Low Concentrations Research Articles

Relation Between Exposure to Tobacco Smoke Assessed by Serum Cotinine Concentration and Questionnaire Method, and Serum Renalase Concentration-the Importance of the Coexistence of Arterial Hypertension and Other Cardiovascular Diseases.

Exposure to tobacco smoke (ETS) is one of the main risk factors for cardiovascular disease (CVD). Renalase is a protein that may play a role in the pathogenesis of CVD. The aim of the study was to assess the relationship between ETS and serum renalase concentration. A group of 109 patients was recruited for this study (49.7 ± 14.7years). In accordance with the questionnaire, patients were divided into the following subgroups: subgroup A- declaring themselves active smokers (n = 36), subgroup B- declaring themselves non-smokers and exposed to environmental tobacco smoke (n = 35), subgroup C- declaring themselves non-smokers and not exposed to environmental tobacco smoke (n = 38). The same patients were divided based on cotinine concentration into the following subgroups: subgroup D- active smokers (n = 42), subgroup E- non-smokers exposed to environmental tobacco smoke (n = 66), and subgroup F- non-smokers not exposed to environmental tobacco smoke (n = 1). Serum cotinine concentration and serum renalase concentration were measured using ELISA tests. Serum renalase concentration was statistically significantly higher in subgroup C than in subgroups A and B and in subgroup E and F than in D. There was a negative correlation between serum cotinine concentration and serum renalase concentration (r = -0.41, p < 0.05). Regression analysis showed that higher BMI, higher diastolic blood pressure, coronary artery disease and higher serum cotinine concentration are independent risk factors of lower serum renalase concentration. The questionnaire method of assessing exposure to tobacco smoke was characterized by high sensitivity, but only moderate specificity, especially in terms of assessing environmental exposure to tobacco smoke. In summary, the study showed an independent relationship between exposure to tobacco smoke and lower serum renalase concentration.

Recent Developments On Activatable Turn-On Fluorogenic Donors of Hydrogen Sulfide (H2S).

Hydrogen sulfide (H2S) is considered the third member of the gasotransmitter family, along with nitric oxide (NO) and carbon monoxide (CO). Besides its role in physiological and pathophysiological conditions, the promising therapeutic potential of this small-molecule makes it advantageous for various pharmaceutical applications. The endogenous production of H2S at a lower concentration is crucial in maintaining redox balance and cellular homeostasis, and the dysregulation leads to various disease states. In the event of H2S deficiency, the exogenous donation of H2S could help maintain the optimal cellular concentration of H2S and cellular homeostasis. Over the last several years, researchers have developed numerous small-molecule non-fluorogenic organosulfur compounds as H2S donors and investigated their pharmacological potentials. However, reports on stimuli-responsive turn-on fluorogenic donors of H2S have appeared recently. Interestingly, the fluorogenic H2S donors offer additional advantages with the non-invasive real-time monitoring of the H2S release utilizing the simultaneous turn-on fluorogenic processes. The review summarizes the recent developments in turn-on fluorogenic donors of H2S and the potential biological applications that have developed over the years.

Gut Microbiota-Derived 3-Hydroxybutyrate Blocks GPR43-Mediated IL6 Signaling to Ameliorate Radiation Proctopathy.

Radiation proctopathy (RP) is a common complication of radiotherapy for pelvic malignancies with high incidence. RP accompanies by microbial dysbiosis. However, how the gut microbiota affects the disease remains unclear. Here, metabolomics reveals that the fecal and serous concentrations of microbiota-derived 3-hydroxybutyrate (3HB) are significantly reduced in RP mice and radiotherapeutic patients. Moreover, the concentration of 3HB is negatively associated with the expression of proinflammatory IL6 that is increased along with the severity of radiation damage. 3HB treatment significantly downregulates IL6 expression and alleviates IL6-mediated radiation damage. Irradiated cell-fecal microbiota co-culture experiments and in vivo assays show that such a radioprotection of 3HB is mediated by GPR43. Microbiome analysis reveals that radiation leads to a distinct bacterial community compared to untreated controls, in which Akkermansia muciniphila is significantly reduced in RP mice and radiotherapeutic patients and is associated with lower 3HB concentration. Gavage of A. muciniphila significantly increases 3HB concentration, downregulates GPR43 and IL6 expression, and ameliorates radiation damage. Collectively, these results demonstrate that the gut microbiota, including A. muciniphila, induce higher concentrations of 3HB to block GPR43-mediated IL6 signaling, thereby conferring radioprotection. The findings reveal a novel implication of the gut-immune axis in radiation pathophysiology, with potential therapeutic applications.

