Concentration Values Research Articles

Hsa_circ_0078767 Enhances Osteosarcoma Chemoresistance to Doxorubicin Through the Regulation of the miR-188-3p/GPX4 Axis.

Osteosarcoma (OS) is a primary malignancy of bone. The emergence of chemoresistance represents a persistent barrier to effective cancer patient care. This analysis sought to examine hsa_circ_0078767 as a mediator of doxorubicin (DOX) resistance in OS. Levels of hsa_circ_0078767, miR-188-3p, and glutathione peroxidase 4 (GPX4) in OS clinical tissue samples and cell lines were evaluated by quantitative polymerase chain reaction (qPCR) and Western blotting. Associations between hsa_circ_0078767 levels in clinical samples and patient overall survival were assessed with Kaplan-Meier curves. CCK-8 assays were utilized as a means of examining DOX half-inhibitory concentration (IC50) values. RNA immunoprecipitation and pull-down, as well as reporter assays, investigated interactions between hsa_circ_0078767, miR-188-3p, and GPX4 within OS cells exhibiting DOX resistance. OS patient tissues and cell lines resistant to DOX exhibited elevated hsa_circ_0078767 and GPX4 expression together with a reduction in miR-188-3p levels. Inhibiting hsa_circ_0078767 expression contributed to a profound decrease in the ability of OS tumors to resist DOX. Mechanistically, it was determined that hsa_circ_0078767 can enhance DOX chemoresistance through its ability to bind and sequester miR-188-3p, which otherwise negatively modulates GPX4 to enhance chemosensitivity. Accordingly, the sequestration of miR-188-3p by hsa_circ_0078767 led to the derepression and upregulation of GPX4. Hsa_circ_0078767 was found to modulate miR-188-3p/GPX4 signaling to enhance OS cell resistance to DOX treatment and facilitate disease progression. As such, hsa_circ_0078767 may represent a valuable biomarker or target for use in the context of OS patient management.

The health impact of PM2.5 and O3 in Beijing modified by infiltration factors from 2014 to 2022.

PM2.5 and O3 are significant threats to the health of residents and modern residents spend more than 80% of their time indoors, so quantifying indoor exposure of residents has a positive influence on formulating policies and improving health indicators. Analysis of monitoring data shows a consistent decrease in the annual average concentration of outdoor PM2.5 in Beijing from 90.1 to 30.4μg/m3, and the equivalent human exposure concentration also declined from 55.2 to 18.6μg/m3 modified by infiltration factors from 2014 to 2022, while during the peak season, the average value of O3-8h concentration in Beijing has consistently remained between 159.3 and 225.3μg/m3; the equivalent human exposure concentration remained between 64.7 and 92.3μg/m3 modified by infiltration factors from 2014 to 2023. The equivalent exposure concentration is calculated by weighting the concentration of indoor and outdoor pollutants, the proportion of indoor and outdoor activity time of the population, and the permeability coefficient of outdoor pollutants into the room, so as to quantify the actual concentration of pollutants exposed to the human body in a certain time. Previous studies have primarily focused on the impact of annual changes in pollutant concentrations on health estimates, often neglecting indoor concentrations and behavior patterns. This limitation should be addressed. Therefore, this study utilized equivalent human exposure concentration and AirQ + , the authoritative software released by the World Health Organization (WHO), to evaluate quantitatively the impact of PM2.5 and O3 on the health of Beijing residents by combining pollutant concentration, annual population, and mortality of various diseases and other indicators to enhance the credibility of the study. The number of deaths related to PM2.5 has decreased from 28,182 people in 2014 to 10,250 people in 2022 (age ≥ 30). The number of premature deaths in 2022 was only 36.4 percent of that in 2014 and was decreasing by 1992 per year. The number of deaths related to O3 varies between 550 and 3358 people. Lowering PM2.5 and O3 concentrations can effectively reduce natural premature death as well as cardiovascular and respiratory diseases caused by air pollution. The government should persist in enhancing the regulation of PM2.5 and accord significance to the oversight of O3. Concurrently, there is a need to reinforce the cooperative regulation addressing both PM2.5 and O3.

