Degradation Products Research Articles

Degradation, transformation and cytotoxicity of triphenyl phosphate on surface of different transition metal salts in atmospheric environment

Triphenyl phosphate (TPhP) and transition metal elements have been ubiquitously detected in the atmosphere, which can participate in atmospheric chemical reactions and induce damage to human health. Currently the understanding of TPhP degradation, transformation and cytotoxicity on atmospheric particles surface are still limited. Therefore, this study used laboratory simulation methods to investigate the influence of irradiation time, transition metal salts, relative humidity (RH) to TPhP degradation, transformation and relative cytotoxicity. TPhP was coated on particle surfaces of four transition metal salts (MnSO4, CuSO4, FeSO4 and Fe2(SO4)3) in the experiment. Within 12 h irradiation, the significant TPhP photodegradation can be observed on all particles surface. Among these influence factors, the irradiation and RH were the crucial aspects to TPhP degradation, which primarily affect the OH concentration in the atmosphere. The transition metal elements only exhibited slightly catalytic effect to TPhP degradation. The mechanism study indicated that the major degradation products of TPhP are diphenyl hydrogen phosphate (DPhP) and OH-DPhP, which originated from the phenoxy bond cleavage and hydroxylation of TPhP induced by OH. As for the cytotoxicity to A549 cells, all the transition metal particles coated with TPhP can cause cellular injury, which was chiefly induced by the transition metal salt. The possible cytotoxicity mechanism of these particles to A549 cells can be attributed to the excessive reactive oxygen species (ROS) production. This study may provide a further understanding of TPhP degradation and related cytotoxicity with the coexistent transition metal salts in the atmosphere.

Innovative materials based on physical melt-blending of cutin from tomato waste and poly(lactic acid)

In the last decades, the improving and the progresses achieved following the principles of circular economy have unveiled virtuous approaches towards environmental challenges regarding the industrial processes. Agri-food waste constitutes a promising starting material for the design of innovative products with a marked improvement of the cradle-to-grave dynamics. In this scenario, the recovery of cutin from tomato peels waste represents an effective example of circular economy.In this work, the feasibility of the discontinuous melt-blending of cutin with poly(lactic acid) (PLA) was evaluated in order to obtain an innovative green material. Different blends of PLA and cutin have been characterized by using a multi-technique approach (FT-IR, DSC, TGA, SEM, rheological study, water vapour permeability) to achieve information on the nature and properties of these new materials. An important decrease of the final torque of the melt blends was observed, together with a decrease of the melt viscosity. Further increase in the cutin content in the blends was associated to a change in the viscosity of the melt. The addition of cutin to the PLA matrix caused a variation in the water vapour permeability, in accordance with the hydrophobic nature of the cutin.The obtained results attested that some degradation phenomena occurred along the process; however, the processability of these new blends is not impaired. The potential applications of these materials will mainly concern the agricultural sector and the production of degradable products with low environmental impact.

Efficient photocatalytic degradation of profenofos by CuO-ZnO nanocomposite

Exposure to organophosphate pesticides, such as profenofos, poses a serious threat to humans and other living organisms and thus, it needs serious precaution measurements. Herein, we have developed bimetallic nanocomposite CuO-ZnO (2:1 ratio) with two band edges (1.60 eV and 3.1 eV) and two band potentials (1.373 eV and − 0.207 eV) as an appealing heterogeneous photocatalyst for the effective adsorption and photocatalytic degradation of profenofos at an ambient condition. The degradation process occurs rapidly, manifesting within a brief duration under light exposure. Notably, the CuO-ZnO) nanocomposite was directly subjected to the highest profenofos dose (1215 mg/L). Impressively, complete photocatalytic degradation (100 %) was achieved within just 80 min of exposure, emphasizing the efficacy of the photocatalytic process as a degradation/transformation pathway. Furthermore, a proposed degradation/transformation and mineralization pathway for the profenofos pesticide was delineated, based on results obtained from spectroscopic and chromatographic techniques. UV–visible spectrophotometric analysis tracked the degradation and transformation of profenofos (275.5 nm) to 2-chloro-3-bromo phenol (287.2 nm), while its mineralization was confirmed through NMR, ATR-IR, and GC–MS analysis. The explored catalytic activities, and degradation pathway intensely suggested that the hydroxyl radical (HO•) radicals are the central active degradation species produced through the “VB” pathway on the surface of CuO-ZnO nanocomposite.The kinetics models showed that the reaction predominantly follows second-order kinetics. Additionally, thermodynamic parameters, like enthalpy (ΔH), entropy (ΔS) and Gibbs free energy (ΔG) were evaluated, revealing the exothermic and spontaneous nature and of the reaction. Besides, CuO-ZnO nanocomposite possesses the optimal recyclability for up to seven rounds with nominal loss in the degradation efficacy and sustaining its structural features proving its robust nature towards the degradation of profenofos. Additionally, the environmental hazard posed by the profenofos pesticide, and its degradation products was assessed using the Estimation Program Interface (EPI) SuiteTM v.4.11, developed by the US Environmental Protection Agency. The estimation models affirmed that the degradation and transformation products exhibit relatively lower toxicity levels compared to profenofos.

