High Activity Research Articles

Effect of a phthalate derivative purified from Bacillus zhangzhouensis SK4 on quorum sensing regulated virulence factors of Pseudomonas aeruginosa

Pseudomonas aeruginosa causes life-threatening diseases and is resistant to almost all conventional antibiotics. The quorum sensing (QS) system of P. aeruginosa contributes to many pathogenic factors some of which are pigment production, motility, and biofilm. The disruption of quorum sensing system may be an impactful strategy to deal with infections. The present study investigates the anti-quorum sensing property of a bioactive molecule extracted from marine epibiotic bacteria present on the surface of seaweeds. Among all the isolates tested against monitor strain Chromobacterium violaceum (MTCC 2656), the one with the highest activity was identified as Bacillus zhangzhouensis SK4. The culture supernatant was extracted with chloroform which was then partially purified by TLC and column chromatography. The probable anti-QS compound was identified as 1,2-benzenedicarboxylic acid, bis (2-methylpropyl ester) by GC-MS and NMR analysis. The treatment of P. aeruginosa MCC 3457 with the lead compound resulted in the reduced production of pyocyanin, rhamnolipids, exopolysaccharide, biofilm, and motility. The observations of light and scanning electron microscopy also supported the biofilm inhibition. The lead compound showed synergism with the meropenem antibiotic and significantly reduced MIC. The molecular docking and pharmacokinetics study predicted 1, 2-benzenedicarboxylic acid, bis (2-methylpropyl ester), a phthalate derivative as a good drug candidate. The molecular dynamics study was also performed to check the stability of the lead compound and LasR complex. Further, lead compounds did not exhibit any cytotoxicity when tested on human embryonic kidney cells. As per our knowledge, this is the first report on the anti-QS activity of B. zhangzhouensis SK4, indicating that epibiotic bacteria can be a possible source of novel compounds to deal with the multidrug resistance phenomenon.

Sm-doped ZnO with enhanced photocatalytic performance toward destruction of RhB

In this work, Sm-doped ZnO was prepared by a Sol-Gel method. The structure, morphology, composition and optical properties of the prepared samples were investigated by X-ray diffraction (XRD), scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), surface photovoltage spectrum (SPS) and X-ray photoelectron spectros­copy (XPS). Sm-doping results in high specific surface area and boosted photogenerated carriers separation efficiency, and produces more active free radicals to participate in the photocatalytic reaction. Photocatalytic activities of the samples toward removal of rhodamine B(RhB) were evaluated under UV light irradiation, the results display that Sm-doped ZnO shows higher photocatalytic activity than the reference ZnO.

Corrosion behavior and mechanism of FeCoNi high-entropy alloy compared with X100 pipeline steel in a simulated alkaline soil environment

In this work, the corrosion behavior of FeCoNi HEA and X100 pipeline steel in a simulated Golmud soil environment was systematically studied utilizing electrochemical tests, surface analysis techniques and immersion measurement. The results indicate that FeCoNi HEA possesses superior anti-corrosion property than X100 steel by comparing the charge transfer resistance (Rct), passive current density (ip) and corrosion morphology. The microstructure and surface film are the principal factors causing the difference in corrosion resistance of the two alloys. More intact, uniform and dense passive film enhances the anti-corrosion performance of the HEA, while the nonprotective, loose and defective corrosion product film covering the surface of X100 steel is not conducive to inhibiting the corrosion of the steel substrate. The appearance of inclusions within the HEA can generate the micro-galvanic corrosion effect with the matrix, which promotes the substrate as an anode to induce pitting. Furthermore, multiple phases of X100 steel exhibits higher electrochemical activity compared to the HEA with a single Face Center Cubic (FCC) phase, which accelerates the corrosion of the steel. Moreover, the matrix of the HEA primarily experiences selected dissolution of Ni element.

FAPi PET/CT for assessment and visualisation of active myositis-related interstitial lung disease: a prospective observational pilot study

