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The many-body expansion, where one computes the total energy of a supersystem as the sum of the dimer, trimer, tetramer, etc., subsystems, provides a convenient approach to compute the lattice energies of molecular crystals. We investigate approximate methods for computing the non-additive three-body contributions to the crystal lattice energy of the polar molecules acetic acid, imidazole, and formamide, comparing to coupled-cluster singles, doubles, and perturbative triples [CCSD(T)] level benchmarks. Second-order Møller–Plesset perturbation theory (MP2), if combined with a properly damped Axilrod–Teller–Muto dispersion potential, displays excellent agreement with CCSD(T) at a substantially reduced cost. Errors between dispersion-corrected MP2 and CCSD(T) are less than 1 kJ mol−1 for all three crystals. However, the three-body energy requires quite large distance cutoffs to converge, up to 20 Å or more. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal. METHODS: We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). We analyzed sleep-wake transition probabilities, EEG spectra, and sleep spindle properties including density, dispersion, and slow oscillation phase coupling. The wake EEG similarity index (WESI) was determined using a machine learning algorithm analyzing the spectral profile of the EEG. RESULTS: At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities (p

BACKGROUND: High-grade endometrial cancers (EAC) are aggressive tumors with a high risk of progression after treatment. As EAC may harbor mutations in the RAS/MAPK pathways, we evaluated the preclinical in vitro and in vivo efficacy of avutometinib, a RAF/MEK clamp, in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718, against multiple primary EAC cell lines and xenografts. METHODS: Whole-exome sequencing (WES) was used to evaluate the genetic landscape of five primary EAC cell lines. The in vitro activity of avutometinib and defactinib as single agents and in combination was evaluated using cell viability, cell cycle, and cytotoxicity assays. Mechanistic studies were performed using Western blot assays while in vivo experiments were completed in UTE10 engrafted mice treated with either vehicle, avutometinib, VS-4718, or their combination through oral gavage. RESULTS: WES results demonstrated multiple EAC cell lines to harbor genetic derangements in the RAS/MAPK pathway including KRAS/PTEN/PIK3CA/BRAF/ARID1A, potentially sensitizing to FAK and RAF/MEK inhibition. Five out of five of the EAC cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition. By Western blot assays, exposure of EAC cell lines to defactinib, avutometinib, and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-MEK and p-ERK. In vivo the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition compared to single-agent treatment and controls starting at Day 9 (p

We calculate electron impact partial and total ionization cross sections of R-carvone (C10H14O), 2-butanol (C4H10O), imidazole (C3H4N2), and 2-nitroimidazole (C3H3N3O2). We have used the Binary Encounter Bethe (BEB) model to obtain total electron impact ionization cross sections (TICSs). The modified BEB method in combination with mass spectrum data of the molecules is used to calculate the partial ionization cross section (PICS) of the cationic fragments dissociating from the parent molecule. Our PICS data for R-carvone and 2-butanol are in good agreement with the experimental data for all the cation fragments along with the TICS data. For imidazole and 2-nitroimidazole, the estimates of the PICS are reported for the first time in the present study. We have found that both the modified BEB method and the mass spectrum dependence method work effectively to estimate PICS if we have information about the appearance energies and relative abundance data of the target under investigation. [ABSTRACT FROM AUTHOR]

Histidine can be protonated on either or both of the two N atoms of the imidazole moiety. Each of the three possible forms occurs as a result of the stereochemical environment of the histidine side chain. In an atomic model, comparing the possible protonation states in situ, looking at possible hydrogen bonding and metal coordination, it is possible to predict which is most likely to be correct. A more direct method is described that uses quantum-mechanical methods to calculate, also in situ, the minimum geometry and energy for comparison, and therefore to more accurately identify the most likely protonation state.

Hydration, as a ubiquitous and vital phenomenon in nature, has attracted great attention in the field of surface science concerning the fundamental interactions between water and organic molecules. However, the role of functional group derivatization is still elusive in terms of its potential impact on hydration. By the combination of high-resolution scanning tunneling microscopy imaging and density functional theory calculations, the hydration of 9mA molecules was realized on Au(111) in real space, forming 9mA–H2O–9mA structures. In comparison with the hydration of adenine molecules, methyl derivatization is experimentally found to remotely regulate the hydration sites from the imidazole ring to the pyrimidine ring and is further theoretically revealed to allow intramolecular electron redistribution and, therefore, steer the priority of the hydration sites. These results provide sub-molecular understandings of the relationship between derivatization and hydration, which would shed light on the regulation of hydration processes in chemically and biologically related systems. [ABSTRACT FROM AUTHOR]

Ponatinib, the only approved all known-BCR::ABL1 inhibitor, is a third-generation tyrosine-kinase inhibitor (TKI) designed to inhibit BCR::ABL1 with or without any single resistance mutation, including T315I, and induced robust and durable responses at 45 mg/day in patients with CP-CML resistant to second-generation TKIs in the PACE trial. However, cardiovascular toxicities, including arterial occlusive events (AOEs), have emerged as treatment-related AEs within this class of TKIs. The OPTIC trial evaluated the efficacy and safety of ponatinib using a novel, response-based, dose-reduction strategy in patients with CP-CML whose disease is resistant to ≥2 TKIs or who harbor T315I. To assess the dose-response relationship and the effect on the safety of ponatinib, we examined the outcomes of patients with CP-CML enrolled in PACE and OPTIC who received 45 mg/day of ponatinib. A propensity score analysis was used to evaluate AOEs across both trials. Survival rates and median time to achieve ≤1% BCR::ABL1IS in OPTIC were similar or better than in PACE. The outcomes of patients with T315I mutations were robust in both trials. Patients in OPTIC had a lower exposure-adjusted incidence of AOEs compared with those in PACE. This analysis demonstrates that response-based dosing for ponatinib improves treatment tolerance and mitigates cardiovascular risk.

Herein, four new cuprous iodide hybrid materials 1–4 were synthesized at room temperature using two types of ligands: imidazoles and triphenylphosphine. Photoluminescence results showed that all the materials exhibited blue emissions with high internal quantum yields (IQYs) ranging from 51% to 64%. Surprisingly, the introduction of triphenylphosphine induced strong aggregation-induced emission (AIE). Additionally, the luminescence lifetimes of these materials were significantly longer, ranging from 11.53 μs to 24.33 μs, which is much longer than those of previous materials. These findings suggest that these materials could be potential candidates for non-rare earth element (REE) lighting phosphors. [ABSTRACT FROM AUTHOR]

