Weak Activity Research Articles

Hydroxylated SiO2-modified {0 0 1}-TiO2 nanosheets as a surface multifunctional photocatalyst for enhanced degradation of gaseous toluene

The relatively weak activity and serious deactivation of anatase TiO2 nanosheet catalysts with highly exposed {001} facets ({001}-TiO2) limits its wide application in photocatalytic degradation of gaseous pollutants. Herein, we propose a hybrid photocatalyst composed of {001}-TiO2 and SiO2 with numerous hydroxyl groups (denoted as {001}-TiO2/HO-SiO2). The catalyst showed excellent performance for gaseous toluene degradation under UV illumination, with 99.2 % removal efficiency and 204.7 μmol L−1 CO2 yield (about 85.9 % mineralization efficiency) within 120 min. It also demonstrated superior durability over five consecutive cycles of toluene photodegradation. The modification of HO–SiO2 on {001}-TiO2 facilitate the selective adsorption of toluene on the catalyst surface by H-bonding interaction, and make the major poisoning species, benzoic acid, easily desorb from the surface, reducing the catalyst inactivation. Most importantly, we found that the formed TiOSi bond promotes the separation of photogenerated electron–hole pairs, and provides abundant available electrons for the formation of reactive oxygen radicals and the left holes for the conversion of toluene to benzyl radicals or oxidation of H2O to hydroxyl radicals, which results in the improved activity. This study highlights the importance of the introduction of secondary components with special functions on TiO2, which is helpful for the design of photocatalysts with high performance and anti-deactivation ability for treatment of volatile organic compounds.

Revisiting the nature and pharmacodynamics of tacrolimus metabolites.

The toxicity of tacrolimus metabolites and their potential pharmacodynamic (PD) interactions with tacrolimus might respectively explain the surprising combination of higher toxicity and lower efficacy of tacrolimus despite normal blood concentrations, described in extensive metabolizers.To evaluate such interactions, we produced tacrolimus metabolites in vitro and characterized them by high resolution mass spectrometry (HRMS, for all) and nuclear magnetic resonance (NMR, for the most abundant, M-I). We quantified tacrolimus metabolites and checked their structure in patient whole blood and peripheral blood mononuclear cells (PBMC). We explored the interactions of M-I with tacrolimus in silico, in vitro and ex vivo.In vitro metabolization produced isoforms of tacrolimus and of its metabolites M-I and M-III, whose HRMS fragmentation suggested an open-ring structure. M-I and M-III open-ring isomers were also observed in patient blood. By contrast, NMR could not detect these open-ring forms. Transplant patients expressing CYP3A5 exhibited higher M-I/TAC ratios in blood and PBMC than non-expressers.Molecular Dynamics simulations showed that: all possible tacrolimus metabolites and isomers bind FKPB12; and the hypothetical open-ring structures induce looser binding between FKBP12 and calcineurins, leading to lower CN inhibition. In vitro, tacrolimus bound FKPB12 with more affinity than purified M-I, and the pool of tacrolimus metabolites and purified M-I had only weak inhibitory activity on IL2 secretion and not at all on NFAT nuclear translocation. M-I showed no competitive effect with tacrolimus on either test. Finally, M-I or the metabolite pool did not significantly interact with tacrolimus MLR suppression, thus eliminating a pharmacodynamic interaction.

Efficient Synthesis and Biological Evaluation of Some New Pyrazolo[1,5‐a]pyrimidine Derivatives as Antimicrobial Activity

AbstractA series of new pyrazolo[1,5‐a]pyrimidine 4–15 derivatives were synthesized starting from 3,5‐diaminopyrazole derivatives 3 a,b as precursor using a simple, efficient procedure, and screened for their in‐vitro antimicrobial activities. All the synthesized compounds were fully characterized by IR, 1HNMR, 13CNMR, MS spectral data, and elemental analysis. Among the investigated against the antimicrobial activity, compounds 4 b, 4 d, 4 e, 8 b, 9 and 12 showed the best activity. The remaining compounds were found to have weak activity against gram‐positive and gram‐negative.

