Hypoxic glioblastoma-cell-derived extracellular vesicles impair cGAS-STING activity in macrophages.

BACKGROUND: Solid tumors such as glioblastoma (GBM) exhibit hypoxic zones that are associated with poor prognosis and immunosuppression through multiple cell intrinsic mechanisms. However, release of extracellular vesicles (EVs) has the potential to transmit molecular cargos between cells. If hypoxic cancer cells use EVs to suppress functions of macrophages under adequate oxygenation, this could be an important underlying mechanism contributing to the immunosuppressive and immunologically cold tumor microenvironment of tumors such as GBM. METHODS: EVs were isolated by differential ultracentrifugation from GBM cell culture supernatant. EVs were thoroughly characterized by transmission and cryo-electron microscopy, nanoparticle tracking analysis (NTA), and EV marker expression by Western blot and fluorescent NTA. EV uptake by macrophage cells was observed using confocal microscopy. The transfer of miR-25/93 as an EV cargo to macrophages was confirmed by miRNA real-time qPCR. The impact of miR-25/93 on the polarization of recipient macrophages was shown by transcriptional analysis, cytokine secretion and functional assays using co-cultured T cells. RESULTS: We show that indirect effects of hypoxia can have immunosuppressive consequences through an EV and microRNA dependent mechanism active in both murine and human tumor and immune cells. Hypoxia enhanced EV release from GBM cells and upregulated expression of miR-25/93 both in cells and in EV cargos. Hypoxic GBM-derived EVs were taken up by macrophages and the miR-25/93 cargo was transferred, leading to impaired cGAS-STING pathway activation revealed by reduced type I IFN expression and secretion by macrophages. The EV-treated macrophages downregulated expression of M1 polarization-associated genes Cxcl9, Cxcl10 and Il12b, and had reduced capacity to attract activated T cells and to reactivate them to release IFN-γ, key components of an efficacious anti-tumor immune response. CONCLUSIONS: Our findings suggest a mechanism by which immunosuppressive consequences of hypoxia mediated via miRNA-25/93 can be exported from hypoxic GBM cells to normoxic macrophages via EVs, thereby contributing to more widespread T-cell mediated immunosuppression in the tumor microenvironment.

Chironomus riparius Larval Gut Bacteriobiota and Its Potential in Microplastic Degradation.

Chironomus riparius are sediment-dwelling invertebrates in freshwater ecosystems and are used as indicators of environmental pollution. Their habitat is threatened by high levels of contaminants such as microplastics and organic matter. A promising strategy for the eco-friendly degradation of pollutants is the use of bacteria and their enzymatic activity. The aim of this study was to characterize for the first time bacteriobiota associated with the gut of C. riparius larvae from nature and laboratory samples, to compare it with sediment and food as potential sources of gut microbiota, and to assess its ability to degrade cellulose, proteins, and three different types of microplastics (polyethylene, polyvinyl chloride, and polyamide). The metabarcoding approach highlighted Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota as most abundant in both gut samples. Culturable microbiota analysis revealed Metabacillus idriensis, Peribacillus simplex, Neobacillus cucumis, Bacillus thuringiensis/toyonensis, and Fictibacillus phosphorivorans as five common species for nature and laboratory samples. Two P. simplex and one P. frigoritolerans isolates showed the ability for intensive growth on polyethylene, polyvinyl chloride, and polyamide. Both cellulolytic and proteolytic activity was observed for Paenibacillus xylanexedens and P. amylolyticus isolates. The characterized strains are promising candidates for the development of environmentally friendly strategies to degrade organic pollution and microplastics in freshwater ecosystems.

Insights into Endophytic and Rhizospheric Bacteria of Five Sugar Beet Hybrids in Terms of Their Diversity, Plant-Growth Promoting, and Biocontrol Properties.