Interstitial lung disease (ILD) is a common manifestation of idiopathic inflammatory myopathies (IIM) and a substantial contributor to hospitalisation, increased morbidity, and mortality. In-vivo evidence of ongoing tissue remodelling in IIM-ILD is scarce. We aimed to evaluate fibroblast activation in lungs of IIM-patients and control individuals using ⁶⁸Ga-labelled inhibitor of Fibroblast-Activation-Protein (FAPi) based positronic emission tomography and computed tomography imaging (PET/CT). In this prospective observational pilot study, consecutive patients with IIM and participants without rheumatic conditions or ILD serving as a control group were recruited at the Medical University of Vienna, Austria, and underwent FAPi PET/CT imaging. Standard-of-care procedures including clinical examination, assessment of severity of dyspnoea, high-resolution computed tomography (HR-CT), and pulmonary function testing (PFT) were performed on all patients with IIM at baseline and for patients with IIM-ILD at follow-up of 12 months. Baseline pulmonary FAPi-uptake was assessed by the maximum (SUVmax) and mean (SUVmean) standardized uptake values (SUV) over the whole lung (wl). SUV was corrected for blood pool background activity and target-to-background ratios (TBR) were calculated. We compared pulmonary FAPi-uptake between patients with IIM-ILD and those without ILD, as well as controls, and correlated baseline FAP-uptake with standard diagnostic tools such as HR-CT and PFT. For predictive implications, we investigated whether patients with IIM and progressive ILD exhibited higher baseline FAPi-uptake compared to those with stable ILD. Metrics are reported as mean with standard deviation (±SD). Between November 16, 2021 and October 10, 2022, a total of 32 patients were enrolled in the study. Three participants from the control group were excluded due to cardiopulmonary disease. In individuals with IIM-ILD (n=14), wlTBRmax and wlTBRmean were significantly increased as compared with both non-ILD-IIM patients (n=5) and the control group (n=16): wlTBRmax: 2.06±1.04 vs. 1.04±0.22 (p=0.019) and 1.08±0.19 (p=0.0012) and wlTBRmean: 0.45±0.19 vs. 0.26±0.06 (p=0.025) and 0.27±0.07 (p=0.0024). Similar values were observed in wlTBRmax or wlTBRmean between non-ILD IIM patients and the control group. Patients with progressive ILD displayed significantly enhanced wlTBRmax and wlTBRmean values at baseline compared to patients with stable ILD: wlTBRmax: 1.30±0.31 vs. 2.63±1.04 (p=0.0084) and wlTBRmean: 0.32±0.08 vs. 0.55±0.19 (p=0.021). Strong correlations were found between FAPi-uptake and disease extent on HR-CT (wlTBRmax: R=0.42, p=0.07; wlTBRmean: R=0.56, p=0.013) and severity of respiratory symptoms determined by the New York Heart Association (NYHA) classification tool (wlTBRmax: R=0.52, p=0.022; wlTBRmean: R=0.59, p=0.0073). Further, pulmonary FAPi-uptake showed inverse correlation with forced vital capacity (FVC) (wlTBRmax: R=-0.56, p=0.012; wlTBRmean: R=-0.64, p=0.0033) and diffusing capacity of the lungs for carbon monoxide (DLCO) (wlTBRmax: R=-0.52, p=0.028; wlTBRmean: R=-0.68, p=0.0017). Our study demonstrates higher fibroblast activation in patients with IIM-ILD compared to non-ILD patients and controls. Intensity of pulmonary FAPi accumulation was associated with progression of ILD. Considering that this study was carried out on a small population, FAPi PET/CT may serve as a useful non-invasive tool for risk stratification of lung disease in IIM. The Austrian Research Fund.

Screening and Activity Evaluation of Novel BCR-ABL/T315I Tyrosine Kinase Inhibitors.

Chronic myeloid leukemia (CML) is a kind of malignant tumor formed by the clonal proliferation of bone marrow hematopoietic stem cells. BCR-ABL fusion protein, found in more than 90% of patients, is a vital target for discovering anti-CML drugs. Up to date, imatinib is the first BCR-ABL tyrosine kinase inhibitor (TKI) approved by the FDA for treating CML. However, the drug resistance problems appeared for many reasons, especially the T135I mutation, a "gatekeeper" of BCR-ABL. Currently, there is no long-term effective and low side effect drug in clinical. This study intends to find novel TKIs targeting BCR-ABL with high inhibitory activity against T315I mutant protein by combining artificial intelligence technology and cell growth curve, cytotoxicity, flow cytometry and western blot experiments. The obtained compound was found to kill leukemia cells, which had good inhibitory efficacy in BaF3/T315I cells. Compound No 4 could induce cell cycle arrest, cause autophagy and apoptosis, and inhibit the phosphorylation of BCR-ABL tyrosine kinase, STAT5 and Crkl proteins. The results indicated that the screened compound could be used as a lead compound for further research to discover ideal chronic myeloid leukemia therapeutic drugs.

In-vitro Antioxidant, In-vitro and In-silico Ovarian Anticancer Activity (Ovarian Cancer Cells-PA1) and Phytochemical Analysis of Cissus quadrangularis L. Ethanolic Extract.

