Low Inhibition Research Articles

Structural effects, corrosion inhibition mechanisms and timeliness of three tetrazole derivatives on copper in a 3.5wt.% NaCl solution

The structural effects, corrosion inhibition mechanisms and timeliness of 5-methyltetrazole (MT), 5-aminotetrazole (AT) and 5-mercapto-1-methyltetrazole (MMT) on copper in a 3.5 wt.% NaCl solution were studied by electrochemical experiments, surface characterizations and theoretical calculations. At the initial soaking stage, MT exhibited higher corrosion inhibition efficiency (99.65 %), which might stem from the electron donating effect and hydrophobic interaction of -CH3. While MMT exhibited lower corrosion inhibition efficiency (92.64 %), which might stem from the electron withdrawing effect and hydrophilicity of -SH. As the soaking time prolonged, the corrosion inhibition efficiencies of AT and MMT increased (99.49 % and 99.51 %). This might be because the N and S atoms of -NH2 and -SH could also provide lone pair electrons to coordinate with copper, especially S atom. As the soaking time was further prolonged, the formation of corrosion products weakened the interaction between N and S with copper, reducing the corrosion inhibition performance of AT and MMT. MT, AT and MMT molecules on Cu (111) surface can mainly undergo perpendicular adsorption, simultaneously accompanied by parallel adsorption.

Anti-SARS-CoV-2 total immunoglobulin and neutralising antibody responses in healthy blood donors throughout the COVID-19 pandemic: a longitudinal observational study.

Quantifying antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and neutralising antibodies may help to understand protection at the individual and population levels. Determination of neutralising antibodies using classical virus neutralisation tests (VNT) is considered the gold standard, but they are costly and time-intensive. Enzyme-linked immunosorbent assay (ELISA)-based surrogate VNTs (sVNT) or anti-SARS-CoV-2 spike protein receptor binding domain immunoglobulins (anti-S-RBD Ig) may be suitable alternatives to VNTs. We aimed to (a) explore the correlations between anti-S-RBD Ig, VNT, and sVNT measurements and (b) describe humoral immunity against SARS-CoV-2 after vaccination, natural infection, and vaccine breakthrough infection in healthy blood donors. We measured total anti-SARS-CoV-2 Ig in 5714 serum samples from 2748 healthy individuals visiting the Swiss Red Cross Blood Donation Centre in Basel from 03/2020 to 04/2022. We used the Elecsys®Anti-SARS-CoV-2 immunoassay (Roche) against the N- and S-receptor binding domain (RBD) proteins. In a subset of 548 samples from 123 donors, we conducted sVNTs against the Wuhan wild-type SARS-CoV-2 (SARS-CoV-2 Neutralizing Antibodies Detection Kit; Adipogen™). In 100 samples from 40 donors, we correlated sVNT and VNTs against the wild-type (D614G WU1) virus. Surveys were sent to the blood donors to collect data on their SARS-CoV-2 infection and vaccination status. Using this data, donors were categorised as "vaccination only", "infection before vaccination", "post-vaccine breakthrough infection", and "natural infection only". Our longitudinal observation study cohort consisted of 50.7% males with a median age of 31 years (range 18-75 y). Anti-SARS-CoV-2 N protein positivity rates per month indicate 57.1% (88/154) of the cohort was infected up to 04/2022. No differences in seropositivity were found between sexes, age groups, blood types (AB0 or RhD), and cytomegalovirus serostatus. We observed a high correlation between anti-S-RBD Ig and inhibition percentage (Spearman'sρ= 0.92, Kendall'sτ= 0.77, p <0.0001). We determined the sensitivity and specificity for the manufacturers' thresholds for detecting virus-neutralising effects and computed the "best" cut-off based on our real-world data. We categorised 722/1138 (63.5%) donors as vaccination only (82.3%), post-vaccine breakthrough infection (7.8%), infection before vaccination (5.8%), and natural infection only (4.2%). We observed a lower inhibition percentage in the natural infection-only group than in all other vaccinated groups. The infection before vaccination group had higher anti-S-RBD Ig titres after the first vaccine dose than the other vaccinated groups. In total, 57.1% of healthy blood donors were infected with SARS-CoV-2, but natural infection without evidence of vaccination seems to result in substantially lower neutralising antibody levels. An estimate of antibody neutralisation may be helpful to assess reinfection risk. Total anti-S-RBD Ig correlates with surrogate virus neutralisation test results, a surrogate for neutralisation; therefore, we suggest that total anti-S-RBD Ig may estimate the level of neutralising antibodies. The threshold for protection from an unfavourable clinical outcome must be evaluated in prospective clinical cohorts.

