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The Journal of Organic Chemistry Jun 2024A series of amides, including α-bromo hydroxamates, -alkoxyamides, and -aryloxyamides, were subjected to phosphine-catalyzed ring-opening -selective addition with...
A series of amides, including α-bromo hydroxamates, -alkoxyamides, and -aryloxyamides, were subjected to phosphine-catalyzed ring-opening -selective addition with cyclopropenones, producing various special -unsaturated esters containing oxime ether motif, in moderate to excellent yields, with high regioselectivity, and exclusive -selectivity. The methodology is highly atom-economical, with simple operation procedures, and compatible with a wide substrate scope (more than 44 examples).
PubMed: 38935753
DOI: 10.1021/acs.joc.4c00941 -
PloS One 2024To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL).
OBJECTIVE
To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL).
METHODS
A rat model for ALI/acute respiratory distress syndrome (ALI/ARDS) was established. Pathological examination of lung tissue was conducted to assess lung injury. Blood gas in the arteries was measured using a blood analyzer. Changes in PaO2, PaO2/FiO2, and lung wet/dry (W/D) weight ratio were carefully compared. ELISA assay was conducted to estimate cell adhesion and inflammation response. Finally, real-time reverse transcription polymerase chain reaction and western blotting assay was used to determine the activation of PI3K/AKT/mTOR pathway.
RESULTS
ARDS in vivo model was successfully constructed by LPS injection. Compared with the sham group, PaO2 and PaO2/FiO2 were significantly lower in the vehicle group, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8 andTNF-αwere significantly increased. After treatment with different doses of sivelestat sodium, we found PaO2, PaO2/FiO2 were prominently increased, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8, TNF-α levels were decreased in the dose-dependent manner. Meanwhile, compared with the vehicle group, the expression levels of Bax, PI3K, Akt and mTOR were significantly lower, and the expression of Bcl-2 was significantly higher after injection with sivelestat sodium.
CONCLUSION
Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway.
Topics: Animals; TOR Serine-Threonine Kinases; Acute Lung Injury; Signal Transduction; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Rats; Male; Glycine; Sulfonamides; Rats, Sprague-Dawley; Lung; Disease Models, Animal
PubMed: 38935660
DOI: 10.1371/journal.pone.0302721 -
Journal of Water and Health Jun 2024The carbapenem-resistant (CRE) pose a pressing public health concern. Here, we investigated the frequency of CRE bacteria, carbapenemase-encoding genes, and the...
The carbapenem-resistant (CRE) pose a pressing public health concern. Here, we investigated the frequency of CRE bacteria, carbapenemase-encoding genes, and the molecular epidemiology of carbapenemase-resistant in wastewater resources and healthy carriers in Iran. Out of 617 bacteria, 24% were carbapenem-resistant. The prevalence of CRE bacteria in livestock and poultry wastewater at 34% and hospital wastewater at 33% was significantly higher ( ≤ 0.05) than those in healthy carriers and municipal wastewater at 22 and 17%, respectively. The overall colonization rate of CRE in healthy individuals was 22%. Regarding individual species, the following percentages of isolates were found to be CRE: (18%), spp. (24%), (28%), spp (40%), spp. (25%), spp. (17%), spp. (31%), spp. (21%), and spp. (36%). The gene was detected in 97% of CRE isolates, while the and genes were detected in 24 and 3% of isolates, respectively. The B2 phylogroup was the most prominent group identified in carbapenem-resistant isolates, accounting for 80% of isolates. High prevalence of CRE with transmissible carbapenemase genes among healthy people and wastewater in Iran underscores the need for assertive measures to prevent further dissemination.
Topics: Wastewater; Iran; Carbapenems; Carbapenem-Resistant Enterobacteriaceae; Humans; Bacterial Proteins; beta-Lactamases; Anti-Bacterial Agents; Enterobacteriaceae; Animals
PubMed: 38935456
DOI: 10.2166/wh.2024.041 -
Environmental Science & Technology Jun 2024Landscape wildfires generate a substantial amount of dissolved black carbon (DBC) annually, yet the molecular nitrogen (N) structures in DBC are poorly understood. Here,...