Sugar beet is the most important crop for sugar production in temperate zones. The plant microbiome is considered an important factor in crop productivity and health. Here, we investigated the bacterial diversity of seeds, roots, and rhizosphere of five sugar beet hybrids named Eduarda (ED), Koala (KO), Tibor (T), Tajfun (TF), and Cercospora-resistant (C). A culture-independent next-generation sequencing approach was used for the further investigation of seed-borne endophytes. Hybrid-associated bacteria were evaluated for their plant growth-promoting (PGP) characteristics, antagonistic activity towards Cercospora beticola and several Fusarium strains in dual culture assays, and drought and salinity tolerance. High-throughput sequencing revealed that the Proteobacteria phylum was most dominant in the seeds of all hybrids, followed by Cyanobacteria and Actinobacteriota. The predominant genus in all hybrids was Pantoea, followed by Pseudomonas, Acinetobacter, Chalicogloea, Corynebacterium, Enterobacter, Enterococcus, Glutamicibacter, Kosakonia, and Marinilactibacillus. Unique genera in the hybrids were Pleurocapsa and Arthrobacter (T), Klebsiella (TF), Apibacter (ED), and Alloscardovia (KO). The genera that were most represented in one hybrid were Weissella and Staphylococcus (TF); Streptococcus (T); Gardnerella, Prevotella, and Rothia (KO); and Gilliamella, Lactobacillus, and Snodgrassella (ED). Thirty-two bacteria out of 156 isolates from the rhizosphere, roots, and seeds were selected with respect to various plant growth-promoting activities in vitro, i.e., nitrogen fixation, phosphate solubilization, siderophore production, indole-3-acetic acid production, 1-aminocyclopropane-1-carboxylic acid deaminase activity, hydrogen cyanide production, exoenzymatic activity (amylase, protease, lipase, cellulase, xylanase, mannanases, gelatinase, and pectinase), mitigation of environmental stresses, and antifungal activity. Mixta theicola KO3-44, Providencia vermicola ED3-10, Curtobacterium pusillum ED2-6, and Bacillus subtilis KO3-18 had the highest potential to promote plant growth due to their multiple abilities (nitrogen fixation, phosphate solubilization, production of siderophores, and IAA). The best antagonistic activity towards phytopathogenic fungi was found for Bacillus velezensis C3-19, Paenibacillus polymyxa C3-36 and Bacillus halotolerans C3-16/2.1. Only four isolates B. velezensis T2-23, B. subtilis T3-4, B. velezensis ED2-2, and Bacillus halotolerans C3-16/2.1 all showed enzymatic activity, with the exception of xylanase production. B. halotolerans C3-16/2.1 exhibited the greatest tolerance to salinity, while two B. subtilis strains (C3-62 and TF2-1) grew successfully at the maximum concentration of PEG. The current study demonstrates that sugar beet-associated bacteria have a wide range of beneficial traits and are therefore highly promising for the formulation of biological control and PGP agents.

Clinical and Cytogenetic Characteristics of Children With Leukemia 20-Year Retrospective Study.

Acute leukemias are the most common malignant diseases in childhood. The aims of this retrospective cohort study were to investigate the frequency of cytogenetic abnormalities in acute pediatric leukemia; the correlation between cytogenetic abnormalities and 5-year survival; and the correlation between cytogenetic abnormalities and clinical and laboratory features. We included 105 patients; acute lymphoblastic leukemia (ALL) had 80.9% patients, B-cell lineage ALL (B-ALL) 84.7% of them, and T-cell lineage (T-ALL) 15.3%. The overall 5-year survival for B-ALL was 85.9% and for T-ALL was 84.6%. The most common cytogenetic abnormalities in patients with B-ALL were t(12;21)(p13.2;q22.1); ETV6-RUNX1 with 22.2% and hyperdiploidy with 19.4%. Our survival analysis showed that t(12;21)(p13.2;q22.1); ETV6-RUNX1 and t(1;19)(q23;p13.3); TCF3-PBX1 had the best 5-year survival with 100% of patients surviving, whereas t(v;11q23.3); KMT2A rearranged had the worst 5-year survival of just 33.3% of patients surviving after 5 years. We found no difference in 5-year survival in B-ALL when comparing clinical features. Acute myelogenous leukemia had 20 patients with 70.6% 5-year survival. The most common cytogenetic abnormality in acute myelogenous leukemia was t(8;21)(q21;q22.1); RUNX1-RUNX1T1 (20%). In conclusion, this study showed the correlation of different cytogenetic abnormalities with 5-year survival in B-ALL patients. Such correlation was not found when comparing clinical features and 5-year survival of patients with B-ALL. This emphasized the significance of cytogenetic analysis in pediatric leukemia.

Bacteriobiota of the Cave Church of Sts. Peter and Paul in Serbia-Culturable and Non-Culturable Communities' Assessment in the Bioconservation Potential of a Peculiar Fresco Painting.

