Related Compounds Research Articles

Artificial intelligence based de-novo design for novel Plasmodium falciparum plasmepsin (PM) X inhibitors

Plasmodium falciparum is the leading cause of malaria with 627,000 deaths annually. Invasion and egress are critical stages for successful infection of the host yet depend on proteins that are extensively pre-processed by various maturases. Plasmepsins (Plasmodium pepsins, abbreviated PM, I-X) are pepsin-like aspartic proteases that are involved in almost all stages of the life cycle. The goal of this study was to use de-novo generative modeling techniques to create novel potential PfPMX inhibitors. A total of 4325 compounds were virtually screened by structural-based docking methods. The obtained hits were utilized to refine a structure-based Ligand Neural Network (L-Net) generative model to generate related compounds. The obtained optimal L-Net Compounds with smina scores ≤ −5.00KCalmol-1 and QED ≥ 0.35 were further taken for amplification utilizing Ligand Based Transformer modeling using Deep generative learning (Drug Explorer/DrugEx). The resulting hits were then subjected to XP Glide conventional Molecular docking and QikProp ADMET screening; molecules with XP Docking score ≤ −7.00KCalmol-1 were retained. Based on their Glide ligand efficiency, originality, and uniqueness, 30 compounds were chosen for binding affinity and MM_GBSA energy determination. Following Induced Fit docking (IFD), 7 compounds were taken for 50 ns MD simulations and FEP/MD calculations. This study reported novel potential PfPMX inhibitors with acceptable ADMET profiles and reasonable synthetic accessibility scores, as well as sufficient docking scores against other PMs were generated. The PfPMX inhibitors reported in this article are promising antimalarials for the next stages of drug development, and the first of their kind to be investigated thoroughly. Communicated by Ramaswamy H. Sarma

Antihypertensive potential of the stem bark of Canarium schweinfurthii Engl. (Burseraceae) in wistar rats: UPLC-ESI-QToF-MS/MS-based prediction of antihypertensive phytochemicals

Ethnopharmacological relevanceCanarium schweinfurthii, also called ‘’Elemierd’Afrique’’, is used in Cameroonian folk medicine (bark decoction) to treat patients suffering from hypertension.Aim of the study: This study aimed at evaluating the antihypertensive activities of the stem bark of Canarium schweinfurthii and identifying potential compounds present in its extract that may support or oppose its ethnomedicinial use. Materials and methodsStem bark extract of Canarium schweinfurthii was prepared by maceration using 70 % ethanol followed by redissolution in methanol and hyphenated. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) analysis for the detection and characterisation of secondary metabolites. Antihypertensive effects were assessed in Wistar rats after induction of hypertension with sodium chloride (NaCl) 18 % at a dose of 0.01mL/gbody weight once a day for four weeks.Hemodynamic parameters were measured weekly by anon-invasive method using the CODA system. ResultsThe ethanolic bark extract of C. schweinfurthii significantly inhibited the increase of blood pressure with a maximum of 23.18 % (systolic pressure, p < 0.0001), 24.77 % (diastolic pressure, p < 0.001) and 22.95 % (mean pressure, p < 0.0001) at a dose of 200 mg/kgbody weight at the 4th week, compared to agroup of Wistar rats that received only NaCl (negative control). Similarly, the extract significantly inhibited the increase in heart rate by 18.84 % (p < 0.001) at 200 mg/kgbody weight at week four. Hematological parameters did not differ significantly between the extract-treated and control groups. The UPLC-MS/MS spectrometric analysis provided evidence for the presence of several C30 terpenoids containing three or five oxygen atoms and exhibiting pentacyclic triterpenoid structures, as well as C29 terpenoids and related compounds containing nitrogen in addition to oxygen, using spectral matching, and in silico molecular formula and structure prediction. Additionally, two features were annotated with high-confidence as lignans, structurally closely related to hinokinin and dehydrocubebin through MS/MS-based in silico structure prediction using CSI: Finger ID in SIRIUS5. The lignans have been previously reported from stem bark of plants belonging to the Burseraceae family. Conclusion: The ethanolic stem bark extract of C. schweinfurthii demonstrated antihypertensive properties on the tested Wistar rats. These results support the ethnopharmacological use of C. schweinfurthii concoctions for the treatment of hypertension and suggest a protective effect against salt damage, hypothetically by the up regulation of antioxidative enzymes and/or lipids, mitigatings membrane peroxidation.