Synthesis, molecular structure, Hirshfeld surface analysis, NCI-RDG, spectral characterization analysis, nonlinear optical properties, and in silico molecular docking of (E)-3-(3-(2-methoxyphenyl)-4-methylthiazol-2(3H)-ylidene) benzo[4,5] imidazo [1,2-c] thiazole-1(3H)-thione

(E)-3-(3-(2-methoxyphenyl)-4-methylthiazol-2(3H)-ylidene) benzo[4,5] imidazo [1,2-c] thiazole-1(3H)-thione (EMBIT) was synthesized and studied thoroughly by means of X-ray diffraction and molecular modeling. In this study, geometrical analysis together with FT-IR, NMR, and UV-Vis characterizations were performed. Using density functional theory and the B3LYP/6–311G++(d,p) set, geometric parameters accurately represent the structure, showing agreement between experimental and theoretical results. Various solvents were included in the calculations of the UV–Vis spectra, frontier molecular orbitals (FMOs), and global chemical reactivity descriptors (GCRD) calculations, revealing their potential for better prediction of energy gap values. The energy gap and some chemical descriptors analysis of the title compound indicated that it would be suitable for nonlinear optical properties and biological activity. Non-covalent bond interaction studies were conducted on EMBIT to investigate the intermolecular interactions. A deeper understanding of the electronic structure and chemical bonding patterns of the structure was gained by LOL and ELF studies.The computed polarizabilities and hyperpolarizabilities indicated that the molecule has non-linear optical properties and assessed the influence of the energetic gap values and electron delocalization character on enhancing NLO proprieties. The predictions of EMBIT's biological activity suggested potential as a cure for glaucoma, and molecular docking revealed the various bonds involved against two potential critical glaucoma factors Rock1 and Rock2. Rock2 is found to have a superior binding affinity, as evidenced by its highest binding energy of -8.7 kcal/mol and a lower Ki inhibition constant of 0.97. The EMBIT ligand's effectiveness in inhibiting the Rock2 protein is highly likely, as suggested by this.

Novel Biological-Based Strategy for Synthesis of Green Nanochitosan and Copper-Chitosan Nanocomposites: Promising Antibacterial and Hematological Agents.

Two novel samples of nanoparticles based on chitosan were greenly synthesized using pomegranate peel extract. The extract served as a nanoparticle precursor, facilitating the precipitation of nanosized chitosan through the ionic gelation method. Additionally, by mixing the green chitosan nanoparticles with copper ions, a nanoscale composite of chitosan and copper oxide was also produced. Structural and morphological investigations (FTIR, XRD, SEM, EDX, and TGA analyses) were performed for greenly synthesized chitosan nanoparticles and their copper oxide composite to determine all the significant characteristics of those nanoparticles. In addition, both samples were tested using some biological investigations, such as antimicrobial activity and hematological effects. The antimicrobial tests yielded promising results for both the green chitosan nanoparticles and the CuO composite when tested using two bacterial strains and two fungal strains. Moreover, the results showed that using a similar concentration of both green-based chitosan samples resulted in a slightly larger inhibition zone and a lower minimum inhibition concentration (MIC) for the copper oxide chitosan composite compared to the chitosan nanoparticles for all microorganisms included in the test. The mean count of blood components (RBCs and platelets), clotting time, and cholesterol levels in three different blood samples were used to indicate the hematological activity of both greenly synthesized nanoparticles. The results verified a slight reduction in blood component count after the addition of green chitosan nanoparticles, but the chitosan copper oxide composite did not have a noticeable effect on the three blood samples. The chitosan nanoparticles were able to cause a considerable reduction in clotting time and cholesterol levels for all blood samples, thus acting as procoagulants. However, the mixing of CuO with chitosan nanoparticles prolonged the rate of clotting in blood samples from hypercholesteremic individuals, and thus, the mixture acted as an anticoagulant agent.