Polymers can be assembled into nanomaterials with different structures. Exploring new assembly methods for hydrophilic polymers in drug delivery is of significant importance. In this work, we further advanced this field by synthesizing novel polymeric nanoparticles via a Zn coordination-induced assembly mechanism. A new hydrophilic copolymer (polyethylene glycol-block-polyacrylic acid-modified-N-(3-aminopropyl)-imidazole (CH3O-PEG2000-b-PAA60-Imi)) was designed by efficiently coupling imidazole pendants onto the PAA chain within CH3O-PEG2000-b-PAA60. The coordination between the imidazole pendants and zinc ions induced the crosslinking of the resulting copolymers into polymeric nanoparticles (CH3O-PEG2000-b-PAA60-(Imi/Zn)). Exposure of the polymeric nanoparticles to slightly acidic conditions disrupted the coordination bond between the imidazole pendants and the zinc ions. The pH-responsive property led to the disintegration of the polymerized nanoparticles and the release of the drug. In vitro results further confirmed that the drug-loaded CH3O-PEG2000-b-PAA60-(Imi/Zn) exhibited toxicity to tumor cells. Accordingly, the coordination-induced assembly mechanism shows great promise for fabricating polymeric nanoparticles, particularly when the use of water as a solvent is essential. [ABSTRACT FROM AUTHOR]

Abstarct: In order to improve the curing rate, this study investigated the influence of various accelerators and their combinations on the curing behavior of epoxy resins. differential scanning calorimetry (DSC) was used to analyze the curing behavior of various accelerators in diglycidyl ether of the bisphenol A epoxy resin and the methyl hexahydrophthalic anhydride curing system, and activation energies were calculated using the Kissinger and Ozawa models. The results indicated a self‐catalytic characteristic in the curing process and showed that the activation energies for tris(dimethylaminomethyl)phenol (DMP‐30) and 1‐cyano‐2‐ethyl‐4‐methylimidazole (2E4MZ‐CN) were significantly lower compared to N,N‐dimethylbenzylamine, demonstrating higher curing reactivity. Furthermore, a novel strategy combining tertiary amine accelerator (DMP‐30) and imidazole accelerator (2E4MZ‐CN) was proposed and the activation energy variations with the degree of cure were analyzed employing the KAS method. When the mass ratio of DMP‐30 to 2E4MZ‐CN was 1:3, the activation energy was 59.08 kJ/mol, approximately 12% lower than using a single accelerator, which indicated the synergistic effects of the accelerators. Finally, the mechanism of synergistic effect of tertiary amine and imidazole accelerators on epoxy resin curing were proposed. [ABSTRACT FROM AUTHOR]

Objective: Opioid metabolism and pharmacodynamics may be affected in hepatic patients. Ketamine and dexmedetomidine are conventional anesthetics used in our daily practice. The opioid-sparing effects of this combination have not been evaluated in patients with liver cirrhosis undergoing liver resection. We aimed to investigate the potential peri-operative opioid-sparing effects of intra-operative dexmedetomidine and ketamine infusions in patients with Child A liver cirrhosis undergoing liver resection. Methods: This study was a randomized controlled double-blind trial. 92 adult patients of both sex with Child class (A) liver cirrhosis aged 18 to 65 years entering and completing the study. We excluded patients with renal or cardiac dysfunction or contraindications from study medications.46 patients in the opioid-sparing group (OS) receiving ketamine and dexmedetomidine infusions and 46 patients in the opioid-based (OB) group as controls. The main outcome measures: were intra-operative fentanyl requirements, postoperative fentanyl requirements, visual analogue pain scores, postoperative nausea, vomiting, ileus, desaturation, intra-operative hemodynamic events, and ICU stay were recorded. Results: The total intra-operative fentanyl consumption was significantly lower in the OS group compared with the OB group, 183.2 ± 35.61 µg and 313.5 ± 75.06 µg, respectively, P < 0.001. The postoperative 1st 48 h fentanyl consumption was significantly lower in the OS group compared with the OB group, 354.5 ± 112.62 µg and 779.1 ± 294.97 ± µg, respectively, P < 0.001. Visual analogue scores were significantly better in the OS group at the early 2-hour assessment point postoperatively. The postoperative adverse events were significantly more frequent in the opioid-based group. ICU stay was significantly shorter in the OS group. Conclusions: Administering dexmedetomidine and ketamine infusions intra-operatively to patients with Child A liver cirrhosis undergoing liver resection resulted in notable opioid-sparing effects, with reductions of approximately 40% intra-operatively and 55% postoperatively. The opioid-sparing group exhibited improved postoperative outcomes, including reduced pain, decreased incidence of opioid-related side effects and shorter ICU stays. [ABSTRACT FROM AUTHOR]

The management of sedation in critically ill adults poses a unique challenge to clinicians. Dexmedetomidine, an α2 agonist, has a unique mechanism and favorable pharmacokinetics, making it an attractive intravenous option for sedation and delirium in the intensive care unit. However, patients may be at risk for withdrawal with prolonged use, adding to the complexity of sedation and agitation management in this patient population. Enteral α2 agents have the benefit of cost savings and ease of administration, thus playing a role in the ability to decrease intravenous sedative use and prevent dexmedetomidine withdrawal. Clonidine and guanfacine are the two most common enteral α2 agents utilized for this purpose, however, there is a paucity of evidence regarding the comparative benefit between the two agents. The decision to use one vs the other agent should be determined based on their differing pharmacology, pharmacokinetics, and side effect profile. The most effective dosing strategy for these agents is also unknown. Ultimately, more robust literature is required to determine enteral α2 agonists place in therapy. This narrative review evaluates the currently available literature on the use of α2 agonists in critically ill adults with an emphasis on sedation, delirium, and withdrawal. [ABSTRACT FROM AUTHOR]

Background: Emergence agitation EA is a state of confusion and harmful aggressiveness during recovery. It is a common complication after rhinoplasty, with risk of trauma, bleeding, and hemodynamic instability. Dexmedetomidine and gabapentin premedication could improve the quality of recovery after rhinoplasty. Methods: One hundred fifty-three participants (ASA I-II, both sexes and age 18–40 years) scheduled for rhinoplasty were randomized into three groups. Group C didn't receive premedication, Group D received intramuscular (IM) dexmedetomidine, and Group G received oral gabapentin. The degree of EA by Riker sedation-agitation scale (RSAS) during recovery, pain severity, and adverse events recorded. Results: The results showed statistically significant differences in EA scores with the lowest values in group D (p-value 0.002). Moreover, the incidence of EA was 17.6% (9/51) in Group D, 41.2% (21/51) in Group G, and 56.9% (29/51) in Group C with P value < 0.001 and significant differences in VAS score at 4, 8, and 12 h with the highest median (range) values in group C 4(3–6) in comparison to group D 2(1–3) and group G 2(1–3) and p-value < 0.001; no significant differences in adverse events. Conclusions: IM dexmedetomidine premedication was more efficient than gabapentin in the reduction of the emergence agitation incidence, severity, and postoperative pain scores after rhinoplasty in adults. Clinical trial registration number ID: NCT05626998 on 25/11/2022. [ABSTRACT FROM AUTHOR]