Cissus quadrangularis is a valuable natural source of traditional medicines. An in vitro investigation was performed to determine whether the ethanolic extract from the whole portions of C. quadrangularis had anticancer and free radical scavenging activities against ovarian cancer cells-PA1. C. quadrangularis is a herb collected from rural areas in Andhra Pradesh, India. C. quadrangularis was air-dried and crushed, and the powder and ethanol (0.5 kg) were used in a Soxhlet device for continuous extraction. Phytochemical analysis of the extracts was performed using a standard procedure. The antioxidant activity of the ethanolic extract of C. quadrangularis was evaluated using DPPH. An in vitro anticancer study used an ethanolic extract against the PA1 cell line. Apoptosis of ovarian cancer cells was studied using DAPI and carboxy-H2DCFDA staining. From LC-MS analysis, quercetin-3-O-alpha-Lrhamnopyranoside and erucic acid were docked with the threonine tyrosine kinase (TTK) enzyme using auto docking. The ethanolic extract of C. quadrangularis demonstrated significant dose-dependent antioxidant activity compared to ascorbic acid. The ethanolic extract of C. quadrangularis was found to have high anticancer activity against ovarian cancer cell lines (PA1), with an IC50 value of 482.057 ± 113.857 μg/ml. DAPI and carboxy-H2DCFDA staining confirmed that C. quadrangularis ethanolic extract induced apoptosis in ovarian cancer cells (p < .001). Molecular docking studies helped identify the binding affinities between the protein and ligand complexes, such as Quercetin-3-O-alpha-Lrhamnopyranoside binding sites of target proteins 5N7V (MET602, GLN672) and erucic acid 5N7V (GLY354). Quercetin-3-O-alpha-L-rhamnopyranoside was reported to bind with 5N7V by hydrogen bonding at MET602 and GLN672 amino acids with 2.02, 2.99 Å bonding length distance and binding affinity of -7.9 kcal/mol. Erucic acid was reported to bind with 5N7V by hydrogen bonding at GLY354 amino acid with 3.18, 2.93 Å bonding length (Å) distance and binding affinity of -4.3 kcal/mol. The current analysis showed that the ethanolic extracts of C. quadrangularis L. exhibited antioxidant and anticancer properties against ovarian PA1 cells. The experimental results confirmed that C. quadrangularis L. is a promising, safe chemotherapeutic plant for ovarian cancer PA1 cells. The docking results demonstrated that Quercetin-3-O-alpha-L-rhamnopyranoside strongly binds threonine tyrosine kinase at the MET602 and GLN672 positions. This study showed that the C. quadrangularis ethanolic extract has Quercetin-3-O-alpha-L-rhamnopyranoside, which can be used as an anticancer agent.

Design, Synthesis, Evaluation and Toxicity Studies of Novel Acridine Derivatives in Zebra Fish Larvae

Background: Alzheimer’s disease (AD) is a complex neurodegenerative condition for which a single protein-targeting medication is not enough to provide a cure. All the medications now available for AD are palliative. FDA has approved five medications for the treatment of AD, i.e., tacrine, donepezil, galantamine, rivastigmine, and memantine. Due to hepatotoxicity, tacrine is no longer utilized in clinical practice. Due to the lack of therapeutic efficiency of single-target medications and the multifaceted etiology of AD, multitarget-directed ligands have been developed. Objectives: The present research focused on incorporating a flavone nucleus into the amino group of 9-amino acridine nucleus to make it an acetylcholinesterase (AChE) and butyryl cholinesterase inhibitor (BuChE) with less toxicity Methods: We designed and synthesized ten flavone-substituted acridine derivatives and evaluated them for in vitro AChE and BuChE inhibitory activity. Molecular modeling studies were conducted using AutoDock Vina with hAChE (PDB ID: 4EY7) and hBuChE (PDB ID: 4TPK). The toxicity profile of the most active novel compound tested on zebrafish larvae for determining the liver and cardiac toxicity and LD50 value of the compound were determined. Results: In vitro AChE and BuChE inhibitory study by Ellman assay showed acceptable results. The compound AF2 showed the highest activity with an IC50 value of 0.99 ± 0.1 µM for AChE and 1.78 ± 0.19 for BuChE. The in vivo acute toxicity studies conducted on zebra fish larvae did not show cardiac and hepatotoxicity, and the LD50 value was found to be 1000 µL Conclusion: The results highlighted the AChE and BuChE inhibitory effects of the novel acridine-flavone hybrids, and they can be promising multitarget-directed ligands for AD.