Functional characterization of a cystatin A from the bat Myotis davidii

Myotis davidii cystatin A (MdCSTA), a stefin A-like from the Chinese native bat species M. davidii, was expressed as a recombinant protein and functionally characterized as a strong inhibitor of the cysteine proteases papain, human cathepsins L and B and the tick cathepsin L-like BmCL1. Despite the highly conserved amino acid sequences among stefins A from different vertebrates, MdCSTA presents a Methionine-2 residue at the N-terminal region and the second binding loop (pos 73–79) that differs from human stefin A (HsCSTA) and might be related to the lower inhibition constant (Ki) value presented by this inhibitor in comparison to human stefin A inhibition to cathepsin B. Therefore, to investigate the importance of these variable regions in cathepsin B inhibition, recombinant stefins A MdCSTA and HsCSTA containing mutations at the second amino acid residue and second binding loop were expressed and evaluated in kinetic assays. Enzymatic inhibition assays with cathepsin B revealed that switching the amino acid residues at position 2 and second binding loop region between bat and human CSTAs improved the HsCSTA's and reduced MdCSTA's inhibitory activity. Additionally, molecular docking analysis estimated lower energy values for the complex between MdCSTA-cathepsin B, in comparison to human CSTA-cathepsin B, while the mutants presented intermediate values, suggesting that other regions might contribute to the higher inhibitory activity against cathepsin B by MdCSTA. In conclusion, MdCSTA, the first bat's stefin A-like inhibitor to be functionally characterized, presented a higher inhibitory activity against cathepsin B in comparison to the human inhibitor, which is partially related to the glutamine-rich second binding loop and Met-2. Further structural analysis should be performed to elucidate potential inhibitor effects on cysteine proteinases.

Pharmacophore Modeling and Binding Affinity of Secondary Metabolites from Angelica keiskei to HMG Co-A Reductase.

Statins are cholesterol-lowering drugs with a mechanism of inhibiting 3-hydroxy-3-methylglutaryl-CoA reductase, but long-term use can cause side effects. An example of a plant capable of reducing cholesterol levels is Angelica keiskei (ashitaba). Therefore, this study aimed to obtain suitable compounds with inhibitory activity against the HMG-CoA reductase enzyme from ashitaba through in silico tests. The experiment began with screening and pharmacophore modeling, followed by molecular docking on ashitaba's compounds, statins groups, and the native ligand was (3R,5R)-7-[4-(benzyl carbamoyl)-2-(4-fluorophenyl)-5-(1-methylethyl)-1H-imidazole-1-yl]-3,5-dihydroxyheptanoic acid (4HI). Based on the results of the molecular docking simulations, 15 hit compounds had a small binding energy (ΔG). Pitavastatin, as the comparator drug (ΔG = -8.24 kcal/mol; Ki = 2.11 µM), had a lower ΔG and inhibition constant (Ki) than the native ligand 4HI (ΔG = -7.84 kcal/mol; Ki = 7.96µM). From ashitaba's compounds, it was found that 4'-O-geranylnaringenin, luteolin, isobavachalcone, dorsmannin A, and 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxychalcone have low ΔG of below -6 kcal/mol. The lowest ΔG value was found in 3'-carboxymethyl-4,2'-dihydroxy-4'-methoxy chalcone with a ΔG of -6.67 kcal/mol and Ki value of 16.66 µM, which was lower than the ΔG value of the other comparator drugs, atorvastatin (ΔG = -5.49 kcal/mol; Ki = 1148.17 µM) and simvastatin (ΔG = -6.50 kcal/mol; Ki = 22.34 µM). This compound also binds to the important amino acid residues, including ASN755D, ASP690C, GLU559D, LYS735D, LYS691C, and SER684C, through hydrogen bonds. Based on the results, the compound effectively binds to six important amino acids with good binding affinity and only requires a small concentration to reduce half of the enzyme activity.

Zinc oxide and copper oxide nanoparticles as a potential solution for controlling Phytophthora infestans, the late blight disease of potatoes

Late blight, caused by Phytophthora infestans, is a major potato disease globally, leading to significant economic losses of $6.7 billion. To address this issue, we evaluated the antifungal activity of ZnO and CuO nanoparticles (NPs) against P. infestans for the first time in laboratory and greenhouse conditions. Nanoparticles were synthesized via a chemical precipitation method and characterized using various techniques. The XRD results revealed that the synthesized ZnO nanoparticles had a pure hexagonal wurtzite crystalline structure, whereas the CuO NPs had a monoclinic crystalline structure. TEM images confirmed the synthesis of quasi-spherical nanoparticles with an average size of 11.5 nm for ZnO NPs and 24.5 nm for CuO NPs. The UV–Vis Spectral Report showed peaks corresponding to ZnO NPs at 364 nm and 252 nm for CuO NPs.In an in vitro study, both ZnO and CuO NPs significantly (p < 0.05) inhibited the radial growth of P. infestans at all tested concentrations compared to the untreated control. The highest inhibitory effect of 100% was observed with ZnO and CuO NPs at 30 mg/L. A lower inhibition of 60.4% was observed with 10 mg/L CuO NPs. Under greenhouse conditions, 100 mg/L ZnO NPs was the most effective treatment for controlling potato late blight, with an efficacy of 71%. CuO NPs at 100 mg/L followed closely, with an efficacy of 69%. Based on these results, ZnO and CuO NPs are recommended as promising eco-friendly fungicides for the management and control of potato late blight after further research.Graphical abstract

The Impact of Sex on Antiplatelet and Anticoagulant Thromboprophylaxis in Patients With Peripheral Artery Disease Post-revascularization.