Background: Patient safety is important in daily anesthesia practices, and providing deep anesthesia is difficult. Current debates on the optimal anesthetic agents highlight the need for safer alternatives. This study was justified by the need for safer and more effective anesthetic protocols for outpatient hysteroscopic procedures, particularly those conducted outside the operating room. Propofol, while widely used, has significant limitations, including respiratory depression, hemodynamic instability, and delayed recovery when higher doses are required for adequate sedation. The addition of opioids to propofol, though beneficial for analgesia, introduces risks such as hypoxemia and hypotension. These challenges necessitate exploring alternative combinations that balance sedation depth with fewer side effects. Objective: To assess the efficacy and safety of deep sedoanalgesia achieved with dexmedetomidine-propofol versus remifentanil-propofol combinations in daily anesthesia practices. Design: Prospective randomized clinical study. Settings: This study was carried out at Dursun Odabaş Medical Center. Patients: Eighty ASA I–II patients, aged 18–65, scheduled for elective hysteroscopic interventions under sedoanalgesia were included in the study. Main outcome measures: The primary aim of our study was to identify an anesthetic agent combination capable of delivering effective and safe deep sedation, with sedation depth assessed via the Ramsey Sedation Score (RSS) and respiratory safety evaluated through desaturation rates. Secondary endpoints included Visual Analogue Scale (VAS) scores, oxygen saturation (SpO2), patient, surgeon, and anesthesiologist satisfaction scores, hemodynamic parameters, the time to achieve an RSS > 4, the time to reach a Modified Aldrete Score (MAS) > 9, and the requirement for mask ventilation and jaw thrust maneuvers. Interventions: Patients were randomized into two groups (n = 40 each): Group DP (Dexmedetomidine–Propofol): A bolus of 1 mg/kg IV propofol and 1 mcg/kg IV dexmedetomidine over 10 min, followed by a continuous infusion of 0.2–1.4 mcg/kg/hour. Group RP (Remifentanil–Propofol): A bolus of 1 mg/kg IV propofol and 0.25 mcg/kg IV remifentanil, followed by a continuous infusion of 0.025–0.1 mcg/kg/minute. Results: Patients in the DP group exhibited significantly lower VAS scores and desaturation rates (p = 0.003) compared to the RP group. Satisfaction scores (patient, surgeon, anesthesiologist) and integrated pulmonary index (IPI) values were significantly higher in the DP group (p < 0.05). Conclusion: The dexmedetomidine-propofol combination is an effective and safe anesthetic regimen for deep sedation in outpatient hysteroscopic procedures, offering adequate sedation and superior preservation of respiratory function. Additionally, the dexmedetomidine-propofol combination ensures more stable hemodynamics, with a lower incidence of hypoxia, and results in higher satisfaction rates among patients, surgeons, and anesthesiologists. Trial registration: Clinical Trials ID is NCT05674201 Date 2022.12.07. Key points: Dexmedetomidine combined with propofol provides adequate depth of anesthesia and analgesia for hysteroscopic procedures. The combination of dexmedetomidine and propofol affects respiratory function less, and hypoxemia is less common in patients. When nonoperating rooms administer dexmedetomidine, one should be prepared for cardiovascular complications, especially bradycardia. [ABSTRACT FROM AUTHOR]

Background: Patients undergoing general anesthesia are more frequently monitored for depth of anesthesia using processed electroencephalography. Opioid-free anesthesia is nowadays an accepted modality for general anesthesia, however it is unclear how to interpret data from processed electroencephalography when using a mixture of non-opioid anesthetic drugs. Our objective was to describe density spectral array patterns and compare processed encephalographic data indices between opioid-free and routine opioid based anesthesia. Methods: This prospective observational cohort study was conducted on 30 adult patients undergoing laparoscopic surgery in a non-tertiary regional hospital. The patients underwent general anesthesia with three different methods and were monitored for anesthesia depth using processed encephalography and density spectral array. Primary outcome is a group-derived mean difference in patient state index and spectral edge frequency. As a secondary outcome a descriptive comparison of the spectral power, derived from the density spectral array, was done between groups. Results: The opioid-free anesthesia group had significantly higher patient state index and spectral edge frequency compared to routine anesthesia. Density spectral array patterns were also different, most notably lacking the high power in alpha frequency spectrum seen in the other routine anesthesia methods. Conclusions: Processed electroencephalography monitoring can be used in opioid-free anesthesia, however clinicians should expect higher values in monitoring indices. The density spectral array pattern using a common protocol for opioid-free anesthesia, with mainly sevoflurane combined with low doses of dexmedetomidine and esketamine, differs from well described opioid and GABA-ergic anesthesia methods. These findings should be further validated using other protocols for opioid-free anesthesia in order to safely monitor anesthesia depth. Trial registration: Clinicaltrials.gov registration number NCT06227143, registration date; 26th of January 2024. [ABSTRACT FROM AUTHOR]

AbstractTetrasubstituted imidazoles are a class of privileged heterocycles with diverse applications in medicinal chemistry, materials science, and catalysis. Organocatalysis has emerged as a powerful tool for the synthesis of these complex molecules. This review provides a critical overview of recent progress in organocatalytic approaches to tetrasubstituted imidazole synthesis, highlighting key advances, challenges, and opportunities in this rapidly evolving field. We discuss the scope of various organocatalytic strategies, and provide insights into the outcomes of these reactions. This review aims to provide a comprehensive and authoritative assessment of the current state of the art in organocatalytic tetrasubstituted imidazole synthesis, and to identify future directions for research in this exciting area. [ABSTRACT FROM AUTHOR]

Diazidodifluoromethane was prepared from dibromodifluoromethane, sodium azide and an alkanethiolate initiator. It represents the first example of a diazidomethane that is stable enough to be used in synthesis. The stability of (poly)azidomethanes was explored with ab initio calculations. Copper(I)-catalysed azide–alkyne cycloaddition of the title azide with alkynes afforded difluoromethylene-containing bis(1,2,3-triazoles)amenable to Rh(II)-catalysed transannulation with nitriles to difluoromethylene bis(imidazoles). [ABSTRACT FROM AUTHOR]

Post-dural puncture headache (PDPH) is a debilitating complication of neuraxial anesthesia, particularly prevalent in obstetric patients, usually characterized by a postural headache. PDPH is hypothesized to result from cerebrospinal fluid leakage through a dural puncture, triggering symptoms like neck stiffness and subjective hearing changes. While conservative measures are common for treatment, more refractory cases may require invasive interventions such as an epidural blood patch (EBP). Recent studies have shown promise in using nebulized dexmedetomidine (nDEX) for PDPH, offering a non-invasive alternative to EBP. Two case presentations illustrate the efficacy of nDEX in resolving PDPH symptoms rapidly and completely. These cases underscore the need for exploring novel therapeutic options, especially in obstetric patients where safe and prompt relief is essential for maternal and newborn well-being. While the EBP remains the gold standard, its limitations of accessibility and invasiveness highlight the significance of investigating alternatives like nDEX. [ABSTRACT FROM AUTHOR]