Finite Element Analysis of Anterior Implant-Supported Restorations with Different CAD-CAM Restorative Materials.

Due to the lack of literature concerning the selection of crown materials for the restoration of anterior teeth, this study aimed to investigate the effects of six distinct computer-aided design and computer-aided manufacturing (CAD-CAM) crown materials on stress and strain distribution within implant-supported maxillary central incisor restorations, employing finite element analysis (FEA). Furthermore, a comparative analysis was conducted between models that incorporated adjacent natural teeth and those that did not, intending to guide the selection of the most suitable modeling approach. Crown materials, including Lava Ultimate, Enamic, Emax CAD, Suprinity, Celtra Duo, and Cercon xt ML, were the subjects of the investigation. FEA models incorporating Coulomb friction were developed. These models were subjected to an oblique load, simulating the average maximum bite force experienced by anterior teeth. The potential for failure in titanium implant components and the prosthesis crown was evaluated through von Mises and principal stress, respectively. Furthermore, the failure of crestal bone was assessed through principal strain values. Stress values for each implant component and strain values of the bone were extracted from the models. To assess the impact of the six groups of crown materials, Kruskal-Wallis analysis of variance and post-hoc comparisons were conducted. Additionally, a statistical comparison between the two groups with Lava Ultimate and Cercon xt ML was performed using the Mann-Whitney U test to determine the difference in the two modeling approaches. Higher crown material stiffness led to decreased stress in the abutment, fixture, and retaining screw, along with reduced strain in the surrounding bone. However, the decrease in stress and strain values became less significant with increasing crown stiffness. Additionally, the model with adjacent teeth showed significantly lower stress and strain concentrations compared to the model without adjacent teeth. Crowns with a high elastic modulus were the optimal choice for anterior teeth restoration. Constructing FEA models with adjacent teeth was highly recommended to gain a deeper understanding of the mechanical behavior of dental implant restorations.

Sequestration of a food dye (sunset yellow) from wastewater using natural adsorbent: a kinetic, isotherm and interference study.

Cocos nucifera, commonly known as coconut is rich in coir dust (CCD) at its outer surface, which is a very significant agri waste used as biosorbent for wastewater treatment. The current work addresses use of CCD for removal of hazardous Sunset Yellow dye (SY) FCF widely used as coloring agent in food industry, from wastewater. The uptake capacity in batch and column mode is 82 mg/g and 160 mg/g respectively. Characterization study including SEM, FTIR and BET results also supported the adsorption process. The comparative analysis with other natural biosorbents showed best results of biosorption with CCD. The output was better at high pH (10) and lower concentration of dye (5 mg/L). The kinetic study suggested pseudo second order rate revealing both adsorbate-adsorbent interdependency. The presence of covalent bonding or valence forces between the interfaces, suggested chemisorption as the rate limiting mechanism with valence forces, hydrogen bonding and pi-pi stacking being the chief forces responsible in binding of the dye molecules to the surface. The isotherm supported Langmuir model with monolayer and uniform adsorption at the interfaces. The interference test confirmed slight decrease in percent adsorption with interference from chloride and sulfate as dominating ions. The techno-economic feasibility highly recommended in field application of the substitute (net profit value, 1.256 Rs/m3, input cost, 0.052 Rs/m3). The industrial sample analysis with lab to land approach justified sustainability and commercial viability of the present work.