Effect of sintering conditions on colossal dielectric properties of (Tb1/2Nb1/2)0.01Ti0.99O2 ceramics

In this study, we investigated various sintering temperatures (1200 °C−1450 °C) and durations (2–6 h) conditions for preparing (Tb1/2Nb1/2)0.01Ti0.99O2 (TNTO) ceramics. By employing high sintering temperatures (≥1350 °C) and extended sintering durations (≥4 h), we successfully achieved ultra–high dielectric permittivity values (ε′ ∼ 2.2 − 4.1 × 104) and remarkably low loss tangent values (∼0.025−0.079). Remarkably, the temperature coefficient of the TNTO ceramic, sintered at 1350 °C, exhibited exceptional stability, maintaining a value of approximately 15% even at 200 °C. Additionally, we examined the phase structure and microstructure of the TNTO ceramics to gain insights into their colossal permittivity (CP) behavior. The analysis revealed the presence of rutile TiO2 and TbNbTiO6 phases, and the ceramics exhibited a high–density microstructure under high–temperature sintering conditions. The impedance spectroscopy analysis revealed that the primary contributor to the observed CP behavior was the interfacial polarization mechanism. The observed increase in the ε′ value, correlated with the enlargement of the average grain size, can be attributed to the effect of the internal barrier layer capacitor. However, when the sintering time ≥4 h, the grain size did not significantly affect the ε′ value, possibly due to reaching the maximum capacity of electron production for the interfacial polarization process (i.e., the maximum intensity of polarizability). This study provides valuable insights into optimizing the sintering conditions for TNTO ceramics and related compounds, laying the groundwork for the development of a new CP oxide suitable for practical applications.

Oxygen diffusion in RBa2Cu3O7−δ superconductors: A brief review

The interest in RBa2Cu3O7–δ (R = lanthanides) stems from its superconducting properties. These represent a very significant advance in solid-state materials physics and have been extensively studied for decades, with the aim of increasing the critical temperature by doping or external parameters such as pressure. In the present review, we briefly discuss oxygen diffusion in RBa2Cu3O7–δ with respect to its composition. We consider related compounds as a comparison.

Zeeman dependence of the quasiparticle scattering rate and ARPES in copper oxides and related materials

Within a strongly interacting Fermi liquid framework, we calculate the effects of the Zeeman energy ω H for a finite magnetic field, in a metallic system with a van Hove peak in the density of states, located close to and below the Fermi surface. We find that the chemical potential increases with the square of ω H . We obtain a characteristic quasiparticle scattering rate linear in the maximum of ω H and temperature, both in the normal and the d-wave superconducting state. We predict that ARPES experiments in copper oxides, and related compounds, should be able to elucidate this behavior of the scattering rate, and in particular, the difference between spin up and down electrons.

Effect of a commercial peptidase on volatile composition and sensory properties of wheat bread crumb and crust

Flavourzyme is a commercial peptidase, primarily exhibiting exopeptidase activity. The effects of Flavourzyme addition (0–1.6 g/kg, flour basis) on chemical composition, volatile profile and sensory properties of bread crumb and crust were systematically studied. Free amino acids (from 999 to 2156 mg/kg with 1.6 g/kg Flavourzyme addition) and trichloroacetic acid-soluble small peptides in dough remarkably increased with Flavourzyme addition. Gas chromatography-mass spectrometry analysis revealed that 3-methyl-1-butanol, 3-(methylthio)-1-propanol, 2-phenylethanol, acetoin and indole enhanced in crumb after Flavourzyme addition. Meanwhile, pyrazines, benzaldehyde, 5-methyl-2-furanmethanol, maltol and 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one accumulated in crust. Descriptive sensory analysis revealed that the cheesy and alcoholic notes of crumb and the caramel, toasted and nutty notes of crust were strengthened with Flavourzyme addition. The Flavourzyme hydrolysis products enhanced yeast activity in fermentation and facilitated Maillard reactions in baking, leading to the accumulation of related volatile compounds. These compounds subsequently modified the aroma properties of crumb and crust.