The aim of this prospective study was to (1) objectively quantify the impact of sex on platelet function in patients with peripheral artery disease (PAD) taking antiplatelet and anticoagulant medications and (2) to develop and test a personalized, iterative algorithm that personalizes thromboprophylaxis that incorporates platelet function testing. Women with PAD have worse outcomes as compared with their male counterparts despite having lower risk factors. This health disparity may be mitigated by personalizing thromboprophylaxis regimens. Patients undergoing revascularization were enrolled. Serial thromboelastography (TEG) and TEG with platelet mapping (TEG-PM) were performed up to 6 months postoperatively to determine objective coagulation profiles. In a subset of patients, the Antiplatelet Coagulation Exactness (ACE) algorithm was implemented, where patients were iteratively evaluated with TEG and given antiplatelet medications to maintain platelet inhibition at >29%. Statistical analysis was performed using unpaired t test, analysis of variance, and Fisher exact test. One hundred eighty-one patients met the study criteria. Fifty-eight (32%) patients were females and 123 (68%) were males. In the Aspirin cohort, females showed significantly greater clot strength as maximum amplitude - arachidonic acid (MA AA ) and significantly lower platelet inhibition than males: (37.26 vs 32.38, P <0.01) and (52.95% vs 61.65%, P <0.05), respectively. In the Clopidogrel cohort, females showed higher Maximum Amplitude - Adenosine Diphosphate (MA ADP ) (42.58 vs 40.35, P = not significant [NS]) compared with males. Females on dual antiplatelet therapy had higher MA ADP (39.74 vs 35.07, P =NS) and lower platelet inhibition (45.25% vs 54.99%, P= NS) than males. The incidence of thrombosis of the revascularized segment, defined as thrombotic event, was objectively identified on an arterial duplex. Women showed significantly higher thrombotic events than men (22.95% vs 10.57%, P< 0.05) on the same medication. In our pilot study, implementation of the ACE algorithm led to a significant decrease in the thrombosis rate (3%), including nonthrombotic events for females, versus the historic thrombotic rate (22%) from our institution. Women with PAD exhibited higher platelet reactivity, clot strength, and reduced platelet inhibition in response to antiplatelet therapy. The use of the ACE algorithm to tailor antiplatelet medication in patients with PAD post-revascularization, resulted in a significant decrease in thrombotic event rates. This may serve as an opportune way to mitigate outcome sex-specific disparities caused by inadequate thromboprophylaxis in women.

Comparative assessment of microplastics and microalgae as vectors of mercury and chlorpyrifos in the copepod Acartia tonsa

Microplastics (MPs) raise concerns not only as pollutants themselves, but also due to their ability to act as vectors of pollutants adsorbed from seawater, transferring them to marine organisms. However, the relevance of MPs as carriers of pollutants compared to microalgae needs further exploration. This study compared the role of MPs (2–10 μm non-oxidized and 10–15 μm oxidized high-density polyethylene) and natural organic particles (Rhodomonas lens microalgae, MA) as carriers of mercury (Hg, 2.3 μg Hg/L) and chlorpyrifos (CPF, 1.0 μg CPF/L) to adult Acartia tonsa copepods, after 24–48 h exposure. Dose-response experiments were first performed with adult female copepods exposed to oxidized MPs (0.25–4.0 mg/L), waterborne Hg (0.01–10.0 μg/L) and Ox MPs + Hg (0.25–4.0 mg oxidized MPs/L + 0.50–8.0 μg Hg/L) for 48 h, to complement previous studies that focused on the pesticide CPF. Effects were evaluated with four replicates for physiological and reproductive responses (6 females/replicate), biochemical techniques (40 individuals/replicate) and Hg/CPF bioaccumulation measurements (1000 individuals/replicate). Copepods accumulated Hg/CPF similarly from dissolved pollutants (6204 ± 2265 ng Hg/g and 1251 ± 646 ng CPF/g) and loaded MPs (3125 ± 1389 ng Hg/g and 1156 ± 266 ng CPF/g), but significantly less from loaded MA (21 ± 8 ng Hg/g and 173 ± 80 ng CPF/g). After 24–48 h, copepods exposed to MPs + Hg/CPF showed generally greater biological effects than those exposed to dissolved Hg/CPF or to MA + Hg/CPF, although differences were not statistically significant. MA + CPF had significantly lower AChE inhibition (1073.4 nmol min−1 mg−1) and MA + Hg lower GRx induction (48.8 nmol min−1 mg−1) compared to MPs + Hg/CPF and dissolved Hg/CPF (182.8–236.4 nmol min−1 mg−1 of AChE and 74.1–101.7 nmol min−1 mg−1 of GRx). Principal component analysis suggested different modes of action for Hg and CPF.