Chemical composition, antioxidant, antimicrobial and anticancer activities of endemic Cephalaria tuteliana

IntroductionThe genus Cephalaria, belonging to the Caprifoliaceae family, is a rich source of secondary metabolites, including mainly saponins which display a variety of biological activities, such as antimicrobial, antioxidant, and anticancerous effects. This study was carried out to observe the biochemical composition and to evaluate the biological activities of Cephalaria tuteliana Kus & Gokturk. MethodsThe composition of endemic C. tuteliana was determined through gas chromatography-mass spectrometry (GC-MS) studies. Antimicrobial effect were determined by the disk diffusion and dilution methods for test bacteria and test fungi. The antioxidant potential of the ethanol extract was also investigated. Cell proliferation and apoptosis analysis were investigated by WST-1 and ELISA methods. The migration level of PC-3 prostate cancer cells after plant extract application was examined by wound healing assay. Also, molecular docking experiments were performed to investigate the anticancer activity of the major component found in the C.tuteliana extract. ResultsGC-MS analysis showed that the predominant compounds were Phenol, 2,2′-methylenebis [6-(1,1dimethyl ethyl)-4-methyl- (23.54%), 9,12,15-octadecatrien-1-ol, (Z,Z,Z)-(6.06%) and n-Hexadecanoic acid (3.03%). The ethanolic extract of C. tuteliana displayed moderate antimicrobial activity against a spectrum of tested microorganisms. Also, it exhibited significant antiproliferative effects on PC-3 human prostate cancer cells while having no harmful effects on healthy control HUVEC cells. Furthermore, enhanced expressions of Caspase-3, 8, and 9 were observed in PC-3 cells after plant extract treatment. Also, cell migration level was notably reduced, especially at a dose of 400 µg/mL in PC-3 cells. The DPPH free radical scavenging activity of ethanolic extracts of C. tuteliana showed higher activity than ascorbic acid. Molecular docking experiments showed potential binding of the major aromatic compound in C.tuteliana extract to human androgen receptor 1E3G protein. ConclusionThese findings highlight the potential of C. tuteliana as a valuable natural resource and pave the way for further in vivo prostate cancer investigations.

Hot deformation behavior of NiTiHf alloy under compression: Effect of deformation heating on flow softening

High-temperature shape memory alloys are suitable materials for substituting hydraulic elements in the aerospace industry due to light weight and high reactive stresses developing during thermoelastic martensitic transformation and acceptable recoverable strain. These properties may be improved by plastic deformation; however, the plastic deformation of NiTiHf alloys along with structure investigation has yet to be studied systematically. Here, the hot deformation behavior of a NiTiHf alloy with hafnium content >20 at.% has been investigated, and the processing map has been elaborated according to the dynamic material model (DMM) based on the Prasad instability criterion. The deformation heating effect has been shown to affect the flow curves and accounts for profound softening during deformation due to quasi-adiabatic deformation mode at high strain rates. NiTiHf alloys have a much higher activation energy of plastic flow, and the instability region of plastic flow is much larger compared to binary NiTi alloys. Microstructural observations have revealed that in the instability regions, oxide bands and crack nucleation occur, whereas outside this region, such defects are not observed. Electron-back scatted diffraction has demonstrated that at high temperatures and slow strain rates, discontinuous dynamic recrystallization occurs resulting in the neckless type structure, while at high strain rates, this phenomenon has not been observed. Based on the obtained results, the preferable deformation conditions are established to be 850–1000 °C and 0.003–0.05 s−1.

Base-free synthesis of renewable furan-2,5-dicarboxylic acid (FDCA) over an earth-abundant magnetic catalyst

Being a biobased alternative to petroleum-based terephthalic acid (TPA), furan-2,5-dicarboxylic acid (FDCA) requires a low-cost and efficient catalytic system for its commercialization. This study describes FDCA production using whey permeate powder (WPP)-derived 5-(hydroxymethyl)furfural (HMF) in a base-free system over a magnetically recyclable catalyst composed of earth-abundant metals (Mn and Fe). The impact of MnCl2·4 H2O loading on the iron core was studied at different levels and found optimal at the ratio of 1:1. The in-situ oxidation of HMF was carried out using ozone and t-BuOOH as the oxidants in a γ-valerolactone (GVL) -water solvent system. It was observed that the ozone pre-treatment (3 h at room temperature) of HMF increased the FDCA yield from 39.7 % (without ozonation) to 60 % at a reaction condition of 130 °C for 2 h. The concentration profiles for the intermediates formed during HMF to FDCA oxidation i.e., 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), furan-2,5-dicarbaldehyde (DFF), and 5-formyl-2-furancarboxylic acid (FFCA) were analyzed at different reaction temperatures to evaluate the reaction kinetics. The kinetic study revealed that the present solvent-catalytic system favored HMFCA formation over DFF due to the requirement of higher activation energy for the latter. The HMF to FDCA catalytic solvent was tested for WPP, which afforded an overall FDCA yield of 14.6 % at 130 °C in 120 min. In addition, the Mn1Fe1 consisted of mixed phases of Mn3O4, Mn2O3, MnO2, Fe2O3, and Fe3O4 and demonstrated variation in oxidation states for Mn (Mn3+↔Mn2+) and Fe (Fe2+↔Fe3+) species.