Large Subunit of the Human Herpes Simplex Virus Terminase as a Promising Target in Design of Anti-Herpesvirus Agents

Herpes simplex virus type 1 (HSV-1) is an extremely widespread pathogen characterized by recurrent infections. HSV-1 most commonly causes painful blisters or sores around the mouth or on the genitals, but it can also cause keratitis or, rarely, encephalitis. First-line and second-line antiviral drugs used to treat HSV infections, acyclovir and related compounds, as well as foscarnet and cidofovir, selectively inhibit herpesvirus DNA polymerase (DNA-pol). It has been previously found that (S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine (compound 1) exhibits selective anti-herpesvirus activity against HSV-1 in cell culture, including acyclovir-resistant mutants, so we consider it as a lead compound. In this work, the selection of HSV-1 clones resistant to the lead compound was carried out. High-throughput sequencing of resistant clones and reference HSV-1/L2 parent strain was performed to identify the genetic determinants of the virus’s resistance to the lead compound. We identified a candidate mutation presumably associated with resistance to the virus, namely the T321I mutation in the UL15 gene encoding the large terminase subunit. Molecular modeling was used to evaluate the affinity and dynamics of the lead compound binding to the putative terminase binding site. The results obtained suggest that the lead compound, by binding to pUL15, affects the terminase complex. pUL15, which is directly involved in the processing and packaging of viral DNA, is one of the crucial components of the HSV terminase complex. The loss of its functional activity leads to disruption of the formation of mature virions, so it represents a promising drug target. The discovery of anti-herpesvirus agents that affect biotargets other than DNA polymerase will expand our possibilities of targeting HSV infections, including those resistant to baseline drugs.

Separation and characterization of related substances of Lurasidone hydrochloride by LC-QTOF-MS techniques

In the present study, a reliable LC-QTOF-MS method was developed and employed for the separation and characterization of process-related substances and forced degradation products of Lurasidone hydrochloride. The chromatographic separation was carried out using an Agilent Poroshell 120 Bonus-RP C18 column (100 mm × 4.6 mm, 2.7 µm) and a mobile phase consisting of a gradient elution of 10 mM ammonium formate solution and methanol. The degradation studies followed the guidelines outlined in ICH Q1A (R2). It was observed that Lurasidone hydrochloride exhibited instability under photolytic, alkaline, and oxidative stress conditions, while remaining relatively stable under acidic and thermal stresses. Through positive ESI-QTOF mass spectrometric analysis, fourteen related compounds in total, including both process-related and stress degradation products, were identified based on the accurate masses of parent and product ions and calculated elemental compositions. Amongst these substances, nine had not been previously reported, and their formation mechanisms were speculated. The process-related substances were further confirmed by NMR spectra determination, and suggestions were proposed to eliminate them. This study highlights the potential for monitoring and controlling related substances during the manufacturing processes, providing valuable insights for process optimization and quality control of Lurasidone hydrochloride.

Disposable, strain-insensitive, and room-temperature-operated flexible humidity and VOC sensor with enhanced sensitivity and selectivity through interface control