Recent Advances in Electronic Structure Modifications of Layered Double Hydroxide (LDH) for the Water Splitting Application

AbstractElectrocatalytic water splitting is a feasible method for large‐scale hydrogen production. Recently, layered double hydroxides (LDH) have been identified as a possible candidate for accelerating the water splitting process. Nevertheless, certain structural alterations are necessary for immaculate LDH because of their weak electrocatalytic activity. These structural changes alter the local reaction environment by modulating the electronic structure of the metal center present in the LDH. This electronic structure tailoring is accomplished by a variety of processes, including heteroatom doping, single atom inclusion, cationic defect, oxygen vacancy creation, and heterostructure formation. Recently, there has been an uptick of advancement in this field, and it is necessary to summarize these developments. This review provides a concise summary of the current reports on the electronic structure manipulation of layered double hydroxide. The review begins by examining the local environmental changes of LDH resulting from the insertion of single atoms. Subsequently, we explore the charge transfer that occurs at the interface between LDH and other transition metal heterostructures. In addition, we explored the impact on the metal center near the vacancies on the basal plane of LDH. Finally, we presented a future perspective and guidance for advancing this field in electrocatalysis.

Characterization of Kunitz-Domain Anticoagulation Peptides Derived from Acinetobacter baumannii Exotoxin Protein F6W77.

Recent studies have revealed that the coagulation system plays a role in mammalian innate defense by entrapping bacteria in clots and generating antibacterial peptides. So, it is very important for the survival of bacteria to defend against the host coagulation system, which suggests that bacterial exotoxins might be a new source of anticoagulants. In this study, we analyzed the genomic sequences of Acinetobacter baumannii and a new bacterial exotoxin protein, F6W77, with five Kunitz-domains, KABP1-5, was identified. Each Kunitz-type domain features a classical six-cysteine framework reticulated by three conserved disulfide bridges, which was obviously similar to animal Kunitz-domain peptides but different from plant Kunitz-domain peptides. Anticoagulation function evaluation showed that towards the intrinsic coagulation pathway, KABP1 and KABP5 had apparently inhibitory activity, KABP4 had weak inhibitory activity, and KBAP2 and KABP3 had no effect even at a high concentration of 20 μg/mL. All five Kunitz-domain peptides, KABP1-5, had no inhibitory activity towards the extrinsic coagulation pathway. Enzyme-inhibitor experiments showed that the high-activity anticoagulant peptide KABP1 had apparently inhibitory activity towards two key coagulation factors, Xa and XIa, which was further confirmed by pull-down experiments that showed that KABP1 can bind to coagulation factors Xa and XIa directly. Structure-function relationship analyses of five Kunitz-type domain peptides showed that the arginine of the P1 site of three new bacterial anticoagulants, KABP1, KABP4 and KABP5, might be the key residue for their anticoagulation activity. In conclusion, with bioinformatics analyses, peptide recombination, and functional evaluation, we firstly found bacterial-exotoxin-derived Kunitz-type serine protease inhibitors with selectively inhibiting activity towards intrinsic coagulation pathways, and highlighted a new interaction between pathogenic bacteria and the human coagulation system.

Metabolite Profiles and Biological Activities of Different Phenotypes of Beech Mushrooms (Hypsizygus marmoreus).

Beech mushrooms (Hypsizygus marmoreus) are edible mushrooms commercially used in South Korea. They can be classified into white and brown according to their pigmentation. This study analyzed the metabolites and biological activities of these mushrooms. Specifically, 42 metabolites (37 volatiles, two phenolics, and three carbohydrates) were quantified in white beech mushrooms, and 47 (42 volatiles, two phenolics, and three carbohydrates) were detected in brown mushrooms. The major volatiles detected were hexanal, pentanal, 1-hexanol, and 1-pentanol. Brown mushrooms contained higher levels of hexanal (64%) than white mushrooms (35%), whereas white mushrooms had higher levels of pentanal (11%) and 1-pentanol (3%). Most volatiles were more abundant in white mushrooms than in brown mushrooms. Furthermore, brown beech mushrooms had a higher phenolic content than white mushrooms. Biological assays revealed that both types of mushroom demonstrated anti-microbial activities against bacterial and yeast pathogens and weak DPPH scavenging activity. The extracts from both mushrooms (50 μg/mL) also exhibited strong anti-inflammatory properties. Brown mushroom extracts showed higher antioxidant, anti-microbial, and anti-inflammatory properties than white mushroom extracts. This study reported that the differences in phenotype, taste, and odor were consistent with the metabolite differences between white and brown beech mushrooms, which have high nutritional and biofunctional values.