Effects of CYP3A5*3 genetic polymorphisms on the pharmacokinetics of perampanel in Chinese pediatric patients with epilepsy.

This study was the first to evaluate the effect of CYP3A5*3 gene polymorphisms on plasma concentration of perampanel (PER) in Chinese pediatric patients with epilepsy. We enrolled 98 patients for this investigation. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final checkup. The plasma concentration showed a linear correlation with the daily dose taken ( r = 0.17; P < 0.05). The ineffective group showed a significantly lower plasma concentration of PER (490.5 ± 297.1 vs. 633.8 ± 305.5 μg/ml; P = 0.019). For the mean concentration-to-dose (C/D) ratio, the ineffective group showed a significantly lower C/D ratio of PER (3.2 ± 1.7 vs. 3.8 ± 2.0; P = 0.040). The CYP3A5*3 CC genotype exhibited the highest average plasma concentration of PER at 562.8 ± 293.9 ng/ml, in contrast to the CT and TT genotypes at 421.1 ± 165.6 ng/ml and 260.0 ± 36.1 ng/ml. The mean plasma PER concentration was significantly higher in the adverse events group (540.8 ± 285.6 vs. 433.0 ± 227.2 ng/ml; P = 0.042). The CYP3A5*3 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A5*3 genetic genotype should be factored in when prescribing PER to patients with epilepsy.

Study on the Typical Environmental Factors in the Middle Part of Zhoushan Fishery Based on HY-1C/D and Other Multi-Source Data

This study utilizes satellite data, including HY-1C/D, along with reanalysis data, to unveil the typical environmental characteristics of the sea surface in the middle of Zhoushan fishery. The article addresses three main issues. The first one is the development of an ocean primary productivity (OPP) inversion algorithm model. The second one is the study of chlorophyll-α (Chl-α) concentration and OPP distribution characteristics in Zhoushan fishery using China’s domestically produced ocean satellite HY-1C/D CZI data. The last one is the revelation of the characteristics of typical environmental factors on the sea surface at Zhoushan fishery by combining HY-1C/D with multi-source data. The results show the following: (1) The middle part of Zhoushan fishery exhibits significant seasonal and regional variations in Chl-α concentration and OPP. Chl-α concentration ranges mainly between 0.2 and 2.9 µg/L, with higher concentrations in spring and summer and lower Chl-α concentrations in autumn and winter. Spatially, Chl-α concentration gradually decreases from west to east. The OPP in the study area ranges from 100 mg·m−2d−1 to 1000 mg·m−2d−1, with high OPP values distributed on the western side, ranging from 400 mg·m−2d−1 to 1000 mg·m−2d−1, and gradually decreasing seaward. The highest OPP occurs in summer and the lowest in winter. (2) The correlation analysis between Chl-α concentration and OPP revealed a strong positive relationship. Consequently, this study developed an empirical model for estimating OPP based on Chl-α concentration and validated its feasibility. The model applies to areas with Chl-α concentrations ranging from 0.2 to 4 µg/L. (3) The convergence of freshwater injection, multiple ocean currents, and seasonal upwelling in the study area brings about a rich supply of nutrients. Additionally, the region is characterized by suitable conditions, including optimal Chl-α concentrations, OPP, SST, salinity, currents, and geological water depths. The synergistic effect of these factors together contributed to the formation of Zhoushan fishery.

A Sarcocystidae-Specific striated fiber assemblin protein SFA5 is required for parasite division in Toxoplasma gondii

