol: two polymorphs: form I and form II, 2-propanol, n-butanol, tert-butanol, n-pentanol, benzonitrile, acetonitrile, DMSO and dioxane) were performed. The comparative solid state structural analysis of a new hydrate and 11 solvates of LAM has been undertaken in order to establish robustness of the supramolecular synthons 1 and 2 found in the crystal structure of LAM itself as well as LAM susceptibility to build methodical solid state supramolecular architecture in the given competitive surrounding of potential hydrogen bonds. The aminopyridine dimer homosynthon 1 [R(8)] has been switched from para-para (P-P) topology to ortho-ortho (O-O) topology in all crystal structures, except in LAM:n-pentanol:water solvate where it remains P-P. Homosynthon 2 [R(8)] of the LAM crystal structure imitates in the LAM solvates as a heterosynthon by replacing the triazine nitrogen proton acceptor atoms of LAM with the proton acceptors of solvates molecules.
PubMed: 38728045
DOI: 10.1107/S2052520624002567 -
BMC Chemistry May 2024This study aimed to measure both the solubility and thermodynamics of salicylic acid in binary solvent mixtures of (2-propanol + ethylene glycol) and...
This study aimed to measure both the solubility and thermodynamics of salicylic acid in binary solvent mixtures of (2-propanol + ethylene glycol) and (2-propanol + propylene glycol) at different temperatures in the range of 293.2-313.2 K. The experimental solubility data were analyzed using various linear and nonlinear cosolvency models, such as the van'tt Hoff, Jouyban-Acree, Jouyban-Acree-van'tt Hoff, mixture response surface and modified Wilson models and to evaluate the models, the mean relative deviations of the back-calculated solubility data were compared with experimental values. Through this analysis, the apparent thermodynamic parameters, including Gibbs energy, enthalpy, and entropy were calculated using the van'tt Hoff and Gibbs equations for this system. Additionally, the density values for salicylic acid saturated mixtures were also measured and represent mathematically using the Jouyban-Acree model.
PubMed: 38724985
DOI: 10.1186/s13065-024-01188-1 -
Chemphyschem : a European Journal of... May 2024The interaction between organic molecules and oxidized catalyst surfaces has frequently been used to study the fuel crossover from the anode to the cathode in direct...
The interaction between organic molecules and oxidized catalyst surfaces has frequently been used to study the fuel crossover from the anode to the cathode in direct liquid fuel cells. In such experiments, the oxidized surface is put in contact with the fuel under open circuit conditions, and the evolution of the potential is registered. The open circuit potential (OCP) vs. time features can then inform on the reactivity of the fuel with the oxidized surface and provide valuable information not only to applications in fuel cells but also to the electrochemical reform of those molecules to produce clean hydrogen. In this paper, we present an experimental investigation of the open circuit interaction between ethanol or 2-propanol with oxidized platinum surfaces. Besides the OCP time traces, we have also employed cyclic voltammetry and fast oxide reduction sweep in the presence of the alcohols. Comparable reaction currents are obtained in the cyclic voltammogram, but the electro-oxidation of 2-propanol sets in at considerably lower overpotentials than that of ethanol. At the high potential region, both the magnitude and the potential of the current peak are nearly identical in both cases. In contrast, under open circuit conditions, the interaction of ethanol with the oxidized platinum surface is more pronounced than that found for 2-propanol, and these results are corroborated by the facile reduction of the platinum oxides along the fast backward sweep for the case of the latter.
PubMed: 38721776
DOI: 10.1002/cphc.202400359 -
Angewandte Chemie (International Ed. in... May 2024n-propanol is an important pharmaceutical and pesticide intermediate. To produce n-propanol by electrochemical reduction of CO2 is a promising way, but is largely...
n-propanol is an important pharmaceutical and pesticide intermediate. To produce n-propanol by electrochemical reduction of CO2 is a promising way, but is largely restricted by the very low selectivity and activity. How to promote the coupling of *C1 and *C2 intermediates to form the *C3 intermediate for n-propanol formation is challenging. Here, we propose the construction of bicontinuous structure of Cu2O/Cu electrocatalyst, which consists of ultra-small Cu2O nanodomains, Cu nanodomains and large amounts of grain boundaries between Cu2O and Cu nanodomains. The n-propanol current density is as high as 101.6 mA cm-2 at the applied potential of -1.1 V vs. reversible hydrogen electrode in flow cell, with the Faradaic efficiency up to 12.1%. Moreover, the catalyst keeps relatively stable during electrochemical CO2 reduction process. Experimental studies and theoretical calculations reveal that the bicontinuous structure of Cu2O/Cu can facilitate the *CO formation, *CO-*CO coupling and *CO-*OCCO coupling for the final generation of n-propanol.
PubMed: 38719782
DOI: 10.1002/anie.202405733