Exploring the influence of sulfadiazine-induced stress on antibiotic removal and transformation pathway using microalgae Chlorella sp.

Sulfadiazine (SDZ) is a kind of anti-degradable antibiotics that is commonly found in wastewater, but its removal mechanism and transformation pathway remain unclear in microalgal systems. This study investigated the effects of initial algae concentration and SDZ-induced stress on microalgal growth metabolism, SDZ removal efficiency, and transformation pathways during Chlorella sp. cultivation. Results showed that SDZ had an inhibitory effect on the growth of microalgae, and increasing the initial algal biomass could alleviate the inhibitory effect of SDZ. When the initial algal biomass of Chlorella sp. was increased to 0.25 g L−1, the SDZ removal rate could reach 53.27%–89.07%. The higher the initial algal biomass, the higher the SOD activity of microalgae, and the better the protective effect on microalgae, which was one of the reasons for the increase in SDZ removal efficiency. Meanwhile, SDZ stress causes changes in photosynthetic pigments, lipids, total sugars and protein content of Chlorella sp. in response to environmental changes. The main degradation mechanisms of SDZ by Chlorella sp. were biodegradation (37.82%) and photodegradation (23%). Most of the degradation products of SDZ were less toxic than the parent compound, and the green algae were highly susceptible to SDZ and its degradation products. The findings from this study offered valuable insights into the tradeoffs between accumulating microalgal biomass and antibiotic toxic risks during wastewater treatment, providing essential direction for the advancement in future research and full-scale application.

Toxicity assessment of dioxins and their transformation by-products from inferred degradation pathways

Due to the significant POPs characteristics, dioxins caused concern in public health and environmental protection. Evaluating the toxicity risk of dioxin degradation pathways is critical. OCDD, 1,2,3,4,6,7,8-HpCDD, and 1,2,3,4,6,7,8-HpCDF, which are highly abundant in the environment and have strong biodegradation capabilities, were selected as precursor molecules in this study. Firstly, their transformation pathways were deduced during the metabolism of biometabolism, microbial aerobic, microbial anaerobic, and photodegradation pathways, and density function theory (DFT) was used to calculate the Gibbs free energy to infer the possibility of the occurrence of the transformation pathway. Secondly, the carcinogenic potential of the precursors and their degradation products was evaluated using the TOPKAT modeling method. With the help of the positive indicator (0–1) normalization method and heat map analysis, a significant increase in the toxic effect of some of the transformation products was found, and it was inferred that it was related to the structure of the transformation products. Meanwhile, the strength of the endocrine disrupting effect of dioxin transformation products was quantitatively assessed using molecular docking and subjective assignment methods, and it was found that dioxin transformation products with a higher content of chlorine atoms and molecules similar to those of thyroid hormones exhibited a higher risk of endocrine disruption. Finally, the environmental health risks caused by each degradation pathway were comprehensively assessed with the help of the negative indicator (1–2) standardization method, which provides a theoretical basis for avoiding the toxicity risks caused by dioxin degradation transformation. In addition, the 3D-QSAR model was used to verify the necessity and rationality of this study. This paper provides theoretical support and reference significance for the toxicity assessment of dioxin degradation by-products from inferred degradation pathways.