The Entropy of Mixing in Self-Assembly and the Role of Surface Tension in Modeling the Critical Micelle Concentration

A theory for the micelle formation of nonionic head-tail amphiphiles (detergents) in aqueous solutions is derived based on the traditional molecular thermodynamic modeling approach and a variant of the Flory–Huggins theory that goes beyond lattice models. The theory is used to analyze experimental values for the critical micelle concentration of n-alkyl-ß-D-maltosides within a mass action model. To correlate those parts of the micellization free energy, which depend on the transfer of hydrophobic molecule parts into the aqueous phase, with molecular surfaces, known data for the solubility of alkanes in water are reanalyzed. The correct surface tension to be used in connection with the solvent-excluded surface of the alky tail is ~30 mN/m. This value is smaller than the measured surface tension of a macroscopic alkane–water interface, because the transfer free energy contains a contribution from the incorporation of the alkane or alkyl chain into water, representing the change in free volume in the aqueous phase. The Flory–Huggins theory works well, if one takes into account the difference in liberation free energy between micelles and monomers, which can be described in terms of the aggregation number as well as the thermal de Broglie wavelength and the free volume of the detergent monomer.

MMP-9 as a clinical marker for endometriosis: a meta-analysis and bioinformatics analysis.

This study systematically evaluated the potential efficacy of serum matrix metalloproteinase-9 (MMP-9) concentration as a diagnostic marker for endometriosis through meta-analysis. Early and accurate diagnosis of endometriosis, a common gynecological disease, is crucial for improving patient prognosis. Hence, this study aimed to comprehensively analyze the data from multiple studies to assess the diagnostic value of serum MMP-9 concentration for endometriosis. Articles investigating the association between MMP-9 and endometriosis, published from the inception of the databases until February 2024, were systematically retrieved from multiple databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and CNKI. Download and analyze the GSE7305, GSE23339, and GSE51981 datasets. Statistical analyses of all eligible studies were conducted using RevMan 5.4, Stata 11.0, and R software version 4.3.3. Fifteen studies fully met the inclusion criteria for the meta-analysis. The concentration of MMP-9 in the blood of patients with endometriosis was significantly higher compared to that of the control group (p < 0.0001). Subgroup analysis based on different stages of endometriosis revealed a trend towards significantly higher serum MMP-9 concentrations in patients, whether in stages I-II or III-IV. Bioinformatics analysis revealed differences in the expression of MMP-9 in endometrial tissue between EMT patients and healthy controls in the GSE7305 and GSE23339 datasets. Additionally, in the GSE51981 dataset, we found significant differences between the normal group and both mild and severe cases of endometriosis. Both the current meta-analysis and bioinformatics analysis indicate differences in MMP-9 concentration levels between endometriosis patients and healthy individuals, with potentially elevated MMP-9 concentrations in serum samples from patients with endometriosis. https://www.crd.york.ac.uk/prospero, identifier CRD42024525864.

Antibacterial and Antifungal Activity of Metabolites from Basidiomycetes: A Review.

Background/Objectives: The search for new antimicrobial molecules is important to expand the range of available drugs, as well as to overcome the drug resistance of pathogens. One of the promising sources of antibacterial and antifungal metabolites is basidial fungi, which have wide biosynthetic capabilities. Methods: The review summarized the results of studying the antimicrobial activity of extracts and metabolites from basidiomycetes published from 2018-2023. Results: In all studies, testing for antibacterial and antifungal activity was carried out in in vitro experiments. To obtain the extracts, mainly the fruiting bodies of basidiomycetes, as well as their mycelia and culture liquid were used. Antimicrobial activity was found in aqueous, methanol, and ethanol extracts. Antimicrobial metabolites of basidiomycetes were isolated mainly from the submerged culture of basidiomycetes. Metabolites active against Gram-positive and Gram-negative bacteria and mycelial and yeast-like fungi were identified. Conclusions: Basidiomycete extracts and metabolites have shown activity against collectible strains of bacteria and fungi and multi-resistant and clinical strains of pathogenic bacteria. The minimum inhibitory concentration (MIC) values of the most active metabolites ranged from 1 to 16.7 µg/mL.

Antimicrobial Activity of Ethanol Extract of Sea Pandan Leaves (Pandanus odorifer) Against Staphylococcus aureus and Escherichia coli