MBL-1/Muscleblind regulates neuronal differentiation and controls the splicing of a terminal selector in Caenorhabditis elegans.

The muscleblind family of mRNA splicing regulators is conserved across species and regulates the development of muscles and the nervous system. However, how Muscleblind proteins regulate neuronal fate specification and neurite morphogenesis at the single-neuron level is not well understood. In this study, we found that the C. elegans Muscleblind/MBL-1 promotes axonal growth in the touch receptor neurons (TRNs) by regulating microtubule stability and polarity. Transcriptomic analysis identified dozens of MBL-1-controlled splicing events in genes related to neuronal differentiation or microtubule functions. Among the MBL-1 targets, the LIM-domain transcription factor mec-3 is the terminal selector for the TRN fate and induces the expression of many TRN terminal differentiation genes. MBL-1 promotes the splicing of the mec-3 long isoform, which is essential for TRN fate specification, and inhibits the short isoforms that have much weaker activities in activating downstream genes. MBL-1 promotes mec-3 splicing through three "YGCU(U/G)Y" motifs located in or downstream of the included exon, which is similar to the mechanisms used by mammalian Muscleblind and suggests a deeply conserved context-dependency of the splicing regulation. Interestingly, the expression of mbl-1 in the TRNs is dependent on the mec-3 long isoform, indicating a positive feedback loop between the splicing regulator and the terminal selector. Finally, through a forward genetic screen, we found that MBL-1 promotes neurite growth partly by inhibiting the DLK-1/p38 MAPK pathway. In summary, our study provides mechanistic understanding of the role of Muscleblind in regulating cell fate specification and neuronal morphogenesis.

Ketamine and Major Ketamine Metabolites Function as Allosteric Modulators of Opioid Receptors.

Ketamine is a glutamate receptor antagonist that was developed over 50 years ago as an anesthetic agent. At subanesthetic doses, ketamine and some metabolites are analgesics and fast-acting antidepressants, presumably through targets other than glutamate receptors. We tested ketamine and its metabolites for activity as allosteric modulators of opioid receptors expressed as recombinant receptors in heterologous systems and with native receptors in rodent brain; signaling was examined by measuring GTP binding, β-arrestin recruitment, MAPK activation, and neurotransmitter release. Although micromolar concentrations of ketamine alone had weak agonist activity at μ opioid receptors, the combination of submicromolar concentrations of ketamine with endogenous opioid peptides produced robust synergistic responses with statistically significant increases in efficacies. All three opioid receptors (μ, δ, and κ) showed synergism with submicromolar concentrations of ketamine and either methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk), and/or dynorphin A17 (Dyn A17), albeit the extent of synergy was variable between receptors and peptides. S-ketamine exhibited higher modulatory effects compared with R-ketamine or racemic ketamine, with ∼100% increase in efficacy. Importantly, the ketamine metabolite 6-hydroxynorketamine showed robust allosteric modulatory activity at μ opioid receptors; this metabolite is known to have analgesic and antidepressant activity but does not bind to glutamate receptors. Ketamine enhanced potency and efficacy of Met-enkephalin signaling both in mouse midbrain membranes and in rat ventral tegmental area neurons as determined by electrophysiology recordings in brain slices. Taken together, these findings support the hypothesis that some of the therapeutic effects of ketamine and its metabolites are mediated by directly engaging the endogenous opioid system. SIGNIFICANCE STATEMENT: This study found that ketamine and its major biologically active metabolites function as potent allosteric modulators of μ, δ, and κ opioid receptors, with submicromolar concentrations of these compounds synergizing with endogenous opioid peptides, such as enkephalin and dynorphin. This allosteric activity may contribute to ketamine's therapeutic effectiveness for treating acute and chronic pain and as a fast-acting antidepressant drug.