Chemical profiling of citrus fruit-peel and stem extracts by modified UHPLC-TOF-MS and their antiplasmodial, antioxidant and antimicrobial activities

Citrus jambhiri (Lush) and paradisi (Macf.) have wide usage as food spices. Therefore, the presence of profiled phytochemicals, the antioxidant, antimicrobial and anti-plasmodial activities of the stem and fruit-peel extracts were studied. The citrus stem and fruit-peel extracts were analyzed using ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-qTOF/MS) and anti-plasmodial activities against chloroquine-sensitive (CQS) strain of Plasmodium falciparum, antimicrobial against Gram-positive and Gram-negative bacterial strains as well as antioxidant potentials were determined in triplicate. Metabolite fingerprinting of C. jambhiri stem and C. paradisi fruit-peel extracts revealed rutamarin and spicatin respectively. The stem and fruit-peel of C. jambhiri showed moderate antimalarial activity. C. paradisi stem revealed a weak activity; however, C. paradisi fruit-peel showed no antimalarial activity (IC50 >100 μg/mL). C. paradisi and C. jambhiri extracts exhibited lower inhibition concentration (IC50: 3.0–7.0 µgmL−1), than ascorbic acid (IC50: 9.0 µgmL−1). C. paradisi stem DCM/methanol extract showed a reducing value of EC50: 8.00 µgmL−1 whereas reference compound used, (ascorbic acid) had EC50: 11.00 µgmL−1. Furthermore, C. jambhiri stem extract showed the best antimicrobial activity against the clinical isolates with high inhibition zones ≥ 15 mm. There is a paucity of information on the identification and importance of rutamarin and spicatin from Citrus extracts as a functional food ingredient with a promising compound implicated in the development of antimalarial drugs. Overall result however showed that the two citrus plants contain antioxidant constituents whereas C. jambhiri could be important source of antimicrobial agents. The study profiled two new compounds from the citrus extract and showed the potentials of the plant as source of antimalaria drug.

Individual differences in representational gesture production are associated with cognitive and empathy skills.

Substantial individual variation exists in the frequency of gestures produced while speaking. This study investigated the associations between cognitive abilities, empathy levels, and personality traits with the frequency of representational gestures. A cartoon narration task and a social dilemma solving task were used to elicit gestures. Predictor variables were selected based on prior research on individual differences in gesture production and the cognitive and communicative functions of gestures in speech. Our findings revealed that an increased frequency of representational gestures was associated with higher empathy levels in the cartoon narration task. However, in the social dilemma solving task, a higher frequency of representational gestures was associated with lower visuospatial working memory, spatial transformation, and inhibition control abilities. Moreover, no significant relationships were found between verbal working memory, personality traits, and the frequency of representational gestures in either task. These findings suggested that predictor variables for representational gesture production vary depending on the nature of the gesture elicitation task (e.g., spatiomotoric vs. abstract topics). Future research should examine the relationship between individuals' cognitive abilities, empathy and gesture production with across a broader range of topics and in more ecologically valid contexts.

Bioaccessibility of bioactive compounds present in Persea americana Mill. seed ingredient during oral-gastric digestion with antibacterial capacity against Helicobacter pylori