Sea pandan (Pandanus odorifer) is used in traditional medicine in India. Sea pandan is efficacious in treating pain, parasites, digestive, liver, and cognitive disorders. Sea pandan is found in coastal areas in South Kalimantan. Sea pandan contains flavonoid compounds that have the potential to be antimicrobials. This study aimed to determine the antimicrobial activity of sea pandan leaf extract. The study began with sample preparation, which included washing the leaves, drying them using an oven, refining the particle size, extracting 70% ethanol, and evaporating the solvent until a thick extract was obtained. Total flavonoid levels in sea pandan leaf extract were determined using the colourimetric method using quercetin standards. Antimicrobial testing was conducted using the diffusion method at concentrations of 30%, 40%, and 50% against Staphylococcus aureus and Escherichia coli. The positive control used was chloramphenicol. The determination of the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values ??was carried out using the dilution method. The results showed that sea pandan leaf extract contains phenolics, flavonoids, saponins, steroids, and tannins. The total flavonoid content in sea pandan leaf extract is 10.01% w/w equivalent of quercetin. The antimicrobial activity of sea pandan leaf extract against Staphylococcus aureus bacteria is 10.15 - 25.36 mm, while against Escherichia coli in the range of 8.15 - 23.16 mm. Ethanol extract of sea pandan leaves at a concentration of 50% is included in the very strong category in inhibiting Staphylococcus aureus and Escherichia coli. Ethanol extract of sea pandan leaves has an MIC value of 7.5% on Staphylococcus aureus and 15% on Escherichia coli. MBC of sea pandan extract is 15% on Escherichia coli bacteria. This study concludes that the ethanol extract of sea pandan leaves has antimicrobial activity against Staphylococcus aureus (bacteriostatic) and Escherichia coli (bactericidal).

Effect of Prophylactic Tranexamic Acid on Peripartum Changes in Hemoglobin Concentration After Vaginal Delivery

Objective: To evaluate the effect of prophylactic intravenous tranexamic acid on postpartum hemoglobin concentration values compared to control. Methods: This is a randomized controlled study involving 80 parturients with no apparent risk for PPH in a tertiary hospital who were grouped into two of 40 each. Group A received 10iu of oxytocin intramuscularly with 1000mg of intravenous tranexamic acid within one minute of having vaginal delivery of the baby while group B received intramuscular oxytocin 10iu with 10mls of sterile water and served as the control group. The primary outcome measure was the difference in admission and postpartum hemoglobin concentration (Hemoglobin change). Result: During the study period, 80 parturients that were recruited, completed the study. The characteristics of the parturients in the two groups had no significant statistical difference in their demographic characteristics and admission parameters (P&gt;0.05). The mean postpartum hemoglobin concentration was significantly higher in the tranexamic acid plus oxytocin group compared to placebo plus oxytocin group (10.28+ 0.59ml) versus (9.44+0.62ml) p&lt;0.005. There was no major maternal side effect in both groups. Conclusion: When compared with placebo plus oxytocin, tranexamic acid plus oxytocin was more effective in reducing postpartum hemoglobin drop after vaginal delivery. Tranexamic acid plus oxytocin is therefore recommended to be part of the active management of the third stage of labor.

Phytochemical Profile and Antibacterial-AntiQuorum Sensing Properties of Citrus medica L.

Introduction: Natural resources are becoming more and more important as the need to find solutions to the antibiotic resistance growing crisis. The assessment of medicinal plants' antibacterial and antiquorum-sensing properties is gaining popularity in this field of research every day. The study reported here aimed to investigate the inhibitory activity of the methanolic extract of Citrus medica L. on the inhibition of violacein pigment production in Chromobacterium violaceum ATCC 12472 and some virulence factors in Pseudomonas aeruginosa PAO1. Additionally, the phenolic content of the extract was also determined by HPLC analysis.Methods: The phytochemical content of the plant extract was determined and its antibacterial activity on some bacteria was tested. Also, antibiofilm effect on PAO1 was determined, and violasin pigment inhibition on C. violaceum was investigated.Results: It was observed that the methanolic extract had an inhibition effect of 32% on violacein pigment production and a strong inhibition effect of 88% on biofilm formation caused by PAO1. According to the results of the phytochemical content analysis, benzoic acid was determined as the major component of the extract with a concentration value of 41.9 μg/mL.Conclusion: Citrus medica L, like many plants, has antibacterial and antiquorum sensing activity and may be a potential agent in the fight against infectious diseases.

A nomogram incorporating linezolid and metabolite concentrations for predicting linezolid induced thrombocytopenia in patients with renal impairment