Tailoring the electronic structure of Fe–N4 sites via heteroatom modification strategy for boosting oxygen reduction in hydrogen fuel cells: A density functional theory study

Heteroatoms-modified Fe–N–C catalysts have garnered significant attention for enhancing the oxygen reduction reaction (ORR). However, revealing the correlation between the type of heteroatoms used for doping and catalytic performance still faces significant challenges. Herein, based on the density functional theory (DFT), a series of heteroatom-modified Fe–N–C models with the tailored Fe–N4-X (X = S, P or B) site are constructed to explore the regulatory mechanism of heteroatoms on the electronic structure and adsorption behavior of Fe centers. Theoretical calculations reveal that the doping of S atoms can optimize the electronic environment of Fe atoms, thus leading the favorable interaction between Fe–N4–S site and OH intermediates. As a result, the Fe–N4–S site possess a lower energy barrier for the desorption of OH* than that of Fe–N4–B and Fe–N4–P, indicating higher catalytic activity and kinetics of S-modified Fe–N–C catalysts.

Design of Multifunctional Electrocatalysts for ORR/OER/HER/HOR: Janus Makes Difference.

Multifunctional electrocatalysts for hydrogen evolution reaction (HER), hydrogen oxidation reaction (HOR), oxygen evolution reaction (OER), and oxygen reduction reaction (ORR) have broad application prospects; However, realization of such kinds of materials remain difficulties because it requires the materials to have not only unique electronic properties, but multiple active centers to deal with different reactions. Here, employing density functional theory (DFT) computations, it is demonstrated that by decorating the Janus-type 2D transition metal dichalcogenide (TMD) of TaSSe with the single atoms, the materials can achieve multifunctionality to catalyze the ORR/OER/HER/HOR. Out of sixteen catalytic systems, Pt-VS (i.e., Pt atom embedded in the sulfur vacancy), Pd-VSe, and Pt-VSe@TaSSe are promising multifunctional catalysts with superior stability. Among them, the Pt-VS@TaSSe catalyst exhibits the highest activity with theoretical overpotentials ηORR = 0.40V, ηOER = 0.39V, and ηHER/HOR = 0.07V, respectively, better than the traditional Pt (111), IrO2 (110). The interplays between the catalyst and the reaction intermediate over the course of the reaction are then systematically investigated. Generally, this study presents a viable approach for the design and development of advanced multifunctional electrocatalysts. It enriches the application of Janus, a new 2D material, in electrochemical energy storage and conversion technology.

Biochemical Characterization of a Heat-Resistant κ-Carrageenase Capable of Tolerating High Temperatures up to 100 °C.

κ-Carrageenase plays a crucial role in the high-value utilization of carrageenan. Heat resistance is a key factor in the practical application of κ-carrageenase, as carrageenan exhibits gel-like properties. Previous studies have shown that the C-terminal noncatalytic domains (nonCDs) can affect the thermostability of κ-carrageenases. In this study, we expressed and characterized a κ-carrageenase, MtKC16A, which contains three nonCDs, from Microbulbifer thermotolerans. MtKC16A has the highest activity at 80 °C and pH 7.0. Surprisingly, it exhibits excellent heat resistance, with 71.58% relative activity at 100 °C and still retains over 50% residual activity after incubation at 100 °C for 60 min. Additionally, MtKC16A has been shown to have a dual substrate hydrolysis activity. It can degrade κ-carrageenan to produce highly single Nκ4 and degrade β/κ-carrageenan to produce Nκ2 and desulfated Nκ4 DA-G-DA-G4S, suggesting its potential in producing κ- and β/κ-hybrid oligosaccharides. Furthermore, we found that the unknown function domain (UNFD) in MtKC16A plays the most vital role among the three nonCDs. When this UNFD is truncated, the resulting mutants completely lose their catalytic ability at 100 °C. Finally, by introducing this UNFD to the C-terminal of another κ-carrageenase CaKC16B, we were able to improve its heat resistance at 100 °C.