The principal aim of this study was to determine bacterial diversity within the Cave Church of Sts. Peter and Paul, via culturable and non-culturable approaches, and elucidate the antifungal potential of autochthonous antagonistic bacterial isolates against biodeteriogenic fungi. Furthermore, whole-genome sequencing of selected bacterial antagonists and the analysis of genes included in the synthesis of secondary metabolites were performed. With the highest RA values, determined in metabarcoding analysis, phyla Actinobacteriota (12.08-54.00%) and Proteobacteria (25.34-44.97%) dominated most of the samples. A total of 44 different species, out of 96 obtained isolates, were determined as part of the culturable bacteriobiota, with the predominance of species from the genus Bacillus. Bacillus simplex was the only isolated species simultaneously present in all investigated substrata within the church. The best antagonistic activity against 10 biodeteriogenic fungi was documented for Streptomyces anulatus, followed by Bacillus altitudinis, Chryseobacterium viscerum, and Streptomyces sp. with their highest PGI% values ranging of from 55.9% to 80.9%. These promising results indicate that characterized bacteria are excellent candidates for developing biocontrol strategies for suppressing deteriogenic fungi responsible for the deterioration of investigated fresco painting. Finally, isolate 11-11MM, characterized as Streptomyces sp., represents a new species for science prompting the need for further study.

IS A DECREASED NITRIC OXIDE CONCENTRATION AFTER TRIAMCINOLONE ACETONIDE INTRAVITREAL INJECTION ONE OF THE REASONS FOR INTRAOCULAR PRESSURE RISE?

Diabetic macular edema is the most common cause of vision loss in patients affected by diabetes mellitus. For eyes with persistent retinal thickening despite anti-VEGF therapy, treatment with intravitreal triamcinolone may be considered, especially in pseudophakic eyes. The aim of this study was to examine aqueous humor nitric oxide concentration changes in pseudophakic eyes with persistent diffuse diabetic macular edema after intravitreal injection of triamcinolone acetonide, as well as the potential impact of these changes on the intraocular pressure values. In 10 pseudophakic eyes with persistent diffuse diabetic macular edema, paracentesis of anterior chamber with aspiration of aqueous humor and nitric oxide concentration measurements were done on the day of the intravitreal application of 20 mg triamcinolone acetonide, and after 1, 3, 6 and 9 months. Also, we were recording intraocular pressure values before the intravitreal triamcinolone acetonide injection and during the next 9 months. One month after the intravitreal triamcinolone acetonide injection, we noticed a decrease of nitric oxide concentration (45.37±5.55 µmol/L) by 31.79% compared to the initial values (66.52±7.66 µmol/L). After that, nitric oxide concentrations began to rise slightly, and at the end of the ninth month the mean nitric oxide concentration was similar to that recorded at the beginning of the study. Intraocular pressure values had increasing trend one month after the intravitreal triamcinolone acetonide injection (23.70±4.08 mm Hg) compared to the initial values (16.21±1.55 mm Hg), but after nine months these values returned to normal levels. Decreased concentration of nitric oxide could be one of the reasons for increased intraocular pressure after intravitreal application of triamcinolone acetonide in the treatment of diffuse diabetic macular edema.

Evaluation of the Potential Release Tendency of Metals and Metalloids from the Estuarine Sediments: Case Study of Rasa Bay.

Assessing the environmental quality of coastal systems is important not only for the management and protection of such areas, but also for improving the quality of water resources. Since sediment itself can often be a source of certain toxic elements, in addition to information on the distribution of metals in the water column and in the sediment itself, it is useful to determine the bioavailable forms of individual elements, particularly toxic ones. In this study, water and sediment geochemical data were supplemented with oxyanion mobility in sediments estimated by diffusion gradients in thin film (DGTs). The data obtained indicate that the chemical composition of the water in the Rasa River estuary primarily reflects the high input of suspended sediment from the catchment, the mixing of freshwater and seawater, and to a lesser extent the effects of anthropogenic activities. Although sediment composition is primarily determined by geological and hydrodynamic conditions in the catchment, it also indicates moderate enrichment in Co, Cr, Mo and Ni. In contrast, the distribution of oxyanions in sediment pore water indicates the influence of sediment as a source of some elements in the bottom water; e.g., sediment contributes to 40% of the arsenic bottom water budget. The obtained depth profiles of the oxyanion distribution in the sediment pore water indicate an early onset of suboxic to anoxic conditions in Rasa Bay, which is prone to rapid sedimentation. All this demonstrates the need to consider the bioavailable forms of elements when assessing environmental quality, as the lack of such information can lead to an incomplete assessment, especially in dynamic coastal systems such as estuaries.