Ethnopharmacological relevanceIn ancient Mexican cultures, the Persea americana Mill seed has been used against gastrointestinal diseases, due to high concentrations of bioactive compounds. According to Traditional Mexican Medicine, P. americana seed aqueous infusion is used against roundworms, intestinal worms, parasites, and gastrointestinal problems, in a dose taken over three or four days. In addition, Mexican Society of Natural History indicates the traditional use of P. americana seed powder as an antiparasitic, and antibacterial. On the other hand, Helicobacter pylori infection is a factor associated with the development of gastric disease, peptic ulcers as well as some types of gastric lymphomas and gastric cancer in humans; in this way is necessary scientific evidence about P. americana seed effect in gastrointestinal disease. Aim of the studyThe work aimed to evaluate bioactive compounds bioaccessibility and antimicrobial potential against Helicobacter pylori during oral-gastric digestion in vitro of food ingredient from Persea americana Mill. seed and elucidate the possible action mechanism using in silico tools. Materials and methodsInitially, P. americana seed oil and aqueous extract of P. americana seed were obtained using ultrasound and maceration respectively, and the food ingredient from P. americana seed was obtained. The samples underwent oral-gastric digestions by the INFOGEST method, to continue identifying and quantifying the bioactive compounds by HPLC-DAD and GC-MS. The anti-Helicobacter pylori activity determination were used fourteen Helicobacter pylori clinical strains and reference strains by Susceptibility testing by Minimal Inhibition Concentration, Kinetics of Growth Inhibition of H. pylori, Urease Inhibitory Kinetic. Finally, to elucidate a possible action mechanism used in silico tools (Software AutoDock 4.2.6 and BioVia Discovery v.19.1.0.1.18287). ResultsThe lipophilic fraction of P. americana seed detected oleic acid, linoleic acid, and avocadenofuran compounds, and the phenolic fraction showed the presence of catechin, rutin, ellagic, and chlorogenic acid, among others. Phenolic compounds conformational changes during oral-gastric digestion due to mechanical and acid hydrolysis, while lipophilic compounds showed a 20% increase in the gastric phase. Persea americana Mill. seed ingredient (3.08 μg/mL) showed total in vitro inhibition of clinical and reference strains of H. pylori, likewise, the lipophilic fraction had a lower inhibition concentration (2.59 μg/mL) regardless of the strains. Among the mechanisms found in silico, inhibition of target proteins such as CagA, BabA, and MUC5 were observed, as virulence factors involving adherence and bacterial pathogenicity. ConclusionsThis research provides evidence that food ingredient from P. americana seed has antimicrobial in vitro potential against H. pylori clinical strains, through phenolic and mainly lipophilic compounds, opening new scientific evidence that supports the P. americana seed's traditional use.

Carboxylesterase and Cytochrome P450 Confer Metabolic Resistance Simultaneously to Azoxystrobin and Some Other Fungicides in Botrytis cinerea.

Plant pathogens have frequently shown multidrug resistance (MDR) in the field, often linked to efflux and sometimes metabolism of fungicides. To investigate the potential role of metabolic resistance in B. cinerea strains showing MDR, the azoxystrobin-sensitive strain B05.10 and -resistant strain Bc242 were treated with azoxystrobin. The degradation half-life of azoxystrobin in Bc242 (9.63 days) was shorter than that in B05.10 (28.88 days). Azoxystrobin acid, identified as a metabolite, exhibited significantly lower inhibition rates on colony and conidia (9.34 and 11.98%, respectively) than azoxystrobin. Bc242 exhibited higher expression levels of 34 cytochrome P450s (P450s) and 11 carboxylesterase genes (CarEs) compared to B05.10 according to RNA-seq analysis. The expression of P450 genes Bcin_02g01260 and Bcin_12g06380, along with the CarEs Bcin_12g06360 in Saccharomyces cerevisiae, resulted in reduced sensitivity to various fungicides, including azoxystrobin, kresoxim-methyl, pyraclostrobin, trifloxystrobin, iprodione, and carbendazim. Thus, the mechanism of B. cinerea MDR is linked to metabolism mediated by the CarE and P450 genes.

Immune profiling of responses to influenza vaccination in patients with myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are associated with immune dysregulation and increased susceptibility to infection, emphasizing the importance of vaccination for patients. This pilot study evaluated immune responses to influenza vaccination in MPN patients compared with healthy donors using mass cytometry and serology. We observed diminished CXCR5+ B-cell, CXCR3+ T-cell, activated CD127+ memory T-cell subsets, and a trend toward lower hemagglutinin inhibition titer in MPN patients. These results indicate that patients with MPN exhibit distinct responses to influenza vaccination suggestive of impaired migration to lymphoid organs and T-cell maturation which may impact the development of protective immunity.