Brominated oxime nucleophiles are efficiently reactivating cholinesterases inhibited by nerve agents.

Six novel brominated bis-pyridinium oximes were designed and synthesized to increase their nucleophilicity and reactivation ability of phosphorylated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Their pKa was valuably found lower to parent non-halogenated oximes. Stability tests showed that novel brominated oximes were stable in water, but the stability of di-brominated oximes was decreased in buffer solution and their degradation products were prepared and characterized. The reactivation screening of brominated oximes was tested on AChE and BChE inhibited by organophosphorus surrogates. Two mono-brominated oximes reactivated AChE comparably to non-halogenated analogues, which was further confirmed by reactivation kinetics. The acute toxicity of two selected brominated oximes was similar to commercially available oxime reactivators and the most promising brominated oxime was tested in vivo on sarin- and VX-poisoned rats. This brominated oxime showed interesting CNS distribution and significant reactivation effectiveness in blood. The same oxime resulted with the best protective index for VX-poisoned rats.

Cross Talking Calcium, IP3 and Buffer Dynamics Alters ATP and NADH Level in Obese and Normal Hepatocyte Cell.

The cross talk between calcium (Ca2+), IP3 and buffer dynamics regulate various mechanisms in hepatocyte cells. The study of independent systems of calcium, IP3, and buffer signaling provides limited information about cell dynamics. In the current study, coupled reaction-diffusion equations are used to design a cross-talk model for IP3, buffer, and calcium dynamics in a hepatocyte cell. The one-way feedback of calcium, buffer, and IP3 in ATP production, ATP degradation, and NADH production rate is incorporated into the model. Numerical simulation has been done using the Finite Element Method (FEM) along the spatial direction and the Crank-Nicolson (C-N) method along the temporal direction. The numerical results are analysed to determine the effects of alterations in processes of cross-talking dynamics of IP3, buffer, and calcium on ATP and NADH production and degradation rate of ATP in a hepatocyte cell under normal and obesity conditions. The comparative analysis of these findings unveils notable distinctions induced by obesity in calcium dynamics, ATP and NADH synthesis, and ATP degradation kinetics.

Non-negligible Toxicity to Fish in the Early Life Stages Triggered by Aqueous Leachate of Takeaway Plastic Containers.

Ordering takeout is a growing social phenomenon and may raise public health concerns. However, the associated health risk of compounds leaching from plastic packaging is unknown due to the lack of chemical and toxicity data. In this study, 20 chemical candidates were tentatively identified in the environmentally relevant leachate from plastic containers through the nontargeted chemical analysis. Three main components with high responses and/or predicted toxicity were further verified and quantified, namely, 3,5-di-tert-butyl-4-hydroxycinnamic acid (BHC), 2,4-di-tert-butylphenol (2,4-DTBP), and 9-octadecenamide (oleamide). The toxicity to zebrafish larvae of BHC, a degradation product of a widely used antioxidant Irganox 1010, was quite similar to that of the whole plastic leachate. In the same manner, RNA-seq-based ingenuity analysis showed that the affected canonical pathways of zebrafish larvae were quite comparable between BHC and the whole plastic leachate, i.e., highly relevant to neurological disease, metabolic disease, and even behavioral disorder. Longer-term exposure (35 days) did not cause any effect on adult zebrafish but led to decreased hatching rate and obvious neurotoxicity in zebrafish offspring. Collectively, this study strongly suggests that plastic containers can leach out a suite of compounds causing non-negligible impacts on the early stages of fish via direct or parental exposure.