Formulation of Novel Liqueurs from Juice Industry Waste: Consumer Acceptance, Phenolic Profile and Preliminary Monitoring of Antioxidant Activity and Colour Changes During Storage.

RESEARCH BACKGROUND: Apple juice is one of the most popular and liked beverages worldwide. Due to the increased health consciousness among consumers, beetroot and chokeberry juices have also rising consumption trends. Despite representing a considerable percentage of the processed fruit and rich source of bioactive compounds, fruit pomace, remaining after juice production, has still been underutilised. Here, the possibility of using apple, beetroot and chokeberry pomace in liqueur formulations is investigated. EXPERIMENTAL APPROACH: Apple and chokeberry liqueurs were produced from apple and chokeberry pomace extracts, respectively. Apple/chokeberry and apple/beetroot liqueurs were obtained by combining apple pomace with chokeberry and beetroot pomace extracts in ratios 50:50 and 70:30, respectively. The sensory quality and acceptability of freshly prepared liqueurs were evaluated by experts and consumers. Sugars and phenolics were identified and quantified by high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD) and high-performance liquid chromatography-diode array detection-tandem mass spectrometry (HPLC-DAD-MS/MS), respectively. Storability was preliminarily evaluated based on monitoring of total phenolic concentration, antioxidant activity and colour each month during 6 months of storage at 4 and 22 °C. RESULTS AND CONCLUSIONS: The expert and the consumer testing indicated that apple and chokeberry pomace could be used as raw materials without any flavour corrections while apple/beetroot pomace liqueur would require modification. High total phenolic content and antioxidant activity were found in all freshly prepared liqueurs, with chokeberry liqueur being by far superior. Among identified phenolics, ellagic acid and phlorizin were quantified as the most prominent, except in chokeberry liqueur, where phlorizin was not quantified. Despite the decrease in total phenolic concentration and antioxidant activity after 6 months, liqueurs still represented a rich source of phytochemicals. The highest phenolic compound retention and antioxidant activity maintenance were observed in chokeberry liqueur. Also, the appealing colour was retained despite the changes detected in chromatic characteristics. NOVELTY AND SCIENTIFIC CONTRIBUTION: The possibility of apple, beetroot and chokeberry pomace restoration into the food chain by the production of liqueurs has been demonstrated for the first time. Functional and sensorial properties of newly developed liqueurs indicated that the selected pomace represents the promising raw material for liqueur production. The applied approach represents a contribution to the circular economy in juice production.

Evaluation of novel green walnut liqueur as a source of antioxidants: Multi-method approach.

In this study, a novel green walnut liqueur (GWL) based on green walnuts, as the main ingredient, with the addition of fruits, aromatic plants, chocolate and honey, was produced at the pilot-scale. Antioxidant activity (AO) of the obtained GWL was determined using multiple AO assays in parallel, standard spectrophotometric (FC, DPPH and FRAP) and recently developed electrochemical ones, HydroxoPerhydroxoMercury(II) Complex and Mercury Reduction Antioxidant Power, and compared to similar commercial alcoholic beverages. Characterization of the GWL in terms of volatile and polyphenolic components was performed using SPE-GC-MS and HPLC-DAD-MS/MS, respectively. Sensory quality assessment was performed by experts in the field of sensory analysis of alcoholic beverages, using a scoring method. According to all AO assays applied, AO activity and total phenolics content of GWL were superior in comparison to commercial spirits considered. The volatile fraction of GWL was mainly composed of eugenol, α-terpineol and vanillin, while the most prevalent phenolic compounds were gallic (5.054 mg/L) and chlorogenic acid (1.307 mg/L) and flavonoids such as catechine (0.882 mg/L), quercetin (0.499 mg/L) and its sugar-conjugated derivatives, quercetin 3-O-glucoside (0.774 mg/L) and quercetin-3-O-rhamnoside (0.614 mg/L). Gallic acid is the major contributor to total AO activity, especially determined by DPPH and FRAP, followed by catechine, quercetin and chlorogenic acid. Among the terpenoids, contribution of eugenol to total AO activity is estimated as the highest. Excellent sensory quality (18.52 of maximum 20 scores) was ascribed to GWL. Consequently, the presence of bioactive compounds and high AO activity of GWL, in addition to high sensory quality score, indicates a high market potential for this high-value product.