A nomogram to estimate the risk of linezolid-induced thrombocytopenia in patients with renal impairment is not available. The aim of the study is to develop a nomogram for predicting linezolid-induced thrombocytopenia in patients with renal impairment and to investigate the incremental value of PNU-142300 concentration beyond clinical factors and linezolid trough concentration (Cmin) for risk prediction. Logistic regression was used to identify independent risk factors for linezolid-induced thrombocytopenia in patients with renal impairment and nomograms were established. The performance of the nomograms was assessed in terms of area under the receiver operating characteristic curve (AUROC), net reclassification improvement (NRI), integrated discrimination improvement (IDI) , decision curve analysis (DCA) and calibration. Internal validation and external validation of the nomograms were also performed. Four nomograms were created: nomogram A including total bilirubin, creatinine clearance and concomitant mannitol use; nomogram B containing linezolid Cmin additionally; nomogram C containing total bilirubin, concomitant mannitol use, linezolid Cmin, and PNU142300 concentration; nomogram D including total bilirubin, concomitant mannitol use, and PNU142300 concentration. Nomogram C improved the prediction performance than nomogram A (AUROC 0.881 vs. 0.749; NRI 0.290; IDI 0.226) and nomogram B (AUROC 0.881 vs. 0.812; NRI 0.152; IDI 0.130) in the training cohort. DCA analysis showed that nomogram C yielded a greater net benefit. Compared with nomogram A and nomogram B, nomogram C also showed superior discriminatory efficacy, good calibration and clinical usefulness in the external validation cohort. The nomogram containing PNU-142300 concentration and linezolid Cmin had better predictive capability than that containing linezolid Cmin for predicting linezolid-induced thrombocytopenia in patients with renal impairment.

Determination of geochemical stability of swamp ecosystems of the taiga zone of Western Siberia to anthropogenic impact

Relevance. The need for scientifically based regulation of impacts on wetland ecosystems taking into account their specificity and geochemical stability. Aim. To determine the geochemical stability of wetlands in the taiga zone of Western Siberia to pollutants for two typical cases associated with: 1) operation of sludge pits; 2) discharge of domestic and industrial wastewater. Methods. Mathematical modeling, statistical methods. Results and conclusions. The authors have carried out the analysis of the results of studies of the chemical composition of wetland waters and extracts from peat and mineral soils of wetlands in the taiga zone of Western Siberia (mainly in the Tomsk region, as well as in the adjacent territories of the Khanty-Mansiysk Autonomous Okrug, Novosibirsk and Omsk regions). They obtained the estimates of the average values of geochemical indicators of wetland waters and peat by the depth of the peat deposit in peat bogs with varying degrees of anthropogenic impact. The paper introduces the method for assessing the anthropogenic impact of wastewater discharge and geomigration on swamps in areas where oil and gas facilities are located (permissible concentrations in wastewater entering swamp ecosystems), taking into account the «geochemical background» and sorption capacity of peat. In particular, the authors substantiated and tested the method for assessing the values of permissible concentrations, which should be considered as a «relatively safe» level of impact on swamp ecosystems, at which secondary pollution of swamp waters is not expected. It is shown that anthropogenic changes are mainly limited vertically by the upper layer of the peat deposit up to 1–2 m, and horizontally (within the active horizon of the peat deposit) – by areas up to 100–200 m.

Activity and cryo-EM structure of the polymerase domain of the human norovirus ProPol precursor.

Human norovirus (HuNV) is a leading cause of acute gastroenteritis worldwide with most infections caused by genogroup I and genogroup II (GII) viruses. Replication of HuNV generates both precursor and mature proteins during processing of the viral polyprotein that are essential to the viral lifecycle. One such precursor is protease-polymerase (ProPol), a multi-functional enzyme comprised of the norovirus protease and polymerase proteins. This work investigated HuNV ProPol by determining the de novo polymerase activity, protein structure, and antiviral inhibition profile. The GII ProPol de novo enzymatic efficiencies (kcat/Km) for RNA templates and ribonucleotides were equal or superior to those of mature GII Pol on all templates measured. Furthermore, GII ProPol was the only enzyme form active on a poly(A) template. The first structure of the polymerase domain of HuNV ProPol in the unliganded state was determined by cryo-electron microscopy at a resolution of 2.6 Å. The active site and overall architecture of ProPol are similar to those of mature Pol. In addition, both galidesivir triphosphate and PPNDS inhibited polymerase activity of GII ProPol, with respective half-maximal inhibitory concentration (IC50) values of 247.5 µM and 3.8 µM. In both instances, the IC50 obtained with ProPol was greater than that of mature Pol, indicating that ProPol can exhibit different responses to antivirals. This study provides evidence that HuNV ProPol possesses overlapping and unique enzyme properties compared with mature Pol and will aid our understanding of the replication cycle of the virus.IMPORTANCEDespite human norovirus (HuNV) being a leading cause of acute gastroenteritis, the molecular mechanisms surrounding replication are not well understood. Reports have shown that HuNV replication generates precursor proteins from the viral polyprotein, one of which is the protease-polymerase (ProPol). This precursor is important for viral replication; however, the polymerase activity and structural differences between the precursor and mature forms of the polymerase remain to be determined. We show that substrate specificity and polymerase activity of ProPol overlap with, but is distinct from, the mature polymerase. We employ cryo-electron microscopy to resolve the first structure of the polymerase domain of ProPol. This shows a polymerase architecture similar to mature Pol, indicating that the interaction of the precursor with substrates likely defines its activity. We also show that ProPol responds differently to antivirals than mature polymerase. Altogether, these findings enhance our understanding of the function of the important norovirus ProPol precursor.

Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights.

Voriconazole (VRC), a broad-spectrum antifungal drug, exhibits nonlinear pharmacokinetics (PK) due to saturable metabolic processes, autoinhibition and metabolite-mediated inhibition on their own formation. VRC PK is also characterised by high inter- and intraindividual variability, primarily associated with cytochrome P450 (CYP)2C19 genetic polymorphism. Additionally, recent in vitro findings indicate that VRC main metabolites, voriconazole N-oxide (NO) and hydroxyvoriconazole (OHVRC), inhibit CYP enzymes responsible for VRC metabolism, adding to its PK variability. This variability poses a significant risk of therapeutic failure or adverse events, which are major challenges in VRC therapy. Understanding the underlying processes and sources of these variabilities is essentialfor safe and effective therapy. This work aimed to develop a whole-body physiologically-based pharmacokinetic (PBPK) modelling framework that elucidates the complex metabolism of VRC and the impact of its metabolites, NO and OHVRC, on the PK of the parent, leveraging both in vitro and in vivo clinical data in a middle-out approach. A coupled parent-metabolite PBPK model for VRC, NO and OHVRC was developed in a stepwise manner using PK-Sim® and MoBi®. Based on available in vitro data, NO formation was assumed to be mediated by CYP2C19, CYP3A4, and CYP2C9, while OHVRC formation was attributed solely to CYP3A4. Both metabolites were assumed to be excreted via renal clearance, with hepatic elimination also considered for NO. Inhibition functions were implemented to describe the complex interaction network of VRC autoinhibition and metabolite-mediated inhibition on each CYP enzyme. Using a combined bottom-up and middle-out approach, incorporating data from multiple clinical studies and existing literature, the model accurately predicted plasma concentration-time profiles across various intravenous dosing regimens in healthy adults, of different CYP2C19 genotype-predicted phenotypes. All (100%) of the predicted area under the concentration-time curve (AUC) and 94% of maximum concentration (Cmax) values of VRC met the 1.25-fold acceptance criterion, with overall absolute average fold errors of 1.12 and 1.14, respectively. Furthermore, all predicted AUC and Cmax values of NO and OHVRC met the twofold acceptance criterion. This comprehensive parent-metabolite PBPK model of VRC quantitatively elucidated the complex metabolism of the drug and emphasised the substantial impact of the primary metabolites on VRC PK. The comprehensive approachcombining bottom-up and middle-out modelling, therebyaccounting for VRC autoinhibition, metabolite-mediated inhibition, and the impact of CYP2C19 genetic polymorphisms, enhances our understanding of VRC PK. Moreover, the model can be pivotal in designing further in vitro experiments, ultimately allowing for extrapolation to paediatric populations, enhance treatment individualisation and improve clinical outcomes.

Investigation of pure and Sn-doped Ca(OH)2 nanoparticles for optical and biomedical applications

The present study explores the synthesis and characterization of pure and Sn-doped Ca(OH)2 nanoparticles, highlighting their potential for optical and biomedical applications. The incorporation of Sn into the Ca(OH)2 matrix is investigated for the first time, providing insights into its impact on the structural, optical, and biological properties of the nanoparticles. A straightforward precipitation method was employed to synthesize pure and Sn-doped calcium hydroxide nanoparticles. The synthesized nanoparticles were characterized by using X-ray diffraction (XRD) pattern, ultraviolet–visible–near infrared (UV-Vis-NIR) spectra, Fourier Scanning Electron Microscope (FESEM) micrographs, and agar well diffusion method for antibacterial study. X-ray diffraction examinations confirmed the polycrystalline nature of the Ca(OH)2 nanoparticles and revealed the structure to be hexagonal. The average crystallite size of the pure and Sn-doped Ca(OH)2 nanoparticles are 49 nm and 66 nm, respectively. The FESEM images of the sample revealed the formation of pure Ca(OH)2 nanoparticles in the form of nanoflakes and the change in the morphology while doping Sn with Ca(OH)2. The prepared samples were assessed using UV-Vis-NIR spectra, showing the UV absorption band at approximately 247 and 263 nm for the samples of pure and Sn-doped Ca(OH)2 nanoparticles, respectively. The calculated direct and indirect allowed band gap energies were found to be 4.04 and 3.92 eV for pure Ca(OH)2, and 3.37 and 2.94 eV in the case of Sn-doped Ca(OH)2. The antibacterial effectiveness of Ca(OH)2 nanoparticles was assessed using the well diffusion method, and it was observed that both the samples of pure and Sn doped Ca(OH)2 nanoparticles exhibited significant antibacterial properties against gram-negative bacterial strains. An elevation in Minimum Inhibitory Concentration (MIC) values for Sn-doped Ca(OH)2 nanoparticles compared to pure Ca(OH)2 nanoparticles was observed when examining their impact on Gram-negative bacteria (Klebsiella pneumoniae), which suggested a requirement for a higher concentration due to the nature of surface charges present in order to inhibit the growth of microorganisms.