Cerium-oxide functionalized iron scaffolds: A synergistic approach for enhanced degradation and reduced cytotoxicity

Biodegradable scaffolds play a crucial role in biomedical restoration. These are three-dimensional (3D) structures that can provide support for the development of newly formed bone tissues. Among the studied metallic biodegradable scaffolds, those composed of iron (Fe) are notable for their high mechanical resistance. However, the slow degradation rate of Fe and the potential cytotoxicity of its degradation products pose challenges to effective osseointegration. Cerium oxide was incorporated into Fe scaffolds to overcome these two inherent limitations.We employed the dynamic hydrogen bubbling template (DHBT) technique, utilizing a citric acid-based electrolyte, to produce iron scaffolds. This same technique was used to embed cerium oxide nanoparticles (CNFe), whereas electrodeposition was used to create a thin cerium oxide coating over the scaffolds (CCFe). The oxidation state of cerium oxide in the functionalized scaffolds was scrutinized through surface characterization techniques. Ensuring similar porosities, we evaluated the degradation of the different distinct scaffolds using electrochemical techniques.The impact of cerium incorporation within or over the scaffolds on their degradation and cell viability was correlated with cerium oxidation states and the nature of the resulting degradation products. The synergistic implications of adding cerium to the iron scaffolds were thoroughly explored, and their potential benefits in future clinical settings were discussed.

PGPg_finder: A comprehensive and user-friendly pipeline for identifying plant growth-promoting genes in genomic and metagenomic data

Identifying and comparing plant growth-promoting traits (PGPT) within whole-genome and metagenomic sequencing data can significantly advance agricultural research and promote sustainable crop production. This study introduces PGPg_finder, a comprehensive pipeline designed to annotate and compare PGPT from both whole-genome and metagenome sequencing datasets. This pipeline utilizes direct sequence annotation alongside de novo assembly methods to accurately detect PGPT. By cross-referencing sequences from the PLaBAse database, it identifies and quantifies the presence of these genes within the original datasets, facilitating an intuitive comparison of the abundance and distribution of PGPT across various samples. We evaluated the performance of PGPg_finder by analyzing genomes from five rhizobacterial strains: Paenibacillus vini, Paenibacillus polymyxa, Fictibacillus sp., Brevibacillus agri, and Bacillus cereus, and also metagenomic samples from bulk soils subjected to forest-to-pasture conversion in the Amazon rainforest. The genomic workflow revealed several genes associated with substrate utilization, abiotic stress neutralization, phosphate solubilization, and iron acquisition. It also identified genes unique to specific lineages, including those associated with colonization and plant-derived substrate usage in P. polymyxa, quorum sensing response and biofilm formation in P. vini, heavy metal detoxification and nitrogen acquisition in B. agri, and spore production and neutralizing biotic stress in B. cereus. The strain Fictibacillus sp. presented several unique genes related to surface attachment, stress response, xenobiotic degradation, phosphate solubilization, and phytohormone production. The use of PGPg_finder highlights its potential to uncover novel inoculants and strains. The metagenomic workflow distinguished plant-growth promotion gene profiles between soils from the Amazon rainforest and pasture, with the latter showing a profile more aligned with simple carbohydrate consumption, abiotic stress tolerance, motility and chemotaxis, and phosphorus mineralization. Native forests exhibited a profile associated with the degradation of complex organic matter, oxidative stress tolerance, xenobiotic degradation, bactericidal activity, iron acquisition, and volatile pathways. These findings underscore the effectiveness and sensitivity of PGPg_finder in accurately identifying and comparing PGPT genes, highlighting both commonalities and variations across samples. The application of this pipeline has the potential to significantly facilitate the identification of plant growth-promoting microbes.

#1980 Past peritonitis episodes are linked to decreased peritoneal Immune Cell Function and Associated with Chronic Increased Peritoneal Inflammation