Background: Cell membrane chromatography (CMC) is a biochromatography with a dual function of recognition and separation, offering a distinct advantage in screening bioactive compounds from Chinese medicines (CMs). Yindan Xinnaotong soft capsule (YD), a CM formulation, has been widely utilized in the treatment of cardiovascular disease. However, a comprehensive mapping of the myocardial protective active compounds remains elusive. Purpose: To establish a stable and efficient 2D H9c2/CMC-RPLC-MS system, and to utilize it for screening the active compounds of YD that are associated with myocardial protection. Methods: An imidazole-modified silica gel exhibiting high modification efficiency and protein binding capacity was synthesized to enhance the longevity and efficiency of H9c2/CMC. Subsequently, the potentially bioactive compounds of YD were screened by integrating the 2D H9c2/CMC-RPLC-MS system with a high-content component knockout strategy. Additionally, an RNA-seq approach was employed to predict the targets and mechanisms of YD and the active compounds for myocardial protection. Results: The developed imidazole-modified H9c2/CMC exhibits remarkable selectivity, specificity, stability, and reproducibility. Following three rounds of screening, a total of 24 potential myocardial protective compounds were identified, comprising 8 flavonoids, 8 phenolic acids, 4 saponins, and 4 tanshinones. Bioinformatic analysis utilizing RNA-seq indicated that the FOXO signaling pathway, with FOXO3 identified as a key target, plays a significant role in the cardioprotective effects of YD. Furthermore, all 24 screened compounds exhibit strong binding affinities with FOXO3 evaluated by molecular docking. Conclusion: A highly stable and efficient 2D imidazole-modified H9c2/CMC-RPLC-MS system was developed, allowing for the screening of potentially active compounds from YD. Through the integration of the bioinformatic analysis, the pharmacodynamic foundation of YD for myocardial protection has been comprehensively characterized. [ABSTRACT FROM AUTHOR]

The efficient removal of dyes is of significant importance for environmental purification and human health. In this study, a novel material (Si-MPTS-IL) has been synthesized by the immobilization of imidazole ionic liquids (ILs) onto nano-silica using the radiation grafting technique. The adsorption performance of Si-MPTS-IL for Coomassie Brilliant Blue (CBB) removal is studied by a series of static adsorption experiments. It is found that Si-MPTS-IL has ultra-fast adsorption kinetics, reaching equilibrium within 2 min. The adsorption process for CBB conforms to the Langmuir model. In addition, Si-MPTS-IL exhibits a negligible impact on the adsorption efficiency of CBB with the increase in salt concentration. After six cycles of adsorption–desorption, the adsorption efficiency of Si-MPTS-IL remained above 80%, indicating excellent regenerative properties and a promising candidate for the treatment of wastewater containing CBB. A study of the mechanism indicates that the CBB capture by Si-MPTS-IL can be attributed to the synergistic effects of electrostatic interactions and pore filling. [ABSTRACT FROM AUTHOR]

The properties (geometry, bond-dissociation enthalpies and proton affinities) of three azoles, pyrrole, imidazole and pyrazole, with twenty-two N-substituents R covering a significant part of the periodic table [1 (lithium group, alkaline), 2 (beryllium group, alkaline earth), 13 (boron group, triel), 14 (carbon group, tetrel), 15 (nitrogen group, pnictogen), 16 (oxygen group, chalcogen) and 17 (fluorine group, halogen) of the periods 2, 3 and 4 plus the hydrogen] have been calculated with the G4 composite ab initio method. These three properties were discussed with regard to the azole and to the group R using as model compound the amines H2N–R. The large set of compounds and their consistency allowed finding many equations that related different calculated properties. General properties such as bond-dissociation enthalpies, BDH, N–R bond lengths and proton affinities were tested in search of simple equations that explain the calculated properties. [ABSTRACT FROM AUTHOR]

Background: There is controversy surrounding the influence of dexmedetomidine on the recovery of postoperative gastrointestinal dysfunction in patients under general anesthesia. The main purpose of this meta-analysis is to evaluate the effect of dexmedetomidine administration during the perioperative period on the recovery of gastrointestinal function in patients under general anesthesia. Methods: A systematic review and meta-analysis with trial sequential analysis was performed to identify randomized controlled trials comparing dexmedetomidine administration with placebo for the recovery of gastrointestinal function. The primary outcomes were gastrointestinal function; first oral feeding time; incidences of postoperative nausea and vomiting, postoperative nausea, and postoperative vomiting; time to first bowel sound; time to first flatus; and time to first defecation. The secondary outcome was the length of hospital stay. Results: A total of 20 studies comparing 2,470 participants were included in this meta-analysis. Perioperative dexmedetomidine administration did not result in a significant reduction in the time to first oral feeding (MD= -7.91, 95% CI = − 16.45 to 0.62, P = 0.07). However, dexmedetomidine administration was associated with a decreased incidence of postoperative nausea and vomiting (RR = 0.72, 95% CI = 0.58 to 0.88, P = 0.001), time to first flatus (MD= -6.73, 95% CI= -10.31 to -3.15, P = 0.0002), and time to first defecation (MD= -12.01, 95% CI = -22.40 to -1.61, P = 0.02). Conclusions: Perioperative dexmedetomidine administration can promote the recovery of gastrointestinal function and reduce the length of hospital stay after abdominal surgery. The optimal dose and timing of dexmedetomidine and the influence on non-abdominal surgery need further investigation. Trial registration: The study protocol was registered in the PROSPERO database (registration number: CRD42023443708) on July 9, 2023. [ABSTRACT FROM AUTHOR]

Nitrate reduction represents a sustainable strategy for water denitrification. Herein we design an AuPt@ZIF-8 composite film, via coating a zeolite imidazole framework-8 (ZIF-8) on a porous AuPt alloy, for an efficient electrocatalytic nitrate reduction. It exhibits a superior ammonia yield of (131.5 ± 3.4) μg h−1 mgcat−1, faradaic efficiency of (95.8 ± 3.0)% and selectivity of 96%, overcoming individual Au, Pt, ZIF-8, and other widely-used Au-based alloys. [ABSTRACT FROM AUTHOR]