As people are paying more attention to the health and comfort of the indoor environment, the sensors detecting the relative humidity (RH) and volatile organic compounds (VOCs) have attracted widely research interests. However, how to improve the sensitivity and selectivity remains a challenge, especially for flexible sensors working at room temperature (around 25 ℃). In this work, the controlling of solid-gas interface was found to be able to enhance the sensitivity and the manipulation of solid-solid interface increased the selectivity of the sensor for VOC detection. The flexible sensor based on electrospinning cellulose (EC) show high sensitivity for humidity detection due to its large solid-gas interface, which can be used for real-time monitoring of human breathing and speech recognition, simultaneously, it can also detect a variety of VOCs. By introducing silver nanowires (AgNWs) to establish solid-solid interface between silver and expanded graphite (EG), the selectivity of the sensor for VOCs detection was improved, which shown higher sensitivity for EtOH with faster response/recovery time, as well as long-term cycle stability and bending insensitivity. Furthermore, the sensor also can be decomposed by burning, offering a sustainable disposal method. This versatile, low-cost and environmentally friendly flexible electronic device may be used for wearable air monitoring and environmental controlling.

Chemical elucidation of recycled plastic pyrolysis oils by means of GC×GC-PI-TOF-MS and GC-VUV

Detailed chemical characterization of the composition of pyrolysis oils produced from plastics is a mandatory step in understanding the recycling process. Even though the chemical composition of pyrolysis plastic waste oils shows similarities with fossil-based oils, e.g. PIONA related compounds, the relative proportions of the chemical classes are significantly different, resulting in important changes in the global properties of these fluids. In this context, an analytical method based on comprehensive two-dimensional gas chromatography (GC×GC), coupled with photoionization (PI) – time-of-flight mass spectrometry (TOF MS) was developed to obtain a detailed chemical characterization of plastic pyrolysis-oil. A group-type analysis was achieved thanks to the detection of molecular ions by soft ionization PI-TOF MS. Moreover, olefins were successfully distinguished from naphthenes by in-depth consideration of MS spectra, even though such compounds elute very close in the 2D chromatographic separation space. A part of the olefins identified by PI was further confirmed by GC coupled to vacuum ultraviolet detection (VUV) since olefins VUV spectra differ from other compounds. The overall combination of the entire set of data of this multi-modal approach was valuable in studying the pyrolyzed plastic oil composition. It was furthermore applied to monitor the efficiency of upgrading processes that were applied to the oils to remove specific contaminants such as the diolefins. This approach has the potential to support the production of plastic pyrolysis oils that could efficiently be reintroduced in the market to sustain economic circularity needs.

Comparative analysis of isonicotinic acid, l-ascorbic acid and calcium chloride on the induction of innate immunity and secondary metabolite production in Catharanthus roseus (L.) G. Don for management of biotic and oxidative stress

Catharanthus roseus (L.) G. Don is an ornamental and pharmacologically important plant. It contains large amount of indole alkaloids having pharmaceutical activities. Production of vinblastine and vincristine, two important anti-cancerous secondary metabolites of C. roseus, are very less and hampered due to pathogen invasion. To overcome this problem here attempt has been made to boost innate immunity and secondary metabolite production in C. roseus by foliar application of three eco-friendly elicitors viz. Calcium chloride (CaCl2), l-Ascorbic acid (L-AA) and Isonicotinic acid (INA), each at two different concentrations. Augmentation of immune responses was observed in terms of increased production of defense related enzymes like PPO (polyphenol oxidase), PO (peroxidase), PAL (phenylalanine ammonia lyase assay), and β-1,3 glucanase; defense related compound production (total flavonoid and phenol content) and antioxidant enzyme activity (ascorbate peroxidase, APX and catalase, CAT) in C. roseus plant. Increased defense responses were noted in INA (1.25 mM), l-AA (5 mM) and CaCl2 (0.5 %) treated plants compared to control. Same concentrations of elicitors were also found effective in the induction of vinblastine and vincristine production which was detected by both qualitative (using dragendroff reagent) and quantitative methods using LC-MS (Liquid Chromatography-Mass Spectrometry). During this study, nitric oxide (NO) production was also found increased in elicitor treated plants and indicating its signaling role. Finally, challenge inoculation with Alternaria alternata showed significantly reduced disease incidence in elicitor treated plants which indicates their potentiality to combat against this pathogen.

Contribution to the Synthesis, Characterization, Separation and Quantification of New N-Acyl Thiourea Derivatives with Antimicrobial and Antioxidant Potential.