Abstract Background and Aims Chronic peritoneal inflammation and infectious complications occur in a significant proportion of PD patients. A relationship between peritoneal IL-6 levels and local immunocompetence is suspected. To analyse local immunocompetence, an ex-vivo stimulation assay of PD effluent was developed. The aim of this study was to analyse peritoneal inflammation and immunocompetence in a PD cohort in relation to clinical outcomes. Method Prospectively, 245 routinely performed 4-hour PETs (143 patients, 2679 patient-months) of patients exclusively receiving 2. generation PD fluids (two-chamber, pH neutral, low amount of glucose degradation products) were analysed. An ex-vivo cell stimulation protocol of the fresh effluents was performed of all PETs. Peritoneal immune cell function was analysed using ex-vivo Toll-like receptor (LPS/Pam3Cys) stimulated IL-6 release as an index of immunocompetence. The molecular effects of effluent components and the addition of alanyl-glutamine to PD fluid were analysed in heterologous cell stimulation experiments and using an effluent proteomics and metabolomics approach. Results IL-6 in the effluent showed no association with various patient characteristics (incl. RRF, underlying disease, peritonitis episodes, time on PD). A significant association of peritoneal IL-6 with solute transport rates and systemic markers of uremic inflammation was found. IL-6 in effluent (HR 2.54) and stimulated 1 h effluent (HR 0.34) was predictive of subsequent peritonitis episodes. An inverse association was observed with ex-vivo stimulated IL-6 release from peritoneal cells (P = .02), most pronounced in patients with a history of peritonitis (P = .008). Patients with above median elevated IL-6 levels showed reduced peritoneal immune cell function. The results were validated in an independent multi-centre PD cohort (n = 48). A proteomics (n = 17) and targeted metabolomics (patients n = 134, 1004 metabolites) analysis of PD effluents show an overrepresentation of apoptosis and neutrophil degranulation pathways in patients with elevated effluent IL-6 levels and reduced response mechanisms to pathogens when compared to effluents from patients with low effluent IL-6 levels. Heterologous donor-PBMC stimulation (4 Healthy donors) with 4h PET PD-effluents of 20 patients showed reduced immunocompetence with elevated IL-6 (P = .038) and improved immunocompetence when 8 mM alanyl-glutamine were added to the PD fluid during the dwell. These results could also be validated in a post-hoc analysis of a RCT testing alanyl-glutamine addition to PD fluid for 8 weeks in PD patients. Conclusion This is the first longitudinal study to show the relationship between peritoneal inflammation and impaired immune function of peritoneal cells, possibly predisposing to infectious complications. The possible underlying mechanistic link may represent the biological correlate (“immune-paralysis”) for PD patients at increased risk for recurrent episodes of peritonitis.

#2401 Association of clinical characteristics with relative changes in plasma lyso-Gb3 levels by enzyme replacement therapy in patients with Fabry disease

Abstract Background and Aims Enzyme replacement therapy (ERT) is an established treatment for Fabry disease (FD), notably for its efficacy in reducing plasma globotriaosylceramide (Gb3) levels. FD is characterized by the accumulation of Gb3 in lysosomes, resulting in the formation of globotriaosylsphingosine (lyso-Gb3), a degradation product associated with disease severity. While numerous studies have demonstrated that ERT can reduce plasma lyso-Gb3 levels, these reductions are usually quantified in absolute terms. This study is the first to explore the relative changes in plasma lyso-Gb3 levels due to ERT and to investigate the association of these changes with patients' clinical characteristics through a retrospective analysis. Method This study included patients with FD who attended the division of Nephrology at our hospital. We excluded patients lacking sufficient clinical data or without plasma lyso-Gb3 measurements both before and after initiating ERT. We considered pre-ERT plasma lyso-Gb3 concentrations as the baseline and evaluated the relative changes at one year post-ERT and at the lowest recorded lyso-Gb3 level after ERT. These variations were compared across various clinical backgrounds to assess their correlation with clinical factors including age, gender, type of ERT medication (agalsidase α or β), and disease severity, as determined by the FASTEX score. Results This study included twelve patients with FD (5 males, 7 females). We observed significantly greater relative declining changes in plasma lyso-Gb3 concentration among males compared to females (one year: −71.9 ± 4.5% in males vs. −20.6 ± 13.7% in females, p < 0.01; minimum levels: −78.5 ± 8.9% in males vs. −48.4 ± 19.6% in females, p = 0.01). No significant difference emerged in lyso-Gb3 reduction between agalsidase α and β treatments over all. One year after treatment, the relative changes in the levels were −45.1 ± 32.6% for agalsidase α and −37.7 ± 24.2% for agalsidase β (p = 0.68). The minimum levels followed suit, with −59.4 ± 26.8% for agalsidase α and −63.2 ± 15.2% for agalsidase β (p = 0.78). Lastly, the relative changes in lyso-Gb3 one year after initiating ERT were significantly associated with age (r = −0.873, p < 0.001), FASTEX score (r = 0.814, p = 0.001), baseline α-galactosidase A activity (r = −0.833, p = 0.001), and baseline lyso-Gb3 levels (r = 0.877, p < 0.001). Additionally, at the lowest levels, the relative changes in lyso-Gb3 showed a significant association with baseline α-galactosidase A activity (r = −0.887, p < 0.001), and baseline lyso-Gb3 levels (r = 0.702, p = 0.011). Conclusion The findings of our study suggest that relative changes in lyso-Gb3 are more pronounced in male patients, those with lower baseline α-galactosidase A activity, and those with higher baseline plasma lyso-Gb3 levels. Patients exhibiting severe α-galactosidase A deficiency and more severe clinical symptoms may experience greater relative declines in plasma lyso-Gb3 concentration following ERT.