Background: Postoperative pain usually occur in patients who have undergone functional endoscopic sinus surgery (FESS). Remimazolam and dexmedetomidine could enhance the quality of recovery (QoR) after surgery. The aim of this study was to compare the effects of remimazolam and dexmedetomidine with respect to the QoR-40 score of patients who have undergone FESS. Methods: A total of 120 patients (18–65 years) scheduled for FESS were randomly allocated to Group R, Group D or Group C. Group R received 0.075 mg/kg remimazolam loading and 0.1 mg/kg/h infusion. Group D received dexmedetomidine (1.0 µg/kg loading, 0.5 µg/kg/h infusion). Group C received a placebo equal to dexmedetomidine. Anaesthesia was induced with propofol, sufentanil and cisatracurium. Anaesthesia maintenance was performed via target-controlled infusions (TCIs) of propofol and remifentanil. The primary outcome was the QoR-40 score on the day before surgery and postoperative Day 1 (POD1). The secondary outcomes were the time to return to consciousness, length of stay in the PACU, sedation score upon PACU arrival, pain, postoperative nausea and vomiting (PONV) and cumulative consumption of propofol and remifentanil. Adverse effects were recorded. Results: The total QoR-40 scores (median, IQR) on POD1 decreased less (154.5, 152.0 -159.0) in Groups R and D (155.0, 154.8 -159.3) than in Group C (139.0, 136.8 -142.0) (P < 0.001). The time to return of consciousness and the length of stay in the PACU were significantly shorter in Groups R and C than in Group D (P < 0.001). The level of sedation upon PACU arrival (median, IQR) in Groups R (-2.0, -2.0—-1.0) and D (-2.0, -3.0—-2.0) was greater than that in Group C (1.0, 0.0 -1.0) (P < 0.001). The cumulative consumption rates of propofol and remifentanil in Groups R and D were lower than that in Group C (P < 0.001). Compared with that in Group C, the pain intensity was lower in Groups R and D (P < 0.001).The number of patients occurring PONV was less in Groups R (3/40) and D (4/40) than in Group C (11/40) (P = 0.024). Fifteen patients had bradycardia in Group D, whereas no bradycardia was noted in Groups R or C (P < 0.001). Conclusion: Administration of remimazolam could provide a similar QoR to that of dexmedetomidine. In addition, remimazolam may be a promising option for improving the QoR of patients who have undergone FESS. Trial registration: ChiCTR2300076209. (Prospectively registered). The initial registration date was 27/9/2023. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer recurrence and metastasis are significant challenges following surgery. Recent research suggests that anesthetic techniques used during cancer surgery may influence oncologic outcomes by affecting the body's immune response, stress levels, and inflammation. This review explores how different anesthetic methods may modulate perioperative pathophysiologic changes. Although the early findings are promising, the impact of anesthesia on long-term cancer outcomes remains unclear. Ongoing clinical trials aim to provide clearer insights into the impact of anesthesia, particularly in lung, breast, and colorectal cancer surgeries. These efforts highlight the importance of tailoring anesthetic care to meet the specific needs of individual patients. As more evidence emerges, it could guide the development of improved anesthetic strategies that not only enhance recovery but also reduce the risk of cancer recurrence. Cancer recurrence and metastasis remain critical challenges following surgical resection, influenced by complex perioperative mechanisms. This review explores how surgical stress triggers systemic changes, such as neuroendocrine responses, immune suppression, and inflammation, which promote the dissemination of residual cancer cells and circulating tumor cells. Key mechanisms, such as epithelial–mesenchymal transition and angiogenesis, further enhance metastasis, while hypoxia-inducible factors and inflammatory responses create a microenvironment conducive to tumor progression. Anesthetic agents and techniques modulate these mechanisms in distinct ways. Inhaled anesthetics, such as sevoflurane, may suppress immune function by increasing catecholamines and cytokines, thereby promoting cancer progression. In contrast, propofol-based total intravenous anesthesia mitigates stress responses and preserves natural killer cell activity, supporting immune function. Opioids suppress immune surveillance and promote angiogenesis through the activation of the mu-opioid receptor. Opioid-sparing strategies using NSAIDs show potential in preserving immune function and reducing recurrence risk. Regional anesthesia offers benefits by reducing systemic stress and immune suppression, though the clinical outcomes remain inconsistent. Additionally, dexmedetomidine and ketamine exhibit dual effects, both enhancing and inhibiting tumor progression depending on the dosage and context. This review emphasizes the importance of individualized anesthetic strategies to optimize long-term cancer outcomes. While retrospective studies suggest potential benefits of propofol-based total intravenous anesthesia and regional anesthesia, further large-scale trials are essential to establish the definitive role of anesthetic management in cancer recurrence and survival. [ABSTRACT FROM AUTHOR]

Benzylic C–H oxidation to form carbonyl compounds, such as ketones, is a fundamental transformation in organic synthesis as it allows for the preparation of versatile intermediates. In this review, we highlight the synthesis of aromatic ketones via catalytic, electrochemical, and photochemical oxidation of alkylarenes using different catalysts and oxidants in the past 5 years. Additionally, we also discuss the synthesis of heterocyclic molecules using benzylic C–H oxidation as a key step. These methods can potentially be used in medicinal, synthetic, and inorganic chemistry. [ABSTRACT FROM AUTHOR]

The solvothermal reactions of ZnCl2·6H2O, benzene-1,3,5-tribenzoic acid (H3btb), and N-heterocyclic ancillary imidazole (Im) or aminopyrimidine (a mp) ligands led to the creation of two-dimensional (2D) zinc(II) based metal–organic frameworks (MOFs), (Me2NH2)2[Zn2(btb)2(Im)2]·2DMF·3MeOH (1) and (Me2NH2)2[Zn2(btb)2(amp)]·H2O·2DMF·MeOH (2). The btb3− ligands in 1 and 2 form an anionic 2D layered structure with a (63) honeycomb (hcb) topology by linking to Zn(II) centres through their carboxylate groups. The incorporation of N-heterocyclic auxiliary ligands Im and amp into the hcb nets resulted in the formation of a 2D hydrogen-bonded and covalently pillared bilayer structure featuring two-fold interpenetrating networks. Each of these networks consists of small channels that are occupied by Me2NH2 cations and solvent molecules. Both 1 and 2 emit blue luminescence emissions in the solid state at room temperature and exhibit a great selectivity and sensitivity for the detection of acetone and multiple heavy metal ions including Hg2+, Cu2+, Fe2+, Pb2+, Cr3+, and Fe3+ ions. At 1 bar, activated 1 and 2 demonstrate moderate capacities for adsorbing CO2 at room temperature, with a preference for CO2 over N2. Notably, at higher pressures (up to 20 bar), their activated samples 1 and 2 show a temperature-dependent enhancement of CO2 uptake while retaining good stability. [ABSTRACT FROM AUTHOR]

A series of mixed-ligand complexes were prepared by reacting by a new primary imidazole azo ligand (4MCFD) and 1,10-phenanthroline as a secondary ligand with divalent ions of cobalt, nickel, mercury, and cadmium, yielding complexes with the general formula [M (4MCFD) (1,10-phen) Cl2]. The synthesized complexes were characterized using C.H.N. analysis, atomic absorption, FT-IR, UV-Vis, magnetic susceptibility, and molar conductivity. The stability constant (KStability) values and the effect of time at 25°C indicated high stability for these complexes. An octahedral geometry was suggested for all complexes, with both primary and secondary ligands acting as bidentate. The inhibition ability of the free ligands at 50 mg/mL in DMSO was found to be lower than that of the complexes against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. [ABSTRACT FROM AUTHOR]