COMPLEXATION OF THE CURCUMIN BY THE CAFEIN IN ETHANOL BY MEANS OF UV – VIS SPETROPHOTOMETER

Why this miraculous and amphiphilic compound, curcumin, which has a very extraordinary therapeutic potential (because can react with many targets in the organism), has a weak bioavailability in the organism and is metabolized in compoumds having very weak activity or inactive compounds? How to improve substantially its bioavailability and therefore its absorption in the organism in order to allow its incorporation in making of pharmaceuticals regardless of its nanoparticles of which the obtention is furthermore hardworking? It seems indicated to search the response in the kinetic and thermodynamic behavior of this compound or in its co – administration with the other compounds (more soluble in water) in vitro in order to understand how to increase its absorption in vivo. So our objective is to make better our understanding of the absorption of natural curcuminoids in the organism without resorting to their chemical transformation in nanoparticles that is additionally hardworking. In this paper, curcumin was examined in the presence of cafein in ethanol with the aim to deepen the knowledge of the interaction between them. The study has revealed the presence of two complexes A6B4 and AB9 (A = curcumin, B = cafein), evidenced by the Job’s method (continuous variations method) whose complexation constants have been calculated and the value of K_(A_6 B_4 ) (1.12 1032) is higher than the value of K_(〖AB〗_9 ) (2.7 10-10) suggesting the great stability of A_6 B_4 .

New Esters of Ferrediol and Sideritriol in Sideritis clandestina subsp. peloponnesiaca: Characterization and Antiproliferative Activity.

17-Isovalerate esters of ferrediol and sideritriol (compounds 1 and 5) and 17-(2-methylbutyrate) ferrediol (compound 2), which have not been earlier described, were isolated along with five known ent-15-kaurene diterpenes (siderol, sideridiol, sideroxol, eubotriol, and epi-candicandiol), one ent-beyerene (flavovirol), and one phytosterol (β-sitosterol) from the aerial parts of Sideritis clandestina subsp. peloponnesiaca (Boiss. & Heldr.) Baden that is a mountain tea species endemic to Northern Peloponnese in Greece. Compounds 1-5 exhibited weak antiproliferative activity against triple-negative MDA-MB-231 and Hs578T breast cancer cells. In MCF-7 breast cancer cells, compounds 1, 2, siderol, and sideridiol were equipotent to 5-fluorouracil (moderate antiproliferative activity).

Waxy- or Putty-Like Materials as a Novel Drug Preparation for Synthetic Cannabinoid Receptor Agonists: Detection in Prisons and InVitro Cannabinoid Receptor Activity.

After the Scottish Prison Service (SPS) introduced mail photocopying procedures in December 2021, a shift in smuggling methods was observed for synthetic cannabinoid receptor agonists (SCRAs) and other new psychoactive substances (NPS) from drug-infused papers back to traditional sample matrices (e.g., tablets and powders), although new matrices also emerged. This study reports on waxy- or putty-like materials as a novel drug preparation for SCRAs and other drugs seized from UK prisons. In 2023, 22 of these new preparations were seized from Scottish prisons, with eight found in sealed vape pods. The materials were positive for SCRAs, phytocannabinoids, novel benzodiazepines, and/or gabapentinoids. Additionally, 11 preparations were seized from an English prison, all containing the SCRAs MDMB-4en-PINACA and MDMB-INACA. MDMB-INACA was pharmacologically characterized using invitro CB1 and CB2 bioassays, revealing moderate efficacy but low potency at CB1. Furthermore, the invitro CB1 bioassay was also used to evaluate the CB1 activating potential of extracts from eight seized samples. Six of these showed high CB1 activity, whereas the samples lacking SCRAs or containing only MDMB-INACA showed no or only weak CB1 activity, respectively. Lastly, applying the bioassay as an activity-based "untargeted" screening method effectively identified the presence of SCRAs in one waxy preparation, which was initially not detected by gas chromatography-mass spectrometry (GC-MS). This underscores the effectiveness of the bioassay for evaluating these new waxy- or putty-like materials for the presence of SCRAs.

Identification of Novel PPARγ Partial Agonists Based on Virtual Screening Strategy: In Silico and In Vitro Experimental Validation.

Thiazolidinediones (TZDs) including rosiglitazone and pioglitazone function as peroxisome proliferator-activated receptor gamma (PPARγ) full agonists, which have been known as a class to be among the most effective drugs for the treatment of type 2 diabetes mellitus (T2DM). However, side effects of TZDs such as fluid retention and weight gain are associated with their full agonistic activities toward PPARγ induced by the AF-2 helix-involved "locked" mechanism. Thereby, this study aimed to obtain novel PPARγ partial agonists without direct interaction with the AF-2 helix. Through performing virtual screening of the Targetmol L6000 Natural Product Library and utilizing molecular dynamics (MD) simulation, as well as molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis, four compounds including tubuloside b, podophyllotoxone, endomorphin 1 and paliperidone were identified as potential PPARγ partial agonists. An in vitro TR-FRET competitive binding assay showed podophyllotoxone displayed the optimal binding affinity toward PPARγ among the screened compounds, exhibiting IC50 and ki values of 27.43 µM and 9.86 µM, respectively. Further cell-based transcription assays were conducted and demonstrated podophyllotoxone's weak agonistic activity against PPARγ compared to that of the PPARγ full agonist rosiglitazone. These results collectively demonstrated that podophyllotoxone could serve as a PPARγ partial agonist and might provide a novel candidate for the treatment of various diseases such as T2DM.