#1288 Bioinformatic analysis of phosphate transporters in peritoneal cells and tissues and phosphate transport kinetics in vitro

Abstract Background and Aims Hyperphosphatemia is frequent in peritoneal dialysis (PD) patients due to limited dialytic clearance, and significantly increases cardiovascular risk. Molecular mechanisms of phosphate removal across the peritoneal membrane remain unclear, PD specific in vitro models for phosphate transport and modulator studies are not established. Method Phosphate transporter expression was assessed by RNAseq in mesothelial cells (HPMC, MeT5A) and human venous and microvascular endothelial cells (HUVEC, HCMEC). Transcriptome profiles of microdissected omental arterioles from 10 children with normal kidney function (NKF), 15 with chronic kidney disease (CKD5), and 10 children on PD were analyzed for phosphate transporter expression. Specific phosphate transporter localization and abundance in parietal peritoneum membranes and in the cell lines were assessed by immunostaining. In Transwell system, a phosphate transport model across polarized monolayers was established. Cell viability and integrity were verified by MTT assay and transepithelial resistance measurement (TER). Results Out of nine identified phosphate transporters, PiT1 (SLC20A1) and PiT2 (SLC20A2) exhibited high expression in all four cell lines, while SLC34A2 was specific in HPMC and SLC34A3 in MeT5A. In human arterioles, four phosphate transporters, SLC34A1, PiT1, PiT2, and SLC17A1, were detected. Arteriolar PiT1 was two-fold more abundant in PD patients treated with low glucose degradation product (GDP) fluids compared to those with CKD5 and NKF. In parietal peritoneal membranes, PiT1 was abundant in mesothelial and endothelial cells, with no difference between children with NKF, CKD5 and low GDP PD treatment. Concentration and time dependent phosphate kinetics across polarized mesothelial cells were studied in Transwells. Upon increased phosphate concentration in medium (1 mM and 2 mM vs. 0.1 mM), cells didn´t show signs of impaired viability, reduced TER or junction dysregulation (ZO-1 abundance) for up to 12 h. Independent of the added phosphate concentration, 60% of expected equilibrium was achieved after 12 h. Addition of PFA (SLC20/34 sodium-phosphate cotransporter inhibitor) alone or in combination with Tenapanor (an NHE3 blocker inhibiting paracellular phosphate transport) reduced phosphate transport across mesothelial cells by 10% and 20%, respectively. Conclusion We describe phosphate transporter expression and localization in peritoneal cells, in arterioles and parietal peritoneal tissues, and the impact of CKD5 and PD. The Transwell system allowed for quantification of phosphate transport across cell barriers and demonstrated the role of peritoneal sodium-phosphate cotransporter and of the paracellular route for phosphate transport across the mesothelial cell barrier. Further, yet unknown phosphate transport mechanisms should be active.

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.