Chemosensing of ions has gained considerable attention by chemists. Insight into the mechanism involved between sensors and ions always fascinates researchers to develop economical, sensitive, selective, and robust sensors. This review comprehensively explores the mechanism of interaction between Imidazole sensors and anions. With most of the research concentrating only on fluoride and cyanide, this review has highlighted a large gap in various anions detection including SCN−, Cr2O72−, CrO42−, H2PO4−, NO2−, and HSO4−.This study also includes a critical analysis of different mechanisms and their respective limits of detection, with a discussion of the reported results. [ABSTRACT FROM AUTHOR]

The increasing prevalence of antibiotic resistance poses a significant global risk to public health. Therefore, there is an urgent necessity to discover innovative antibacterial materials. In this study, we introduced a novel synthesis method that yielded 18 unique di-cationic ionic liquids (DILs), intricately crafted through a fusion of quaternization and metathesis reactions. These innovative compounds boasted imidazolium, pyridinium, and quaternary ammonium as their cationic constituents, accompanied by acetate and bisulfate ions as their anionic counterparts. The incorporation of spacer chains, specifically trans-1,4-dibromo-2-butene and α, α′-dibromo-p-xylene, facilitated the synthesis of these di-cations. Thorough characterization of the synthesized DILs was conducted using advanced spectroscopic techniques, including FTIR and nuclear magnetic resonance, ensuring a comprehensive understanding of their structural attributes. The central objective of this research was to assess the effectiveness of these DILs in combating a diverse spectrum of resilient bacterial strains commonly encountered in various environmental settings. This evaluation encompassed both gram-positive and gram-negative species. [ABSTRACT FROM AUTHOR]

Ketoconazole is a broad-spectrum Imidazole derivative antifungal that is effective for both superficial and systemic fungal infections that cannot be completely absorbed when administered orally because it has low solubility. This can be overcome by forming a ketoconazole niosome delivery system. Niosomes are vesicular systems formed using non-ionic surfactants that could increase the solubility and bioavailability of drugs. The purpose of this study was to form a ketoconazole niosome system to increase the bioavailability and therapeutic effectiveness of ketoconazole. Niosomes were made into nine formulas using 100 mg surfactant with variations in the combination of non-ionic surfactant concentrations Span 60 (70.80-98.29%):Sucrose Ester Palmitate (SEP) (1.71-29.20%), which produced Hydrophilic Liphophilic Balance (HLB) values between 4-8. The evaluations on niosomes were organoleptic tests, particle size tests, polydispersity indexes, zeta potentials, structural analysis using Forrier Transform Infra Red (FTIR), morphological analysis using Transmission Electron Microscope (TEM), entrapment efficiency tests and drug release tests. The results showed that the niosome system with an HLB value of 7.5 produced a vesicle size 336,13±3,14 nm, polydispersity index 0,000, zeta potensial - 52,16±1,54 mV, spherical form of vesicle and no found chemistry interaction between the components (result of TEM and FTIR), an entrapment efficiency value of 87.86±0.18% and a drug release test value for 24 hours of 97.23±2.16%. This showed that the ketoconazole niosome system made using a combination of span 60 surfactants and SEP with an HLB value of 7.5 was able to produce an excellent niosome system. [ABSTRACT FROM AUTHOR]

The opioid crisis has emphasized identification of opioid‐sparing analgesics. This study was designed as a prospective trial with retrospective control group to determine feasibility for implementing a high‐dose prolonged magnesium sulfate infusion for adjuvant analgesia in the pediatric intensive care unit. Approval was granted for study of children receiving total pancreatectomy with islet cell autotransplantation and liver transplantation ages 3–18 years. Study exclusions were pregnancy, neuromuscular disease, hypersensitivity, preoperative creatinine >1.5 times upper limit normal, arrhythmia or pacemaker presence, and clinician concern. Eleven patients were enrolled between January 2020 and December 2022. Magnesium sulfate bolus (50 mg/kg) followed by intravenous infusion (15 mg/kg/h) was initiated in the operating room and extended postoperatively (maximum 48 h). Serum magnesium levels were monitored serially. To prioritize safety, infusion dose was decreased by 5 mg/kg/h for levels greater than 3.5 mg/dL. Clinical team otherwise followed standard multimodal pain practice. Primary outcome was oral morphine equivalent per kg per day during intensive care course (maximum 7 days). Secondary outcomes focused primarily on magnesium safety, including hemodynamic variables, electrolyte variables, respiratory support, and opioid‐related side effects. There were no serious adverse events. Treatment group trended toward slightly higher intravenous fluid requirement (~1 bolus), however no increase in blood product. Treatment and control groups were otherwise comparable in targeted outcomes and overall adverse event profile. Use of a high‐dose magnesium sulfate infusion protocol for analgesic postoperative use in select transplant recipients appears feasible for continued optimization of study in the PICU. [ABSTRACT FROM AUTHOR]

Analgesia and sedation are often provided during mechanical ventilation in extremely preterm neonates. Opioids and benzodiazepines are the most frequently used agents but can have adverse effects. Dexmedetomidine, an alpha‐2 agonist, might be interesting to spare opioid and benzodiazepine use. The objective of this study was to describe a cohort of mechanically ventilated extremely, preterm infants treated with morphine with or without dexmedetomidine. This was a retrospective, observational, single‐center study in the neonatal intensive care unit of Creteil. We included preterm neonates born before 28 weeks of gestation and/or weighting less than 1000 g hospitalized between July 2017 and June 2020, on mechanical ventilation for at least 72 h and who received morphine with or without dexmedetomidine as a second‐ or third‐line treatment. We described morphine and midazolam exposure, respiratory, and digestive outcomes for patients who received dexmedetomidine and those who did not. Twenty nine preterm infants received morphine and dexmedetomidine, and 44 received morphine without dexmedetomidine. Dexmedetomidine was used in patients of 25.7 [25.1–26.7] weeks, 680 [600–750] g and significantly more often in patients with vascular complications during pregnancy (p = 0.008), intrauterine growth restriction (p = 0.01) and in patients who received higher cumulative doses of morphine (p = 0.01). Morphine and midazolam doses tended to decrease after the introduction of dexmedetomidine. Dexmedetomidine was never discontinued because of side effects. In this study, dexmedetomidine, used as a second or third‐line treatment during mechanical ventilation, was associated with a decrease in morphine and midazolam doses after introduction. Dexmedetomidine was used in a specific population of extremely preterm infants, with severe respiratory disease, who required prolonged mechanical ventilation and high morphine doses. This study highlights the need for pharmacokinetic/pharmacodynamic studies in this population, followed by randomized controlled trials and studies on the long‐term effects of dexmedetomidine to determine its place in analgosedation of ventilated preterm infants. [ABSTRACT FROM AUTHOR]

BackgroundBone biomarkers are strongly prognostic for overall survival (OS) in men with castration-resistant prostate cancer but not fully established for hormone-sensitive prostate cancer (HSPC).ObjectiveBone biomarkers in HSPC were prospectively evaluated as part of a phase 3 study of androgen deprivation therapy ± the CYP17 inhibitor orteronel.Design, setting, and participantsPatients were randomly divided into training (n = 316) and validation (n = 633) sets. Recursive partitioning and Cox proportional hazard models were employed.Outcome measurements and statistical analysisBone resorption (C-telopeptide and pyridinoline) and bone formation markers (C-terminal collagen propeptide and bone alkaline phosphatase) were assessed from patient sera.Results and limitationsOf 1279 men, 949 had evaluable baseline bone biomarkers. Optimal cutoffs were identified to define elevated levels of each of the four biomarkers (all p

In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684.