Performance of aquatic weed - Waste Myriophyllum spicatum immobilized in alginate beads for the removal of Pb(II).

A new biosorbent - alginate encapsulated with Myriophyllum spicatum - MsA was investigated for lead ions removal. This biosorbent was characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), zeta potential, X ray Diffraction (XRD) and size distribution analysis. FT-IR analysis demonstrated that the lead ions sequestration mechanism included ion exchange and lead complexation with the carboxyl, carbonyl and hydroxyl groups in MsA. In order to better understand the mechanisms of the binding of Pb(II) on immobilized M. spicatum beads, 3 reaction and one diffusion based kinetic models were applied on kinetic data removal lead ions on three materials: M. spicatum, Ca-alginate and MsA. Myriophyllum spicatum encapsulated with alginate - MsA have higher adsorption capacity than M. spicatum. Among examined six isotherms Redlich-Peterson and the Langmuir isotherm model exhibited the best fit to the experimental data, with capacities ranging from 230 to 268.7 mg/g. Among the various tested desorption agents, nitric acid has proven to be the best. The obtained results suggest that the immobilized M. spicatum biosorbent holds great potential for lead wastewater treatment applications.

New herbal bitter liqueur with high antioxidant activity and lower sugar content: innovative approach to liqueurs formulations.

Herbal liqueurs are spirits with numerous functional properties, due to the presence of bioactive extractable compounds deriving from herbs. The aim of this study was to obtain new herbal bitter liqueur (HBL) on the basis of twelve selected bitter and aromatic plants extracts, with an optimal sensory profile for consumer acceptance. Also, the determination of optimal sugar content in HBL was done. Furthermore, antioxidant (AO) capacity and total phenolic content (TPC) of HBL was evaluated and compared to similar commercial herbal spirits. Among five tested formulations, assessed by 9-point hedonic scale, HBL with the ratio of bitter and aromatic plants 1:4 was the most acceptable. Ideal concentration of sugar in HBL, determined using a just-about-right scale, was found to be 80.32 g/l of sucrose, which is approximately 20% less than the minimum stipulated by European Union Regulation and several times lower than in the majority of commercial liqueurs. Obtained result indicates the possibility of sugar reduction in liqueurs, and suggests the need to carry out sensory analysis before production of these high-calorie beverages. Radical scavenging ability against DPPH and ABTS radicals, as well as ferric reducing antioxidant power and TPC of HBL were convincingly superior in comparison to similar commercial herbal alcoholic beverages. High correlation coefficients between TPC and other assays applied strongly support the significant role of the polyphenols in the total AO capacity of the HBL and other tested commercial herbal spirits. Headspace GC/MS revealed that the most abundant terpenes were menthone (3.75%), eucalyptol (3.42%) and menthol (3.10%), whereas methanol was present in a small amount (4.97 mg/l).

Boric Acid and Commercial Organoboron Products as Inhibitors of Drug-Resistant Candida albicans.

Clinical use of boric acid as a topical antifungal in women who have failed standard antifungal therapy with azole drugs has been used sporadically for decades. Our previous in vitro work showing inhibition of Candida albicans growth was conducted on clinical isolates without antifungal drug susceptibility profiling. Here, we report that boric acid restricts growth of drug-resistant Candida albicans and inhibits hyphal growth and diminishes cell volume. The availability of over-the-counter organoboron compounds intended for use as oral nutritional supplements led us to determine if these also were inhibitory toward resistant Candida and show here that they also possess antifungal activity. Candida glabrata was also found to be inhibited by boric acid and organoboron compounds. Further development of organoboron compounds as topical therapeutics is of potential value.

Transcatheter aortic valve implantation with a Sapien 3 Commander 20 mm valves in patients with degenerated 19 mm bioprosthetic aortic valve.