The photodegradation of oxytetracycline by Degussa P25-TiO2/Fe0/ZnO ternary chain heterojunction in the presence of persulfate under visible light irradiation: The optimization and kinetic study

Degussa P25-TiO2/ZnO was impregnated with (Fe (NO3)3·9H2O) solution to give a ternary chain heterojunction of P25-TiO2/1.5 wt% Fe0/ZnO (denoted as P25/Fe0/ZnO) (Gap Energy, Eg = 2.84 eV). The obtained nanocomposite was used in the presence of K2S2O8 for the degradation of oxytetracycline (OTC) in an aqueous solution under visible-light irradiation. The response surface methodology (RSM) was employed to understand the effects of catalyst dosage, pH, and K2S2O8 on OTC degradation. The RSM could correlate the experimental value of OTC degradation with the predicted values. The best OTC degradation efficiency (89.3 %) was obtained with 0.28 g/L of P25/Fe0/ZnO at 3.02 mg/L of [K2S2O8] and pH 7.5 for 120 min. The superior performance of the catalytic system was attributed to the attraction effects between the negative charge on the catalyst surface and the positive charge on the dimethylammonium functional group on OTC at pH = 7.5. The OTC adsorption rate on P25/Fe0/ZnO was investigated using the linear form of the pseudo-second-order kinetic model. The heterogeneous nature of the catalyst was studied by a hot filtration test. Finally, the generated products of photocatalytic degradation were determined using GC–MS analysis, and the oxidation route and an acceptable mechanism were suggested.

A non-canonical role of ELN protects from cellular senescence by limiting iron-dependent regulation of gene expression

The ELN gene encodes tropoelastin which is used to generate elastic fibers that insure proper tissue elasticity. Decreased amounts of elastic fibers and/or accumulation of bioactive products of their cleavage, named elastokines, are thought to contribute to aging. Cellular senescence, characterized by a stable proliferation arrest and by the senescence-associated secretory phenotype (SASP), increases with aging, fostering the onset and progression of age-related diseases and overall aging, and has so far never been linked with elastin. Here, we identified that decrease in ELN either by siRNA in normal human fibroblasts or by knockout in mouse embryonic fibroblasts results in premature senescence. Surprisingly this effect is independent of elastic fiber degradation or elastokines production, but it relies on the rapid increase in HMOX1 after ELN downregulation. Moreover, the induction of HMOX1 depends on p53 and NRF2 transcription factors, and leads to an increase in iron, further mediating ELN downregulation-induced senescence. Screening of iron-dependent DNA and histones demethylases revealed a role for histone PHF8 demethylase in mediating ELN downregulation-induced senescence. Collectively, these results unveil a role for ELN in protecting cells from cellular senescence through a non-canonical mechanism involving a ROS/HMOX1/iron accumulation/PHF8 histone demethylase pathway reprogramming gene expression towards a senescence program.

Complete removal of N-nitrosamines using in-situ constructed sequential microreactors: Synergies of catalysis-adsorption between N-nitrosamines and their degradation products

The removal of N-nitrosamines from water faces the challenges of their difficult adsorption, and incomplete mineralization of degradation products. Herein, we report a new strategy by in-situ constructing microreactor on carbon cloth arrayed CoNi spinel oxide through membrane encapsulation. The NiCo2O4-nanoarrays activate peroxonosulfate, generating reactive oxygen species that rapidly degrade N-nitrosamines. The breaking N-N bond of N-nitrosamines provides an effective binding site for adsorbing degradation products (secondary amines). Meanwhile, electrons conducted from secondary amines adsorbed on Ni sites reconstruct the charge of CoNi sites, bolstering the peroxonosulfate activation to further remove N-nitrosamines and secondary amines. Moreover, the microreactive interface formed between membrane substrate and NiCo2O4-nanoarrays improved the reaction efficiency. It maintains efficient N-nitrosamines removal (96–99%) even in the presence of humic acid. Actual wastewater experiments confirmed its effective control of both N-nitrosamines and N-nitrosodimethylamine formation potential. This study provides a novel approach for eliminating the risk of N-nitrosamines in water.

Detoxification of Mycotoxin Patulin by the Yeast Kluyveromyces marxianus YG-4 in Apple Juice.