Apicomplexan encompass a variety of intracellular parasites responsible for significant diseases in humans and animals, such as malaria and toxoplasmosis. Among these, Toxoplasma gondii (T. gondii) serves as an exemplary organism for understanding the intricate biological characteristics of the phylum. At the parasite's apical tip, a striated fiber was discovered and proposed to be evotionarily derived from the algal flagellum. However, the protein composition (the striated fiber assemblin, SFA) of this fiber remains poorly understood. Here, we took advantage of a proximity biotin labeling approach to identify potential SFA proteins by fusion of an engeneered biotin ligase TurboID with SFA2, from which we identified several novel components of the fiber. Evolutionary analysis suggested that SFA4 is conserved in the Apicomplexa phylum with the exception of piroplasmida, while SFA5 is specific to species of Sarcocystidae. Confocal imaging analysis showed that SFA4 and SFA5 are substantially co-localized with the bait SFA2. Using a new version (OsTIR1F74G) of the plant auxin-inducible degron system that we adapted in this study, we found that SFA4 and SFA5 were efficiently depleted by addition of a much lower concentration of inducer (5-Ph-IAA, instead of IAA). Detailed phenotypical analyses demonstrated that SFA5 is essential for daughter parasite formation and separation of parasite nuclei during division, supporting the localization of SFA5 at the striated fiber that connects the centriole and the apical conoid. The mouse assay suggested the essentiality of SFA5 in the parasites. Thus, this study provided a new repertoile of the stiated fiber, and new data supporting association of the fiber with parasite division.

Direct Parental (DIPA) CRISPR in the jewel wasp, Nasonia vitripennis.

While CRISPR-Cas9 technology has demonstrated remarkable promise as a gene editing tool, its application in certain insects, such as the jewel wasp, Nasonia vitripennis, has been hindered by a lack of a tractable method for reagent delivery. Direct Parental-CRISPR (DIPA-CRISPR) recently emerged as a facile way to induce gene lesions because it involves adult injection with commercially available Cas9-sgRNA with no helper reagent. However, DIPA-CRISPR has so far been tested in only a few insects. Here, we have assessed the viability of DIPA-CRISPR in N. vitripennis by targeting two eye-pigmentation genes, cinnabar and vermilion, which function in the ommochrome pathway. Successful generation of lesions in both genes demonstrated the functionality of DIPA-CRISPR in N. vitripennis and its potential application to other genes, thereby expanding the range of insects suitable for this method. We varied two parameters, Cas9-sgRNA concentration and injection volume, to determine optimal injection conditions. We found that the larger injection volume coupled with either higher or lower concentration was needed for consistent mutation production. However, DIPA-CRISPR yields an overall low mutation rate in N. vitripennis when compared to other tested insects, a characteristic that may be attributed to a proportionally low vitellogenic import efficiency in the jewel wasp. We discuss different factors that may be considered in determining when DIPA-CRISPR may be preferable over other reagent delivery methods.

Unveiling the Potential of Halide Perovskites for Seasonally Adaptive CO2 Photoreduction under Low Light Conditions

AbstractThe viability of double perovskite Cs2AgBiBr6 in low‐light environments is studied for CO2 photoreduction. It is observed that light intensity significantly influences product formation with I0.56 depending on the overall product formation rate. The photodetection measurement reveals that photocurrent as a function of incident power follows a power law ∝ I0α with α = 0.80, which is attributed to the carrier trapping at higher light power. Furthermore, power‐dependent transient absorption spectroscopy is studied and observed that at higher fluence, carrier scattering can be dominating. Interestingly, it is found that at higher power, hot carrier relaxation dynamics are altered, and electron‐phonon coupling is enhanced, resulting in a lower carrier concentration participating in the photocatalytic reaction, which can limit charge carrier extraction and CO2 reduction. This study highlights the potential of perovskite semiconductors as promising candidates for photocatalytic reactions in low‐light conditions, broadening their applicability in real‐world scenarios.

A novel disulfide death-related genes prognostic signature identifies the role of IPO4 in glioma progression