Revealing Molecular Structures of Nitrogen-Containing Compounds in Dissolved Black Carbon Using Ultrahigh-Resolution Mass Spectrometry Combined with Thermodynamic Calculations.
Landscape wildfires generate a substantial amount of dissolved black carbon (DBC) annually, yet the molecular nitrogen (N) structures in DBC are poorly understood. Here, we systematically compared the chemodiversity of N-containing molecules among three different DBC samples from rice straw biochar pyrolyzed at 300, 400, and 500 °C, one leached dissolved organic carbon (LDOC) sample from composted rice straw, and one fire-affected soil dissolved organic matter (SDOM) sample using Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS). N-Containing molecules contributed 20.0%, 36.1%, and 43.7% of total compounds in Combined DBC (pooling together the three DBC), LDOC, and SDOM, respectively, and molecules with fewer N atoms had higher proportions (i.e., N > N > N). The N-containing molecules in Combined DBC were dominated by polycyclic aromatic (62.2%) and aromatic (14.4%) components, while those in LDOC were dominated by lignin-like (50.4%) and aromatic (30.1%) components. The composition and structures of N-containing molecules in SDOM were more similar to those in DBC than in LDOC. As the temperature rose, the proportion of the nitrogenous polycyclic aromatic component in DBC significantly increased with concurrent enhanced oxidation and unsaturation of N. As indicated by density functional theory (DFT)-based thermodynamic calculations, the proportion of aliphatic amide N decreased from 23.2% to 7.9%, whereas that of nitroaromatic N increased from 10.0% to 39.5% as the temperature increased from 300 to 500 °C; alternatively, the proportion of aromatic N in the 5/6 membered ring remained relatively stable (∼31%) and that of aromatic amide N peaked at 400 °C (32.7%). Our work first provides a comprehensive and thorough description of molecular N structures of DBC, which helps to better understand and predict their fate and biogeochemical behavior.
PubMed: 38935345
DOI: 10.1021/acs.est.4c01829 -
Indian Journal of Dental Research :... Jan 2024Compare the efficacy of 2% lidocaine with adrenaline (1:200,000) and 4% articaine with adrenaline (1:100,000) in inferior alveolar nerve block prior to extraction of... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIMS
Compare the efficacy of 2% lidocaine with adrenaline (1:200,000) and 4% articaine with adrenaline (1:100,000) in inferior alveolar nerve block prior to extraction of bilateral teeth posterior to canine in interval of one week.
METHODS AND MATERIAL
Thirty-five patients were selected for the study. Patients were divided into two different groups: Group 1 - (2% lignocaine with adrenaline (1:200,000)) and Group 2 - (4% articaine with adrenaline (1:100,000)) solution. The study variables for each anaesthetic agent were: onset of action and depth of anaesthesia. A pulp tester was used to demonstrate quantitative values and a visual analogue scale (VAS) was used for qualitative evaluation of the two anaesthetic drugs in 2 min cycle for 10 min with respect to test canine. Anaesthesia was considered successful when pulp tester value 64 was achieved in 10 min for both the anaesthetic agent.
STATISTICAL ANALYSIS USED
The difference in the efficacy of lignocaine and articaine was analysed using Student's t test. Within group comparison of the response to the pulp vitality test and VAS over various time periods was analysed using repeated measures Analysis of Variance (ANOVA) with post-hoc Bonferroni test.
RESULTS
Data analysis showed statistical differences in onset and depth of anaesthesia between the two groups (P < 0.05).
CONCLUSIONS
4% Articaine with adrenaline (1:100,000) onset of action is faster and depth of anaesthesia is better compared to 2% lignocaine with adrenaline (1:200,000). Many previous studies reported onset of anaesthesia, but this study evaluates onset and depth of both the anaesthetic agent quantitatively and qualitatively.
Topics: Humans; Carticaine; Lidocaine; Anesthetics, Local; Nerve Block; Mandibular Nerve; Epinephrine; Adult; Anesthesia, Dental; Young Adult; Male; Dental Pulp Test; Dental Pulp; Pain Measurement; Female; Tooth Extraction; Vasoconstrictor Agents; Adolescent; Cuspid; Time Factors; Treatment Outcome
PubMed: 38934747
DOI: 10.4103/ijdr.ijdr_678_23 -
Archivio Italiano Di Urologia,... Jun 2024The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors...