The present study aimed to synthesize, characterize, and validate a separation and quantification method of new N-acyl thiourea derivatives (1a-1o), incorporating thiazole or pyridine nucleus in the same molecule and showing antimicrobial potential previously predicted in silico. The compounds have been physiochemically characterized by their melting points, IR, NMR and MS spectra. Among the tested compounds, 1a, 1g, 1h, and 1o were the most active against planktonic Staphylococcus aureus and Pseudomonas aeruginosa, as revealed by the minimal inhibitory concentration values, while 1e exhibited the best anti-biofilm activity against Escherichia coli (showing the lowest value of minimal inhibitory concentration of biofilm development). The total antioxidant activity (TAC) assessed by the DPPH method, evidenced the highest values for the compound 1i, followed by 1a. A routine quality control method for the separation of highly related compounds bearing a chlorine atom on the molecular backbone (1g, 1h, 1i, 1j, 1m, 1n) has been developed and validated by reversed-phase high-performance liquid chromatography (RP-HPLC), the results being satisfactory for all validation parameters recommended by the ICH guidelines (i.e., system suitability, specificity, the limits of detection and quantification, linearity, precision, accuracy and robustness) and recommending it for routine separation of these highly similar compounds.

Formation and conversion of flavour related compounds of thermal cooked Ruditapes philippinarum soup

SummaryThermal reactions affect flavour, but how different thermal reactions influence the flavour of cooked soup has rarely been investigated. Herein, the effect of heat treatment (0–50 min) at different temperatures (120, 140 and 160 °C) on Ruditapes philippinarum soup was studied. The acceptable heating of Ruditapes philippinarum soup was assigned at 140 °C for 30 min by human sensory evaluation and compound analysis. In addition, the detailed relationship between the formation of key volatile compounds and heating temperature was revealed by partial least squares discriminant analysis (PLS‐DA) and the odour coding method. A total of 28 key volatile compounds were selected according to the results of variables important in the projection (VIP) and odour activity value (OAV). Whereas 3‐ethyl‐2,5‐dimethyl pyrazine and 2‐heptylfuran were the most important volatiles produced only in the thermal reaction at 140 °C and associated with cocoa and roasted nut odours. These results indicated the relationship between thermal reactions and flavour formation. The odour coding obtained from OAV could be as a reference benchmark for heating seafood soup products.

3‐Amino‐thiophene‐2‐carbohydrazide Derivatives as Anti Colon Cancer Agents: Synthesis, Characterization, In‐Silico and In‐Vitro Biological Activity Studies

AbstractIn this study, starting from 3‐amino‐thiophene‐2‐carboxylic acid methyl ester, eighteen new arylidenehydrazide derivatives (4–21) were synthesized. To determine cytotoxic activity of target compounds they were tested against human colon cancer and human umbilical vein endothelial cell lines. To determine prospective inhibition mechanism, binding affinity and complex stability molecular docking and molecular dynamics studies were carried out on transforming growth factor beta‐2 (TGFβ2) and vascular endothelial growth factor receptor 2 (VEGFR2) proteins. According to the biological activity studies compounds (E)‐2,4‐dichloro‐N‐(2‐(2‐(4‐fluorobenzylidene)hydrazine‐1‐carbonyl)thiophen‐3‐yl)benzamide (11) was found as the highest selective and active compound. Anti‐cancer activity results compared to reference drugs doxorubicin and gefitinib. Most active compound was found as 7‐fold and 4‐fold more selective than doxorubicin and gefitinib, respectively. The detailed in vitro and in silico biological activity studies revealed that related compound demonstrated strong and selective anti‐colon cancer effect and also it has promising inhibitory effects on TGFβ2 and VEGFR2. As a result, this compound is a promising candidate for further exploration and development in the field of colon cancer treatment.

Synthesis and characterization of related compounds of Bisoprolol fumarate: a β-blocker agent

Synthesis and characterization of related compounds of Bisoprolol fumarate: a β-blocker agent

Non-Hydrolysable Analogues of Cyclic and Branched Condensed Phosphates: Chemistry and Chemical Proteomics.