Background“Disulfide death,” a form of cellular demise, is triggered by the abnormal accumulation of intracellular disulfides under conditions of glucose deprivation. However, its role in the prognosis of glioma remains undetermined. Therefore, the main objective of this study is to establish prognostic signature based on disulfide death-related genes (DDRGs) and to provide new solutions in choosing the effective treatment of glioma.MethodsThe RNA transcriptome, clinical information, and mutation data of glioma samples were sourced from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), while normal samples were obtained from the Genotype-Tissue Expression (GTEx). DDRGs were compiled from previous studies and selected through differential analysis and univariate Cox regression analysis. The molecular subtypes were determined through consensus clustering analysis. Further, LASSO analysis was employed to select characteristic genes, and subsequently, a risk model comprising seven DDRGs was constructed based on multivariable Cox analysis. Kaplan-Meier survival curves were employed to assess survival differences between high and low-risk groups. Additionally, functional analyses (GO, KEGG, GSEA) were conducted to explore the potential biological functions and signaling pathways of genes associated with the model. The study also explored immune checkpoint (ICP) genes, immune cell infiltration levels, and immune stromal scores. Finally, the effect of Importin-4(IPO4) on glioma has been further confirmed through RT-qPCR, Western blot, and cell functional experiments.Results7 genes associated with disulfide death were obtained and two subgroups of patients with different prognosis and clinical characteristics were identified. Risk signature was subsequently developed and proved to serve as an prognostic predictor. Notably, the high-risk group exhibited an immunosuppressive microenvironment characterized by a high concentration of M2 macrophages and regulatory T cells (Tregs). In contrast, the low-risk group showed lower half-maximal inhibitory concentration (IC50) values. Therefore, patients in the high-risk group may benefit more from immunotherapy, while patients in the low-risk group may benefit more from chemotherapy. In addition, in vitro experiments have shown that inhibition of the expression of IPO4 leads to a significant reduction in the proliferation, migration, and invasion of glioma cells.ConclusionThis study identified two glioma subtypes and constructed a prognostic signature based on DDRGs. The signature has the potential to optimize the selection of patients for immune- and chemotherapy and provided a potential therapeutic target for glioma.

The signalling role of the government‐market relationship in debt financing: Evidence from China

AbstractA proper government‐market relationship (GMR) serves as an important institutional environment for investors to make rational economic decisions. Theoretically, by embedding the GMR into the signalling model, this study finds that (a) the improvement in the GMR can enable high‐return firms to obtain more debt financing and (b) the mechanism is that a higher GMR, as a signal, increases the accuracy of investors' inference on firms' returns. Using data of Chinese A‐share listed firms (2009–2019) and the two‐step system GMM, this study empirically demonstrates that the GMR does help investors infer firms' returns more accurately, thus enlarging the debt financing scales of high‐return firms. Moreover, the positive impact of the GMR on high‐return firms is significant within privately owned firms and more substantial in markets characterised by lower industry concentration.

Swelling Behaviors of Natural Rubber/Solvent Systems Based on the Extended Modified Double Lattice Model

AbstractSwelling experiments are conducted on nonfiller natural rubber using four solvents (toluene, cyclohexane, tetrahydrofuran (THF), and methylethylketone (MEK)) over temperatures from 10 to 70 °C. Toluene, cyclohexane, and THF, classified as effective solvents, show swelling ratios between 3 and 7, influenced by the crosslink density of the rubber. MEK, however, has a lower ratio of 1.5 to 2. Temperature has a minor impact on swelling compared to the crosslink density. The study evaluates the Extended Modified Double Lattice (EMDL) model for its mixing contribution in polymer network swelling, aiming to improve the Flory–Hüggins (FH) model. The superiority of EMDL above FH is in the boundary condition at the unvulcanized state, the former aligning its interaction energy with values from solvent activities in primary linear polymer/solvent solutions, unlike the FH model. The EMDL model also accounts for oriented interactions in polar solvents through a secondary lattice, linking specific interaction energy with solvent dipole moments. The study observes a nonlinear correlation between crosslinking density and sulfur amount, proposing a nonrandom mixing at lower sulfur concentrations. This model shows strong alignment with experimental data, suggesting that replacing the FH model's mixing contribution with the EMDL model could improve results with minimal additional complexity.

Injectable and Dynamically Crosslinked Zwitterionic Hydrogels for Anti-Fouling and Tissue Regeneration Applications.