This article analyzes the effect of the type of surface modification (using silane coupling agents and dicarboxylic acids) on titanium dioxide particles used as fillers in polylactic acid composites, which were exposed to a photodegradative process. The thermomechanical properties of the composites were analyzed; it was found that the silane coupling agent with Imidazole allowed the composites to have Young's modulus values 60% lower than the composite without filler. On the other hand, the crystallization rate was 30% higher for composites with azelaic Acid attached to TiO2 particles than for composites without filler at a cooling rate of 5°C min−1. Once degraded composites containing azelaic acid were the least brittle, with a minor increment in Young's Modulus compared to pure polylactic acid composites. When a mixture of modified titanium dioxide particles (with imidazole and either azelaic acid or pimelic acid) was used, there was a synergistic effect regarding photostability. [ABSTRACT FROM AUTHOR]

Background: Spinal anesthesia for transurethral resection of the prostate (TURP) has a short duration, which poses challenges for postoperative pain management. The present study aimed to investigate the effects of intravenous (IV) dexmedetomidine at a dosage of 0.4 µg/kg in prolonging the duration of spinal anesthesia and minimizing postoperative pain in elderly patients undergoing TURP. Methods: This prospective randomized controlled trial enrolled 38 patients aged 60–80 years who underwent elective TURP with spinal anesthesia. The patients were randomly assigned to two treatment groups: Group D received IV 0.4 µg/kg dexmedetomidine, whereas Group C received IV normal saline after spinal anesthesia administration. The primary outcome was the time to 2-dermatome regression. Results: The 2-dermatome regression time was longer in Group D than in Group C (104.44 ± 16.97 min vs. 80.63 ± 15.59 min, p < 0.05). The peak sensory block levels were significantly higher in Group D [T7 (T6–T8)] than in Group C [T10 (T7–T10)] (p = 0.017). The incidence of hypotension and bradycardia and postoperative pain at 0, 6, 12, and 24 h were not different between two groups. Conclusion: Intravenous dexmedetomidine at a dosage of 0.4 µg/kg significantly prolongs the duration of spinal sensory blockade. Although postoperative analgesia was not different, it provided hemodynamic stability without increasing the side effects. [ABSTRACT FROM AUTHOR]

Background: The syndrome has these features: 3-methylglutaconic aciduria (MEG), deafness(D), encephalopathy (E), Leigh-like syndrome (L). This disorder is caused by biallelic mutations in serine active site-containing protein 1 (SERAC1) gene. When these patients experience hepatopathy (H) in addition to the above manifestations, the syndrome is referred to as MEGD(H)EL. The pathology of this syndrome shares features with diverse types of inborn errors of metabolism. Case presentation: We discussed the anaesthetic management of an infant 2-year-old suffering from MEGD(H)EL syndrome undergoing cochlear implant. We discuss the pathology, genetics and significant aspects of this sporadic disease which is important for anaesthesiologist. Conclusions: The usage of dexmedetomidine as the main anaesthetic drug might have the benefit of a non-triggering anaesthetic agent in patients with a mitochondrial disease. Mixture of dexmedetomidine and ketamine provide an effective combination for procedural sedation, predominantly in select populations who are at a high risk of perioperative complications due to underlying co-morbid conditions. [ABSTRACT FROM AUTHOR]

Herein, we present a method for the diastereoselective synthesis of N‐heterocycle‐substituted cyclobutanes from commercially available bromocyclobutanes. This method enables the efficient formation of various heterocyclic aminocyclobutane esters and amides using simple reagents. Notably, N‐nucleophiles such as imidazoles, azoles, and nucleobase derivatives were successfully incorporated, enhancing the chemical diversity of small ring building blocks for medicinal chemistry applications. [ABSTRACT FROM AUTHOR]

Delirium can result in undesirable outcomes including increased length of stays and mortality in patients admitted to the intensive care unit (ICU). Dexmedetomidine has emerged for delirium prevention in these patients; however, optimal dosing is challenging. A reinforcement learning-based Artificial Intelligence model for Delirium prevention (AID) is proposed to optimize dexmedetomidine dosing. The model was developed and internally validated using 2416 patients (2531 ICU admissions) and externally validated on 270 patients (274 ICU admissions). The estimated performance return of the AID policy was higher than that of the clinicians' policy in both derivation (0.390 95% confidence interval [CI] 0.361 to 0.420 vs. −0.051 95% CI −0.077 to −0.025) and external validation (0.186 95% CI 0.139 to 0.236 vs. −0.436 95% CI −0.474 to −0.402) cohorts. Our finding indicates that AID might support clinicians' decision-making regarding dexmedetomidine dosing to prevent delirium in ICU patients, but further off-policy evaluation is required. [ABSTRACT FROM AUTHOR]

A synthetic approach to imidazoles annulated to saturated six‐membered cycles featuring S, SO2, NH, NCbz was developed. It was achieved by combining the Neber rearrangement and the Marckwald reaction. The Neber rearrangement applied to cyclic ketones allowed us to prepare in hundred gram quantities previously unknown α‐amino ketones. Unstable tosyl ketoximes were used without purification immediately after their preparation. α‐Amino ketones react with potassium thiocyanate and cyanate in almost a quantitative yield affording highly pure imidazol‐2‐thiones or imidazol‐2‐ones. Desulfurization of imidazole‐2‐thiones using Raney nickel led to the formation of previously unknown 2‐unsubstituted fused imidazoles in high yields. [ABSTRACT FROM AUTHOR]