OBJECTIVE
The management of chronic prostatitis/ chronic pelvic pain syndrome type III (CP/CPPS) has been always considered complex due to several biopsychological factors underlying the disease. In this clinical study, we aimed to evaluate the efficacy of the treatment with Palmitoylethanolamide, Epilobium and Calendula extract in patients with CP/CPPS III.
MATERIALS AND METHODS
From June 2023 to July 2023, we enrolled 45 consecutive patients affected by CP/CPPS type III in three different institution. We included patients aged between 18 and 75 years with symptoms of pelvic pain for 3 months or more before the study, a total National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score ≥ 12 point and diagnosed with NIH category III, according to 4-glass test Meares-Stamey test. Patients were then allocated to receive rectal suppositories of PEA, Epilobium and Calendula, 1 suppository/ die for 1 month. All patients have been tested with standard urinalysis in order to assess urinary leukocytes (U-WBC). The primary endpoint of the study was the reduction of NIHCPSI. The secondary outcomes were the change of peak flow, post-void residual (PVR), IIEF-5, VAS score, PSA and decrease of U-WBC.
RESULTS
A total of 45 patients concluded the study protocol. At baseline, the median age of all the patients included in the cohort was 49 years, the median PSA was 2.81 ng/ml, the median NIH-CPSI was 18.55, the median IIEF-5 was 18.27, the median U-WBC was 485.3/mmc, the median VAS score was 6.49, the median PVR was 26.5 ml and the median peak flow was 16.3 ml/s. After 1 month of therapy we observed a statistically significant improvement of NIH-CPSI, U-WBC, PSA, IIEF-5, peak flow, PVR and VAS.
CONCLUSIONS
In this observational study, we showed the clinical efficacy of the treatment with PEA, Epilobium and Calendula, 1 suppository/die for 1 month, in patients with CP/CPPS III. The benefits of this treatment could be related to the reduction of inflammatory cells in the urine that could imply a reduction of inflammatory cytokines. These results should be confirmed in further studies with greater sample size.
Topics: Humans; Male; Middle Aged; Adult; Prostatitis; Suppositories; Amides; Aged; Palmitic Acids; Treatment Outcome; Young Adult; Ethanolamines; Plant Extracts; Epilobium; Calendula; Adolescent; Chronic Disease; Pelvic Pain
PubMed: 38934521
DOI: 10.4081/aiua.2024.12582 -
European Journal of Emergency Medicine... Aug 2024
Topics: Humans; Etomidate; Emergency Service, Hospital; Blood Pressure; Rapid Sequence Induction and Intubation; Male; Female; Hypnotics and Sedatives; Middle Aged; Shock; Adult
PubMed: 38934075
DOI: 10.1097/MEJ.0000000000001144 -
Frontiers in Medicine 2024Propofol and etomidate are the most commonly used sedative agents in procedural sedation, each with its own advantages and disadvantages. However, there remains...
OBJECTIVE
Propofol and etomidate are the most commonly used sedative agents in procedural sedation, each with its own advantages and disadvantages. However, there remains considerable controversy regarding the optimal ratio for the mixture of these two drugs, warranting further investigation. Therefore, this study aims to investigate the optimal ratio for combining propofol and etomidate during gastroscopy.
METHODS
This study is a prospective, double-blinded, randomized controlled clinical trial. One hundred and sixty-two patients from July 2019 to December 2022 were evenly classified into three groups using a random number table as follows: (1) P group (propofol); (2) EP1 group (5 mL etomidate +10 mL propofol); (3) EP2 group (10 mL etomidate +10 mL), 54 patients per group. The medications, including a pre-sedation dose of 50 μg/kg dezocine followed by sedatives, ceasing when the patient's eyelash reflex vanished, indicating adequate sedation. Mean arterial pressure (MAP), heart rate (HR), and peripheral oxygen saturation (SpO) measurements taken before anesthesia (T1), immediately after the administration of sedatives (T2), immediately gastroscopic insertion (T3) and immediately recovery (T4) were determined. Additional, perioperative related outcomes and adverse events were also recorded.