A zwitterionic injectable and degradable hydrogel based on hydrazide and aldehyde-functionalized [2-(methacryloyloxy)ethyl] dimethyl-(3-sulfopropyl)ammonium hydroxide (DMAPS) precursor polymers that can address practical in vivo needs is reported. Zwitterion fusion interactions between the zwitterionic precursor polymers create a secondary physically crosslinked network to enable much more rapid gelation than previously reported with other synthetic polymers, facilitating rapid gelation at much lower polymer concentrations or degrees of functionalization than previously accessible in addition to promoting zero swelling and long-term degradation responses and significantly stiffer mechanics than are typically accessed with previously reported low-viscosity precursor gelation systems. The hydrogels maintain the highly anti-fouling properties of conventional zwitterionic hydrogels against proteins, mammalian cells, and bacteria while also promoting anti-fibrotic tissue responses in vivo. Furthermore, the use of the hydrogels for effective delivery and subsequent controlled release of viable cells with tunable profiles both in vitro and in vivo is demonstrated, including the delivery of myoblasts in a mouse skeletal muscle defect model for reducing the time between injury and functional mobility recovery. The combination of the injectability, degradability, and tissue compatibility achieved offers the potential to expand the utility of zwitterionic hydrogels in minimally invasive therapeutic applications.

Beta-Cyfluthrin-Induced Hepatic Alterations in Zebrafish: Enzymatic Profiles and Oxidative Stress Responses

Beta-Cyfluthrin is a widely used pesticide belonging to class of synthetic pyrethroids which affects the central and peripheral nervous systems. The current study investigates the impact of beta-Cyfluthrin on the biochemical parameters of liver of zebrafish (Danio sp.). Adult zebrafish were exposed to concentrations of 0.25, 0.5, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin for acute (96 hours) and chronic (21 days) exposure periods respectively (n=20). It was observed that exposure to beta-Cyfluthrin led to variations in biochemical markers in both acute and chronic exposure groups. Liver function tests revealed significant elevated activity of alanine transaminase (ALT) and aspartate transaminase (AST) at exposure concentrations of 2.0 and 4.0 µg/L of beta-Cyfluthrin in both acute and chronic groups, while acid phosphatase (ACP) and alkaline phosphatase (ALP) activity decreased significantly at concentrations of 1.0, 2.0 and 4.0 µg/L in the chronic group. Lipid peroxidation exhibited a concentration and time-dependent increase with significant difference at 1.0, 2.0 and 4.0 µg/L in both acute and chronic groups, while superoxide dismutase (SOD) and peroxidase (PER) levels declined significantly in both acute and chronic exposure groups at exposure concentrations of 1.0, 2.0 and 4.0 µg/L for SOD and 2.0 and 4.0 µg/L for PER. Catalase (CAT) initially increased significantly in acute groups of 1.0, 2.0 and 4.0 µg/L but decreased in chronic ones. Glutathione S-transferase (GST) levels exhibited a significant increase at lower concentrations of 0.25 µg/L but a decrease at higher concentrations, 1.0, 2.0 and 4.0 µg/L of beta-Cyfluthrin. The level of significance were considered at p&lt;0.05 and p&lt;0.01. This research suggests that exposure to beta-Cyfluthrin leads to hepatic damage in adult zebrafish. This indicates a potential risk to non-target aquatic fauna, through runoff where beta-Cyfluthrin is used as an agricultural pesticide.

The Role of Life Stages in the Sensitivity of Hediste diversicolor to Nanoplastics: A Case Study with Poly(Methyl)Methacrylate (PMMA)