A comparative study of the biosynthesis of CuNPs by Niallia circulans G9 and Paenibacillus sp. S4c strains: characterization and application as antimicrobial agents

BackgroundBiosynthesis of metallic nanoparticles using microorganisms are a fabulous and emerging eco-friendly science with well-defined sizes, shapes and controlled monodispersity. Copper nanoparticles, among other metal particles, have sparked increased attention due to their applications in electronics, optics, catalysis, and antimicrobial agents.ResultsThis investigation explains the biosynthesis and characterization of copper nanoparticles from soil strains, Niallia circulans G9 and Paenibacillus sp. S4c by an eco-friendly method. The maximum reduction of copper ions and maximum synthesis CuNPs was provided by these strains. Biogenic formation of CuNPs have been characterized by UV–visible absorption spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray analysis and transmission electron microscopy analysis. Using UV-visible spectrum scanning, the synthesised CuNPs’ SPR spectra showed maximum absorption peaks at λ304&308 nm. TEM investigation of the produced CuNPs revealed the development of spherical/hexagonal nanoparticles with a size range of 13–100 nm by the G9 strain and spherical nanoparticles with a size range of 5–40 nm by the S4c strain. Functional groups and chemical composition of CuONPs were also confirmed. The antimicrobial activity of the biosynthesized CuNPs were investigated against some human pathogens. CuNPs produced from the G9 strain had the highest activity against Candida albicans ATCC 10,231 and the lowest against Pseudomonas aeruginosa ATCC 9027. CuNPs from the S4c strain demonstrated the highest activity against Escherichia coli ATCC 10,231 and the lowest activity against Klebsiella pneumonia ATCC 13,883.ConclusionThe present work focused on increasing the CuNPs production by two isolates, Niallia circulans G9 and Paenibacillus sp. S4c, which were then characterized alongside. The used analytics and chemical composition techniques validated the existence of CuONPs in the G9 and S4c biosynthesized nano cupper. CuNPs of S4c are smaller and have a more varied shape than those of G9 strain, according to TEM images. In terms of antibacterial activity, the biosynthesized CuNPs from G9 and S4c were found to be more effective against Candida albicans ATCC 10,231 and E. coli ATCC 10,231, respectively.

Influence of Solvent Polarity on Phytochemicals, Antioxidants, and Antimicrobial Properties of Delphinium Denudatum: A Medicinal Herb from Sainj Valley, Himachal Pradesh, India

Plants with medicinal properties play an important role in pharmaceutical industries for their disease prevention and treatment applications. Delphinium denudatum, commonly known as jadwar, is an important medicinal plant of the Himalayan region. Therefore, in the present study, the effect of solvent polarity (using seven different solvents i.e., methanol, ethanol, acetone, chloroform, ethyl acetate, hexane, and water separately) was estimated for its secondary metabolites production, antioxidants, and antimicrobial activities. Among the seven different extracting solvents used, the methanol extract of leaf rendered the highest phenolic content (80.52 mg GAE/g (dry weight (dw)). Acetone extracts for the shoot were found to be most efficient with the extraction of the highest flavonoid content (57.53 mg QE/g (dw) while the methanol extract of root rendered the highest tannin content 18.78 mg TAE/g (dw). Likewise, the methanol extract of the leaf showed the highest flavonol content 34.76 mg QE/g (dw). For antioxidant activity, the IC50 value for ABTS activity ranged from 35.15 to 103.08 µg/mL, and for DPPH activity it was 75.23 to 256.21 µg/mL. Further, all the plant parts i.e., leaf, shoot, and root, showed antimicrobial activity against Bacillus subtilis, Escherichia coli, and Serratia marcescens having MIC between 400 to 900 µg/mL. Among all the tested plant parts, polar solvent leaf extracts had higher antioxidant activity. Furthermore, phenols, flavonols, tannins, and ABTS activity from leaf, shoot, and root have shown a positive relation with solvent polarity. In all three plant parts; phenols, flavonols, and tannin positively correlate with antibacterial activity. The present study further revealed that the secondary metabolites in the leaf, shoot, and root extracts of D. denudatum are an excellent source of antioxidant and antimicrobial activities, thus validating the species’ therapeutic potential.

Effect of bicarbonate and polyvinyl alcohol on in vitro capacitation and fertilization ability of cryopreserved equine spermatozoa.