Executive functioning in child victims of sexual abuse: A multi-informant comparative study

BackgroundResearch examining the association between child sexual abuse and executive functions is limited. Yet, exposure to traumatic situations at a young age has been associated with changes in the prefrontal cortex, which hosts executive functions (Wesarg et al., 2020). These functions are crucial for social adaptation, as they make it possible to inhibit maladaptive behavior and respond flexibly to the demands of the environment. As middle childhood is a sensitive period for the development of self-regulatory abilities, exploring executive functioning in school-age children could provide potential intervention targets (Dajani & Uddin, 2015). ObjectiveUsing multiple informants, this study compared executive functioning of sexually abused children to that of non-sexually victimized children and examined whether the differences were moderated by sex. MethodsThe sample consisted of 225, 6-to-12 years old children with a history of child sexual abuse (CSA) and 97 children without a history of CSA. Children completed two executive functioning tasks measuring cognitive flexibility and inhibition. Parents and teachers completed questionnaires evaluating children's executive functioning. ResultsIn comparison to non-abused children, children with a history of CSA displayed greater executive functioning difficulties as assessed by both informant-reported questionnaires and self-completed tasks. Significant interaction effects were found, such as CSA predicting lower inhibition and executive functions at school in boys but not in girls. ConclusionThis study is a first step in understanding the association between CSA and executive functioning and offers a clearer picture of the differential impact of sexual trauma according to children's sex.

CdgB Regulates Morphological Differentiation and Toyocamycin Production in Streptomyces diastatochromogenes 1628.

Bis (3',5')-cyclic diguanylic acid (c-di-GMP) is a ubiquitous second messenger that controls several metabolic pathways in bacteria. In Streptomyces, c-di-GMP is associated with morphological differentiation, which is related to secondary metabolite production. In this study, we identified and characterized a diguanylate cyclase (DGC), CdgB, from Streptomyces diastatochromogenes 1628, which may be involved in c-di-GMP synthesis, through genetic and biochemical analyses. To further investigate the role of CdgB, the cdgB-deleted mutant strain Δ-cdgB and the cdgB-overexpressing mutant strain O-cdgB were constructed by genetic engineering. A phenotypic analysis revealed that the O-cdgB colonies exhibited reduced mycelium formation, whereas the Δ-cdgB colonies displayed wrinkled surfaces and shriveled mycelia. Notably, O-cdgB demonstrated a significant increase in the toyocamycin (TM) yield by 47.3%, from 253 to 374 mg/L, within 10 days. This increase was accompanied by a 6.7% elevation in the intracellular concentration of c-di-GMP and a higher transcriptional level of the toy cluster within four days. Conversely, Δ-cdgB showed a lower c-di-GMP concentration (reduced by 6.2%) in vivo and a reduced toyocamycin production (decreased by 28.9%, from 253 to 180 mg/L) after 10 days. In addition, S. diastatochromogenes 1628 exhibited a slightly higher inhibitory effect against Fusarium oxysporum f. sp. cucumerinum and Rhizoctonia solani compared to Δ-cdgB, but a lower inhibition rate than that of O-cdgB. The results imply that CdgB provides a foundational function for metabolism and the activation of secondary metabolism in S. diastatochromogenes 1628.

Corticospinal and spinal responses following a single session of lower limb motor skill and resistance training.

Prior studies suggest resistance exercise as a potential form of motor learning due to task-specific corticospinal responses observed in single sessions of motor skill and resistance training. While existing literature primarily focuses on upper limb muscles, revealing a task-dependent nature in eliciting corticospinal responses, our aim was to investigate such responses after a single session of lower limb motor skill and resistance training. Twelve participants engaged in a visuomotor force tracking task, self-paced knee extensions, and a control task. Corticospinal, spinal, and neuromuscular responses were measured using transcranial magnetic stimulation (TMS) and peripheral nerve stimulation (PNS). Assessments occurred at baseline, immediately post, and at 30-min intervals over two hours. Force steadiness significantly improved in the visuomotor task (P < 0.001). Significant fixed-effects emerged between conditions for corticospinal excitability, corticospinal inhibition, and spinal excitability (all P < 0.001). Lower limb motor skill training resulted in a greater corticospinal excitability compared to resistance training (mean difference [MD] = 35%, P < 0.001) and control (MD; 37%, P < 0.001). Motor skill training resulted in a lower corticospinal inhibition compared to control (MD; - 10%, P < 0.001) and resistance training (MD; - 9%, P < 0.001). Spinal excitability was lower following motor skill training compared to control (MD; - 28%, P < 0.001). No significant fixed effect of Time or Time*Condition interactions were observed. Our findings highlight task-dependent corticospinal responses in lower limb motor skill training, offering insights for neurorehabilitation program design.