Objective: Mesenchymal stem cells (MSCs) have been highly confirmed for their critical role in the treatment of different diseases. This study focuses on the mechanism of umbilical cord–derived MSCs (UC‐MSCs) in the treatment of ornidazole (ORN)‐induced asthenozoospermia (AS) in rats via the AKT/mTOR pathway. Methods: An animal model of AS was established in ORN‐induced rats, followed by treatment of UC‐MSCs and rapamycin (autophagy activator) or MK‐2206 (AKT inhibitor). The sperm motility, concentration, and viability of rats were measured by an automatic sperm analyzer. Hematoxylin and eosin (HE) staining was conducted to observe the pathological injury of testicular tissue in rats. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was utilized to evaluate the apoptosis rate of testicular cells. Western blot analysis was performed to determine the expression of apoptosis‐related proteins, autophagy‐related proteins, and AKT, p‐AKT, mTOR, and p‐mTOR. The rate of light chain 3 (LC3)–positive cells in testicular tissue was detected by immunohistochemistry (IHC). Results: In ORN‐induced AS rats, sperm motility, concentration, and viability as well as the number of mesenchymal cells and spermatogenic cells were significantly decreased, spermatogenic tubule space, apoptosis rate, and cleaved caspase‐3, LC3II/I, Beclin‐1, and LC3‐positive cell rates were increased, and Bcl2 was downregulated. UC‐MSCs could improve sperm quality and testicular injury in AS rats by inhibiting excessive autophagy. Besides, UC‐MSCs could activate the AKT/mTOR pathway. Moreover, inhibition of the AKT/mTOR pathway partially reversed the therapeutic effect of UC‐MSCs on ORN‐induced AS rats. Conclusion: UC‐MSCs inhibit autophagy and improve sperm quality in AS rats through the AKT/mTOR pathway, highlighting a new idea for the treatment of AS. [ABSTRACT FROM AUTHOR]

Background: Thiol-disulfide homeostasis (TDH) plays a pivotal role in various physiological mechanisms, including antioxidant defence, detoxification, apoptosis, regulation of enzyme activities and cellular signal transduction. TDH can be used as a biomarker to detect oxidative stress (OS) levels and ischemia status in the tissues. Coronary artery bypass grafting (CABG) surgery is a procedure associated with high oxidative stress. Dexmedetomidine, an alpha-2 agonist anaesthetic agent, has antioxidant effects. In this study, the effects of dexmedetomidine on oxidative stress in CABG surgery were investigated. Methods: Patients who underwent on-pump CABG surgery were divided into two groups: those receiving dexmedetomidine (Group D) and those not receiving dexmedetomidine (Group C). From anesthesia induction to the end of surgery, patients in Group D received intravenous infusions of 0.05–0.2 mcg/kg/min remifentanil and 0.2–0.7 mcg/kg/h dexmedetomidine. Patients in Group C received intravenous infusion of 0.05–0.2 mcg/kg/min remifentanil. Blood samples were collected from the patients 30 min before induction of anesthesia (T1), 30 min after removal of the aortic cross-clamp (T2), and at the end of the surgery (T3). Thiol-disulfide homeostasis (TDH) was assessed using a novel method. A novel automated method enables the determination of native thiols, total thiols and disulfides levels in plasma, allowing the calculation of their respective ratios. Results: In patients receiving dexmedetomidine, lower postoperative levels of disulfide, disulfide/native thiol, and disulfide/total thiol, along with higher native thiol/total thiol, were observed compared to the control group. (p < 0.05) Postoperative native thiol and total thiol levels were similar for both groups. (p > 0.05) Conclusions: In our study, through dynamic thiol-disulfide measurements, we found that levels of oxidative stress (OS) were lower in patients who received dexmedetomidine. We believe that the positive effects of dexmedetomidine on OS could be beneficial in CABG surgery. Furthermore, we anticipate that with further studies conducted in larger patient cohorts, the clinical utilization of dexmedetomidine will become more widespread. Trial registration number: NCT05895331 / 06.07.2023. [ABSTRACT FROM AUTHOR]

We describe the use of acyl imidazoles derived from aliphatic carboxylic acids for the N-heterocyclic carbene/organic photoredox co-catalyzed meta -selective functionalization of electron-rich arenes. Compared to our previous work, a change of the wavelength of the applied LED light from 440 nm to 390 nm promotes this reaction efficiently. [ABSTRACT FROM AUTHOR]

Hybride white organic light‐emitting diodes (WOLEDs) have experienced great success as a prospective technology for the new generation lighting source. Nevertheless, WOLEDs exhibiting excellent effciency and good color stability at high operation brightness are still rare. Herein, a simple but efficient blue molecule, pyrenoimidazole‐biphenyl (PPyIM), which exhibits promising external quantum efficiency (EQE) of 7.6% and 7.2% at the luminescence of 1000 −and 5000 cd m−2 in nondoped blue OLED, is first developed. And then, phenanthroimidazole‐biphenyl (PPIM) with analogous molecular skeleton of PPyIM is chosen as the host of phosphorescent dye PO‐01, and the resulting doped device achieves excellent EQE of 26.5% at the high luminescence of 5000 cd m−2. Furthermore, adopting PPyIM as nondoped blue emissive layer, the two‐color hybrid WOLED exhibites stable warm white emission with CIE coordinates of (0.454, 0.439), color rendering index (CRI) of 45, and correlated color temperature (CCT) of 2996 K. The maximum EQE reaches 23.5%, and the EQE still maintains 21.2% even at the luminance of 5000 cd m−2. Notably, this device exhibits exceptionally stable warm white emission, the CIE coordinates variation is only (0.004, 0.003) in the wide luminance range from 400 to 10000 cd m−2, representing the best outcome for hybrid WOLEDs to date. [ABSTRACT FROM AUTHOR]

A novel, highly efficient, eco-friendly, and quick microwave-assisted synthesis of 2, 4, 5- substituted imidazoles by one-pot cyclo condensation of acenaphthoquinone, aromatic aldehydes, and ammonium acetate was reported under solvent-free conditions using ammonium chloride as a catalyst with excellent yield. The present methodology offers several advantages, such as mild reaction conditions, easy workup, short reaction time, excellent yield, purification of products by the non-chromatographic method, and reproducibility in large-scale synthesis. Compounds were characterized by IR, 1HNMR, 13C NMR spectroscopy and their melting points were compared with the literature reports. [ABSTRACT FROM AUTHOR]

The asymmetric unit of the title compound, [Co(C8Br4O4)(C3H4N2)2(H2O)2]n or [Co(Br4bdc)(im)2(H2O)2]n, comprises half of CoII ion, tetra­bromo­benzene­dicarboxylate (Br4bdc2−), imidazole (im) and a water mol­ecule. The CoII ion exhibits a six-coordinated octa­hedral geometry with two oxygen atoms of the Br4bdc2− ligand, two oxygen atoms of the water mol­ecules, and two nitro­gen atoms of the im ligands. The carboxyl­ate group is nearly perpendicular to the benzene ring and shows monodentate coordination to the CoII ion. The CoII ions are bridged by the Br4bdc2− ligand, forming a one-dimensional chain. The carboxyl­ate group acts as an inter­molecular hydrogen-bond acceptor toward the im ligand and a coordinated water mol­ecule. The chains are connected by inter­chain N—H⋯O(carboxyl­ate) and O—H(water)⋯O(carboxyl­ate) hydrogen-bonding inter­actions and are not arranged in parallel but cross each other via inter­chain hydrogen bonding and π–π inter­actions, yielding a three-dimensional network. [ABSTRACT FROM AUTHOR]