Patulin (PAT) is a mycotoxin produced by Penicillium species, which often contaminates fruit and fruit-derived products, posing a threat to human health and food safety. This work aims to investigate the detoxification of PAT by Kluyveromyces marxianus YG-4 (K. marxianus YG-4) and its application in apple juice. The results revealed that the detoxification effect of K. marxianus YG-4 on PAT includes adsorption and degradation. The adsorption binding sites were polysaccharides, proteins, and some lipids on the cell wall of K. marxianus YG-4, and the adsorption groups were hydroxyl groups, amino acid side chains, carboxyl groups, and ester groups, which were combined through strong forces (ion interactions, electrostatic interactions, and hydrogen bonding) and not easily eluted. The degradation active substance was an intracellular enzyme, and the degradation product was desoxypatulinic acid (DPA) without cytotoxicity. K. marxianus YG-4 can also effectively adsorb and degrade PAT in apple juice. The contents of organic acids and polyphenols significantly increased after detoxification, significantly improving the quality of apple juice. The detoxification ability of K. marxianus YG-4 toward PAT would be a novel approach for the elimination of PAT contamination.

Genetic evidence for functional diversification of gram-negative intermembrane phospholipid transporters.

The outer membrane of Gram-negative bacteria is a barrier to chemical and physical stress. Phospholipid transport between the inner and outer membranes has been an area of intense investigation and, in E. coli K-12, it has recently been shown to be mediated by YhdP, TamB, and YdbH, which are suggested to provide hydrophobic channels for phospholipid diffusion, with YhdP and TamB playing the major roles. However, YhdP and TamB have different phenotypes suggesting distinct functions. We investigated these functions using synthetic cold sensitivity (at 30 °C) caused by deletion of yhdP and fadR, a transcriptional regulator controlling fatty acid degradation and unsaturated fatty acid production, but not by ΔtamB ΔfadR or ΔydbH ΔfadR,. Deletion of tamB suppresses the ΔyhdP ΔfadR cold sensitivity suggesting this phenotype is related to phospholipid transport. The ΔyhdP ΔfadR strain shows a greater increase in cardiolipin upon transfer to the non-permissive temperature and genetically lowering cardiolipin levels can suppress cold sensitivity. These data also reveal a qualitative difference between cardiolipin synthases in E. coli, as deletion of clsA and clsC suppresses cold sensitivity but deletion of clsB does not despite lower cardiolipin levels. In addition to increased cardiolipin, increased fatty acid saturation is necessary for cold sensitivity and lowering this level genetically or through supplementation of oleic acid suppresses the cold sensitivity of the ΔyhdP ΔfadR strain. Although indirect effects are possible, we favor the parsimonious hypothesis that YhdP and TamB have differential substrate transport preferences, most likely with YhdP preferentially transporting more saturated phospholipids and TamB preferentially transporting more unsaturated phospholipids. We envision cardiolipin contributing to this transport preference by sterically clogging TamB-mediated transport of saturated phospholipids. Thus, our data provide a potential mechanism for independent control of the phospholipid composition of the inner and outer membranes in response to changing conditions.

Synthesis, magnetic properties, biotoxicity and potential mechanism of modified nano zero-valent iron for decolorization of dye wastewater

ABSTRACT SiO2-coated nano zero-valent iron (nZVI) has emerged as a fine material for the treatment of dye wastewater due to its large specific surface area, high surface activity, and strong reducibility. However, the magnetic properties based on which SiO2-coated nZVI (SiO2-nZVI) could effectively separate and recover from treated wastewater, and the biotoxicity analysis of degradation products of the dye wastewater treated by SiO2-nZVI remain unclear. In this study, SiO2-nZVI was synthesized using a modified one-step synthesis method. The SiO2-nZVI nanoparticles were characterized using Transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, Fully automatic specific surface and porosity analyzer, Vibrating sample magnetometer, and Zeta potential analyzer. The removal rate of methyl orange (MO) by SiO2-nZVI composite reached 98.35% when the degradation performance of SiO2-nZVI treating MO was optimized. Since SiO2-nZVI analysed by magnetic hysteresis loops had large saturation magnetization and strong magnetic properties, SiO2-nZVI exhibited excellent ferromagnetic behaviour. The analysis of the degradation products showed that the MO treated by SiO2-nZVI was converted into a series of intermediates, resulting in reducing the toxicity of MO. The potential mechanism of MO degradated by SiO2-nZVI was speculated through degradation process and degradation kinetics analysis. Overall, the SiO2-nZVI composite may be regarded as a promising catalyst for decolorization of dye wastewater.