Rosmarinic Acid Exhibits Antifungal and Antibiofilm Activities Against Candida albicans: Insights into Gene Expression and Morphological Changes.

Candida species, opportunistic pathogens that cause various infections, pose a significant threat due to their ability to form biofilms that resist antifungal treatments and immune responses. The increasing resistance of Candida spp. and the limited availability of effective treatments have prompted the research of natural compounds as alternative therapies. This study assessed the antifungal properties of RA against Candida species, focusing on its impact on C. albicans biofilms and the underlying mechanisms. The antifungal efficacy of RA was evaluated using the CLSI M27-A3 microdilution method on both fluconazole-susceptible and -resistant strains. Biofilm formation by C. albicans was assessed through a crystal violet assay, while its antibiofilm activity was analyzed using an MTT assay and field emission scanning electron microscopy (FESEM). Gene expression related to biofilm formation was studied using quantitative real-time PCR (qRT-PCR), and statistical analysis was performed with an ANOVA. Among the 28 Candida strains tested, RA exhibited minimum inhibitory concentration (MIC) values ranging from 160 to 1280 μg/mL. At a 640 μg/mL concentration, it significantly reduced the expression of genes associated with adhesion (ALS3, HWP1, and ECE1), hyphal development (UME6 and HGC1), and hyphal cAMP-dependent protein kinase regulators (CYR1, RAS1, and EFG1) in RAS1-cAMP-EFG1 pathway (p < 0.05). FESEM analysis revealed a reduction in hyphal networks and disruptions on the cell surface. Our study is the first to demonstrate the effects of RA on C. albicans adhesion, hyphae development, and biofilm formation through gene expression analysis with findings supported by FESEM. This approach distinguishes our study from previous studies on the effect of RA on Candida. However, the high MIC values of RA limit its antifungal potential. Therefore, more extensive research using innovative methods is required to increase the antifungal effect of RA.

Essential Oil of Hyptis suaveolens (L.) Poit: A comprehensive study of its chemical and biological properties for therapeutic and industrial applications

The essential oil from the leaves of Hyptis suaveolens was extracted through steam distillation, yielding an average of 0.08% with a density of 0.8. The chemical composition was determined using Gas Chromatography (GC) and Gas Chromatography-Mass Spectrometry (GC-MS), identifying 24 compounds, predominantly sesquiterpenes. Antimicrobial activity tests were conducted using the microdilution method to evaluate the efficacy of the oil against 14 bacterial strains. The essential oil was mainly composed of β-Caryophyllene (33.9%), Germacrene D (25.4%), α-Humulene (8.3%), and Germacrene B (8.2%). Antibacterial tests revealed bactericidal activity against most of the tested strains, with Minimum Inhibitory Concentration (MIC) values ranging from 0.3 to 12.2 mg/mL and slightly higher Minimum Bactericidal Concentrations (MBC). The essential oil of Hyptis suaveolens shows significant antibacterial activity, making it a potential preservative agent for the food industry. Further studies on its antifungal, anticancer activities, and other physical parameters such as refractive index are suggested to explore its full potential.

Ethanolic cashew leaf extract: Antifungal activity and its application for shelf-life extension of dried salted tilapia fillets.