The presence of plastic particles in oceans has been recognized as a major environmental concern. The decrease in particle size increases their ability to directly interact with biota, with particles in the nanometer size range (nanoplastics—NPs) displaying a higher ability to penetrate biological membranes, which increases with the decrease in particle size. This study aimed to evaluate the role of life stages in the effects of poly(methyl)methacrylate (PMMA) NPs on the polychaete Hediste diversicolor, a key species in the marine food web and nutrient cycle. Thus, behavioral (burrowing activity in clean and spiked sediment) and biochemical endpoints (neurotransmission, energy reserves, antioxidant defenses, and oxidative damage) were assessed in juvenile and adult organisms after 10 days of exposure to spiked sediment (between 0.5 and 128 mg PMMA NPs/Kg sediment). Overall, the results show that H. diversicolor is sensitive to the presence of PMMA NPs. In juveniles, exposed organisms took longer to burrow in sediment, with significant differences from the controls being observed at all tested concentrations when the test was performed with clean sediment, whereas in PMMA NP-spiked sediment, effects were only found at the concentrations 8, 32, and 128 mg PMMA NPs/Kg sediment. Adults displayed lower sensitivity, with differences to controls being found, for both sediment types, at 8, 32, and 128 mg PMMA NPs/Kg sediment. In terms of Acetylcholinesterase, used as a marker of effects on neurotransmission, juveniles and adults displayed opposite trends, with exposed juveniles displaying increased activity (suggesting apoptosis), whereas in adults, overall decreased activity was found. Energy-related parameters revealed a generally similar pattern (increase in exposed organisms) and higher sensitivity in juveniles (significant effects even at the lower concentrations). NPs also demonstrated the ability to increase antioxidant defenses (higher in juveniles), with oxidative damage only being found in terms of protein carbonylation (all tested NPs conditions) in juveniles. Overall, the data reveal the potential of PMMA NPs to affect behavior and induce toxic effects in H. diversicolor, with greater effects in juveniles.

Cornus mas L. Extract-Mediated Modulations of the Redox State Induce Cytotoxicity in Schizosaccharomyces pombe

The Cornus mas L. fruit is well known for having a high presence of bioactive substances that include phenolic compounds, anthocyanins, vitamins, flavonoids, carotenoids, and ursolic acid. The health-promoting effects of those substances are mainly associated with their antimicrobial, anti-inflammatory, and antioxidant properties. In this study, we investigated the role of Cornus mas L. fruit ethanolic extract on the cell vitality of a model eukaryotic organism, the yeast Schizosaccharomyces pombe. The effect of Cornus mas L. fruit ethanolic extract on cell viability was determined by analyses of cell growth and cell doubling time during exposure to the extract. To determine the ability of Cornus mas L. to reduce or induce oxidative stress, quantification of intracellular reactive oxygen species and malondialdehyde levels was performed. Additionally, the enzyme activity of superoxide dismutase and catalase was evaluated together with the determination of changes in the expression of genes related to oxidative stress response. The data suggest a dose-dependent cytotoxic effect of the Cornus mas L. fruit ethanol extract, as a higher concentration (2%) led to increased oxidative stress and reduced cell viability of S. pombe cells, while a lower concentration (0.5%) showed only a subtle effect on the analyzed parameters. This study provides a new perspective on the possible antimicrobial or medicinal properties of Cornus mas L. fruit ethanol extract due to its ability to induce oxidative stress in the cell.

Acute Kidney Injury, Systemic Inflammation and Long-term Cognitive Function: ASSESS-AKI.

Cognitive dysfunction is a well-known complication of chronic kidney disease, but it is less known whether cognitive decline occurs in survivors after acute kidney injury (AKI). We hypothesized that an episode of AKI is associated with poorer cognitive function, mediated, at least in part, by persistent systemic inflammation. ASSESS-AKI enrolled patients surviving three months after hospitalization with and without AKI matched based on demographics, comorbidities, and baseline kidney function. A subset underwent cognitive testing using the modified mini-mental status examination (3MS) at 3, 12, and 36 months. We examined the association of AKI with 3MS scores using mixed linear models and assessed the proportion of risk mediated by systemic inflammatory biomarkers. Among 1538 participants in ASSESS-AKI, 1420 (92%) completed the 3MS assessment at 3 months and had a corresponding matched participant. Participants with AKI had lower 3MS scores at three years (difference -1.1 (95% CI: -2.0, -0.3) P=0.009) compared to participants without AKI. A higher proportion of AKI participants had a clinically meaningful (≥ 5 point) reduction in 3MS scores at three years compared to participants without AKI (14% vs. 10%, P=0.04). In mediation analyses, plasma soluble tumor necrosis factor receptor-1 (sTNFR-1) at three months after AKI mediated 35% (P=0.02) of the AKI related risk for 3MS scores at three years. AKI was associated with lower 3MS scores and sTNFR-1 concentrations appeared to mediate a significant proportion of the risk of long-term cognitive impairment. Further work is needed to determine if AKI is causal or a marker for cognitive impairment.