Factors contributing to the limited success of in vitro fertilization in horses remain to be studied. In this work, we elucidated the effect of different essential capacitation media components, bicarbonate, and bovine serum albumin or polyvinyl-alcohol, and the incubation microenvironment on sperm parameters associated with capacitation, acrosome reaction, and their ability to activate oocytes via heterologous intracytoplasmic spermatozoa injection in equine cryopreserved spermatozoa. Frozen-thawed spermatozoa underwent incubation at different time intervals in either Tyrode's albumin lactate pyruvate medium (non-capacitating; NC) or Tyrode's albumin lactate pyruvate supplemented with bicarbonate, bicarbonate and polyvinyl-alcohol, bicarbonate and bovine serum albumin, polyvinyl-alcohol and bovine serum albumin alone. Protein kinase A-phosphorylated substrates and tyrosine phosphorylation levels, sperm motility, and acrosome reaction percentages were evaluated. After determining the best condition media (capacitating; CAP), heterologous intracytoplasmic spermatozoa injection on pig oocytes was performed and the phospholipase C zeta sperm localization pattern was evaluated. Incubation of frozen-thawed equine spermatozoa with bicarbonate and polyvinyl-alcohol in atmospheric air for 45min induced an increase in protein kinase A-phosphorylated substrates and tyrosine phosphorylation levels compared to NC condition. Sperm incubation in bicarbonate and polyvinyl-alcohol medium showed an increase in total motility and progressive motility with respect to NC (p ≤ 0.05). Interestingly, three parameters associated with sperm hyperactivation were modulated under bicarbonate and polyvinyl-alcohol conditions. The kinematic parameters curvilinear velocity and amplitude of lateral head displacement significantly increased, while straightness significantly diminished (curvilinear velocity: bicarbonate and polyvinyl-alcohol=120.9±2.9 vs. NC=76.91±6.9µm/s) (amplitude of lateral head displacement: bicarbonate and polyvinyl-alcohol=1.15±0.02 vs. NC=0.77±0.03µm) (straightness: bicarbonate and polyvinyl-alcohol=0.76±0.01 vs. NC=0.87±0.02) (p ≤ 0.05). Moreover, the spontaneous acrosome reaction significantly increased in spermatozoa incubated in this condition. Finally, bicarbonate and polyvinyl-alcohol medium was established as CAP medium. Although no differences were found in phospholipase C zeta localization pattern in spermatozoa incubated under CAP, equine spermatozoa pre-incubated in CAP condition for 45min showed higher fertilization rates when injected into matured pig oocytes (NC: 47.6% vs. CAP 76.5%; p ≤ 0.05). These findings underscore the importance of bicarbonate and polyvinyl-alcohol in supporting critical events associated with in vitro sperm capacitation in the horse, resulting in higher oocyte activation percentages following heterologous intracytoplasmic spermatozoa injection. This protocol could have an impact on reproductive efficiency in the equine breeding industry.

ANTIBACTERIAL AND ANTIOXIDANT PROPERTIES OF SOME PLANT EXTRACTS WITH PROPOLIS

For many years, plants have been utilized in food, healing materials, and curing for many illnesses. Lately, improvements in biological searches have displayed the notable potential of natural compounds.Objective: In this study, biological activities of extracts of herbal mixtures with propolis were investigated.Materials and Methodology: Ethanol and hexane extracts of propolis-Syzygium aromaticum mixture, propolis-Papaver somniferum mixture, propolis-Foeniculum sp. mixture were used in the assays.Results: Ethanol extracts exhibited higher antibacterial activity compared to hexane extracts. While ethanol extracts inhibited bacterial growth ranges from 7±1.41 mm to 19.5±2.12 mm, hexane extracts showed inhibition zones ranges from 7±0.00 mm to 14±1.41 mm. The maximum and the minimum total phenolic contents were detected in propolis-S. aromaticum ethanol extracts as 389.81±0,001 μg GAE/mL and in propolis-Foeniculum sp. as 100.57±0.012 μg GAE/mL, respectively.Conclusion: Studied plant extracts with propolis might be an option to synthetic antioxidant and antibacterial compounds.