Studies into the biology of condensed phosphates almost exclusively cover linear polyphosphates. However, there is evidence for the presence of cyclic polyphosphates (metaphosphates) in organisms and for enzymatic digestion of branched phosphates (ultraphosphates) with alkaline phosphatase. Further research of non-linear condensed phosphates in biology would profit from interactome data of such molecules, however, their stability in biological media is limited. Here we present syntheses of modified, non-hydrolysable analogues of cyclic and branched condensed phosphates, called meta- and ultraphosphonates, and their application in a chemical proteomics approach using yeast cell extracts. We identify putative interactors with overlapping hits for structurally related capture compounds underlining the quality of our results. The datasets serve as starting point to study the biological relevance and functions of meta- and ultraphosphates. In addition, we examine the reactivity of meta- and ultraphosphonates with implications for their "hydrolysable" analogues: Efforts to increase the ring-sizes of meta- or cyclic ultraphosphonates revealed a strong preference to form trimetaphosphate-analogue structures by cyclization and/or ring-contraction. Using carbodiimides for condensation, the so far inaccessible dianhydro product of ultraphosphonate, corresponding to P4 O11 2- , was selectively obtained and then ring-opened by different nucleophiles yielding modified cyclic ultraphosphonates.

Effect of biosurfactant on thiocyanate degradation by automobile service station soil isolates Brachybacterium sp. and Bacillus albus

This study investigated the effect of biosurfactants on the microbial degradation of thiocyanate (SCN−), with the aim of finding a sustainable solution for the treatment of industrial wastes containing thiocyanate and related compounds. Isolates VK8 and VT7, screened from amongst 40 automobile service station soil isolates, showed promising growth in the presence of high thiocyanate concentration (500 mg/L). Biosurfactant BS1-S1W from isolate S1W (Brucella intermedia) enhanced the degradation of SCN− by Brachybacterium sp. (VT7) and Bacillus albus (VK8) by 92% and 95%, respectively, at 200 mg/L. Biosurfactant BS2-VO6 from isolate VO6-2 (Brevundimonas naejangsanensis) caused increment in the reduction of SCN- by 88% and 80%, respectively. FTIR and LC-MS analysis of the purified biosurfactants confirmed their glycolipid nature. Enhanced effect of biosurfactant was more pronounced at higher KSCN concentration. Little is known about the effects of microbial products on the enhancement of microbial biodegradation of SCN−. Production and application of biosurfactant from B. naejangsanensis has not been reported earlier and hence can lead to more effective biological agents of enhanced biomedical and environmental relevance. This is the first report of the application of Brachybacterium and B. albus for thiocyanate degradation and the effect of biosurfactant on the same.

Study of the Structural Chemistry of the Inclusion Complexation of 4-Phenylbutyrate and Related Compounds with Cyclodextrins in Solution: Differences in Inclusion Mode with Cavity Size Dependency.

4-phenylbutyrate (PB) and structurally related compounds hold promise for treating many diseases, including cancers. However, pharmaceutical limitations, such as an unpleasant taste or poor aqueous solubility, impede their evaluation and clinical use. This study explores cyclodextrin (CD) complexation as a strategy to address these limitations. The structural chemistry of the CD complexes of these compounds was analyzed using phase solubility, nuclear magnetic resonance (NMR) spectroscopic techniques, and molecular modeling to inform the choice of CD for such application. The study revealed that PB and its shorter-chain derivative form 1:1 αCD complexes, while the longer-chain derivatives form 1:2 (guest:host) complexes. αCD includes the alkyl chain of the shorter-chain compounds, depositing the phenyl ring around its secondary rim, whereas two αCD molecules sandwich the phenyl ring in a secondary-to-secondary rim orientation for the longer-chain derivatives. βCD includes each compound to form 1:1 complexes, with their alkyl chains bent to varying degrees within the CD cavity. γCD includes two molecules of each compound to form 2:1 complexes, with both parallel and antiparallel orientations plausible. The study found that αCD is more suitable for overcoming the pharmaceutical drawbacks of PB and its shorter-chain derivative, while βCD is better for the longer-chain derivatives.