INTRODUCTION: Transcatheter aortic valve implantation (TAVI) in patients with degenerated bioprosthetic aortic valve has been successfully performed as an alternative to surgery. We describe our initial experience of valve-in-valve TAVI in five patients, using new generation Edwards Sapien 3 transcatheter heart valves implanted into degenerated 19 mm bioprosthetic valves. 20-mm Edwards S3 valves were offered for compassionate use. All patients had significant aortic valve stenosis. METHODS AND RESULTS: The main vascular access was achieved and pre-closed with two Proglide closure devices in one patient and Prostar closure devices in four patients. For each TAVI procedure an Edwards 14 French sheath was inserted without complication and sutured in place. The Sapien 3 Commander delivery system was inserted and the valve was aligned in the descending aorta. The 20-mm Sapien 3 valve was deployed with slow continuous inflation during rapid right ventricular pacing. The cranial edge of the Edwards S3 valve was aligned with the cranial radiopaque markers of bioprosthesis to minimize paravalvular leak. Post-deployment angiography, transesophageal echocardiography and aortogram confirmed absence of mild aortic insufficiency and no increase in trans-aortic gradient when compared to a naïve 19 mm bioprosthetic valve. CONCLUSION: Valve-in-valve TAVI with the Edwards S3 transcatheter heart valve for degenerative bioprosthetic aortic valves is technically feasible. The proper position of the stented valve minimizes the risk for post-procedure paravalvular insufficiency and provides good transaortic pressure gradient. © 2016 Wiley Periodicals, Inc.

Gauging the response to cardiac resynchronization therapy: The important interplay between predictor variables and definition of a favorable outcome.

AIMS: Selection of patients who are viable candidates for cardiac resynchronization therapy (CRT), prediction of the response to CRT as well as an optimal definition of a favorable response, all require further exploration. The purpose of this study was to evaluate the interplay between the prediction of the response to CRT and the definition of a favorable outcome. METHODS: Seventy patients who received CRT were included. All patients met current guideline criteria for CRT. Forty-three echocardiographic parameters were evaluated before CRT and at 1, 3, 6, and 12 months. M-mode, 2D echocardiography, and Doppler imaging were used to quantify left ventricular (LV) systolic and diastolic function, mitral regurgitation, right ventricular systolic function, pulmonary artery pressure, and myocardial mechanical dyssynchrony. The following definitions of a favorable CRT response were used: left ventricular ejection fraction (LVEF) improvement more >5% acutely following CRT, LVEF improvement >20% at 12-month follow-up, and a LV end-systolic volume (LVESV) decrease >15% at 12-month follow-up. RESULTS: For the LVEF improvement >5%, the best predictor was isovolumetric relaxation time (IVRT; P=.035). For improvement of LVEF >20%, the best predictors were left ventricular stroke index (LVSI; P=.044) and left ventricular fractional shortening (LVFS; P=.031). For the drop in left ventricular systolic volume (LVESV >15%), the best predictor was septal-to-lateral wall delay (ΔT) (P=.043, RR=1.023, 95% CI for RR=1.001-1.045). CONCLUSION: The definition of a favorable CRT response influenced the optimal predictor variable(s). Standardization of defining a favorable response to CRT is needed to guide clinical decision making processes.

Alkali modified hydrochar of grape pomace as a perspective adsorbent of Pb(2+) from aqueous solution.

Hydrochar produced via hydrothermal carbonization of grape pomace was considered as novel sorbent of Pb(2+) from aqueous solution. In order to enhance the adsorption capacity, hydrochar was chemically modified using 2 M KOH solution. Both materials were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy and X-ray diffraction technique. Batch experiments were performed to examine the effect of sorbent dosage, pH and contact time. Obtained results showed that the KOH treatment increased the sorption capacity of hydrochar from 27.8 mg g(-1) up to 137 mg g(-1) at pH 5. Adsorption of lead on either of the materials was achieved through ion-exchange mechanism, chemisorption and Pb(2+)-π interaction. The Sips isotherm model gave the best fit with the experimental data obtained for Pb(2+) sorption using activated hydrochar. The adsorption kinetic followed a pseudo second-order model. Thermodynamic parameters implied that the Pb(2+) binding for hydrochar surface was spontaneous and exothermic process. Findings from this work suggest that the hydrothermal carbonization is a promising route for production of efficient Pb (2+) sorbents for wastewater treatment.

Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function.

BACKGROUND: Insulin resistance (IR) assessed by the Homeostatic Model Assessment (HOMA) index in the acute phase of myocardial infarction in non-diabetic patients was recently established as an independent predictor of intrahospital mortality. In this study we postulated that acute IR is a dynamic phenomenon associated with the development of myocardial and microvascular injury and larger final infarct size in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (pPCI). METHODS: In 104 consecutive patients with the first anterior STEMI without diabetes, the HOMA index was determined on the 2nd and 7th day after pPCI. Worst-lead residual ST-segment elevation (ST-E) on postprocedural ECG, coronary flow reserve (CFR) determined by transthoracic Doppler echocardiography on the 2nd day after pPCI and fixed perfusion defect on single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) determined six weeks after pPCI were analyzed according to HOMA indices. RESULTS: IR was present in 55 % and 58 % of patients on day 2 and day 7, respectively. Incomplete post-procedural ST-E resolution was more frequent in patients with IR compared to patients without IR, both on day 2 (p = 0.001) and day 7 (p < 0.001). The HOMA index on day 7 correlated with SPECT-MPI perfusion defect (r = 0.331), whereas both HOMA indices correlated well with CFR (r = -0.331 to -0.386) (p < 0.01 for all). In multivariable backward logistic regression analysis adjusted for significant univariate predictors and potential confounding variables, IR on day 2 was an independent predictor of residual ST-E ≥ 2 mm (OR 11.70, 95% CI 2.46-55.51, p = 0.002) and CFR < 2 (OR = 5.98, 95% CI 1.88-19.03, p = 0.002), whereas IR on day 7 was an independent predictor of SPECT-MPI perfusion defect > 20% (OR 11.37, 95% CI 1.34-96.21, p = 0.026). CONCLUSION: IR assessed by the HOMA index during the acute phase of the first anterior STEMI in patients without diabetes treated by pPCI is independently associated with poorer myocardial reperfusion, impaired coronary microcirculatory function and potentially with larger final infarct size.

Cardiomyopathy in Celiac Disease: A Systematic Review.

(1) Background: Cardiomyopathy in celiac disease or celiac cardiomyopathy (CCM) is a serious and potentially life-threatening disease that can occur in both adults and children. However, data supporting the causal relationship between celiac disease (CD) and cardiomyopathy (CMP) are still inconsistent. The aim of this study was to review and synthesize data from the literature on this topic and potentially reveal a more evidence-based causal relationship. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to search Medline, Embase, and Scopus databases from database inception until September 2023. A total of 1187 original articles were identified. (3) Results: We identified 28 CCM patients (19 adult and 9 pediatric) with a mean age of 27.4 ± 18.01 years. Adult patients with CCM were predominantly male (84.2%) while pediatric patients were predominantly female (75%). The most common comorbidities associated with CCM were anemia (75%) and pulmonary hemosiderosis (20%). In 35% of patients, CCM occurred before the diagnosis of CD, while in 48% of patients, CCM and CD were diagnosed at the same time. Diagnosis of CD preceded diagnosis of CCM in only 18% of patients. Diagnosis of CCM is often delayed with an average, from the onset of symptoms to diagnosis, of 16 months. All patients were treated with a gluten-free diet in addition to guideline-directed medical therapy. At 11-month follow-up, cardiovascular improvement was seen in 60.7% of patients. Pediatric mortality was 33.3%, while adult mortality was 5.3%. (4) Conclusions: Clinicians should be aware of the possible association between CD and CMP, and we recommend CD work-up in all patients with CMP who have concomitant anemia. While we identified only 28 cases in the literature, many cases might go unreported due to a lack of awareness regarding CCM. A high degree of clinical suspicion and a prompt diagnosis of CCM are essential to minimizing the risks of morbidity and mortality, as the combination of a gluten-free diet and guideline-directed medical therapy can improve clinical outcomes.

Potential application of green extracts rich in phenolics for innovative functional foods: natural deep eutectic solvents as media for isolation of biocompounds from berries.