Regional Mean Sea Level Variability Due to Tropical Cyclones: Insights from August Typhoons

This study investigates the interannual variations in regional mean sea levels (MSLs) of the northeast Asian marginal seas (NEAMS) during August, focusing on the role of typhoon activity from 1993 to 2019. The NEAMS are connected to the Pacific through the East China Sea (ECS) and narrow, shallow straits in the east, where inflow from the southern boundary (ECS), unless balanced by eastern outflow, leads to significant convergence or divergence, as well as subsequent changes in regional MSLs. Satellite altimetry and tide-gauge data reveal that typhoon-induced Ekman transport plays a key role in MSL variability, with increased inflow raising MSLs during active typhoon seasons. In contrast, weak typhoon activity reduces inflow, resulting in lower MSLs. This study’s findings have significant implications for coastal management, as the projected changes in tropical cyclone frequency and intensity due to climate change could exacerbate sea level rise and flooding risks. Coastal communities in the NEAMS region will need to prioritize enhanced flood defenses, early warning systems, and adaptive land use strategies to mitigate these risks. This is the first study to link typhoon frequency directly to NEAMS MSL variability, highlighting the critical role of wind-driven processes in regional sea level changes.

Phenolic content, antioxidant activity, and tyrosinase inhibitor potential for both skin and physical health: test of extract, skin content and content of Garcinia Cowa fruit

Skin aging leads to reduced structural integrity and reduced skin function. Medicinal plant extracts that have antioxidant properties and are able to inhibit tyrosinase have become a trend in various uses for anti-aging. One of the commonly used plants in traditional medicine that grows in many Asian countries is garcinia cowa. Currently, no one has studied the fruit from two different aspects, namely for the skin and to help in physical improvement. The purpose of this study is to test the phenolic content, antioxidants, and tyrosinase inhibition activity of the extract from the skin and pulp of garcinia cowa as well as its effectiveness on the physical ability and function of the skin. The stages carried out start from the collection of garcina cowa fruits, the determination of total phenolic levels, the determination of antioxidant activity, and the determination of tyrosinase inhibition activity. The total phenolic content was determined by the folin-ciocalteu method. The phenolic content of garcinia cowa fruit peel extract is 17.789 mg of gallic acid equivalent extract (GAE)/g, while the meat extract is 12.078 mg GAE/g extract. Furthermore, the flesh of garcinia cowa showed weak antioxidant activity with an IC50 value of 490.2 μg/mL, but the fruit peel extract showed moderate antioxidant activity at 243.3 μg/mL. The skin of garcinia cowa fruit shows tyrosinase inhibition activity in vitro, which is more significant than the pulp. Garcinia cowa peel and pulp extracts both contain phenolic compounds and show the antioxidant activity, but it was found that the fruit peel extract has a higher content. This means that with its antioxidant content, it can ward off free radicals, prevent cell damage, and reduce the risk of chronic diseases. The combination of phenolic content, antioxidant activity, and tyrosinase inhibitor potential provides significant benefits for skin health and overall physical health.

Sedimentary Environment of the Permian Marine Shale in the Kaijiang‐Liangping Trough, Sichuan Basin, China: Implications for Organic Matter (OM) Accumulation