Development and Validation of a Stability-indicating UPLC-DAD Method for the Simultaneous Determination of Ivermectin and Praziquantel in Pharmaceutical Tablets and Dissolution Media.

Currently, there is no single rapid and accurate stability-indicating quantitative method that can simultaneously determine both ivermectin and praziquantel and their related compounds. Thus, the goal of this research is to develop and validate a new rapid, accurate, and stability-indicating ultra-performance liquid chromatography (UPLC) method. The method uses a water, acetonitrile, and methanol gradient. The chromatographic separation was achieved on a C18 (1.7 μm, 2.1 × 50 mm) column with a flow rate of 0.7 mL/min, and the column temperature was maintained at 40°C. Analytes are detected at 245 nm. The method was validated in accordance with ICH Q2R1 guidelines. The linearity (R2) was >0.9987 and 0.9997 for praziquantel and ivermectin, respectively. The corresponding accuracy ranged between 98.0 and 102.0%. Intermediate precision (assessed as inter-day precision) was determined by calculating the cumulative %CV of eighteen assay preparations and was less than 2.0% for both praziquantel and ivermectin. The specificity of the method was shown by the resolution of the two active pharmaceutical ingredients (APIs) from any interfering excipients, impurities, or degradation products. The limit of detection and quantitation for ivermectin was 26.80 ng/mL and 81.22 ng/mL, respectively. The limit of detection and quantitation for praziquantel was 1.39 μg/mL and 4.22 μg/mL, respectively. The robustness study proved that method performance is stable against small variations in sample processing parameters (shaking, sonication time, and acetonitrile % in solvent solution) and also against small variations in the initial % of mobile phase components and gradient slope. Using ICH Q2R2 criteria, the method was demonstrated to be specific, accurate, stability indicating, and robust to small variations of chromatographic variables.

Multiomics Revealed the Multi-Dimensional Effects of Late Sleep on Gut Microbiota and Metabolites in Children in Northwest China.

Background Sleep plays a pivotal role in children's mental and physical development and has been linked to the gut microbiota in animals and adults. However, the characteristics of the gut microbiota and metabolites and the relationship to late bedtimes in children remain unclear. Methods In total, 88 eligible children, aged from 3 to 8 years, were recruited and divided into two groups according to the bedtime collected by designed questionnaires (early, before 22:00: n = 48; late, after 22:00, n = 40). Stools and plasma samples were collected to examine the characteristics of the gut microbiota and metabolites by shotgun metagenomics and metabolomics. Results The richness and diversity of the gut microbiota in children with early bedtime were significantly increased compared with the late ones. Coprococcus, Collinsella, Akkermansia muciniphila, and Bifidobacterium adolescentis were significantly more abundant in children with early bedtime, while Bacteroides and Clostridium sp. CAG-253 were obviously enriched in the late ones. A total of 106 metabolic pathways, including biosynthesis of ribonucleotide, peptidoglycan, and amino acids, and starch degradation were enriched in children with early bedtime, while 42 pathways were abundant in those with late bedtime. Notably, more gut microbial metabolites were observed in children with late bedtime, which included aldehyde, ketones, esters, amino acids and their metabolites, benzene and substituted derivatives, bile acids, heterocyclic compounds, nucleotide and metabolites, organic acid and derivatives, sugars and acyl carnitine. In plasma, fatty amides, lipids, amino acids, metabolites, hormones, and related compounds were enriched in children with early bedtime, while bile acids were higher in children with late bedtime. Association studies revealed that the different microbial species were correlated with metabolites from gut microbiota and plasma. Conclusions The results of our study revealed that the gut microbiota diversity and richness, and metabolic pathways were significantly extensive in children with early bedtime, whereas the gut microbial metabolites were significantly decreased, which might be related to gut microbial differences.