Chronic inhibition of angiotensin converting enzyme lowers blood pressure in spontaneously hypertensive rats by attenuation of sympathetic tone: The role of enhanced baroreflex sensitivity

Spontaneously hypertensive rats (SHR) are characterized by sympathetic hyperactivity and insufficient parasympathetic activity, and their high blood pressure (BP) can be lowered by long-term inhibition of the renin-angiotensin system. The aim of our study was to determine the influence of chronic inhibition of angiotensin converting enzyme (ACE) by captopril on cardiovascular regulation by the sympathetic and parasympathetic nervous system. Implanted radiotelemetric probes or arterial cannulas were used to measure mean arterial pressure (MAP), heart rate (HR), and arterial baroreflex in adult SHR and Wistar-Kyoto (WKY) rats under basal or stress conditions. MAP and the low-frequency component of systolic blood pressure variability (LF-SBPV, marker of sympathetic activity) were greater in SHR than in WKY rats. Under basal conditions chronic captopril treatment reduced both parameters more effectively in SHR, and the same was true during acute restraint stress. HR was similar in control rats of both strains, but WKY rats showed greater heart rate variability (HRV), indicating higher parasympathetic activity. Captopril administration increased HR in both strains, whereas HRV was decreased only in WKY. Chronic captopril treatment improved the impaired baroreflex-HR control in SHR by increasing the sensitivity but not the capacity of vagal arm of arterial baroreflex. Captopril treatment attenuated BP changes elicited by dimethylphenylpiperazinium (DMPP, agonist of nicotinic acetylcholine receptors), especially in SHR, indicating that sympathetic nerve transmission is facilitated by angiotensin II more in hypertensive than in normotensive animals. Thus, chronic ACE inhibition improves baroreflex sensitivity and lowers BP through both central and peripheral attenuation of sympathetic tone.

Diagnostic biomarkers for ST-segment elevation myocardial infarction using RNA methylation regulators

AimsAdditional evidence has indicated a correlation between N6-methyladenosine (m6A) RNA methylation and cardiovascular disease. Nevertheless, the alterations in RNA methylation modification and the expression of numerous genes remains unclear. This study aimed to identify the role of m6A in ST-segment elevation myocardial infarction (STEMI).MethodsTwo microarray datasets (GSE123342 and GSE59867) were downloaded from the GEO database. After merging the data and batch normalization, differentially expressed regulators were identified using the limma package. Subtyping consistency analysis was performed to group samples. The random forest algorithm and support vector machine were used to identify diagnostic biomarkers. Immune infiltration and inflammation levels among the subtypes were assessed using a single-sample gene set enrichment analysis.ResultsA total of 15 key differential m6A regulators (RBM15B, ELAVL1, ALKBH5, METTL16, ZC3H13, RBM15, YTHDC1, YTHDC2, YTHDF3, HNRNPC, FMR1, LRPPRC, HNRNPA2B1, RBMX, FTO) were identified using the random forest classifier and were found to be highly correlated by PPI analysis. Two distinct RNA modification patterns (cluster A and B) were validated based on the expression levels of the 15 key m6A regulators. GO and KEGG annotations showed that immunity and inflammation pathways were enriched. Immune infiltration analysis revealed that cluster 2 had higher immune activation than cluster 1. Further analysis showed that cluster 2 had a higher inflammation level, with IL-4 and IL-33 showing differential expression (p < 0.05).ConclusionA set of 15 m6A RNA methylation regulators could alter the STEMI microenvironment to improve risk stratification and clinical treatment.

Furfural Hydrogenation Over Reduced Pure (LaBO3) and Substituted (LaB0.5B'0.5O3) (B, B': Fe, Co, Ni) Perovskites

AbstractA series of pure and 50 % substituted Fe‐containing (LaFeO3, LaFe0.5Ni0.5O3 and LaFe0.5Co0.5O3) and Co/Ni‐containing (LaCoO3, LaNiO3, and LaCo0.5Ni0.5O3) perovskites were used as precursors to synthesize metallic reduced catalysts to be tested for the liquid hydrogenation of furfural. The catalytic reaction was carried out in a batch reactor at 200 °C and 3.0 MPa of H2 pressure. The calcined perovskites and reduced catalysts were characterized by X‐ray diffraction (XRD), N2 physisorption at 77 K, temperature programmed reduction (H2‐TPR), temperature programmed CO2 and NH3 desorption (CO2‐TPD and NH3‐TPD), Atomic Absorption Spectroscopy (AAS) and X‐ray photoelectron spectroscopy (XPS) techniques. The LaCo0.5Ni0.5O3 reduced catalyst display the highest activity in furfural conversion, which was attributed to a cooperative effect between highly dispersed nickel and cobalt metal nanoparticles after reduction process. The effect of the nature of B‐cation have a high impact on the products selectivity in the hydrogenation of furfural, suggesting that enriched‐Ni metal surface was selectivity to tetrahydrofurfuryl alcohol, meanwhile enriched‐Co metal surface was selective to furfuryl alcohol formation, which was also supported with adsorption mode of furfural over the active sites obtained by quantum calculation.