ABSTRACTThe Permian shales in the Kaijiang‐Liangping Trough within the Sichuan Basin represent a promising frontier for marine shale gas exploration, whereas there has been limited systematic research on their sedimentary environment and organic matter (OM) enrichment mechanisms. Therefore, we present total organic carbon (TOC) analysis, major/trace element analyses and scanning electron microscope experiments for the Permian marine shales from the trough to determine their paleoenvironmental conditions and influencing factors of OM enrichment. The results show that the paleoclimate changed from dry climate to humid and warm climate (P3w1 [the first member of the Wujiaping Formation]) and semi‐humid to semi‐arid climate (P3w2 [the second member of the Wujiaping Formation]) and P3d‐I (Dalong Formation‐I) and then to arid climate again during the shale deposition period from the P2g (Gufeng Formation) to the P3d‐II. The shales with the highest TOC contents (TOC > 3%, P3d‐I and P2g), lower TOC contents (TOC < 1%, P3w1 and P3w2) and higher TOC contents (1% < TOC < 2%, P3d‐II) were formed under the control of anoxic environment and high paleoproductivity, oxic‐suboxic environment and high paleoproductivity, anoxic‐euxinic environment and lower productivity, respectively. Only appropriate sedimentation rates promote OM enrichment. Terrestrial input, paleoclimate, volcanic activity and hydrothermal upwelling mainly indirectly affect OM accumulation by influencing paleoproductivity. The degree of redox conditions is the primary factor affecting OM enrichment, followed by paleoproductivity. Nonetheless, anoxic to euxinic environments are most appropriate for OM preservation. Weak volcanic activity can boost paleoproductivity, but severe volcanic activity might introduce excessive harmful compounds that limit organism survival, resulting in a fall in paleoproductivity. Additionally, element P brought by volcanic ashes doesn't contribute to OM accumulation.

Artemisia afra and COVID-19, the Media Storm Versus the Current State-of-the-Art

AbstractDuring the COVID-19 pandemic, the traditional herbal medicine Artemisia afra Jacq. ex Willd., Asteraceae, was widely used as a remedy, and a true media storm erupted in (South) Africa regarding this matter. Throughout the pandemic, A. afra was not only extensively used, but the herb was also exceedingly difficult to find, which is reminiscent of its historical popularity during the influenza pandemic of 1918. This popularity was further fueled by the launch of Covid-Organics in Madagascar, containing Artemisia annua L., which led to international media attention regarding Artemisia as a treatment for COVID-19. In 2020, millions in research funding were made available in South Africa to study promising traditional medicines, including A. afra, and for the development of an effective remedy which was lacking at the time. Due to its popularity and widespread use, this updated overview of A. afra aimed to collate all scientific data on its chemistry, general in vitro and in vivo biological bioactivity, and its antiviral and Sars-Cov-2 activity reported since 2019. Several studies reported good in vitro antiparasitic activity and in vivo antispasmodic activity. However, many studies reported on biological activities that were many orders of magnitude less active than their positive controls. Surprisingly, not a single in vivo study, patent, or (registered) clinical trial could be found regarding A. afra and COVID-19. Only one study, conducted by a German-Danish research group, reported on the in vitro activity of A. afra extracts against Sars-Cov-2. The results indicated that there was relatively weak activity of 0.09 mg/ml ± 0.03 (selectivity index of 26.22), but the context cannot be established due to the absence of a positive control, which did not exist at the time. Artemisia afra is still widely used as a general antiviral remedy, and in-depth research in this field must be conducted. Several promising results regarding antispasmodic and antischistosomal activity should also be further explored. Graphical Abstract

Structural analysis of the CJ0600 protein from Campylobacter jejuni

The Campylobacter jejuni bacterium, which causes foodborne enteritis in humans, expresses the uncharacterized protein CJ0600. Based on sequence analysis, CJ0600 has been proposed to function as a 1-aminocyclopropane-1-carboxylate (ACC) deaminase (AccDA) or cysteine desulfhydrase (CysDS). However, it has never been investigated whether CJ0600 exerts AccDA or CysDS activity or how CJ0600 mediates its enzymatic activity. To reveal the structural features necessary for the function of CJ0600, we determined the crystal structure of CJ0600 and characterized its enzymatic activity. CJ0600 contains two domains and features an interdomain pocket, which accommodates a pyridoxal 5′-phosphate (PLP) molecule as a Schiff base with its lysine residue (K35), as observed in its structural homologs, including AccDA, CysDS, and serine deaminase (SerDA). However, unlike its structural homologs, CJ0600 exists as a monomer and exhibits unique structural features throughout its structure. Moreover, CJ0600 contains unique active site residues that are not observed in AccDA, CysDS, or SerDA. Consistently, phylogenetic analysis indicates that CJ0600 and its orthologs are evolutionarily distinct from AccDA, CysDS, and SerDA. Indeed, CJ0600 showed no CysDS or SerDA activity and extremely weak AccDA activity. These observations suggest that CJ0600 functions as a unique PLP-dependent enzyme that has not been reported.