Factors associated with clopidogrel resistance and clinical outcomes in ischemic cerebrovascular disease: A retrospective study

ObjectiveClopidogrel resistance may lead to the recurrence of cerebrovascular diseases. We aimed to identify potential factors associated with clopidogrel resistance and evaluate the clinical outcomes of the patients. Materials and methodsIn this retrospective study, patients with ischemic cerebrovascular disease treated with clopidogrel were included and classified into 2 groups according to the adenosine diphosphate (ADP)-induced platelet aggregation. Patients with the ADP inhibition rate of <30 % were included in clopidogrel resistance group, otherwise were included in clopidogrel sensitive group. CYP2C19 genotype and other clinical data were analyzed to identify factors and clinical features in the multivariate analysis. The outcomes were vascular events in 6 months. ResultsIn total, 139 patients were enrolled with 81 (58.27 %) in clopidogrel sensitive group and 58 (41.73 %) in clopidogrel resistance group. Female and CYP2C19 *2*3 carrying were risk factors for clopidogrel resistance, and female was an independent risk factor (OR 2.481, 95 % CI 1.066-5.771, P=0.035). The clopidogrel resistance group showed a higher use rate of argatroban (P=0.030) and a lower arachidonic acid-induced inhibition of platelet aggregation (P=0.036). Clopidogrel resistance was related to the progressing stroke (HR 3.521, 95 % CI 1.352-9.170, P=0.010), but had no influence on the bleeding events (P>0.05). ConclusionsThe risk of clopidogrel resistance increased significantly in female patients. Patients with clopidogrel resistance may have an increased incidence of stroke progression in the acute phase.

Pharmacological Activities of Six Species of Hedychium J. Koenig from Nepal

Species of Hedychium Koenig are perennial herbs. Some of the species like H. ellipticum, H. spicatum, H. coronarium are traditionally used as medicinal plants. In the present study, methanolic rhizome extracts of six different species of Hedychium namely H. spicatum, H. ellipticum, H. thyrsiforme, H. coccineum, H. gardnerianum and H. coronarium were analysed for their antioxidant, antidiabetic and antibacterial activities. The antioxidant activity analysed by DPPH assay showed the highest potential (lowest IC50 value) in H. coccineum (148.82±2.83 µg/ml) and lowest potential (maximum IC50 value) in H. thyrsiforme (996.55±9.42 µg/ml). The rhizome extracts of different species showed moderate α-amylase inhibition activity in vitro. The highest α-amylase inhibition (79.67%) was observed for H. coronarium while the lowest inhibition (64.0%) was observed in H. thyrsiforme. However, these values were found lower than the value (92.37%) obtained for positive control, i.e., Acarbose. The antibacterial activity was determined against two Gram-positive (Bacillus subtilis and Staphylococcus aureus) and two Gram-negative (Klebsiella pneumoniae and Pseudomonas aeruginosa) bacterial strains by agar well diffusion method. Except for H. ellipticum the extracts of all other species showed antibacterial activity against all the bacterial strains tested. The extracts of H. ellipticum showed antibacterial activity only against B. subtilis and K. pneumoniae. The extract of H. coronarium showed the highest zone of inhibition (16.67±1.15 mm) against B. subtilis. However, the antibacterial activity was weak compared to standard antibiotics for all the extracts and at all concentration tested. These results show that rhizomes of other species can also be used in the same manner as that of H. coronarium and H. spicatum, two species most used in various ethnomedicinal applications.

Conductive adsorbents enhance phenol removal from wastewater by direct interspecies electron transfer "DIET"-based anaerobic biodegradation process

This study examined the hybrid adsorption and anaerobic biodegradation processes of phenol by using activated carbon cloth (CC) to stimulate direct interspecies electron transfer (DIET). Phenol biodegradation was tested over three sequential runs using 100 mL lab-scale bioreactors and compared with two different types of CC and granular activated carbons (GAC). The addition of the carbon adsorbents to the bioreactors significantly accelerated the methane production rate. This high rate of methane production was also accompanied by the complete removal of phenol, and a high COD(s) removal rate of about 95%, compared to 43.68% and 48.65% in the control sets in the first and second runs, respectively. The enhancement of the phenol biodegradation is attributed to the synergy of the adsorption and biodegradation processes. An initial adsorption stage has contributed to a significant and rapid reduction of phenol, leading to a lower inhibition effect of phenol, followed by anaerobic biodegradation of the adsorbed phenol stimulated by the DIET process. Specifically, the optimal concentration for Single Weave carbon cloth (CCSW) of 1.6 g L−1 promoted both the DIET and the adsorption processes. Microbial community composition analysis revealed that CCSW facilitated the growth of syntrophic bacterial groups (Rikenellae, Syntrophorhabdaceae, Gracilibacteraceae, and DTU014), and archaea (Methanosaetaceae and Methanoregulaceae), previously reported as key players in the DIET processes to promote phenol degradation. To the best of our knowledge, this is the first work that demonstrates the contribution of CC to stimulate DIET mechanism of anaerobic biodegradation synergistically combined with adsorption process for enhanced phenol removal.