Does online high-volume hemodiafiltration offer greater efficiency and sustainability compared to high-flux hemodialysis? A detailed simulation analysis anchored in real-world data

Abstract Recent findings, including the CONVINCE study report, suggests the superiority of high-volume hemodiafiltration over high-flux hemodialysis in improving patients’ outcomes. Despite positive patient outcomes, concerns have arisen about the potential negative environmental impact of high-volume hemodiafiltration, as it may lead to increased water and dialysis fluid consumption and higher waste production. In this manuscript, we address the environmental impact of high-volume HDF, focusing on three key factors: water treatment consumption, dialysis fluid consumption, and solute efficiency markers of HD and HDF. By optimizing HDF prescription through adjustments in operational capabilities, such as reducing the QD/QB ratio to 1,2 rather than 1,5 and incorporating automated ultrafiltration and substitution control, it has been demonstrated that HDF delivers a higher dialysis dose for small and middle-molecule uremic compounds with the same dialysis fluid consumption and at equal dialysis doses dialysis fluid consumption is reduced. This finding is supported by real-world data from 26 031 patients who underwent high-volume postdilution hemodiafiltration at a reduced dialysis flow (550 ml/min) and achieved an effective OCMKt/V of 1.70. In addition, simulation modeling calculations, using blood extraction coefficient, dialysate saturation coefficient, and solute clearances with urea (small MW) and ß2M (middle MW), consistently show postdilution HDF's superiority to HD. This holds true even with a significant reduction in dialysis flow down to 440 ml/min reflecting QD/QB ratio of 1,2. Postdilution HDF generates high ultrafiltrate flow (up to 35% of blood flow), delivering saturated ultrafiltrate to the lower solute concentration containing effluent dialysate, thus enhancing solute clearance which opens the way to reduce the dialysis flow. In conclusion, our analysis, combining simulation and real-world data, suggests that postdilution HDF could be a more environmentally friendly treatment option compared to conventional hemodialysis. Additionally, automated user-friendly functions that minimize dialysis fluid use, can further strengthen this environmental benefit while enhancing efficiency.

Umami Altering Salivary Proteome: A Study across a Sensitivity Spectrum on Subjects.

This study delved into the relationship between umami taste sensitivity (UTS) and variations in the salivary proteome among 12 healthy nonsmokers utilizing 4D data-independent acquisition-based proteomics. By assessing UTS through monosodium l-glutamate (MSG) detection thresholds, we discovered notable differences: individuals with high UTS detected umami at significantly lower MSG concentrations (0.20 ± 0.12 mM) compared to their low UTS counterparts (2.51 ± 1.21 mM). Both groups showed an upregulation of the S100A1 protein under MSG stimulation, indicating a potent biochemical response to umami stimuli. The high UTS group exhibited enhanced metabolic pathways including those for amino acid, lipid, and organic acid biosynthesis, essential for maintaining taste receptor functionality and enhancing signal transduction. This group also demonstrated increased activity in cytochrome P450 enzymes and ribonucleoprotein complexes, suggesting a readiness to manage metabolic challenges and optimize umami perception. In contrast, the low UTS group showed adaptive mechanisms, possibly through modulation of receptor availability and function, with an upregulation of structural and ribosomal proteins that may support taste receptor production and turnover. These findings suggest that varying biological mechanisms underpin differences in umami perception, which could significantly influence dietary preferences and nutritional outcomes, highlighting the intricate interplay of genetic, physiological, and metabolic factors in taste sensitivity.