Inhibition of Citronella Essential Oil (Cymbopogon Nardus) Bengkulu on Bacterial Growth after Endodontic Treatment

Background: Root canal treatment aims to address pulpal infection and prevent reinfection, which is often caused by bacteria such as Enterococcus faecalis and Staphylococcus aureus. Citronella essential oil (Cymbopogon nardus) from Bengkulu, containing antibacterial compounds, has potential to inhibit the growth of these bacteria. Objective: This study evaluated the effectiveness of citronella essential oil against E. faecalis and S. aureus. Materials and Methods: The method used was the disc diffusion technique with 20 samples each of E. faecalis and S. aureus in BHI media. Citronella essential oil was tested at concentrations of 50%, 75%, and 100%, with 2% CHX as the positive control. The inhibition zones were measured after 24 hours. Results: The highest inhibition for E. faecalis was found at 100% concentration (2.56 mm), while for S. aureus, it was at 50% concentration (1.67 mm). Significant differences (p<0.05) were observed at all concentrations of citronella essential oil for both bacteria. Conclusion: Citronella essential oil from Bengkulu exhibited weak antibacterial activity against E. faecalis and S. aureus. Its potential as an alternative for root canal treatment requires further development.

Pregnancy-related hormonal changes and thyroid growth: do they have an impact on the higher incidence of differentiated thyroid cancer in women?

To analyze whether pregnancy could play a role in the higher prevalence of differentiated thyroid carcinoma (DTC) in women. Estrogens strongly modify thyroid economy by increasing iodine clearance, thyroid hormone requirement and production. Human chorionic gonadotropin (hCG) contributes to the increased thyroid hormone synthesis. Both estrogens and hCG can interfere with the regulation of thyroid volume and with thyroid nodule development and progression. The potential effect of hCG is exclusively related to its weak agonistic activity on TSH receptor. Estrogen implication on normal and nodule-derived thyrocyte growth has been demonstrated in vitro and in animal models. Furthermore, there is solid clinical evidence showing a promoting effect of pregnancy on thyroid volume and nodule development. Two metanalysis, one including retrospective and another prospective observational studies, failed to show an association between pregnancy and DTC. A large pooled prospective analysis using multivariable-adjusted Cox proportional hazard models did not demonstrate an association between DTC and parity. Similarly, no association between PTC occurrence and parity was observed in a prospective cohort analysis by linkage to the statewide Surveillance, Epidemiology, and End Results (SEER). The presently available evidence does not support an involvement of pregnancy in DTC etiology.

Biosynthesis of Iron Oxide Nanoparticles by Marine Streptomyces sp. SMGL39 with Antibiofilm Activity: In Vitro and In Silico Study

One of the major global health threats in the present era is antibiotic resistance. Biosynthesized iron oxide nanoparticles (FeNPs) can combat microbial infections and can be synthesized without harmful chemicals. In the present investigation, 16S rRNA gene sequencing was used to discover Streptomyces sp. SMGL39, an actinomycete isolate utilized to reduce ferrous sulfate heptahydrate (FeSO4.7H2O) to biosynthesize FeNPs, which were then characterized using UV–Vis, XRD, FTIR, and TEM analyses. Furthermore, in our current study, the biosynthesized FeNPs were tested for antimicrobial and antibiofilm characteristics against different Gram-negative, Gram-positive, and fungal strains. Additionally, our work examines the biosynthesized FeNPs’ molecular docking and binding affinity to key enzymes, which contributed to bacterial infection cooperation via quorum sensing (QS) processes. A bright yellow to dark brown color shift indicated the production of FeNPs, which have polydispersed forms with particle sizes ranging from 80 to 180 nm and UV absorbance ranging from 220 to 280 nm. Biosynthesized FeNPs from actinobacteria significantly reduced the microbial growth of Fusarium oxysporum and L. monocytogenes, while they showed weak antimicrobial activity against P. aeruginosa and no activity against E. coli, MRSA, or Aspergillus niger. On the other hand, biosynthesized FeNPs showed strong antibiofilm activity against P. aeruginosa while showing mild and weak activity against B. subtilis and E. coli, respectively. The collaboration of biosynthesized FeNPs and key enzymes for bacterial infection exhibits hydrophobic and/or hydrogen bonding, according to this research. These results show that actinobacteria-biosynthesized FeNPs prevent biofilm development in bacteria.