The health-promoting effects of berries have attracted attention due to the possible application of their extracts as functional ingredients in food products. Natural deep eutectic solvents (NADESs) are a new generation of environmentally friendly solvents for the extraction of natural products, and they are green alternatives to organic solvents, and they can improve the solubility, stability, and bioavailability of isolated biocompounds. In this study, an efficient eco-friendly method was used for the extraction of phenolic compounds from different berries: chokeberries, blueberries, and black goji berries with a range of eutectic solvents consisting of hydrogen bond acceptors (HBAs) such as choline chloride, L-proline, L-glycine, and L-lysine and hydrogen bond donors (HBDs) such as malic, citric, tartaric, lactic and succinic acids, glucose and glycerol. The obtained results indicated the ability of NADESs towards selective extraction of phenolics; the eutectic system choline chloride : malic acid showed selective extraction of anthocyanins, while choline chloride : glycerol and choline chloride : urea showed selectivity towards flavonoids and phenolic acids. The methodology for screening of the NADES extraction performance, which included chromatographic profiling via high-performance thin layer chromatography combined with chemometrics and spectrophotometric essays, allowed effective assessment of optimal eutectic solvents for isolation of different groups of phenolics. Great antioxidant and antimicrobial activities of extracts, along with the green nature of eutectic solvents, enable NADES berry extracts to be used as "green-labelled" functional foods or ingredients.

SPRTN is involved in hepatocellular carcinoma development through the ER stress response.

Endoplasmic reticulum (ER) stress, prompted by the accumulation of misfolded or unfolded proteins, triggers the activation of the unfolded protein response (UPR) pathway to restore ER homeostasis. This stress response is implicated in the development of hepatocellular carcinoma (HCC). A biallelic mutation in SPRTN is currently the only known single-gene mutation implicated in the early onset of HCC. However, the exact mechanism linking SPRTN mutations to HCC remains unclear. In our study, we analyzed SPRTN and UPR in 21 human HCC tissue samples using RT-qPCR, immunoblot, and immunohistochemistry. We found alterations in the expression levels of SPRTN and UPR-related genes and proteins in HCC samples. The impact of SPRTN on the ER stress response was assessed in SPRTN-depleted HepG2 cells through RNA sequencing, pull-down assay, comet assay, and mitotic index calculation. We demonstrated that SPRTN interacts with the UPR sensor GRP78. Furthermore, we observed a decrease in SPRTN levels during ER stress, and increased sensitivity to ER stress in SPRTN-depleted cells. These findings suggest an essential role for SPRTN in the ER stress response and provide new insights into HCC pathogenesis. This newly discovered function of SPRTN could significantly enhance our understanding and treatment of HCC.

Prognostic Impact of Prefrailty and Frailty in Women Undergoing TAVR: Insights From the WIN-TAVI Registry.

BACKGROUND: The risks of prefrail and frail women undergoing transcatheter aortic valve replacement (TAVR) have not been fully examined. The aim of the analysis was to assess the prognostic impact of prefrailty and frailty in women undergoing TAVR. METHODS: Women at intermediate or high surgical risk with severe aortic stenosis undergoing TAVR from the prospective multicentre WIN-TAVI (Women's International Transcatheter Aortic Valve Implantation) registry were stratified based on the number of Fried frailty criteria (weight loss, exhaustion, low physical activity, slow gait, weakness) met: nonfrail (no criteria), prefrail (1 or 2 criteria), or frail (3 or more criteria). The primary outcome at 1 year was the Valve Academic Research Consortium 2 (VARC-2) efficacy end point, a composite of mortality, stroke, myocardial infarction, hospitalisation for valve-related symptoms or heart failure, and valve-related dysfunction; secondary outcomes included the composite of VARC-2 life-threatening or major bleeding. RESULTS: Out of 1019 women, 297 (29.1%) met at least 1 frailty criterion: 264 (25.9%) had prefrailty and 33 (3.2%) frailty. The 1-year risk of the primary outcome was significantly higher in prefrail and frail (20.2%) than in nonfrail (14.9%) women (adjusted hazard ratio [aHR] 1.51, 95% confidence interval [CI] 1.07-2.12). The risk of VARC-2 life-threatening or major bleeding was higher in prefrail or frail (19.9%) than in nonfrail (10.0%) women (aHR 2.06, 95% CI 1.42-2.97). These risks were consistently increased in the prefrail and frail groups assessed separately. CONCLUSIONS: In women undergoing TAVR, the presence of prefrailty or frailty conferred an increased risk of the VARC-2 efficacy end point and of VARC-2 life-threatening or major bleeding.