RESULTS
The EP2 group exhibited a higher MAP at T2 compared to the P and EP1 groups ( < 0.05). Calculated decreases in MAP revealed values of 19.1, 18.8, and 13.8% for the P, EP1, and EP2 groups at T2, respectively. Adverse events: Group EP2 exhibited a significantly lower hypotension incidence (11.1%) compared to the Propofol group (50%) and EP1 (31.5%). Concerning injection pain, Group EP2 also showing a significant decrease in comparison to P and EP1 groups ( < 0.05).
CONCLUSION
The use of a mixture of 10 mL etomidate and 10 mL propofol (at a 1:1 ratio) combined with dezocine for painless gastroscopy demonstrates hemodynamic stability, a low incidence of adverse reactions.
CLINICAL TRIAL REGISTRATION
https://www.chictr.org.cn/showproj.html?proj=39874.
PubMed: 38933106
DOI: 10.3389/fmed.2024.1392141 -
Rapid Communications in Mass... Sep 2024Sphingomyelins (SMs) and resulting metabolic products serve important functional and cell signaling roles and can act as potential biomarkers and therapeutic targets in...
RATIONALE
Sphingomyelins (SMs) and resulting metabolic products serve important functional and cell signaling roles and can act as potential biomarkers and therapeutic targets in many pathological disorders. SMs each contain a sphingoid base, an amide-linked fatty acyl chain, and a phosphocholine headgroup. Despite these simple building blocks, variations and modifications of both the sphingoid base and the fatty acyl chain result in a diverse array of structurally complicated SM compounds. Conventional tandem mass spectrometry (MS/MS) using the collision-induced dissociation (CID) method only provides limited structural information, necessitating other tools to unravel the structural complexity of these lipids.
METHODS
We utilize electron-induced dissociation (EID) and sequential CID/EID approaches to elucidate detailed structural features of SMs. Integrating the CID/EID method into an imaging MS workflow enables accurate identification of SMs directly from kidney tissue.
RESULTS
The application of EID enables identification of SMs at the molecular species level, identifying the sphingosine base and the amide-linked fatty acyl chains. Furthermore, removal of the phosphocholine headgroup via CID followed by sequential EID in an MS analysis (CID/EID) enhances the structural information obtained. CID/EID provides diagnostic fragmentation patterns revealing the hydroxylation site and double bond position in both the sphingosine base and amide-linked fatty acyl chains.
CONCLUSIONS
Detailed structural information of SMs from synthetic standards and biological tissue samples is obtained using an alternative electron-based dissociation method. Accurate characterization of SMs promises to better inform studies of tissue biochemistry, lipid metabolism, and molecular pathology.
Topics: Sphingomyelins; Tandem Mass Spectrometry; Animals; Kidney; Electrons
PubMed: 38932679
DOI: 10.1002/rcm.9844 -
Angewandte Chemie (International Ed. in... Jun 2024Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more...
Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more efficient strategy for late-stage structural derivatisation of a peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non-native moieties. Utilising an allenamide, we report the first semi-synthesis of antimicrobial lipopeptides leveraging a highly efficient thia-Michael addition of chemically diverse lipophilic thiols. Using chemoenzymatically prepared polymyxin B nonapeptide (PMBN) as a model scaffold, an optimised allenamide-mediated thia-Michael addition effected rapid and near quantitative lipidation, affording vinyl sulfide-linked lipopeptide derivatives. Harnessing the utility of this new methodology, 22 lipophilic thiols of unprecedented chemical diversity were introduced to the PMBN framework. These included alkyl thiols, substituted aromatic thiols, heterocyclic thiols and those bearing additional functional groups (e.g., amines), ultimately yielding analogues with potent Gram-negative antimicrobial activity and substantially attenuated nephrotoxicity. Furthermore, we report facile routes to transform the allenamide into a β-keto amide on unprotected peptides, offering a powerful "jack-of-all-trades" synthetic intermediate to enable further peptide modification.
PubMed: 38932510
DOI: 10.1002/anie.202407764