Ethanolic cashew leaf extract (ECLE) is rich in phenolic compounds with diverse bioactivities and can serve as a safe natural preservative. This study evaluated the antifungal activity and application of ECLE for shelf-life extension of dried salted tilapia fillets. Several extraction methods, antifungal activity, and application of ECLE in dried salted tilapia fillets were investigated. Ultrasonication followed by the Soxhlet extraction resulted in the highest yield (26.78%), total phenolic content (TPC), and total flavonoid content (TFC) (p<0.05). Conversely, the Soxhlet extraction method rendered lower yield (14.35%), TPC, and TFC (p<0.05). NaCl at high concentrations decreased both TPC and TFC in all ECLE samples, demonstrating the decomposition of those compounds induced by NaCl. ECLE obtained via the Soxhlet extraction method exhibited lower minimum inhibitory concentration (MIC) and minimum fungicidal concentration values than those prepared using other extraction methods. Thus, the former showed higher efficacy in inhibiting fungal growth and reducing mycelium growth than others (p<0.05), despite being less effective than potassium sorbate. At 4MIC, ECLE inhibited mycelium growth (56.83%-78.66%) and spore germination (87.5%-100%) after 72h and 10-16h of treatment, respectively. ECLE (4MIC) could inhibit the toxin production of fungi. For the challenge test, in which ECLE at 400 and 600mg/kg was added to dried salted tilapia fillet inoculated with Aspergillus flavus, fungal growth was retarded over 9 days of storage at 25±2°C (room temperature). Thus, ECEL could act as a natural food preservative to prevent fungal contamination. Toxin from fungi could be avoided, and the quality of dried salted fish was maintained. PRACTICAL APPLICATION: Cashew leaf extract rich in polyphenols can inhibit fungal proliferation, reduce mycelium expansion, prevent spore germination, and limit aflatoxin production. The extract canenhance the safety of dried salted fish, especially when contaminated with Aspergillus flavus in the humid atmosphere (80% relative humidity), particularly for small and medium enterprises. Nevertheless, this extract can also be applied in the fish processing industry, in which the synthetic antifungal agent could be replaced by the natural additive.

The Growth Performance, Haematological Parameters and Serum Biochemistry of the Flathead Grey Mullet Mugil cephalus Under Recirculating Aquaculture System and Traditional Culture Systems.

The present investigation explored the growth performance, haematological parameters and serum biochemistry of flathead grey mullet under recirculating aquaculture system (RAS) and traditional culture systems. Nine hundred healthy fish, weighing 43.80 ± 3.55 g and length 16.54 ± 0.82 cm were randomly distributed to three treatments of RAS and traditional culture systems (T1: 20% of water changed daily; T2: once-through system 250 L/h; T3: RAS-20% of water changed weekly) in nine concrete tanks of 4000 L at stocking density of 100 fish/tank and each treatment had three replicates. Fish were fed (33.1% crude protein, 3 mm pellets) twice a day at a rate of 3% for 12 weeks. These findings suggest that the T3 followed by T2 led to notable improvements in growth performance compared to other culture systems. Significantly elevated values of weight gain, length gain, specific growth rate, average daily gain and survival % were observed in T3. The RBCs exhibited a significant decrease under T2. Haemoglobin concentrations and WBC counts significantly increased under RAS. Significant values of mean cell haemoglobin and mean cell haemoglobin concentration were recorded in T2. Total protein, albumin and globulin enhanced significantly under RAS, whereas the highest values of cortisol were observed in T2 and T3. These findings demonstrate that the RAS followed by once-through system significantly improve growth performance, feed efficiency and survival, as well as enhancing the haematology and serum biochemical status of flathead grey mullet. In conclusion, RAS provides ideal conditions for optimizing physiological functions, growth performance and fish health.

In-line spectroscopy for iodine quantification in dynamic contrast-enhanced dedicated breast CT.

In 4D dynamic contrast-enhanced dedicated breast computed tomography (4D DCE-bCT), the functional properties of the breast will be characterized by monitoring the uptake and washout of iodine-based contrast agents over time. This information could be valuable in breast cancer treatment. However, prior to clinical implementation, it is crucial to validate the quantitative estimates of iodine concentrations at each time point during acquisition. To develop an in-line spectroscopy system capable of measuring iodine concentrations in a dynamic x-ray breast phantom in real-time. Potassium iodide served as the contrast agent. The system was set-up at both the entrance and exit of the phantom. It comprises a fiber-coupled green LED and collimator, which together ensure that a parallel beam passes through the sample holder. Transmitted light is captured by a collimator on the opposite side and directed through a fiber optic cable to a photodetector for intensity measurement. The relationship between 13 iodine concentrations (0-6mg I/mL) and light transmission was tested, and the system's repeatability and accuracy were determined. The system exhibited a strong correlation between iodine concentration and transmission values, achieving a root-mean-square error of 0.007. The repeated measurements had relative standard deviations of 0.04% and 0.1% for repeated water measurements at the phantom's entrance and exit, respectively. Furthermore, the accuracy measurements gave a mean error of fitting of 0.008(±0.07) mg I/mL. The in-line spectroscopy system can effectively monitor iodine concentrations in a dynamic breast phantom, providing a reliable method for quantitative validation of 4D DCE-bCT.

Clinical characteristics of patients with granulomatous lobular mastitis associated with Corynebacterium parakroppenstedtii infection and drug sensitivity analysis of the isolated strains

BackgroundIt is presently considered that Corynebacterium especially Corynebacterium kroppenstedtii (CK) infection, is one of the important causes of granulomatous lobular mastitis (GLM). However, the pathogen of mastitis in the past two years has been identified as a newly discovered Corynebacterium. But it is unclear whether the pathogen associated with the occurrence of GLM is also this bacterium.MethodsGLM female patients with positive bacterial culture in pus specimens from February 2023 to February 2024 who were identified as CK infection by mass spectrometer were selected as the research objects in this study, and the clinical isolates were identified by 16S rDNA sequencing technology to identify the specific pathogen of GLM-related bacterial infection. Subsequently, the clinical characteristics of the patients were compared with those of GLM patients without bacterial infection during the same period, to explore the effect of this particular type of Corynebacterium infection on disease development in GLM patients. Finally, we tested the minimum inhibitory concentration (MIC) values of antibiotics when inhibiting these separation strains in vitro through the E-Test experiment, to evaluate their medicine sensitivity.ResultsA total of 31 GLM patients initially diagnosed with Corynebacterium kroppenstedtii (CK) infection via MALDI-TOF MS were enrolled in the study. However, subsequent 16S rDNA sequencing revealed that 28 isolates (90.32%) were actually identified as the newly recognized Corynebacterium parakroppenstedtii (CPK). This discovery challenges the conventional belief that CK is the primary pathogen of GLM, suggesting instead that CPK is the predominant pathogen associated with GLM bacterial infections. Comparative analysis of the clinical characteristics between the two groups revealed a significantly higher recurrence rate among CPK-infected GLM patients compared to those without CPK infection, along with elevated prolactin levels (P < 0.05). The sensitivity test results indicated high sensitivity of the isolates to vancomycin, linezolid, and rifampicin.ConclusionIn conclusion, this study highlights that Corynebacterium kroppenstedtii strains isolated from GLM specimens were Corynebacterium parakroppenstedtii, serving as the primary pathogen closely linked to GLM’s occurrence. CPK infection significantly increases the risk of recurrence in GLM patients, with elevated prolactin levels potentially playing a pivotal role in this process. In clinical antimicrobial treatment, antimicrobials other than penicillin and ciprofloxacin may be empirically administered when sensitivity test results are inconclusive.

An Axially CBD‐Containing Novel Pt(IV) Prodrug Designed to Synergistically Enhance Antitumor Activity by Inducing Mitochondrial Dysfunction

ABSTRACTIn recent years, significant attention has been given to the strategy of linking novel active molecules with different biological targets and antitumor mechanisms to the axial positions of Pt(IV) complexes, aiming to synthesize new Pt(IV) antitumor complexes with excellent properties. In this study, Satraplatin analogs and the highly lipophilic bioactive molecule cannabidiol (CBD) were chosen as the main research subjects. By combining these two and introducing other bioactive small molecules, we aimed to enrich the functionalities of Pt(IV) antitumor complexes. Five new multifunctional Pt(IV) antitumor complexes, P1–P5, were prepared. All Pt(IV) prodrugs demonstrated antitumor effects in various tumor cell lines. Notably, compound P1 exhibited significant inhibitory effects, with half‐maximal inhibitory concentration (IC50) values that were 2.1, 1.5, and 1.3 times higher than those of satraplatin in HCT‐116, A549, and HeLa cell lines, respectively, and 2.4, 1.5, and 2.0 times higher than those of the combination of satraplatin and CBD. The cytotoxicity of P1 toward cancer cell lines is significantly higher than that of the combination therapy group, providing preliminary evidence that the strategy of combining CBD and platinum‐based antitumor drugs into a complex is highly effective in simultaneously enhancing the cytotoxicity of both, resulting in a good synergistic antitumor effect. Further research shows that after treating cells with P1, the induced ROS generation increases in a dose‐dependent manner, disrupting the cell's redox homeostasis, leading to oxidative stress, and ultimately causing cell apoptosis. This strategy of introducing the bioactive molecule CBD into platinum‐based drug formation complexes to improve efficacy has been shown to be feasible and deserves further study.